9606:ASIC4
gene id: 9606:ASIC4
uniprot id: A0A8I5KPF5
uniprot id: Q96FT7
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the amiloride-sensitive sodium channel (TC 1.A.6) family.
messages: Belongs to the amiloride-sensitive sodium channel (TC 1.A.6) family. ASIC4 subfamily.
messages: Expressed in pituitary gland. Weakly expressed in brain, vestibular system and organ of Corti.
messages: Homotrimer or heterotrimer with other ASIC proteins.
messages: Membrane
messages: Probable cation channel with high affinity for sodium. In vitro, has no proton-gated channel activity.

9606:RELL2
gene id: 9606:RELL2
uniprot id: Q8NC24
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the RELT family.
messages: Cell membrane
messages: Induces activation of MAPK14/p38 cascade, when overexpressed (PubMed:28688764). Induces apoptosis, when overexpressed (PubMed:19969290).
messages: Interacts with RELT, RELL1 and OXSR1 (PubMed:16389068). Interacts with PLSCR1 (PubMed:22052202). Interacts with TRAF2 (PubMed:19969290).
messages: Phosphorylated in vitro by OXSR1.
messages: Primarily expressed in spleen, thymus, testis, peripheral blood leukocytes, brain and placenta. Not detected in prostate, ovary, small intestine, colon, heart, lung, liver, skeletal muscle, kidney and pancreas.

9606:CYFIP1
gene id: 9606:CYFIP1
uniprot id: Q7L576
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the CYFIP family.
messages: Breakpoint hotspot for the Prader-Willi/Angelman syndromes and may be implicated in autism. Commonly altered in tumors.
messages: Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression. In the CYFIP1-EIF4E-FMR1 complex this subunit is an adapter between EIF4E and FMR1. Promotes the translation repression activity of FMR1 in brain probably by mediating its association with EIF4E and mRNA (By similarity). Regulates formation of membrane ruffles and lamellipodia. Plays a role in axon outgrowth. Binds to F-actin but not to RNA. Part of the WAVE complex that regulates actin filament reorganization via its interaction with the Arp2/3 complex. Actin remodeling activity is regulated by RAC1. Regulator of epithelial morphogenesis. As component of the WAVE1 complex, required for BDNF-NTRK2 endocytic trafficking and signaling from early endosomes (By similarity). May act as an invasion suppressor in cancers.
messages: Component of the WAVE1 complex composed of ABI2, CYFIP1 or CYFIP2, BRK1, NCKAP1 and WASF1/WAVE1. Within the complex, a heterodimer containing NCKAP1 and CYFIP1 interacts with a heterotrimer formed by WAVE1, ABI2 and BRK1. Component of the CYFIP1-EIF4E-FMR1 complex which is composed of CYFIP, EIF4E and FMR1. Interacts with FMR1 but does not bind to related proteins FXR1 or FXR2. Interaction with EIF4E stimulates FMR1 binding. Component of the WAVE2 complex composed of ABI1, CYFIP1/SRA1, NCKAP1/NAP1 (NCKAP1l/HEM1 in hematopoietic cells) and WASF2/WAVE2 (PubMed:16417406). Interacts with the active GTP-bound form of RAC1. Interacts through its C-terminus with the C-terminus of DPYSL2/CRMP2 which is necessary for DPYSL2-induced axon outgrowth. Interacts with NYAP1, NYAP2 and MYO16. Interacts with TMEM108 (via N-terminus); the interaction associates TMEM108 with the WAVE1 complex (By similarity).
messages: Cytoplasm
messages: lamellipodium
messages: perinuclear region
messages: ruffle
messages: synaptosome

9606:UBE2E3
gene id: 9606:UBE2E3
uniprot id: Q969T4
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-11'- and 'Lys-48'-, as well as 'Lys-63'-linked polyubiquitination. Participates in the regulation of transepithelial sodium transport in renal cells. May be involved in cell growth arrest.
messages: Belongs to the ubiquitin-conjugating enzyme family.
messages: Cytoplasm
messages: Nucleus
messages: The ubiquitin-loaded form interacts specifically with importin-11 (IPO11), leading to its import into the nucleus. Interacts with NEDD4L.
messages: Ubiquitously expressed at low levels. Highly expressed in skeletal muscle.

9606:HCAR3
gene id: 9606:HCAR3
uniprot id: P49019
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Expression largely restricted to adipose tissue and spleen.
messages: Receptor for 3-OH-octanoid acid mediates a negative feedback regulation of adipocyte lipolysis to counteract prolipolytic influences under conditions of physiological or pathological increases in beta-oxidation rates. Acts as a low affinity receptor for nicotinic acid. This pharmacological effect requires nicotinic acid doses that are much higher than those provided by a normal diet.

9606:KNCN
gene id: 9606:KNCN
uniprot id: A6PVL3
names: Function
names: Subcellular Location Annotation
messages: May play a role in stabilizing dense microtubular networks or in vesicular trafficking.
messages: Membrane

9606:RGS9BP
gene id: 9606:RGS9BP
uniprot id: Q6ZS82
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the RGS7BP/RGS9BP family.
messages: Membrane
messages: Regulator of G protein-coupled receptor (GPCR) signaling in phototransduction. Participates in the recovery phase of visual transduction via its interaction with RGS9-1 isoform. Acts as a membrane-anchor that mediates the targeting of RGS9-1 to the photoreceptor outer segment, where phototransduction takes place. Enhances the ability of RGS9-1 to stimulate G protein GTPase activity, allowing the visual signal to be terminated on the physiologically time scale. It also controls the proteolytic stability of RGS9-1, probably by protecting it from degradation (By similarity).
messages: Specifically interacts with isoform RGS9-1 of RGS9. Component of the RGS9-1-Gbeta5 complex composed of RGS9-1, Gbeta5 (GNB5) and RGS9BP (By similarity).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:PHAF1
gene id: 9606:PHAF1
uniprot id: Q9BSU1
names: Caution
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the PHAF1 family.
messages: Cytoplasm
messages: Interacts with BCAS3; the interaction is requrired for the association with the phagophore.
messages: Plays a regulatory role in autophagic activity. In complex with BCAS3, associates with the autophagosome formation site during both non-selective and selective autophagy.
messages: Preautophagosomal structure
messages: Was originally (Ref.1) thought to be a lin-10 homolog.

9606:DIO1
gene id: 9606:DIO1
uniprot id: A8K415
uniprot id: P49895
names: Disease Annotation
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the iodothyronine deiodinase family.
messages: Endoplasmic reticulum membrane
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. The UGA codon in position 34 may either function as a selenocysteine codon or a translation termination codon.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. The UGA codon in position 59 may either function as a selenocysteine codon or a translation termination codon.
messages: Responsible for the deiodination of T4 (3,5,3',5'-tetraiodothyronine) into T3 (3,5,3'-triiodothyronine) and of T3 into T2 (3,3'-diiodothyronine). Plays a role in providing a source of plasma T3 by deiodination of T4 in peripheral tissues such as liver and kidney.
messages: Responsible for the deiodination of T4 (3,5,3',5'-tetraiodothyronine).
messages: The UGA codon in position 83 may either function as a selenocysteine codon or a translation termination codon.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:DENND2B
gene id: 9606:DENND2B
uniprot id: P78524
names: Function
names: Miscellaneous
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cell membrane
messages: Guanine nucleotide exchange factor (GEF) which may activate RAB9A and RAB9B. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form.
messages: Interacts with ITSN1 and GRB2 (PubMed:29030480). Isoform 1 interacts with the SH3 domain of ABL1.
messages: May be involved in cytoskeletal organization and tumorogenicity. Seems to be involved in a signaling transduction pathway leading to activation of MAPK1/ERK2. Plays a role in EGFR trafficking from recycling endosomes back to the cell membrane (PubMed:29030480).
messages: May block ERK2 activation stimulated by ABL1 (Probable). May alter cell morphology and cell growth (Probable).
messages: Phosphorylated. Phosphorylation decreases ITSN1 binding.
messages: Produced by alternative promoter usage.
messages: Produced by alternative splicing of isoform 1.
messages: Recycling endosome
messages: Widely expressed with the exception of peripheral blood lymphocytes. Isoform 1 is expressed in several epithelial and fibroblast (including tumorigenic) but absent in lymphoid cell lines (at protein level). Isoform 3 is expressed in primary cell or weakly tumorigenic but not in tumorigenic cell lines (at protein level).
messages: cell cortex

9606:CYS1
gene id: 9606:CYS1
uniprot id: Q717R9
names: Developmental Stage
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Expressed at high levels in the kidney and pancreas. Moderate expression seen in the skeletal muscle, liver and heart. A weak expression seen in the brain, lung, uterus, prostate, testis, small intestine and colon.
messages: Fetal kidney.
messages: Interacts (when myristoylated) with UNC119 and UNC119B; interaction is required for localization to cilium.
messages: cilium axoneme
messages: cilium membrane

9606:IGFL2
gene id: 9606:IGFL2
uniprot id: Q6UWQ7
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the IGFL family.
messages: Detected in cerebellum, heart, placenta, spleen, stomach, testis and thymus.
messages: Potential ligand of the IGFLR1 cell membrane receptor.
messages: Secreted

9606:GDPD1
gene id: 9606:GDPD1
uniprot id: Q8N9F7
names: Activity Regulation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the glycerophosphoryl diester phosphodiesterase family.
messages: Cytoplasm
messages: Endoplasmic reticulum
messages: Hydrolyzes lysoglycerophospholipids to produce lysophosphatidic acid (LPA) and the corresponding amines (PubMed:27637550, PubMed:25596343). Shows a preference for 1-O-alkyl-sn-glycero-3-phosphocholine (lyso-PAF), lysophosphatidylethanolamine (lyso-PE) and lysophosphatidylcholine (lyso-PC) (PubMed:27637550, PubMed:25596343). May be involved in bioactive N-acylethanolamine biosynthesis from both N-acyl-lysoplasmenylethanolamin (N-acyl-lysoPlsEt) and N-acyl-lysophosphatidylethanolamin (N-acyl-lysoPE) (PubMed:27637550, PubMed:25596343). In addition, hydrolyzes glycerophospho-N-acylethanolamine to N-acylethanolamine (PubMed:27637550). Does not display glycerophosphodiester phosphodiesterase activity, since it cannot hydrolyze either glycerophosphoinositol or glycerophosphocholine (By similarity).
messages: Lysophospholipase D activity is increased by magnesium and manganese and inhibited by calcium in a concentration dependent manner (PubMed:27637550). Loss of lysophospholipase D activity by addition of EDTA (By similarity).
messages: Membrane
messages: Widely expressed with high expression level in testis.
messages: perinuclear region

9606:NUDT9
gene id: 9606:NUDT9
uniprot id: Q9BW91
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the Nudix hydrolase family. NudF subfamily.
messages: Hydrolyzes ADP-ribose (ADPR) to AMP and ribose 5'-phosphate.
messages: Inhibited by fluoride and N-acetyl-p-benzoquinoneimine.
messages: Mitochondrion
messages: Monomer. Interacts with GLOD4.
messages: Ubiquitously expressed but isoform 1 is the most predominant isoform.

9606:INSM1
gene id: 9606:INSM1
uniprot id: Q01101
names: Domain
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the INSM1 family.
messages: Expressed in pancreatic duct cells. Expressed in several tumor cell lines of neuroendocrine origin including pheochromocytoma, medullary thyroid carcinoma, insulinoma, medulloblastoma, retinoblastoma, pheochromacytoma, medullary thyroid carcinoma and small cell lung carcinoma.
messages: Interacts (via the SNAG domain) with HDAC1 (PubMed:16569215). Interacts (via the SNAG domain) with HDAC2 (By similarity). Interacts (via the SNAG domain) with KDM1A (PubMed:23721412). Interacts (via the SNAG domain) with RCOR1. Interacts with SORBS1 (By similarity). Interacts (via the N-terminal region) with CCND1 (via cyclin N-terminal domain); the interaction competes with the binding of CCND1 to CDK4 during cell cycle progression and increases its transcriptional repressor activity (PubMed:16569215, PubMed:18417529, PubMed:19124461). Interacts with HDAC3; the interaction increases its transcriptional repressor activity (PubMed:16569215, PubMed:18417529).
messages: Nucleus
messages: Sequence-specific DNA-binding transcriptional regulator that plays a key role in neurogenesis and neuroendocrine cell differentiation during embryonic and/or fetal development. Binds to the consensus sequence 5'-[TG][TC][TC][TT][GA]GGG[CG]A-3' in target promoters. Acts as a transcriptional repressor of NEUROD1 and INS expression via its interaction with cyclin CCND1 in a cell cycle-independent manner. Negatively regulates skeletal muscle-specific gene expression in endocrine cells of the pituitary by inhibiting the Notch signaling pathway. Represses target gene transcription by recruiting chromatin-modifying factors, such as HDAC1, HDAC2, HDAC3, KDM1A and RCOR1 histone deacetylases. Binds to its own promoter, suggesting autoregulation as a self-control feedback mechanism. Competes with histone H3 for the same binding site on the histone demethylase complex formed by KDM1A and RCOR1, and thereby inhibits demethylation of histone H3 at 'Lys-4' (PubMed:23721412). Promotes the generation and expansion of neuronal basal progenitor cells in the developing neocortex. Involved in the differentiation of endocrine cells of the developing anterior pituitary gland, of the pancreas and intestine, and of sympatho-adrenal cells in the peripheral nervous system. Promotes cell cycle signaling arrest and inhibition of cellular proliferation.
messages: The C-terminal region is necessary for NEUROD1 promoter DNA-binding and transcriptional repressor activity.
messages: Up-regulated by transcription factors, such as MASH1, NEUROD1, NEUROG3, NGN3 and TCF3.

9606:REST
gene id: 9606:REST
uniprot id: Q13127
names: Caution
names: Developmental Stage
names: Disease Annotation
names: Domain
names: Function
names: Induction
names: Miscellaneous
names: PTM
names: Sequence Caution
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: An intronic variant that affects alternative splicing of REST into isoform 3 and inactivation of REST repressor activity is associated with progressive hearing loss and deafness.
messages: Binds to the 3' region of the neuron-restrictive silencer element (NRSE), with lower affinity than full-length REST isoform 1 (By similarity). Exhibits weaker repressor activity compared to isoform 1 (PubMed:11779185). May negatively regulate the repressor activity of isoform 1 by binding to isoform 1, thereby preventing its binding to NRSE and leading to derepression of target genes (PubMed:11779185). However, in another study, does not appear to be implicated in repressor activity of a NRSE motif-containing reporter construct nor in inhibitory activity on the isoform 1 transcriptional repressor activity (PubMed:11741002). Post-transcriptional inactivation of REST by SRRM4-dependent alternative splicing into isoform 3 is required in mechanosensory hair cells in the inner ear for derepression of neuronal genes and hearing (By similarity).
messages: Contaminating sequence. Potential poly-A sequence.
messages: Controversial data exists concerning the repressor activity of isoform 3. A study showed that isoform 3 exhibits weak repressor activity of a NRSE motif-containing reporter construct (PubMed:11779185). Another report, however, does not observe any isoform 3 transcriptional repressor activity of a NRSE motif-containing reporter construct (PubMed:11741002). Controversial data also exists regarding the function of isoform 3 on the negative regulation of isoform 1. It was shown that isoform 3 negatively regulates the repressor activity of isoform 1 by binding to isoform 1, thereby preventing its binding to NRSE and leading to derepression of target genes (PubMed:11779185). Another study, however, did not observe any inhibitory activity of isoform 3 on the isoform 1 transcriptional repressor activity (PubMed:11741002).
messages: Cytoplasm
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry.
messages: Expressed in neurons of the prefrontal cortex, in hippocampal pyramidal neurons, dentate gyrus granule neurons and cerebellar Purkinje and granule neurons (at protein level) (PubMed:24670762). Expressed in dopaminergic neurons of the substantia nigra (at protein level) (PubMed:30684677). Expressed in neural progenitor cells (at protein level) (PubMed:21258371). In patients suffering from Alzheimer disease, frontotemporal dementia or dementia with Lewy bodies, decreased nuclear levels have been observed in neurons of the prefrontal cortex and the hippocampus, but not in neurons of the dentate gyrus and cerebellum (at protein level) (PubMed:24670762). In patients with Parkinson disease or dementia with Lewy bodies, decreased nuclear levels have been observed in dopaminergic neurons and in cortical neurons and localization to Lewy bodies and pale bodies was detected (at protein level) (PubMed:30684677). Expressed at higher levels in weakly invasive breast cancer cell lines and at lower levels in highly invasive breast cancer lines (at protein level) (PubMed:26053433). Ubiquitous (PubMed:8568247). Expressed at higher levels in the tissues of the lymphocytic compartment, including spleen, thymus, peripheral blood lymphocytes and ovary (PubMed:8568247).
messages: Expression is cell cycle-dependent with decreased levels in G2 phase; mediated by proteasomal degradation (at protein level) (PubMed:18354482). In aged individuals, increased expression in hippocampal CA1, CA3 and CA4 pyramidal neurons and in dentate granule cell neurons, but not in the cerebellum (PubMed:24670762).
messages: Isoform 1 and isoform 3 form heterodimers (By similarity). Isoform 3: Forms homodimers and homooligomers; binds to the neuron-restrictive silencer element (NRSE) as monomer (By similarity). Interacts with SIN3A, SIN3B and RCOR1 (PubMed:10449787, PubMed:10734093, PubMed:16288918). Interacts with CDYL (PubMed:19061646). Interacts with EHMT1 and EHMT2 only in the presence of CDYL (PubMed:19061646). Part of a complex containing at least CDYL, REST, WIZ, SETB1, EHMT1 and EHMT2 (PubMed:19061646). Interacts (via zinc-finger DNA-binding domain) with ZFP90 (via N- and C-termini); the interaction inhibits REST repressor activity (PubMed:21284946). Interacts (via C2H2-type zinc finger 5) with PRICKLE1 (PubMed:14645515, PubMed:16442230). Interacts with FBXW11 and BTRC (PubMed:18354482). Interacts with USP7 (PubMed:21258371).
messages: Nucleus
messages: O-glycosylated.
messages: Phosphorylated; phosphorylation is required for ubiquitination.
messages: Produced by SRRM4-dependent alternative splicing in neurons and inner ear hair cells (By similarity). Lacks the four C-terminal zinc fingers and the RCOR1 corepressor interaction site found in full length REST isoform 1, which are required for full DNA-binding and repressive activity (PubMed:11741002).
messages: The C2H2-type zinc finger 5 is required for nuclear localization.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The disease may be caused by variants affecting the gene represented in this entry. An intronic variant that affects alternative splicing of REST and inactivation of REST repressor activity fully segregates with deafness in a 3-generation family.
messages: Transcriptional repressor which binds neuron-restrictive silencer element (NRSE) and represses neuronal gene transcription in non-neuronal cells (PubMed:12399542, PubMed:26551668, PubMed:7697725, PubMed:7871435, PubMed:8568247, PubMed:11741002, PubMed:11779185). Restricts the expression of neuronal genes by associating with two distinct corepressors, SIN3A and RCOR1, which in turn recruit histone deacetylase to the promoters of REST-regulated genes (PubMed:10449787, PubMed:10734093). Mediates repression by recruiting the BHC complex at RE1/NRSE sites which acts by deacetylating and demethylating specific sites on histones, thereby acting as a chromatin modifier (By similarity). Transcriptional repression by REST-CDYL via the recruitment of histone methyltransferase EHMT2 may be important in transformation suppression (PubMed:19061646). Represses the expression of SRRM4 in non-neural cells to prevent the activation of neural-specific splicing events and to prevent production of REST isoform 3 (By similarity). Repressor activity may be inhibited by forming heterodimers with isoform 3, thereby preventing binding to NRSE or binding to corepressors and leading to derepression of target genes (PubMed:11779185). Also maintains repression of neuronal genes in neural stem cells, and allows transcription and differentiation into neurons by dissociation from RE1/NRSE sites of target genes (By similarity). Thereby is involved in maintaining the quiescent state of adult neural stem cells and preventing premature differentiation into mature neurons (PubMed:21258371). Plays a role in the developmental switch in synaptic NMDA receptor composition during postnatal development, by repressing GRIN2B expression and thereby altering NMDA receptor properties from containing primarily GRIN2B to primarily GRIN2A subunits (By similarity). Acts as a regulator of osteoblast differentiation (By similarity). Key repressor of gene expression in hypoxia; represses genes in hypoxia by direct bindi…
messages: Ubiquitinated; ubiquitination is mediated by BTRC and leads to proteasomal degradation in G2 phase (PubMed:18354482, PubMed:21258371). Ubiquitination increases during neuronal differentiation (PubMed:21258371). Deubiquitinated by USP7; leading to its stabilization and promoting the maintenance of neural progenitor cells (PubMed:21258371).
messages: Up-regulated by Wnt signaling (PubMed:24670762). Up-regulated in the brain of aging individuals but not in Alzheimer disease patients (PubMed:24670762). Up-regulated by oxidative stress (PubMed:24670762). Down-regulated during neural progenitor cell differentiation (PubMed:21258371).

9606:CNKSR2
gene id: 9606:CNKSR2
uniprot id: A0A2R8Y622
uniprot id: A0A2R8Y700
uniprot id: A0A2R8Y7A1
uniprot id: A0A2U3TZH5
uniprot id: Q8WXI2
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the CNKSR family.
messages: Cytoplasm
messages: Interacts with RAF1, RAB2L and RAL GTPase proteins.
messages: May function as an adapter protein or regulator of Ras signaling pathways.
messages: Membrane
messages: Phosphorylated on tyrosine.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:SCN1A
gene id: 9606:SCN1A
uniprot id: P35498
names: Activity Regulation
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the sodium channel (TC 1.A.1.10) family. Nav1.1/SCN1A subfamily.
messages: Cell membrane
messages: Inactivation of this channel is specifically inhibited by the spider toxins Hm1a and Hm1b (H.maculata, AC P60992 and AC P0DOC5) in somatosensory neurons to elicit acute pain and mechanical allodynia.
messages: Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient (PubMed:14672992). Plays a key role in brain, probably by regulating the moment when neurotransmitters are released in neurons. Involved in sensory perception of mechanical pain: activation in somatosensory neurons induces pain without neurogenic inflammation and produces hypersensitivity to mechanical, but not thermal stimuli.
messages: Phosphorylation at Ser-1516 by PKC in a highly conserved cytoplasmic loop slows inactivation of the sodium channel and reduces peak sodium currents.
messages: SCN1A mutations may be involved in Panayiotopoulos syndrome, a benign age-related focal seizure disorder occurring in early and mid-childhood. It is characterized by seizures, often prolonged, with predominantly autonomic symptoms, and by an electroencephalogram that shows shifting and/or multiple foci, often with occipital predominance. Autonomic seizures in Panayiotopoulos syndrome consist of episodes of disturbed autonomic function with emesis as the predominant symptom. Cardiorespiratory arrest is exceptional.
messages: The S3b-S4 and S1-S2 loops of repeat IV are targeted by H.maculata toxins Hm1a and Hm1b, leading to inhibit fast inactivation of Nav1.1/SCN1A. Selectivity for H.maculata toxins Hm1a and Hm1b depends on S1-S2 loops of repeat IV.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The sequence contains 4 internal repeats, each with 5 hydrophobic segments (S1, S2, S3, S5, S6) and one positively charged segment (S4). Segments S4 are probably the voltage-sensors and are characterized by a series of positively charged amino acids at every third position.
messages: The voltage-sensitive sodium channel consists of an ion conducting pore forming alpha-subunit regulated by one or more beta-1 (SCN1B), beta-2 (SCN2B), beta-3 (SCN3B) and/or beta-4 (SCN4B). Beta-1 (SCN1B) and beta-3 (SCN3B) are non-covalently associated with alpha, while beta-2 (SCN2B) and beta-4 (SCN4B) are covalently linked by disulfide bonds. Interacts with FGF13 (PubMed:21566136). Interacts with SCN1B (PubMed:17928445, PubMed:15525788). Interacts with the conotoxin GVIIJ (PubMed:24497506). Interacts with the spider beta/delta-theraphotoxin-Pre1a (PubMed:28428547).

9606:RAPGEF5
gene id: 9606:RAPGEF5
uniprot id: Q92565
names: Function
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Guanine nucleotide exchange factor (GEF) for RAP1A, RAP2A and MRAS/M-Ras-GTP. Its association with MRAS inhibits Rap1 activation.
messages: Nucleus
messages: Widely expressed with highest levels in brain.

9606:NCDN
gene id: 9606:NCDN
uniprot id: Q9UBB6
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Abundantly expressed in whole adult brain and in all individual brain regions examined, including spinal cord. Weakly expressed in ovary, testis, fetal brain and small intestine.
messages: Belongs to the neurochondrin family.
messages: Endosome membrane
messages: Interacts with MCHR1 (PubMed:16945926). Interacts with SEMA4C (By similarity). Interacts with DIAPH1 (via FH3 domain) (By similarity). Interacts with GRM5 (By similarity).
messages: Palmitoylated. Palmitoylation by ZDHHC1, ZDHHC3 and ZDHHC11 regulates the association of NCDN with endosome membranes. May also be palmitoylated by ZDHHC7.
messages: Postsynapse
messages: Probably involved in signal transduction in the nervous system, via increasing cell surface localization of GRM5/mGluR5 and positively regulating its signaling (PubMed:33711248). Required for the spatial learning process. Acts as a negative regulator of Ca(2+)-calmodulin-dependent protein kinase 2 (CaMK2) phosphorylation. May play a role in modulating melanin-concentrating hormone-mediated functions via its interaction with MCHR1 that interferes with G protein-coupled signal transduction. May be involved in bone metabolism. May also be involved in neurite outgrowth (Probable).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: cytosol
messages: dendrite

9606:TRAPPC11
gene id: 9606:TRAPPC11
uniprot id: Q7Z392
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the TRAPPC11 family.
messages: Component of the multisubunit TRAPP (transport protein particle) complex, which includes at least TRAPPC2, TRAPPC2L, TRAPPC3, TRAPPC3L, TRAPPC4, TRAPPC5, TRAPPC8, TRAPPC9, TRAPPC10, TRAPPC11 and TRAPPC12.
messages: Golgi apparatus
messages: Involved in endoplasmic reticulum to Golgi apparatus trafficking at a very early stage.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: cis-Golgi network

9606:PSG8
gene id: 9606:PSG8
uniprot id: Q9UQ74
names: Developmental Stage
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the immunoglobulin superfamily. CEA family.
messages: PSBG are produced in high quantity during pregnancy.
messages: Secreted

9606:CA7
gene id: 9606:CA7
uniprot id: P43166
names: Activity Regulation
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Activated by histamine, L-adrenaline, L- and D-histidine, and L- and D-phenylalanine. Inhibited by coumarins, sulfonamide derivatives such as acetazolamide (AZA), by saccharin and Foscarnet (phosphonoformate trisodium salt).
messages: Belongs to the alpha-carbonic anhydrase family.
messages: Cytoplasm
messages: Reversible hydration of carbon dioxide.

9606:KCND1
gene id: 9606:KCND1
uniprot id: Q9NSA2
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the potassium channel family. D (Shal) (TC 1.A.1.2) subfamily. Kv4.1/KCND1 sub-subfamily.
messages: Homotetramer or heterotetramer with KCND2 and/or KCND3. Associates with the regulatory subunits KCNIP1, KCNIP2, KCNIP3 and KCNIP4 (By similarity). Interacts with DPP10 (Probable).
messages: Membrane
messages: Pore-forming (alpha) subunit of voltage-gated rapidly inactivating A-type potassium channels. May contribute to I(To) current in heart and I(Sa) current in neurons. Channel properties are modulated by interactions with other alpha subunits and with regulatory subunits.
messages: The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.
messages: Widely expressed. Highly expressed in brain, in particular in cerebellum and thalamus; detected at lower levels in the other parts of the brain.
messages: dendrite

9606:MKI67
gene id: 9606:MKI67
uniprot id: P46013
names: Biotechnology
names: Caution
names: Developmental Stage
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: Chromosome
messages: Expression occurs preferentially during late G1, S, G2 and M phases of the cell cycle, while in cells in G0 phase the antigen cannot be detected (at protein level) (PubMed:6206131). Present at highest level in G2 phase and during mitosis (at protein level). In interphase, forms fiber-like structures in fibrillarin-deficient regions surrounding nucleoli (PubMed:2674163, PubMed:8799815).
messages: Interacts with KIF15 (PubMed:10878014). Interacts (via the FHA domain) with NIFK (PubMed:11342549, PubMed:14659764, PubMed:16244663). Interacts with PPP1CC (PubMed:24867636). Component of a complex at least composed of ZNF335, HCFC1, CCAR2, EMSY, MKI67, RBBP5, ASH2L and WDR5; the complex is formed as a result of interactions between components of a nuclear receptor-mediated transcription complex and a histone methylation complex (PubMed:19131338). Interacts with ZNF335 (PubMed:19131338, PubMed:23178126).
messages: Nucleus
messages: Phosphorylated. Hyperphosphorylated in mitosis (PubMed:10502411, PubMed:10653604). Hyperphosphorylated form does not bind DNA.
messages: Required to maintain individual mitotic chromosomes dispersed in the cytoplasm following nuclear envelope disassembly (PubMed:27362226). Associates with the surface of the mitotic chromosome, the perichromosomal layer, and covers a substantial fraction of the chromosome surface (PubMed:27362226). Prevents chromosomes from collapsing into a single chromatin mass by forming a steric and electrostatic charge barrier: the protein has a high net electrical charge and acts as a surfactant, dispersing chromosomes and enabling independent chromosome motility (PubMed:27362226). Binds DNA, with a preference for supercoiled DNA and AT-rich DNA (PubMed:10878551). Does not contribute to the internal structure of mitotic chromosomes (By similarity). May play a role in chromatin organization (PubMed:24867636). It is however unclear whether it plays a direct role in chromatin organization or whether it is an indirect consequence of its function in maintaining mitotic chromosomes dispersed (Probable).
messages: Was thought to play a key role in cell proliferation, and is commonly used as a marker of cell proliferation (PubMed:6339421, PubMed:21960707). However, its primary function is uncoupled from cell proliferation: it is required to maintain mitotic chromosomes dispersed by forming a steric and electrostatic charge barrier (PubMed:27362226).
messages: Widely used as a marker to assess cell proliferation, as it is detected in the nucleus of proliferating cells only (PubMed:6339421, PubMed:21960707). In cancer research field for example, MKI67 is the most widely used marker for comparing proliferation between tumor samples (PubMed:21960707, PubMed:26680267).
messages: nucleolus

9606:FAM136A
gene id: 9606:FAM136A
uniprot id: B0AZT6
uniprot id: E7EQY1
uniprot id: Q96C01
names: Similarity
messages: Belongs to the FAM136 family.

9606:LIMD1
gene id: 9606:LIMD1
uniprot id: Q9UGP4
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Adapter or scaffold protein which participates in the assembly of numerous protein complexes and is involved in several cellular processes such as cell fate determination, cytoskeletal organization, repression of gene transcription, cell-cell adhesion, cell differentiation, proliferation and migration. Positively regulates microRNA (miRNA)-mediated gene silencing and is essential for P-body formation and integrity. Acts as a hypoxic regulator by bridging an association between the prolyl hydroxylases and VHL enabling efficient degradation of HIF1A. Acts as a transcriptional corepressor for SNAI1- and SNAI2/SLUG-dependent repression of E-cadherin transcription. Negatively regulates the Hippo signaling pathway and antagonizes phosphorylation of YAP1. Inhibits E2F-mediated transcription, and suppresses the expression of the majority of genes with E2F1-responsive elements. Regulates osteoblast development, function, differentiation and stress osteoclastogenesis. Enhances the ability of TRAF6 to activate adapter protein complex 1 (AP-1) and negatively regulates the canonical Wnt receptor signaling pathway in osteoblasts. May act as a tumor suppressor by inhibiting cell proliferation.
messages: Belongs to the zyxin/ajuba family.
messages: Cytoplasm
messages: Down-regulated in lung cancer.
messages: Expressed in normal and breast cancer tissues (at protein level). Ubiquitous.
messages: Interacts (via LIM domains) with TRAF6. Found in a complex with TRAF6, PRKCZ and SQSTM1. Interacts (via LIM domains) SNAI2/SLUG (via SNAG domain) and SCRT1 (via SNAG domain) (By similarity). Interacts with SQSTM1 and RB1. Found in a complex composed of LIMD1, VHL, EGLN1/PHD2, ELOB and CUL2. Interacts with EIF4E, AGO1, AGO2, DCP2, DDX6, LATS1, LATS2, EGLN1/PHD2, EGLN2/PHD1 and EGLN3/PHD3. Interacts (via LIM zinc-binding 2) with isoform 1 and isoform 3 of VHL. Interacts (via LIM domains) with SNAI1 (via SNAG domain).
messages: Nucleus
messages: P-body
messages: Phosphorylated during mitosis.
messages: adherens junction
messages: focal adhesion

9606:STAG1
gene id: 9606:STAG1
uniprot id: Q4LE48
uniprot id: Q8WVM7
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the SCC3 family.
messages: Chromosome
messages: Cohesin complexes are composed of a heterodimer between a SMC1 protein (SMC1A or SMC1B) and SMC3, which are attached via their hinge domain, and RAD21 which link them at their heads, and one STAG protein (STAG1, STAG2 or STAG3) (PubMed:11076961, PubMed:22628566, PubMed:32409525). In cohesin complexes, STAG1 is mutually exclusive with STAG2 and STAG3 (PubMed:11076961). Interacts directly with RAD21 in cohesin complex (By similarity). The cohesin complex interacts with the cohesin loading complex subunits NIPBL/Scc2 (via HEAT repeats) and MAU2/Scc4. NIPBL directly contacts all members of the complex, RAD21, SMC1A/B, SMC3 and STAG1 (PubMed:32409525).
messages: Component of cohesin complex, a complex required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate.
messages: Component of cohesin complex, a complex required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. The cohesin complex may also play a role in spindle pole assembly during mitosis.
messages: Nucleus
messages: Part of the cohesin complex which is composed of a heterodimer between a SMC1 protein (SMC1A or SMC1B) and SMC3, which are attached via their hinge domain, and RAD21 which link them at their heads, and one STAG protein.
messages: Phosphorylated by PLK1. The large dissociation of cohesin from chromosome arms during prophase is partly due to its phosphorylation (By similarity).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: centromere

9606:TFF3
gene id: 9606:TFF3
uniprot id: Q07654
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cytoplasm
messages: Expressed in goblet cells of the intestines and colon (at protein level). Expressed by goblet cells of small and large intestinal epithelia and also by the uterus. Also expressed in the hypothalamus where it is detected in paraventricular, periventricular and supraoptic nuclei (at protein level).
messages: Involved in the maintenance and repair of the intestinal mucosa. Promotes the mobility of epithelial cells in healing processes (motogen).
messages: Monomer. Homodimer; disulfide-linked.
messages: extracellular matrix

9606:NRIP1
gene id: 9606:NRIP1
uniprot id: P48552
names: Disease Annotation
names: Domain
names: Function
names: Induction
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: Acetylation regulates its nuclear translocation and corepressive activity (By similarity). Acetylation abolishes interaction with CTBP1. Phosphorylation enhances interaction with YWHAH.
messages: Contains 9 Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs, which have different affinities for nuclear receptors. The C-terminal LTKTNPILYYMLQK motif is required for ligand-dependent interaction with RAAR and RXRB homodimers and heterodimers, for the corepressor activity, and for the formation of an HDAC3 complex with RARA/RXRB (By similarity). Contains at least four autonomous repression domains (RD1-4). RD1 functions via a histone deacetylase (HDAC)-independent mechanism, whereas RD2, RD3 and RD4 can function by HDAC-dependent or independent mechanisms, depending on cell type. RD2 is dependent on CTBP binding.
messages: Expressed in a circadian manner in the liver (at protein level).
messages: Interacts with RARA and RXRB homodimers and RARA/RXRB heterodimers in the presence of ligand. Interacts with HDAC1 and HDAC3 via its N-terminal domain. Interacts with NR2C1 (sumoylated form and via the ligand-binding domain); the interaction results in promoting the repressor activity of NR2C1 (By similarity). Interacts with CTBP1, CTBP2, ESR1, HDAC1, HDAC2, HDAC5, HDAC6, NR2C2, NR3C1, NR3C2, YWHAH, JUN and FOS. Found in a complex with both NR3C1 and YWHAH. Interacts with ZNF366. Interacts with RORA.
messages: Modulates transcriptional activation by steroid receptors such as NR3C1, NR3C2 and ESR1. Also modulates transcriptional repression by nuclear hormone receptors. Positive regulator of the circadian clock gene expression: stimulates transcription of BMAL1, CLOCK and CRY1 by acting as a coactivator for RORA and RORC. Involved in the regulation of ovarian function (By similarity). Plays a role in renal development (PubMed:28381549).
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:GLUL
gene id: 9606:GLUL
uniprot id: A8YXX4
uniprot id: P15104
names: Activity Regulation
names: Developmental Stage
names: Disease Annotation
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the glutamine synthetase family.
messages: By glucocorticoids. Vitamin D and the Wnt signaling pathway inhibit its expression and activity.
messages: Cell membrane
messages: Decamer; composed of two pentamers (PubMed:18005987). Interacts with PALMD (By similarity). Interacts with RHOJ (PubMed:30158707).
messages: Expressed during early fetal stages.
messages: Expressed in endothelial cells.
messages: Glutamine synthetase activity is inhibited by methionine sulfoximine (MSO).
messages: Glutamine synthetase that catalyzes the ATP-dependent conversion of glutamate and ammonia to glutamine (PubMed:30158707, PubMed:16267323). Its role depends on tissue localization: in the brain, it regulates the levels of toxic ammonia and converts neurotoxic glutamate to harmless glutamine, whereas in the liver, it is one of the enzymes responsible for the removal of ammonia (By similarity). Essential for proliferation of fetal skin fibroblasts (PubMed:18662667). Independently of its glutamine synthetase activity, required for endothelial cell migration during vascular development: acts by regulating membrane localization and activation of the GTPase RHOJ, possibly by promoting RHOJ palmitoylation (PubMed:30158707). May act as a palmitoyltransferase for RHOJ: able to autopalmitoylate and then transfer the palmitoyl group to RHOJ (PubMed:30158707). Plays a role in ribosomal 40S subunit biogenesis (PubMed:26711351).
messages: Membrane
messages: Microsome
messages: Mitochondrion
messages: Palmitoylated; undergoes autopalmitoylation.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitinated by ZNRF1.
messages: cytosol

9606:SUMO3
gene id: 9606:SUMO3
uniprot id: P55854
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the ubiquitin family. SUMO subfamily.
messages: Cleavage of precursor form by SENP1, SENP2 or SENP5 is necessary for function.
messages: Covalently attached to a number of proteins. Interacts with BMAL1 (By similarity). Interacts with USP25 (via ts SIM domain); the interaction sumoylates USP25 and inhibits its ubiquitin hydrolyzing activity. Interacts with SAE2 and UBE2I.
messages: Cytoplasm
messages: Expressed predominantly in liver.
messages: Nucleus
messages: PML body
messages: Polymeric chains can be formed through Lys-11 cross-linking.
messages: Ubiquitin-like protein which can be covalently attached to target lysines either as a monomer or as a lysine-linked polymer. Does not seem to be involved in protein degradation and may function as an antagonist of ubiquitin in the degradation process. Plays a role in a number of cellular processes such as nuclear transport, DNA replication and repair, mitosis and signal transduction. Covalent attachment to its substrates requires prior activation by the E1 complex SAE1-SAE2 and linkage to the E2 enzyme UBE2I, and can be promoted by an E3 ligase such as PIAS1-4, RANBP2 or CBX4 (PubMed:11451954, PubMed:18538659, PubMed:21965678). Plays a role in the regulation of sumoylation status of SETX (PubMed:24105744).

9606:USP33
gene id: 9606:USP33
uniprot id: Q8TEY7
names: Developmental Stage
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the peptidase C19 family. USP20/USP33 subfamily.
messages: Deubiquitinating enzyme involved in various processes such as centrosome duplication, cellular migration and beta-2 adrenergic receptor/ADRB2 recycling. Involved in regulation of centrosome duplication by mediating deubiquitination of CCP110 in S and G2/M phase, leading to stabilize CCP110 during the period which centrioles duplicate and elongate. Involved in cell migration via its interaction with intracellular domain of ROBO1, leading to regulate the Slit signaling. Plays a role in commissural axon guidance cross the ventral midline of the neural tube in a Slit-dependent manner, possibly by mediating the deubiquitination of ROBO1. Acts as a regulator of G-protein coupled receptor (GPCR) signaling by mediating the deubiquitination of beta-arrestins (ARRB1 and ARRB2) and beta-2 adrenergic receptor (ADRB2). Plays a central role in ADRB2 recycling and resensitization after prolonged agonist stimulation by constitutively binding ADRB2, mediating deubiquitination of ADRB2 and inhibiting lysosomal trafficking of ADRB2. Upon dissociation, it is probably transferred to the translocated beta-arrestins, leading to beta-arrestins deubiquitination and disengagement from ADRB2. This suggests the existence of a dynamic exchange between the ADRB2 and beta-arrestins. Deubiquitinates DIO2, thereby regulating thyroid hormone regulation. Mediates deubiquitination of both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains.
messages: Golgi apparatus
messages: Increased expression in S and early G2 phases and lower levels in late G2 and M phases.
messages: Interacts with VHL, leading to its ubiquitination and subsequent degradation (PubMed:11739384). Interacts with ARRB1 and ARRB2 (PubMed:19363159). Interacts with ADRB2 (PubMed:19424180). Interacts with DIO2 (PubMed:12865408). Interacts with ROBO1. Interacts with SELENBP1; in a selenium-dependent manner (PubMed:19118533). Interacts with CCP110 (PubMed:23486064). Interacts with ADRB2 (PubMed:23166351).
messages: The UBP-type zinc finger binds 3 zinc ions. However, it does not bind ubiquitin, probably because the conserved Arg in position 86 is replaced by a Glu residue.
messages: Ubiquitinated via a VHL-dependent pathway for proteasomal degradation.
messages: Widely expressed.
messages: centrosome
messages: perinuclear region

9606:EYA4
gene id: 9606:EYA4
uniprot id: A0A0S2Z3Q2
uniprot id: A0A0S2Z3V9
uniprot id: B4DIV6
uniprot id: B4DRQ6
uniprot id: F2Z2Y1
uniprot id: O95677
uniprot id: Q96CJ7
names: Cofactor
names: Disease Annotation
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the HAD-like hydrolase superfamily. EYA family.
messages: Binds 1 Mg(2+) ion per subunit.
messages: Cytoplasm
messages: Highly expressed in heart and skeletal muscle.
messages: Interacts with SIX3; translocates EYA4 from the cytoplasm to the nucleus and promotes activation of their target genes.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Tyrosine phosphatase that specifically dephosphorylates 'Tyr-142' of histone H2AX (H2AXY142ph). 'Tyr-142' phosphorylation of histone H2AX plays a central role in DNA repair and acts as a mark that distinguishes between apoptotic and repair responses to genotoxic stress. Promotes efficient DNA repair by dephosphorylating H2AX, promoting the recruitment of DNA repair complexes containing MDC1. Its function as histone phosphatase probably explains its role in transcription regulation during organogenesis. May be involved in development of the eye (By similarity).

9606:NEB
gene id: 9606:NEB
uniprot id: P20929
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Monomer and homooligomer (PubMed:23615443). Interacts with TTN/titin (PubMed:12482578). Interacts with SVIL (PubMed:18639526). Interacts (via nebulin repeats 160-164) with DES (PubMed:23615443).
messages: Muscle specific. Located in the thin filament of striated muscle.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: This giant muscle protein may be involved in maintaining the structural integrity of sarcomeres and the membrane system associated with the myofibrils. Binds and stabilize F-actin.
messages: cytoskeleton
messages: sarcomere

9606:GEMIN4
gene id: 9606:GEMIN4
uniprot id: P57678
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Cytoplasm
messages: Nucleus
messages: Part of the core SMN complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8 and STRAP/UNRIP (PubMed:18984161, PubMed:16314521, PubMed:17178713). Part of the SMN-Sm complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8, STRAP/UNRIP and the Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG (PubMed:18984161, PubMed:16314521). Interacts with GEMIN3; the interaction is direct (PubMed:18984161, PubMed:17178713). Interacts with GEMIN5 (PubMed:33963192). Interacts with GEMIN8; the interaction is direct (PubMed:17178713). Interacts with several snRNP SM core proteins, including SNRPB, SNRPD1, SNRPD2, SNRPD3 and SNRPE (PubMed:18984161). Interacts with PPP4R2 (PubMed:12668731).
messages: The SMN complex catalyzes the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs. Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP (Sm core). In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP. To assemble core snRNPs, the SMN complex accepts the trapped 5Sm proteins from CLNS1A forming an intermediate. Binding of snRNA inside 5Sm triggers eviction of the SMN complex, thereby allowing binding of SNRPD3 and SNRPB to complete assembly of the core snRNP.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: gem
messages: nucleolus

9606:C16orf89
gene id: 9606:C16orf89
uniprot id: Q6UX73
names: Miscellaneous
names: PTM
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Aberrant splicing.
messages: Belongs to the UPF0764 family.
messages: Glycosylated.
messages: Homodimer.
messages: Major isoform, represents 80% of transcripts.
messages: Predominantly expressed in thyroid tissue.
messages: Secreted

9606:GPALPP1
gene id: 9606:GPALPP1
uniprot id: Q8IXQ4
names: Sequence Caution
messages: Contaminating sequence. Potential poly-A sequence.

9606:TYW3
gene id: 9606:TYW3
uniprot id: Q6IPR3
names: Function
names: Similarity
messages: Belongs to the TYW3 family.
messages: Probable S-adenosyl-L-methionine-dependent methyltransferase that acts as a component of the wybutosine biosynthesis pathway. Wybutosine is a hyper modified guanosine with a tricyclic base found at the 3'-position adjacent to the anticodon of eukaryotic phenylalanine tRNA (By similarity).

9606:POU1F1
gene id: 9606:POU1F1
uniprot id: P28069
names: Disease Annotation
names: Domain
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Altered in its ability to trans-activate compared to isoform B.
messages: Belongs to the POU transcription factor family. Class-1 subfamily.
messages: Interacts with PITX1 (PubMed:26612202). Interacts with LHX3 (PubMed:26612202). Interacts with ELK1 (PubMed:26612202).
messages: Nucleus
messages: The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Transcription factor involved in the specification of the lactotrope, somatotrope, and thyrotrope phenotypes in the developing anterior pituitary. Specifically binds to the consensus sequence 5'-TAAAT-3'. Activates growth hormone and prolactin genes (PubMed:22010633, PubMed:26612202).

9606:SYT2
gene id: 9606:SYT2
uniprot id: Q8N9I0
names: Cofactor
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the synaptotagmin family.
messages: Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2 domains.
messages: Cytoplasm
messages: Exhibits calcium-dependent phospholipid and inositol polyphosphate binding properties (By similarity). May have a regulatory role in the membrane interactions during trafficking of synaptic vesicles at the active zone of the synapse (By similarity). Plays a role in dendrite formation by melanocytes (PubMed:23999003).
messages: Expressed at the neuromuscular junction (PubMed:33659639). Expressed in melanocytes (PubMed:23999003).
messages: Homotetramer (Probable). Heterodimer; heterodimerizes with SYT1 in presence of calcium (By similarity). Interacts with STON2 (PubMed:11381094). Interacts with SCAMP5 (PubMed:19234194). Interacts with PRRT2 (By similarity).
messages: Phosphorylation at Thr-199 by WNK1, changes the calcium requirement for SYT2-binding to phospholipid membranes.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The first C2 domain mediates Ca(2+)-dependent phospholipid binding.
messages: The second C2 domain mediates interaction with Stonin 2. The second C2 domain mediates phospholipid and inositol polyphosphate binding in a calcium-independent manner.
messages: chromaffin granule membrane
messages: synaptic vesicle membrane

9606:ZNF737
gene id: 9606:ZNF737
uniprot id: O75373
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:MPHOSPH9
gene id: 9606:MPHOSPH9
uniprot id: Q99550
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: Golgi apparatus membrane
messages: Interacts with CCP110, CEP97 and KIF24.
messages: Negatively regulates cilia formation by recruiting the CP110-CEP97 complex (a negative regulator of ciliogenesis) at the distal end of the mother centriole in ciliary cells (PubMed:30375385). At the beginning of cilia formation, MPHOSPH9 undergoes TTBK2-mediated phosphorylation and degradation via the ubiquitin-proteasome system and removes itself and the CP110-CEP97 complex from the distal end of the mother centriole, which subsequently promotes cilia formation (PubMed:30375385).
messages: TTBK2-mediated phosphorylation at Ser-781 and Ser-788, promotes its ubiquitination at Lys-784 leading to proteasomal degradation, loss of MPHOSPH9 facilitates the removal of the CP110-CEP97 complex from the mother centrioles, promoting the initiation of ciliogenesis (PubMed:30375385). Phosphorylated in M (mitotic) phase (PubMed:8885239).
messages: Ubiquitinated at Lys-784, leading to proteasomal degradation.
messages: centriole
messages: centrosome

9606:TAF7L
gene id: 9606:TAF7L
uniprot id: Q5H9L4
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the TAF7 family.
messages: Cytoplasm
messages: Nucleus
messages: Probably functions as a spermatogenesis-specific component of the DNA-binding general transcription factor complex TFIID, a multimeric protein complex that plays a central role in mediating promoter responses to various activators and repressors. May play a role in spermatogenesis (By similarity).
messages: TFIID is composed of TATA binding protein (TBP) and a number of TBP-associated factors (TAFs). TAF7L may replace TAF7 in a spermatogenesis-specific form of TFIID. Interacts with TBP; the interaction occurs in a sub-population of cells (pachytene and haploid round spermatids) and is developmentally regulated through differential intracellular localization of the two proteins. Interacts with TAF1 (By similarity).
messages: Testis-specific.

9606:MAP3K4
gene id: 9606:MAP3K4
uniprot id: Q9Y6R4
names: Activity Regulation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.
messages: Component of a protein kinase signal transduction cascade. Activates the CSBP2, P38 and JNK MAPK pathways, but not the ERK pathway. Specifically phosphorylates and activates MAP2K4 and MAP2K6.
messages: Expressed at high levels in heart, placenta, skeletal muscle and pancreas, and at lower levels in other tissues.
messages: Monomer and homodimer. Homodimerization enhances kinase activity. Interacts with TRAF4; this promotes homodimerization (PubMed:16157600). Binds both upstream activators and downstream substrates in multimolecular complexes. Interacts with AXIN1 and DIXDC1; interaction with DIXDC1 prevents interaction with AXIN1 (PubMed:15262978). Interacts with GADD45 and MAP2K6 (PubMed:12052864). Interacts with ZFP36; this interaction enhances the association with SH3KBP1/CIN85 (PubMed:20221403). Interacts with SH3KBP1; this interaction enhances the association with ZFP36 (PubMed:20221403). Interacts with CDC42 (By similarity).
messages: N-terminal autoinhibitory domain interacts with the C-terminal kinase domain, inhibiting kinase activity, and preventing interaction with its substrate, MAP2K6. The GADD45 proteins activate the kinase by binding to the N-terminal domain. Activated by phosphorylation on Thr-1505.
messages: perinuclear region

9606:CEP70
gene id: 9606:CEP70
uniprot id: A0A140VJG2
uniprot id: B7Z2D2
uniprot id: Q8NHQ1
names: Domain
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Directly interacts with tubulin-gamma; this interaction determines centrosomal localization.
messages: Plays a role in the organization of both preexisting and nascent microtubules in interphase cells. During mitosis, required for the organization and orientation of the mitotic spindle.
messages: The coiled-coil domains may be important for tubulin-gamma-binding and hence for centrosomal localization.
messages: centrosome

9606:COPG1
gene id: 9606:COPG1
uniprot id: Q9Y678
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the COPG family.
messages: COPI-coated vesicle membrane
messages: Cytoplasm
messages: Golgi apparatus membrane
messages: Oligomeric complex that consists of at least the alpha, beta, beta', gamma, delta, epsilon and zeta subunits. Interacts with ZNF289/ARFGAP2 through its C-terminal appendage domain. Interacts with EGFR upon EGF treatment; interaction is essential for regulation of EGF-dependent nuclear transport of EGFR by retrograde trafficking from the Golgi to the ER. Interacts with COPB1. Interacts with TMED10 (via C-terminus). Interacts with TMED2, TMED3, TMED7 and TMED9.
messages: The coatomer is a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Golgi network. Coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins. In mammals, the coatomer can only be recruited by membranes associated to ADP-ribosylation factors (ARFs), which are small GTP-binding proteins; the complex also influences the Golgi structural integrity, as well as the processing, activity, and endocytic recycling of LDL receptors. Required for limiting lipid storage in lipid droplets. Involved in lipid homeostasis by regulating the presence of perilipin family members PLIN2 and PLIN3 at the lipid droplet surface and promoting the association of adipocyte triglyceride lipase (PNPLA2) with the lipid droplet surface to mediate lipolysis (By similarity).

9606:ANAPC2
gene id: 9606:ANAPC2
uniprot id: Q9UJX6
names: Function
names: Similarity
names: Subunit
messages: Belongs to the cullin family.
messages: The mammalian APC/C is composed at least of 14 distinct subunits ANAPC1, ANAPC2, CDC27/APC3, ANAPC4, ANAPC5, CDC16/APC6, ANAPC7, CDC23/APC8, ANAPC10, ANAPC11, CDC26/APC12, ANAPC13, ANAPC15 and ANAPC16 that assemble into a complex of at least 19 chains with a combined molecular mass of around 1.2 MDa; APC/C interacts with FZR1 and FBXO5 (PubMed:25043029, PubMed:26083744). In the context of the APC/C complex, directly interacts with UBE2C and UBE2S (PubMed:27259151). Interacts (via cullin domain) with ANAPC11 and with UBCH10 (PubMed:11739784). Interacts with NEUROD2 (By similarity). Interacts with FBXO43; the interaction is direct.
messages: Together with the RING-H2 protein ANAPC11, constitutes the catalytic component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains. The CDC20-APC/C complex positively regulates the formation of synaptic vesicle clustering at active zone to the presynaptic membrane in postmitotic neurons. CDC20-APC/C-induced degradation of NEUROD2 drives presynaptic differentiation.

9606:CCL3L3
gene id: 9606:CCL3L3
uniprot id: P16619
names: Function
names: PTM
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the intercrine beta (chemokine CC) family.
messages: Chemotactic for lymphocytes and monocytes. Is a ligand for CCR1, CCR3 and CCR5. Is an inhibitor of HIV-1-infection. The processed form LD78-beta(3-70) shows a 20-fold to 30-fold higher chemotactic activity and is a very potent inhibitor of HIV-1-infection. LD78-beta(3-70) is also a ligand for CCR1, CCR3 and CCR5.
messages: Secreted
messages: The N-terminal processed forms LD78-beta(3-70) and LD78-beta(5-70) are produced by proteolytic cleavage after secretion from peripheral blood monocytes. The cleavage to yield LD78-beta(3-70) is probably achieved by DPP4.
messages: The copy number of the CCL3L1 gene varies among individuals; most individuals have 1-6 copies in the diploid genome, although rare individuals have zero or more than 6 copies.

9606:TFPI
gene id: 9606:TFPI
uniprot id: P10646
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Subcellular Location Annotation
names: Tissue Specificity
messages: GPI-anchored.
messages: Inhibits factor X (X(a)) directly and, in a Xa-dependent way, inhibits VIIa/tissue factor activity, presumably by forming a quaternary Xa/LACI/VIIa/TF complex. It possesses an antithrombotic action and also the ability to associate with lipoproteins in plasma.
messages: Microsome membrane
messages: Mostly in endothelial cells.
messages: O-glycosylated.
messages: Secreted
messages: This inhibitor contains three inhibitory domains. The first domain interacts with VIIa and TF, the second one with Xa.

9606:CD6
gene id: 9606:CD6
uniprot id: P30203
uniprot id: Q6AZ88
uniprot id: Q8N4Q7
names: Caution
names: Function
names: Miscellaneous
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: After T-cell activation, becomes hyperphosphorylated on Ser and Thr residues and phosphorylated on Tyr residues.
messages: Cell adhesion molecule that mediates cell-cell contacts and regulates T-cell responses via its interaction with ALCAM/CD166 (PubMed:15048703, PubMed:15294938, PubMed:16352806, PubMed:16914752, PubMed:24945728, PubMed:24584089). Contributes to signaling cascades triggered by activation of the TCR/CD3 complex (PubMed:24584089). Functions as costimulatory molecule; promotes T-cell activation and proliferation (PubMed:15294938, PubMed:16352806, PubMed:16914752). Contributes to the formation and maturation of the immunological synapse (PubMed:15294938, PubMed:16352806). Functions as calcium-dependent pattern receptor that binds and aggregates both Gram-positive and Gram-negative bacteria. Binds both lipopolysaccharide (LPS) from Gram-negative bacteria and lipoteichoic acid from Gram-positive bacteria (PubMed:17601777). LPS binding leads to the activation of signaling cascades and down-stream MAP kinases (PubMed:17601777). Mediates activation of the inflammatory response and the secretion of pro-inflammatory cytokines in response to LPS (PubMed:17601777).
messages: Cell membrane
messages: Detected on thymocytes (PubMed:15294938). Detected on peripheral blood T-cells (PubMed:15048703, PubMed:16352806). Detected on natural killer (NK) cells (PubMed:16352806). Soluble CD6 is detected in blood serum (at protein level) (PubMed:17601777). Detected in spleen, thymus, appendix, lymph node and peripheral blood leukocytes (PubMed:9013954). Expressed by thymocytes, mature T-cells, a subset of B-cells known as B-1 cells, and by some cells in the brain.
messages: Glycosylated.
messages: Interacts (via extracellular domain) with ALCAM/CD166 (via extracellular domain) (PubMed:15048703, PubMed:16352806, PubMed:16914752, PubMed:24945728, PubMed:26146185). Interacts with the TCR/CD3 complex subunit CD3E (PubMed:15294938). Interacts (via tyrosine phosphorylated C-terminus) with LCP2 (via SH2 domain) (PubMed:16914752). Interacts with VAV1 (By similarity). Interacts (via glycosylated extracellular domain) with LGALS1 and LGALS3 (PubMed:24945728). Interaction with LGALS1 or LGALS3 inhibits interaction with ALCAM (PubMed:24945728).
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: Lacks the third SRCR domain and doesn't bind ALCAM/CD166. Doesn't localize to the immunological synapse.
messages: Lacks the third SRCR domain and doesn't bind ALCAM/CD166. Doesn't localize to the immunological synapse. Constitutes the only expressed species in a small percentage of T-cells.
messages: Secreted

9606:KRT72
gene id: 9606:KRT72
uniprot id: Q14CN4
names: Caution
names: Function
names: Miscellaneous
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Belongs to the intermediate filament family.
messages: Has a role in hair formation. Specific component of keratin intermediate filaments in the inner root sheath (IRS) of the hair follicle (Probable).
messages: Heterotetramer of two type I and two type II keratins.
messages: Highly expressed in hair follicles from scalp and eyebrow. Also expressed in palmoplantar epidermis. Not expressed in face skin despite the presence of fine hairs histologically. In hair, it is specifically present in the inner root sheath (IRS) of the hair follicle. Present in the IRS cuticle, but not in Henle or Huxley layers of the IRS. In the IRS cuticle, its presence is delayed up to the height of the apex of the dermal papilla (at protein level).
messages: There are two types of cytoskeletal and microfibrillar keratin, I (acidic) and II (neutral to basic) (40-55 and 56-70 kDa, respectively).
messages: Was initially thought to be the ortholog of mouse KRT71.

9606:TLR8
gene id: 9606:TLR8
uniprot id: Q9NR97
names: Activity Regulation
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Activated by RNAs having enough uridines.
messages: Belongs to the Toll-like receptor family.
messages: Endosomal receptor that plays a key role in innate and adaptive immunity (PubMed:25297876, PubMed:32433612). Controls host immune response against pathogens through recognition of RNA degradation products specific to microorganisms that are initially processed by RNASET2 (PubMed:31778653). Recognizes GU-rich single-stranded RNA (GU-rich RNA) derived from SARS-CoV-2, SARS-CoV-1 and HIV-1 viruses (PubMed:33718825). Upon binding to agonists, undergoes dimerization that brings TIR domains from the two molecules into direct contact, leading to the recruitment of TIR-containing downstream adapter MYD88 through homotypic interaction (PubMed:23520111, PubMed:25599397, PubMed:26929371, PubMed:33718825). In turn, the Myddosome signaling complex is formed involving IRAK4, IRAK1, TRAF6, TRAF3 leading to activation of downstream transcription factors NF-kappa-B and IRF7 to induce pro-inflammatory cytokines and interferons, respectively (PubMed:16737960, PubMed:17932028, PubMed:29155428).
messages: Endosome membrane
messages: Expressed in myeloid dendritic cells, monocytes, and monocyte-derived dendritic cells.
messages: Homodimer (PubMed:23520111, PubMed:25599397, PubMed:26929371, PubMed:29155428). Interacts with MYD88 via their respective TIR domains (Probable). Interacts with UNC93B1 (By similarity). Interacts with BTK (PubMed:17932028). Interacts with SMPDL3B (By similarity).
messages: Proteolytic processing occurs in monocytes and monocyte-derived macrophages by both furin-like proprotein convertase and cathepsins (PubMed:25297876). The cleavage is necessary for dimer formation and subsequent activation (PubMed:26929371).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitinated by RNF216; leading to degradation by the proteasome.

9606:KLC1
gene id: 9606:KLC1
uniprot id: Q07866
uniprot id: Q7RTQ2
names: Caution
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts with adenovirus hexon-interlacing protein; this interaction leads to capsid disruption at the nuclear pore complex during virus entry into host cell.
messages: Belongs to the kinesin light chain family.
messages: Cytoplasmic vesicle
messages: Found in a variety of tissues. Mostly abundant in brain and spine.
messages: It is uncertain whether Met-1 or Met-5 is the initiator.
messages: Kinesin is a microtubule-associated force-producing protein that may play a role in organelle transport (PubMed:21385839). The light chain may function in coupling of cargo to the heavy chain or in the modulation of its ATPase activity (By similarity).
messages: Kinesin is a microtubule-associated force-producing protein that play a role in organelle transport.
messages: Oligomeric complex composed of two heavy chains and two light chains.
messages: Oligomeric complex composed of two heavy chains and two light chains. Interacts with SPAG9 (By similarity). Interacts with ATCAY; may link mitochondria to KLC1 and regulate mitochondria localization into neuron projections (By similarity). Interacts (via TPR repeats) with TOR1A; the interaction associates TOR1A with the kinesin oligomeric complex (PubMed:14970196). Interacts with BORCS5 (PubMed:25898167). Interacts with MAPK8IP3/JIP3 and NTRK2/TRKB; interaction with NTRK2/TRKB is mediated by MAPK8IP3/JIP3 (By similarity). Interacts with CLSTN1; phosphorylation at Ser-460 inhibits interaction with CLSTN1 (PubMed:21385839).
messages: Phosphorylation at Ser-460 by ERK inhibits interaction with CLSTN1 and localization to cytoplasmic vesicles.
messages: cytoskeleton
messages: growth cone

9606:VCX2
gene id: 9606:VCX2
uniprot id: Q9H322
names: Function
names: Similarity
names: Tissue Specificity
messages: Belongs to the VCX/VCY family.
messages: Expressed exclusively in testis.
messages: May mediate a process in spermatogenesis or may play a role in sex ratio distortion.

9606:RIN3
gene id: 9606:RIN3
uniprot id: Q6NSK7
uniprot id: Q6ZRC2
uniprot id: Q8TB24
names: Function
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Aberrant splicing.
messages: Belongs to the RIN (Ras interaction/interference) family.
messages: Cytoplasm
messages: Cytoplasmic vesicle
messages: Early endosome
messages: Interacts with CD2AP, RAB5B, RAB31 and BIN1.
messages: Intron retention.
messages: Ras effector protein that functions as a guanine nucleotide exchange (GEF) for RAB5B and RAB31, by exchanging bound GDP for free GTP. Required for normal RAB31 function.
messages: Widely expressed.

9606:MORN5
gene id: 9606:MORN5
uniprot id: Q5VZ52
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Expressed in sperm (at protein level).
messages: flagellum

9606:GOLGA8N
gene id: 9606:GOLGA8N
uniprot id: F8WBI6
names: Similarity
messages: Belongs to the GOLGA8 family.

9606:MS4A15
gene id: 9606:MS4A15
uniprot id: B4DTI9
uniprot id: Q8N5U1
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the MS4A family.
messages: May be involved in signal transduction as a component of a multimeric receptor complex.
messages: Membrane

9606:SLC35A2
gene id: 9606:SLC35A2
uniprot id: A6NFI1
uniprot id: A6NKM8
uniprot id: B4DE15
uniprot id: P78381
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the nucleotide-sugar transporter family. SLC35A subfamily.
messages: Endoplasmic reticulum membrane
messages: Golgi apparatus membrane
messages: Interacts with B4GALT4.
messages: Interacts with SLC35A3; the interaction is reduced in the presence of SLC35A4 (PubMed:23089177, PubMed:28167211). Found in a complex with SLC35A3 and SLC35A4 (PubMed:28167211).
messages: Membrane
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Transports uridine diphosphate galactose (UDP-galactose) from the cytosol into the Golgi apparatus, functioning as an antiporter that exchanges UDP-galactose for UMP (PubMed:9010752, PubMed:12682060). It is also able to exchange UDP-galactose for AMP and CMP, and to transport UDP-N-acetylgalactosamine (UDP-GalNAc) and other nucleotide sugars (PubMed:12682060, PubMed:11784306). As a provider of UDP-galactose to galactosyltransferases present in the Golgi apparatus, it is necessary for globotriaosylceramide/globoside (Gb3Cer) synthesis from lactosylceramide (PubMed:30817854).

9606:RCSD1
gene id: 9606:RCSD1
uniprot id: Q6JBY9
names: Function
names: PTM
names: Subunit
names: Tissue Specificity
messages: Dephosphorylation results in its dissociation from CAPZA2.
messages: Highly expressed in skeletal muscle and more weakly in cardiac muscle. Also expressed in several lymphoid organs, including spleen, thymus, peripheral blood leukocytes, lymph node and bone marrow.
messages: Interacts with CAPZA2 and CAPZB.
messages: Stress-induced phosphorylation of CAPZIP may regulate the ability of F-actin-capping protein to remodel actin filament assembly.

9606:FKBP14
gene id: 9606:FKBP14
uniprot id: Q9NWM8
names: Activity Regulation
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Endoplasmic reticulum lumen
messages: Inhibited by tacrolimus/FK506.
messages: Monomer (PubMed:24821723, PubMed:24272907). Homodimer (PubMed:24821723, PubMed:24272907). Interacts with type III, type IV and type X collagens (PubMed:24821723).
messages: PPIase which accelerates the folding of proteins during protein synthesis. Has a preference for substrates containing 4-hydroxylproline modifications, including type III collagen. May also target type VI and type X collagens.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:BBC3
gene id: 9606:BBC3
uniprot id: Q96PG8
uniprot id: Q9BXH1
names: Domain
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the Bcl-2 family.
messages: Contrary to isoforms 1 and 2, isoforms 3 and 4 do not contain any BH3 motif.
messages: Does not affect cell growth.
messages: Does not interact with BCL2.
messages: Essential mediator of p53/TP53-dependent and p53/TP53-independent apoptosis (PubMed:11463391, PubMed:23340338). Promotes partial unfolding of BCL2L1 and dissociation of BCL2L1 from p53/TP53, releasing the bound p53/TP53 to induce apoptosis (PubMed:23340338). Regulates ER stress-induced neuronal apoptosis (By similarity).
messages: Interacts with MCL1 and BCL2A1 (By similarity). Interacts (via BH3 domain) with BCL2 (PubMed:11463391). Interacts with BCL2L1/BCL-XL (PubMed:23340338). Interacts (via BH3 domain) with NOL3/ARC (via CARD domain); this interaction prevents BBC3 association with BCL2 and results in CASP8 activation (By similarity).
messages: Mitochondrion
messages: The BH3 motif is intrinsically disordered in the absence of a binding partner but folds upon binding (PubMed:23340338). Folds when bound to BCL2L1 (PubMed:23340338). Also folds when bound to MCL1 (By similarity).
messages: Ubiquitously expressed.
messages: Up-regulated by TP53 (PubMed:11463392, PubMed:11572983). Up-regulated by DNA damage, glucocorticoid treatment and growth factor deprivation (PubMed:11572983). Up-regulated by ER stress in a DDIT3/CHOP-dependent manner (PubMed:22761832).
messages: Up-regulated by TP53.

9606:CHIC2
gene id: 9606:CHIC2
uniprot id: Q9UKJ5
names: Disease Annotation
names: PTM
names: Similarity
names: Subcellular Location Annotation
messages: A chromosomal aberration involving CHIC2 is found in a form of acute myeloid leukemia (AML). Translocation t(4;12)(q12;p13) with ETV6.
messages: Belongs to the CHIC family.
messages: Cell membrane
messages: Cytoplasmic vesicle
messages: Palmitoylation in the CHIC motif is required for membrane association.

9606:DIAPH1
gene id: 9606:DIAPH1
uniprot id: A0A2R8Y5N1
uniprot id: O60610
uniprot id: Q6URC4
names: Developmental Stage
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Actin nucleation and elongation factor required for the assembly of F-actin structures, such as actin cables and stress fibers (By similarity). Binds to the barbed end of the actin filament and slows down actin polymerization and depolymerization (By similarity). Required for cytokinesis, and transcriptional activation of the serum response factor (By similarity). DFR proteins couple Rho and Src tyrosine kinase during signaling and the regulation of actin dynamics (By similarity). Functions as a scaffold protein for MAPRE1 and APC to stabilize microtubules and promote cell migration (By similarity). Has neurite outgrowth promoting activity. Acts in a Rho-dependent manner to recruit PFY1 to the membrane (By similarity). In hear cells, it may play a role in the regulation of actin polymerization in hair cells (PubMed:20937854, PubMed:21834987, PubMed:26912466). The MEMO1-RHOA-DIAPH1 signaling pathway plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex (PubMed:20937854, PubMed:21834987). It controls the localization of APC and CLASP2 to the cell membrane, via the regulation of GSK3B activity (PubMed:20937854, PubMed:21834987). In turn, membrane-bound APC allows the localization of the MACF1 to the cell membrane, which is required for microtubule capture and stabilization (PubMed:20937854, PubMed:21834987). Plays a role in the regulation of cell morphology and cytoskeletal organization. Required in the control of cell shape (PubMed:20937854, PubMed:21834987). Plays a role in brain development (PubMed:24781755). Also acts as an actin nucleation and elongation factor in the nucleus by promoting nuclear actin polymerization inside the nucleus to drive serum-dependent SRF-MRTFA activity (By similarity).
messages: Belongs to the formin homology family. Diaphanous subfamily.
messages: Cell membrane
messages: Cytoplasm
messages: Expressed in brain, heart, placenta, lung, kidney, pancreas, liver, skeletal muscle and cochlea. Expressed in platelets (PubMed:26912466).
messages: Homodimer (By similarity). Interacts with the GTP-bound form of RHOA (PubMed:23325789). Interacts with RHOC, PFY1, MAPRE1 and BAIAP2 (By similarity). Interacts with APC; acts as a scaffold protein for MAPRE1 and APC to stabilize microtubules and promote cell migration (By similarity). Interacts with SCAI (By similarity). Interacts with DCAF7, via FH2 domain (By similarity). Interacts with NCDN (By similarity). Interacts with OSBPL10, OSBPL2, VIM, TUBB and DYN1 (PubMed:23325789).
messages: Intron retention.
messages: Nucleus
messages: Phosphorylation at Thr-768 is stimulated by cAMP and regulates stability, complex formation and mitochondrial movement.
messages: Strongly expressed in ventricular and subventricular zone progenitor cells of the neocortical wall at 12 weeks post-conception.
messages: The DAD domain regulates activation via by an autoinhibitory interaction with the GBD/FH3 domain (By similarity). This autoinhibition is released upon competitive binding of an activated GTPase (By similarity). The release of DAD allows the FH2 domain to then nucleate and elongate nonbranched actin filaments (By similarity).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: centrosome
messages: cytoskeleton
messages: ruffle membrane
messages: spindle

9606:UGT2B15
gene id: 9606:UGT2B15
uniprot id: P54855
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the UDP-glycosyltransferase family.
messages: Endoplasmic reticulum membrane
messages: Expressed in many tissues. Present in liver, prostate and testis.
messages: UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:7835232, PubMed:9295060, PubMed:16595710, PubMed:18719240, PubMed:23288867). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:7835232). Catalyzes the glucuronidation of endogenous steroid hormones such as androgens (testosterone, androsterone) and estrogens (estradiol, epiestradiol, estriol, catechol estrogens) (PubMed:7835232, PubMed:9295060, PubMed:16595710, PubMed:18719240, PubMed:23288867). Displays glucuronidation activity toward several classes of xenobiotic substrates, including phenolic compounds (eugenol, 4-nitrophenol, 4-hydroxybiphenyl) and phenylpropanoids (naringenin, coumarins) (PubMed:7835232). Catalyzes the glucuronidation of monoterpenoid alcohols such as borneol, menthol and isomenthol, a class of natural compounds used in essential oils (By similarity).

9606:DECR2
gene id: 9606:DECR2
uniprot id: Q9NUI1
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Auxiliary enzyme of beta-oxidation. Participates in the degradation of unsaturated fatty enoyl-CoA esters having double bonds in both even- and odd-numbered positions in peroxisome. Catalyzes the NADP-dependent reduction of 2,4-dienoyl-CoA to yield trans-3-enoyl-CoA. Has activity towards short and medium chain 2,4-dienoyl-CoAs, but also towards 2,4,7,10,13,16,19-docosaheptaenoyl-CoA, suggesting that it does not constitute a rate limiting step in the peroxisomal degradation of docosahexaenoic acid.
messages: Belongs to the short-chain dehydrogenases/reductases (SDR) family. 2,4-dienoyl-CoA reductase subfamily.
messages: Monomer, dimer and oligomer.
messages: Peroxisome

9606:POTEH
gene id: 9606:POTEH
uniprot id: Q6S545
names: Similarity
messages: Belongs to the POTE family.

9606:ZXDA
gene id: 9606:ZXDA
uniprot id: P98168
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the ZXD family.
messages: Cooperates with CIITA to promote transcription of MHC class I and MHC class II genes.
messages: May be expressed in brain, heart, kidney, liver, lung, muscle and placenta.
messages: Nucleus
messages: Self-associates. Interacts with ZXDC and CIITA.

9606:LRRC39
gene id: 9606:LRRC39
uniprot id: Q96DD0
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Component of the sarcomeric M-band which plays a role in myocyte response to biomechanical stress. May regulate expression of other M-band proteins via an SRF-dependent pathway. Important for normal contractile function in heart.
messages: Highly expressed in skeletal muscle and heart. Not detected in other tissues tested.
messages: Interacts with MYH7 (via C-terminus).
messages: M line

9606:ZSWIM8
gene id: 9606:ZSWIM8
uniprot id: A7E2V4
names: Function
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Aberrant splicing.
messages: Belongs to the ZSWIM8 family.
messages: Component of the SCF-like E3 ubiquitin-protein ligase complex which contains CUL3, RBX1, ELOB, ELOC and ZSWIM8.
messages: Probable cloning artifact.
messages: Substrate recognition component of a SCF-like E3 ubiquitin-protein ligase complex that promotes target-directed microRNA degradation (TDMD), a process that mediates degradation of microRNAs (miRNAs) (PubMed:33184234, PubMed:33184237). The SCF-like E3 ubiquitin-protein ligase complex acts by catalyzing ubiquitination and subsequent degradation of AGO proteins (AGO1, AGO2, AGO3 and/or AGO4), thereby exposing miRNAs for degradation (PubMed:33184234, PubMed:33184237). Specifically recognizes and binds AGO proteins when they are engaged with a TDMD target (PubMed:33184234). May also act as a regulator of axon guidance: specifically recognizes misfolded ROBO3 and promotes its ubiquitination and subsequent degradation (PubMed:24012004).
messages: cytosol

9606:TMEM53
gene id: 9606:TMEM53
uniprot id: Q5TDE2
uniprot id: Q6P2H8
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the TMEM53 family.
messages: Ensures normal bone formation, through the negative regulation of bone morphogenetic protein (BMP) signaling in osteoblast lineage cells by blocking cytoplasm-nucleus translocation of phosphorylated SMAD1/5/9 proteins.
messages: Membrane
messages: Nucleus outer membrane
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Widely expressed.

9606:ZNF704
gene id: 9606:ZNF704
uniprot id: Q6ZNC4
names: Domain
names: Function
names: Subcellular Location Annotation
messages: Nucleus
messages: The CR1 and CR2 motifs mediate sequence-specific DNA binding, and are important for binding to the MYOD1 enhancer.
messages: Transcription factor which binds to RE2 sequence elements in the MYOD1 enhancer.

9606:NEUROG1
gene id: 9606:NEUROG1
uniprot id: Q92886
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acts as a transcriptional regulator. Involved in the initiation of neuronal differentiation. Activates transcription by binding to the E box (5'-CANNTG-3'). Associates with chromatin to enhancer regulatory elements in genes encoding key transcriptional regulators of neurogenesis (By similarity).
messages: Efficient DNA binding requires dimerization with another bHLH protein.
messages: Expression restricted to the embryonic nervous system.
messages: Nucleus

9606:DEFA5
gene id: 9606:DEFA5
uniprot id: Q01523
names: Caution
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Acts as a target for S.flexneri infection by binding to the bacterium, possibly via bacterial surface proteins, and thereby augmenting infectivity via enhanced bacterial adhesion and invasion of epithelial cells and tissues.
messages: (Microbial infection) The disulfide bridges and homodimerization are a prerequisite for the enhancement of S.flexneri adhesion and invasion.
messages: Belongs to the alpha-defensin family.
messages: Expressed in the gastrointestinal, reproductive, and urinary tracts (at protein level) (PubMed:1429669, PubMed:12021776, PubMed:9588893, PubMed:22359618). Expressed in Paneth cells of the small intestine (at protein level) (PubMed:1429669, PubMed:12021776). Expressed throughout the urothelium of the lower urinary tract and in the collecting tubules of the kidney (at protein level) (PubMed:22359618). Expressed in stratified squamous epithelial cells of the female genital tract epithelia, such as in vagina, ectocervix, endocervix, endometrium, and fallopian tube (at protein level) (PubMed:9588893). Endometrial expression correlates with stages of the menstrual cycle: Expression is low during the early proliferative phase, increased during the mid- to late proliferative phase, peaks during the early secretory phase of the cycle, and decreases during the mid- to late secretory phase (PubMed:9588893).
messages: Glycosylated.
messages: Homodimer (PubMed:17088326, PubMed:22573326, PubMed:25782105, PubMed:29858013). Homotetramer (PubMed:23163963). Interacts with B.antracis lef/lethal factor (PubMed:22573326).
messages: Host-defense peptide that maintains sterility in the urogenital system (PubMed:12021776, PubMed:12660734, PubMed:15616305, PubMed:22359618, PubMed:25354318, PubMed:30808760, PubMed:19589339, PubMed:22573326, PubMed:25782105). Has antimicrobial activity against a wide range of bacteria, including Gram-negative E.coli, P.aeruginosa and S.typhimurium, and Gram-positive E.aerogenes, S.aureus, B.cereus, E.faecium and L.monocytogenes (PubMed:12021776, PubMed:15616305, PubMed:22359618, PubMed:25354318, PubMed:30808760, PubMed:19589339, PubMed:22573326). Confers resistance to intestinal infection by S.typhimurium (PubMed:12660734). Exhibits antimicrobial activity against enteric commensal bacteria such as B.adolescentis, L.acidophilus, B.breve, L.fermentum, B.longum and S.thermophilus (PubMed:25354318). Binds to bacterial membranes and causes membrane disintegration (PubMed:25782105). Induces the secretion of the chemokine IL-8 by intestinal epithelial cells (PubMed:19589339). Binds to B.antracis lef/lethal factor, a major virulence factor from B.anthracis, and neutralizes its enzymatic activity (PubMed:22573326).
messages: It was shown by two studies that dimerization of DEFA5 is crucial for antimicrobial activity (PubMed:17088326, PubMed:22573326). Another study, however, states that dimer formation is not indispensable for antimicrobial activity of DEFA5 (PubMed:25782105).
messages: Proteolytically cleaved at Arg-62 by trypsin (PubMed:12021776). Both the propeptide form proHD5/HD5(20-94) and HD5(56-94) are cleaved into the lumenal peptide form HD5(63-94) by trypsin (PubMed:12021776). Unprocessed proHD5 exerts antimicrobial activities, but peptide potency is enhanced by peptide processing (PubMed:12021776). Proteolytically cleaved in duodenal fluid; derived fragments are antimicrobially active against commensal bacteria (in vitro) (PubMed:30808760).
messages: Secreted
messages: Up-regulated in fallopian tubes upon infection (PubMed:9588893). Increased expression in kidneys with pyelonephritis (PubMed:22359618).
messages: secretory vesicle

9606:TMEM185A
gene id: 9606:TMEM185A
uniprot id: Q8NFB2
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the TMEM185 family.
messages: Interacts with MAP1B.
messages: Membrane
messages: dendrite

9606:GSTP1
gene id: 9606:GSTP1
uniprot id: P09211
uniprot id: V9HWE9
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the GST superfamily. Pi family.
messages: Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.
messages: Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Involved in the formation of glutathione conjugates of both prostaglandin A2 (PGA2) and prostaglandin J2 (PGJ2) (PubMed:9084911). Participates in the formation of novel hepoxilin regioisomers (PubMed:21046276). Regulates negatively CDK5 activity via p25/p35 translocation to prevent neurodegeneration.
messages: Cytoplasm
messages: Homodimer.
messages: Homodimer. Interacts with CDK5.
messages: Mitochondrion
messages: Nucleus

9606:GARS1
gene id: 9606:GARS1
uniprot id: P41250
names: Activity Regulation
names: Disease Annotation
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Ap4A synthesis is inhibited by tRNA, via the disruption of the second ATP-binding site by direct blocking and/or by tRNA-induced conformational change.
messages: Belongs to the class-II aminoacyl-tRNA synthetase family.
messages: Catalyzes the ATP-dependent ligation of glycine to the 3'-end of its cognate tRNA, via the formation of an aminoacyl-adenylate intermediate (Gly-AMP) (PubMed:17544401, PubMed:28675565, PubMed:24898252). Also produces diadenosine tetraphosphate (Ap4A), a universal pleiotropic signaling molecule needed for cell regulation pathways, by direct condensation of 2 ATPs. Thereby, may play a special role in Ap4A homeostasis (PubMed:19710017).
messages: Cytoplasm
messages: Expressed in brain, spinal cord, muscle, heart and spleen.
messages: Expressed in brain, spinal cord, muscle, heart, spleen and liver.
messages: Homodimer.
messages: Human GlyRS uses direct ATP condensation to synthesize Ap4A, a unique amino acid-independent mechanism, in contrast to the classical amino acid-dependent mechanism for synthesis of Ap4A by a tRNA synthetase, that involves the generation of an enzyme-bound aminoacyl-AMP which is then attacked by ATP to form Ap4A.
messages: Mitochondrion
messages: Secreted
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The isoform 2 translation is regulated by an Internal Ribosome Entry Site (IRES) and an upstream Open Reading Frame. Both are important in hindering the synthesis of the mitochondrial GARS and target the translation of the cytosolic enzyme to ER-bound ribosomes.
messages: Widely expressed, including in brain and spinal cord.
messages: axon
messages: extracellular exosome

9606:KLKB1
gene id: 9606:KLKB1
uniprot id: P03952
names: Activity Regulation
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the peptidase S1 family. Plasma kallikrein subfamily.
messages: Forms a heterodimer with SERPINA5. The zymogen is activated by factor XIIa, which cleaves the molecule into a light chain, which contains the active site, and a heavy chain, which associates with HMW kininogen. These chains are linked by one or more disulfide bonds.
messages: Inhibited by SERPINA5.
messages: Secreted
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The enzyme cleaves Lys-Arg and Arg-Ser bonds. It activates, in a reciprocal reaction, factor XII after its binding to a negatively charged surface. It also releases bradykinin from HMW kininogen and may also play a role in the renin-angiotensin system by converting prorenin into renin.

9606:PARD3B
gene id: 9606:PARD3B
uniprot id: Q8TEW8
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the PAR3 family.
messages: Cell junction
messages: Endomembrane system
messages: Highly expressed in kidney, lung and skeletal muscle. Expressed at intermediate levels in brain, heart, placenta, liver and pancreas. Isoform 1 is predominant, while isoform 2 and isoform 3 are expressed at lower levels.
messages: Interacts with PARD6B. Interacts with INSC/inscuteable.
messages: Putative adapter protein involved in asymmetrical cell division and cell polarization processes. May play a role in the formation of epithelial tight junctions.
messages: The N-terminal part (1-351) part blocks the association of the tight junction marker TJP1 with the cell-cell boundary when it is overexpressed.
messages: tight junction

9606:CTSO
gene id: 9606:CTSO
uniprot id: P43234
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the peptidase C1 family.
messages: Expressed in all tissues examined. High levels seen in the ovary, kidney and placenta while low levels seen in thymus and skeletal muscle.
messages: Lysosome
messages: Proteolytic enzyme possibly involved in normal cellular protein degradation and turnover.

9606:NRAP
gene id: 9606:NRAP
uniprot id: Q86VF7
names: Function
names: Sequence Caution
names: Subunit
names: Tissue Specificity
messages: Contaminating sequence. Potential poly-A sequence.
messages: Expressed in cardiac and skeletal muscle.
messages: Interacts with actin, alpha-actinin, KLHL41, TLN1 and VCL. Interacts with CSRP3.
messages: May be involved in anchoring the terminal actin filaments in the myofibril to the membrane and in transmitting tension from the myofibrils to the extracellular matrix.

9606:ZFP69
gene id: 9606:ZFP69
uniprot id: Q49AA0
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: Expressed in visceral and subcutaneous adipose tissue.
messages: Nucleus
messages: Putative transcription factor that appears to regulate lipid metabolism.
messages: Up-regulated in both visceral and subcutaneous adipose tissue of diabetic individuals.

9606:G6PC2
gene id: 9606:G6PC2
uniprot id: Q9NQR9
names: Function
names: PTM
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the glucose-6-phosphatase family.
messages: Endoplasmic reticulum membrane
messages: Genetic variations in G6PC2 define the fasting plasma glucose levels quantitative trait locus 1 (FGQTL1) [MIM:612108]. The normal fasting plasma glucose level in the plasma is defined as less than 100 mg per deciliter (5.55 mmol per liter). Higher fasting plasma glucose levels predict type 2 diabetes in young adults and increases the risk of mortality.
messages: May hydrolyze glucose-6-phosphate to glucose in the endoplasmic reticulum. May be responsible for glucose production through glycogenolysis and gluconeogenesis (By similarity).
messages: N-glycosylated; the non-glycosylated form is more unstable and is degraded through the proteasome.
messages: Specifically expressed in pancreas and also detected to a lower extent in testis. Expressed by most islet cells in the pancreas (at protein level).

9606:C16orf82
gene id: 9606:C16orf82
uniprot id: Q7Z2V1
names: Tissue Specificity
messages: Preferentially expressed in teratocarcinoma rather than in normal testis.

9606:ZNF565
gene id: 9606:ZNF565
uniprot id: Q8N9K5
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:ENDOD1
gene id: 9606:ENDOD1
uniprot id: O94919
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the DNA/RNA non-specific endonuclease family.
messages: Interacts with RNF26; this interaction is important to modulate innate immune signaling through the cGAS-STING pathway (PubMed:32614325).
messages: May act as a DNase and a RNase. Plays a role in the modulation of innate immune signaling through the cGAS-STING pathway by interacting with RNF26.
messages: Secreted

9606:KIF21A
gene id: 9606:KIF21A
uniprot id: Q7Z4S6
names: Disease Annotation
names: Function
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family.
messages: Contaminating sequence. Potential poly-A sequence.
messages: Interacts (via residues 1146-1167) with KANK1 (via ankyrin repeats 1-5) and KANK2 (via ankyrin repeats 1-5).
messages: Microtubule-binding motor protein probably involved in neuronal axonal transport. In vitro, has a plus-end directed motor activity.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: axon
messages: cytoskeleton
messages: dendrite

9606:ZNF33A
gene id: 9606:ZNF33A
uniprot id: Q06730
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: Interacts with MAP3K20/ZAK.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:ASAP3
gene id: 9606:ASAP3
uniprot id: Q8TDY4
names: Function
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Cytoplasm
messages: Highly expressed in primary hepatocarcinoma. Detected in lung, liver and blood leukocytes.
messages: Promotes cell proliferation.

9606:SYNDIG1
gene id: 9606:SYNDIG1
uniprot id: Q9H7V2
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the CD225/Dispanin family.
messages: Cell membrane
messages: Early endosome membrane
messages: Homodimer. Interacts with GRIA1 and GRIA2 (By similarity).
messages: May regulate AMPA receptor content at nascent synapses, and have a role in postsynaptic development and maturation.
messages: Postsynaptic density membrane
messages: Synapse
messages: dendrite
messages: dendritic spine

9606:HEXB
gene id: 9606:HEXB
uniprot id: A0A024RAJ6
uniprot id: P07686
uniprot id: Q5URX0
names: Activity Regulation
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Addition of GM2A stimulates the hydrolysis of sulfated glycosphingolipid SM2 and the ganglioside GM2.
messages: Belongs to the glycosyl hydrolase 20 family.
messages: Cortical granule
messages: Hydrolyzes the non-reducing end N-acetyl-D-hexosamine and/or sulfated N-acetyl-D-hexosamine of glycoconjugates, such as the oligosaccharide moieties from proteins and neutral glycolipids, or from certain mucopolysaccharides (PubMed:11707436, PubMed:9694901, PubMed:8672428, PubMed:8123671). The isozyme B does not hydrolyze each of these substrates, however hydrolyzes efficiently neutral oligosaccharide (PubMed:11707436). Only the isozyme A is responsible for the degradation of GM2 gangliosides in the presence of GM2A (PubMed:9694901, PubMed:8672428, PubMed:8123671). During fertilization is responsible, at least in part, for the zona block to polyspermy. Present in the cortical granules of non-activated oocytes, is exocytosed during the cortical reaction in response to oocyte activation and inactivates the sperm galactosyltransferase-binding site, accounting for the block in sperm binding to the zona pellucida (By similarity).
messages: Lysosome
messages: N-linked glycans at Asn-142 and Asn-190 consist of Man(3)-GlcNAc(2) and Man(5 to 7)-GlcNAc(2), respectively.
messages: The beta-A and beta-B chains are produced by proteolytic processing of the precursor beta chain.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: There are 3 forms of beta-hexosaminidase: hexosaminidase A is an heterodimer composed of one subunit alpha and one subunit beta (chain A and B); hexosaminidase B is an homodimer of two beta subunits (two chains A and B); hexosaminidase S is a homodimer of two alpha subunits (By similarity). The composition of the dimer (isozyme A versus isozyme S) has a significant effect on the substrate specificity of the alpha subunit active site (PubMed:8672428).

9606:ZNF354A
gene id: 9606:ZNF354A
uniprot id: O60765
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: Expressed in kidney and inner ear.
messages: Nucleus

9606:POLR2E
gene id: 9606:POLR2E
uniprot id: B4DJ89
uniprot id: E5KT65
uniprot id: P19388
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Interacts with HBV protein X.
messages: Belongs to the archaeal Rpo5/eukaryotic RPB5 RNA polymerase subunit family.
messages: Component of the RNA polymerase I (Pol I), RNA polymerase II (Pol II) and RNA polymerase III (Pol III) complexes consisting of at least 13, 12 and 17 subunits, respectively (PubMed:9852112, PubMed:16809778). In RNA Pol II, this subunit is present in 2-fold molar excess over the other subunits (PubMed:9852112). Component of the PAQosome complex which is responsible for the biogenesis of several protein complexes and which consists of R2TP complex members RUVBL1, RUVBL2, RPAP3 and PIH1D1, URI complex members PFDN2, PFDN6, PDRG1, UXT and URI1 as well as ASDURF, POLR2E and DNAAF10/WDR92 (PubMed:31738558). Interacts with URI1 (PubMed:9819440).
messages: DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Common component of RNA polymerases I, II and III which synthesize ribosomal RNA precursors, mRNA precursors and many functional non-coding RNAs, and small RNAs, such as 5S rRNA and tRNAs, respectively. Pol II is the central component of the basal RNA polymerase II transcription machinery. Pols are composed of mobile elements that move relative to each other. In Pol II, POLR2E/RPB5 is part of the lower jaw surrounding the central large cleft and thought to grab the incoming DNA template. Seems to be the major component in this process (By similarity).
messages: DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Common component of RNA polymerases I, II and III which synthesize ribosomal RNA precursors, mRNA precursors and many functional non-coding RNAs, and small RNAs, such as 5S rRNA and tRNAs, respectively. Pol II is the central component of the basal RNA polymerase II transcription machinery. Pols are composed of mobile elements that move relative to each other. In Pol II, POLR2E/RPB5 is part of the lower jaw surrounding the central large cleft and thought to grab the incoming DNA template. Seems to be the major component in this process.
messages: Nucleus

9606:CTSE
gene id: 9606:CTSE
uniprot id: A0A7P0MPN9
uniprot id: B4DNU8
uniprot id: P14091
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the peptidase A1 family.
messages: Dubious isoform produced through aberrant splice sites.
messages: Endosome
messages: Expressed abundantly in the stomach, the Clara cells of the lung and activated B-lymphocytes, and at lower levels in lymph nodes, skin and spleen. Not expressed in resting B-lymphocytes.
messages: Glycosylated. The nature of the carbohydrate chain varies between cell types. In fibroblasts, the proenzyme contains a high mannose-type oligosaccharide, while the mature enzyme contains a complex-type oligosaccharide. In erythrocyte membranes, both the proenzyme and mature enzyme contain a complex-type oligosaccharide.
messages: Homodimer; disulfide-linked.
messages: May have a role in immune function. Probably involved in the processing of antigenic peptides during MHC class II-mediated antigen presentation. May play a role in activation-induced lymphocyte depletion in the thymus, and in neuronal degeneration and glial cell activation in the brain.
messages: Two forms are produced by autocatalytic cleavage, form I begins at Ile-54, form II begins at Thr-57.

9606:NIPAL2
gene id: 9606:NIPAL2
uniprot id: Q9H841
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the NIPA family.
messages: Membrane

9606:GPR89B
gene id: 9606:GPR89B
uniprot id: B7ZAQ6
uniprot id: P0CG08
uniprot id: X5D7G6
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the Golgi pH regulator (TC 1.A.38) family.
messages: Does not seem to be able to bind GTP.
messages: Golgi apparatus membrane
messages: Homotrimer (PubMed:18794847). Interacts with RABL3; the interaction stabilizes GPR89A (By similarity).
messages: Homotrimer (PubMed:18794847). Interacts with RABL3; the interaction stabilizes GPR89B (By similarity).
messages: Membrane
messages: Ubiquitous.
messages: Voltage dependent anion channel required for acidification and functions of the Golgi apparatus that may function in counter-ion conductance (PubMed:12761501, PubMed:18794847). Plays a role in lymphocyte development, probably by acting as a RABL3 effector in hematopoietic cells (By similarity).
messages: Voltage dependent anion channel required for acidification and functions of the Golgi apparatus that may function in counter-ion conductance (PubMed:18794847). Plays a role in lymphocyte development, probably by acting as a RABL3 effector in hematopoietic cells (By similarity).

9606:GOLGA8A
gene id: 9606:GOLGA8A
uniprot id: A7E2F4
names: Caution
names: Function
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
messages: A family of highly similar proteins (GOLGA8A, GOLGA8B, GOLGA8C, GOLGA8D, GOLGA8E, GOLGA8F, GOLGA8G) are encoded by a repeated region on chromosome 15q11-15q13. Our sequences are in agreement with HGNC nomenclature.
messages: Belongs to the GOLGA8 family.
messages: Golgi stack membrane
messages: May be involved in maintaining Golgi structure.
messages: Probable cloning artifact.

9606:HEYL
gene id: 9606:HEYL
uniprot id: Q9NQ87
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the HEY family.
messages: By activation of the Notch signaling pathway.
messages: Downstream effector of Notch signaling which may be required for cardiovascular development (By similarity). Transcriptional repressor which binds preferentially to the canonical E box sequence 5'-CACGTG-3' (By similarity). Represses transcription by the cardiac transcriptional activators GATA4 and GATA6.
messages: Nucleus
messages: Self-associates. Interacts with GATA4, GATA6, HES1, HEY1 and HEY2. Interacts with HDAC1, NCOR1 and SIN3A.

9606:MAFA
gene id: 9606:MAFA
uniprot id: Q8NHW3
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the bZIP family. Maf subfamily.
messages: Expressed in the islets of Langerhans (at protein level).
messages: Forms homodimers or heterodimers (PubMed:12011435, PubMed:23148532). Monomers and dimers are able to bind DNA, but the off-rate is faster for monomers (PubMed:23148532). Interacts with NEUROD1 and PDX1 (By similarity). May interact with MAFB, FOS, JUN and PCAF (By similarity).
messages: Nucleus
messages: Phosphorylated at tyrosines.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Transcription factor that activates insulin gene expression (PubMed:15993959, PubMed:12011435). Acts synergistically with NEUROD1/BETA2 and PDX1 (PubMed:15993959). Binds the insulin enhancer C1/RIPE3b element (PubMed:12011435). Binds to consensus TRE-type MARE 5'-TGCTGACTCAGCA-3' DNA sequence (PubMed:23148532, PubMed:29339498).
messages: Ubiquitinated, leading to its degradation by the proteasome.

9606:OTUD5
gene id: 9606:OTUD5
uniprot id: Q96G74
names: Activity Regulation
names: Disease Annotation
names: Function
names: Induction
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the peptidase C85 family.
messages: Deubiquitinating enzyme that functions as negative regulator of the innate immune system (PubMed:17991829, PubMed:22245969, PubMed:23827681, PubMed:33523931). Has peptidase activity towards 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains (PubMed:22245969). Can also cleave 'Lys-11'-linked ubiquitin chains (in vitro) (PubMed:22245969). Acts via TRAF3 deubiquitination and subsequent suppression of type I interferon (IFN) production (PubMed:17991829). Controls neuroectodermal differentiation through cleaving 'Lys-48'-linked ubiquitin chains to counteract degradation of select chromatin regulators such as ARID1A, HDAC2 and HCF1 (PubMed:33523931). Acts as a positive regulator of mTORC1 and mTORC2 signaling following phosphorylation by MTOR: acts by mediating deubiquitination of BTRC, leading to its stability (PubMed:33110214).
messages: Dubious isoform produced through aberrant splice sites.
messages: Expressed in various tissues, including the liver and placenta, as well as in peripheral blood leukocytes.
messages: Inhibited by N-ethyl-maleimide (NEM).
messages: Interacts with TRAF3.
messages: Nucleus
messages: Phosphorylation at Ser-177 is required for deubiquitinating activity (PubMed:22245969, PubMed:33523931). Phosphorylation at Ser-328, Ser-337 and Ser-508 by MTOR promotes its activity (PubMed:33110214).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Up-regulated by bacterial lipopolysaccharide (LPS) in bone marrow-derived macrophages.

9606:ARSA
gene id: 9606:ARSA
uniprot id: A0A0C4DFZ2
uniprot id: B4DVI5
uniprot id: P15289
names: Activity Regulation
names: Cofactor
names: Disease Annotation
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the sulfatase family.
messages: Binds 1 Ca(2+) ion per subunit.
messages: Endoplasmic reticulum
messages: Homodimer at neutral pH and homooctamer at acidic pH. Exists both as a single chain of 58 kDa (component A) or as a chain of 50 kDa (component B) linked by disulfide bond(s) to a 7 kDa chain (component C). Interacts with SUMF1.
messages: Hydrolyzes cerebroside sulfate.
messages: Inhibited by phosphate. The phosphate forms a covalent bond with the active site 3-oxoalanine.
messages: Lysosome
messages: The conversion to 3-oxoalanine (also known as C-formylglycine, FGly), of a serine or cysteine residue in prokaryotes and of a cysteine residue in eukaryotes, is critical for catalytic activity. This post-translational modification is severely defective in multiple sulfatase deficiency (MSD).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The metal cofactor was first identified as magnesium ion, based on the structure of the recombinant protein, but when purified from human placenta, the protein contains 1 calcium ion per subunit.
messages: The protein represented in this entry is involved in disease pathogenesis. Arylsulfatase A activity is impaired in multiple sulfatase deficiency due to mutations in SUMF1 (PubMed:15146462). SUMF1 mutations result in defective post-translational modification of ARSA at residue Cys-69 that is not converted to 3-oxoalanine (PubMed:7628016).

9606:NUDT3
gene id: 9606:NUDT3
uniprot id: O95989
names: Activity Regulation
names: Cofactor
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the Nudix hydrolase family. DIPP subfamily.
messages: Binds 3 Mg(2+) ions per subunit.
messages: Cleaves a beta-phosphate from the diphosphate groups in PP-InsP5 (diphosphoinositol pentakisphosphate) and [PP]2-InsP4 (bisdiphosphoinositol tetrakisphosphate), suggesting that it may play a role in signal transduction (PubMed:12370170, PubMed:9822604, PubMed:10585413). InsP6 (inositol hexakisphosphate) is not a substrate (PubMed:9822604). Acts as a negative regulator of the ERK1/2 pathway (By similarity). Also able to catalyze the hydrolysis of dinucleoside oligophosphates, with diadenosine 5',5'''-P1,P6-hexaphosphate (Ap6A) and diadenosine 5',5'''- P1,P5-pentaphosphate (Ap5A) being the preferred substrates (PubMed:12370170, PubMed:10419486). The major reaction products are ADP and p4a from Ap6A and ADP and ATP from Ap5A (PubMed:12370170). Also able to hydrolyze 5-phosphoribose 1-diphosphate (PubMed:12370170). Acts as a decapping enzyme that modulates the stability of a subset of mRNAs implicated in cell motility (PubMed:26932476). Hydrolyzes monomethylated capped RNA after both the alpha- and beta-phosphates generating m7GMP + ppRNA and m7GDP + pRNA (PubMed:32727897). Can hydrolyze unmethylated capped RNAs (By similarity). Divalent cations zinc, magnesium and manganese determine its substrate specificity (PubMed:34788624). Exhibits diphosphoinositol polyphosphate phosphohydrolase in the presence of magnesium ions, diadenosine hexaphosphate hydrolase activity in the presence of manganese ions and endopolyphosphatase activity in the presence of zinc ions (PubMed:34788624). Plays an important role in limiting DNA damage and maintaining cell survival upon oxidative stress via its endopolyphosphatase activity (PubMed:34788624).
messages: Cytoplasm
messages: Endopolyphospahatase activity is inhibited by NaF, NaPPi, beta-glycerol phosphate and heparin (PubMed:34788624). 5-diphosphoinositol pentakisphosphate (5-InsP7) inhibits its mRNA decapping activity (PubMed:32727897).
messages: Monomer.
messages: Nucleus
messages: Widely expressed. Expressed at higher level in brain, heart, pancreas and liver. Also expressed in placenta, lung and kidney.

9606:TMPRSS15
gene id: 9606:TMPRSS15
uniprot id: P98073
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the peptidase S1 family.
messages: Heterodimer of a catalytic (light) chain and a multidomain (heavy) chain linked by a disulfide bond.
messages: Intestinal brush border.
messages: Membrane
messages: Responsible for initiating activation of pancreatic proteolytic proenzymes (trypsin, chymotrypsin and carboxypeptidase A). It catalyzes the conversion of trypsinogen to trypsin which in turn activates other proenzymes including chymotrypsinogen, procarboxypeptidases, and proelastases.
messages: The chains are derived from a single precursor that is cleaved by a trypsin-like protease.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:SNX16
gene id: 9606:SNX16
uniprot id: P57768
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the sorting nexin family.
messages: Cytoplasm
messages: Detected in placenta, lung, liver,heart and pancreas.
messages: Early endosome membrane
messages: Homooligomer. Interacts with EGFR (By similarity).
messages: Late endosome membrane
messages: Lysosome
messages: May be involved in several stages of intracellular trafficking. Plays a role in protein transport from early to late endosomes. Plays a role in protein transport to the lysosome. Promotes degradation of EGFR after EGF signaling. Plays a role in intracellular transport of vesicular stomatitis virus nucleocapsids from the endosome to the cytoplasm.
messages: The PX domain mediates interaction with membranes enriched in phosphatidylinositol 3-phosphate.

9606:SKP2
gene id: 9606:SKP2
uniprot id: Q13309
names: Function
names: PTM
names: Sequence Caution
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Interacts with hepatitis C virus/HCV non-structural protein NS5A; promotes the ubiquitin-mediated proteasomal degradation of NS5A.
messages: Acetylation at Lys-68 and Lys-71 increases stability through impairment of APC/C-mediated proteolysis and promotes cytoplasmic retention. Deacetylated by SIRT3.
messages: Cytoplasm
messages: Nucleus
messages: Part of a SCF(SKP2) complex consisting of CUL1, RBX1, SKP1 and SKP2. Component of a SCF(SKP2)-like complex containing CUL1, SKP1, TRIM21 and SKP2. Interacts directly with CUL1 and SKP1. Interacts with CKS1. Interacts with ASB2 which is the substrate-recognition component of a probable ECS E3 ubiquitin-protein ligase complex; ASB2 is likely to bridge the formation of dimeric E3-ubiquitin-protein ligase complexes composed of an ECS complex and an SCF(SKP2) complex (PubMed:21119685). Interacts with the cyclin-A-CDK2 complex. Interacts with ORC1, phosphorylated CDT1, phosphorylated RBL2, ELF4, phosphorylated RAG2, FOXO1, UBP43, MYC, TOB1, TAL1 and KMT2A/MLL1. Interacts with TRIM21. Interacts with cyclin-E (By similarity). Interacts with IFI27; promotes the ubiquitin-mediated proteasomal degradation of hepatitis C virus/HCV non-structural protein NS5A (PubMed:27194766). Interacts with CARM1 (By similarity).
messages: Probable cloning artifact.
messages: Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins involved in cell cycle progression, signal transduction and transcription (PubMed:11931757, PubMed:12435635, PubMed:12769844, PubMed:12840033, PubMed:15342634, PubMed:15668399, PubMed:15949444, PubMed:16103164, PubMed:16262255, PubMed:16581786, PubMed:16951159, PubMed:17908926, PubMed:17962192, PubMed:22770219, PubMed:32267835). Specifically recognizes phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition (By similarity). Degradation of CDKN1B/p27kip also requires CKS1. Recognizes target proteins ORC1, CDT1, RBL2, KMT2A/MLL1, CDK9, RAG2, FOXO1, UBP43, YTHDF2, and probably MYC, TOB1 and TAL1 (PubMed:11931757, PubMed:12435635, PubMed:12769844, PubMed:12840033, PubMed:15342634, PubMed:15668399, PubMed:15949444, PubMed:16103164, PubMed:17962192, PubMed:16581786, PubMed:16951159, PubMed:17908926, PubMed:32267835). Degradation of TAL1 also requires STUB1 (PubMed:17962192). Recognizes CDKN1A in association with CCNE1 or CCNE2 and CDK2 (PubMed:16262255). Promotes ubiquitination and destruction of CDH1 in a CK1-dependent manner, thereby regulating cell migration (PubMed:22770219).
messages: Through the ubiquitin-mediated proteasomal degradation of hepatitis C virus non-structural protein 5A, has an antiviral activity towards that virus.
messages: Ubiquitinated by the APC/C complex, leading to its degradation by the proteasome. Deubiquitinated by USP13.

9606:ENTPD4
gene id: 9606:ENTPD4
uniprot id: Q9Y227
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the GDA1/CD39 NTPase family.
messages: Catalyzes the hydrolysis of nucleoside triphosphates and diphosphates in a calcium- or magnesium-dependent manner, with a preference for pyrimidines. Preferentially hydrolyzes UTP and TTP. AMP, ADP, ATP and UMP are not substrates (PubMed:10858452, PubMed:9556635). Preferentially activated by Ca(2+) over Mg(2+) (PubMed:10858452).
messages: Golgi apparatus membrane
messages: Has a broad substrate specificity with the ability of cleaving all nucleotide di- and triphosphates with the exception of adenosine di- and triphosphate (ADP and ATP). Preferentially hydrolyzes CTP, UDP, CDP, GTP and GDP. Can use either Ca(2+) or Mg(2+) equally.
messages: Lysosome membrane
messages: Ubiquitous. Highest expression in testis and lowest in bladder.
messages: autophagosome membrane

9606:GGCX
gene id: 9606:GGCX
uniprot id: P38435
names: Disease Annotation
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the vitamin K-dependent gamma-carboxylase family.
messages: Endoplasmic reticulum membrane
messages: Mediates the vitamin K-dependent carboxylation of glutamate residues to calcium-binding gamma-carboxyglutamate (Gla) residues with the concomitant conversion of the reduced hydroquinone form of vitamin K to vitamin K epoxide (PubMed:17073445). Catalyzes gamma-carboxylation of various proteins, such as blood coagulation factors (F2, F7, F9 and F10), osteocalcin (BGLAP) or matrix Gla protein (MGP) (PubMed:17073445).
messages: Monomer (PubMed:11570873). May interact with CALU (By similarity).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The vitamin K-dependent protein substrates of carboxylase have usually a propeptide that binds to a high-affinity site on the carboxylase. CO(2), O(2) and reduced vitamin K are cosubstrates.

9606:QSER1
gene id: 9606:QSER1
uniprot id: Q2KHR3
names: Function
names: Sequence Caution
names: Subcellular Location Annotation
names: Subunit
messages: Chromosome
messages: Contaminating sequence. Potential poly-A sequence.
messages: Interacts with TET1.
messages: Plays an essential role in the protection and maintenance of transcriptional and developmental programs. Protects many bivalent promoters and poised enhancers from hypermethylation, showing a marked preference for these regulatory elements over other types of promoters or enhancers. Mechanistically, cooperates with TET1 and binds to DNA in a common complex to inhibit the binding of DNMT3A/3B and therefore de novo methylation.

9606:PAK3
gene id: 9606:PAK3
uniprot id: O75914
names: Activity Regulation
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Activated by binding small G proteins. Binding of GTP-bound CDC42 or RAC1 to the autoregulatory region releases monomers from the autoinhibited dimer, enables phosphorylation of Thr-436 and allows the kinase domain to adopt an active structure (By similarity).
messages: Autophosphorylated when activated by CDC42/p21.
messages: Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.
messages: Cytoplasm
messages: Interacts tightly with GTP-bound but not GDP-bound CDC42/p21 and RAC1. Shows highly specific binding to the SH3 domains of phospholipase C-gamma and of adapter protein NCK. Interacts with the C-terminal of APP (By similarity). Interacts with ARHGEF6 and ARHGEF7. Interacts with GIT1 and GIT2 (PubMed:10896954).
messages: Neddylated.
messages: Restricted to the nervous system. Highly expressed in postmitotic neurons of the developing and postnatal cerebral cortex and hippocampus.
messages: Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell migration, or cell cycle regulation. Plays a role in dendrite spine morphogenesis as well as synapse formation and plasticity. Acts as downstream effector of the small GTPases CDC42 and RAC1. Activation by the binding of active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Phosphorylates MAPK4 and MAPK6 and activates the downstream target MAPKAPK5, a regulator of F-actin polymerization and cell migration. Additionally, phosphorylates TNNI3/troponin I to modulate calcium sensitivity and relaxation kinetics of thin myofilaments. May also be involved in early neuronal development. In hippocampal neurons, necessary for the formation of dendritic spines and excitatory synapses; this function is dependent on kinase activity and may be exerted by the regulation of actomyosin contractility through the phosphorylation of myosin II regulatory light chain (MLC) (By similarity).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:ATP1A4
gene id: 9606:ATP1A4
uniprot id: Q13733
names: Activity Regulation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIC subfamily.
messages: Cell membrane
messages: Specifically expressed in testis. Found in very low levels in skeletal muscle. Expressed in mature sperm (at protein level).
messages: Specifically inhibited by an endogenous cardiac glycoside, ouabain.
messages: The sodium/potassium-transporting ATPase is composed of a catalytic alpha subunit, an auxiliary non-catalytic beta subunit and an additional regulatory subunit.
messages: This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium ions, providing the energy for active transport of various nutrients. Plays a role in sperm motility.

9606:FAM170A
gene id: 9606:FAM170A
uniprot id: A1A519
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Acts as a nuclear transcription factor that positively regulates the expression of heat shock genes. Binds to heat shock promoter elements (HSE).
messages: Belongs to the FAM170 family.
messages: Expressed strongly in testis and brain and weakly in prostate, spleen, pancreas and uterus.
messages: Nucleus
messages: The N-terminus is necessary for nuclear localization. The C-terminus is necessary for transcriptional activity.

9606:PRKACA
gene id: 9606:PRKACA
uniprot id: A0A8V8TL59
uniprot id: A8K8B9
uniprot id: P17612
names: Activity Regulation
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: A number of inactive tetrameric holoenzymes are produced by the combination of homo- or heterodimers of the different regulatory subunits associated with two catalytic subunits. cAMP causes the dissociation of the inactive holoenzyme into a dimer of regulatory subunits bound to four cAMP and two free monomeric catalytic subunits. The cAMP-dependent protein kinase catalytic subunit binds PJA2. Both isoforms 1 and 2 forms activate cAMP-sensitive PKAI and PKAII holoenzymes by interacting with regulatory subunit (R) of PKA, PRKAR1A/PKR1 and PRKAR2A/PKR2, respectively. Interacts with PRKAR1A and PRKAR2B (PubMed:33058759). Interacts with NFKB1, NFKB2 and NFKBIA in platelets; these interactions are disrupted by thrombin and collagen. Binds to ABL1 in spermatozoa and with CDC25B in oocytes. Interacts with APOBEC3G and AICDA. Interacts with RAB13; downstream effector of RAB13 involved in tight junction assembly. Found in a complex at least composed of MROH2B, PRKACA isoform 2 and TCP11 (By similarity). Interacts with MROH2B (By similarity). Isoform 2 interacts with TCP11 (By similarity). Interacts with HSF1 (PubMed:21085490). Interacts with TBC1D31; in regulation of OFD1 (PubMed:33934390). Interacts in free form with SMO (via C-terminus); the interaction leads to sequestration of PRKACA at the membrane, preventing PRKACA-mediated phosphorylation of GLI transcription factors (By similarity).
messages: Allosterically activated by various compounds, including ATP. Activated by cAMP; the nucleotide acts as a dynamic and allosteric activator by coupling the two lobes of apo PKA, enhancing the enzyme dynamics synchronously and priming it for catalysis. Inhibited by H89 (N-[2-[[3-(4-Bromophenyl)-2-propenyl]amino]ethyl]-5-isoquinolinesulfonamide), spiroindoline, azole-based inhibitors, (3s)-amino-aminomethylbenzamide analogs, ARC-1032 (6-{[(2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]formamido}-N-[(1R)-4-carbamimidamido-1-carbamoylbutyl]hexanamide), ARC-1034 (6-{[(2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]formamido}-N-[(1R)-4-carbamimidamido-1-{[(1R)-4-carbamimidamido-1-carbamoylbutyl]carbamoyl}butyl]hexanamide), ARC-582, ARC-902 (Adc-6-aminohexanoic acid-(D-Arg)(6)-NH(2)), ARC-1012 ((2R)-6-amino-2-(6-{[(2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]formamido}hexanamido)-N-(5-{[(1R)-4-carbamimidamido-1-{[(1R)-4-carbamimidamido-1-carbamoylbutyl]carbamoyl}butyl]carbamoyl}pentyl)hexanamide) and ARC-1039 (6-{[(2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]formamido}-N-[(1R)-1-[(5-{[(1R)-4-carbamimidamido-1-{[(1R)-4-carbamimidamido-1-carbamoylbutyl]carbamoyl}butyl]carbamoyl}pentyl)carbamoyl]ethyl]he xanamide).
messages: Asn-3 is partially deaminated to Asp-3 giving rise to 2 major isoelectric variants, called CB and CA respectively.
messages: Autophosphorylated. Phosphorylation is enhanced by vitamin K(2) (PubMed:12372837, PubMed:17909264). Phosphorylated on threonine and serine residues. Phosphorylation on Thr-198 is required for full activity (PubMed:16765046, PubMed:20137943, PubMed:20481595, PubMed:20732331, PubMed:21774789, Ref.43). Phosphorylated at Tyr-331 by activated receptor tyrosine kinases EGFR and PDGFR; this increases catalytic efficiency (By similarity).
messages: Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. cAMP subfamily.
messages: Cell membrane
messages: Cytoplasm
messages: Isoform 1 is ubiquitous. Isoform 2 is sperm-specific and is enriched in pachytene spermatocytes but is not detected in round spermatids.
messages: Membrane
messages: Mitochondrion
messages: Nucleus
messages: Phosphorylates a large number of substrates in the cytoplasm and the nucleus (PubMed:15642694, PubMed:15905176, PubMed:16387847, PubMed:17333334, PubMed:17565987, PubMed:17693412, PubMed:18836454, PubMed:19949837, PubMed:20356841, PubMed:21085490, PubMed:21514275, PubMed:21812984, PubMed:31112131). Phosphorylates CDC25B, ABL1, NFKB1, CLDN3, PSMC5/RPT6, PJA2, RYR2, RORA, SOX9 and VASP (PubMed:15642694, PubMed:15905176, PubMed:16387847, PubMed:17333334, PubMed:17565987, PubMed:17693412, PubMed:18836454, PubMed:19949837, PubMed:20356841, PubMed:21085490, PubMed:21514275, PubMed:21812984). Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis (PubMed:21423175). RORA is activated by phosphorylation (PubMed:21514275). Required for glucose-mediated adipogenic differentiation increase and osteogenic differentiation inhibition from osteoblasts (PubMed:19949837). Involved in chondrogenesis by mediating phosphorylation of SOX9 (By similarity). Involved in the regulation of platelets in response to thrombin and collagen; maintains circulating platelets in a resting state by phosphorylating proteins in numerous platelet inhibitory pathways when in complex with NF-kappa-B (NFKB1 and NFKB2) and I-kappa-B-alpha (NFKBIA), but thrombin and collagen disrupt these complexes and free active PRKACA stimulates platelets and leads to platelet aggregation by phosphorylating VASP (PubMed:15642694, PubMed:20356841). Prevents the antiproliferative and anti-invasive effects of alpha-difluoromethylornithine in breast cancer cells when activated (PubMed:17333334). RYR2 channel activity is potentiated by phosphorylation in presence of luminal Ca(2+), leading to reduced amplitude and increased frequency of store overload-induced Ca(2+) release (SOICR) characterized by an increased rate of Ca(2+) release and propagation velocity of spontaneous Ca(2+) waves, de…
messages: Phosphorylates and activates ABL1 in sperm flagellum to promote spermatozoa capacitation.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: When myristoylated, Ser-11 is autophosphorylated probably in conjunction with deamidation of Asn-3.
messages: acrosome
messages: flagellum

9606:XPO7
gene id: 9606:XPO7
uniprot id: Q9UIA9
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the exportin family.
messages: Binds to nucleoporins. Found in a complex with XPO7, EIF4A1, ARHGAP1, VPS26A, VPS29, VPS35 and SFN. Interacts with ARHGAP1 and SFN. Interacts with Ran and cargo proteins in a GTP-dependent manner.
messages: Cytoplasm
messages: Mediates the nuclear export of proteins (cargos) with broad substrate specificity. In the nucleus binds cooperatively to its cargo and to the GTPase Ran in its active GTP-bound form. Docking of this trimeric complex to the nuclear pore complex (NPC) is mediated through binding to nucleoporins. Upon transit of a nuclear export complex into the cytoplasm, disassembling of the complex and hydrolysis of Ran-GTP to Ran-GDP (induced by RANBP1 and RANGAP1, respectively) cause release of the cargo from the export receptor. XPO7 then return to the nuclear compartment and mediate another round of transport. The directionality of nuclear export is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus.
messages: Nucleus
messages: Strong expression in testis, thyroid and bone marrow, low expression in lung, liver and small intestine, no expression in thymus, and remaining tissues studied have moderate expression. Expressed in red blood cells; overexpressed in red blood cells (cytoplasm) of patients with hereditary non-spherocytic hemolytic anemia of unknown etiology.

9606:SCAMP5
gene id: 9606:SCAMP5
uniprot id: A0A0A8K8F5
uniprot id: Q8TAC9
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the SCAMP family.
messages: Belongs to the SCAMP family. SCAMP5 subfamily.
messages: By endoplasmic reticulum stress.
messages: Cell membrane
messages: Expressed both by neuronal and non-neuronal tissues. Expressed in brain, stomach, thyroid, spinal cord, lymph node, trachea, adrenal gland, bone marrow and in the different parts of brain. In thyroid tissues, it is expressed by the follicular epithelial cells. In the adrenal gland tissues it is detected in the zona fasciculata of the cortex region (at protein level).
messages: Golgi apparatus membrane
messages: Interacts (via C-terminal part) with SYT1 and SYT2; interaction with synaptotagmins making a link with the SNARE molecules. Interacts with SLC9A7.
messages: Membrane
messages: Recycling endosome membrane
messages: Required for the calcium-dependent exocytosis of signal sequence-containing cytokines such as CCL5. Probably acts in cooperation with the SNARE machinery. May play a role in accumulation of expanded polyglutamine (polyQ) protein huntingtin (HTT) in case of endoplasmic reticulum stress by inhibiting the endocytosis pathway.
messages: synaptic vesicle membrane
messages: trans-Golgi network membrane

9606:GPR15
gene id: 9606:GPR15
uniprot id: B2R8H6
uniprot id: B6V9G9
uniprot id: P49685
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Probable chemokine receptor. Alternative coreceptor with CD4 for HIV-1 infection.

9606:CRIPT
gene id: 9606:CRIPT
uniprot id: Q9P021
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable). Involved in the cytoskeletal anchoring of DLG4 in excitatory synapses (By similarity).
messages: Belongs to the CRIPT family.
messages: Component of the minor spliceosome. Within this complex, interacts with RNF113A, as well as with SF3B1/SF3b155, SF3B2/SF3b145 and PHF5A/SF3b14b (PubMed:33509932). Interacts with TUBB1. Interacts strongly with the PDZ3 domain of members of the DLG4 family. Associates with microtubules (By similarity). Interacts with DLG4.
messages: Cytoplasm
messages: Synapse
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: dendritic spine

9606:KIF5A
gene id: 9606:KIF5A
uniprot id: Q12840
names: Disease Annotation
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. Kinesin subfamily.
messages: Composed of three structural domains: a large globular N-terminal domain which is responsible for the motor activity of kinesin (it hydrolyzes ATP and binds microtubule), a central alpha-helical coiled coil domain that mediates the heavy chain dimerization; and a small globular C-terminal domain which interacts with other proteins (such as the kinesin light chains), vesicles and membranous organelles.
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry. The mutation NM_004984.2:c.33019A>G encoding the predicted missence variant p.Arg1007Gly, may also affect splicing and induce the skipping of exon 27, resulting in a frameshift and a premature stop codon producing a truncated protein p.Asn999Valfs*39.
messages: Distributed throughout the CNS but is highly enriched in subsets of neurons.
messages: Microtubule-dependent motor required for slow axonal transport of neurofilament proteins (NFH, NFM and NFL). Can induce formation of neurite-like membrane protrusions in non-neuronal cells in a ZFYVE27-dependent manner. The ZFYVE27-KIF5A complex contributes to the vesicular transport of VAPA, VAPB, SURF4, RAB11A, RAB11B and RTN3 proteins in neurons. Required for anterograde axonal transportation of MAPK8IP3/JIP3 which is essential for MAPK8IP3/JIP3 function in axon elongation.
messages: Oligomer composed of two heavy chains and two light chains. Interacts with GRIP1. Interacts with FMR1 (via C-terminus); this interaction is increased in a mGluR-dependent manner. Interacts with ZFYVE27. Interacts with VAPA, VAPB, SURF4, RAB11A (GDP-bound form), RAB11B (GDP-bound form) and RTN3 in a ZFYVE27-dependent manner (By similarity). Interacts with BORCS5 (PubMed:25898167). Interacts with BICD2 (PubMed:20386726). Interacts with DTNB (By similarity).
messages: Perikaryon
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: cytoskeleton
messages: perinuclear region

9606:COG3
gene id: 9606:COG3
uniprot id: Q96JB2
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the COG3 family.
messages: Component of the conserved oligomeric Golgi complex which is composed of eight different subunits and is required for normal Golgi morphology and localization. Interacts with TMEM115.
messages: Golgi stack membrane
messages: Involved in ER-Golgi transport.
messages: Widely expressed with highest levels in pancreas and testis and lowest levels in lung.

9606:TXNL1
gene id: 9606:TXNL1
uniprot id: O43396
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Active thioredoxin with a redox potential of about -250 mV.
messages: Component of the 19S regulatory cap of the 26S proteasome. Interacts with PSMD14/RPN11. Interacts with, and reduces EEF1A1.
messages: Cytoplasm
messages: Nucleus
messages: Ubiquitous.

9606:SLC27A5
gene id: 9606:SLC27A5
uniprot id: Q9Y2P5
names: Activity Regulation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: 3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholestanate (THCA) inhibits the activation of cholate.
messages: Belongs to the ATP-dependent AMP-binding enzyme family.
messages: Cell membrane
messages: Endoplasmic reticulum membrane
messages: May mediate the import of long-chain fatty acids (LCFA) by facilitating their transport across cell membranes (PubMed:20448275, PubMed:20530735). Also catalyzes the ATP-dependent formation of fatty acyl-CoA using LCFA and very-long-chain fatty acids (VLCFA) as substrates (PubMed:10479480). Mainly functions as a bile acyl-CoA synthetase catalyzing the activation of bile acids via ATP-dependent formation of bile acid CoA thioesters which is necessary for their subsequent conjugation with glycine or taurine (PubMed:10749848, PubMed:11980911). Both primary bile acids (cholic acid and chenodeoxycholic acid) and secondary bile acids (deoxycholic acid and lithocholic acid) are the principal substrates (PubMed:10749848, PubMed:11980911). In vitro, activates 3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholestanate ((25R)-3alpha,7alpha,12alpha-trihydroxy-5beta-cholestan-26-oate or THCA), the C27 precursor of cholic acid deriving from the de novo synthesis from cholesterol (PubMed:11980911). Plays an important role in hepatic fatty acid uptake and bile acid reconjugation and recycling but not in de novo synthesis of bile acids (By similarity).
messages: Microsome
messages: Predominantly expressed in liver.

9606:TMEM181
gene id: 9606:TMEM181
uniprot id: Q9P2C4
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Interacts with cytolethal distending toxin.
messages: Mediates action of cytolethal distending toxins (CDT), which are secreted by many pathogenic bacteria. Expression level of TMEM181 is rate-limiting for intoxication.
messages: Membrane

9606:CCL13
gene id: 9606:CCL13
uniprot id: Q99616
names: Function
names: Induction
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the intercrine beta (chemokine CC) family.
messages: By IL1/interleukin-1 and TNF.
messages: Chemotactic factor that attracts monocytes, lymphocytes, basophils and eosinophils, but not neutrophils. Signals through CCR2B and CCR3 receptors. Plays a role in the accumulation of leukocytes at both sides of allergic and non-allergic inflammation. May be involved in the recruitment of monocytes into the arterial wall during the disease process of atherosclerosis. May play a role in the monocyte attraction in tissues chronically exposed to exogenous pathogens.
messages: One major form (form long), and two minor forms (short chain and medium chain) are produced by differential signal peptide cleavage. The medium chain is about 30-fold less active than the long chain.
messages: Secreted
messages: This protein can bind heparin.
messages: Widely expressed. Found in small intestine, thymus, colon, lung, trachea, stomach and lymph node. Low levels seen in the pulmonary artery smooth muscle cells.

9606:HSFX2
gene id: 9606:HSFX2
uniprot id: A0A140VK21
uniprot id: Q9UBD0
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the HSF family.
messages: Cytoplasm
messages: Nucleus
messages: Testis-specific.

9606:DYRK3
gene id: 9606:DYRK3
uniprot id: O43781
names: Activity Regulation
names: Domain
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MNB/DYRK subfamily.
messages: By EPO/erythropoietin.
messages: Cytoplasm
messages: Cytoplasmic granule
messages: Dual-specificity protein kinase that promotes disassembly of several types of membraneless organelles during mitosis, such as stress granules, nuclear speckles and pericentriolar material (PubMed:29973724). Dual-specificity tyrosine-regulated kinases (DYRKs) autophosphorylate a critical tyrosine residue in their activation loop and phosphorylate their substrate on serine and threonine residues (PubMed:9748265, PubMed:29634919). Acts as a central dissolvase of membraneless organelles during the G2-to-M transition, after the nuclear-envelope breakdown: acts by mediating phosphorylation of multiple serine and threonine residues in unstructured domains of proteins, such as SRRM1 and PCM1 (PubMed:29973724). Does not mediate disassembly of all membraneless organelles: disassembly of P-body and nucleolus is not regulated by DYRK3 (PubMed:29973724). Dissolution of membraneless organelles at the onset of mitosis is also required to release mitotic regulators, such as ZNF207, from liquid-unmixed organelles where they are sequestered and keep them dissolved during mitosis (PubMed:29973724). Regulates mTORC1 by mediating the dissolution of stress granules: during stressful conditions, DYRK3 partitions from the cytosol to the stress granule, together with mTORC1 components, which prevents mTORC1 signaling (PubMed:23415227). When stress signals are gone, the kinase activity of DYRK3 is required for the dissolution of stress granule and mTORC1 relocation to the cytosol: acts by mediating the phosphorylation of the mTORC1 inhibitor AKT1S1, allowing full reactivation of mTORC1 signaling (PubMed:23415227). Also acts as a negative regulator of EPO-dependent erythropoiesis: may place an upper limit on red cell production during stress erythropoiesis (PubMed:10779429). Inhibits cell death due to cytokine withdrawal in hematopoietic progenitor cells (PubMed:10779429). Promotes cell survival upon genotoxic stress through phosphorylation of SIRT1: this in turn inhibits p53/TP53 activity an…
messages: Interacts with SIRT1.
messages: Isoform 1: Highly expressed in testis and in hematopoietic tissue such as fetal liver, and bone marrow (PubMed:10779429). Isoform 1: Predominant form in fetal liver and bone marrow (PubMed:10779429). Isoform 1: Present at low levels in heart, pancreas, lymph node and thymus (PubMed:10779429). Isoform 2: Highly expressed in testis and in hematopoietic tissue such as fetal liver, and bone marrow (PubMed:10779429). Isoform 2: Predominant form in testis. Isoform 2: Present at low levels in heart, pancreas, lymph node and thymus (PubMed:10779429).
messages: Nucleus
messages: Nucleus speckle
messages: Protein kinase activity is activated following autophosphorylation at Tyr-369 (Probable). Autophosphorylation at Ser-350 stabilizes the protein and enhances the protein kinase activity (PubMed:9748265).
messages: Protein kinase activity is activated following autophosphorylation at Tyr-369 (PubMed:9748265). Inhibited by harmine, an ATP competitive inhibitor (PubMed:29634919). Inhibited by small-compound GSK-626616 (PubMed:29973724).
messages: The N-terminal domain, which is intrinsically disordered, is required for stress granule localization.
messages: Ubiquitinated at anaphase by the anaphase-promoting complex (APC/C), leading to its degradation by the proteasome.
messages: centrosome

9606:LGALS7
gene id: 9606:LGALS7
uniprot id: P47929
names: Function
names: Induction
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: By p53/TP53.
messages: Could be involved in cell-cell and/or cell-matrix interactions necessary for normal growth control. Pro-apoptotic protein that functions intracellularly upstream of JNK activation and cytochrome c release.
messages: Cytoplasm
messages: Mainly expressed in stratified squamous epithelium.
messages: Monomer.
messages: Nucleus
messages: Secreted

9606:MPV17
gene id: 9606:MPV17
uniprot id: A0A0S2Z3Z9
uniprot id: P39210
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the peroxisomal membrane protein PXMP2/4 family.
messages: Membrane
messages: Mitochondrion inner membrane
messages: Non-selective channel that modulates the membrane potential under normal conditions and oxidative stress, and is involved in mitochondrial homeostasis (PubMed:25861990). Involved in mitochondrial deoxynucleoside triphosphates (dNTP) pool homeostasis and mitochondrial DNA (mtDNA) maintenance (PubMed:26760297). May be involved in the regulation of reactive oxygen species metabolism and the control of oxidative phosphorylation (By similarity).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitous. Expressed in pancreas, kidney, muscle, liver, lung, placenta, brain and heart.

9606:EPHA4
gene id: 9606:EPHA4
uniprot id: P54764
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily.
messages: Cell membrane
messages: Early endosome
messages: Heterotetramer upon binding of the ligand. The heterotetramer is composed of an ephrin dimer and a receptor dimer. Oligomerization is probably required to induce biological responses. Interacts (phosphorylated at position Tyr-602) with FYN. Interacts with CDK5, CDK5R1 and NGEF; upon activation by EFNA1 induces NGEF phosphorylation by the kinase CDK5. Interacts with CHN1; effector of EPHA4 in axon guidance linking EPHA4 activation to RAC1 regulation (By similarity). Interacts (via PDZ motif) with SIPA1L1 (via PDZ domain); controls neuronal morphology through regulation of the RAP1 (RAP1A or RAP1B) and RAP2 (RAP2A, RAP2B or RAP2C) GTPases. Forms a ternary complex composed of ADAM10, CADH1 and EPHA4; within the complex, CADH1 is cleaved by ADAM10 which disrupts adherens junctions (By similarity).
messages: Postsynaptic density membrane
messages: Receptor tyrosine kinase which binds membrane-bound ephrin family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Highly promiscuous, it has the unique property among Eph receptors to bind and to be physiologically activated by both GPI-anchored ephrin-A and transmembrane ephrin-B ligands including EFNA1 and EFNB3. Upon activation by ephrin ligands, modulates cell morphology and integrin-dependent cell adhesion through regulation of the Rac, Rap and Rho GTPases activity. Plays an important role in the development of the nervous system controlling different steps of axonal guidance including the establishment of the corticospinal projections. May also control the segregation of motor and sensory axons during neuromuscular circuit development. In addition to its role in axonal guidance plays a role in synaptic plasticity. Activated by EFNA1 phosphorylates CDK5 at 'Tyr-15' which in turn phosphorylates NGEF regulating RHOA and dendritic spine morphogenesis. In the nervous system, also plays a role in repair after injury preventing axonal regeneration and in angiogenesis playing a role in central nervous system vascular formation. Additionally, its promiscuity makes it available to participate in a variety of cell-cell signaling regulating for instance the development of the thymic epithelium. During development of the cochlear organ of Corti, regulates pillar cell separation by forming a ternary complex with ADAM10 and CADH1 which facilitates the cleavage of CADH1 by ADAM10 and disruption of adherens junctions (By similarity). Phosphorylates CAPRIN1, promoting CAPRIN1-dependent formation of a membraneless compartment (By similarity).
messages: The protein kinase domain mediates interaction with NGEF.
messages: Ubiquitous.
messages: adherens junction
messages: axon
messages: dendrite

9606:FMC1
gene id: 9606:FMC1
uniprot id: Q96HJ9
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the FMC1 family.
messages: Interacts with ATPAF2 (PubMed:28719601).
messages: Mitochondrion
messages: Plays a role in the assembly/stability of the mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) (PubMed:28719601).

9606:TM4SF20
gene id: 9606:TM4SF20
uniprot id: Q53R12
names: Disease Annotation
names: Domain
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the L6 tetraspanin family.
messages: Cleaved by signal peptidase at Ser-14 but the peptide does not act as a signal peptide. Cleavage is inhibited by ceramide which inverts the orientation of TM4SF20 in membranes exposing the N-terminus to the cytosol and not to the endoplasmic reticulum lumen.
messages: Endoplasmic reticulum membrane
messages: Expressed in the brain, with high levels in the parietal lobe, hippocampus, pons, white matter and cerebellum.
messages: Glycosylated at Asn-132, Asn-148 and Asn-163 in presence of ceramide which inverts the orientation of TM4SF20 in membranes exposing these residues to the endoplasmic reticulum lumen.
messages: Membrane
messages: Polytopic transmembrane protein that inhibits regulated intramembrane proteolysis (RIP) of CREB3L1, inhibiting its activation and the induction of collagen synthesis (PubMed:25310401, PubMed:27499293). In response to ceramide, which alters TM4SF20 membrane topology, stimulates RIP activation of CREB3L1 (PubMed:27499293). Ceramide reverses the direction through which transmembrane helices are translocated into the endoplasmic reticulum membrane during translation of TM4SF20, this mechanism is called 'regulated alternative translocation' (RAT) and regulates the function of the transmembrane protein (PubMed:27499293).
messages: TGFB1 inhibits TM4SF20 expression to activate CREB3L1 (PubMed:25310401).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The first transmembrane helix plays a critical role for the insertion orientation in the endoplasmic reticulum membrane.

9606:CCDC81
gene id: 9606:CCDC81
uniprot id: Q6ZN84
names: Subcellular Location Annotation
messages: centrosome

9606:ISG15
gene id: 9606:ISG15
uniprot id: P05161
names: Disease Annotation
names: Domain
names: Function
names: Induction
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interaction with influenza B NS1 protein inhibits its conjugation.
messages: (Microbial infection) Interacts (via C-terminus) with Crimean-Congo hemorrhagic fever virus (CCHFV) RNA-directed RNA polymerase L (via N-terminus); the deISGylase activity of the viral protein interferes with antiviral signaling pathways mediated by NF-kappaB and IRF signalings.
messages: (Microbial infection) Interacts with vaccinia virus protein E3.
messages: Both the Ubiquitin-like 1 and Ubiquitin-like 2 domains are required for its efficient conjugation to cellular proteins. The two domains play different roles in the ISGylation pathway: Ubiquitin-like 2 domain is necessary for the first two steps allowing the linking of ISG15 to the E1 and E2 enzymes while Ubiquitin-like 1 domain is essential for the final, E3-mediated transfer of ISG15, from the E2 to the Lys of the target protein (PubMed:18356159).
messages: Cytoplasm
messages: Detected in lymphoid cells, striated and smooth muscle, several epithelia and neurons. Expressed in neutrophils, monocytes and lymphocytes. Enhanced expression seen in pancreatic adenocarcinoma, endometrial cancer, and bladder cancer, as compared to non-cancerous tissue. In bladder cancer, the increase in expression exhibits a striking positive correlation with more advanced stages of the disease.
messages: Homodimer; disulfide-linked (PubMed:2440890). Interacts with, and is conjugated to its targets by UBE1L (E1 enzyme) and UBE2E2 (E2 enzyme) (PubMed:11157743, PubMed:15131269). Interacts with NEDD4 (PubMed:18305167).
messages: Induced as an inactive, precursor protein that is cleaved by specific proteases to expose the C-terminal diglycine (LRLRGG) motif. This motif is essential not only for its conjugation to substrates but also for its recognition by the relevant processing proteases.
messages: S-nitrosylation decreases its dimerization, thereby increasing the availability as well as the solubility of monomeric ISG15 for its conjugation to cellular proteins.
messages: Secreted
messages: Strongly induced upon exposure to type I interferons, viruses, LPS, and other stresses, including certain genotoxic stresses.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitin-like protein which plays a key role in the innate immune response to viral infection either via its conjugation to a target protein (ISGylation) or via its action as a free or unconjugated protein. ISGylation involves a cascade of enzymatic reactions involving E1, E2, and E3 enzymes which catalyze the conjugation of ISG15 to a lysine residue in the target protein (PubMed:33727702). Its target proteins include IFIT1, MX1/MxA, PPM1B, UBE2L6, UBA7, CHMP5, CHMP2A, CHMP4B and CHMP6. Isgylation of the viral sensor IFIH1/MDA5 promotes IFIH1/MDA5 oligomerization and triggers activation of innate immunity against a range of viruses, including coronaviruses, flaviviruses and picornaviruses (PubMed:33727702). Can also isgylate: EIF2AK2/PKR which results in its activation, RIGI which inhibits its function in antiviral signaling response, EIF4E2 which enhances its cap structure-binding activity and translation-inhibition activity, UBE2N and UBE2E1 which negatively regulates their activity, IRF3 which inhibits its ubiquitination and degradation and FLNB which prevents its ability to interact with the upstream activators of the JNK cascade thereby inhibiting IFNA-induced JNK signaling. Exhibits antiviral activity towards both DNA and RNA viruses, including influenza A, HIV-1 and Ebola virus. Restricts HIV-1 and ebola virus via disruption of viral budding. Inhibits the ubiquitination of HIV-1 Gag and host TSG101 and disrupts their interaction, thereby preventing assembly and release of virions from infected cells. Inhibits Ebola virus budding mediated by the VP40 protein by disrupting ubiquitin ligase activity of NEDD4 and its ability to ubiquitinate VP40. ISGylates influenza A virus NS1 protein which causes a loss of function of the protein and the inhibition of virus replication. The secreted form of ISG15 can: induce natural killer cell proliferation, act as a chemotactic factor for neutrophils and act as a IFN-gamma-inducing cytokine playing an essential role in antim…

9606:ZNF217
gene id: 9606:ZNF217
uniprot id: O75362
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: Binds to the promoters of target genes and functions as repressor. Promotes cell proliferation and antagonizes cell death. Promotes phosphorylation of AKT1 at 'Ser-473'.
messages: Component of a histone deacetylase complex that contains HDAC2, KDM1A, CTBP1 and ZNF217. May be a component of a BHC histone deacetylase complex that contains HDAC1, HDAC2, HMG20B/BRAF35, KDM1A, RCOR1/CoREST, PHF21A/BHC80, ZMYM2, ZNF217, ZMYM3, GSE1 and GTF2I. Interacts with CTBP1 and CTBP2.
messages: Nucleus

9606:PER3
gene id: 9606:PER3
uniprot id: A0A087WV69
uniprot id: A2I2N5
uniprot id: P56645
names: Disease Annotation
names: Function
names: PTM
names: Polymorphism
names: Subcellular Location Annotation
names: Subunit
messages: Cytoplasm
messages: Homodimer. Component of the circadian core oscillator, which includes the CRY proteins, CLOCK or NPAS2, BMAL1 or BMAL2, CSNK1D and/or CSNK1E, TIMELESS and the PER proteins. Interacts directly with PER1, PER2, CRY1, CRY2, and TIMELESS; interaction with CRY1 and CRY2 is weak and not rhythmic. Interacts with FBXW11 and BTRC.
messages: Nucleus
messages: Originally described as a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots 'circa' (about) and 'diem' (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN. The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle. Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day. Transcription and translation of core clock components (CLOCK, NPAS2, BMAL1, BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle). A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a period shorter…
messages: Phosphorylation by CSNK1E is weak and appears to require association with PER1 and translocation to the nucleus.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The number of repeats of 18 amino acids in positions 966 to 1055 is polymorphic and varies among at least 2 different alleles. Alleles corresponding in size to a 4 (PER3.4) and 5 (PER3.5) repeats have been described. The sequence shown is that of allele PER3.5. In most populations around 10% of individuals are homozygous for the 5-repeat (PER3.5), whereas approximately 50% are homozygous for the 4-repeat (PER3.4). In some populations in Papua New Guinea the prevalence of the various genotypes appears to be reversed. These repeats and polymorphism are not present in non-primate mammals. Homozygosity for PER3.5 is more likely to show morning preference, whereas homozygosity for the PER3.4 associates with evening preferences. PER3.5 homozygous show vulnerability to sleep loss with a greater cognitive decline in response to total sleep deprivation (PubMed:11306557, PubMed:17346965, PubMed:19716732, PubMed:24439663, PubMed:24577121).
messages: Ubiquitinated.

9606:ST20-MTHFS
gene id: 9606:ST20-MTHFS
uniprot id: A0A0A6YYL1
names: Similarity
messages: Belongs to the 5-formyltetrahydrofolate cyclo-ligase family.

9606:PXN
gene id: 9606:PXN
uniprot id: A0A140VJQ8
uniprot id: P49023
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the paxillin family.
messages: Cytoskeletal protein involved in actin-membrane attachment at sites of cell adhesion to the extracellular matrix (focal adhesion). Recruits other proteins such as TRIM15 to focal adhesion.
messages: Interacts in vitro with VCL/vinculin as well as to the SH3 domain of SRC and, when tyrosine phosphorylated, to the SH2 domain of CRK (PubMed:7534286). Interacts with GIT1 (PubMed:10938112). Interacts with NUDT16L1/SDOS (By similarity). Interacts with PTK2/FAK1 (PubMed:14527389). Interacts with PTK2B/PYK2 (PubMed:19358827). Interacts with ASAP2 (PubMed:10749932). Interacts with unphosphorylated ITGA4 (PubMed:10604475). Interacts with RNF5 (PubMed:12861019). Interacts with PDCD10 (PubMed:20489202). Interacts with NEK3, the interaction is prolactin-dependent (PubMed:17297458). Interacts with PTK6 (PubMed:15572663). Interacts with TGFB1I1 (By similarity). Interacts with SORBS1 (PubMed:17462669). Interacts with PARVB (PubMed:22869380). Interacts (via LD motif 4) with PARVA/PARVIN (PubMed:15817463, PubMed:18508764, PubMed:18940607). Interacts (via LD motif 4) with ILK (PubMed:15817463, PubMed:18508764, PubMed:18940607). Interacts (via cytoplasmic domain) with CEACAM1; the interaction is phosphotyrosyl-dependent (PubMed:11035932). Interacts with LIMA1; this complex stabilizes actin dynamics (PubMed:24694988). Interacts with CD36 (via C-terminus) (PubMed:20037584). Interacts with TRIM15 (PubMed:25015296).
messages: Interacts strongly with PTK2/FAK1 and weakly with VCL/vinculin.
messages: Interacts strongly with VCL/vinculin but only weakly with PTK2/FAK1.
messages: Phosphorylated by MAPK1/ERK2 (By similarity). Phosphorylated on tyrosine residues during integrin-mediated cell adhesion, embryonic development, fibroblast transformation and following stimulation of cells by mitogens. Phosphorylation at Ser-244 by CDK5 reduces its interaction with PTK2/FAK1 in matrix-cell focal adhesions (MCFA) during oligodendrocytes (OLs) differentiation. Phosphorylation at Tyr-31 and Tyr-118 by PTK6 promote the activation of RAC1 via CRK/CrKII, thereby promoting migration and invasion. Phosphorylation at Ser-250 by SLK is required for PXN redistribution and cell motility (PubMed:23128389).
messages: cell cortex
messages: cytoskeleton
messages: focal adhesion

9606:RELCH
gene id: 9606:RELCH
uniprot id: Q9P260
names: Function
names: Subcellular Location Annotation
messages: Recycling endosome
messages: Regulates intracellular cholesterol distribution from recycling endosomes to the trans-Golgi network through interactions with RAB11 and OSBP (PubMed:29514919). Functions in membrane tethering and promotes OSBP-mediated cholesterol transfer between RAB11-bound recycling endosomes and OSBP-bound Golgi-like membranes (PubMed:29514919).
messages: trans-Golgi network

9606:TTC38
gene id: 9606:TTC38
uniprot id: Q5R3I4
names: Similarity
messages: Belongs to the TTC38 family.

9606:WNT6
gene id: 9606:WNT6
uniprot id: Q8N2E5
uniprot id: Q9Y6F9
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the Wnt family.
messages: Expressed in gastric cancer cell lines and gastric cancer tissues (at protein level). Detected in the apical gland region of the gastric foveolar epithelium (at protein level).
messages: Interacts with PORCN.
messages: Ligand for members of the frizzled family of seven transmembrane receptors.
messages: Ligand for members of the frizzled family of seven transmembrane receptors. Probable developmental protein. May be a signaling molecule which affects the development of discrete regions of tissues. Is likely to signal over only few cell diameters. Together with CAV1 may promote chemoresistance of gastric cancer cells to DNA-damaging anthracycline drugs through the activation of the canonical Wnt receptor signaling pathway.
messages: Palmitoleoylation is required for efficient binding to frizzled receptors. Depalmitoleoylation leads to Wnt signaling pathway inhibition.
messages: extracellular matrix

9606:PITPNM1
gene id: 9606:PITPNM1
uniprot id: B2R787
uniprot id: O00562
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the PtdIns transfer protein family. PI transfer class IIA subfamily.
messages: Catalyzes the transfer of phosphatidylinositol (PI) between membranes (PubMed:22822086, PubMed:10531358). Binds PI, phosphatidylcholine (PC) and phosphatidic acid (PA) with the binding affinity order of PI > PA > PC (PubMed:22822086). Regulates RHOA activity, and plays a role in cytoskeleton remodeling (PubMed:11909959). Necessary for normal completion of cytokinesis (PubMed:15125835). Plays a role in maintaining normal diacylglycerol levels in the Golgi apparatus (PubMed:15723057). Necessary for maintaining the normal structure of the endoplasmic reticulum and the Golgi apparatus (PubMed:15545272). Required for protein export from the endoplasmic reticulum and the Golgi (PubMed:15723057). Binds calcium ions (PubMed:10022914).
messages: Cleavage furrow
messages: Cytoplasm
messages: Endoplasmic reticulum membrane
messages: Golgi stack membrane
messages: Interacts with PIK4CA (By similarity). Interacts with PTK2B via its C-terminus. Interacts with RHOA. Has higher affinity for the inactive, GDP-bound form of RHOA. The CDK1-phosphorylated form interacts with PLK1. Interacts with VAPB.
messages: Lipid droplet
messages: Midbody
messages: Phosphorylated on multiple sites by CDK1 at the onset of mitosis. Phosphorylation facilitates dissociation from the Golgi complex and is required for interaction with PLK1.
messages: Phosphorylated on threonine residues upon treatment with oleic acid.
messages: Phosphorylated on tyrosine residues by PTK2B.
messages: Ubiquitous.

9606:GATB
gene id: 9606:GATB
uniprot id: O75879
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Allows the formation of correctly charged Gln-tRNA(Gln) through the transamidation of misacylated Glu-tRNA(Gln) in the mitochondria. The reaction takes place in the presence of glutamine and ATP through an activated gamma-phospho-Glu-tRNA(Gln).
messages: Belongs to the GatB/GatE family. GatB subfamily.
messages: Mitochondrion
messages: Predominantly expressed in tissues characterized by high rates of oxidative phosphorylation (OxPhos), including muscle and heart.
messages: Subunit of the heterotrimeric GatCAB amidotransferase (AdT) complex, composed of A (QRSL1), B (GATB) and C (GATC) subunits.
messages: The disease may be caused by variants affecting the gene represented in this entry.

9606:CGB3
gene id: 9606:CGB3
uniprot id: A0A0F7RQP8
uniprot id: P0DN86
names: Developmental Stage
names: Function
names: Miscellaneous
names: Pharmaceutical
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Available under the names Novarel (Ferring) and Profasi (Serono). Used as adjunctive therapy in the treatment of obesity. There is no substantial evidence that it increases weight loss beyond that resulting from caloric restriction, that it causes a more attractive or 'normal' distribution of fat, or that it decreases the hunger and discomfort associated with calorie-restricted diets.
messages: Belongs to the glycoprotein hormones subunit beta family.
messages: Beta subunit of the human chorionic gonadotropin (hCG). hCG is a complex glycoprotein composed of two glycosylated subunits alpha and beta which are non-covalently associated. The alpha subunit is identical to those in the pituitary gonadotropin hormones (LH, FSH and TSH). The beta subunits are distinct in each of the hormones and confer receptor and biological specificity. Has an essential role in pregnancy and maternal adaptation. Stimulates the ovaries to synthesize the steroids that are essential for the maintenance of pregnancy.
messages: Encoded by a cluster of genes that have evolved by duplication from LHB. HCG-beta is encoded by six non-allelic genes (CGB) clustered on chromosome 19q13.3 and named CGB1, CGB2, CGB3, CGB5, CGB7 and CGB8. Two specific hCGb proteins that differ by three amino acids in positions 2,4 and 117 have been described: type 1 (CGB7) and type 2 (CGB3, CGB5, CGB8). The CGB gene first arose in the common ancestor of the anthropoid primates.
messages: Expressed continuously during the whole pregnancy with a peak during the first trimester.
messages: Heterodimer of a common alpha chain identical in LH, FSH, TSH and HCG and a unique beta chain distinct in each of the hormones.
messages: High expression in the placenta throughout pregnancy.
messages: Secreted

9606:NT5C2
gene id: 9606:NT5C2
uniprot id: A0A384MED8
uniprot id: A8K6K2
uniprot id: P49902
names: Activity Regulation
names: Cofactor
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Allosterically activated by various compounds including ATP, 2,3-BPG/2,3-Bisphosphoglyceric acid and Ap4A/P1,P4-bis(5'-adenosyl) tetraphosphate (PubMed:1659319, PubMed:10092873, PubMed:21396942). Binding of an allosteric activator is a prerequisiste to magnesium and substrate binding (PubMed:21396942). Inhibited by inorganic phosphate (PubMed:10092873).
messages: Belongs to the 5'(3')-deoxyribonucleotidase family.
messages: Binds 1 Mg(2+) ion per subunit.
messages: Broad specificity cytosolic 5'-nucleotidase that catalyzes the dephosphorylation of 6-hydroxypurine nucleoside 5'-monophosphates (PubMed:1659319, PubMed:9371705, PubMed:10092873, PubMed:12907246). In addition, possesses a phosphotransferase activity by which it can transfer a phosphate from a donor nucleoside monophosphate to an acceptor nucleoside, preferably inosine, deoxyinosine and guanosine (PubMed:1659319, PubMed:9371705). Has the highest activities for IMP and GMP followed by dIMP, dGMP and XMP (PubMed:1659319, PubMed:9371705, PubMed:10092873, PubMed:12907246). Could also catalyze the transfer of phosphates from pyrimidine monophosphates but with lower efficiency (PubMed:1659319, PubMed:9371705). Through these activities regulates the purine nucleoside/nucleotide pools within the cell (PubMed:1659319, PubMed:9371705, PubMed:10092873, PubMed:12907246).
messages: Homotetramer.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Widely expressed.
messages: cytosol

9606:PPT2
gene id: 9606:PPT2
uniprot id: A0A1U9X8D2
uniprot id: Q9UMR5
names: Caution
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the palmitoyl-protein thioesterase family.
messages: Broadly expressed, with highest levels in skeletal muscle.
messages: Catalytically inactive due to lack of His-283. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Lysosome
messages: Removes thioester-linked fatty acyl groups from various substrates including S-palmitoyl-CoA. Has the highest S-thioesterase activity for the acyl groups palmitic and myristic acid followed by other short- and long-chain acyl substrates. However, because of structural constraints, is unable to remove palmitate from peptides or proteins.
messages: Was originally referred as a palmitoyl-protein thioesterase (palmitoyl-protein hydrolase).

9606:SLAMF1
gene id: 9606:SLAMF1
uniprot id: Q13291
names: Domain
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Acts as a receptor for Measles virus; also including isoform 4.
messages: (Microbial infection) Interacts with measles hemagglutinin protein.
messages: Cell membrane
messages: Constitutively expressed on peripheral blood memory T-cells, T-cell clones, immature thymocytes and a proportion of B-cells, and is rapidly induced on naive T-cells after activation (PubMed:7617038). Activated B-cells express isoform 1, isoform 3 and a cytoplasmic isoform (PubMed:9091591). Isoform 4 is expressed in B-cells, primary T-cells, dendritic cells and macrophages. Isoform 4 is expressed in tumors of the central nervous system (PubMed:25710480).
messages: Interacts (via cytoplasmic domain) with SH2D1A and SH2D1B; SH2D1A mediates association with FYN; SH2D1A binds to phosphorylated and not phosphorylated ITSM 1 (PubMed:9774102, PubMed:11313386, PubMed:11806999, PubMed:12458214). Interacts (via cytoplasmic domain phosphorylated on tyrosine residues) with INPP5D and PTPN11; presence of SH2D1A facilitates binding to INPP5D (PubMed:11313386, PubMed:12458214). Interacts with MAP4K1 (PubMed:20231852). Interacts with PIK3C3, BECN1 and UVRAG; indicative for an association with PI3K complex II (PI3KC3-C2) (PubMed:20818396).
messages: Phosphorylated on tyrosine residues by FYN.
messages: Secreted
messages: Self-ligand receptor of the signaling lymphocytic activation molecule (SLAM) family. SLAM receptors triggered by homo- or heterotypic cell-cell interactions are modulating the activation and differentiation of a wide variety of immune cells and thus are involved in the regulation and interconnection of both innate and adaptive immune response. Activities are controlled by presence or absence of small cytoplasmic adapter proteins, SH2D1A/SAP and/or SH2D1B/EAT-2. SLAMF1-induced signal-transduction events in T-lymphocytes are different from those in B-cells. Two modes of SLAMF1 signaling seem to exist: one depending on SH2D1A (and perhaps SH2D1B) and another in which protein-tyrosine phosphatase 2C (PTPN11)-dependent signal transduction operates. Initially it has been proposed that association with SH2D1A prevents binding to inhibitory effectors including INPP5D/SHIP1 and PTPN11/SHP-2 (PubMed:11806999). However, signaling is also regulated by SH2D1A which can simultaneously interact with and recruit FYN which subsequently phosphorylates and activates SLAMF1 (PubMed:12458214). Mediates IL-2-independent proliferation of activated T-cells during immune responses and induces IFN-gamma production (By similarity). Downstreaming signaling involves INPP5D, DOK1 and DOK2 leading to inhibited IFN-gamma production in T-cells, and PRKCQ, BCL10 and NFKB1 leading to increased T-cell activation and Th2 cytokine production (By similarity). Promotes T-cell receptor-induced IL-4 secretion by CD4(+) cells (By similarity). Inhibits antigen receptor-mediated production of IFN-gamma, but not IL-2, in CD4(-)/CD8(-) T-cells (By similarity). Required for IL-4 production by germinal centers T follicular helper (T(Fh))cells (By similarity). May inhibit CD40-induced signal transduction in monocyte-derived dendritic cells (PubMed:16317102). May play a role in allergic responses and may regulate allergen-induced Th2 cytokine and Th1 cytokine secretion (By similarity). In conjunction with SLAMF6 con…
messages: The ITSMs (immunoreceptor tyrosine-based switch motifs) with the consensus sequence T-X-Y-X-X-[VI] present in SLAM family receptors have overlapping specificity for activating and inhibitory SH2 domain-containing binding partners. Especially they mediate the interaction with the SH2 domain of SH2D1A and SH2D1B. For SLAMF1 a 'two-out-of-three-pronged' mechanism is proposed involving threonine (position -2), phosphorylated tyrosine (position 0) and valine/isoleucine (position +3). SH2D1A binding is mediated by either three 'prongs' (for high affinity binding involving ITSM 1) or a combination of any two also including non-phosphorylated Tyr-281 of ITSM 1 thus providing a positive feedback loop implicating SH2D1A-dependent recruitment of activating FYN. ITSM 2 needs to be phosphorylated on Tyr-327 for SH2D1A binding.

9606:COX10
gene id: 9606:COX10
uniprot id: Q12887
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the UbiA prenyltransferase family.
messages: Converts protoheme IX and farnesyl diphosphate to heme O.
messages: Mitochondrion membrane
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:OR4D2
gene id: 9606:OR4D2
uniprot id: A0A126GWK0
uniprot id: P58180
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Membrane
messages: Odorant receptor.

9606:SPOUT1
gene id: 9606:SPOUT1
uniprot id: Q5T280
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the class IV-like SAM-binding methyltransferase superfamily.
messages: Depletion with RNAi causes a significant accumulation of cells in later prometaphase with misaligned chromosomes.
messages: Interacts with INCA1.
messages: Required for association of the centrosomes with the poles of the bipolar mitotic spindle during metaphase (PubMed:20813266, PubMed:25657325). Also involved in chromosome alignment (PubMed:20813266). May promote centrosome maturation probably by recruiting A-kinase anchor protein AKAP9 to centrosomes in early mitosis (PubMed:25657325). Binds specifically to miRNA MIR145 hairpin, regulates MIR145 expression at a postranscriptional level (PubMed:28431233).
messages: centrosome
messages: kinetochore
messages: spindle

9606:KRT81
gene id: 9606:KRT81
uniprot id: Q14533
names: Disease Annotation
names: Miscellaneous
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Abundantly expressed in the differentiating cortex of growing (anagen) hair. Expression is restricted to the keratinocytes of the hair cortex and is absent from inner root sheath and medulla. Expressed in malignant lymph node tissue in breast carcinoma tissue.
messages: Belongs to the intermediate filament family.
messages: Heterotetramer of two type I and two type II keratins.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: There are two types of hair/microfibrillar keratin, I (acidic) and II (neutral to basic).

9606:ZNG1E
gene id: 9606:ZNG1E
uniprot id: Q5RIA9
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the SIMIBI class G3E GTPase family. ZNG1 subfamily.
messages: Nucleus
messages: Zinc chaperone that directly transfers zinc cofactor to target metalloproteins, thereby activating them. Catalyzes zinc insertion into the active site of methionine aminopeptidase METAP1, which function to cleave the initiator methionine from polypeptides during or after protein translation. Mechanistically, the N-terminal psi-PxLVp motif binds to the C6H2-type zinc finger of inactive form of METAP1. After formation of the docked complex, zinc is transferred from the CXCC motif in the GTPase domain of ZNG1E to the zinc binding site in the peptidase domain of METAP1 in a process requiring GTP hydrolysis. GTP/GDP exchange is required for release of active METAP1.

9606:DEK
gene id: 9606:DEK
uniprot id: P35659
names: Disease Annotation
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: A chromosomal aberration involving DEK is found in a subset of acute myeloid leukemia (AML); also known as acute non-lymphocytic leukemia (PubMed:1549122). Translocation t(6;9)(p23;q34) with NUP214/CAN (PubMed:1549122). It results in the formation of a DEK-NUP214 fusion gene (PubMed:1549122).
messages: Found in a mRNA splicing-dependent exon junction complex (EJC) with DEK, RBM8A, RNPS1, SRRM1 and ALYREF/THOC4. Interacts with histones H2A, H2B, H3, H4, acetylated histone H4, non-phosphorylated DAXX and HDAC2. Component of the B-WICH complex, at least composed of SMARCA5/SNF2H, BAZ1B/WSTF, SF3B1, DEK, MYO1C, ERCC6, MYBBP1A and DDX21. Binds DNA.
messages: Involved in chromatin organization.
messages: Nucleus
messages: Phosphorylated by CK2. Phosphorylation fluctuates during the cell cycle with a moderate peak during G(1) phase, and weakens the binding of DEK to DNA.
messages: Ubiquitous. Expressed at relatively high levels.

9606:BICDL2
gene id: 9606:BICDL2
uniprot id: A1A5D9
names: Similarity
names: Subunit
messages: Belongs to the BICDR family.
messages: Interacts with RAB13.

9606:TCF24
gene id: 9606:TCF24
uniprot id: Q7RTU0
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Efficient DNA binding requires dimerization with another bHLH protein.
messages: Nucleus
messages: Putative transcription factor.

9606:TSPEAR
gene id: 9606:TSPEAR
uniprot id: Q8WU66
names: Disease Annotation
names: Function
names: Sequence Caution
names: Subcellular Location Annotation
messages: Cell surface
messages: Intron retention.
messages: Plays a critical role in tooth and hair follicle morphogenesis through regulation of the Notch signaling pathway (PubMed:27736875). May play a role in development or function of the auditory system (PubMed:22678063).
messages: Secreted
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: stereocilium

9606:DCAF12
gene id: 9606:DCAF12
uniprot id: Q5T6F0
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the WD repeat DCAF12 family.
messages: Component of the DCX(DCAF12) E3 ubiquitin ligase complex, at least composed of CUL4 (CUL4A or CUL4B), DDB1, DCAF12 and RBX1.
messages: Cytoplasm
messages: Highly expressed in lung cancer tissues and some cancer cell lines (PubMed:18957058). Restricted expression in normal testis (PubMed:18957058).
messages: Nucleus
messages: Substrate-recognition component of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation (PubMed:16949367, PubMed:16964240, PubMed:29779948). The C-degron recognized by the DesCEND pathway is usually a motif of less than ten residues and can be present in full-length proteins, truncated proteins or proteolytically cleaved forms (PubMed:29779948). The DCX(DCAF12) complex specifically recognizes proteins with a diglutamate (Glu-Glu) at the C-terminus, such as MAGEA3, MAGEA6 and CCT5, leading to their ubiquitination and degradation (PubMed:29779948, PubMed:31267705). Ubiquitination of MAGEA3, MAGEA6 by DCX(DCAF12) complex is required for starvation-induced autophagy (PubMed:31267705). Also directly recognizes the C-terminal glutamate-leucine (Glu-Leu) degron as an alternative degron in proteins such as MOV10, leading to their ubiquitination and degradation. Controls the protein level of MOV10 during spermatogenesis and in T cells, especially after their activation (PubMed:34065512).
messages: centrosome

9606:RPS6KL1
gene id: 9606:RPS6KL1
uniprot id: Q9Y6S9
names: Similarity
messages: Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. S6 kinase subfamily.

9606:CLDND2
gene id: 9606:CLDND2
uniprot id: Q8NHS1
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the PMP-22/EMP/MP20 family.
messages: Membrane

9606:DLGAP2
gene id: 9606:DLGAP2
uniprot id: A0A1B0GTN4
names: Similarity
messages: Belongs to the SAPAP family.

9606:CXCL6
gene id: 9606:CXCL6
uniprot id: P80162
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the intercrine alpha (chemokine CxC) family.
messages: Chemotactic for neutrophil granulocytes. Signals through binding and activation of its receptors (CXCR1 and CXCR2). In addition to its chemotactic and angiogenic properties, it has strong antibacterial activity against Gram-positive and Gram-negative bacteria (90-fold-higher when compared to CXCL5 and CXCL7).
messages: Secreted

9606:SSTR3
gene id: 9606:SSTR3
uniprot id: P32745
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Brain, pituitary and pancreas.
messages: Cell membrane
messages: Homodimer and heterodimer with SSTR2. Heterodimerization with SSTR2 inactivates SSTR3 receptor function (By similarity).
messages: Phosphorylated. Phosphorylation increases upon somatostatin binding (By similarity).
messages: Receptor for somatostatin-14 and -28. This receptor is coupled via pertussis toxin sensitive G proteins to inhibition of adenylyl cyclase.

9606:EDEM2
gene id: 9606:EDEM2
uniprot id: Q9BV94
names: Caution
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the glycosyl hydrolase 47 family.
messages: Endoplasmic reticulum lumen
messages: Expressed ubiquitously in all tissues tested with slightly higher levels detected in small intestine and peripheral blood leukocytes and weakest levels in brain and skeletal muscle.
messages: Has similarity to alpha 1,2-mannosidases, but the catalytic activity of this protein is controversial (PubMed:15537790, PubMed:25092655). One study shows that it is important for a specific oligosaccharide trimming step from Man9GlcNAc2 to Man8GlcNAc2, suggesting activity as a mannosidase (PubMed:25092655). However, another study reports that this protein has no mannosidase activity (PubMed:15537790).
messages: Involved in the endoplasmic reticulum-associated degradation (ERAD) pathway that targets misfolded glycoproteins for degradation in an N-glycan-dependent manner (PubMed:15537790, PubMed:25092655). May initiate ERAD by promoting the first mannose trimming step of ERAD substrates, from Man9GlcNAc2 to Man8GlcNAc2 (PubMed:25092655). Seems to recognize and bind to exposed hydrophobic regions in target proteins (By similarity).
messages: N-glycosylated.

9606:ESR2
gene id: 9606:ESR2
uniprot id: A0A348FV93
uniprot id: F1D8N3
uniprot id: Q0PTK2
uniprot id: Q7LCB3
uniprot id: Q92731
names: Caution
names: Disease Annotation
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the nuclear hormone receptor family. NR3 subfamily.
messages: Binds DNA as a homodimer. Can form a heterodimer with ESR1. Interacts with NCOA1, NCOA3, NCOA5 and NCOA6 coactivators, leading to a strong increase of transcription of target genes. Interacts with UBE1C. Interacts with AKAP13. Interacts with DNTTIP2. Interacts with isoform 4 of TXNRD1. Interacts with CCDC62 in the presence of estradiol/E2; this interaction seems to enhance the transcription of target genes, including cyclin-D1/CCND1 AP-1 promoter. Interacts with DNAAF4 (By similarity). Interacts with PRMT2. Interacts with CCAR2 (via N-terminus) in a ligand-independent manner. Interacts with RBM39, in the presence of estradiol (E2) (By similarity).
messages: Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.
messages: Does not form homodimers.
messages: Expressed in spleen, thymus, testis and ovary and at a lower level in skeletal muscle, prostate, colon, small intestine, leukocytes, bone marrow, mammary gland and uterus.
messages: Expressed in testis and ovary, and at a lower level in heart, brain, placenta, liver, skeletal muscle, spleen, thymus, prostate, colon, bone marrow, mammary gland and uterus. Also found in uterine bone, breast, and ovarian tumor cell lines, but not in colon and liver tumors.
messages: Expressed in testis, and at a lower level in spleen, thymus, ovary, mammary gland and uterus.
messages: Expressed in testis, placenta, skeletal muscle, spleen and leukocytes, and at a lower level in heart, lung, liver, kidney, pancreas, thymus, prostate, colon, small intestine, bone marrow, mammary gland and uterus. Not expressed in brain.
messages: Expressed in the testis.
messages: Had previously been shown to interact with PELP1. However this paper was retracted as cell-based data was viewed as unreliable.
messages: Lacks ligand binding ability and has no or only very low ERE binding activity resulting in the loss of ligand-dependent transactivation ability.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1/ER-alpha, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner (PubMed:20074560).
messages: Nucleus
messages: Phosphorylation at Ser-87 and Ser-105 recruits NCOA1.
messages: Preferentially forms a heterodimer with ESR1 rather than ESR2 isoform 1 and inhibits DNA-binding by ESR1.
messages: The disease may be caused by variants affecting the gene represented in this entry.

9606:MICOS13
gene id: 9606:MICOS13
uniprot id: A0A140TA84
uniprot id: A0A140TA86
uniprot id: Q5XKP0
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the MICOS complex subunit Mic13 family.
messages: Component of the MICOS complex, a large protein complex of the mitochondrial inner membrane that plays crucial roles in the maintenance of crista junctions, inner membrane architecture, and formation of contact sites to the outer membrane.
messages: Component of the MICOS complex, a large protein complex of the mitochondrial inner membrane that plays crucial roles in the maintenance of crista junctions, inner membrane architecture, and formation of contact sites to the outer membrane. Constituent of mature MICOS complex, it is required for the formation of cristae junction (CJ) and maintenance of cristae morphology. Required for the incorporation of MICOS10/MIC10 into the MICOS complex.
messages: Component of the mitochondrial contact site and cristae organizing system (MICOS) complex, composed of at least MICOS10/MIC10, CHCHD3/MIC19, CHCHD6/MIC25, APOO/MIC26, MICOS13/MIC13, APOOL/MIC27 and IMMT/MIC60. The MICOS complex associates with mitochondrial outer membrane proteins SAMM50, MTX1 and MTX2 (together described as components of the mitochondrial outer membrane sorting assembly machinery (SAM) complex) and DNAJC11, mitochondrial inner membrane protein TMEM11 and with HSPA9. The MICOS and SAM complexes together with DNAJC11 are part of a large protein complex spanning both membranes termed the mitochondrial intermembrane space bridging (MIB) complex.
messages: Component of the mitochondrial contact site and cristae organizing system (MICOS) complex.
messages: Membrane
messages: Mitochondrion inner membrane
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:C5
gene id: 9606:C5
uniprot id: A0A8Q3SID6
uniprot id: P01031
uniprot id: Q59GS8
names: Disease Annotation
names: Function
names: Polymorphism
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Interacts with Staphylococcus aureus protein SSL5.
messages: Activation of C5 by a C5 convertase initiates the spontaneous assembly of the late complement components, C5-C9, into the membrane attack complex. C5b has a transient binding site for C6. The C5b-C6 complex is the foundation upon which the lytic complex is assembled.
messages: An association study of C5 haplotypes and genotypes in individuals with chronic hepatitis C virus infection shows that individuals homozygous for the C5_1 haplotype have a significantly higher stage of liver fibrosis than individuals carrying at least 1 other allele.
messages: C5 precursor is first processed by the removal of 4 basic residues, forming two chains, beta and alpha, linked by a disulfide bond. C5 convertase activates C5 by cleaving the alpha chain, releasing C5a anaphylatoxin and generating C5b (beta chain + alpha' chain). Interacts with the tick complement inhibitors OmCI, RaCI1 and CirpT1 (PubMed:18536718, PubMed:27018802, PubMed:31871188). Interacts with cobra venom factor (CVF) (PubMed:21217642).
messages: C5 variants are responsible for poor response to eculizumab [MIM:615749]. Eculizumab is a monoclonal antibody highly effective in reducing intravascular hemolysis in patients with paroxysmal nocturnal hemoglobinuria. It specifically binds to the terminal complement protein C5, inhibits its cleavage into C5a and C5b, and prevents the formations of the cytolytic complement pore (PubMed:24521109).
messages: Derived from proteolytic degradation of complement C5, C5a anaphylatoxin is a mediator of local inflammatory process. Binding to the receptor C5AR1 induces a variety of responses including intracellular calcium release, contraction of smooth muscle, increased vascular permeability, and histamine release from mast cells and basophilic leukocytes (PubMed:8182049). C5a is also a potent chemokine which stimulates the locomotion of polymorphonuclear leukocytes and directs their migration toward sites of inflammation.
messages: Interacts with C5AR1.
messages: Secreted
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:ADORA1
gene id: 9606:ADORA1
uniprot id: P30542
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Receptor for adenosine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase.

9606:CD79A
gene id: 9606:CD79A
uniprot id: P11912
names: Disease Annotation
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Arginine methylation in the ITAM domain may interfere with the binding of SYK. It promotes signals leading to B-cell differentiation (By similarity).
messages: B-cells.
messages: Cell membrane
messages: Heterodimer of alpha and beta chains; disulfide-linked. Part of the B-cell antigen receptor complex where the alpha/beta chain heterodimer is non-covalently associated with an antigen-specific membrane-bound surface immunoglobulin of two heavy chains and two light chains. Interacts through its phosphorylated ITAM domain with the SH2 domains of SYK which stimulates SYK autophosphorylation and activation. Also interacts, when phosphorylated on Tyr-210, with the SH2 domain of BLNK/SLP65, bringing BLNK into proximity with SYK and allowing SYK to phosphorylate BLNK which is necessary for trafficking of the BCR to late endosomes. Interacts with Src-family tyrosine kinases including FYN and LYN, increasing their activity (By similarity).
messages: Phosphorylated on tyrosine, serine and threonine residues upon B-cell activation. Phosphorylation of tyrosine residues by Src-family kinases is an early and essential feature of the BCR signaling cascade. The phosphorylated tyrosines serve as docking sites for SH2-domain containing kinases, leading to their activation which in turn leads to phosphorylation of downstream targets. Phosphorylated by LYN. Phosphorylation of serine and threonine residues may prevent subsequent tyrosine phosphorylation.
messages: Required in cooperation with CD79B for initiation of the signal transduction cascade activated by binding of antigen to the B-cell antigen receptor complex (BCR) which leads to internalization of the complex, trafficking to late endosomes and antigen presentation. Also required for BCR surface expression and for efficient differentiation of pro- and pre-B-cells. Stimulates SYK autophosphorylation and activation. Binds to BLNK, bringing BLNK into proximity with SYK and allowing SYK to phosphorylate BLNK. Also interacts with and increases activity of some Src-family tyrosine kinases. Represses BCR signaling during development of immature B-cells.
messages: The disease is caused by variants affecting the gene represented in this entry. Two different mutations, one at the splice donor site of intron 2 and the other at the splice acceptor site for exon 3, have been identified. Both mutations give rise to a truncated protein.

9606:PRAMEF17
gene id: 9606:PRAMEF17
uniprot id: Q5VTA0
names: Similarity
messages: Belongs to the PRAME family.

9606:POTEA
gene id: 9606:POTEA
uniprot id: Q6S8J7
names: Similarity
messages: Belongs to the POTE family.

9606:CFAP91
gene id: 9606:CFAP91
uniprot id: Q7Z4T9
names: Disease Annotation
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the CFAP91 family.
messages: Cytoplasm
messages: Does not interact with MYCBP.
messages: Interacts with MYCBP and AKAP1. Part of a complex containing MYCBP, AKAP1 and PRKAR2B.
messages: Involved in sperm flagellum axonemal organization and function (PubMed:12223483, PubMed:32161152). May regulate cilium motility through its role in the assembly of the axonemal radial spokes (By similarity).
messages: May be produced by alternative promoter usage.
messages: Mitochondrion
messages: Phosphorylated by PKA.
messages: Strongly expressed in the liver.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Widely expressed, but strongly expressed in all spermatogenesis-related tissues, including the testis, the epithelium of cauda and the corpus epididymis, as well as the spermatid and mature sperm. Also expressed in Leydig cells.
messages: cilium axoneme

9606:COA4
gene id: 9606:COA4
uniprot id: Q9NYJ1
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the COA4 family.
messages: Mitochondrion
messages: Putative COX assembly factor.
messages: Up-regulated by estrogen.

9606:PRR20A
gene id: 9606:PRR20A
uniprot id: P86478
uniprot id: P86479
uniprot id: P86480
uniprot id: P86481
uniprot id: P86496
names: Similarity
messages: Belongs to the PRR20 family.

9606:ADAMTS3
gene id: 9606:ADAMTS3
uniprot id: O15072
names: Caution
names: Cofactor
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Binds 1 zinc ion per subunit.
messages: Cleaves the propeptides of type II collagen prior to fibril assembly. Does not act on types I and III collagens.
messages: Found in cartilage and skin.
messages: Glycosylated. Can be O-fucosylated by POFUT2 on a serine or a threonine residue found within the consensus sequence C1-X(2)-(S/T)-C2-G of the TSP type-1 repeat domains where C1 and C2 are the first and second cysteine residue of the repeat, respectively. Fucosylated repeats can then be further glycosylated by the addition of a beta-1,3-glucose residue by the glucosyltransferase, B3GALTL. Fucosylation mediates the efficient secretion of ADAMTS family members. Can also be C-glycosylated with one or two mannose molecules on tryptophan residues within the consensus sequence W-X-X-W of the TPRs, and N-glycosylated. These other glycosylations can also facilitate secretion (By similarity).
messages: Has sometimes been referred to as ADAMTS4.
messages: Secreted
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The precursor is cleaved by a furin endopeptidase.
messages: The spacer domain and the TSP type-1 domains are important for a tight interaction with the extracellular matrix.
messages: extracellular matrix

9606:DNER
gene id: 9606:DNER
uniprot id: Q8NFT8
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Activator of the NOTCH1 pathway. May mediate neuron-glia interaction during astrocytogenesis (By similarity).
messages: Cell membrane
messages: Expressed in brain, spinal cord and adrenal gland.
messages: Interacts with AP1G1. Interacts with NOTCH1 (By similarity).

9606:INHBC
gene id: 9606:INHBC
uniprot id: P55103
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the TGF-beta family.
messages: Expressed in benign prostatic hyperplasia.
messages: Homodimeric or heterodimeric through association with alpha and beta subunits, linked by one or more disulfide bonds. Inhibins are heterodimers of one alpha and one beta subunit. Activins are homo- or heterodimers of beta subunits only (By similarity).
messages: Inhibins and activins inhibit and activate, respectively, the secretion of follitropin by the pituitary gland. Inhibins/activins are involved in regulating a number of diverse functions such as hypothalamic and pituitary hormone secretion, gonadal hormone secretion, germ cell development and maturation, erythroid differentiation, insulin secretion, nerve cell survival, embryonic axial development or bone growth, depending on their subunit composition. Inhibins appear to oppose the functions of activins.
messages: Secreted

9606:GKN2
gene id: 9606:GKN2
uniprot id: Q86XP6
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Expressed in gastric mucosa.
messages: Interacts with TFF2 (By similarity). Heterodimer with TFF1; disulfide linked.
messages: Secreted

9606:TMEM235
gene id: 9606:TMEM235
uniprot id: A6NFC5
names: Developmental Stage
names: PTM
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the PMP-22/EMP/MP20 family.
messages: Endoplasmic reticulum
messages: Membrane
messages: N-glycosylated.
messages: Not detected before gestational days 53-54. Expressed in the eye at gestational week 10.

9606:TNIP1
gene id: 9606:TNIP1
uniprot id: Q15025
names: Function
names: Miscellaneous
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts with Shigella flexneri ipah9.8; the interaction promotes polyubiquitination of IKBKG.
messages: Cytoplasm
messages: Inhibits NF-kappa-B activation and TNF-induced NF-kappa-B-dependent gene expression by regulating TAX1BP1 and A20/TNFAIP3-mediated deubiquitination of IKBKG; proposed to link A20/TNFAIP3 to ubiquitinated IKBKG (PubMed:21885437). Involved in regulation of EGF-induced ERK1/ERK2 signaling pathway; blocks MAPK3/MAPK1 nuclear translocation and MAPK1-dependent transcription. Increases cell surface CD4(T4) antigen expression. Involved in the anti-inflammatory response of macrophages and positively regulates TLR-induced activation of CEBPB. Involved in the prevention of autoimmunity; this function implicates binding to polyubiquitin. Involved in leukocyte integrin activation during inflammation; this function is mediated by association with SELPLG and dependent on phosphorylation by SRC-family kinases. Interacts with HIV-1 matrix protein and is packaged into virions and overexpression can inhibit viral replication. May regulate matrix nuclear localization, both nuclear import of PIC (Preintegration complex) and export of GAG polyprotein and viral genomic RNA during virion production. In case of infection, promotes association of IKBKG with Shigella flexneri E3 ubiquitin-protein ligase ipah9.8 p which in turn promotes polyubiquitination of IKBKG leading to its proteasome-dependent degradation and thus is perturbing NF-kappa-B activation during bacterial infection.
messages: Interacts with TNFAIP3 and IKBKG (polyubiquitinated); facilitates TNFAIP3-mediated de-ubiquitination of NEMO/IKBKG. Interacts with polyubiquitin. Interacts with MAPK1, SELPLG and PIK3CD. Interacts with IRAK1 (polyubiquitinated). Interacts with MYD88; the interaction is indicative for participation in an activated TLR-signaling complex. Interacts with HIV-1 matrix protein. Interacts with TAX1BP1 (PubMed:21885437).
messages: Less effective in the NF-kappa-B inhibitory effect.
messages: Nucleus
messages: Phosphorylation at Tyr-552 by SRC-family kinases recruits phosphoinositide-3-kinase (PI3K) PIK3CD:p85 heterodimer which results in integrin activation and leukocyte adhesion to activated endothelium during inflammation.
messages: Ubiquitous. Strongly expressed in peripheral blood lymphocytes, spleen and skeletal muscle, and is weakly expressed in the brain. In peripheral blood mononucleocytes, isoform 4 is mainly expressed and isoform 1 and isoform 7 are almost not expressed. Expression of isoform 1 and isoform 7 increases in leukemic cells.

9606:SERPINB1
gene id: 9606:SERPINB1
uniprot id: P30740
uniprot id: V9HWH1
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the serpin family.
messages: Belongs to the serpin family. Ov-serpin subfamily.
messages: Cytolytic granule
messages: Cytoplasm
messages: Early endosome
messages: In human bone marrow, present in all CD45+ populations. Expression levels are highest in the neutrophil lineage, intermediate in monocytic, and lowest in lymphocytic lineage. Within the neutrophil lineage, expression is highest in promyelocytes.
messages: Monomer (PubMed:23269243). Interacts (via C-terminus) with CASP1; CASP4 (via CARD domain) and CASP5; these interactions regulate the activity of inflammatory caspases (PubMed:30692621). Interacts with PRTN3 (PubMed:30692621). Interacts with GZMH (PubMed:23269243).
messages: Neutrophil serine protease inhibitor that plays an essential role in the regulation of the innate immune response, inflammation and cellular homeostasis (PubMed:30692621). Acts primarily to protect the cell from proteases released in the cytoplasm during stress or infection. These proteases are important in killing microbes but when released from granules, these potent enzymes also destroy host proteins and contribute to mortality. Regulates the activity of the neutrophil proteases elastase, cathepsin G, proteinase-3, chymase, chymotrypsin, and kallikrein-3 (PubMed:11747453, PubMed:30692621). Acts also as a potent intracellular inhibitor of GZMH by directly blocking its proteolytic activity (PubMed:23269243). During inflammation, limits the activity of inflammatory caspases CASP1, CASP4 and CASP5 by suppressing their caspase-recruitment domain (CARD) oligomerization and enzymatic activation (PubMed:30692621). When secreted, promotes the proliferation of beta-cells via its protease inhibitory function (PubMed:26701651).
messages: Reactive bond 1 is specific for reaction with chymotrypsin-like protease such as cathepsin G, chymotrypsin, chymase or granzyme H, while reactive bond 2 is specific for reaction with elastase-like protease such as neutrophil elastase, proteinase-3, pancreatic elastase or PSA.
messages: Secreted

9606:CARD18
gene id: 9606:CARD18
uniprot id: P57730
names: Function
names: Induction
names: Subunit
names: Tissue Specificity
messages: Inhibits generation of IL-1-beta by interacting with caspase-1 and preventing its association with RIP2. Down-regulates the release of IL1B.
messages: Interacts with pro-CASP1. Interacts with CARD8.
messages: Primarily expressed in the heart and placenta.
messages: Up-regulated in response to TNF and bacterial lipopolysaccharides (LPS).

9606:GGT6
gene id: 9606:GGT6
uniprot id: B4DKN3
uniprot id: J3KPJ0
uniprot id: Q6P531
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the gamma-glutamyltransferase family.
messages: Cleaved by autocatalysis into a large and a small subunit and the autocatalytic cleavage is essential to the functional activation of the enzyme.
messages: Heterodimer composed of the light and heavy chains. The active site is located in the light chain.
messages: Hydrolyzes and transfers gamma-glutamyl moieties from glutathione and other gamma-glutamyl compounds to acceptors.
messages: Membrane

9606:LIN28B
gene id: 9606:LIN28B
uniprot id: Q6ZN17
names: Domain
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the lin-28 family.
messages: Cytoplasm
messages: Expressed at high levels in the placenta and, at mucher lower, in testis and fetal liver (PubMed:16971064). Isoform 1 is only detected in placenta and in moderately and poorly differentiated hepatocellular carcinoma cells (at protein level). Isoform 2 is detected in fetal liver, non-tumor liver tissues, as well as well-differentiated tumor tissues (at protein level). Tends to be up-regulated in triple-negative (ER-,PR-,HER2-) breast tumors, as well as in liver, ovarian, and thyroid carcinomas (PubMed:22118463).
messages: Might be negatively regulated by the microRNA let-7b.
messages: Nucleus
messages: Suppressor of microRNA (miRNA) biogenesis, including that of let-7 and possibly of miR107, miR-143 and miR-200c. Binds primary let-7 transcripts (pri-let-7), including pri-let-7g and pri-let-7a-1, and sequester them in the nucleolus, away from the microprocessor complex, hence preventing their processing into mature miRNA (PubMed:22118463). Does not act on pri-miR21 (PubMed:22118463). The repression of let-7 expression is required for normal development and contributes to maintain the pluripotent state of embryonic stem cells by preventing let-7-mediated differentiation. When overexpressed, recruits ZCCHC11/TUT4 uridylyltransferase to pre-let-7 transcripts, leading to their terminal uridylation and degradation (PubMed:19703396). This activity might not be relevant in vivo, as LIN28B-mediated inhibition of let-7 miRNA maturation appears to be ZCCHC11-independent (PubMed:22118463). Interaction with target pre-miRNAs occurs via an 5'-GGAG-3' motif in the pre-miRNA terminal loop. Mediates MYC-induced let-7 repression (By similarity). When overexpressed, isoform 1 stimulates growth of the breast adenocarcinoma cell line MCF-7. Isoform 2 has no effect on cell growth.
messages: The tandem zinc fingers, also referred as zinc knuckle domain (ZKD), mediate specific binding to the GGAG/GGUG motif while the CSD shows only limited pyrimidine-rich sequence specificity. Both domains bind single-stranded nucleic acids.
messages: nucleolus

9606:PRPS1L1
gene id: 9606:PRPS1L1
uniprot id: P21108
names: Activity Regulation
names: Caution
names: Function
names: Similarity
names: Subunit
names: Tissue Specificity
messages: According to PubMed:2168892, this sequence initiates from a non-AUG codon; N-terminal ACG codon did serve as a start codon.
messages: Activated by magnesium and inorganic phosphate.
messages: Belongs to the ribose-phosphate pyrophosphokinase family.
messages: Catalyzes the synthesis of phosphoribosylpyrophosphate (PRPP) that is essential for nucleotide synthesis.
messages: Homodimer. The active form is probably a hexamer composed of 3 homodimers (By similarity).
messages: Testis.

9606:TRIM74
gene id: 9606:TRIM74
uniprot id: Q86UV6
names: Similarity
messages: Belongs to the TRIM/RBCC family.

9606:ALOX12
gene id: 9606:ALOX12
uniprot id: P18054
names: Activity Regulation
names: Cofactor
names: Disease Annotation
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Activated by EGF (PubMed:8912711). Arachidonic acid conversion is inhibited by (13S,14S)-epoxy-(4Z,7Z,9E,11E,16Z,19Z)-docosahexaenoate (13S,14S-epoxy-DHA) (PubMed:23504711). Arachidonate 12-lipoxygenase activity is decreased when PH decreases from 7.4 to 6 (By similarity).
messages: Belongs to the lipoxygenase family.
messages: Binds 1 Fe cation per subunit.
messages: Catalyzes the regio and stereo-specific incorporation of molecular oxygen into free and esterified polyunsaturated fatty acids generating lipid hydroperoxides that can be further reduced to the corresponding hydroxy species (PubMed:17493578, PubMed:1851637, PubMed:8319693, PubMed:8500694, PubMed:18311922, PubMed:32404334). Mainly converts arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate) to the specific bioactive lipid (12S)-hydroperoxyeicosatetraenoate/(12S)-HPETE (PubMed:17493578, PubMed:22984144, PubMed:24282679, PubMed:8319693, PubMed:8500694). Through the production of bioactive lipids like (12S)-HPETE it regulates different biological processes including platelet activation (PubMed:8319693, PubMed:8500694). It can also catalyze the epoxidation of double bonds of polyunsaturated fatty acids such as (14S)-hydroperoxy-docosahexaenoate/(14S)-HPDHA resulting in the formation of (13S,14S)-epoxy-DHA (PubMed:23504711). Furthermore, it may participate in the sequential oxidations of DHA ((4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate) to generate specialized pro-resolving mediators (SPMs) like resolvin D5 ((7S,17S)-diHPDHA) and (7S,14S)-diHPDHA, that actively down-regulate the immune response and have anti-aggregation properties with platelets (PubMed:32404334). An additional function involves a multistep process by which it transforms leukotriene A4/LTA4 into the bioactive lipids lipoxin A4/LXA4 and lipoxin B4/LXB4, both are vasoactive and LXA4 may regulate neutrophil function via occupancy of specific recognition sites (PubMed:8250832). Can also peroxidize linoleate ((9Z,12Z)-octadecadienoate) to (13S)-hydroperoxyoctadecadienoate/ (13S-HPODE) (By similarity). Due to its role in regulating both the expression of the vascular endothelial growth factor (VEGF, an angiogenic factor involved in the survival and metastasis of solid tumors) and the expression of integrin beta-1 (known to affect tumor cell migration and proliferation), it can be regarded as protumorigenic (PubMed:97…
messages: Disease susceptibility may be associated with variants affecting the gene represented in this entry. Gln at position 261 may confer interindividual susceptibility to colorectal cancer (PubMed:17460548).
messages: Disease susceptibility may be associated with variants affecting the gene represented in this entry. Gln at position 261 may confer interindividual susceptibility to esophageal cancer (PubMed:17460548).
messages: Down-regulated upon starvation, by UV-irradiation and 15-lipoxygenase metabolites.
messages: Expressed in vascular smooth muscle cells.
messages: Membrane
messages: cytosol

9606:VEZF1
gene id: 9606:VEZF1
uniprot id: Q14119
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: Interacts with ARHGAP22.
messages: Nucleus
messages: Possible transcription factor. Specifically binds to the CT/GC-rich region of the interleukin-3 promoter and mediates tax transactivation of IL-3.
messages: The disease may be caused by variants affecting the gene represented in this entry.
messages: Ubiquitously expressed. Highest levels in skeletal muscle and kidney.

9606:LCN12
gene id: 9606:LCN12
uniprot id: A0A384MDV4
uniprot id: Q6JVE5
uniprot id: Q8IW14
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the calycin superfamily. Lipocalin family.
messages: Binds all-trans retinoic acid and may act as a retinoid carrier protein within the epididymis. May play a role in male fertility (By similarity).
messages: Monomer.
messages: Secreted

9606:CLEC4E
gene id: 9606:CLEC4E
uniprot id: Q9ULY5
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Calcium-dependent lectin that acts as a pattern recognition receptor (PRR) of the innate immune system: recognizes damage-associated molecular patterns (DAMPs) of abnormal self and pathogen-associated molecular patterns (PAMPs) of bacteria and fungi (PubMed:18509109, PubMed:23602766). The PAMPs notably include mycobacterial trehalose 6,6'-dimycolate (TDM), a cell wall glycolipid with potent adjuvant immunomodulatory functions (PubMed:23602766, PubMed:24101491). Interacts with signaling adapter Fc receptor gamma chain/FCER1G to form a functional complex in myeloid cells (By similarity). Binding of mycobacterial trehalose 6,6'-dimycolate (TDM) to this receptor complex leads to phosphorylation of the immunoreceptor tyrosine-based activation motif (ITAM) of FCER1G, triggering activation of SYK, CARD9 and NF-kappa-B, consequently driving maturation of antigen-presenting cells and shaping antigen-specific priming of T-cells toward effector T-helper 1 and T-helper 17 cell subtypes (By similarity). Also recognizes alpha-mannose residues on pathogenic fungi of the genus Malassezia and mediates macrophage activation (By similarity). Through recognition of DAMPs released upon nonhomeostatic cell death, enables immune sensing of damaged self and promotes inflammatory cell infiltration into the damaged tissue (By similarity).
messages: Cell membrane
messages: Expressed in monocytes and macrophages.
messages: Monomer and homodimer (PubMed:18509109). Interacts with signaling adapter Fc receptor gamma chain/FCER1G to form a functional complex; the interaction is direct (By similarity). Alternatively, acts as a bridge for interaction between CLEC4D and FCER1G. A heterodimer of CLEC4E and CLEC4D associates with FCER1G to form a functional complex (By similarity). Interacts with SAP130 nuclear protein that is released from necrotic cells; the interaction is direct (By similarity).
messages: phagocytic cup

9606:ZBTB40
gene id: 9606:ZBTB40
uniprot id: Q9NUA8
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:THBS2
gene id: 9606:THBS2
uniprot id: P35442
names: Disease Annotation
names: Function
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions. Ligand for CD36 mediating antiangiogenic properties.
messages: Belongs to the thrombospondin family.
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry.
messages: High expression in invertebral disk tissue.
messages: Homotrimer; disulfide-linked. Interacts (via the TSP type I repeats) with CD36; the interaction conveys an antiangiogenic effect. Interacts (via the TSP type I repeats) with HRG; the interaction blocks the antiangiogenic effect of THBS2 with CD36 (By similarity). Can bind to fibrinogen, fibronectin, laminin and type V collagen.

9606:HYAL4
gene id: 9606:HYAL4
uniprot id: Q2M3T9
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the glycosyl hydrolase 56 family.
messages: Detected in placenta and skeletal muscle.
messages: Endo-hyaluronidase that degrades hyaluronan to smaller oligosaccharide fragments. Has also chondroitin sulfate hydrolase activity, The best substrate being the galactosaminidic linkage in the sequence of a trisulfated tetrasaccharide.
messages: Membrane

9606:THY1
gene id: 9606:THY1
uniprot id: P04216
names: Function
names: Subcellular Location Annotation
messages: Cell membrane
messages: May play a role in cell-cell or cell-ligand interactions during synaptogenesis and other events in the brain.

9606:TMEM273
gene id: 9606:TMEM273
uniprot id: Q5T292
names: Subcellular Location Annotation
messages: Membrane

9606:DNAI4
gene id: 9606:DNAI4
uniprot id: Q5VTH9
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Dynein axonemal particle
messages: Part of the multisubunit axonemal dynein complex formed at least of two heavy chains and a number of intermediate and light chains. Associated with axonemal dynein subunits such as, DNAH2, DNAI3, and DYNLT1. Interacts with DYNLT1.
messages: Plays a critical role in the assembly of axonemal dynein complex, thereby playing a role in ciliary motility.
messages: cilium axoneme
messages: flagellum axoneme

9606:RIF1
gene id: 9606:RIF1
uniprot id: Q5UIP0
names: Developmental Stage
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the RIF1 family.
messages: Chromosome
messages: Expression peaks in late G2/S phase of the cell cycle.
messages: Highly expressed in testis.
messages: Interacts with TP53BP1 (when phosphorylated by ATM) (PubMed:23333306, PubMed:28241136). May interact with TRF2 (By similarity). Interacts with SHLD2 (PubMed:29789392). Interacts with ERCC6 (via WHD region) (PubMed:29203878).
messages: Key regulator of TP53BP1 that plays a key role in the repair of double-strand DNA breaks (DSBs) in response to DNA damage: acts by promoting non-homologous end joining (NHEJ)-mediated repair of DSBs (PubMed:15342490, PubMed:28241136). In response to DNA damage, interacts with ATM-phosphorylated TP53BP1 (PubMed:23333306, PubMed:28241136). Interaction with TP53BP1 leads to dissociate the interaction between NUDT16L1/TIRR and TP53BP1, thereby unmasking the tandem Tudor-like domain of TP53BP1 and allowing recruitment to DNA DSBs (PubMed:28241136). Once recruited to DSBs, RIF1 and TP53BP1 act by promoting NHEJ-mediated repair of DSBs (PubMed:23333306). In the same time, RIF1 and TP53BP1 specifically counteract the function of BRCA1 by blocking DSBs resection via homologous recombination (HR) during G1 phase (PubMed:23333306). Also required for immunoglobulin class-switch recombination (CSR) during antibody genesis, a process that involves the generation of DNA DSBs (By similarity). Promotes NHEJ of dysfunctional telomeres (By similarity).
messages: Nucleus
messages: spindle
messages: telomere

9606:LIX1
gene id: 9606:LIX1
uniprot id: Q8N485
names: Similarity
messages: Belongs to the LIX1 family.

9606:ZNF282
gene id: 9606:ZNF282
uniprot id: A0A090N8Y3
uniprot id: Q9UDV7
names: Caution
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: Binds to the U5 repressive element (U5RE) of the human T cell leukemia virus type I long terminal repeat. It recognizes the 5'-TCCACCCC-3' sequence as a core motif and exerts a strong repressive effect on HTLV-I LTR-mediated expression.
messages: Nucleus
messages: The sequence shown here is derived from an EMBL/GenBank/DDBJ whole genome shotgun (WGS) entry which is preliminary data.
messages: Ubiquitous.

9606:MRGPRX2
gene id: 9606:MRGPRX2
uniprot id: Q96LB1
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor 1 family. Mas subfamily.
messages: Cell membrane
messages: Mainly expressed in mast cells. Has a limited expression profile, both peripheral and within the central nervous system, with highest levels in dorsal root ganglion (PubMed:12915402). Detected in blood vessels, scattered lymphocytes, and gastrointestinal ganglia (at protein level) (PubMed:16161007).
messages: Mast cell-specific receptor for basic secretagogues, i.e. cationic amphiphilic drugs, as well as endo- or exogenous peptides, consisting of a basic head group and a hydrophobic core (PubMed:25517090). Recognizes and binds small molecules containing a cyclized tetrahydroisoquinoline (THIQ), such as non-steroidal neuromuscular blocking drugs (NMBDs), including tubocurarine and atracurium. In response to these compounds, mediates pseudo-allergic reactions characterized by histamine release, inflammation and airway contraction (By similarity). Acts as a receptor for a number of other ligands, including peptides and alkaloids, such as cortistatin-14, proadrenomedullin N-terminal peptides PAMP-12 and, at lower extent, PAMP-20, antibacterial protein LL-37, PMX-53 peptide, beta-defensins, and complanadine A.

9606:RAB5IF
gene id: 9606:RAB5IF
uniprot id: Q9BUV8
names: Disease Annotation
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the EMC6 family.
messages: Component of the GET- and EMC-like (GEL) complex, composed of RAB5IF/OPTI and TMCO1 (PubMed:36261522). The GEL complex is part of the multi-pass translocon (MPT) complex, composed of three subcomplexes, the GEL complex (composed of RAB5IF/OPTI and TMCO1), the BOS complex (composed of NCLN/Nicalin, NOMO and TMEM147) and the PAT complex (composed of WDR83OS/Asterix and CCDC47) (PubMed:36261522). The MPT complex associates with the SEC61 complex (PubMed:36261522). Interacts with NDUFS3, NDUFA4, NDUFV1, NDUFA9 and NDUFS8 of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) (PubMed:31536960). Interacts with UQCRC2 of the ubiquinol-cytochrome c reductase complex (Complex III) (PubMed:31536960). Interacts with COX5A and COX7C of the cytochrome c oxidase complex (Complex IV) (PubMed:31536960).
messages: Component of the multi-pass translocon (MPT) complex that mediates insertion of multi-pass membrane proteins into the lipid bilayer of membranes (PubMed:36261522). The MPT complex takes over after the SEC61 complex: following membrane insertion of the first few transmembrane segments of proteins by the SEC61 complex, the MPT complex occludes the lateral gate of the SEC61 complex to promote insertion of subsequent transmembrane regions (PubMed:36261522). Within the MPT complex, the GEL subcomplex may mediate insertion of transmembrane regions into the membrane (PubMed:36261522). In addition to its role in multi-pass membrane insertion, RAB5IF/OPTI also acts as an assembly factor for mitochondrial respiratory complexes (PubMed:31536960).
messages: Endoplasmic reticulum membrane
messages: Expressed in embryonic stem cells and differentiated neuronal cells.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Mitochondrion inner membrane
messages: The disease may be caused by variants affecting the gene represented in this entry. Loss of RAB5IF in fibroblasts from a CFSMR2 patient carrying RAB5IF variant p.Trp25ter and negative for TMCO1 pathogenic variants, is associated with lack of TMCO1 expression. This suggests a possible functional relation between the two proteins and involvement in a common disease mechanism.

9606:RNASEH2B
gene id: 9606:RNASEH2B
uniprot id: Q5TBB1
uniprot id: Q8N451
names: Disease Annotation
names: Function
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the RNase H2 subunit B family.
messages: Contaminating sequence. Potential poly-A sequence.
messages: Non catalytic subunit of RNase H2, an endonuclease that specifically degrades the RNA of RNA:DNA hybrids. Participates in DNA replication, possibly by mediating the removal of lagging-strand Okazaki fragment RNA primers during DNA replication. Mediates the excision of single ribonucleotides from DNA:RNA duplexes.
messages: Nucleus
messages: The RNase H2 complex is a heterotrimer composed of the catalytic subunit RNASEH2A and the non-catalytic subunits RNASEH2B and RNASEH2C.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Widely expressed.

9606:TNFSF11
gene id: 9606:TNFSF11
uniprot id: O14788
uniprot id: Q54A98
uniprot id: Q5T9Y4
names: Disease Annotation
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the tumor necrosis factor family.
messages: Cell membrane
messages: Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. Osteoclast differentiation and activation factor. Augments the ability of dendritic cells to stimulate naive T-cell proliferation. May be an important regulator of interactions between T-cells and dendritic cells and may play a role in the regulation of the T-cell-dependent immune response. May also play an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy (PubMed:22664871). Induces osteoclastogenesis by activating multiple signaling pathways in osteoclast precursor cells, chief among which is induction of long lasting oscillations in the intracellular concentration of Ca (2+) resulting in the activation of NFATC1, which translocates to the nucleus and induces osteoclast-specific gene transcription to allow differentiation of osteoclasts. During osteoclast differentiation, in a TMEM64 and ATP2A2-dependent manner induces activation of CREB1 and mitochondrial ROS generation necessary for proper osteoclast generation (By similarity).
messages: Cytoplasm
messages: Highest in the peripheral lymph nodes, weak in spleen, peripheral blood Leukocytes, bone marrow, heart, placenta, skeletal muscle, stomach and thyroid.
messages: Homotrimer (By similarity). Interacts with TNFRSF11B (PubMed:22664871). Interacts with TNFRSF11A. Interacts with FBN1 (via N-terminal domain) in a Ca(+2)-dependent manner (By similarity). Interacts with TNFAIP6 (via both Link and CUB domains).
messages: Homotrimer.
messages: Membrane
messages: Secreted
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The soluble form of isoform 1 derives from the membrane form by proteolytic processing (By similarity). The cleavage may be catalyzed by ADAM17.
messages: Up-regulated by T-cell receptor stimulation.

9606:CSRNP1
gene id: 9606:CSRNP1
uniprot id: Q96S65
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the AXUD1 family.
messages: Binds to the consensus sequence 5'-AGAGTG-3' and has transcriptional activator activity (By similarity). May have a tumor-suppressor function. May play a role in apoptosis.
messages: Nucleus
messages: Ubiquitous. Most abundantly expressed in lung, placenta, skeletal muscle, pancreas and leukocyte. Frequently down-regulated in lung, kidney, liver and colon cancers compared with their corresponding normal tissues.

9606:IPO5
gene id: 9606:IPO5
uniprot id: B3KWG6
uniprot id: O00410
uniprot id: Q9BVS9
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Interacts with HIV-1 Rev.
messages: Belongs to the importin beta family. Importin beta-3 subfamily.
messages: Cytoplasm
messages: Functions in nuclear protein import as nuclear transport receptor. Serves as receptor for nuclear localization signals (NLS) in cargo substrates. Is thought to mediate docking of the importin/substrate complex to the nuclear pore complex (NPC) through binding to nucleoporin and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to the importin, the importin/substrate complex dissociates and importin is re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus (By similarity). Mediates the nuclear import of ribosomal proteins RPL23A, RPS7 and RPL5 (PubMed:9687515, PubMed:11682607). In vitro, mediates nuclear import of H2A, H2B, H3 and H4 histones. Binds to CPEB3 and mediates its nuclear import following neuronal stimulation (By similarity). In case of HIV-1 infection, binds and mediates the nuclear import of HIV-1 Rev.
messages: Interacts with RPS7 and RPL5 (PubMed:9687515). Interacts with RPL23A (via BIB domain) (PubMed:9687515, PubMed:11682607). Interacts with H2A, H2B, H3 and H4 histones (By similarity). Interacts with CPEB3; this mediates CPEB3 nuclear import following neuronal stimulation which enhances the interaction in a RAN-regulated manner (PubMed:22730302). Interacts with AIFM2; this interaction likely mediates the translocation of AIFM2 into the nucleus upon oxidative stress. Interacts with STX3 (isoform 3) (PubMed:29475951). Interacts with SRP19 (PubMed:11682607).
messages: Nucleus
messages: nucleolus

9606:H3C7
gene id: 9606:H3C7
uniprot id: P68431
names: Caution
names: Developmental Stage
names: Disease Annotation
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Acetylation is generally linked to gene activation. Acetylation on Lys-10 (H3K9ac) impairs methylation at Arg-9 (H3R8me2s). Acetylation on Lys-19 (H3K18ac) and Lys-24 (H3K24ac) favors methylation at Arg-18 (H3R17me). Acetylation at Lys-123 (H3K122ac) by EP300/p300 plays a central role in chromatin structure: localizes at the surface of the histone octamer and stimulates transcription, possibly by promoting nucleosome instability.
messages: Asymmetric dimethylation at Arg-18 (H3R17me2a) by CARM1 is linked to gene activation. Symmetric dimethylation at Arg-9 (H3R8me2s) by PRMT5 is linked to gene repression. Asymmetric dimethylation at Arg-3 (H3R2me2a) by PRMT6 is linked to gene repression and is mutually exclusive with H3 Lys-5 methylation (H3K4me2 and H3K4me3). H3R2me2a is present at the 3' of genes regardless of their transcription state and is enriched on inactive promoters, while it is absent on active promoters.
messages: Belongs to the histone H3 family.
messages: Butyrylation of histones marks active promoters and competes with histone acetylation. It is present during late spermatogenesis.
messages: Chromosome
messages: Citrullination at Arg-9 (H3R8ci) and/or Arg-18 (H3R17ci) by PADI4 impairs methylation and represses transcription.
messages: Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
messages: Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.
messages: Dopaminylated by TGM2 at Gln-6 (H3Q5dop) in ventral tegmental area (VTA) neurons (PubMed:32273471). H3Q5dop mediates neurotransmission-independent role of nuclear dopamine by regulating relapse-related transcriptional plasticity in the reward system (By similarity).
messages: Expressed during S phase, then expression strongly decreases as cell division slows down during the process of differentiation.
messages: HIST1H3B or HIST1H3C mutations affecting residue Lys-37 of histone H3.1 are involved in the pathogenesis of pediatric undifferentiated soft tissue sarcomas. The mechanism through which mutations lead to tumorigenesis involves altered histones methylation with gain of global H3K27 methylation, altered Polycomb repressive complex 1 (PRC1) activity, aberrant epigenetic regulation of gene expression and impaired differentiation of mesenchimal progenitor cells.
messages: Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.
messages: Lysine deamination at Lys-5 (H3K4all) to form allysine is mediated by LOXL2. Allysine formation by LOXL2 only takes place on H3K4me3 and results in gene repression.
messages: Methylation at Lys-5 (H3K4me), Lys-37 (H3K36me) and Lys-80 (H3K79me) are linked to gene activation. Methylation at Lys-5 (H3K4me) facilitates subsequent acetylation of H3 and H4. Methylation at Lys-80 (H3K79me) is associated with DNA double-strand break (DSB) responses and is a specific target for TP53BP1. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are linked to gene repression. Methylation at Lys-10 (H3K9me) is a specific target for HP1 proteins (CBX1, CBX3 and CBX5) and prevents subsequent phosphorylation at Ser-11 (H3S10ph) and acetylation of H3 and H4. Methylation at Lys-5 (H3K4me) and Lys-80 (H3K79me) require preliminary monoubiquitination of H2B at 'Lys-120'. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are enriched in inactive X chromosome chromatin. Monomethylation at Lys-57 (H3K56me1) by EHMT2/G9A in G1 phase promotes interaction with PCNA and is required for DNA replication.
messages: Monoubiquitinated by RAG1 in lymphoid cells, monoubiquitination is required for V(D)J recombination (By similarity). Ubiquitinated by the CUL4-DDB-RBX1 complex in response to ultraviolet irradiation. This may weaken the interaction between histones and DNA and facilitate DNA accessibility to repair proteins.
messages: Nucleus
messages: Phosphorylated at Thr-4 (H3T3ph) by HASPIN during prophase and dephosphorylated during anaphase. Phosphorylation at Ser-11 (H3S10ph) by AURKB is crucial for chromosome condensation and cell-cycle progression during mitosis and meiosis. In addition phosphorylation at Ser-11 (H3S10ph) by RPS6KA4 and RPS6KA5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or UV irradiation and result in the activation of genes, such as c-fos and c-jun. Phosphorylation at Ser-11 (H3S10ph), which is linked to gene activation, prevents methylation at Lys-10 (H3K9me) but facilitates acetylation of H3 and H4. Phosphorylation at Ser-11 (H3S10ph) by AURKB mediates the dissociation of HP1 proteins (CBX1, CBX3 and CBX5) from heterochromatin. Phosphorylation at Ser-11 (H3S10ph) is also an essential regulatory mechanism for neoplastic cell transformation. Phosphorylated at Ser-29 (H3S28ph) by MAP3K20 isoform 1, RPS6KA5 or AURKB during mitosis or upon ultraviolet B irradiation. Phosphorylation at Thr-7 (H3T6ph) by PRKCB is a specific tag for epigenetic transcriptional activation that prevents demethylation of Lys-5 (H3K4me) by LSD1/KDM1A. At centromeres, specifically phosphorylated at Thr-12 (H3T11ph) from prophase to early anaphase, by DAPK3 and PKN1. Phosphorylation at Thr-12 (H3T11ph) by PKN1 or isoform M2 of PKM (PKM2) is a specific tag for epigenetic transcriptional activation that promotes demethylation of Lys-10 (H3K9me) by KDM4C/JMJD2C. Phosphorylation at Thr-12 (H3T11ph) by chromatin-associated CHEK1 regulates the transcription of cell cycle regulatory genes by modulating acetylation of Lys-10 (H3K9ac). Phosphorylation at Tyr-42 (H3Y41ph) by JAK2 promotes exclusion of CBX5 (HP1 alpha) from chromatin.
messages: Serine ADP-ribosylation by PARP1 or PARP2 constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage (PubMed:30257210, PubMed:34874266). Serine ADP-ribosylation at Ser-11 (H3S10ADPr) promotes recruitment of CHD1L (PubMed:34874266). H3S10ADPr is mutually exclusive with phosphorylation at Ser-11 (H3S10ph) and impairs acetylation at Lys-10 (H3K9ac) (PubMed:30257210).
messages: Serotonylated by TGM2 at Gln-6 (H3Q5ser) during serotonergic neuron differentiation (PubMed:30867594). H3Q5ser is associated with trimethylation of Lys-5 (H3K4me3) and enhances general transcription factor IID (TFIID) complex-binding to H3K4me3, thereby facilitating transcription (PubMed:30867594).
messages: Succinylation at Lys-80 (H3K79succ) by KAT2A takes place with a maximum frequency around the transcription start sites of genes (PubMed:29211711). It gives a specific tag for epigenetic transcription activation (PubMed:29211711). Desuccinylation at Lys-123 (H3K122succ) by SIRT7 in response to DNA damage promotes chromatin condensation and double-strand breaks (DSBs) repair (PubMed:27436229).
messages: The gene represented in this entry is involved in disease pathogenesis. HIST1H3B mutations affecting residue Lys-28 involved in post-translational modifications of histone H3.1 are recurrent in malignant, aggressive gliomas including pediatric non-brain stem glioblastoma and diffuse intrinsic pontine glioma (DIPG) (PubMed:22286216). The mechanism through which mutations lead to tumorigenesis involves altered histone methylation, impaired regulation of Polycomb repressive complex 2 (PRC2) activity, and aberrant epigenetic regulation of gene expression (PubMed:23603901).
messages: The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. Interacts with TONSL; CHAF1A; CHAF1B; MCM2 and DNAJC9 (PubMed:33857403).
messages: The original paper reporting lysine deamination at Lys-5 by LOXL2 has been retracted due to inappropriate manipulation of figure data (PubMed:22483618, PubMed:27392148). However, this modification was confirmed in a subsequent publication (PubMed:27735137).
messages: This histone is only present in mammals and is enriched in acetylation of Lys-15 and dimethylation of Lys-10 (H3K9me2).

9606:INTU
gene id: 9606:INTU
uniprot id: Q9ULD6
names: Disease Annotation
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the inturned family.
messages: Cell surface
messages: Cytoplasm
messages: Interacts with CPLANE1. Interacts with FUZ and WDPCP; FUZ, INTU and WDPCP probably form the core CPLANE (ciliogenesis and planar polarity effectors) complex (By similarity). Interacts with NPHP4 and DAAM1; INTU is mediating the interaction between NPHP4 and DAAM1 (PubMed:26644512).
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Plays a key role in ciliogenesis and embryonic development. Regulator of cilia formation by controlling the organization of the apical actin cytoskeleton and the positioning of the basal bodies at the apical cell surface, which in turn is essential for the normal orientation of elongating ciliary microtubules. Plays a key role in definition of cell polarity via its role in ciliogenesis but not via conversion extension. Has an indirect effect on hedgehog signaling (By similarity). Proposed to function as core component of the CPLANE (ciliogenesis and planar polarity effectors) complex involved in the recruitment of peripheral IFT-A proteins to basal bodies (PubMed:27158779).
messages: The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry. SRTD7/20 can be caused by co-occurrence of WDR35 variant p.Trp311Leu and INTU p.Gln276Ter. One such patient has been reported.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: cilium basal body

9606:PCF11
gene id: 9606:PCF11
uniprot id: O94913
names: Function
names: PTM
names: Sequence Caution
names: Subcellular Location Annotation
names: Subunit
messages: Associates with the phosphorylated CTD domain of POLR2A /RNA polymerase II.
messages: Component of pre-mRNA cleavage complex II, which promotes transcription termination by RNA polymerase II.
messages: Contaminating sequence. Potential poly-A sequence.
messages: Nucleus
messages: Phosphorylation at Ser-120 and/or Thr-121 by WNK1 weakens its association with POLR2A/RNA polymerase II, promoting transcript release from the chromatin template and mRNA export to the cytoplasm.

9606:SLC12A3
gene id: 9606:SLC12A3
uniprot id: P55017
names: Activity Regulation
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Apical cell membrane
messages: Belongs to the SLC12A transporter family.
messages: Cell membrane
messages: Electroneutral sodium and chloride ion cotransporter, which acts as a key mediator of sodium and chloride reabsorption in kidney distal convoluted tubules (PubMed:21613606, PubMed:18270262, PubMed:22009145, PubMed:36351028, PubMed:36792826). Also acts as a receptor for the pro-inflammatory cytokine IL18, thereby contributing to IL18-induced cytokine production, including IFNG, IL6, IL18 and CCL2 (By similarity). May act either independently of IL18R1, or in a complex with IL18R1 (By similarity).
messages: Homodimer (PubMed:36351028, PubMed:36792826). Interacts with KLHL3 (PubMed:22406640). Interacts with IL18R1; this interaction is increased by IL18 treatment (By similarity).
messages: Interaction between the cytoplasmic N-terminal and C-terminal domains (NTD and CTD, respectively) is essential for SLC12A3/NCC transporter activity (PubMed:36792826). Phosphorylation by OXSR1/OSR1 and STK39/SPAK may activate SLC12A3/NCC by facilitating this interaction (PubMed:36792826).
messages: Phosphorylated at Thr-46, Thr-55, Thr-60 and Ser-91 by OXSR1/OSR1 and STK39/SPAK downstream of WNK4, promoting its activity (PubMed:18270262). Phosphorylated in response to IL18 (By similarity).
messages: Phosphorylation by OXSR1/OSR1 and STK39/SPAK in kidney distal convoluted tubules downstream of WNK4 promotes its activity (PubMed:18270262). Also activated by OXSR1/OSR1 and STK39/SPAK downstream of WNK3 (PubMed:21613606). Target of thiazide diuretics used in the treatment of high blood pressure (PubMed:8528245, PubMed:36792826). Thiazide drugs, such as polythiazide, specifically inhibit SLC12A3/NCC transporter activity by competing with chloride for binding and by locking SLC12A3/NCC in an outward-facing conformation (PubMed:36792826).
messages: Predominantly expressed in the kidney (at protein level) (PubMed:29993276, PubMed:8812482). Localizes to the distal convoluted tubules (at protein level)(PubMed:29993276). Not detected in normal aorta, but abundantly expressed in fatty streaks and advanced atherosclerotic lesions (at protein level) (PubMed:26099046).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitinated; ubiquitination is essential for regulation of endocytosis. The BCR(KLHL3) complex was initially identified as a candidate ubiquitin ligase for SLC12A3 (PubMed:22406640). However, it was later shown that it is not the case.

9606:AP1S1
gene id: 9606:AP1S1
uniprot id: P61966
names: Disease Annotation
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Adaptor protein complex 1 (AP-1) is a heterotetramer composed of two large adaptins (gamma-type subunit AP1G1 and beta-type subunit AP1B1), a medium adaptin (mu-type subunit AP1M1 or AP1M2) and a small adaptin (sigma-type subunit AP1S1 or AP1S2 or AP1S3).
messages: Belongs to the adaptor complexes small subunit family.
messages: Cytoplasmic vesicle membrane
messages: Golgi apparatus
messages: Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or endosomes. The AP complexes mediate both the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Up-regulated in response to enterovirus 71 (EV71) infection.
messages: Widely expressed.
messages: clathrin-coated pit

9606:TBRG4
gene id: 9606:TBRG4
uniprot id: Q969Z0
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the FAST kinase family.
messages: Mitochondrion matrix
messages: Plays a role in processing of mitochondrial RNA precursors and in stabilization of a subset of mature mitochondrial RNA species, such as MT-CO1, MT-CO2, MT-CYB, MT-CO3, MT-ND3, MT-ND5 and MT-ATP8/6. May play a role in cell cycle progression (PubMed:9383053).
messages: RAP domain is required for TBRG4 function in mRNA stability and translation.
messages: Ubiquitously expressed (PubMed:12759187). Expression detected in spleen, thymus, testis, ovary, colon, heart, smooth muscle, kidney, brain, lung, liver and white adipose tissue with highest expression in smooth muscle (PubMed:20869947).

9606:PSMD12
gene id: 9606:PSMD12
uniprot id: A0A0S2Z489
uniprot id: O00232
names: Disease Annotation
names: Function
names: Similarity
names: Subunit
messages: Belongs to the proteasome subunit p55 family.
messages: Component of the 19S proteasome regulatory particle complex (PubMed:27428775, PubMed:27342858). The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP) (PubMed:27428775, PubMed:27342858). The regulatory particle is made of a lid composed of 9 subunits including PSMD12, a base containing 6 ATPases and few additional components (PubMed:27428775, PubMed:27342858). Interacts with ERCC6 (PubMed:26030138).
messages: Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:CLCA4
gene id: 9606:CLCA4
uniprot id: Q14CN2
names: Domain
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Apical cell membrane
messages: Belongs to the CLCR family.
messages: Cell membrane
messages: Down-regulated in oral tongue squamous cell carcinomas.
messages: May be involved in mediating calcium-activated chloride conductance.
messages: Primarily expressed in the digestive tract, mainly in colon. Detected in smaller amounts in brain, urogenital organs, testis, and salivary and mammary glands. Highly expressed in the epithelial layer and submucosal gland of the inferior turbinate mucosa. Lower levels in the epithelial layer of nasal polyp.
messages: Secreted
messages: The metalloprotease region is responsible for autoproteolytic processing. It can also cross-cleave other CLCA substrates.
messages: The translation product is autoproteolytically cleaved by the metalloprotease domain in the endoplasmic reticulum into a N-terminal and a C-terminal products that remain physically associated with each other. The cleavage is necessary for calcium-activated chloride channel (CaCC) activation activity.

9606:HHAT
gene id: 9606:HHAT
uniprot id: B7Z5N1
uniprot id: Q5VTY9
names: Activity Regulation
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the membrane-bound acyltransferase family. HHAT subfamily.
messages: Endoplasmic reticulum membrane
messages: Golgi apparatus membrane
messages: Inhibited by NaCl concentrations above 150 mM.
messages: Membrane
messages: Palmitoyl acyltransferase that catalyzes N-terminal palmitoylation of SHH; which is required for SHH signaling (PubMed:18534984, PubMed:31875564, PubMed:24784881). It also catalyzes N-terminal palmitoylation of DHH (PubMed:24784881). Promotes the transfer of palmitoyl-CoA from the cytoplasmic to the luminal side of the endoplasmic reticulum membrane, where SHH palmitoylation occurs (PubMed:31875564). It is an essential factor for proper embryonic development and testicular organogenesis (PubMed:24784881).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Widely expressed. Expressed in fetal ovary and testis, with high levels of expression observed in Sertoli cells (PubMed:24784881).

9606:CENPQ
gene id: 9606:CENPQ
uniprot id: Q7L2Z9
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the CENP-Q/OKP1 family.
messages: Component of the CENPA-CAD (nucleosome distal) complex, a complex recruited to centromeres which is involved in assembly of kinetochore proteins, mitotic progression and chromosome segregation. May be involved in incorporation of newly synthesized CENPA into centromeres via its interaction with the CENPA-NAC complex (PubMed:16622420). Plays an important role in chromosome congression and in the recruitment of CENP-O complex (which comprises CENPO, CENPP, CENPQ and CENPU), CENPE and PLK1 to the kinetochores (PubMed:25395579).
messages: Component of the CENPA-CAD complex, composed of CENPI, CENPK, CENPL, CENPO, CENPP, CENPQ, CENPR and CENPS. The CENPA-CAD complex interacts with the CENPA-NAC complex, at least composed of CENPA, CENPC, CENPH, CENPM, CENPN, CENPT and CENPU.
messages: Nucleus
messages: Phosphorylation at Ser-50 is essential for CENPE recruitment to kinetochores and orderly chromosome congression.
messages: centromere

9606:S1PR5
gene id: 9606:S1PR5
uniprot id: Q9H228
names: Developmental Stage
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: At 24 weeks of gestation, fragments of radial glial fibers are positive within the cortical plate and subplate of allocortical areas. These positive fragments often appear enlarged as varicosities and some of them terminate at blood vessels. Between 28 and 30 weeks of gestation, all iso- and allocortical areas contain immunolabeled radial glial fibers revealing curvature next to sulci. After 32 weeks of gestation, radial glial fibers gradually disappear; instead positive transitional stages between radial glia and astrocytes were found.
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Receptor for the lysosphingolipid sphingosine 1-phosphate (S1P). S1P is a bioactive lysophospholipid that elicits diverse physiological effect on most types of cells and tissues. Is coupled to both the G(i/0)alpha and G(12) subclass of heteromeric G-proteins (By similarity). May play a regulatory role in the transformation of radial glial cells into astrocytes and may affect proliferative activity of these cells.
messages: Widely expressed in the brain, most prominently in the corpus callosum, which is predominantly white matter. Detected in spleen, peripheral blood leukocytes, placenta, lung, aorta and fetal spleen. Low-level signal detected in many tissue extracts. Overexpressed in leukemic large granular lymphocytes. Isoform 1 is predominantly expressed in peripheral tissues. Isoform 2 is expressed in brain, spleen and peripheral blood leukocytes.

9606:AAR2
gene id: 9606:AAR2
uniprot id: Q9Y312
names: Function
names: Similarity
names: Subunit
messages: Belongs to the AAR2 family.
messages: Component of the U5 snRNP complex that is required for spliceosome assembly and for pre-mRNA splicing.
messages: Interacts with PRPF8 (via RNase H homology domain) (PubMed:26527271). Component of a U5 snRNP complex that contains PRPF8 (By similarity).

9606:AP3B1
gene id: 9606:AP3B1
uniprot id: A0A0S2Z5J4
uniprot id: O00203
names: Disease Annotation
names: Function
names: PTM
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Adaptor protein complex 3 (AP-3) is a heterotetramer composed of two large adaptins (delta-type subunit AP3D1 and beta-type subunit AP3B1 or AP3B2), a medium adaptin (mu-type subunit AP3M1 or AP3M2) and a small adaptin (sigma-type subunit APS1 or AP3S2) (Probable). AP-3 associates with the BLOC-1 complex (By similarity). Interacts with KIF3A; interaction is direct; interaction is impaired by pyrophosphorylation of AP3B1 (PubMed:19934039).
messages: Belongs to the adaptor complexes large subunit family.
messages: Golgi apparatus
messages: Phosphorylated on serine residues.
messages: Pyrophosphorylation by 5-diphosphoinositol pentakisphosphate (5-IP7) impairs interaction with KIF3A (PubMed:19934039). Serine pyrophosphorylation is achieved by Mg(2+)-dependent, but enzyme independent transfer of a beta-phosphate from a inositol pyrophosphate to a pre-phosphorylated serine residue (PubMed:19934039).
messages: Subunit of non-clathrin- and clathrin-associated adaptor protein complex 3 (AP-3) that plays a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or endosomes. The AP complexes mediate both the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules. AP-3 appears to be involved in the sorting of a subset of transmembrane proteins targeted to lysosomes and lysosome-related organelles. In concert with the BLOC-1 complex, AP-3 is required to target cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitously expressed.
messages: Wrong choice of CDS.
messages: clathrin-coated vesicle membrane

9606:LCMT1
gene id: 9606:LCMT1
uniprot id: Q9UIC8
names: Function
names: Similarity
messages: Belongs to the methyltransferase superfamily. LCMT family.
messages: Methylates the carboxyl group of the C-terminal leucine residue of protein phosphatase 2A catalytic subunits to form alpha-leucine ester residues.

9606:CLPSL1
gene id: 9606:CLPSL1
uniprot id: A2RUU4
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the colipase family.
messages: Exclusively expressed in epididymis, in the corpus region.
messages: Secreted

9606:BHLHE41
gene id: 9606:BHLHE41
uniprot id: Q9C0J9
names: Function
names: Polymorphism
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Genetic variations in BHLHE41 are associated with the familial natural short sleep 1 (FNSS1) phenotype, an autosomal dominant trait [MIM:612975]. Individuals with this trait require less sleep in any 24-hour period than is typical for their age group.
messages: Highly expressed in skeletal muscle and brain, moderately expressed in pancreas and heart, weakly expressed in placenta, lung, liver and kidney.
messages: Homodimer (By similarity). Heterodimer with BHLHE40/DEC1 (PubMed:15193144). Interacts with CIART and BMAL1 (By similarity). Interacts with RXRA (PubMed:19786558). Interacts with NR0B2 and HNF1A (By similarity).
messages: Nucleus
messages: Transcriptional repressor involved in the regulation of the circadian rhythm by negatively regulating the activity of the clock genes and clock-controlled genes (PubMed:11278948, PubMed:14672706, PubMed:15193144, PubMed:15560782, PubMed:18411297, PubMed:19786558, PubMed:25083013). Acts as the negative limb of a novel autoregulatory feedback loop (DEC loop) which differs from the one formed by the PER and CRY transcriptional repressors (PER/CRY loop). Both these loops are interlocked as it represses the expression of PER1 and in turn is repressed by PER1/2 and CRY1/2. Represses the activity of the circadian transcriptional activator: CLOCK-BMAL1 heterodimer by competing for the binding to E-box elements (5'-CACGTG-3') found within the promoters of its target genes (PubMed:25083013). Negatively regulates its own expression and the expression of DBP and BHLHE41/DEC2. Acts as a corepressor of RXR and the RXR-LXR heterodimers and represses the ligand-induced RXRA/B/G, NR1H3/LXRA, NR1H4 and VDR transactivation activity. Inhibits HNF1A-mediated transactivation of CYP1A2, CYP2E1 AND CYP3A11 (By similarity).

9606:BRAP
gene id: 9606:BRAP
uniprot id: Q7Z569
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cytoplasm
messages: Expressed in breast epithelial cell lines.
messages: Interacts with the nuclear localization signal of BRCA1 and with the N-terminal of KSR1. The C-terminal portion of BCRA1 interacts with DDB1.
messages: Negatively regulates MAP kinase activation by limiting the formation of Raf/MEK complexes probably by inactivation of the KSR1 scaffold protein. Also acts as a Ras responsive E3 ubiquitin ligase that, on activation of Ras, is modified by auto-polyubiquitination resulting in the release of inhibition of Raf/MEK complex formation. May also act as a cytoplasmic retention protein with a role in regulating nuclear transport.

9606:ZNF446
gene id: 9606:ZNF446
uniprot id: Q8NDK2
uniprot id: Q9NWS9
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:RPS25
gene id: 9606:RPS25
uniprot id: P62851
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the eukaryotic ribosomal protein eS25 family.
messages: Component of the small ribosomal subunit (PubMed:23636399). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399).
messages: Component of the small ribosomal subunit.
messages: Cytoplasm

9606:PPP1R37
gene id: 9606:PPP1R37
uniprot id: O75864
names: Function
names: Miscellaneous
names: Similarity
names: Subunit
messages: Belongs to the PPP1R37 family.
messages: Due to an intron retention.
messages: Inhibits phosphatase activity of protein phosphatase 1 (PP1) complexes.
messages: Interacts with PPP1CA.

9606:GLS2
gene id: 9606:GLS2
uniprot id: A0A087X004
uniprot id: Q9UI32
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the glutaminase family.
messages: Highly expressed in liver. Expressed in brain and pancreas. Not observed in heart, placenta, lung, skeletal muscle and kidney. Expression is significantly reduced in hepatocellular carcinomas.
messages: Homotetramer, dimer of dimers (Probable). Does not assemble into higher oligomers (By similarity). Interacts with the PDZ domain of the syntrophin SNTA1. Interacts with the PDZ domain of TAX1BP3 (PubMed:11163757).
messages: Mitochondrion
messages: Plays an important role in the regulation of glutamine catabolism. Promotes mitochondrial respiration and increases ATP generation in cells by catalyzing the synthesis of glutamate and alpha-ketoglutarate. Increases cellular anti-oxidant function via NADH and glutathione production. May play a role in preventing tumor proliferation.
messages: Up-regulated by P53 (at protein and mRNA level) under both stressed and non-stressed conditions.

9606:SLCO1B3
gene id: 9606:SLCO1B3
uniprot id: B3KP78
uniprot id: Q9NPD5
names: Caution
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: A conserved histidine residue in the third TMD (His-115) may play an essential role in the pH sensitivity of SLCO1B3/OATP1B3-mediated substrate transport.
messages: Basal cell membrane
messages: Basolateral cell membrane
messages: Belongs to the organo anion transporter (TC 2.A.60) family.
messages: Cell membrane
messages: Highly expressed in liver, in particular at the basolateral membrane of hepatocytes near the central vein (PubMed:10779507, PubMed:15159445). Expressed in the placenta (PubMed:12409283). In testis, primarily localized to the basal membrane of Sertoli cells and weakly expressed in Leydig cells and within the tubules (PubMed:35307651).
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: Mediates the Na(+)-independent uptake of organic anions (PubMed:15159445, PubMed:17412826, PubMed:10779507). Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (17-beta-glucuronosyl estradiol, dehydroepiandrosterone sulfate (DHEAS), and estrone 3-sulfate), as well as eicosanoid leukotriene C4, prostaglandin E2 and L-thyroxine (T4) (PubMed:15159445, PubMed:17412826, PubMed:10779507, PubMed:12568656, PubMed:11159893, PubMed:19129463). Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions (PubMed:19129463). Shows a pH-sensitive substrate specificity towards sulfated steroids, taurocholate and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment (PubMed:19129463). Involved in the clearance of bile acids and organic anions from the liver (PubMed:22232210). Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop (PubMed:22232210). Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition (PubMed:26383540). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins) such as pitavastatin, a clinically important class of hypolipidemic drugs (PubMed:15159445). May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drugs methotrexate and paclitaxel (PubMed:23243220). May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver (PubMed:16627748, PubMed:16624871).
messages: Membrane
messages: N-glycosylated.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:LTC4S
gene id: 9606:LTC4S
uniprot id: Q16873
names: Activity Regulation
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the MAPEG family.
messages: Catalyzes the conjugation of leukotriene A4 with reduced glutathione (GSH) to form leukotriene C4 with high specificity (PubMed:7937884, PubMed:27791009, PubMed:27365393, PubMed:9153254, PubMed:23409838). Can also catalyze the transfer of a glutathionyl group from glutathione (GSH) to 13(S),14(S)-epoxy-docosahexaenoic acid to form maresin conjugate in tissue regeneration 1 (MCTR1), a bioactive lipid mediator that possess potent anti-inflammatory and proresolving actions (PubMed:27791009).
messages: Detected in lung, platelets and the myelogenous leukemia cell line KG-1 (at protein level). LTC4S activity is present in eosinophils, basophils, mast cells, certain phagocytic mononuclear cells, endothelial cells, vascular smooth muscle cells and platelets.
messages: Endoplasmic reticulum membrane
messages: Homotrimer (PubMed:17632548, PubMed:17632546). Interacts with ALOX5AP and ALOX5 (PubMed:19233132).
messages: Inhibited by MK886.
messages: LTC4 synthase deficiency is associated with a neurometabolic developmental disorder characterized by muscular hypotonia, psychomotor retardation, failure to thrive, and microcephaly.
messages: Nucleus membrane
messages: Nucleus outer membrane
messages: Phosphorylation at Ser-36 by RPS6KB1 inhibits the leukotriene-C4 synthase activity.

9606:PGLYRP3
gene id: 9606:PGLYRP3
uniprot id: Q96LB9
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the N-acetylmuramoyl-L-alanine amidase 2 family.
messages: Detected in skin epidermis, eccrine sweat glands and ducts, ciliary body epithelial cells of the eye, in small intestine, colon, stomach and in mature epithelial cells of the tongue (at protein level). Highly expressed in skin and esophagus, expressed also in tonsils and thymus and to a much lesser extent in the stomach, descending colon, rectum and brain.
messages: Monomer. Homodimer; disulfide-linked. Heterodimer with PGLYRP4; disulfide-linked.
messages: N-glycosylated.
messages: Pattern receptor that binds to murein peptidoglycans (PGN) of Gram-positive bacteria. Has bactericidal activity towards Gram-positive bacteria. May kill Gram-positive bacteria by interfering with peptidoglycan biosynthesis. Binds also to Gram-negative bacteria, and has bacteriostatic activity towards Gram-negative bacteria. Plays a role in innate immunity.
messages: Secreted
messages: Up-regulated by exposure to Gram-positive and Gram-negative bacteria.

9606:CEACAM7
gene id: 9606:CEACAM7
uniprot id: Q14002
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Apical cell membrane
messages: Belongs to the immunoglobulin superfamily. CEA family.
messages: Cell membrane
messages: Expressed in columnar epithelial cells of the colon (at protein level) (PubMed:10436421). Strongly down-regulated in colonic adenocarcinomas.
messages: Homodimer.

9606:SHQ1
gene id: 9606:SHQ1
uniprot id: Q6PI26
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the SHQ1 family.
messages: Directly interacts with DKC1 alone, but not in the context of the core trimer composed of DKC1, NOP10 and NHP2, nor in the presence of NAF1. Does not interact with NAF1.
messages: Required for the quantitative accumulation of H/ACA ribonucleoproteins (RNPs), including telomerase, probably through the stabilization of DKC1, from the time of its synthesis until its association with NOP10, NHP2, and NAF1 at the nascent H/ACA RNA.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: cytosol
messages: nucleoplasm

9606:TOP6BL
gene id: 9606:TOP6BL
uniprot id: Q8N6T0
names: Disease Annotation
names: Domain
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the TOP6B-like family.
messages: Chromosome
messages: Component of a topoisomerase 6 complex specifically required for meiotic recombination. Together with SPO11, mediates DNA cleavage that forms the double-strand breaks (DSB) that initiate meiotic recombination. The complex promotes relaxation of negative and positive supercoiled DNA and DNA decatenation through cleavage and ligation cycles.
messages: Contains a signal peptide sequence at position 1-23.
messages: Despite a weak sequence similarity, retains most of the structural features of the ancestral archaeal Top6B subunit (AC O05207), including the transducer domain that interacts with the SPO11 subunit and the ATP-binding fold, also named GHKL fold.
messages: Detected in lung, spleen,colon and in skeletal muscle. Expressed in the ovaries, Fallopian tubes and uterus (PubMed:30388401).
messages: Expansion of a polymorphic CGG repeat within the 5'-UTR of this gene may be the cause of folate-sensitive fragile site FRA11A. The expansion is identified in the 15-year-old proband with intellectual disability as well as in phenotypically normal members of the family.
messages: Heterotetramer of SPO11 and 2 TOP6BL chains. Interacts with SPO11.
messages: The disease may be caused by variants affecting the gene represented in this entry.

9606:TRIM43B
gene id: 9606:TRIM43B
uniprot id: A6NCK2
names: Similarity
messages: Belongs to the TRIM/RBCC family.

9606:ZC3HAV1
gene id: 9606:ZC3HAV1
uniprot id: Q7Z2W4
names: Domain
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Antiviral protein which inhibits the replication of viruses by recruiting the cellular RNA degradation machineries to degrade the viral mRNAs. Binds to a ZAP-responsive element (ZRE) present in the target viral mRNA, recruits cellular poly(A)-specific ribonuclease PARN to remove the poly(A) tail, and the 3'-5' exoribonuclease complex exosome to degrade the RNA body from the 3'-end. It also recruits the decapping complex DCP1-DCP2 through RNA helicase p72 (DDX17) to remove the cap structure of the viral mRNA to initiate its degradation from the 5'-end. Its target viruses belong to families which include retroviridae: human immunodeficiency virus type 1 (HIV-1), moloney and murine leukemia virus (MoMLV) and xenotropic MuLV-related virus (XMRV), filoviridae: ebola virus (EBOV) and marburg virus (MARV), togaviridae: sindbis virus (SINV) and Ross river virus (RRV). Specifically targets the multiply spliced but not unspliced or singly spliced HIV-1 mRNAs for degradation. Isoform 1 is a more potent viral inhibitor than isoform 2. Isoform 2 acts as a positive regulator of RIGI signaling resulting in activation of the downstream effector IRF3 leading to the expression of type I IFNs and IFN stimulated genes (ISGs).
messages: Belongs to the ARTD/PARP family.
messages: By type I interferon (IFN) and viruses. Isoform 2 is up-regulated by 3'-PPP-RNA.
messages: Cytoplasm
messages: Homodimer or homooligomer. Homooligomerization is essential for its antiviral activity. Interacts with EXOSC5 (By similarity). Interacts (via N-terminal domain) with DDX17 in an RNA-independent manner (By similarity). Interacts with EXOSC3, EXOSC7, DCP2 and DCP1A. Interacts with PARN in an RNA-independent manner. Interacts with XRN1 in an RNA-dependent manner. Isoform 2 interacts (via zinc-fingers) with RIGI in an RNA-dependent manner. Interacts (via N-terminal domain) with DHX30 (via N-terminus) in an RNA-independent manner.
messages: Nucleus
messages: Phosphorylation at Ser-275 is essential for sequential phosphorylation of Ser-271, Ser-267, Ser-263 and Ser-257 by GSK3-beta. Phosphorylation by GSK3-beta enhances its antiviral activity (By similarity).
messages: The N-terminal domain is sufficient to bind to viral RNAs and promote their degradation. The second and fourth zinc fingers are involved in binding to specific viral RNAs (PubMed:20451500). Contains a divergent PARP homology ADP-ribosyltransferase domain which lacks the structural requirements for NAD[+] binding (PubMed:25635049). It is therefore inactive (PubMed:25043379, PubMed:25635049).

9606:CHRD
gene id: 9606:CHRD
uniprot id: E7ESX1
uniprot id: Q9H2X0
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the chordin family.
messages: Cleaved by tolloid proteases; cleavage participates in dorsoventral patterning during early development.
messages: Dorsalizing factor. Key developmental protein that dorsalizes early vertebrate embryonic tissues by binding to ventralizing TGF-beta family bone morphogenetic proteins (BMPs) and sequestering them in latent complexes (By similarity).
messages: Dorsalizing factor. Key developmental protein that dorsalizes early vertebrate embryonic tissues by binding to ventralizing TGF-beta family bone morphogenetic proteins (BMPs) and sequestering them in latent complexes.
messages: Expressed at the highest level in liver.
messages: Interacts with TWSG1 and/or BMP4.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Secreted

9606:RHCE
gene id: 9606:RHCE
uniprot id: A0A1L3H056
uniprot id: A0A220QMN8
uniprot id: P18577
names: Disease Annotation
names: Function
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the ammonium transporter (TC 2.A.49) family. Rh subfamily.
messages: Component of the ankyrin-1 complex, a multiprotein complex involved in the stability and shape of the erythrocyte membrane (PubMed:35835865). Mediates the primary membrane attachment site for ANK1 when associated with RHAG (PubMed:35835865). May participate in the ammonium and carbon dioxide transport through the heterotrimer form (Probable).
messages: Heterotrimer; a RHCE monomer interacts with a RHAG homodimer (PubMed:35835865). Component of the ankyrin-1 complex in the erythrocyte, composed of ANK1, RHCE, RHAG, SLC4A1, EPB42, GYPA, GYPB and AQP1 (PubMed:35835865). Interacts (via the N- and C-terminal) with ANK1 (via ANk 1-5 repeats); mediates the primary membrane attachment site for ANK1 (PubMed:35835865).
messages: Membrane
messages: Restricted to tissues or cell lines expressing erythroid characters. Isoform 4g and isoform RhPI-Alpha are expressed in immature erythroblasts but not in mature erythroblasts.
messages: RhCE and RhD are responsible for the RH blood group system. The molecular basis of the E=Rh3/e=Rh5 blood group antigens is a single variation in position 226; Pro-226 corresponds to Rh3 and Ala-226 to Rh5. The molecular basis of the C=Rh2/c=Rh4 blood group antigens is a single variation in position 103; Ser-103 corresponds to Rh2 and Pro-103 to Rh4.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:SSTR1
gene id: 9606:SSTR1
uniprot id: P30872
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Fetal kidney, fetal liver, and adult pancreas, brain, lung, jejunum and stomach.
messages: Interacts with SKB1.
messages: Receptor for somatostatin with higher affinity for somatostatin-14 than -28. This receptor is coupled via pertussis toxin sensitive G proteins to inhibition of adenylyl cyclase. In addition it stimulates phosphotyrosine phosphatase and Na(+)/H(+) exchanger via pertussis toxin insensitive G proteins.

9606:SH3BGR
gene id: 9606:SH3BGR
uniprot id: C9JJT2
uniprot id: P55822
names: Caution
names: Similarity
names: Tissue Specificity
messages: Belongs to the SH3BGR family.
messages: Expressed in heart and skeletal muscle.
messages: It is uncertain whether Met-1 or Met-64 is the initiator.

9606:PLCB3
gene id: 9606:PLCB3
uniprot id: Q01970
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Cytoplasm
messages: Interacts with SHANK2 (By similarity). Interacts with LPAR2 (PubMed:15143197).
messages: Membrane
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes.

9606:MYO1B
gene id: 9606:MYO1B
uniprot id: B0I1S9
uniprot id: E9PDF6
uniprot id: O43795
names: Caution
names: Function
names: Similarity
messages: Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.
messages: Motor protein that may participate in process critical to neuronal development and function such as cell migration, neurite outgrowth and vesicular transport.
messages: Represents an unconventional myosin. This protein should not be confused with the conventional myosin-1 (MYH1).

9606:SLC25A10
gene id: 9606:SLC25A10
uniprot id: A0A0S2Z382
uniprot id: A0A0S2Z3G3
uniprot id: F6RGN5
uniprot id: Q9UBX3
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the mitochondrial carrier (TC 2.A.29) family.
messages: Catalyzes the electroneutral exchange or flux of physiologically important metabolites such as dicarboxylates (malonate, malate, succinate), inorganic sulfur-containing anions, and phosphate, across mitochondrial inner membrane (PubMed:29211846). Plays an important role in gluconeogenesis, fatty acid metabolism, urea synthesis, and sulfur metabolism, particularly in liver, by supplying the substrates for the different metabolic processes. Regulates fatty acid release from adipocytes, and contributes to systemic insulin sensitivity (By similarity).
messages: Membrane
messages: Mitochondrion inner membrane
messages: Present in high amounts in liver and kidney, and at lower levels in all the other tissues analyzed.
messages: The disease may be caused by variants affecting the gene represented in this entry.

9606:CALML4
gene id: 9606:CALML4
uniprot id: Q96GE6
names: Similarity
names: Tissue Specificity
messages: Belongs to the calmodulin family.
messages: Expressed in breast cancer cell lines.

9606:GSPT1
gene id: 9606:GSPT1
uniprot id: B2RCT6
uniprot id: P15170
uniprot id: Q7KZX8
names: Caution
names: Function
names: Similarity
names: Subunit
messages: Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. EF-Tu/EF-1A subfamily.
messages: Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. ERF3 subfamily.
messages: Component of the eRF1-eRF3-GTP ternary complex, composed of ETF1/ERF1 and ERF3 (GSPT1/ERF3A or GSPT2/ERF3B) and GTP (PubMed:19417105, PubMed:27863242). Component of the transient SURF (SMG1-UPF1-eRF1-eRF3) complex (PubMed:19417104). The ETF1-GSPT1 complex interacts with JMJD4 (PubMed:24486019). Interacts with PABPC1 (By similarity). Interacts with SHFL (PubMed:30682371).
messages: GTPase component of the eRF1-eRF3-GTP ternary complex, a ternary complex that mediates translation termination in response to the termination codons UAA, UAG and UGA (PubMed:2511002, PubMed:15987998, PubMed:19417105, PubMed:27863242). GSPT1/ERF3A mediates ETF1/ERF1 delivery to stop codons: The eRF1-eRF3-GTP complex binds to a stop codon in the ribosomal A-site (PubMed:27863242). GTP hydrolysis by GSPT1/ERF3A induces a conformational change that leads to its dissociation, permitting ETF1/ERF1 to accommodate fully in the A-site (PubMed:16777602, PubMed:27863242). Component of the transient SURF complex which recruits UPF1 to stalled ribosomes in the context of nonsense-mediated decay (NMD) of mRNAs containing premature stop codons (PubMed:24486019). Required for SHFL-mediated translation termination which inhibits programmed ribosomal frameshifting (-1PRF) of mRNA from viruses and cellular genes (PubMed:30682371).
messages: eRF3 antibodies used in PubMed:19417104 do not differentiate between GSPT1/ERF3A and GSPT2/ERF3B.

9606:TARBP2
gene id: 9606:TARBP2
uniprot id: Q15633
names: Caution
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Binds to the HIV-1 TAR RNA which is located in the long terminal repeat (LTR) of HIV-1, and stimulates translation of TAR-containing RNAs (PubMed:2011739, PubMed:11438532, PubMed:12475984). This is achieved in part at least by binding to and inhibiting EIF2AK2/PKR, thereby reducing phosphorylation and inhibition of EIF2S1/eIF-2-alpha (PubMed:11438532). May also promote translation of TAR-containing RNAs independently of EIF2AK2/PKR (PubMed:12475984). Mediates recruitment of FTSJ3 methyltransferase to HIV-1 RNA, leading to 2'-O-methylation of the viral genome, allowing HIV-1 to escape the innate immune system (PubMed:30626973).
messages: (Microbial infection) Interacts with FTSJ3; forms a complex with FTSJ3 and HIV-1 TAR RNA.
messages: (Microbial infection) Interacts with ebolavirus VP30; this interaction, which occurs only in the presence of siRNA, prevents TARBP2 binding to DICER1 and thus allows the virus to counteract host RNA silencing.
messages: (Microbial infection) Interacts with ebolavirus VP35; this interaction prevents TARBP2 binding to DICER1 and thus allows the virus to counteract host RNA silencing.
messages: A paper describing truncating mutations of TARBP2 in tumor cells and resultant effects on DICER1 stability and miRNA processing has been retracted, due to concerns of image duplication in some of the figures.
messages: Belongs to the TARBP2 family.
messages: Cytoplasm
messages: Nucleus
messages: Required for formation of the RNA induced silencing complex (RISC). Component of the RISC loading complex (RLC), also known as the micro-RNA (miRNA) loading complex (miRLC), which is composed of DICER1, AGO2 and TARBP2. Within the RLC/miRLC, DICER1 and TARBP2 are required to process precursor miRNAs (pre-miRNAs) to mature miRNAs and then load them onto AGO2. AGO2 bound to the mature miRNA constitutes the minimal RISC and may subsequently dissociate from DICER1 and TARBP2. May also play a role in the production of short interfering RNAs (siRNAs) from double-stranded RNA (dsRNA) by DICER1 (By similarity) (PubMed:15973356, PubMed:16142218, PubMed:16271387, PubMed:16357216, PubMed:16424907, PubMed:17452327, PubMed:18178619). Binds in vitro to the PRM1 3'-UTR (By similarity). Seems to act as a repressor of translation (By similarity). For some pre-miRNA substrates, may also alter the choice of cleavage site by DICER1 (PubMed:23063653). Negatively regulates IRF7-mediated IFN-beta signaling triggered by viral infection by inhibiting the phosphorylation of IRF7 and promoting its 'Lys'-48-linked ubiquitination and degradation (PubMed:30927622).
messages: Self-associates. Component of the RISC loading complex (RLC), or micro-RNA (miRNA) loading complex (miRLC), which is composed of DICER1, AGO2 and TARBP2. Note that the trimeric RLC/miRLC is also referred to as RISC. Interacts with EIF2AK2/PKR and inhibits its protein kinase activity. Interacts with DHX9 and PRKRA. Interacts with DICER1, AGO2, MOV10, EIF6 and RPL7A (60S ribosome subunit); they form a large RNA-induced silencing complex (RISC) (PubMed:17507929). Interacts with IRF7; this interaction prevents IRF7 phosphorylation and activation (PubMed:30927622).
messages: perinuclear region

9606:RNF7
gene id: 9606:RNF7
uniprot id: Q9UBF6
names: Domain
names: Function
names: Induction
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the RING-box family.
messages: By 1,10-phenanthroline.
messages: Cytoplasm
messages: Expressed in heart, liver, skeletal muscle and pancreas. At very low levels expressed in brain, placenta and lung.
messages: Inactive.
messages: Nucleus
messages: Phosphorylation by CK2 is required for efficient degradation of NFKBIA and CDKN1B.
messages: Probable component of the SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins involved in cell cycle progression, signal transduction and transcription (PubMed:10851089). CRLs complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins, ARIH1 mediating addition of the first ubiquitin on CRLs targets (By similarity). Through the RING-type zinc finger, seems to recruit the E2 ubiquitination enzyme to the complex and brings it into close proximity to the substrate. Promotes the neddylation of CUL5 via its interaction with UBE2F. May play a role in protecting cells from apoptosis induced by redox agents.
messages: Probable part of SCF complexes, which consist of SKP1, CUL1, RNF7/RBX2 and a F-box protein. Interacts (preferentially) with CUL5. Also interacts (with lower preference) with CUL1, CUL2, CUL3, CUL4A and CUL4B. Interacts with UBE2F. Interacts with CSNK2B, the interaction is not affected by phosphorylation by CK2. May also interact with DCUN1D1, DCUN1D2, DCUN1D3, DCUN1D4 and DCUN1D5 (PubMed:26906416).
messages: The RING-type zinc finger domain is essential for ubiquitin ligase activity. It coordinates an additional third zinc ion.

9606:SLC15A5
gene id: 9606:SLC15A5
uniprot id: A6NIM6
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the major facilitator superfamily. Proton-dependent oligopeptide transporter (POT/PTR) (TC 2.A.17) family.
messages: Membrane
messages: Proton oligopeptide cotransporter.

9606:LRRC17
gene id: 9606:LRRC17
uniprot id: Q8N6Y2
names: Function
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Expressed in osteoblast cell lines. Well expressed in ovary, heart, pancreas, skeletal muscle, lung, and fetal kidney and lung and only at the basal levels in the other tissues examined including adult kidney. More expressed in S-type neuroblastoma cells than in N-type neuroblastoma cells.
messages: Involved in bone homeostasis. Acts as a negative regulator of RANKL-induced osteoclast precursor differentiation from bone marrow precursors (By similarity).
messages: extracellular space

9606:SERTAD2
gene id: 9606:SERTAD2
uniprot id: Q14140
names: Developmental Stage
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acts at E2F-responsive promoters as coregulator to integrate signals provided by PHD- and/or bromodomain-containing transcription factors. May act as coactivator as well as corepressor of E2F1-TFDP1 and E2F4-TFDP1 complexes on E2F consensus binding sites, which would activate or inhibit E2F-target genes expression. Modulates fat storage by down-regulating the expression of key genes involved in adipocyte lipolysis, thermogenesis and oxidative metabolism.
messages: Cytoplasm
messages: Expressed in adipose tissue.
messages: Interacts with XPO1; which mediates nuclear export. Interacts with TFDP1; modulates transactivation activity of TFDP1/E2F complexes.
messages: Nucleus
messages: Polyubiquitinated, which promotes proteasomal degradation.
messages: Transcript levels remain constant in all phases of the cell cycle. In contrast, protein levels accumulate at the G1/S phase boundary and decrease progressively through S phase until G2/M phase is reached, residual expression is observed in the G2/M and early G1 phases.

9606:PPP2R2C
gene id: 9606:PPP2R2C
uniprot id: Q9Y2T4
names: Caution
names: Function
names: Similarity
names: Subunit
messages: Belongs to the phosphatase 2A regulatory subunit B family.
messages: PP2A consists of a common heterodimeric core enzyme, composed of a 36 kDa catalytic subunit (subunit C) and a 65 kDa constant regulatory subunit (PR65 or subunit A), that associates with a variety of regulatory subunits. Proteins that associate with the core dimer include three families of regulatory subunits B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56 families), the 48 kDa variable regulatory subunit, viral proteins, and cell signaling molecules (By similarity). Interacts with IER5 (PubMed:25816751).
messages: The B regulatory subunit might modulate substrate selectivity and catalytic activity, and also might direct the localization of the catalytic enzyme to a particular subcellular compartment.
messages: The EMBL entry for PubMed:10574460 is not complete, the paper shows the rest of the sequence (residues 1 to 23).

9606:TMEM97
gene id: 9606:TMEM97
uniprot id: Q5BJF2
names: Caution
names: Function
names: Induction
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the TMEM97/sigma-2 receptor family.
messages: Interacts with NPC1.
messages: Intracellular orphan receptor that binds numerous drugs and which is highly expressed in various proliferating cancer cells (PubMed:28559337). Corresponds to the sigma-2 receptor, which is thought to play important role in regulating cell survival, morphology and differentiation (PubMed:23922215, PubMed:25620095). Under investigation for its potential diagnostic and therapeutic uses (PubMed:23922215, PubMed:25620095). May play a role as a regulator of cellular cholesterol homeostasis (PubMed:19583955). May function as sterol isomerase (PubMed:25566323). May alter the activity of some cytochrome P450 proteins (PubMed:22292588).
messages: Nucleus membrane
messages: Potentially useful for cancer diagnostics or as target for anticancer therapeutics or adjuvant anticancer treatment agents (PubMed:23922215). Some exogenous ligands display a neuroprotective effect (PubMed:25620095).
messages: Rough endoplasmic reticulum membrane
messages: Sigma receptors are classified into two subtypes (Sigma-1 and Sigma-2) based on their different pharmacological profile. Sigma-2 receptors are identified by radioligand-binding studies as a binding site with high affinity for di-o-tolylguanidine (DTG) and haloperidol.
messages: The molecular identity of the sigma-2 receptor has been unclear for a long time. It is now identified as TMEM97 (PubMed:28559337). Previously identified as PGRMC1 (AC O00264) (PubMed:22292588, PubMed:28007569).
messages: Up-regulated in ovarian surface epithelial (OSE) cells with progesterone.
messages: Widely expressed in normal tissues. Expressed in pancreatic, renal, breast, colon, ovarian surface epithelial (OSE) cells. Highly expressed in various proliferating cancer cells (PubMed:23922215).

9606:SERGEF
gene id: 9606:SERGEF
uniprot id: Q9UGK8
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Cytoplasm
messages: Interacts with SEC5. The interaction occurs only in the presence of magnesium or manganese and is stimulated by dCTP or GTP.
messages: Nucleus
messages: Probable guanine nucleotide exchange factor (GEF), which may be involved in the secretion process.

9606:TEX22
gene id: 9606:TEX22
uniprot id: C9J3V5
names: Subcellular Location Annotation
messages: Cytoplasm
messages: acrosome

9606:TBRG1
gene id: 9606:TBRG1
uniprot id: Q3YBR2
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acts as a growth inhibitor. Can activate p53/TP53, causes G1 arrest and collaborates with CDKN2A to restrict proliferation, but does not require either protein to inhibit DNA synthesis. Redistributes CDKN2A into the nucleoplasm. Involved in maintaining chromosomal stability.
messages: Belongs to the TBRG1 family.
messages: Interacts with CDKN2A and MDM2.
messages: Nucleus
messages: Ubiquitinated; mediated by MDM2 and leading to its subsequent proteasomal degradation.
messages: Widely expressed at low levels in most tissues, with highest levels in pancreas, lung and liver. Expression is decreased in primary tumors including lung, liver, breast, pancreas and kidney carcinomas, chronic lymphocytic leukemia and diffuse large B-cell lymphoma.

9606:MLLT6
gene id: 9606:MLLT6
uniprot id: P55198
names: Disease Annotation
names: Subcellular Location Annotation
names: Subunit
messages: A chromosomal aberration involving MLLT6 is associated with acute leukemias. Translocation t(11;17)(q23;q21) with KMT2A/MLL1. The result is a rogue activator protein.
messages: Interacts with histone H3; interaction is necessary for MLLT6 binding to nucleosomes; interaction is inhibited by histone H3 'Lys-27' methylations (H3K27me1, H3K27me2 and H3K27me3).
messages: Nucleus

9606:NAT1
gene id: 9606:NAT1
uniprot id: F5H5R8
uniprot id: P18440
uniprot id: Q400J6
names: Caution
names: Function
names: Miscellaneous
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the arylamine N-acetyltransferase family.
messages: Cytoplasm
messages: N-acetylation polymorphism is determined by a low or high NAT activity in liver and has been implicated in the action and toxicity of amine-containing drugs. Slow acetylation genotypes have been associated with significant lung cancer risk. Candidate risk factor for susceptibility to neural tube defects. The NAT1*10 allele has been associated with increased risk of colon and urinary bladder cancers and with higher levels of N-acetyltransferase activity and DNA adducts in aromatic amine tumor target organs such as colon and urinary bladder (PubMed:7585580).
messages: NAT1 was historically considered to be monomorphic in nature but reports of allelic variations at the NAT1 locus suggest that it is a polymorphically expressed enzyme.
messages: Participates in the detoxification of a plethora of hydrazine and arylamine drugs. Catalyzes the N- or O-acetylation of various arylamine and heterocyclic amine substrates and is able to bioactivate several known carcinogens.
messages: The allelic variation Ile-149 designated as NAT1*17 is part of the NAT1*11 allelic variation as reported by the nomenclature committee.

9606:GNE
gene id: 9606:GNE
uniprot id: Q9Y223
names: Activity Regulation
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Allosterically regulated (Probable); feedback inhibited by cytidine monophosphate-N-acetylneuraminic acid (CMP-Neu5Ac), the end product of neuraminic acid biosynthesis. Activity is dependent on oligomerization. The monomer is inactive, whereas the dimer catalyzes only the phosphorylation of N-acetylmannosamine; the hexamer is fully active for both enzyme activities (By similarity). Up-regulated after PKC-dependent phosphorylation.
messages: Cytoplasm
messages: Highest expression in liver and placenta. Also found in heart, brain, lung, kidney, skeletal muscle and pancreas. Isoform 1 is expressed in heart, brain, kidney, liver, placenta, lung, spleen, pancreas, skeletal muscle and colon. Isoform 2 is expressed mainly in placenta, but also in brain, kidney, liver, lung, pancreas and colon. Isoform 3 is expressed at low level in kidney, liver, placenta and colon.
messages: Homodimer and homohexamer.
messages: In the C-terminal section; belongs to the ROK (NagC/XylR) family.
messages: In the N-terminal section; belongs to the UDP-N-acetylglucosamine 2-epimerase family.
messages: Phosphorylated by PKC.
messages: Regulates and initiates biosynthesis of N-acetylneuraminic acid (NeuAc), a precursor of sialic acids. Plays an essential role in early development (By similarity). Required for normal sialylation in hematopoietic cells. Sialylation is implicated in cell adhesion, signal transduction, tumorigenicity and metastatic behavior of malignant cells.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:SLC6A11
gene id: 9606:SLC6A11
uniprot id: P48066
names: Activity Regulation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A11 subfamily.
messages: Cell membrane
messages: GABA transport is inhibited by SNAP-5114.
messages: Mediates sodium- and chloride-dependent transport of gamma-aminobutyric acid (GABA) (PubMed:7874447). Can also mediate transport of beta-alanine and to a lower extent that of taurine and hypotaurine (By similarity).
messages: Widespread distribution in the brain.

9606:OSR1
gene id: 9606:OSR1
uniprot id: Q8TAX0
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the Odd C2H2-type zinc-finger protein family.
messages: Expressed in adult colon, small intestine, prostate, testis, and fetal lung.
messages: Nucleus
messages: Transcription factor that plays a role in the regulation of embryonic heart and urogenital development.

9606:OR51E1
gene id: 9606:OR51E1
uniprot id: A0A126GVF8
uniprot id: Q8TCB6
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Highly expressed in prostate. Very low levels may be detected in some other tissues, such as placenta, skeletal muscle, heart, ovary and testis. Up-regulated in prostate cancers.
messages: Membrane
messages: Odorant receptor.

9606:CFAP53
gene id: 9606:CFAP53
uniprot id: Q96M91
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the CFAP53 family.
messages: Expressed in skin fibroblasts (at protein level). Expressed in airway epithelial cells (PubMed:36191189).
messages: Interacts with PIERCE1 and PIERCE2; the interactions link outer dynein arms docking complex (ODA-DC) to the internal microtubule inner proteins (MIP) in cilium axoneme.
messages: Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating (PubMed:36191189). May play a role in the beating of primary cilia and thereby be involved in the establishment of organ laterality during embryogenesis (PubMed:26531781).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: cilium axoneme

9606:PDE8A
gene id: 9606:PDE8A
uniprot id: O60658
names: Activity Regulation
names: Cofactor
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Sequence Caution
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Belongs to the cyclic nucleotide phosphodiesterase family. PDE8 subfamily.
messages: Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions.
messages: Composed of a C-terminal catalytic domain containing two putative divalent metal sites and an N-terminal regulatory domain.
messages: Expressed in most tissues except thymus and peripheral blood leukocytes. Highest levels in testis, ovary, small intestine and colon.
messages: Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes (PubMed:18983167). May be involved in maintaining basal levels of the cyclic nucleotide and/or in the cAMP regulation of germ cell development (PubMed:18983167). Binding to RAF1 reduces RAF1 'Ser-259' inhibitory-phosphorylation and stimulates RAF1-dependent EGF-activated ERK-signaling (PubMed:23509299). Protects against cell death induced by hydrogen peroxide and staurosporine (PubMed:23509299).
messages: Inhibited by dipyridimole. Insensitive to selective PDE inhibitors including rolipram and zaprinast as well as to the non-selective inhibitor, IBMX. Unaffected by cGMP.
messages: Interacts with RAF1. The interaction promotes RAF1 activity.
messages: Intron retention.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Phosphorylated at Ser-359 by PKA under elevated cAMP conditions, this enhances catalytic activity.

9606:DOCK2
gene id: 9606:DOCK2
uniprot id: H0YB76
uniprot id: Q5XG91
uniprot id: Q92608
names: Disease Annotation
names: Domain
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the DOCK family.
messages: Endomembrane system
messages: Homodimer (Probable). Interacts with RAC1 and RAC2. Interacts with CRKL and VAV. Interacts with CD3Z.
messages: Involved in cytoskeletal rearrangements required for lymphocyte migration in response of chemokines. Activates RAC1 and RAC2, but not CDC42, by functioning as a guanine nucleotide exchange factor (GEF), which exchanges bound GDP for free GTP. May also participate in IL2 transcriptional activation via the activation of RAC2.
messages: Specifically expressed in hematopoietic cells. Highly expressed in peripheral blood leukocytes, and expressed at intermediate level in thymus and spleen. Expressed at very low level in the small intestine and colon.
messages: Splicing donor and acceptor sites between exon 6 and exon 7 are not canonical.
messages: The DOCKER domain may mediate the GEF activity.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: cytoskeleton

9606:DEF6
gene id: 9606:DEF6
uniprot id: Q9H4E7
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Broadly expressed in the immune system. Highly expressed in T cells (PubMed:31308374).
messages: Cell membrane
messages: Cytoplasm
messages: Interacts with ZAP70 (By similarity). Interacts with IRF4, activated RAC1 and F-actin. Both the phosphorylated and non-phosphorylated forms bind phosphatidylinositol 3,4,5-trisphosphate (PtdInsP3). Interacts with RAB11A (PubMed:31308374).
messages: Nucleus
messages: Phosphatidylinositol 3,4,5-trisphosphate-dependent guanine nucleotide exchange factor (GEF) which plays a role in the activation of Rho GTPases RAC1, RhoA and CDC42 (PubMed:12651066, PubMed:15023524). Can regulate cell morphology in cooperation with activated RAC1 (By similarity). Involved in immune homeostasis by ensuring proper trafficking and availability of T-cell regulator CTLA-4 at T-cell surface (PubMed:31308374). Plays a role in Th2 (T helper cells) development and/or activation, perhaps by interfering with ZAP70 signaling (By similarity).
messages: The PH domain is essential for phosphatidylinositol 3,4,5-trisphosphate binding.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Tyrosine-phosphorylated by tyrosine-protein kinase LCK in response to T-cell activation.
messages: cytoskeleton
messages: filopodium
messages: perinuclear region

9606:SLCO4A1
gene id: 9606:SLCO4A1
uniprot id: Q96BD0
names: Developmental Stage
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: A conserved histidine residue in the third TMD (His-191) may play an essential role in the pH sensitivity of SLCO4A1/OATP4A1-mediated substrate transport.
messages: Belongs to the organo anion transporter (TC 2.A.60) family.
messages: Cell membrane
messages: Expressed in fetal brain, heart, kidney, liver, lung, skeletal muscle, spleen and pancreas (PubMed:10873595).
messages: Organic anion antiporter with apparent broad substrate specificity. Recognizes various substrates including thyroid hormones 3,3',5-triiodo-L-thyronine (T3), L-thyroxine (T4) and 3,3',5'-triiodo-L-thyronine (rT3), conjugated steroids such as estrone 3-sulfate and estradiol 17-beta glucuronide, bile acids such as taurocholate and prostanoids such as prostaglandin E2, likely operating in a tissue-specific manner (PubMed:10873595, PubMed:19129463, PubMed:30343886). May be involved in uptake of metabolites from the circulation into organs such as kidney, liver or placenta. Possibly drives the selective transport of thyroid hormones and estrogens coupled to an outward glutamate gradient across the microvillous membrane of the placenta (PubMed:30343886). The transport mechanism, its electrogenicity and potential tissue-specific counterions remain to be elucidated (Probable).
messages: Widely expressed (PubMed:10873595, PubMed:11316767). Expressed in placental trophoblasts (PubMed:10873595, PubMed:12409283). Expressed in pancreas, kidney, skeletal muscle, liver, lung, brain, heart, colon, small intestine, ovary, testis, prostate, thymus and spleen. In testis, primarily localized to Leydig cells (PubMed:35307651).

9606:CPQ
gene id: 9606:CPQ
uniprot id: Q9Y646
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the peptidase M28 family.
messages: Carboxypeptidase that may play an important role in the hydrolysis of circulating peptides. Catalyzes the hydrolysis of dipeptides with unsubstituted terminals into amino acids. May play a role in the liberation of thyroxine hormone from its thyroglobulin (Tg) precursor.
messages: Endoplasmic reticulum
messages: Golgi apparatus
messages: Homodimer. The monomeric form is inactive while the homodimer is active.
messages: Lysosome
messages: Mainly detected in blood plasma. Abundant in placenta and kidney. Present at low level in muscles, liver and skin fibroblasts. Not detected in brain or white blood cells (at protein level).
messages: N-glycosylated. The secreted form is modified by hybrid or complex type oligosaccharide chains (By similarity).
messages: Secreted
messages: Up-regulated in the majority of hepatitis C virus-associated hepatocellular carcinoma.

9606:KLHL36
gene id: 9606:KLHL36
uniprot id: Q8N4N3
names: Function
names: Subunit
messages: Interacts with CUL3.
messages: Probable substrate-specific adapter of an E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.

9606:SNAP29
gene id: 9606:SNAP29
uniprot id: O95721
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts with Hantaan hantavirus nucleoprotein; this interaction prevents the breakdown of the viral glycoprotein N by virus-triggered autophagy.
messages: (Microbial infection) The interaction with STX17 is decreased in presence of SARS coronavirus-2/SARS-CoV-2 ORF3A protein.
messages: Belongs to the SNAP-25 family.
messages: Cytoplasm
messages: Forms a SNARE complex, composed of VAMP8, SNAP29 and STX17, involved in fusion of autophagosome with lysosome (PubMed:23217709, PubMed:25686604). Interacts with multiple syntaxins including STX6 (By similarity). Interacts with EIPR1 (PubMed:27440922). Interacts with STX17; this interaction is increased in the absence of TMEM39A (PubMed:31806350, PubMed:33422265).
messages: Found in brain, heart, kidney, liver, lung, placenta, skeletal muscle, spleen and pancreas.
messages: Golgi apparatus membrane
messages: SNAREs, soluble N-ethylmaleimide-sensitive factor-attachment protein receptors, are essential proteins for fusion of cellular membranes. SNAREs localized on opposing membranes assemble to form a trans-SNARE complex, an extended, parallel four alpha-helical bundle that drives membrane fusion. SNAP29 is a SNARE involved in autophagy through the direct control of autophagosome membrane fusion with the lysososome membrane. Also plays a role in ciliogenesis by regulating membrane fusions.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: autophagosome membrane
messages: cilium membrane

9606:CLINT1
gene id: 9606:CLINT1
uniprot id: Q14677
names: Function
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the epsin family.
messages: Binds clathrin heavy chain and AP-2 (PubMed:12213833, PubMed:12429846, PubMed:12538641). Interacts with VTI1B (PubMed:18033301). Interacts with GGA2 (via GAE domain) (PubMed:12213833, PubMed:14665628). Interacts with AP1G1 (via GAE domain) (PubMed:12213833, PubMed:12429846, PubMed:12538641, PubMed:14665628). Interacts with AP1G2 (via GAE domain) (PubMed:14665628).
messages: Binds to membranes enriched in phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). May have a role in transport via clathrin-coated vesicles from the trans-Golgi network to endosomes. Stimulates clathrin assembly.
messages: Cytoplasm
messages: Genetic variations in CLINT1 may contribute to susceptibility to schizophrenia (SCZD1) and psychotic disorders in some populations.
messages: Membrane
messages: Ubiquitously expressed at low to intermediate levels.
messages: clathrin-coated vesicle
messages: perinuclear region

9606:CFAP36
gene id: 9606:CFAP36
uniprot id: Q96G28
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the CFAP36 family.
messages: Cytoplasm
messages: Expressed in several human tissues including brain, testis, heart, lung, pancreas and spleen (at protein level).
messages: Interacts with ARL3.
messages: May act as an effector for ARL3.
messages: Nucleus
messages: flagellum

9606:ZNF284
gene id: 9606:ZNF284
uniprot id: Q2VY69
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: Expressed in lung, liver, pancreas and thymus. Lower expression in heart, placenta, spleen, prostate, ovary, small intestine and colon. No expression seen in brain, skeletal muscle, kidney, testis and peripheral blood leukocyte.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:BTLA
gene id: 9606:BTLA
uniprot id: Q7Z6A9
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: Cell membrane
messages: Inhibitory receptor on lymphocytes that negatively regulates antigen receptor signaling via PTPN6/SHP-1 and PTPN11/SHP-2 (PubMed:12796776, PubMed:14652006, PubMed:15568026, PubMed:18193050). May interact in cis (on the same cell) or in trans (on other cells) with TNFRSF14 (PubMed:19915044). In cis interactions, appears to play an immune regulatory role inhibiting in trans interactions in naive T cells to maintain a resting state. In trans interactions, can predominate during adaptive immune response to provide survival signals to effector T cells (PubMed:19915044).
messages: Interacts with tyrosine phosphatases PTPN6/SHP-1 and PTPN11/SHP-2 (PubMed:12796776, PubMed:14652006). Interacts with TNFRSF14/HVEM (via cysteine-rich domain 1) (PubMed:15568026, PubMed:18193050, PubMed:19915044).
messages: N-glycosylated.
messages: Phosphorylated on Tyr residues by TNFRSF14 and by antigen receptors cross-linking, both inducing association with PTPN6 and PTPN11.

9606:TRAF4
gene id: 9606:TRAF4
uniprot id: Q9BUZ4
names: Domain
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Adapter protein with E3 ligase activity that is involved in many diverse biological processes including cell proliferation, migration, differentiation, DNA repair, platelet activation or apoptosis (PubMed:30352854, PubMed:31076633, PubMed:32268273, PubMed:33991522). Promotes EGFR-mediated signaling by facilitating the dimerization of EGFR and downstream AKT activation thereby promoting cell proliferation (PubMed:30352854). Ubiquitinates SMURF2 through 'Lys-48'-linked ubiquitin chain leading to SMURF2 degradation through the proteasome and subsequently osteogenic differentiation (PubMed:31076633). Promotes 'Lys-63'-mediated ubiquitination of CHK1 which in turn activates cell cycle arrest and activation of DNA repair (PubMed:32357935). In addition, promotes an atypical 'Lys-29'-linked ubiquitination at the C-terminal end of IRS1 which is crucial for insulin-like growth factor (IGF) signal transduction (PubMed:33991522). Regulates activation of NF-kappa-B in response to signaling through Toll-like receptors. Required for normal skeleton development, and for normal development of the respiratory tract (By similarity). Required for activation of RPS6KB1 in response to TNF signaling. Modulates TRAF6 functions. Inhibits adipogenic differentiation by activating pyruvate kinase PKM activity and subsequently the beta-catenin signaling pathway (PubMed:32268273).
messages: Belongs to the TNF receptor-associated factor family. B subfamily.
messages: Cell membrane
messages: Cytoplasm
messages: Expressed in epithelial cells of thymus, dendritic cells of lymph node, and in the basal cell layer of epithelia such as epidermis, nasopharynx, respiratory tract, salivary gland, and esophagus.
messages: Homotrimer (Probable). Interacts with LTBR/TNFRSF3, NGFR/TNFRSF16, RPS6KB1 and TGFB1I1. Interacts with SMURF1. Interacts (via TRAF domain) with MAP3K4 (via kinase domain). Interacts with NCF1, TICAM1, IRAK1 and TRAF6, and is probably part of a complex containing TRAF4, NCF1, TICAM1, IRAK1 and TRAF6. Interacts (via MATH domain) with GP6 and GP1BB (PubMed:20946164, PubMed:29073066). Interacts with EGFR (via C-terminal region); this interaction promotes the formation of EGFR asymmetric dimers (PubMed:30352854). Interacts with PKM; this interaction promotes PKM kinase activity (PubMed:32268273).
messages: Nucleus
messages: Polyubiquitinated, leading to its proteasomal degradation (PubMed:19937093). Ubiquitinated at Lys-263 by the SCF(FBXL2) complex, leading to its degradation by the proteasome (By similarity).
messages: The MATH/TRAF domain binds to receptor cytoplasmic domains.
messages: The coiled coil domain mediates homo- and hetero-oligomerization.
messages: Up-regulated by bacterial lipopolysaccharides (LPS) and by single-stranded CpG oligodeoxynucleotide.
messages: cytoskeleton
messages: perinuclear region
messages: tight junction

9606:LTBP2
gene id: 9606:LTBP2
uniprot id: Q14767
names: Caution
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: A publication reported that a complex is formed with TGFB1 (PubMed:7798248). According to another report, there is no association with TGFB1 (PubMed:10930463).
messages: Belongs to the LTBP family.
messages: Contains hydroxylated asparagine residues.
messages: Expressed in the aorta (at protein level). Expressed in lung, weakly expressed in heart, placenta, liver and skeletal muscle.
messages: Forms part of the large latent transforming growth factor beta precursor complex; removal is essential for activation of complex (PubMed:7798248). Interacts with SDC4 (PubMed:20382221). Interacts (via C-terminal domain) with FBN1 (via N-terminal domain) in a Ca(+2)-dependent manner (PubMed:17293099).
messages: May play an integral structural role in elastic-fiber architectural organization and/or assembly.
messages: N-Glycosylated.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: extracellular matrix

9606:MVB12A
gene id: 9606:MVB12A
uniprot id: Q96EY5
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the MVB12 family.
messages: Component of the ESCRT-I complex (endosomal sorting complex required for transport I) which consists of TSG101, VPS28, a VPS37 protein (VPS37A to -D) and MVB12A or MVB12B in a 1:1:1:1 stoichiometry. Interacts with CD2AP and CIN85/SH3KBP1. Interacts with CD2AP (via one of the SH3 domains). Interacts with TSG101; the association appears to be mediated by the TSG101-VPS37 binary subcomplex. Interacts with VPS28. Interacts with VPS37B; the association appears to be mediated by the TSG101-VPS37 binary subcomplex. Interacts with VPS37C; the association appears to be mediated by the TSG101-VPS37 binary subcomplex. Interacts with VPS37D; the association appears to be mediated by the TSG101-VPS37 binary subcomplex. Interacts with CEP55.
messages: Component of the ESCRT-I complex, a regulator of vesicular trafficking process. Required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies. May be involved in the ligand-mediated internalization and down-regulation of EGF receptor.
messages: Cytoplasm
messages: Does not interact with CD2AP.
messages: Endosome
messages: Late endosome membrane
messages: Nucleus
messages: Phosphorylated on Tyr-204 upon EGF stimulation. Phosphorylation is required for interaction with CD2AP and CIN85/SH3KBP1.
messages: Ubiquitously expressed except in skeletal muscle.
messages: centrosome

9606:OR8I2
gene id: 9606:OR8I2
uniprot id: Q8N0Y5
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Odorant receptor.

9606:SLC5A7
gene id: 9606:SLC5A7
uniprot id: B2RCU2
uniprot id: B4DUU7
uniprot id: Q2T9H3
uniprot id: Q9GZV3
names: Activity Regulation
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the sodium:solute symporter (SSF) (TC 2.A.21) family.
messages: Cell membrane
messages: Choline uptake activity is regulated by SLC5A7/CHT1 internalization (inactive form) from the cell surface and recycling of internalized SLC5A7/CHT1 into the cell surface (active form) (PubMed:12969261, PubMed:15953352) (Probable). Activated by extracellular chloride ion (PubMed:11068039, PubMed:17005849, PubMed:12237312). Specifically inhibited by nanomolar concentrations of hemicholinium 3 (PubMed:11027560, PubMed:11068039, PubMed:12969261, PubMed:17005849, PubMed:23132865, PubMed:12237312).
messages: Early endosome membrane
messages: Expressed in putamen, spinal cord and medulla (PubMed:11027560, PubMed:11068039). Expressed in cholinergic neurons (PubMed:27569547).
messages: High-affinity Na(+)-coupled choline transmembrane symporter (PubMed:11027560, PubMed:11068039, PubMed:12969261, PubMed:17005849, PubMed:23141292, PubMed:23132865, PubMed:12237312, PubMed:27569547). Functions as an electrogenic, voltage-dependent transporter with variable charge/choline stoichiometry (PubMed:17005849). Choline uptake and choline-induced current is also Cl(-)-dependent where Cl(-) is likely a regulatory ion rather than cotransported ion (PubMed:11068039, PubMed:17005849, PubMed:12237312). Plays a critical role in acetylcholine (ACh) synthesis by taking up the substrate choline from the synaptic cleft into the presynaptic nerve terminals after neurotransmitter release (PubMed:27569547). SLC5A7/CHT1-mediated choline high-affinity transport in cholinergic neurons is the rate-limiting step for production of ACh, thereby facilitating communication by subsequent action potentials (PubMed:11027560). Localized predominantly in presynaptic terminal intracellular organelles, and translocated to the plasma membrane in active form in response to neuronal activity (PubMed:12969261, PubMed:15953352).
messages: Homooligomerizes at cell surface (PubMed:23132865). Interacts with SEC14L1; may regulate SLC5A7 (PubMed:17092608).
messages: Membrane
messages: Phosphorylated.
messages: Presynaptic cell membrane
messages: The C-terminal dileucine-like motif (DKTILV) controls SLC5A7/CHT1 internalization in clathrin-coated vesicles to early endosomes as well as choline transporter activity.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: axon
messages: synaptic vesicle membrane

9606:CLIP1
gene id: 9606:CLIP1
uniprot id: B3KXA5
uniprot id: P30622
names: Domain
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Binds to the plus end of microtubules and regulates the dynamics of the microtubule cytoskeleton. Promotes microtubule growth and microtubule bundling. Links cytoplasmic vesicles to microtubules and thereby plays an important role in intracellular vesicle trafficking. Plays a role macropinocytosis and endosome trafficking.
messages: Cytoplasm
messages: Cytoplasmic vesicle membrane
messages: Detected in dendritic cells (at protein level). Highly expressed in the Reed-Sternberg cells of Hodgkin disease.
messages: Interacts with MTOR; phosphorylates and regulates CLIP1 (PubMed:12231510). Interacts (via CAP-Gly domains) with tubulin (PubMed:17563362, PubMed:17889670). Interacts with SLAIN2 (PubMed:21646404). Interacts (via zinc finger) with DCTN1 (PubMed:17828275, PubMed:20679239). Interacts with TUBA1B, MAPRE1 and MAPRE3 (PubMed:17563362). Binds preferentially to tyrosinated microtubules, and only marginally to detyrosinated microtubules (By similarity).
messages: Intramolecular interaction between the zinc finger domain and the CAP-Gly domains may inhibit interaction with tubulin.
messages: Phosphorylated. Phosphorylation induces conformational changes by increasing the affinity of the N-terminus for C-terminus, resulting in inhibition of its function thus decreasing its binding to microtubules and DCTN1. Exhibits a folded, autoinhibited conformation when phosphorylated and an open conformation when dephosphorylated with increased binding affinity to microtubules and DCTN1. Phosphorylation regulates its recruitment to tyrosinated microtubules and the recruitment of vesicular cargo to microtubules in neurons (By similarity). Phosphorylation by MTOR may positively regulate CLIP1 association with microtubules (PubMed:12231510).
messages: cytoskeleton
messages: ruffle

9606:TTLL12
gene id: 9606:TTLL12
uniprot id: Q14166
names: Caution
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Although it belongs to the tubulin--tyrosine ligase family, the TTL domain lacks some of the ATP binding sites predicted to be essential for TTL activity (PubMed:23251473). Lacks tyrosine ligase activity in vitro (PubMed:23251473). Lacks glutamylation activity in vitro (By similarity). Although TTLL12 contains a potential SET-like domain in the N-terminus, it does not have lysine methyltransferase activity towards histone in vitro (PubMed:23251473).
messages: Belongs to the tubulin--tyrosine ligase family.
messages: Cytoplasm
messages: Expressed in the basal layer of prostate and endothelial cells. Increased expression in prostatic intraepithelial neoplasia and metastatic lesions.
messages: Interacts with MAVS; the interaction prevents MAVS binding to TBK1 and IKBKE (PubMed:28011935). Interacts (via N-terminus) with TBK1 (via protein kinase domain) (PubMed:28011935). Interacts (via TTL domain) with IKBKE (via protein kinase domain) (PubMed:28011935). Interacts with tubulin alpha (PubMed:23251473). Interacts with histone H3 and histone H4 (when trimethylated at 'Lys-20' (H4K20me3)) (PubMed:23251473). Interacts with CBX3 (PubMed:23251473).
messages: Midbody
messages: Negatively regulates post-translational modifications of tubulin, including detyrosination of the C-terminus and polyglutamylation of glutamate residues (PubMed:20162578, PubMed:23251473). Also, indirectly promotes histone H4 trimethylation at 'Lys-20' (H4K20me3) (PubMed:23251473). Probably by controlling tubulin and/or histone H4 post-translational modifications, plays a role in mitosis and in maintaining chromosome number stability (PubMed:20162578, PubMed:23251473). During RNA virus-mediated infection, acts as a negative regulator of the RIG-I pathway by preventing MAVS binding to TBK1 and IKBKE (PubMed:28011935).
messages: Nucleus
messages: centrosome
messages: spindle

9606:HCRTR1
gene id: 9606:HCRTR1
uniprot id: A6NMV7
uniprot id: O43613
names: Domain
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Membrane
messages: Moderately selective excitatory receptor for orexin-A and, with a lower affinity, for orexin-B neuropeptide (PubMed:9491897, PubMed:26950369). Triggers an increase in cytoplasmic Ca(2+) levels in response to orexin-A binding (PubMed:9491897, PubMed:26950369).
messages: The N-terminal region is required for orexin signaling.
messages: The antagonists suvorexant and SB-674042 bind at the cognate neuropeptide binding site that is situated between the transmembrane helices and accessible from the extracellular side of the membrane.

9606:ERVMER34-1
gene id: 9606:ERVMER34-1
uniprot id: Q9H9K5
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the gamma type-C retroviral envelope protein family.
messages: Cell membrane
messages: Cleaved by some metalloproteinase at 432-Gln-Arg-433 (mainly) or 433-Arg-Gln-434, leading to release the secreted form (Endogenous retroviral envelope protein HEMO, secreted form) in the extracellular medium.
messages: Endogenous envelope proteins originate from retroviral envelope proteins, which mediate receptor recognition and membrane fusion during early infection. Endogenous envelope proteins may have kept, lost or modified their original function during evolution.
messages: Expressed at high level in the placenta and stem cells (at protein level) (PubMed:28739914). Also expressed in the kidney but at a lower level (PubMed:28739914). Endogenous retroviral envelope protein HEMO, secreted form: Present in the blood of pregnant women (at protein level) (PubMed:28739914).
messages: N-glycosylated.
messages: Secreted

9606:COQ4
gene id: 9606:COQ4
uniprot id: Q9Y3A0
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the COQ4 family.
messages: Component of a multi-subunit COQ enzyme complex, composed of at least COQ3, COQ4, COQ5, COQ6, COQ7 and COQ9.
messages: Component of the coenzyme Q biosynthetic pathway. May play a role in organizing a multi-subunit COQ enzyme complex required for coenzyme Q biosynthesis. Required for steady-state levels of other COQ polypeptides.
messages: Expressed ubiquitously, but at high levels in liver, lung and pancreas.
messages: Mitochondrion inner membrane
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:CYP2C9
gene id: 9606:CYP2C9
uniprot id: P11712
uniprot id: S5RV20
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
messages: A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and steroids (PubMed:7574697, PubMed:9866708, PubMed:9435160, PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:7574697, PubMed:9866708, PubMed:9435160, PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:7574697, PubMed:15766564, PubMed:19965576, PubMed:9866708). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Exhibits low catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes bisallylic hydroxylation and hydroxylation with double-bond migration of polyunsaturated fatty acids (PUFA) (PubMed:9866708, PubMed:9435160). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan (PubMed:25994031).
messages: Belongs to the cytochrome P450 family.
messages: By rifampicin.
messages: Endoplasmic reticulum membrane
messages: Microsome membrane

9606:GRID2
gene id: 9606:GRID2
uniprot id: O43424
names: Disease Annotation
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. GRID2 subfamily.
messages: Cell membrane
messages: Postsynaptic cell membrane
messages: Receptor for glutamate. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists. Promotes synaptogenesis and mediates the D-Serine-dependent long term depression signals and AMPA receptor endocytosis of cerebellar parallel fiber-Purkinje cell (PF-PC) synapses through the beta-NRX1-CBLN1-GRID2 triad complex (PubMed:27418511).
messages: Tetramer; dimer of dimers (PubMed:27418511). Interacts with EML2, MAGI2 (via PDZ domains) and AP4M1 (By similarity). Interacts with BECN1, GOPC, GRID2IP, SHANK1 and SHANK2. Interacts with CBLN2, but not with CBLN4 (By similarity). Interacts with CBLN1 (via C1q domain); the interaction is CBLN1-NRX1 complex formation-dependent; CBLN1-binding is calcium-independent; CBLN1 hexamers anchor GRID2 N-terminal domain dimers to monomeric NRXN1 isoform beta; promotes synaptogenesis and mediates the D-Serine-dependent long term depression signals and AMPA receptor endocytosis (PubMed:27418511).
messages: The PDZ-binding motif mediates interaction with GOPC.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:BMAL1
gene id: 9606:BMAL1
uniprot id: O00327
names: Activity Regulation
names: Function
names: Miscellaneous
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Regulates SARS coronavirus-2/SARS-CoV-2 entry and replication in lung epithelial cells probably through the post-transcriptional regulation of ACE2 and interferon-stimulated gene expression.
messages: Acetylated on Lys-538 by CLOCK during the repression phase of the circadian cycle. Acetylation facilitates recruitment of CRY1 protein and initiates the repression phase of the circadian cycle. Acetylated at Lys-538 by KAT5 during the activation phase of the cycle, leading to recruitment of the positive transcription elongation factor b (P-TEFb) and BRD4, followed by productive elongation of circadian transcripts. Deacetylated by SIRT1, which may result in decreased protein stability.
messages: CLOCK-BMAL1 double mutations within the PAS domains result in synergistic desensitization to high levels of CRY on repression of CLOCK-BMAL1 transcriptional activity of PER1 and, disrupt circadian rhythmicity.
messages: Component of the circadian clock oscillator which includes the CRY1/2 proteins, CLOCK or NPAS2,BMAL1 or BMAL2, CSNK1D and/or CSNK1E, TIMELESS and the PER1/2/3 proteins (By similarity). Forms a heterodimer with CLOCK (PubMed:9616112, PubMed:23229515). The CLOCK-BMAL1 heterodimer is required for E-box-dependent transactivation, for CLOCK nuclear translocation and degradation, and, for phosphorylation of both CLOCK and BMAL1 (By similarity). Part of a nuclear complex which also includes RACK1 and PRKCA; RACK1 and PRKCA are recruited to the complex in a circadian manner (By similarity). Interacts with NPAS2 (By similarity). Interacts with EZH2 (By similarity). Interacts with SUMO3 (By similarity). Interacts with SIRT1 (By similarity). Interacts with AHR (PubMed:9079689). Interacts with ID1, ID2 and ID3 (By similarity). Interacts with DDX4 (By similarity). Interacts with OGT (By similarity). Interacts with EED and SUZ12 (By similarity). Interacts with MTA1 (By similarity). Interacts with CIART (PubMed:24385426). Interacts with HSP90 (PubMed:9079689). Interacts with KAT2B and EP300 (PubMed:14645221). Interacts with BHLHE40/DEC1 and BHLHE41/DEC2 (By similarity). Interacts with RELB and the interaction is enhanced in the presence of CLOCK (By similarity). Interacts with PER1, PER2, CRY1 and CRY2 and this interaction requires a translocation to the nucleus (By similarity). Interaction of the CLOCK-BMAL1 heterodimer with PER or CRY inhibits transcription activation (By similarity). Interaction of the CLOCK-BMAL1 with CRY1 is independent of DNA but with PER2 is off DNA (By similarity). The CLOCK-BMAL1 heterodimer interacts with GSK3B (By similarity). Interacts with KDM5A (PubMed:21960634). Interacts with KMT2A; in a circadian manner (By similarity). Interacts with UBE3A (PubMed:24728990). Interacts with PRKCG (By similarity). Interacts with MAGEL2 (By similarity). Interacts with NCOA2 (By similarity). Interacts with THRAP3 (By similarity). The CLOCK-BMAL1 heterodimer interacts…
messages: Cytoplasm
messages: Hair follicles (at protein level). Highly expressed in the adult brain, skeletal muscle and heart.
messages: Nucleus
messages: O-glycosylated; contains O-GlcNAc. O-glycosylation by OGT prevents protein degradation by inhibiting ubiquitination. It also stabilizes the CLOCK-BMAL1 heterodimer thereby increasing CLOCK-BMAL1-mediated transcription of genes in the negative loop of the circadian clock such as PER1/2/3 and CRY1/2.
messages: PML body
messages: Phosphorylated upon dimerization with CLOCK. Phosphorylation enhances the transcriptional activity, alters the subcellular localization and decreases the stability of the CLOCK-BMAL1 heterodimer by promoting its degradation. Phosphorylation shows circadian variations in the liver with a peak between CT10 to CT14. Phosphorylation at Ser-90 by CK2 is essential for its nuclear localization, its interaction with CLOCK and controls CLOCK nuclear entry (By similarity). Dephosphorylation at Ser-78 is important for dimerization with CLOCK and transcriptional activity (PubMed:23229515).
messages: Sumoylated on Lys-259 upon dimerization with CLOCK. Predominantly conjugated to poly-SUMO2/3 rather than SUMO1 and the level of these conjugates undergo rhythmic variation, peaking at CT9-CT12. Sumoylation localizes it exclusively to the PML body and promotes its ubiquitination in the PML body, ubiquitin-dependent proteasomal degradation and the transcriptional activity of the CLOCK-BMAL1 heterodimer.
messages: There is conflicting data about the effect of NAD cofactors on activity. PubMed:11441146 suggests that the redox state of the cell can modulate the transcriptional activity of the CLOCK-BMAL1 heterodimer; NADH and NADPH enhance the DNA-binding activity of the heterodimer. PubMed:23229515 reports that NADH and NADPH have no significant effect on DNA-binding activity of the CLOCK-BMAL1 heterodimer.
messages: Transcriptional activator which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots 'circa' (about) and 'diem' (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN. The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle. Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day. Transcription and translation of core clock components (CLOCK, NPAS2, BMAL1, BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle). A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a …
messages: Ubiquitinated, leading to its proteasomal degradation (PubMed:24728990). Deubiquitinated by USP9X (PubMed:29626158).
messages: Undergoes lysosome-mediated degradation in a time-dependent manner in the liver.

9606:RAB2A
gene id: 9606:RAB2A
uniprot id: P61019
names: Activity Regulation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the small GTPase superfamily. Rab family.
messages: Endoplasmic reticulum membrane
messages: Endoplasmic reticulum-Golgi intermediate compartment membrane
messages: Golgi apparatus membrane
messages: Interacts with PRKCI (PubMed:14570876). Interacts with TRIP11 (PubMed:25473115). Interacts (in GTP-bound form) with GARIN1B (By similarity).
messages: Melanosome
messages: Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP, GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity, and GDP dissociation inhibitors which inhibit the dissociation of the nucleotide from the GTPase.
messages: The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between active GTP-bound and inactive GDP-bound states. In their active state, drive transport of vesicular carriers from donor organelles to acceptor organelles to regulate the membrane traffic that maintains organelle identity and morphology. Required for protein transport from the endoplasmic reticulum to the Golgi complex. Regulates the compacted morphology of the Golgi.
messages: acrosome

9606:ETV5
gene id: 9606:ETV5
uniprot id: P41161
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the ETS family.
messages: Binds to DNA sequences containing the consensus nucleotide core sequence 5'-GGAA.-3'.
messages: Interacts (via C-terminal) with ZMYM5 (via N-terminal 120 amino acid region).
messages: Nucleus
messages: Ubiquitous.

9606:KRBOX4
gene id: 9606:KRBOX4
uniprot id: Q5JUW0
names: Caution
names: Tissue Specificity
messages: Despite its name, it does not contain a canonical C2H2-type zinc-finger, seems to be a partial inverted duplication of ZNF674.
messages: Expressed in brain, ovary, testis, prostate, tonsil, heart, bone marrow, colon, breast and kidney.

9606:MGST2
gene id: 9606:MGST2
uniprot id: Q99735
names: Activity Regulation
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the MAPEG family.
messages: Catalyzes several different glutathione-dependent reactions (PubMed:8703034, PubMed:9278457, PubMed:23409838, PubMed:26656251, PubMed:26066610). Catalyzes the glutathione-dependent reduction of lipid hydroperoxides, such as 5-HPETE (PubMed:9278457, PubMed:23409838). Has glutathione transferase activity, toward xenobiotic electrophiles, such as 1-chloro-2, 4-dinitrobenzene (CDNB) (PubMed:23409838, PubMed:8703034). Catalyzes also the conjugation of leukotriene A4 with reduced glutathione to form leukotriene C4 (LTC4) (PubMed:23409838, PubMed:26656251). Involved in oxidative DNA damage induced by ER stress and anticancer agents by activating LTC4 biosynthetic machinery in nonimmune cells (PubMed:26656251).
messages: Each monomer can bind on GSH molecule but only one subunit is catalytically active.
messages: Endoplasmic reticulum membrane
messages: Homotrimer.
messages: Liver, spleen, skeletal muscle, heart, adrenals, pancreas, prostate, testis, fetal liver, and fetal spleen. Very low expression in lung, brain, placenta and bone marrow (PubMed:8703034). Abundantly expressed in human umbilical vein endothelial cells (at protein level) (PubMed:11322876).
messages: Microsome membrane
messages: Upon ER stress with brefeldin A or with tunicamycin, MGST2 is down-regulated, in several non-haematopoietic cell types, during the early, protective phase of the unfolded protein response (UPR), and up-regulated at the late, death-promoting phase of the unfolded protein response (UPR).

9606:PIGK
gene id: 9606:PIGK
uniprot id: Q92643
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the peptidase C13 family.
messages: Component of the GPI transamidase complex, necessary for transfer of GPI to proteins (PubMed:34576938). Mediates GPI anchoring in the endoplasmic reticulum, by replacing a protein's C-terminal GPI attachment signal peptide with a pre-assembled GPI. During this transamidation reaction, the GPI transamidase forms a carbonyl intermediate with the substrate protein.
messages: Endoplasmic reticulum membrane
messages: Forms a complex with PIGT, PIGS, PIGU and GAA1.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The disulfide bond between PIGK/GPI8 and PIGT is important for normal enzyme activity.

9606:DCAF15
gene id: 9606:DCAF15
uniprot id: Q66K64
names: Activity Regulation
names: Function
names: Subunit
messages: Aryl sulfonamide anticancer drugs change the substrate specificity of DCAF15 by acting as a molecular glue that promotes binding between DCAF15 and weak affinity interactors, such as RBM39.
messages: Binding of aryl sulfonamide anticancer drugs, such as indisulam (E7070) or E7820, change the substrate specificity of the DCX(DCAF15) complex, leading to promote ubiquitination and degradation of splicing factor RBM39 (PubMed:28437394, PubMed:28302793, PubMed:31693891, PubMed:31452512). RBM39 degradation results in splicing defects and death in cancer cell lines (PubMed:28437394, PubMed:28302793, PubMed:31693891). Aryl sulfonamide anticancer drugs change the substrate specificity of DCAF15 by acting as a molecular glue that promotes binding between DCAF15 and weak affinity interactor RBM39 (PubMed:31686031, PubMed:31819272). Aryl sulfonamide anticancer drugs also promote ubiquitination and degradation of RBM23 and PRPF39 (PubMed:31693891, PubMed:31626998, PubMed:31686031).
messages: Component of the DCX(DCAF15) complex, also named CLR4(DCAF15) complex, composed of DCAF15, DDB1, cullin-4 (CUL4A or CUL4B), DDA1 and RBX1.
messages: Substrate-recognition component of the DCX(DCAF15) complex, a cullin-4-RING E3 ubiquitin-protein ligase complex that mediates ubiquitination and degradation of target proteins (PubMed:16949367, PubMed:31452512). The DCX(DCAF15) complex acts as a regulator of the natural killer (NK) cells effector functions, possibly by mediating ubiquitination and degradation of cohesin subunits SMC1A and SMC3 (PubMed:31452512). May play a role in the activation of antigen-presenting cells (APC) and their interaction with NK cells (PubMed:31452512).

9606:ATF1
gene id: 9606:ATF1
uniprot id: P18846
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the bZIP family. ATF subfamily.
messages: Binds DNA as a dimer (PubMed:2516827). Interacts with HIPK2 and CDK3 (PubMed:18794154, PubMed:20980392). Interacts with MOTS-c, a peptide produced by the mitochondrially encoded 12S rRNA MT-RNR1; the interaction occurs in the nucleus following metabolic stress (PubMed:29983246).
messages: Nucleus
messages: Phosphorylated at Ser-198 by HIPK2 in response to genotoxic stress. This phosphorylation promotes transcription repression of FTH1 and other antioxidant detoxification genes. The CDK3-mediated phosphorylation at Ser-63 promotes its transactivation and transcriptional activities. Phosphorylated at Ser-63 by RPS6KA4 and RPS6KA5 in response to mitogenic or stress stimuli.
messages: The gene represented in this entry may be involved in disease pathogenesis. Chromosomal aberrations involving ATF1 are found in patients with angiomatoid fibrous histiocytoma. Translocation t(12;16)(q13;p11.2) with FUS generates a chimeric ATF1/FUS protein. Translocation t(12;22)(q13;q12) with EWSR1 generates a chimeric ATF1/EWSR1 protein.
messages: This protein binds the cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3'), a sequence present in many viral and cellular promoters. Binds to the Tax-responsive element (TRE) of HTLV-I. Mediates PKA-induced stimulation of CRE-reporter genes. Represses the expression of FTH1 and other antioxidant detoxification genes. Triggers cell proliferation and transformation.

9606:ELK4
gene id: 9606:ELK4
uniprot id: P28324
uniprot id: Q8IXL1
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the ETS family.
messages: Interacts with SIRT7.
messages: Involved in both transcriptional activation and repression. Interaction with SIRT7 leads to recruitment and stabilization of SIRT7 at promoters, followed by deacetylation of histone H3 at 'Lys-18' (H3K18Ac) and subsequent transcription repression. Forms a ternary complex with the serum response factor (SRF). Requires DNA-bound SRF for ternary complex formation and makes extensive DNA contacts to the 5'side of SRF, but does not bind DNA autonomously.
messages: Nucleus

9606:NMRK2
gene id: 9606:NMRK2
uniprot id: Q9NPI5
names: Function
names: Induction
names: Sequence Caution
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Aberrant splicing.
messages: Belongs to the uridine kinase family. NRK subfamily.
messages: Catalyzes the phosphorylation of nicotinamide riboside (NR) and nicotinic acid riboside (NaR) to form nicotinamide mononucleotide (NMN) and nicotinic acid mononucleotide (NaMN). Reduces laminin matrix deposition and cell adhesion to laminin, but not to fibronectin. Involved in the regulation of PXN at the protein level and of PXN tyrosine phosphorylation. May play a role in the regulation of terminal myogenesis.
messages: Down-regulated during myoblast differentiation.
messages: Monomer (By similarity). Interacts with ITGB1 alone or when associated with alpha-7, but not with alpha-5.
messages: Predominantly expressed in skeletal muscle and, at a much lower level, in the heart (at protein level). No expression in brain, kidney, liver, lung, pancreas nor placenta.

9606:LSG1
gene id: 9606:LSG1
uniprot id: Q9H089
names: Domain
names: Function
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the TRAFAC class YlqF/YawG GTPase family. LSG1 subfamily.
messages: Cajal body
messages: Contaminating sequence. Potential poly-A sequence.
messages: Cytoplasm
messages: Endoplasmic reticulum
messages: GTPase required for the XPO1/CRM1-mediated nuclear export of the 60S ribosomal subunit. Probably acts by mediating the release of NMD3 from the 60S ribosomal subunit after export into the cytoplasm (Probable).
messages: In contrast to other GTP-binding proteins, this family is characterized by a circular permutation of the GTPase motifs described by a G4-G1-G3 pattern.

9606:MIS12
gene id: 9606:MIS12
uniprot id: A8K1M4
uniprot id: Q9H081
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the mis12 family.
messages: Component of the MIS12 complex composed of MIS12, DSN1, NSL1 and PMF1. Also interacts with KNL1, CBX3, CBX5, NDC80 and ZWINT.
messages: Part of the MIS12 complex which is required for normal chromosome alignment and segregation and for kinetochore formation during mitosis (PubMed:12515822, PubMed:15502821, PubMed:16585270). Essential for proper kinetochore microtubule attachments (PubMed:23891108).
messages: kinetochore

9606:OAZ3
gene id: 9606:OAZ3
uniprot id: A0A0G2JH29
uniprot id: H0Y7Y4
uniprot id: Q9UMX2
names: Developmental Stage
names: Function
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the ODC antizyme family.
messages: Cytoplasm
messages: Expression starts early in spermiogenesis and finishes in the late spermatid phase.
messages: Interacts with ODC1 and thereby sterically blocks ODC homodimerization (By similarity). Interacts with AZIN2; this interaction disrupts the interaction between the antizyme and ODC1 (PubMed:17900240). Interacts with GGN (By similarity).
messages: Nucleus
messages: Ornithine decarboxylase (ODC) antizyme protein that negatively regulates ODC activity and intracellular polyamine biosynthesis and uptake in response to increased intracellular polyamine levels. Binds to ODC monomers, inhibiting the assembly of the functional ODC homodimers. Does not target the ODC monomers for degradation, which allows a protein synthesis-independent restoration of ODC activity (PubMed:17900240). Stabilizes AZIN2 by interfering with its ubiquitination. Involved in the translocation of AZNI2 from ER-Golgi intermediate compartment (ERGIC) to the cytosol. Probably plays a key role in spermatogenesis by regulating the intracellular concentration of polyamines in haploid germ cells (By similarity).
messages: Testis specific.
messages: Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.

9606:VWA5A
gene id: 9606:VWA5A
uniprot id: O00534
names: Function
names: Tissue Specificity
messages: Expressed at low level in many tissues. Not expressed in 80% of tumor cell lines tested.
messages: May play a role in tumorigenesis as a tumor suppressor. Altered expression of this protein and disruption of the molecular pathway it is involved in, may contribute directly to or modify tumorigenesis.

9606:OR1S1
gene id: 9606:OR1S1
uniprot id: Q8NH92
names: Caution
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: It is uncertain whether Met-1 or Met-14 is the initiator.
messages: Odorant receptor.

9606:EHF
gene id: 9606:EHF
uniprot id: Q9NZC4
names: Domain
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the ETS family.
messages: By IL1B/interleukin-1 beta and TNF in bronchial smooth muscle cells and fibroblasts. By IL10/interleukin-10 and IFNG/IFN-gamma in monocyte-derived dendritic cells.
messages: Expressed exclusively in tissues with a high content of epithelial cells. Highly expressed in salivary gland, mammary gland, prostate, and lung. Weakly expressed in kidney and colon. Not detected in heart, brain, placenta, liver, skeletal muscle, spleen, thymus, testis, ovary, small intestine or peripheral blood leukocytes.
messages: Nucleus
messages: The PNT domain acts as a transcriptional activator.
messages: Transcriptional activator that may play a role in regulating epithelial cell differentiation and proliferation. May act as a repressor for a specific subset of ETS/AP-1-responsive genes and as a modulator of the nuclear response to mitogen-activated protein kinase signaling cascades. Binds to DNA sequences containing the consensus nucleotide core sequence GGAA. Involved in regulation of TNFRSF10B/DR5 expression through Ets-binding sequences on the TNFRSF10B/DR5 promoter. May contribute to development and carcinogenesis by acting as a tumor suppressor gene or anti-oncogene.

9606:LPAR4
gene id: 9606:LPAR4
uniprot id: Q99677
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: High expression in ovary. Not detected in the brain regions thalamus, putamen, caudate, frontal cortex, pons, hypothalamus and hippocampus.
messages: Receptor for lysophosphatidic acid (LPA), a mediator of diverse cellular activities. Transduces a signal by increasing the intracellular calcium ions and by stimulating adenylyl cyclase activity. The rank order of potency for agonists of this receptor is 1-oleoyl- > 1-stearoyl- > 1-palmitoyl- > 1-myristoyl- > 1-alkyl- > 1-alkenyl-LPA.

9606:RICTOR
gene id: 9606:RICTOR
uniprot id: Q6R327
names: Function
names: Miscellaneous
names: PTM
names: Sequence Caution
names: Similarity
names: Subunit
messages: (Microbial infection) Interacts with vaccinia virus protein F17; this interaction dysregulates mTOR.
messages: Belongs to the RICTOR family.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Part of the mechanistic target of rapamycin complex 2 (mTORC2) which contains MTOR, MLST8, PRR5, RICTOR, MAPKAP1 and DEPTOR (PubMed:15268862, PubMed:15467718, PubMed:17461779, PubMed:17599906, PubMed:34519268). Contrary to mTORC1, mTORC2 does not bind to and is not sensitive to FKBP12-rapamycin. Binds directly to MTOR and PRR5 within the TORC2 complex; interaction with MTOR is enhanced by deubiquitination of RICTOR by USP9X (PubMed:15268862, PubMed:17461779, PubMed:17599906, PubMed:33378666). Interaction with MAPKAP1 is not enhanced by RICTOR deubiquitination by USP9X (PubMed:33378666). Interacts with CCDC28B (PubMed:23727834). Interacts with NBN (PubMed:23762398). Interacts with PRR5L (PubMed:17461779, PubMed:21964062). Interacts with SIK3 (PubMed:30232230). Interacts with NCKAP1L (PubMed:32647003). Interacts with kinases GSK3A and GSK3B; the interactions lead to phosphorylation of RICTOR at 'Thr-1695' which facilitates its FBXW7-mediated ubiquitination and subsequent degradation (PubMed:25897075). Interacts with FBXW7; the interaction is enhanced by GSK3-mediated phosphorylation of 'Thr-1695' and results in RICTOR ubiquitination and degradation (PubMed:25897075). Interacts with USP9X; the interaction results in deubiquitination of RICTOR and protection from proteasomal degradation, thus promoting mTORC2 complex assembly (PubMed:33378666). Interacts with ARMH4 (via cytoplasmic tail); this interaction bridges ARMH4 to the mTORC2 complex and inhibits the mTORC2 kinase activity (By similarity).
messages: Phosphorylated by MTOR; when part of mTORC2 (PubMed:15467718). Phosphorylated at Thr-1135 by RPS6KB1; phosphorylation of RICTOR inhibits mTORC2 and AKT1 signaling (PubMed:19995915). Phosphorylated at Thr-1695 by GSK3A and GSK3B which facilitates RICTOR ubiquitination and subsequent degradation (PubMed:25897075).
messages: Subunit of mTORC2, which regulates cell growth and survival in response to hormonal signals. mTORC2 is activated by growth factors, but, in contrast to mTORC1, seems to be nutrient-insensitive. mTORC2 seems to function upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors. mTORC2 promotes the serum-induced formation of stress-fibers or F-actin. mTORC2 plays a critical role in AKT1 'Ser-473' phosphorylation, which may facilitate the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDK1 which is a prerequisite for full activation. mTORC2 regulates the phosphorylation of SGK1 at 'Ser-422'. mTORC2 also modulates the phosphorylation of PRKCA on 'Ser-657'. Plays an essential role in embryonic growth and development.
messages: Ubiquitinated by the SCF(FBXW7) complex, leading to its degradation by the proteasome (PubMed:25897075). Deubiquitinated by USP9X; deubiquitination stabilizes RICTOR and enhances its binding to MTOR, thus promoting mTORC2 complex assembly (PubMed:33378666).
messages: Wrong choice of CDS.

9606:SLC33A1
gene id: 9606:SLC33A1
uniprot id: O00400
names: Disease Annotation
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acetyl-CoA transporter that mediates active acetyl-CoA import through the endoplasmic reticulum (ER) membrane into the ER lumen where specific ER-based acetyl-CoA:lysine acetyltransferases are responsible for the acetylation of ER-based protein substrates, such as BACE1 (PubMed:24828632, PubMed:20826464). Necessary for O-acetylation of gangliosides (PubMed:9096318).
messages: Belongs to the SLC33A transporter family.
messages: Endoplasmic reticulum membrane
messages: Expression is induced in presence of ceramide.
messages: Homodimerizes.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitous. Detected in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. With strongest signals in pancreas.

9606:TLE5
gene id: 9606:TLE5
uniprot id: Q08117
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the WD repeat Groucho/TLE family.
messages: Found predominantly in muscle, heart and Placenta. In fetal tissues, abundantly expressed in the heart, lung, kidney, brain and liver.
messages: Homooligomer and heterooligomer with other family members. Binds TCF7 (By similarity). Binds the NF-kappa-B subunit RELA. Interacts with PHF12. Interacts (via Q domain) with SIX3. Interacts with SIX6.
messages: Lacks the C-terminal WD repeats.
messages: Nucleus
messages: Transcriptional corepressor. Acts as dominant repressor towards other family members. Inhibits NF-kappa-B-regulated gene expression. May be required for the initiation and maintenance of the differentiated state. Essential for the transcriptional repressor activity of SIX3 during retina and lens development.
messages: Ubiquitinated by XIAP/BIRC4.

9606:CTSK
gene id: 9606:CTSK
uniprot id: P43235
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Apical cell membrane
messages: Belongs to the peptidase C1 family.
messages: Lysosome
messages: Predominantly expressed in osteoclasts (bones) (PubMed:7805878). Expressed in thyroid epithelial cells (PubMed:11082042).
messages: Secreted
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Thiol protease involved in osteoclastic bone resorption and may participate partially in the disorder of bone remodeling. Displays potent endoprotease activity against fibrinogen at acid pH. May play an important role in extracellular matrix degradation. Involved in the release of thyroid hormone thyroxine (T4) by limited proteolysis of TG/thyroglobulin in the thyroid follicle lumen (PubMed:11082042).

9606:ZNF718
gene id: 9606:ZNF718
uniprot id: Q3SXZ3
uniprot id: Q658L4
names: Function
names: Subcellular Location Annotation
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:ENDOG
gene id: 9606:ENDOG
uniprot id: E5KNL5
uniprot id: Q14249
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the DNA/RNA non-specific endonuclease family.
messages: Endonuclease that preferentially catalyzes the cleavage of double-stranded 5-hydroxymethylcytosine (5hmC)-modified DNA (PubMed:25355512). The 5hmC-modified nucleotide does not increase the binding affinity, but instead increases the efficiency of cutting and specifies the site of cleavage for the modified DNAs (By similarity). Shows significantly higher affinity for four-stranded Holliday junction over duplex and single-stranded DNAs (By similarity). Promotes conservative recombination when the DNA is 5hmC-modified (PubMed:25355512). Promotes autophagy through the suppression of mTOR by its phosphorylation-mediated interaction with YWHAG and its endonuclease activity-mediated DNA damage response (PubMed:33473107). GSK3-beta mediated phosphorylation of ENDOG enhances its interaction with YWHAG, leading to the release of TSC2 and PIK3C3 from YWHAG resulting in mTOR pathway suppression and autophagy initiation (PubMed:33473107). Promotes cleavage of mtDNA in response to oxidative and nitrosative stress, in turn inducing compensatory mtDNA replication (PubMed:29719607).
messages: GSK3-beta-mediated dual phosphorylations at Thr-128 and Ser-288 is necessary for its interaction with YWHAG and the induction of autophagy.
messages: Homodimer; disulfide-linked (By similarity). Homodimerization is essential for enzyme activity (By similarity). Interacts with YWHAG (PubMed:33473107).
messages: Mitochondrion

9606:PLPPR3
gene id: 9606:PLPPR3
uniprot id: Q6T4P5
names: Caution
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the PA-phosphatase related phosphoesterase family.
messages: Has most probably no phospholipid phosphatase activity (By similarity). This is supported by the fact that the phosphatase sequence motifs as well as the His residue acting as a nucleophile in active phosphatases of the PA-phosphatase related phosphoesterase family are not conserved (By similarity).
messages: Membrane

9606:SMPX
gene id: 9606:SMPX
uniprot id: Q9UHP9
names: Caution
names: Disease Annotation
names: Function
names: Similarity
names: Tissue Specificity
messages: Belongs to the SMPX family.
messages: It is uncertain whether Met-1 or Met-3 is the initiator.
messages: Plays a role in the regulatory network through which muscle cells coordinate their structural and functional states during growth, adaptation, and repair.
messages: Preferentially and abundantly expressed in heart and skeletal muscle.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The disease may be caused by variants affecting the gene represented in this entry.

9606:WDR46
gene id: 9606:WDR46
uniprot id: A0A1U9X8W1
uniprot id: A8K806
uniprot id: B4DP15
uniprot id: O15213
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3 (PubMed:34516797). Interacts with DDX21, NCL, NOP2 and EBNA1BP2 (PubMed:23848194).
messages: Scaffold component of the nucleolar structure. Required for localization of DDX21 and NCL to the granular compartment of the nucleolus (PubMed:23848194). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797).
messages: nucleolus

9606:EXOC3
gene id: 9606:EXOC3
uniprot id: O60645
uniprot id: Q69YP2
names: Function
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the SEC6 family.
messages: Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane.
messages: Cytoplasm
messages: Expressed in epididymis (at protein level).
messages: Golgi apparatus
messages: Midbody
messages: Probable cloning artifact.
messages: The exocyst complex is composed of EXOC1, EXOC2, EXOC3, EXOC4, EXOC5, EXOC6, EXOC7 and EXOC8 (By similarity). Interacts with EXOC3L1 (By similarity). Interacts with BIRC6/bruce. Interacts with MYRIP (By similarity). Interacts with SLC6A9 (By similarity).
messages: growth cone
messages: neuron projection
messages: perinuclear region

9606:ILK
gene id: 9606:ILK
uniprot id: Q13418
uniprot id: V9HWF0
names: Activity Regulation
names: Domain
names: Function
names: PTM
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: A PH-like domain is involved in phosphatidylinositol phosphate binding.
messages: Autophosphorylated on serine residues.
messages: Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.
messages: Cell membrane
messages: Highly expressed in heart followed by skeletal muscle, pancreas and kidney. Weakly expressed in placenta, lung and liver.
messages: Interacts with the cytoplasmic domain of ITGB1 (PubMed:10712922). Could also interact with integrin ITGB2, ITGB3 and/or ITGB5 (PubMed:10712922). Interacts (via ANK repeats) with LIMS1 and LIMS2 (PubMed:12167643, PubMed:19074270, PubMed:19117955). Interacts with PARVA (via C-terminus) and PARVB; these compete for the same binding site (PubMed:11402068, PubMed:15284246, PubMed:15817463, PubMed:20005845, PubMed:20117114). Interacts probably also with TGFB1I1 (By similarity). Interacts (via ANK repeats) with EPHA1 (via SAM domain); stimulated by EFNA1 but independent of the kinase activity of EPHA1 (PubMed:19118217). Interacts with FERMT2 (By similarity). Interacts with LIMD2; leading to activate the protein kinase activity (PubMed:24590809). Interacts with PXN/PAXILLIN (via LD motif 4) (PubMed:15817463). Interacts with CCDC25 (via cytoplasmic region); initiating the ILK-PARVB cascade to induce cytoskeleton rearrangement and directional migration of cells (PubMed:32528174).
messages: Probable cloning artifact. Was originally thought to be distinct gene (ILK2) (PubMed:10871859).
messages: Receptor-proximal protein kinase regulating integrin-mediated signal transduction (PubMed:8538749, PubMed:9736715). May act as a mediator of inside-out integrin signaling (PubMed:10712922). Focal adhesion protein part of the complex ILK-PINCH (PubMed:10712922). This complex is considered to be one of the convergence points of integrin- and growth factor-signaling pathway (PubMed:10712922). Could be implicated in mediating cell architecture, adhesion to integrin substrates and anchorage-dependent growth in epithelial cells (PubMed:10712922). Regulates cell motility by forming a complex with PARVB (PubMed:32528174). Phosphorylates beta-1 and beta-3 integrin subunit on serine and threonine residues, but also AKT1 and GSK3B (PubMed:8538749, PubMed:9736715).
messages: Stimulated rapidly but transiently by both cell fibronectin interactions, as well as by insulin, in a PI3-K-dependent manner, likely via the binding of PtdIns(3,4,5)P3 with a PH-like domain of ILK. The protein kinase activity is stimulated by LIMD2 (PubMed:24590809).
messages: focal adhesion
messages: lamellipodium
messages: sarcomere

9606:UPRT
gene id: 9606:UPRT
uniprot id: Q96BW1
names: Caution
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the UPRTase family.
messages: Cytoplasm
messages: Highly expressed in leukocytes, liver, spleen and thymus, with lower expression in brain, lung and skeletal muscle.
messages: No UPRTase activity has been detected in vitro and the uracil binding region known from UPRTases is missing.
messages: Nucleus

9606:WDR54
gene id: 9606:WDR54
uniprot id: Q9H977
names: Domain
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cross-linked to tightly form both dimers and trimers by TGM2. Cross-linking enhances the activation of EGF receptor-mediated signaling pathway (PubMed:30458214). Cross-linking is inhibited by EGF (PubMed:30458214).
messages: Expressed in epithelial cells (at protein level) (PubMed:29987896). Isoform 3 expression is highly increased in colorectal cancer cells (PubMed:29987896).
messages: Homodimer and homotrimer; forms tight forms of dimers and trimers.
messages: Ubiquitinated. EGF increases ubiquitination.
messages: Vesicle
messages: WD6 repeat is required for cross-linking by TGM2.
messages: When cross-linked to form dimers and trimers, it has a regulatory effect on ERK signaling pathway activity in response to EGF stimulation. Colocalizes with the EGF receptor in WDR54-specific vesicle where it sustains the internalization and controls the degradation of the EGF receptor after EGF stimulation.

9606:ABCF1
gene id: 9606:ABCF1
uniprot id: Q8NE71
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the ABC transporter superfamily. ABCF family. EF3 subfamily.
messages: By TNF in cultured synoviocytes.
messages: Cytoplasm
messages: Isoform 2 interacts (via N-terminus) with EIF2S1; the interaction is independent of its phosphorylated status. Isoform 2 associates (via both ABC transporter domains) with the ribosomes.
messages: Isoform 2 is phosphorylated at phosphoserine and phosphothreonine. Isoform 2 phosphorylation on Ser-109 and Ser-140 by CK2 inhibits association of EIF2 with ribosomes.
messages: Isoform 2 is required for efficient Cap- and IRES-mediated mRNA translation initiation. Isoform 2 is not involved in the ribosome biogenesis.
messages: Nucleus envelope
messages: Ubiquitous.
messages: nucleoplasm

9606:NME5
gene id: 9606:NME5
uniprot id: A0A0S2Z4L9
uniprot id: P56597
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the NDK family.
messages: Component of the axonemal radial spoke complex 1 (RS1), at least composed of spoke head proteins RSPH1, RSPH3, RSPH9 and the cilia-specific component RSPH4A or sperm-specific component RSPH6A, spoke stalk proteins RSPH14, DNAJB13, DYDC1, ROPN1L and NME5, and the anchor protein IQUB (By similarity). Interacts with IQUB (By similarity).
messages: Functions as part of axonemal radial spoke complexes that play an important part in the motility of sperm and cilia. Does not seem to have NDK kinase activity. Confers protection from cell death by Bax and alters the cellular levels of several antioxidant enzymes including Gpx5. May play a role in spermiogenesis by increasing the ability of late-stage spermatids to eliminate reactive oxygen species (By similarity).
messages: Specifically expressed in testis germinal cells.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: cilium
messages: flagellum axoneme

9606:GTF3C1
gene id: 9606:GTF3C1
uniprot id: Q12789
names: Function
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the TFIIIC subunit 1 family.
messages: Contaminating sequence. Potential vector sequence at the N-terminus.
messages: Nucleus
messages: Part of the TFIIIC subcomplex TFIIIC2, consisting of six subunits, GTF3C1, GTF3C2, GTF3C3, GTF3C4, GTF3C5 and GTF3C6 (PubMed:19299493). Interacts with IGHMBP2. Interacts with MAF1 (PubMed:18377933).
messages: Required for RNA polymerase III-mediated transcription. Component of TFIIIC that initiates transcription complex assembly on tRNA and is required for transcription of 5S rRNA and other stable nuclear and cytoplasmic RNAs. Binds to the box B promoter element.

9606:MED30
gene id: 9606:MED30
uniprot id: Q96HR3
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the Mediator complex subunit 30 family.
messages: Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors.
messages: Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP.
messages: Expressed in brain, heart, kidney, liver, lung, pancreas, placenta and skeletal muscle.
messages: Nucleus

9606:ARX
gene id: 9606:ARX
uniprot id: Q96QS3
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the paired homeobox family. Bicoid subfamily.
messages: Expressed predominantly in fetal and adult brain and skeletal muscle. Expression is specific to the telencephalon and ventral thalamus. There is an absence of expression in the cerebellum throughout development and also in adult.
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The disease is caused by variants affecting the gene represented in this entry. Also called X-linked lissencephaly with abnormal genitalia (XLAG).
messages: Transcription factor (PubMed:22194193, PubMed:31691806). Binds to specific sequence motif 5'-TAATTA-3' in regulatory elements of target genes, such as histone demethylase KDM5C (PubMed:22194193, PubMed:31691806). Positively modulates transcription of KDM5C (PubMed:31691806). Activates expression of KDM5C synergistically with histone lysine demethylase PHF8 and perhaps in competition with transcription regulator ZNF711; synergy may be related to enrichment of histone H3K4me3 in regulatory elements (PubMed:31691806). Required for normal brain development (PubMed:11889467, PubMed:12379852, PubMed:14722918). Plays a role in neuronal proliferation, interneuronal migration and differentiation in the embryonic forebrain (By similarity). May also be involved in axonal guidance in the floor plate (By similarity).

9606:PPP1CB
gene id: 9606:PPP1CB
uniprot id: P62140
uniprot id: V9HW04
names: Activity Regulation
names: Caution
names: Cofactor
names: Disease Annotation
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the PPP phosphatase family. PP-1 subfamily.
messages: Binds 2 manganese ions per subunit.
messages: Cytoplasm
messages: Inhibited by the toxins okadaic acid, tautomycin and microcystin Leu-Arg (By similarity). The phosphatase activity of the PPP1R15A-PP1 complex toward EIF2S1 is specifically inhibited by Salubrinal, a drug that protects cells from endoplasmic reticulum stress.
messages: Nucleus
messages: PP1 comprises a catalytic subunit, PPP1CA, PPP1CB or PPP1CC, which is folded into its native form by inhibitor 2 and glycogen synthetase kinase 3, and then complexed to one or several targeting or regulatory subunits. The targeting or regulatory subunits determine the substrate specificity of PP1. PPP1R12A, PPP1R12B and PPP1R12C mediate binding to myosin. PPP1R3A (in skeletal muscle), PPP1R3B (in liver), PPP1R3C, PPP1R3D and PPP1R3F (in brain) mediate binding to glycogen. Part of a complex containing PPP1R15B, PP1 and NCK1/2 (By similarity). Interacts with PPP1R7 and PPP1R12C. PPP1R15A and PPP1R15B mediate binding to EIF2S1. Interacts with PPP1R16B. Component of the PTW/PP1 phosphatase complex, composed of PPP1R10/PNUTS, TOX4, WDR82, and PPP1CA or PPP1CB or PPP1CC. Interacts with PPP1R8. Interacts with TRIM28; the interaction is weak. Interacts with PPP1R12A and NUAK1; the interaction is direct. Interacts with FOXP3. Interacts with RRP1B (PubMed:20926688). Interacts with SERPINE1 (PubMed:28296156). Interacts with LZTR1 (PubMed:30368668).
messages: Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets. Protein phosphatase (PP1) is essential for cell division, it participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Involved in regulation of ionic conductances and long-term synaptic plasticity. Component of the PTW/PP1 phosphatase complex, which plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase. In balance with CSNK1D and CSNK1E, determines the circadian period length, through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation. May dephosphorylate CSNK1D and CSNK1E. Dephosphorylates the 'Ser-418' residue of FOXP3 in regulatory T-cells (Treg) from patients with rheumatoid arthritis, thereby inactivating FOXP3 and rendering Treg cells functionally defective (PubMed:23396208).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Up-regulated in synovial fluid mononuclear cells and peripheral blood mononuclear cells from patients with rheumatoid arthritis.
messages: Was originally thought to be part of the MLL5-L complex, at least composed of KMT2E, STK38, PPP1CA, PPP1CB, PPP1CC, HCFC1, ACTB and OGT (PubMed:19377461). However, the corresponding article has been retracted (PubMed:24336203).
messages: nucleolus
messages: nucleoplasm

9606:PLCXD1
gene id: 9606:PLCXD1
uniprot id: Q9NUJ7
names: Miscellaneous
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Cytoplasm
messages: The gene coding for this protein is located in the pseudoautosomal region 1 (PAR1) of X and Y chromosomes.
messages: Widely expressed.

9606:PCDHGB1
gene id: 9606:PCDHGB1
uniprot id: Q9Y5G3
names: Function
names: Subcellular Location Annotation
messages: Cell membrane
messages: Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain.

9606:SP4
gene id: 9606:SP4
uniprot id: A0A3B3IRW4
uniprot id: Q02446
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Abundant in brain.
messages: Belongs to the Sp1 C2H2-type zinc-finger protein family.
messages: Binds to GT and GC boxes promoters elements. Probable transcriptional activator.
messages: Nucleus
messages: The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. In SP4, the motif is inactive.

9606:TTK
gene id: 9606:TTK
uniprot id: P33981
names: Activity Regulation
names: Function
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.
messages: Inhibited by the ATP-competitive kinase inhibitor, SP600125.
messages: Interacts with TPR; the interactions occurs in a microtubule-independent manner (PubMed:19273613). Interacts with MAD1L1 and MAD2L1 (PubMed:29162720).
messages: Phosphorylates proteins on serine, threonine, and tyrosine (PubMed:18243099, PubMed:29162720). Probably associated with cell proliferation (PubMed:18243099). Phosphorylates MAD1L1 to promote mitotic checkpoint signaling (PubMed:29162720). Essential for chromosome alignment by enhancing AURKB activity (via direct CDCA8 phosphorylation) at the centromere, and for the mitotic checkpoint (PubMed:18243099).
messages: Present in rapidly proliferating cell lines.

9606:MAF1
gene id: 9606:MAF1
uniprot id: Q9H063
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the MAF1 family.
messages: Cytoplasm
messages: Interacts with TFIIIB subunits BRF1 and BRF2 (PubMed:17505538, PubMed:18377933). Interacts with Pol III subunit POLR3F. Interacts with TFIIIC subunit GTF3C1 (PubMed:18377933).
messages: Nucleus
messages: Phosphorylated at Ser-60, Ser-68 and Ser-75; the major sites of phosphorylation. Nuclear accumulation correlates with a concomitant dephosphorylation. Phosphorylation may attenuate its RNA polymerase III-repressive function.
messages: Plays a role in the repression of RNA polymerase III-mediated transcription in response to changing nutritional, environmental and cellular stress conditions to balance the production of highly abundant tRNAs, 5S rRNA, and other small non-coding RNAs with cell growth and maintenance (PubMed:18377933, PubMed:20233713, PubMed:20516213, PubMed:20543138). Also plays a key role in cell fate determination by promoting mesorderm induction and adipocyte differentiation (By similarity). Mechanistically, associates with the RNA polymerase III clamp and thereby impairs its recruitment to the complex made of the promoter DNA, TBP and the initiation factor TFIIIB (PubMed:20887893, PubMed:17505538). When nutrients are available and mTOR kinase is active, MAF1 is hyperphosphorylated and RNA polymerase III is engaged in transcription. Stress-induced MAF1 dephosphorylation results in nuclear localization, increased targeting of gene-bound RNA polymerase III and a decrease in the transcriptional readout (PubMed:26941251). Additionally, may also regulate RNA polymerase I and RNA polymerase II-dependent transcription through its ability to regulate expression of the central initiation factor TBP (PubMed:17499043).
messages: Sumoylated with SUMO1 and SUMO2, mainly on Lys-35. Desumoylated by SENP1. SUMOylation promotes the ability of MAF1 to repress transcription and suppress colony formation.

9606:DHX35
gene id: 9606:DHX35
uniprot id: Q9H5Z1
names: Function
names: Similarity
names: Subunit
messages: Belongs to the DEAD box helicase family. DEAH subfamily.
messages: Identified in the spliceosome C complex.
messages: May be involved in pre-mRNA splicing.

9606:TMED10
gene id: 9606:TMED10
uniprot id: A0A024R6I3
uniprot id: P49755
names: Domain
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the EMP24/GP25L family.
messages: Cargo receptor involved in protein vesicular trafficking and quality control in the endoplasmic reticulum (ER) and Golgi (PubMed:10052452, PubMed:11726511, PubMed:16641999, PubMed:17288597, PubMed:19296914, PubMed:20427317, PubMed:21219331, PubMed:27569046). The p24 protein family is a group of transmembrane proteins that bind coat protein complex I/COPI and coat protein complex II/COPII involved in vesicular trafficking between the membranes (PubMed:10052452). Acts at the lumenal side for incorporation of secretory cargo molecules into transport vesicles and involved in vesicle coat formation at the cytoplasmic side (PubMed:20427317, PubMed:27569046). Mainly functions in the early secretory pathway and cycles between the ER, ER-Golgi intermediate compartment (ERGIC) and Golgi, mediating cargo transport through COPI and COPII-coated vesicles (PubMed:10052452, PubMed:10852829, PubMed:12237308). In COPII vesicle-mediated anterograde transport, involved in the transport of GPI-anchored proteins by acting together with TMED2 as their cargo receptor; the function specifically implies SEC24C and SEC24D of the COPII vesicle coat and lipid raft-like microdomains of the ER (PubMed:20427317, PubMed:27569046). Recognizes GPI anchors structural remodeled in the ER by the GPI inositol-deacylase/PGAP1 and the metallophosphoesterase MPPE1/PGAP5 (By similarity). In COPI vesicle-mediated retrograde transport, involved in the biogenesis of COPI vesicles and vesicle coat recruitment (PubMed:11726511). Involved in trafficking of amyloid beta A4 protein and soluble APP-beta release (independent from the modulation of gamma-secretase activity) (PubMed:17288597). Involved in the KDELR2-mediated retrograde transport of the toxin A subunit (CTX-A-K63)together with COPI and the COOH terminus of KDELR2 (By similarity). On Golgi membranes, acts as primary receptor for ARF1-GDP, a GTP-binding protein involved in COPI-vesicle formation (PubMed:11726511). Increases coatomer-dependent GTPase-activ…
messages: Cell membrane
messages: Ectopic expression of TMED10 alone does not result in its proper cis-Golgi network localization (PubMed:10852829). Interaction of TMED10 with TMED2 is both necessary and sufficient for transport of the couple to the cis-Golgi network, and TMED3 and/or TMED9 contribute to facilitating the process (PubMed:10852829).
messages: Endoplasmic reticulum membrane
messages: Endoplasmic reticulum-Golgi intermediate compartment membrane
messages: Golgi apparatus membrane
messages: Melanosome
messages: Membrane
messages: Predominantly dimeric and to a lesser extent monomeric in the ER (PubMed:12237308). Monomer and dimer in ERGIC and cis-Golgi network (PubMed:12237308). Forms homooligomer (via GOLD domain); the assembly is promoted by direct binding with leaderless cargos and may form a protein channel that facilitates cargo entry into the ERGIC (PubMed:32272059). Forms heterooligomeric complexes with other members of the p24 family such as TMED2, TMED7 and TMED9 (PubMed:9472029, PubMed:10359607, PubMed:20427317, PubMed:32272059). Interacts (via GOLD domain) with TMED2 (via GOLD domain); the complex is required for export of TMED10 from the ER to the cis-Golgi network; the complex is proposed to be involved in cis-Golgi network dynamics and / or biogenesis (PubMed:10852829, PubMed:27569046). Associates with the COPI vesicle coat subunits (coatomer) (PubMed:9472029, PubMed:11056392, PubMed:16940185). Tetramerization of the cytoplasmic domain at the Golgi membrane in vitro; the complex is proposed to interact with COPI coatomer and induce budding of the vesicles (By similarity). Interacts with COPG1; the interaction involves TMED10 homodimer (PubMed:16940185). Interacts with ARF1 (GDP-bound); the interaction probably involves a TMED10 oligomer (PubMed:11726511). Interacts with SEC23A, SEC24B, SEC24C and SEC24D components of the coat protein complex II/COPII, indicative of an association of TMED10 with the COPII vesicle coat (PubMed:9472029). Interacts with CD59 (PubMed:20427317). Interacts with MPPE1/PGAP5; the complex might recruit and sort GPI-anchored proteins to the ER-exit site, or the interaction might lead to recycling of PGAP5 between the ER and the Golgi (PubMed:19837036). Interacts with F2LR1/PAR2 (PubMed:21219331). Interacts with KDELR2/ERD2; the interaction is disrupted by KDELR2 ligand (By similarity). Found in a complex composed at least of SURF4, TMED2 and TMED10 (PubMed:18287528). Associates with the presenilin-dependent gamma-secretase complex (PubMed:16641999). Inter…
messages: The GOLD domain is required for proper p24 heterooligomeric complex formation and efficient transport of GPI-anchored proteins.
messages: The lumenal domain mediates localization to the plasma membrane by partially overriding the ER retention by the cytoplasmic domain.
messages: cis-Golgi network membrane
messages: secretory vesicle membrane
messages: trans-Golgi network membrane

9606:ATP6V1G1
gene id: 9606:ATP6V1G1
uniprot id: O75348
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Apical cell membrane
messages: Belongs to the V-ATPase G subunit family.
messages: Kidney; localizes to early distal nephron, encompassing thick ascending limbs and distal convoluted tubules (at protein level) (PubMed:29993276). Ubiquitous (PubMed:12384298).
messages: Subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons (PubMed:33065002, PubMed:32001091). V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment (PubMed:32001091). In aerobic conditions, involved in intracellular iron homeostasis, thus triggering the activity of Fe(2+) prolyl hydroxylase (PHD) enzymes, and leading to HIF1A hydroxylation and subsequent proteasomal degradation (PubMed:28296633).
messages: V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex (PubMed:33065002). The V1 complex consists of three catalytic AB heterodimers that form a heterohexamer, three peripheral stalks each consisting of EG heterodimers, one central rotor including subunits D and F, and the regulatory subunits C and H (PubMed:33065002). The proton translocation complex V0 consists of the proton transport subunit a, a ring of proteolipid subunits c9c'', rotary subunit d, subunits e and f, and the accessory subunits ATP6AP1/Ac45 and ATP6AP2/PRR (PubMed:33065002).

9606:DNAJB6
gene id: 9606:DNAJB6
uniprot id: O75190
names: Disease Annotation
names: Domain
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Has a stimulatory effect on the ATPase activity of HSP70 in a dose-dependent and time-dependent manner and hence acts as a co-chaperone of HSP70 (PubMed:10954706, PubMed:28233300). Plays an indispensable role in the organization of KRT8/KRT18 filaments (PubMed:10954706). Acts as an endogenous molecular chaperone for neuronal proteins including huntingtin (PubMed:11896048, PubMed:22366786). Suppresses aggregation and toxicity of polyglutamine-containing, aggregation-prone proteins (PubMed:20159555, PubMed:22366786). Also reduces cellular toxicity and caspase-3 activity (PubMed:11896048).
messages: Homooligomer (PubMed:22366786). Interacts with BAG3, HSPB8 and STUB1 (PubMed:22366786). Interacts with ALKBH1 (By similarity). Interacts with HSP70, KRT18 and PTTG (PubMed:10954706, PubMed:9915854).
messages: Interacts with histone deacetylases HDAC4, HDAC6, and SIRT2, HDAC activity is required for antiaggregation.
messages: Isoform B but not isoform A inhibits huntingtin aggregation.
messages: Nucleus
messages: The antiaggregation activity of isoform B resides in the serine-rich region and the C-terminus.
messages: The disease is caused by variants affecting the gene represented in this entry. There is evidence that LGMDD1 is caused by dysfunction of isoform B (PubMed:22366786).
messages: Widely expressed. Highest levels in testis and brain, and lower levels in heart, spleen, intestine, ovary, placenta, lung, kidney, pancreas, thymus, prostate, skeletal muscle, liver and leukocytes. In testis, expressed in germ cells in the earlier stages of differentiation pathway as well as in spermatids. In brain, expressed at a higher level in hippocampus and thalamus and a lower level in amygdala, substantia nigra, corpus callosum and caudate nucleus.
messages: Z line
messages: perinuclear region

9606:OR2T1
gene id: 9606:OR2T1
uniprot id: A0A126GVY3
uniprot id: A0A126GWK9
uniprot id: O43869
names: Caution
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: It is uncertain whether Met-1 or Met-52 is the initiator.
messages: Membrane
messages: Odorant receptor.

9606:ESCO1
gene id: 9606:ESCO1
uniprot id: Q5FWF5
names: Caution
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acetyltransferase required for the establishment of sister chromatid cohesion (PubMed:15958495, PubMed:18614053). Couples the processes of cohesion and DNA replication to ensure that only sister chromatids become paired together. In contrast to the structural cohesins, the deposition and establishment factors are required only during S phase. Acts by mediating the acetylation of cohesin component SMC3 (PubMed:18614053).
messages: Belongs to the acetyltransferase family. ECO subfamily.
messages: Chromosome
messages: It is uncertain whether Met-1 or Met-2 is the initiator.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Nucleus
messages: Phosphorylated during mitosis, when associated with chromosomes.
messages: The N-terminal region seems to be responsible for association with chromosomes, thus excluding any involvement of the Zn finger in this process.
messages: The subunit structure is controversial. Monomer (PubMed:27803161). Homodimer (PubMed:27112597).
messages: Widely expressed. Expressed in heart, brain, liver, placenta, lung, kidney and pancreas. Highly expressed in muscle.
messages: Wrong choice of frame.

9606:SOCS4
gene id: 9606:SOCS4
uniprot id: Q8WXH5
names: Domain
names: Function
names: Induction
messages: SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. Substrate-recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Inhibits EGF signaling by mediating the degradation of the Tyr-phosphorylated EGF receptor/EGFR.
messages: The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes.
messages: Up-regulated by EGF.

9606:PSMD10
gene id: 9606:PSMD10
uniprot id: O75832
names: Caution
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acts as a chaperone during the assembly of the 26S proteasome, specifically of the PA700/19S regulatory complex (RC). In the initial step of the base subcomplex assembly is part of an intermediate PSMD10:PSMC4:PSMC5:PAAF1 module which probably assembles with a PSMD5:PSMC2:PSMC1:PSMD2 module. Independently of the proteasome, regulates EGF-induced AKT activation through inhibition of the RHOA/ROCK/PTEN pathway, leading to prolonged AKT activation. Plays an important role in RAS-induced tumorigenesis.
messages: Acts as an proto-oncoprotein by being involved in negative regulation of tumor suppressors RB1 and p53/TP53. Overexpression is leading to phosphorylation of RB1 and proteasomal degradation of RB1. Regulates CDK4-mediated phosphorylation of RB1 by competing with CDKN2A for binding with CDK4. Facilitates binding of MDM2 to p53/TP53 and the mono- and polyubiquitination of p53/TP53 by MDM2 suggesting a function in targeting the TP53:MDM2 complex to the 26S proteasome. Involved in p53-independent apoptosis. Involved in regulation of NF-kappa-B by retaining it in the cytoplasm. Binds to the NF-kappa-B component RELA and accelerates its XPO1/CRM1-mediated nuclear export.
messages: Cytoplasm
messages: Nucleus
messages: Part of transient complex containing PSMD10, PSMC4, PSMC5 and PAAF1 formed during the assembly of the 26S proteasome. Stays associated throughout the assembly of the PA700/19S RC and is released upon association with the 20S core. Interacts with PSMC4. Interacts with RB1. Interacts with CDK4. Interacts with MDM2. Interacts with RELA. Associates with a CDK4:CCND2 serine/threonine kinase complex. Interacts with ARHGDIA and increases the interaction between ARHGDIA and RHOA, hence promotes ARHGDIA inactivation of RHOA and ROCK.
messages: Tends to be up-regulated in cancer cells with RAS mutations, including lung cancers and adenocarconimas (at protein level).
messages: Was initially identified as a genuine component of the 26S proteasome.

9606:CDK11B
gene id: 9606:CDK11B
uniprot id: P21127
names: Activity Regulation
names: Caution
names: Function
names: Induction
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts with human herpes virus 1 (HHV-1) transcriptional regulator ICP22.
messages: Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.
messages: Cleaved isoform SV9 (p110C) binds to the serine/threonine kinase PAK1 and RANBP9. p110C interacts with RNPS1. Isoform 7, but not isoform SV9, nor its cleavage product p110C, interacts with CCND3. Interacts with CCNL1 and CCNL2. Forms complexes with pre-mRNA-splicing factors, including at least SRSF1, SRSF2 and SRSF7/SLU7. Interacts with isoform 5 of MYO18A (PubMed:25965346).
messages: Cytoplasm
messages: Duplicated gene. CDK11A and CDK11B encode almost identical protein kinases of 110 kDa that contain at their C-termini the open reading frame of a smaller 58 kDa isoform which is expressed following IRES-mediated alternative initiation of translation.
messages: During FAS- or TNF-induced apoptosis, isoform SV9 is cleaved by caspases to produce p110C, a fragment that contains the C-terminal kinase domain.
messages: Expressed ubiquitously. Some evidence of isoform-specific tissue distribution.
messages: Isoform 7 is induced in G2/M phase of the cell cycle.
messages: Many references talk about 'p110 isoforms' but it is not yet known if this refers to CDK11A and/or CDK11B or one/some of the isoforms of each.
messages: Nucleus
messages: Phosphorylation at Ser-115 creates a binding site for 14-3-3 proteins. p110C can be autophosphorylated.
messages: Phosphorylation at Thr-448 or Tyr-449 inactivates the enzyme, while phosphorylation at Thr-595 activates it.
messages: Plays multiple roles in cell cycle progression, cytokinesis and apoptosis. Involved in pre-mRNA splicing in a kinase activity-dependent manner. Isoform 7 may act as a negative regulator of normal cell cycle progression.
messages: Produced by alternative initiation at Met-357 of isoform SV9 via an internal ribosomal entry site (IRES).

9606:MOCOS
gene id: 9606:MOCOS
uniprot id: Q96EN8
names: Disease Annotation
names: Function
names: Similarity
messages: Belongs to the class-V pyridoxal-phosphate-dependent aminotransferase family. MOCOS subfamily.
messages: Sulfurates the molybdenum cofactor. Sulfation of molybdenum is essential for xanthine dehydrogenase (XDH) and aldehyde oxidase (ADO) enzymes in which molybdenum cofactor is liganded by 1 oxygen and 1 sulfur atom in active form. In vitro, the C-terminal domain is able to reduce N-hydroxylated prodrugs, such as benzamidoxime.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:SYNC
gene id: 9606:SYNC
uniprot id: Q9H7C4
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Atypical type III intermediate filament (IF) protein that may play a supportive role in the efficient coupling of mechanical stress between the myofibril and fiber exterior. May facilitate lateral force transmission during skeletal muscle contraction. Does not form homofilaments nor heterofilaments with other IF proteins.
messages: Belongs to the intermediate filament family.
messages: May link the dystrophin-associated glycoprotein complex (DAPC) to intracellular desmin (DES) filaments. Interacts with DES and DTNA.
messages: Up-regulated at the sarcolemma in individuals with various forms of neuromuscular disease.
messages: perinuclear region

9606:LIPT1
gene id: 9606:LIPT1
uniprot id: Q9Y234
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the LplA family.
messages: Catalyzes the transfer of the lipoyl group from lipoyl-AMP to the specific lysine residue of lipoyl domains of lipoate-dependent enzymes.
messages: Highly expressed in skeletal muscle and heart, moderately in kidney and pancreas, and detected at lower levels in liver, brain, placenta and lung.
messages: Mitochondrion
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:NAV1
gene id: 9606:NAV1
uniprot id: Q8NEY1
names: Developmental Stage
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the Nav/unc-53 family.
messages: Broadly expressed at low levels. Expressed at high levels in heart, skeletal muscle and placenta.
messages: Expressed in fetal brain and heart.
messages: Interacts with tubulin.
messages: May be involved in neuronal migration.
messages: cytoskeleton

9606:H3C11
gene id: 9606:H3C11
uniprot id: P68431
names: Caution
names: Developmental Stage
names: Disease Annotation
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Acetylation is generally linked to gene activation. Acetylation on Lys-10 (H3K9ac) impairs methylation at Arg-9 (H3R8me2s). Acetylation on Lys-19 (H3K18ac) and Lys-24 (H3K24ac) favors methylation at Arg-18 (H3R17me). Acetylation at Lys-123 (H3K122ac) by EP300/p300 plays a central role in chromatin structure: localizes at the surface of the histone octamer and stimulates transcription, possibly by promoting nucleosome instability.
messages: Asymmetric dimethylation at Arg-18 (H3R17me2a) by CARM1 is linked to gene activation. Symmetric dimethylation at Arg-9 (H3R8me2s) by PRMT5 is linked to gene repression. Asymmetric dimethylation at Arg-3 (H3R2me2a) by PRMT6 is linked to gene repression and is mutually exclusive with H3 Lys-5 methylation (H3K4me2 and H3K4me3). H3R2me2a is present at the 3' of genes regardless of their transcription state and is enriched on inactive promoters, while it is absent on active promoters.
messages: Belongs to the histone H3 family.
messages: Butyrylation of histones marks active promoters and competes with histone acetylation. It is present during late spermatogenesis.
messages: Chromosome
messages: Citrullination at Arg-9 (H3R8ci) and/or Arg-18 (H3R17ci) by PADI4 impairs methylation and represses transcription.
messages: Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
messages: Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.
messages: Dopaminylated by TGM2 at Gln-6 (H3Q5dop) in ventral tegmental area (VTA) neurons (PubMed:32273471). H3Q5dop mediates neurotransmission-independent role of nuclear dopamine by regulating relapse-related transcriptional plasticity in the reward system (By similarity).
messages: Expressed during S phase, then expression strongly decreases as cell division slows down during the process of differentiation.
messages: HIST1H3B or HIST1H3C mutations affecting residue Lys-37 of histone H3.1 are involved in the pathogenesis of pediatric undifferentiated soft tissue sarcomas. The mechanism through which mutations lead to tumorigenesis involves altered histones methylation with gain of global H3K27 methylation, altered Polycomb repressive complex 1 (PRC1) activity, aberrant epigenetic regulation of gene expression and impaired differentiation of mesenchimal progenitor cells.
messages: Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.
messages: Lysine deamination at Lys-5 (H3K4all) to form allysine is mediated by LOXL2. Allysine formation by LOXL2 only takes place on H3K4me3 and results in gene repression.
messages: Methylation at Lys-5 (H3K4me), Lys-37 (H3K36me) and Lys-80 (H3K79me) are linked to gene activation. Methylation at Lys-5 (H3K4me) facilitates subsequent acetylation of H3 and H4. Methylation at Lys-80 (H3K79me) is associated with DNA double-strand break (DSB) responses and is a specific target for TP53BP1. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are linked to gene repression. Methylation at Lys-10 (H3K9me) is a specific target for HP1 proteins (CBX1, CBX3 and CBX5) and prevents subsequent phosphorylation at Ser-11 (H3S10ph) and acetylation of H3 and H4. Methylation at Lys-5 (H3K4me) and Lys-80 (H3K79me) require preliminary monoubiquitination of H2B at 'Lys-120'. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are enriched in inactive X chromosome chromatin. Monomethylation at Lys-57 (H3K56me1) by EHMT2/G9A in G1 phase promotes interaction with PCNA and is required for DNA replication.
messages: Monoubiquitinated by RAG1 in lymphoid cells, monoubiquitination is required for V(D)J recombination (By similarity). Ubiquitinated by the CUL4-DDB-RBX1 complex in response to ultraviolet irradiation. This may weaken the interaction between histones and DNA and facilitate DNA accessibility to repair proteins.
messages: Nucleus
messages: Phosphorylated at Thr-4 (H3T3ph) by HASPIN during prophase and dephosphorylated during anaphase. Phosphorylation at Ser-11 (H3S10ph) by AURKB is crucial for chromosome condensation and cell-cycle progression during mitosis and meiosis. In addition phosphorylation at Ser-11 (H3S10ph) by RPS6KA4 and RPS6KA5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or UV irradiation and result in the activation of genes, such as c-fos and c-jun. Phosphorylation at Ser-11 (H3S10ph), which is linked to gene activation, prevents methylation at Lys-10 (H3K9me) but facilitates acetylation of H3 and H4. Phosphorylation at Ser-11 (H3S10ph) by AURKB mediates the dissociation of HP1 proteins (CBX1, CBX3 and CBX5) from heterochromatin. Phosphorylation at Ser-11 (H3S10ph) is also an essential regulatory mechanism for neoplastic cell transformation. Phosphorylated at Ser-29 (H3S28ph) by MAP3K20 isoform 1, RPS6KA5 or AURKB during mitosis or upon ultraviolet B irradiation. Phosphorylation at Thr-7 (H3T6ph) by PRKCB is a specific tag for epigenetic transcriptional activation that prevents demethylation of Lys-5 (H3K4me) by LSD1/KDM1A. At centromeres, specifically phosphorylated at Thr-12 (H3T11ph) from prophase to early anaphase, by DAPK3 and PKN1. Phosphorylation at Thr-12 (H3T11ph) by PKN1 or isoform M2 of PKM (PKM2) is a specific tag for epigenetic transcriptional activation that promotes demethylation of Lys-10 (H3K9me) by KDM4C/JMJD2C. Phosphorylation at Thr-12 (H3T11ph) by chromatin-associated CHEK1 regulates the transcription of cell cycle regulatory genes by modulating acetylation of Lys-10 (H3K9ac). Phosphorylation at Tyr-42 (H3Y41ph) by JAK2 promotes exclusion of CBX5 (HP1 alpha) from chromatin.
messages: Serine ADP-ribosylation by PARP1 or PARP2 constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage (PubMed:30257210, PubMed:34874266). Serine ADP-ribosylation at Ser-11 (H3S10ADPr) promotes recruitment of CHD1L (PubMed:34874266). H3S10ADPr is mutually exclusive with phosphorylation at Ser-11 (H3S10ph) and impairs acetylation at Lys-10 (H3K9ac) (PubMed:30257210).
messages: Serotonylated by TGM2 at Gln-6 (H3Q5ser) during serotonergic neuron differentiation (PubMed:30867594). H3Q5ser is associated with trimethylation of Lys-5 (H3K4me3) and enhances general transcription factor IID (TFIID) complex-binding to H3K4me3, thereby facilitating transcription (PubMed:30867594).
messages: Succinylation at Lys-80 (H3K79succ) by KAT2A takes place with a maximum frequency around the transcription start sites of genes (PubMed:29211711). It gives a specific tag for epigenetic transcription activation (PubMed:29211711). Desuccinylation at Lys-123 (H3K122succ) by SIRT7 in response to DNA damage promotes chromatin condensation and double-strand breaks (DSBs) repair (PubMed:27436229).
messages: The gene represented in this entry is involved in disease pathogenesis. HIST1H3B mutations affecting residue Lys-28 involved in post-translational modifications of histone H3.1 are recurrent in malignant, aggressive gliomas including pediatric non-brain stem glioblastoma and diffuse intrinsic pontine glioma (DIPG) (PubMed:22286216). The mechanism through which mutations lead to tumorigenesis involves altered histone methylation, impaired regulation of Polycomb repressive complex 2 (PRC2) activity, and aberrant epigenetic regulation of gene expression (PubMed:23603901).
messages: The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. Interacts with TONSL; CHAF1A; CHAF1B; MCM2 and DNAJC9 (PubMed:33857403).
messages: The original paper reporting lysine deamination at Lys-5 by LOXL2 has been retracted due to inappropriate manipulation of figure data (PubMed:22483618, PubMed:27392148). However, this modification was confirmed in a subsequent publication (PubMed:27735137).
messages: This histone is only present in mammals and is enriched in acetylation of Lys-15 and dimethylation of Lys-10 (H3K9me2).

9606:ANKRD53
gene id: 9606:ANKRD53
uniprot id: Q8N9V6
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: Interacts with PSRC1; recruited by PSRC1 to the spindle during mitosis (PubMed:26820536).
messages: Phosphorylated during mitosis (PubMed:26820536).
messages: Required for normal progression through mitosis. Involved in chromosome alignment and cytokinesis via regulation of microtubules polymerization.
messages: spindle
messages: spindle pole

9606:ZCWPW1
gene id: 9606:ZCWPW1
uniprot id: Q9H0M4
names: Domain
names: Function
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Chromosome
messages: Dual histone methylation reader specific for PRDM9-catalyzed histone marks (H3K4me3 and H3K36me3) (PubMed:32744506, PubMed:20826339). Facilitates the repair of PRDM9-induced meiotic double-strand breaks (DSBs) (By similarity). Essential for male fertility and spermatogenesis (By similarity). Required for meiosis prophase I progression in male but not in female germ cells (By similarity).
messages: Nucleus
messages: Testis.
messages: The CW-TYPE zinc finger mediates its binding to trimethylated histone H3K4me3.

9606:RAB4B
gene id: 9606:RAB4B
uniprot id: P61018
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the small GTPase superfamily. Rab family.
messages: Cell membrane
messages: Serotonylation of Gln-67 by TGM2 during activation and aggregation of platelets leads to constitutive activation of GTPase activity.
messages: Small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state (By similarity). Protein transport. Probably involved in vesicular traffic (By similarity). Acts as a regulator of platelet alpha-granule release during activation and aggregation of platelets (By similarity).

9606:DPYS
gene id: 9606:DPYS
uniprot id: Q14117
names: Cofactor
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Belongs to the metallo-dependent hydrolases superfamily. Hydantoinase/dihydropyrimidinase family.
messages: Binds 2 Zn(2+) ions per subunit.
messages: Carboxylation allows a single lysine to coordinate two zinc ions.
messages: Catalyzes the second step of the reductive pyrimidine degradation, the reversible hydrolytic ring opening of dihydropyrimidines. Can catalyze the ring opening of 5,6-dihydrouracil to N-carbamyl-alanine and of 5,6-dihydrothymine to N-carbamyl-amino isobutyrate.
messages: Homotetramer.
messages: Liver and kidney.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:CCNO
gene id: 9606:CCNO
uniprot id: P22674
names: Caution
names: Developmental Stage
names: Disease Annotation
names: Function
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the cyclin family.
messages: Cytoplasm
messages: Maximum levels during G(1) phase. Levels decrease through S and G(2) phases.
messages: Present in respiratory cells (at protein level).
messages: Sequencing errors.
messages: Specifically required for generation of multiciliated cells, possibly by promoting a cell cycle state compatible with centriole amplification and maturation. Acts downstream of MCIDAS to promote mother centriole amplification and maturation in preparation for apical docking.
messages: The disease is caused by variants affecting the gene represented in this entry. Marked reduction of cilia in multiciliate cells due to defective mother centriole generation and placement. Remaining cilia correctly express axonemal motor proteins, are motile and do not show beating defects. Defects are probably caused by a strong reduction in the number of multiple motile cilia covering the cell surface in respiratory epithelial cells (PubMed:24747639).
messages: Was originally thought to have uracil-DNA glycosylase (UDG) activity and wrongly named UNG2 and UDG2 (PubMed:2001396). It was later shown that it is a member of the cyclin family (PubMed:8419333). UNG2 corresponds to the isoform 2 of UNG gene.
messages: nucleolus

9606:ASB10
gene id: 9606:ASB10
uniprot id: A0A090N8I2
uniprot id: Q8WXI3
names: Disease Annotation
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the ankyrin SOCS box (ASB) family.
messages: Cytoplasm
messages: Expressed in the eye. The highest expression is observed in the iris, with moderate levels in the trabecular meshwork (TM), the lamina, and the optic nerve; slightly lower levels in the ciliary body, retina, and choroid; and very low levels in the lens.
messages: May be a substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.
messages: Nucleus
messages: The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin-protein ligase complexes.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:MINPP1
gene id: 9606:MINPP1
uniprot id: Q9UNW1
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Acts as a phosphoinositide 5- and phosphoinositide 6-phosphatase and regulates cellular levels of inositol pentakisphosphate (InsP5) and inositol hexakisphosphate (InsP6) (PubMed:33257696). Also acts as a 2,3-bisphosphoglycerate 3-phosphatase, by mediating the dephosphorylation of 2,3-bisphosphoglycerate (2,3-BPG) to produce phospho-D-glycerate without formation of 3-phosphoglycerate. May play a role in bone development (endochondral ossification). May play a role in the transition of chondrocytes from proliferation to hypertrophy (By similarity). Through the regulation of intracellular inositol polyphosphates, may control intracellular cation homeostasis, including that of calcium and iron, hence affecting free cation availability required for neural cell signaling (PubMed:33257696).
messages: Belongs to the histidine acid phosphatase family. MINPP1 subfamily.
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry.
messages: Endoplasmic reticulum lumen
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Widely expressed with highest levels in kidney, liver, cerebellum and placenta.

9606:DENND3
gene id: 9606:DENND3
uniprot id: A2RUS2
names: Domain
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Cytoplasm
messages: Forms oligomers. Interacts with 6 of the 7 known isoforms of 14-3-3 proteins.
messages: Guanine nucleotide exchange factor (GEF) activating RAB12. Promotes the exchange of GDP to GTP, converting inactive GDP-bound RAB12 into its active GTP-bound form (PubMed:20937701). Regulates autophagy in response to starvation through RAB12 activation. Starvation leads to ULK1/2-dependent phosphorylation of Ser-472 and Ser-490, which in turn allows recruitment of 14-3-3 adapter proteins and leads to up-regulation of GEF activity towards RAB12 (By similarity). Also plays a role in protein transport from recycling endosomes to lysosomes, regulating, for instance, the degradation of the transferrin receptor and of the amino acid transporter PAT4 (PubMed:20937701). Starvation also induces phosphorylation at Tyr-858, which leads to up-regulated GEF activity and initiates autophagy (By similarity).
messages: Inactive DENND3 is found in a closed conformation, in which the linker region interacts with the DENN domain. Phosphorylation of Tyr-858 in the linker region intereferes with this interaction leading to an open conformation and enhances the GEF activity of the protein towards RAB12.

9606:TNFAIP8L2-SCNM1
gene id: 9606:TNFAIP8L2-SCNM1
uniprot id: Q9BWG6
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (PubMed:36084634). Plays a role in the regulation of primary cilia length and Hedgehog signaling (PubMed:36084634).
messages: Component of the minor spliceosome, which splices U12-type introns (PubMed:33509932, PubMed:17656373). Within this complex, interacts with RNF113A, as well as with SF3B1/SF3b155, SF3B2/SF3b145, SF3B3/SF3b130 and CDC5L (PubMed:33509932). May interact with LUC7L2 and SNRNP70 (By similarity).
messages: Nucleus speckle
messages: The disease is caused by variants affecting the gene represented in this entry. The genetic variation producing the missense variant p.P51Q, associated with OFD19, has been shown to create a new acceptor splice site, leading to the deletion of 31 nucleotides, resulting in a frameshift and an early termination codon (p.F42YfsTer8). The variant mRNA is predicted to undergo nonsense-mediated mRNA decay.
messages: nucleoplasm

9606:NUP210L
gene id: 9606:NUP210L
uniprot id: Q5VU65
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the NUP210 family.
messages: Membrane

9606:TRMT10A
gene id: 9606:TRMT10A
uniprot id: Q8TBZ6
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the class IV-like SAM-binding methyltransferase superfamily. TRM10 family.
messages: Expressed in embryonic and fetal brain. It is expressed throughout the dorsal telencephalon at 8 and 11 weeks of gestation, with highest expression in ventricular zone and marginal zone. Detected in cerebellar cortex and nuclei, but not in dorsal telencephalon, at later stages.
messages: Interacts with tRNA.
messages: Nucleus
messages: S-adenosyl-L-methionine-dependent guanine N(1)-methyltransferase that catalyzes the formation of N(1)-methylguanine at position 9 (m1G9) in tRNAs (PubMed:23042678, PubMed:25053765). Probably not able to catalyze formation of N(1)-methyladenine at position 9 (m1A9) in tRNAs (PubMed:23042678).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: nucleolus

9606:SLC13A3
gene id: 9606:SLC13A3
uniprot id: B4DF27
uniprot id: Q8WWT9
names: Activity Regulation
names: Disease Annotation
names: Function
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the SLC13A/DASS transporter (TC 2.A.47) family. NADC subfamily.
messages: Cell membrane
messages: Expression is highest in kidney (PubMed:16331647). Detected in placenta, brain, liver and pancreas.
messages: High-affinity sodium-dicarboxylate cotransporter that accepts a range of substrates with 4-6 carbon atoms, such as the citric acid cycle intermediates succinate and alpha-ketoglutarate (2-oxoglutarate), as well as other compounds including N-acetyl-L-aspartate (PubMed:10794676, PubMed:10992006, PubMed:15561973, PubMed:17426067, PubMed:17356845, PubMed:24247155, PubMed:30635937). Transports the dicarboxylate into the cell with a probable stoichiometry of 3 Na(+) for 1 divalent dicarboxylate, rendering the process electrogenic (PubMed:10794676, PubMed:10992006). Can transport citrate in a Na(+)-dependent manner, recognizing the divalent form of citrate rather than the trivalent form which is normally found in blood (PubMed:10794676).
messages: Li(+) decreases succinate transport in the presence of Na(+).
messages: Membrane
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: erroneous CDS prediction.

9606:CNTFR
gene id: 9606:CNTFR
uniprot id: P26992
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the type I cytokine receptor family. Type 3 subfamily.
messages: Binds to CNTF. The alpha subunit provides the receptor specificity. Receptor for heterodimeric neurotropic cytokine composed of CLCF1/CLC and CRLF1/CLF-1 (PubMed:26858303). Acts as a receptor for the neuroprotective peptide humanin as part of a complex with IL6ST/GP130 and IL27RA/WSX1 (PubMed:19386761).
messages: Cell membrane
messages: Forms a heterotrimer with LIFR and IL6ST. Interacts with heterodimeric neurotropic cytokine composed of CLCF1/CLC and CRLF1/CLF-1 (PubMed:26858303). Either alone or in complex with the heterodimer CLCF1-CRLF1 interacts with SORL1; this interaction may promote internalization and lysosomal degradation (PubMed:26858303). Component of a receptor complex composed of IL6ST/GP130, IL27RA/WSX1 and CNTFR which interacts with the neuroprotective peptide humanin (PubMed:19386761).
messages: Nervous system and skeletal muscle.
messages: The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.

9606:TIMM8A
gene id: 9606:TIMM8A
uniprot id: O60220
names: Disease Annotation
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the small Tim family.
messages: Heterohexamer; composed of 3 copies of TIMM8A and 3 copies of TIMM13, named soluble 70 kDa complex. Associates with the TIM22 complex, whose core is composed of TIMM22.
messages: Highly expressed in fetal and adult brain, followed by fetal lung, liver and kidney. Also expressed in heart, placenta, lung, liver, kidney, pancreas, skeletal muscle and heart.
messages: Mitochondrial intermembrane chaperone that participates in the import and insertion of some multi-pass transmembrane proteins into the mitochondrial inner membrane. Also required for the transfer of beta-barrel precursors from the TOM complex to the sorting and assembly machinery (SAM complex) of the outer membrane. Acts as a chaperone-like protein that protects the hydrophobic precursors from aggregation and guide them through the mitochondrial intermembrane space. The TIMM8-TIMM13 complex mediates the import of proteins such as TIMM23, SLC25A12/ARALAR1 and SLC25A13/ARALAR2, while the predominant TIMM9-TIMM10 70 kDa complex mediates the import of much more proteins. Probably necessary for normal neurologic development.
messages: Mitochondrion inner membrane
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of TIMM8A from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane (By similarity).

9606:XCL1
gene id: 9606:XCL1
uniprot id: P47992
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the intercrine gamma family.
messages: Chemotactic activity for lymphocytes but not for monocytes or neutrophils. In thymus, mediates medullary accumulation of thymic dendritic cells and contributes to regulatoy T cell development, playing a role in self-tolerance establishment.
messages: Highest level in spleen, lower in peripheral leukocytes and very low levels in lung, colon and small intestine.
messages: Secreted

9606:BTBD7
gene id: 9606:BTBD7
uniprot id: Q9P203
names: Function
names: Sequence Caution
names: Subcellular Location Annotation
messages: Acts as a mediator of epithelial dynamics and organ branching by promoting cleft progression. Induced following accumulation of fibronectin in forming clefts, leading to local expression of the cell-scattering SNAIL2 and suppression of E-cadherin levels, thereby altering cell morphology and reducing cell-cell adhesion. This stimulates cell separation at the base of forming clefts by local, dynamic intercellular gap formation and promotes cleft progression (By similarity).
messages: Nucleus
messages: Probable cloning artifact.

9606:GALNT8
gene id: 9606:GALNT8
uniprot id: Q9NY28
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the glycosyltransferase 2 family. GalNAc-T subfamily.
messages: Golgi apparatus membrane
messages: Probably catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor.
messages: The ricin B-type lectin domain binds to GalNAc and contributes to the glycopeptide specificity.
messages: There are two conserved domains in the glycosyltransferase region: the N-terminal domain (domain A, also called GT1 motif), which is probably involved in manganese coordination and substrate binding and the C-terminal domain (domain B, also called Gal/GalNAc-T motif), which is probably involved in catalytic reaction and UDP-Gal binding.
messages: Widely expressed. Expressed in heart, skeletal muscle, kidney, liver, small intestine and placenta. Weakly expressed in colon, thymus, spleen, lung and leukocyte.

9606:PHF6
gene id: 9606:PHF6
uniprot id: Q8IWS0
names: Disease Annotation
names: Domain
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Interacts with UBTF. Interacts with the NuRD complex component RBBP4 (via the nucleolar localization motif), the interaction mediates transcriptional repression activity.
messages: Nucleus
messages: The PHD-type zinc finger 1 mediates both nucleolar localization and interaction with UBTF.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The ePHD2 domain folds as an integrated structural module comprizing the C2HC pre-PHD-type 2 zinc finger and the PHD-type 2 zinc finger. It mediates non-specific binding to dsDNA, but doesn't bind histones in contrast to many PHD-type zinc fingers.
messages: Transcriptional regulator that associates with ribosomal RNA promoters and suppresses ribosomal RNA (rRNA) transcription.
messages: Ubiquitously expressed.
messages: kinetochore
messages: nucleolus

9606:SESN2
gene id: 9606:SESN2
uniprot id: P58004
names: Domain
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the sestrin family.
messages: Cytoplasm
messages: Functions as an intracellular leucine sensor that negatively regulates the mTORC1 signaling pathway through the GATOR complex (PubMed:18692468, PubMed:25263562, PubMed:25457612, PubMed:26449471, PubMed:26612684, PubMed:26586190, PubMed:31586034, PubMed:35114100, PubMed:35831510, PubMed:36528027). In absence of leucine, binds the GATOR subcomplex GATOR2 and prevents mTORC1 signaling (PubMed:18692468, PubMed:25263562, PubMed:25457612, PubMed:26449471, PubMed:26612684, PubMed:26586190, PubMed:31586034, PubMed:35114100, PubMed:35831510, PubMed:36528027). Binding of leucine to SESN2 disrupts its interaction with GATOR2 thereby activating the TORC1 signaling pathway (PubMed:26449471, PubMed:26586190, PubMed:35114100, PubMed:35831510, PubMed:36528027). This stress-inducible metabolic regulator also plays a role in protection against oxidative and genotoxic stresses. May negatively regulate protein translation in response to endoplasmic reticulum stress, via mTORC1 (PubMed:24947615). May positively regulate the transcription by NFE2L2 of genes involved in the response to oxidative stress by facilitating the SQSTM1-mediated autophagic degradation of KEAP1 (PubMed:23274085). May also mediate TP53 inhibition of TORC1 signaling upon genotoxic stress (PubMed:18692468). Moreover, may prevent the accumulation of reactive oxygen species (ROS) through the alkylhydroperoxide reductase activity born by the N-terminal domain of the protein (PubMed:26612684). Was originally reported to contribute to oxidative stress resistance by reducing PRDX1 (PubMed:15105503). However, this could not be confirmed (PubMed:19113821).
messages: Interacts with the GATOR2 complex which is composed of MIOS, SEC13, SEH1L, WDR24 and WDR59; the interaction is negatively regulated by leucine (PubMed:25263562, PubMed:25457612, PubMed:26449471, PubMed:35114100, PubMed:35831510, PubMed:36528027). Conveys leucine availability via direct interaction with SEH1L and WDR24 components of the GATOR2 complex (PubMed:35831510, PubMed:36528027). Interacts with RRAGA, RRAGB, RRAGC and RRAGD; may function as a guanine nucleotide dissociation inhibitor for RRAGs and regulate them (PubMed:25259925). May interact with the TORC2 complex (By similarity). Interacts with KEAP1, RBX1, SQSTM and ULK1; to regulate the degradation of KEAP1 (PubMed:23274085, PubMed:25040165). May also associate with the complex composed of TSC1, TSC2 and the AMP-responsive protein kinase/AMPK to regulate TORC1 signaling (PubMed:18692468). May interact with PRDX1 (PubMed:15105503).
messages: Phosphorylated by ULK1 at multiple sites.
messages: The C-terminal domain mediates interaction with GATOR2 through which it regulates TORC1 signaling.
messages: The N-terminal domain has an alkylhydroperoxide reductase activity.
messages: Ubiquitinated at Lys-175 by RNF167 via 'Lys-63'-linked polyubiquitination in response to leucine deprivation: ubiquitination promotes SESN2-interaction with the GATOR2 complex, leading to inhibit the TORC1 signaling pathway (PubMed:35114100). Deubiquitinated at Lys-175 by STAMBPL1, promoting the TORC1 signaling pathway (PubMed:35114100). Ubiquitinated by RNF186; ubiquitination mediates proteasomal degradation (PubMed:31586034).
messages: Up-regulated by hypoxia and DNA damage (PubMed:12203114). Up-regulated by treatments inducing endoplasmic reticulum stress (PubMed:24947615).
messages: Widely expressed.

9606:TAPBPL
gene id: 9606:TAPBPL
uniprot id: Q9BX59
names: Function
names: Induction
names: Miscellaneous
names: Subcellular Location Annotation
names: Subunit
messages: By interferon gamma.
messages: Cell membrane
messages: Component of the antigen processing and presentation pathway, which binds to MHC class I coupled with beta2-microglobulin/B2M. Association between TAPBPR and MHC class I occurs in the absence of a functional peptide-loading complex (PLC).
messages: Does not interact with MHC class I.
messages: Endoplasmic reticulum membrane
messages: Golgi apparatus membrane
messages: Has reduced cell surface expression, and does not down-regulate MHC class I surface expression as efficiently as isoform alpha.
messages: Interacts with peptide-free HLA-A*02-B2M complexes or those loaded with low affinity peptides, likely facilitating peptide exchange onto higher affinity peptides.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Microsome membrane

9606:FCRL5
gene id: 9606:FCRL5
uniprot id: Q96RD9
names: Disease Annotation
names: Domain
names: Function
names: Subcellular Location Annotation
names: Tissue Specificity
messages: A chromosomal aberration involving FCRL5 has been found in cell lines with 1q21 abnormalities derived from Burkitt lymphoma. Duplication dup(1)(q21q32).
messages: Cell membrane
messages: Contains 2 copies of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM).
messages: Expressed in marginal zone B-cells, immunoblasts, tonsillar germinal center centrocytes and in the intraepithelial and interfollicular regions of the tonsil. Expressed in many lymphoma cell lines and on hairy cell leukemia cells. Isoform 1, isoform 3, isoform 4 and isoform 5 are detected in lymph node, spleen, bone marrow, and small intestine with preponderance of isoform 3. Expressed in mature and memory B-cells and down-regulated in germinal center cells (at protein level).
messages: May be involved in B-cell development and differentiation in peripheral lymphoid organs and may be useful markers of B-cell stages. May have an immunoregulatory role in marginal zone B-cells. May play a role in fertilization (By similarity).

9606:ELSPBP1
gene id: 9606:ELSPBP1
uniprot id: A0A384NKL6
uniprot id: Q96BH3
names: Caution
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the seminal plasma protein family.
messages: Binds to spermatozoa upon ejaculation and may play a role in sperm capacitation. Has phosphorylcholine-binding activity (By similarity).
messages: Detected in cauda epididymidal fluid and on sperm membrane (at protein level).
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: N-glycosylated.
messages: Secreted

9606:GJC2
gene id: 9606:GJC2
uniprot id: A0A654IBV7
uniprot id: Q5T442
names: Caution
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: A connexon is composed of a hexamer of connexins.
messages: A connexon is composed of a hexamer of connexins. Interacts with TJP1 (By similarity).
messages: Belongs to the connexin family.
messages: Belongs to the connexin family. Gamma-type subfamily.
messages: Cell membrane
messages: Expressed in central nervous system, in sciatic nerve and sural nerve. Also detected in skeletal muscles.
messages: It is uncertain whether Met-1 or Met-4 is the initiator.
messages: Membrane
messages: One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell.
messages: One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell. May play a role in myelination in central and peripheral nervous systems.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: gap junction

9606:CEP85
gene id: 9606:CEP85
uniprot id: Q6P2H3
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Acts as a negative regulator of NEK2 to maintain the centrosome integrity in interphase. Suppresses centrosome disjunction by inhibiting NEK2 kinase activity (PubMed:26220856).
messages: Belongs to the CEP85 family.
messages: centrosome
messages: nucleolus
messages: spindle pole

9606:ZBTB8A
gene id: 9606:ZBTB8A
uniprot id: Q96BR9
names: Function
names: Subcellular Location Annotation
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:JRKL
gene id: 9606:JRKL
uniprot id: Q9Y4A0
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Abundantly expressed in the majority of tissues examined, including brain and skeletal muscle.
messages: Belongs to the tigger transposable element derived protein family.
messages: Nucleus

9606:CPNE8
gene id: 9606:CPNE8
uniprot id: Q86YQ8
names: Cofactor
names: Function
names: Similarity
messages: Belongs to the copine family.
messages: Binds 3 Ca(2+) ions per C2 domain.
messages: Probable calcium-dependent phospholipid-binding protein that may play a role in calcium-mediated intracellular processes.

9606:TMEM115
gene id: 9606:TMEM115
uniprot id: A0A024R2Y2
uniprot id: Q12893
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the TMEM115 family.
messages: Expressed strongly in kidney and skeletal muscle, followed by liver, placenta, pancreas, and lung, with low amounts in heart and only traces in brain (PubMed:11085536). Widely expressed with ubiquitous expression in epithelial tissues (at protein level) (PubMed:17973242).
messages: Golgi stack membrane
messages: Homooligomer (PubMed:24806965). Interacts with COPB1 (PubMed:24806965). May interact with LMAN1 (PubMed:24806965). Interacts with the COG complex; probably through COG3 (PubMed:24806965).
messages: May play a role in retrograde transport of proteins from the Golgi to the endoplasmic reticulum. May indirectly play a role in protein glycosylation in the Golgi.
messages: Membrane

9606:OPTN
gene id: 9606:OPTN
uniprot id: Q96CV9
names: Disease Annotation
names: Domain
names: Function
names: Induction
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts with E3 14.7 kDa protein of group C human adenovirus (PubMed:9488477). Interacts with Bluetongue virus protein NS3 (PubMed:27538435).
messages: (Microbial infection) May constitute a cellular target for various viruses, such as adenovirus E3 14.7 or Bluetongue virus, to inhibit innate immune response (PubMed:9488477, PubMed:27538435). During RNA virus infection, such as that of Sendai virus, negatively regulates the induction of IFNB1 (PubMed:20174559).
messages: (Microbial infection) Up-regulated in response to Sendai virus infection or double stranded RNA treatment (at protein level); the up-regulation is direct and not mediated through a response to type I interferons; this may negatively regulate the interferon response to RNA-activated antiviral signaling pathways.
messages: Cytoplasmic vesicle
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry.
messages: Golgi apparatus
messages: Phosphorylated by TBK1, leading to restrict bacterial proliferation in case of infection. Phosphorylation is induced by phorbol esters and decreases its half-time.
messages: Plays an important role in the maintenance of the Golgi complex, in membrane trafficking, in exocytosis, through its interaction with myosin VI and Rab8 (PubMed:27534431). Links myosin VI to the Golgi complex and plays an important role in Golgi ribbon formation (PubMed:27534431). Plays a role in the activation of innate immune response during viral infection. Mechanistically, recruits TBK1 at the Golgi apparatus, promoting its trans-phosphorylation after RLR or TLR3 stimulation (PubMed:27538435). In turn, activated TBK1 phosphorylates its downstream partner IRF3 to produce IFN-beta/IFNB1. Plays a neuroprotective role in the eye and optic nerve. May act by regulating membrane trafficking and cellular morphogenesis via a complex that contains Rab8 and hungtingtin (HD). Mediates the interaction of Rab8 with the probable GTPase-activating protein TBC1D17 during Rab8-mediated endocytic trafficking, such as that of transferrin receptor (TFRC/TfR); regulates Rab8 recruitment to tubules emanating from the endocytic recycling compartment (PubMed:22854040). Autophagy receptor that interacts directly with both the cargo to become degraded and an autophagy modifier of the MAP1 LC3 family; targets ubiquitin-coated bacteria (xenophagy), such as cytoplasmic Salmonella enterica, and appears to function in the same pathway as SQSTM1 and CALCOCO2/NDP52.
messages: Present in aqueous humor of the eye (at protein level). Expressed in the trabecular meshwork (at protein level) (PubMed:11834836, PubMed:12379221, PubMed:12646749). Expressed in nonpigmented ciliary epithelium (at protein level) (PubMed:11834836). Expressed at high levels in skeletal muscle, also detected in heart, brain, pancreas, kidney, placenta and liver (PubMed:9488477). Expressed in dermal fibroblasts (at protein level) (PubMed:11834836).
messages: Recycling endosome
messages: Self-associates (PubMed:23669351). Interacts with HD (PubMed:9700202, PubMed:11137014). Interacts with GTF3A (PubMed:10756201). Interacts with MYO6 (PubMed:31371777). Interacts (via UBAN) with ubiquitinated TFRC (PubMed:20085643). Interacts with GTP-bound Rab8 (RAB8A and/or RAB8B) (PubMed:11137014, PubMed:20085643, PubMed:22854040). Interacts with TBC1D17 (PubMed:22854040). Interacts with TBK1 (PubMed:20174559, PubMed:27538435, PubMed:23669351). Interacts with TRAF3 (PubMed:20174559). Binds to linear ubiquitin chains (PubMed:20085643). Interacts with LC3 family members MAP1LC3A, MAP1LC3B, GABARAP, GABARAPL1 and GABARAPL2; OPTN phosphorylation increases the association (at least with MAP1LC3B). Interacts with RAB12; the interaction may be indirect. Interacts with TBK1; this interaction leads to the Golgi localization of TBK1 and its subsequent activation. Interacts with palmitoyltransferase ZDHHC17/HIP14; the interaction does not lead to palmitoylation of OPTN (PubMed:24705354). Interacts with CYLD (PubMed:32185393). Interacts with TOM1; the interaction is indirect and is mediated by MYO6, which acts as a bridge between TOM1 and OPTN (PubMed:31371777).
messages: The LIR (LC3-interacting region) motif mediates the interaction with ATG8 family proteins.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitin-binding motif (UBAN), also called UBD, is essential for subcellular localization to recycling endosomes and for proper trafficking of transferrin to the juxtanuclear region. It is involved in interaction with ubiquitinated TFRC.
messages: Up-regulated by TNF (PubMed:9488477, PubMed:10807909, PubMed:12379221). Up-regulated by IFNG. TNF and IFNG act synergistically to stimulate OPTN expression (PubMed:10807909). Induced by glucocorticoids, such as dexamethasone (PubMed:12379221). In an in vitro experimental setting, in which donor eyes are subjected to increased perfusion pressure (10 to 30 mm Hg) in the anterior chamber, there is no up-regulation in the trabecular meshwork at the transcript level for periods ranging between 1 and 24 hours (PubMed:12646749). However, exposure to continuous elevated pressure for several days shows an induction of OPTN expression, with a 56% increase after 7 days (PubMed:12379221).
messages: autophagosome
messages: perinuclear region
messages: trans-Golgi network

9606:HLA-DRB1
gene id: 9606:HLA-DRB1
uniprot id: A0A224MM52
uniprot id: D7RIH8
uniprot id: P01911
uniprot id: X5DNQ0
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Polymorphism
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Acts as a receptor for Epstein-Barr virus on lymphocytes.
messages: (Microbial infection) Interacts with Epstein-Barr virus gp42 protein.
messages: (Microbial infection) Interacts with Staphylococcus aureus enterotoxin A/entA, enterotoxin B/entB, enterotoxin C1/entC1, enterotoxin D/entD and enterotoxin H/entH. Enterotoxins bind outside the peptide-binding cleft of MHCII: enterotoxin H/entH interacts via the beta-1 domain of MHCII and in a zinc-dependent way, whereas enterotoxin B/entB interacts primarily via the alpha-1 domain.
messages: A beta chain of antigen-presenting major histocompatibility complex class II (MHCII) molecule. In complex with the alpha chain HLA-DRA, displays antigenic peptides on professional antigen presenting cells (APCs) for recognition by alpha-beta T cell receptor (TCR) on HLA-DRB1-restricted CD4-positive T cells. This guides antigen-specific T-helper effector functions, both antibody-mediated immune response and macrophage activation, to ultimately eliminate the infectious agents and transformed cells (PubMed:29884618, PubMed:22327072, PubMed:27591323, PubMed:8642306, PubMed:15265931, PubMed:31495665, PubMed:16148104). Typically presents extracellular peptide antigens of 10 to 30 amino acids that arise from proteolysis of endocytosed antigens in lysosomes (PubMed:8145819). In the tumor microenvironment, presents antigenic peptides that are primarily generated in tumor-resident APCs likely via phagocytosis of apoptotic tumor cells or macropinocytosis of secreted tumor proteins (PubMed:31495665). Presents peptides derived from intracellular proteins that are trapped in autolysosomes after macroautophagy, a mechanism especially relevant for T cell selection in the thymus and central immune tolerance (PubMed:17182262, PubMed:23783831). The selection of the immunodominant epitopes follows two processing modes: 'bind first, cut/trim later' for pathogen-derived antigenic peptides and 'cut first, bind later' for autoantigens/self-peptides (PubMed:25413013). The anchor residue at position 1 of the peptide N-terminus, usually a large hydrophobic residue, is essential for high affinity interaction with MHCII molecules (PubMed:8145819).
messages: Allele DRB1*01:01: Displays an immunodominant epitope derived from Bacillus anthracis pagA/protective antigen, PA (KLPLYISNPNYKVNVYAVT), to both naive and PA-specific memory CD4-positive T cells (PubMed:22327072). Presents immunodominant HIV-1 gag peptide (FRDYVDRFYKTLRAEQASQE) on infected dendritic cells for recognition by TRAV24-TRBV2 TCR on CD4-positive T cells and controls viral load (PubMed:29884618). May present to T-helper 1 cells several HRV-16 epitopes derived from capsid proteins VP1 (PRFSLPFLSIASAYYMFYDG) and VP2 (PHQFINLRSNNSATLIVPYV), contributing to viral clearance (PubMed:27591323). Displays commonly recognized peptides derived from IAV external protein HA (PKYVKQNTLKLAT and SNGNFIAPEYAYKIVK) and from internal proteins M, NP and PB1, with M-derived epitope (GLIYNRMGAVTTEV) being the most immunogenic (PubMed:8145819, PubMed:9075930, PubMed:25413013, PubMed:32668259). Presents a self-peptide derived from COL4A3 (GWISLWKGFSF) to TCR (TRAV14 biased) on CD4-positive, FOXP3-positive regulatory T cells and mediates immune tolerance to self (PubMed:28467828). May present peptides derived from oncofetal trophoblast glycoprotein TPBG 5T4, known to be recognized by both T-helper 1 and regulatory T cells (PubMed:31619516). Displays with low affinity a self-peptide derived from MBP (VHFFKNIVTPRTP) (PubMed:9075930).
messages: Allele DRB1*03:01: May present to T-helper 1 cells an HRV-16 epitope derived from capsid protein VP2 (NEKQPSDDNWLNFDGTLLGN), contributing to viral clearance (PubMed:27591323). Displays self-peptides derived from retinal SAG (NRERRGIALDGKIKHE) and thyroid TG (LSSVVVDPSIRHFDV) (PubMed:25413013). Presents viral epitopes derived from HHV-6B gH/U48 and U85 antigens to polyfunctional CD4-positive T cells with cytotoxic activity implicated in control of HHV-6B infection (PubMed:31020640). Presents several immunogenic epitopes derived from C. tetani neurotoxin tetX, playing a role in immune recognition and long-term protection (PubMed:19830726).
messages: Allele DRB1*04:01: Presents an immunodominant bacterial epitope derived from M. tuberculosis esxB/culture filtrate antigen CFP-10 (EISTNIRQAGVQYSR), eliciting CD4-positive T cell effector functions such as IFNG production and cytotoxic activity (PubMed:15265931). May present to T-helper 1 cells an HRV-16 epitope derived from capsid protein VP2 (NEKQPSDDNWLNFDGTLLGN), contributing to viral clearance (PubMed:27591323). Presents tumor epitopes derived from melanoma-associated TYR antigen (QNILLSNAPLGPQFP and DYSYLQDSDPDSFQD), triggering CD4-positive T cell effector functions such as GMCSF production (PubMed:8642306). Displays preferentially citrullinated self-peptides derived from VIM (GVYATR/citSSAVR and SAVRAR/citSSVPGVR) and ACAN (VVLLVATEGR/ CitVRVNSAYQDK) (PubMed:24190431). Displays self-peptides derived from COL2A1 (PubMed:9354468).
messages: Allele DRB1*04:02: Displays native or citrullinated self-peptides derived from VIM.
messages: Allele DRB1*04:04: May present to T-helper 1 cells several HRV-16 epitopes derived from capsid proteins VP1 (HIVMQYMYVPPGAPIPTTRN) and VP2 (RGDSTITSQDVANAVVGYGV), contributing to viral clearance (PubMed:27591323). Displays preferentially citrullinated self-peptides derived from VIM (SAVRAR/citSSVPGVR) (PubMed:24190431).
messages: Allele DRB1*04:05: May present to T-helper 1 cells an immunogenic epitope derived from tumor-associated antigen WT1 (KRYFKLSHLQMHSRKH), likely providing for effective antitumor immunity in a wide range of solid and hematological malignancies.
messages: Allele DRB1*05:01: Presents an immunodominant HIV-1 gag peptide (FRDYVDRFYKTLRAEQASQE) on infected dendritic cells for recognition by TRAV24-TRBV2 TCR on CD4-positive T cells and controls viral load.
messages: Allele DRB1*07:01: Upon EBV infection, presents latent antigen EBNA2 peptide (PRSPTVFYNIPPMPLPPSQL) to CD4-positive T cells, driving oligoclonal expansion and selection of a dominant virus-specific memory T cell subset with cytotoxic potential to directly eliminate virus-infected B cells (PubMed:31308093). May present to T-helper 1 cells several HRV-16 epitopes derived from capsid proteins VP1 (PRFSLPFLSIASAYYMFYDG) and VP2 (VPYVNAVPMDSMVRHNNWSL), contributing to viral clearance (PubMed:27591323). In the context of tumor immunesurveillance, may present to T-helper 1 cells an immunogenic epitope derived from tumor-associated antigen WT1 (MTEYKLVVVGAVGVGKSALTIQLI), likely providing for effective antitumor immunity in a wide range of solid and hematological malignancies (PubMed:22929521). In metastatic epithelial tumors, presents to intratumoral CD4-positive T cells a KRAS neoantigen (MTEYKLVVVGAVGVGKSALTIQLI) carrying G12V hotspot driver mutation and may mediate tumor regression (PubMed:30282837).
messages: Allele DRB1*11:01: Displays an immunodominant HIV-1 gag peptide (FRDYVDRFYKTLRAEQASQE) on infected dendritic cells for recognition by TRAV24-TRBV2 TCR on CD4-positive T cells and controls viral load (PubMed:29884618). May present to T-helper 1 cells an HRV-16 epitope derived from capsid protein VP2 (SDRIIQITRGDSTITSQDVA), contributing to viral clearance (PubMed:27591323). Presents several immunogenic epitopes derived from C. tetani neurotoxin tetX, playing a role in immune recognition and longterm protection (PubMed:19830726). In the context of tumor immunesurveillance, may present tumor-derived neoantigens to CD4-positive T cells and trigger anti-tumor helper functions (PubMed:31495665).
messages: Allele DRB1*13:01: Presents viral epitopes derived from HHV-6B antigens to polyfunctional CD4-positive T cells implicated in control of HHV-6B infection.
messages: Allele DRB1*15:01 is associated with increased susceptibility to Goodpasture syndrome. Can present a self-peptide derived from COL4A3 (GWISLWKGFSF) on TCR (TRAV19 biased) in pathogenic CD4-positive T-helper 1 and T-helper 17 cells, triggering autoimmune inflammation.
messages: Allele DRB1*15:01: May present to T-helper 1 cells an HRV-16 epitope derived from capsid protein VP2 (SNNSATLIVPYVNAVPMDSM), contributing to viral clearance (PubMed:27591323). Displays a self-peptide derived from MBP (ENPVVHFFKNIVTPR) (PubMed:9782128, PubMed:25413013). May present to T-helper 1 cells an immunogenic epitope derived from tumor-associated antigen WT1 (KRYFKLSHLQMHSRKH), likely providing for effective antitumor immunity in a wide range of solid and hematological malignancies.
messages: Allele DRB1*15:02: Displays an immunodominant HIV-1 gag peptide (FRDYVDRFYKTLRAEQASQE) on infected dendritic cells for recognition by TRAV24-TRBV2 TCR on CD4-positive T cells and controls viral load (PubMed:29884618). May present to T-helper 1 cells an immunogenic epitope derived from tumor-associated antigen WT1 (KRYFKLSHLQMHSRKH), likely providing for effective antitumor immunity in a wide range of solid and hematological malignancies (PubMed:19120973).
messages: Autolysosome membrane
messages: Cell membrane
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry. Alleles DRB1*04:01; DRB1*04:04; DRB1*04:05; DRB1*04:08; DRB1*10:01; DRB1*01:01 and DRB1*01:02 are associated with increased susceptibility to rheumatoid arthritis, where affected individuals have antibodies to cyclic citrullinated peptide (anti-CCP-positive rheumatoid arthritis). Variations at position 40 in the peptide-binding cleft of these alleles explain most of the association to rheumatoid arthritis risk.
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry. Alleles DRB1*04:02, DRB1*11:01 and DRB1*12:01 are associated with sarcoidosis. Allele DRB1*04:02 is significantly associated with specific sarcodosis phenotypes such as eye, parotid and salivary gland involvement.
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry. In populations of European descent, allele DRB1*15:01 has the strongest association with multiple sclerosis among all HLA class II alleles. Additional risk is associated with the strongly linked alleles DRB1*03:01 and DQB1*02:01 as well as with allele DRB1*13:03 (PubMed:21833088). It is postulated that bacterial or viral infection triggers the autoimmune MS. Microbial peptides having low affinity crossreactivity to MBP autoantigen, may stimulate autoreactive T cells via molecular mimicry and initiate the autoimmune inflammation (PubMed:19303388).
messages: Endoplasmic reticulum membrane
messages: Endosome membrane
messages: Expressed in professional APCs: monocyte/macrophages, dendritic cells and B cells (at protein level) (PubMed:31495665, PubMed:23783831, PubMed:19830726). Expressed in thymic epithelial cells (at protein level) (PubMed:23783831).
messages: Heterotrimer that consists of an alpha chain HLA-DRA, a beta chain HLA-DRB1 and a peptide (peptide-MHCII) (PubMed:7477400, PubMed:9354468, PubMed:9782128, PubMed:31619516, PubMed:32668259). Newly synthesized alpha and beta chains forms a heterodimer (MHCII) that associates with the CD74/invariant chain (Ii) in the endoplasmic reticulum (ER). Ii is a trimer composed of three subunits and each subunit interacts with one MHCII dimer, blocking the peptide-binding cleft. As a result, MHCII molecules cannot bind peptides present in the ER (PubMed:7479981). The complex of MHCII and CD74/Ii is transported in vesicles from ER to Golgi to lysosomes, where it encounters antigenic peptides generated via proteolysis of endocytosed antigens. MHCII dimers are dissociated from CD74/Ii by the combined action of proteolysis and HLA-DM (PubMed:25413013). Lysosomal enzymes such as cathepsin, degrade CD74/Ii leaving a 24 amino acid remnant called class II-associated Ii or CLIP. Interacts (via the peptide binding cleft) with CLIP; this interaction inhibits antigen peptide binding before entry in the endosomal compartment (PubMed:7477400, PubMed:9075930). The displacement of CLIP and replacement by a high affinity peptide in lysosomes is performed by HLA-DM heterodimer. HLA-DM catalyzes CLIP dissociation from MHCII, stabilizes empty MHCII and mediates the selection of high affinity peptides (PubMed:23260142, PubMed:11070170, PubMed:9075930). Interacts with HLA-DM heterodimer; this interaction is direct (PubMed:25413013). Interacts with TCR (via CDR3) (PubMed:29884618). Interacts (via beta-2 domain) with CD4 coreceptor (via Ig-like V-type domain); this interaction is of exceptionally low affinity yet necessary for optimal recognition of antigenic peptides (PubMed:21900604, PubMed:27114505).
messages: Highly polymorphic. Polymorphic residues encode for the beta-1 domain of the peptide-binding cleft, where they contribute to variations in peptide binding and TCR recognition among different alleles. The sequence shown is that of DRB1*15:01. The sequences of common representative alleles of serologically distinct allele groups as defined in the catalog of common and well-documented HLA alleles, are described as variants of DRB1*15:01 (PubMed:23510415). In the context of hematological malignancy and T cell transplantation, alleles DRB1*03:01 and DRB1*13:01 present minor histocompatibility antigens derived respectively from host MTHFD1 and LY75 proteins, contributing to T cell-mediated graft-versus-leukemia effect and complete remission (PubMed:19706888).
messages: In populations of European descent, allele DRB1*01:03 is associated with increased susceptibility to Crohn disease and colonic ulcerative colitis. Decreased heterozygosity in individuals with colonic ulcerative colitis suggests that it acts as a recessive risk allele.
messages: Late endosome membrane
messages: Lysosome membrane
messages: The beta-1 domain is a structural part of the peptide-binding cleft. It contains one alpha helix and 4 beta sheets, respectively forming part of the wall and the floor of the peptide-binding cleft. The other 4 beta sheets of the floor and the second alpha helix wall is formed by the alpha-1 domain of HLA-DRA. Forms hydrogen bonds with the peptide main chain via conserved amino acid in most HLA-DRB molecules. The polymorphic residues accomodate the side chains of the peptide conferring peptide specificity to distinct HLA-DRB1 alleles (PubMed:8145819, PubMed:28467828, PubMed:9782128, PubMed:9354468). The peptide-bound beta-1 domain forms hydrogen bonds with CDR2 and CDR3 alpha-domains of TCR (PubMed:19303388).
messages: The beta-2 Ig-like domain mediates the interaction with CD4 coreceptor.
messages: Ubiquitinated by MARCHF1 and MARCHF8 at Lys-254 leading to sorting into the endosome system and down-regulation of MHCII.

9606:BCHE
gene id: 9606:BCHE
uniprot id: P06276
names: Activity Regulation
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the type-B carboxylesterase/lipase family.
messages: Detected in blood plasma (at protein level). Present in most cells except erythrocytes.
messages: Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.
messages: Homotetramer; disulfide-linked. Dimer of dimers.
messages: Inhibited by mercury. Inhibited by Tabun. Tabun forms a covalent adduct with Ser-226 that becomes irreversible upon aging.
messages: N-glycosylated. No other PTM detected (PubMed:20946535). The major N-glycan structures are of the complex diantennary type with 1 and 2 N-acetylneuraminic acid molecules (Neu5Ac) making up approximately 33% and 47% of the total N-glycans, respectively. Only low amounts of fucosylated diantennary N-glycans are detected (approximately 2%). Triantennary N-glycans with or without fucose amount to approximately 13%, whereas 5% of the total N-glycans are of the oligomannosidic or hybrid type.
messages: Secreted
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:GINS4
gene id: 9606:GINS4
uniprot id: Q9BRT9
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the GINS4/SLD5 family.
messages: Chromosome
messages: Component of the GINS complex which is a heterotetramer of GINS1, GINS2, GINS3 and GINS4. Forms a stable subcomplex with GINS1. GINS complex interacts with DNA primase in vitro (PubMed:17170760, PubMed:17417653, PubMed:17545466, PubMed:17557111, PubMed:17652513, PubMed:28414293, PubMed:32453425). Component of the CMG helicase complex, a hexameric ring of related MCM2-7 subunits stabilized by CDC45 and the tetrameric GINS complex (PubMed:34700328, PubMed:34694004, PubMed:32453425).
messages: Cytoplasm
messages: Nucleus
messages: Required for correct functioning of the GINS complex, a complex that plays an essential role in the initiation of DNA replication, and progression of DNA replication forks (PubMed:17417653, PubMed:28414293). GINS complex is a core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built (PubMed:32453425, PubMed:34694004, PubMed:34700328, PubMed:35585232).
messages: Significantly up-regulated in aggressive melanomas.

9606:KCMF1
gene id: 9606:KCMF1
uniprot id: Q9P0J7
names: Function
names: Induction
names: Similarity
names: Tissue Specificity
messages: Belongs to the KCMF1 family.
messages: Has intrinsic E3 ubiquitin ligase activity and promotes ubiquitination.
messages: Spleen, small intestine, ovary, peripheral blood, lung, kidney and pancreas. Expressed at low levels in the thymus, prostate, testis, colon, heart, brain, placenta and liver.
messages: Up-regulated by FGF2 in gastric cancer cells.

9606:ATL1
gene id: 9606:ATL1
uniprot id: A0A0S2Z5A2
uniprot id: A0A0S2Z5B0
uniprot id: Q53F53
uniprot id: Q8WXF7
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the TRAFAC class dynamin-like GTPase superfamily. GB1/RHD3 GTPase family.
messages: Belongs to the TRAFAC class dynamin-like GTPase superfamily. GB1/RHD3 GTPase family. GB1 subfamily.
messages: Endoplasmic reticulum membrane
messages: Expressed predominantly in the adult and fetal central nervous system. Measurable expression in all tissues examined, although expression in adult brain is at least 50-fold higher than in other tissues. Detected predominantly in pyramidal neurons in the cerebral cortex and the hippocampus of the brain. Expressed in upper and lower motor neurons (at protein level).
messages: GTPase tethering membranes through formation of trans-homooligomers and mediating homotypic fusion of endoplasmic reticulum membranes. Functions in endoplasmic reticulum tubular network biogenesis (PubMed:27619977). May also regulate Golgi biogenesis. May regulate axonal development.
messages: Golgi apparatus membrane
messages: Monomer as apoprotein and in the GDP-bound form. Homodimer in the GTP-bound form. Interacts (via N-terminal region) with MAP4K4 (via CNH regulatory domain). Interacts with REEP5, RTN3 and RTN4 (via the transmembrane region). Interacts with SPAST; interaction is direct. May interact with TMED2. Interacts with REEP1. Interacts with CPT1C. Interacts with ARL6IP1 (By similarity). Interacts with ZFYVE27 (PubMed:23969831).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: axon

9606:PSG5
gene id: 9606:PSG5
uniprot id: Q15238
names: Developmental Stage
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the immunoglobulin superfamily. CEA family.
messages: PSBG are produced in high quantity during pregnancy.
messages: Secreted
messages: Synthesized by syncytiotrophoblast of the placenta.

9606:KIF6
gene id: 9606:KIF6
uniprot id: Q6ZMV9
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family.
messages: cytoskeleton

9606:SCAPER
gene id: 9606:SCAPER
uniprot id: Q9BY12
names: Developmental Stage
names: Disease Annotation
names: Function
names: PTM
names: Sequence Caution
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: CCNA2/CDK2 regulatory protein that transiently maintains CCNA2 in the cytoplasm.
messages: Contaminating sequence. Potential poly-A sequence.
messages: Endoplasmic reticulum
messages: Expressed at each stage of the cell cycle, including G0, although the expression is somewhat higher in late G1 and S phases.
messages: Interacts with CCNA2/CDK2 complex, but not with CCNA2/CDC2, CCNB1/CDC2 or CCNE1/CDK2 complexes, at multiple phases of the cell cycle, including S and G2/M.
messages: Nucleus
messages: Phosphorylated in vitro by the CCNA2/CDK2 complex.
messages: Probable cloning artifact.
messages: The disease may be caused by variants affecting the gene represented in this entry.
messages: Widely expressed with high expression in testis. Isoform 1 is detected in various tissues, including retina, fetal and adult brain. Isoform 2 is expressed in the retina at high levels, and in the brain at very low levels (PubMed:28794130).

9606:SRSF11
gene id: 9606:SRSF11
uniprot id: Q05519
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the splicing factor SR family.
messages: Interacts with PUF60.
messages: May function in pre-mRNA splicing.
messages: Nucleus

9606:ADRA2B
gene id: 9606:ADRA2B
uniprot id: P18089
names: Disease Annotation
names: Function
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: A rare polymorphic frameshift in position 451 produces a protein of 545 residues.
messages: Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is clonidine > norepinephrine > epinephrine = oxymetazoline > dopamine > p-tyramine = phenylephrine > serotonin > p-synephrine / p-octopamine. For antagonists, the rank order is yohimbine > chlorpromazine > phentolamine > mianserine > spiperone > prazosin > alprenolol > propanolol > pindolol.
messages: Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRA2B sub-subfamily.
messages: Cell membrane
messages: Interacts with RAB26 (PubMed:23105096). Interacts with PPP1R9B (PubMed:24114805). Interacts with GGA1, GGA2 and GGA3 (PubMed:27901063, PubMed:26811329).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:IL25
gene id: 9606:IL25
uniprot id: Q9H293
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the IL-17 family.
messages: Cytokine produced by various cells such as eosinophils, T-helper type 2 (Th2) cells or epithelial cells that plays a role in internal safety of adaptive immune responses by regulating cytokine production (PubMed:25821217, PubMed:15860795). Promotes and augments T-helper type 2 responses locally or systemically (PubMed:25821217). Exerts its activity via its receptor composed of IL17RA and IL17RB for signal transduction (By similarity). In turn, stimulates the JAK2-STAT5A pathway and promotes the secretion of type-2 associated cytokines including IL4, IL9 and IL13 (PubMed:25821217). Induces also the release of IL8, and IL6 from eosinophils through the combined activation of MAPK and NF-kappa-B pathways (PubMed:15860795). Inhibits the differentiation of T-helper (Th17) cells via the production of IL4, IL5 and IL13 (PubMed:11754819).
messages: Expressed at low levels in several tissues, including brain, kidney, lung, prostate, testis, spinal cord, adrenal gland, and trachea.
messages: Secreted

9606:FCAMR
gene id: 9606:FCAMR
uniprot id: Q8WWV6
names: Function
names: Induction
names: PTM
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Cell membrane
messages: Expressed by mesangial cells.
messages: Functions as a receptor for the Fc fragment of IgA and IgM. Binds IgA and IgM with high affinity and mediates their endocytosis. May function in the immune response to microbes mediated by IgA and IgM.
messages: N-glycosylated.
messages: Up-regulated by IFNG/IFN-gamma in mesangial cells.

9606:LDLRAD2
gene id: 9606:LDLRAD2
uniprot id: Q5SZI1
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the LDLR family.
messages: Membrane

9606:ACVR1
gene id: 9606:ACVR1
uniprot id: D3DPA4
uniprot id: Q04771
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily.
messages: Bone morphogenetic protein (BMP) type I receptor that is involved in a wide variety of biological processes, including bone, heart, cartilage, nervous, and reproductive system development and regulation (PubMed:20628059, PubMed:22977237). As a type I receptor, forms heterotetrameric receptor complexes with the type II receptors AMHR2, ACVR2A or ACVR2B (PubMed:17911401). Upon binding of ligands such as BMP7 or GDF2/BMP9 to the heteromeric complexes, type II receptors transphosphorylate ACVR1 intracellular domain (PubMed:25354296). In turn, ACVR1 kinase domain is activated and subsequently phosphorylates SMAD1/5/8 proteins that transduce the signal (PubMed:9748228). In addition to its role in mediating BMP pathway-specific signaling, suppresses TGFbeta/activin pathway signaling by interfering with the binding of activin to its type II receptor (PubMed:17911401). Besides canonical SMAD signaling, can activate non-canonical pathways such as p38 mitogen-activated protein kinases/MAPKs (By similarity). May promote the expression of HAMP, potentially via its interaction with BMP6 (By similarity).
messages: Expressed in normal parenchymal cells, endothelial cells, fibroblasts and tumor-derived epithelial cells.
messages: Interacts with FKBP1A (PubMed:22484487, Ref.14). Interacts with FCHO1 (PubMed:22484487). Interacts with CLU (PubMed:8555189). Interacts with type II receptors AMHR2 and ACVR2A (PubMed:17911401). Interacts with BMP7 (PubMed:9748228). Interacts with GDF2/BMP9 (PubMed:20628059). Interacts with BMP6 (when glycosylated); the interaction may induce HAMP expression (PubMed:18070108, PubMed:31800957). Interacts with TSC22D1/TSC-22 (PubMed:21791611).
messages: Membrane
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:PLEKHF2
gene id: 9606:PLEKHF2
uniprot id: Q9H8W4
names: Domain
names: Function
names: Induction
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Early endosome membrane
messages: Endoplasmic reticulum
messages: Expressed in placenta, ovary and small intestine, as well as in heart and pancreas. Also expressed in peripheral blood mononuclear cells and dendritic cells.
messages: May interact with EEA1.
messages: May play a role in early endosome fusion upstream of RAB5, hence regulating receptor trafficking and fluid-phase transport. Enhances cellular sensitivity to TNF-induced apoptosis (PubMed:18288467).
messages: The PH and FYVE domains may be important for TNF-induced localization to the endoplasmic reticulum and for enhanced cellular sensitivity to TNF-induced apoptosis (PubMed:18288467). The FYVE domain is important for binding to the endosomal membrane.
messages: Up-regulated by TNF, bacterial lipopolysaccharides (LPS) and phorbol myristate acetate (PMA) (at protein level).

9606:CITED2
gene id: 9606:CITED2
uniprot id: A0A0A0MTM3
uniprot id: D9ZGF1
uniprot id: Q99967
names: Disease Annotation
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the CITED family.
messages: By hypoxia and deferoxamine.
messages: Interacts (via C-terminus) with SMAD2. Interacts (via C-terminus) with SMAD3 (via MH2 domain). Interacts with LHX2 (via LIM domains). Interacts with WT1 (By similarity). Interacts (via C-terminus) with EP300 (via CH1 domain); the interaction is stimulated in response to hypoxia. Interacts with PPARA. Interacts (via C-terminus) with TFAP2A, TFAP2B and TFAP2C.
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Transcriptional coactivator of the p300/CBP-mediated transcription complex. Acts as a bridge, linking TFAP2 transcription factors and the p300/CBP transcriptional coactivator complex in order to stimulate TFAP2-mediated transcriptional activation. Positively regulates TGF-beta signaling through its association with the SMAD/p300/CBP-mediated transcriptional coactivator complex. Stimulates the peroxisome proliferator-activated receptors PPARA transcriptional activity. Enhances estrogen-dependent transactivation mediated by estrogen receptors. Acts also as a transcriptional corepressor; interferes with the binding of the transcription factors HIF1A or STAT2 and the p300/CBP transcriptional coactivator complex. Participates in sex determination and early gonad development by stimulating transcription activation of SRY. Plays a role in controlling left-right patterning during embryogenesis; potentiates transcriptional activation of NODAL-mediated gene transcription in the left lateral plate mesoderm (LPM). Plays an essential role in differentiation of the adrenal cortex from the adrenogonadal primordium (AGP); stimulates WT1-mediated transcription activation thereby up-regulating the nuclear hormone receptor NR5A1 promoter activity. Associates with chromatin to the PITX2 P1 promoter region.

9606:AKAP8
gene id: 9606:AKAP8
uniprot id: O43823
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Anchoring protein that mediates the subcellular compartmentation of cAMP-dependent protein kinase (PKA type II) (PubMed:9473338). Acts as an anchor for a PKA-signaling complex onto mitotic chromosomes, which is required for maintenance of chromosomes in a condensed form throughout mitosis. Recruits condensin complex subunit NCAPD2 to chromosomes required for chromatin condensation; the function appears to be independent from PKA-anchoring (PubMed:10601332, PubMed:10791967, PubMed:11964380). May help to deliver cyclin D/E to CDK4 to facilitate cell cycle progression (PubMed:14641107). Required for cell cycle G2/M transition and histone deacetylation during mitosis. In mitotic cells recruits HDAC3 to the vicinity of chromatin leading to deacetylation and subsequent phosphorylation at 'Ser-10' of histone H3; in this function may act redundantly with AKAP8L (PubMed:16980585). Involved in nuclear retention of RPS6KA1 upon ERK activation thus inducing cell proliferation (PubMed:22130794). May be involved in regulation of DNA replication by acting as scaffold for MCM2 (PubMed:12740381). Enhances HMT activity of the KMT2 family MLL4/WBP7 complex and is involved in transcriptional regulation. In a teratocarcinoma cell line is involved in retinoic acid-mediated induction of developmental genes implicating H3 'Lys-4' methylation (PubMed:23995757). May be involved in recruitment of active CASP3 to the nucleus in apoptotic cells (PubMed:16227597). May act as a carrier protein of GJA1 for its transport to the nucleus (PubMed:26880274). May play a repressive role in the regulation of rDNA transcription. Preferentially binds GC-rich DNA in vitro. In cells, associates with ribosomal RNA (rRNA) chromatin, preferentially with rRNA promoter and transcribed regions (PubMed:26683827). Involved in modulation of Toll-like receptor signaling. Required for the cAMP-dependent suppression of TNF-alpha in early stages of LPS-induced macrophage activation; the function probably implicates target…
messages: Belongs to the AKAP95 family.
messages: Binds to the PKA RII-alpha regulatory subunit PRKAR2A (phosphorylated at 'Thr-54') during mitosis (PubMed:9473338, PubMed:10601332, PubMed:10764601, PubMed:11591814). Interacts (via C-terminus) with FIGN (By similarity). Interacts with NCAPD2, CCND1, MCM2, RPS6KA1, PDE4A (PubMed:10601332, PubMed:11964380, PubMed:11591814, PubMed:12740381, PubMed:14641107, PubMed:15470020, PubMed:22130794). Interacts with CCND3, CCNE1, DDX5, CASP3. Interacts with NFKB1; detetcted in the cytoplasm. Interacts with MYCBP; MYCBP is translocated to the nucleus and the interaction prevents the association of the PKA catalytic subunit leading to suppression of PKA activity (By similarity). Interacts with DPY30; mediating AKAP8 association with at least the MLL4/WBP7 HMT complex (PubMed:23995757). Interacts with HDAC3; increased during mitosis (PubMed:16980585). Interacts with GJA1; in the nucleus and in the nuclear membrane; the nuclear association increases with progress of cell cycle G1, S and G2 phase and decreases in M phase (PubMed:26880274).
messages: Cytoplasm
messages: Highly expressed in heart, liver, skeletal muscle, kidney and pancreas. Expressed in mature dendritic cells.
messages: Nucleus
messages: Nucleus matrix
messages: Phosphorylated on tyrosine residues probably by SRC subfamily protein kinases; multiple phosphorylation is leading to dissociation from nuclear structures implicated in chromatin structural changes.
messages: nucleolus

9606:NLGN2
gene id: 9606:NLGN2
uniprot id: Q8NFZ4
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the type-B carboxylesterase/lipase family.
messages: Cell membrane
messages: Expressed in the blood vessel walls. Detected in colon, brain and pancreas islets of Langerhans (at protein level). Detected in brain, and at lower levels in pancreas islet beta cells.
messages: Interacts with neurexins NRXN1, NRXN2 and NRXN3 (By similarity). Interaction with neurexins is mediated by heparan sulfate glycan modification on neurexin (By similarity). Interacts (via its C-terminus) with DLG4/PSD-95 (via PDZ domain 3) (PubMed:9278515). Interacts with PATJ (By similarity). Interacts with GPHN (By similarity). Interacts with MDGA1 and MDGA2 (By similarity). Found in a complex with MAGI2 and IGSF9B, where it interacts with MAGI2 (via WW 1, WW 2 and PDZ 2 domains) (PubMed:23751499). Identified in a complex of 720 kDa composed of LHFPL4, NLGN2, GABRA1, GABRB2, GABRG2 and GABRB3 (By similarity). Interacts with LHFPL4; leading to mutual regulation of the protein level and synaptic clustering (By similarity). Interacts with NLGN2 (By similarity).
messages: Postsynaptic cell membrane
messages: Presynaptic cell membrane
messages: Transmembrane scaffolding protein involved in cell-cell interactions via its interactions with neurexin family members. Mediates cell-cell interactions both in neurons and in other types of cells, such as Langerhans beta cells. Plays a role in synapse function and synaptic signal transmission, especially via gamma-aminobutyric acid receptors (GABA(A) receptors). Functions by recruiting and clustering synaptic proteins. Promotes clustering of postsynaptic GABRG2 and GPHN. Promotes clustering of postsynaptic LHFPL4 (By similarity). Modulates signaling by inhibitory synapses, and thereby plays a role in controlling the ratio of signaling by excitatory and inhibitory synapses and information processing. Required for normal signal amplitude from inhibitory synapses, but is not essential for normal signal frequency. May promote the initial formation of synapses, but is not essential for this. In vitro, triggers the de novo formation of presynaptic structures. Mediates cell-cell interactions between Langerhans beta cells and modulates insulin secretion (By similarity).

9606:DHX36
gene id: 9606:DHX36
uniprot id: Q9H2U1
names: Activity Regulation
names: Domain
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: ATPase activity is enhanced in the presence of homomeric poly(U) RNAs, but not by double-stranded DNA (dsDNA), double-stranded RNA (dsRNA) and tRNA.
messages: Belongs to the DEAD box helicase family. DEAH subfamily.
messages: Cytoplasm
messages: Found in a multi-helicase-TICAM1 complex at least composed of DHX36, DDX1, DDX21 and TICAM1; this complex exists in resting cells with or without dsRNA poly(I:C) ligand stimulation (By similarity). Interacts (via C-terminus) with TICAM1 (via TIR domain) (By similarity). Interacts (via C-terminus) with DDX21; this interaction serves as bridges to TICAM1 (By similarity). Interacts with TERT; this interaction is dependent on the ability of DHX36 to bind to the G-quadruplex RNA (G4-RNA) structure present in the telomerase RNA template component (TERC) (PubMed:21846770). Interacts with DKC1; this interaction is dependent on the ability of DHX36 to bind to the G4-RNA structure present in TERC (PubMed:21846770). Interacts with PARN; this interaction stimulates PARN to enhance uPA mRNA decay (PubMed:14731398). Interacts with EXOSC3; this interaction occurs in a RNase-insensitive manner (PubMed:14731398). Interacts with EXOSC10; this interaction occurs in a RNase-insensitive manner (PubMed:14731398). Interacts with ILF3; this interaction occurs in a RNA-dependent manner (PubMed:14731398). Interacts with ELAVL1; this interaction occurs in an RNA-dependent manner (PubMed:14731398, PubMed:26489465). Interacts with DDX5; this interaction occurs in a RNA-dependent manner (PubMed:18279852). Interacts with DDX17; this interaction occurs in a RNA-dependent manner (PubMed:18279852). Interacts with HDAC1; this interaction occurs in a RNA-dependent manner (PubMed:18279852). Interacts with HDAC3; this interaction occurs in a RNA-dependent manner (PubMed:18279852). Interacts with HDAC4 (By similarity). Interacts with AGO1 (PubMed:17932509). Interacts with AGO2 (PubMed:17932509). Interacts with ERCC6 (PubMed:26030138).
messages: Highly expressed in testis.
messages: Mitochondrion
messages: More unstable than isoform 1.
messages: Multifunctional ATP-dependent helicase that unwinds G-quadruplex (G4) structures (PubMed:16150737, PubMed:18854321, PubMed:20472641, PubMed:21586581). Plays a role in many biological processes such as genomic integrity, gene expression regulations and as a sensor to initiate antiviral responses (PubMed:14731398, PubMed:18279852, PubMed:21993297, PubMed:22238380, PubMed:25579584). G4 structures correspond to helical structures containing guanine tetrads (By similarity). Binds with high affinity to and unwinds G4 structures that are formed in nucleic acids (G4-ADN and G4-RNA) (PubMed:16150737, PubMed:18842585, PubMed:20472641, PubMed:21586581, PubMed:24369427, PubMed:26195789). Plays a role in genomic integrity (PubMed:22238380). Converts the G4-RNA structure present in telomerase RNA template component (TREC) into a double-stranded RNA to promote P1 helix formation that acts as a template boundary ensuring accurate reverse transcription (PubMed:20472641, PubMed:21149580, PubMed:21846770, PubMed:22238380, PubMed:24151078, PubMed:25579584). Plays a role in transcriptional regulation (PubMed:21586581, PubMed:21993297). Resolves G4-DNA structures in promoters of genes, such as YY1, KIT/c-kit and ALPL and positively regulates their expression (PubMed:21993297). Plays a role in post-transcriptional regulation (PubMed:27940037). Unwinds a G4-RNA structure located in the 3'-UTR polyadenylation site of the pre-mRNA TP53 and stimulates TP53 pre-mRNA 3'-end processing in response to ultraviolet (UV)-induced DNA damage (PubMed:27940037). Binds to the precursor-microRNA-134 (pre-miR-134) terminal loop and regulates its transport into the synapto-dendritic compartment (By similarity). Involved in the pre-miR-134-dependent inhibition of target gene expression and the control of dendritic spine size (By similarity). Plays a role in the regulation of cytoplasmic mRNA translation and mRNA stability (PubMed:24369427, PubMed:26489465). Binds to both G4-RNA structures and alternative non…
messages: Nucleus
messages: Nucleus speckle
messages: Perikaryon
messages: Stress granule
messages: The DHX36-specific motif (DSM) form folds into a DNA-binding-induced alpha-helix that together with the oligonucleotide and oligosaccharide-binding-fold-like (OB-fold-like) subdomain, selectively bind to Myc-promoter G4-DNA-containing structure in an ATP-dependent manner. Upon G4-DNA-binding, DHX36 pulls on DSM in the 3'-direction, inducing rearrangement of the RecA-like 1 and 2 and the degenerate-winged-helix (WH) regions; these rearrangements are propbably responsible for the ATP-independent repetitive G4-DNA unfolding activity, one residue at a time. Upon resolving of G4-DNA into separate nucleotide strands, and ATP hydrolysis, the apoprotein of DHX36 seems incompatible with G4-DNA-binding (By similarity). The N-terminus is necessary for its recruitment to cytoplasmic stress granules (SGs) upon arsenite-induced treatment (PubMed:18854321).
messages: axon
messages: cytosol
messages: dendrite
messages: telomere

9606:MICOS10
gene id: 9606:MICOS10
uniprot id: A0A087WU07
uniprot id: Q5TGZ0
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the MICOS complex subunit Mic10 family.
messages: Component of the MICOS complex, a large protein complex of the mitochondrial inner membrane that plays crucial roles in the maintenance of crista junctions, inner membrane architecture, and formation of contact sites to the outer membrane.
messages: Component of the mitochondrial contact site and cristae organizing system (MICOS) complex, composed of at least MICOS10/MIC10, CHCHD3/MIC19, CHCHD6/MIC25, APOOL/MIC27, IMMT/MIC60, APOO/MIC23/MIC26 and MICOS13/MIC13. This complex was also known under the names MINOS or MitOS complex. The MICOS complex associates with mitochondrial outer membrane proteins SAMM50, MTX1 and MTX2 (together described as components of the mitochondrial outer membrane sorting assembly machinery (SAM) complex) and DNAJC11, mitochondrial inner membrane protein TMEM11 and with HSPA9. The MICOS and SAM complexes together with DNAJC11 are part of a large protein complex spanning both membranes termed the mitochondrial intermembrane space bridging (MIB) complex. Interacts with IMMT/MIC60 and MICOS13/MIC13. Interacts with APOO/MIC23/MIC26 and APOOL/MIC27. Interacts with ARMC1 (PubMed:31644573).
messages: Component of the mitochondrial contact site and cristae organizing system (MICOS) complex.
messages: Mitochondrion inner membrane

9606:SMIM9
gene id: 9606:SMIM9
uniprot id: A6NGZ8
names: Subcellular Location Annotation
messages: Cell membrane

9606:C12orf57
gene id: 9606:C12orf57
uniprot id: F5GXW5
uniprot id: Q99622
uniprot id: U3KQ85
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the UPF0456 family.
messages: Cytoplasm
messages: In brain, may be required for corpus callosum development.
messages: The disease is caused by variants affecting the gene represented in this entry. A variant resulting in a GUG start codon may be able to produce some protein because of a consensus Kozak sequence, although less efficiently than the wild type. This would explain the phenotypic variability observed.
messages: Ubiquitously expressed, with higher expression in lung and fetal brain.

9606:CAVIN1
gene id: 9606:CAVIN1
uniprot id: Q6NZI2
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the CAVIN family.
messages: Cell membrane
messages: Component of the CAVIN complex composed of CAVIN1, CAVIN2, CAVIN3 and CAVIN4. Homotrimer (By similarity). Interacts with TTF1 (PubMed:9582279). Interacts with RNA polymerase I. Binds the 3' end of pre-rRNA. Interacts with transcription factor ZNF148 (By similarity). Interacts with LIPE in the adipocyte cytoplasm (PubMed:17026959). Interacts with CAV1 and CAVIN3 (By similarity). Interacts with CAVIN2 (PubMed:19525939, PubMed:24567387). Interacts with CAVIN4 and CAV3 (PubMed:24567387).
messages: Endoplasmic reticulum
messages: Five truncated forms are found in the caveolae. These are thought to be the result of proteolysis and may be phosphorylation-dependent.
messages: Microsome
messages: Mitochondrion
messages: Monoubiquitinated.
messages: Nucleus
messages: Phosphorylated. Present in active and inactive forms. Changes in phosphorylation pattern may alter activity. Phosphorylation at Tyr-156 is essential for its functionin the regulation of ribosomal transcriptional activity.
messages: Plays an important role in caveolae formation and organization. Essential for the formation of caveolae in all tissues (PubMed:18056712, PubMed:18191225, PubMed:19726876). Core component of the CAVIN complex which is essential for recruitment of the complex to the caveolae in presence of calveolin-1 (CAV1). Essential for normal oligomerization of CAV1. Promotes ribosomal transcriptional activity in response to metabolic challenges in the adipocytes and plays an important role in the formation of the ribosomal transcriptional loop. Dissociates transcription complexes paused by DNA-bound TTF1, thereby releasing both RNA polymerase I and pre-RNA from the template (By similarity) (PubMed:18056712, PubMed:18191225, PubMed:19726876). The caveolae biogenesis pathway is required for the secretion of proteins such as GASK1A (By similarity).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The leucine-zipper domain 1 is essential for its localization in the caveolae.
messages: caveola
messages: cytosol

9606:DNAJC2
gene id: 9606:DNAJC2
uniprot id: Q99543
names: Domain
names: Function
names: Induction
names: Miscellaneous
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acts both as a chaperone in the cytosol and as a chromatin regulator in the nucleus. When cytosolic, acts as a molecular chaperone: component of the ribosome-associated complex (RAC), a complex involved in folding or maintaining nascent polypeptides in a folding-competent state. In the RAC complex, stimulates the ATPase activity of the ribosome-associated pool of Hsp70-type chaperones HSPA14 that bind to the nascent polypeptide chain. When nuclear, mediates the switching from polycomb-repressed genes to an active state: specifically recruited at histone H2A ubiquitinated at 'Lys-119' (H2AK119ub), and promotes the displacement of the polycomb PRC1 complex from chromatin, thereby facilitating transcription activation.
messages: Component of ribosome-associated complex (RAC), a heterodimer composed of Hsp70/DnaK-type chaperone HSPA14 and Hsp40/DnaJ-type chaperone DNAJC2 (PubMed:16002468). Interacts (via ZRF1-UBD region) with ID1 (By similarity).
messages: Constitutes a myeloid leukemia-associated antigen and might be a target for leukemia T-cell therapy.
messages: Expression is repressed by CEBPA. Strongly overexpressed in leukemic cells.
messages: Nucleus
messages: Phosphorylated in M (mitotic) phase.
messages: The ZRF1-UBD region specifically recognizes and binds H2AK119ub. The ZRF1-UBD region is also involved in protein-protein interactions with other proteins, suggesting that it may be masked by some regulator, thereby preventing its association with H2AK119ub.
messages: Widely expressed.
messages: cytosol

9606:BACE1
gene id: 9606:BACE1
uniprot id: B7Z3K2
uniprot id: B7Z3Z4
uniprot id: P56817
uniprot id: Q5W9H2
names: Activity Regulation
names: Domain
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acetylated in the endoplasmic reticulum at Lys-126, Lys-275, Lys-279, Lys-285, Lys-299, Lys-300 and Lys-307. Acetylation by NAT8 and NAT8B is transient and deacetylation probably occurs in the Golgi. Acetylation regulates the maturation, the transport to the plasma membrane, the stability and the expression of the protein.
messages: Belongs to the peptidase A1 family.
messages: Cell membrane
messages: Cell surface
messages: Cytoplasmic vesicle membrane
messages: DXXLL motif is required for a proper endocytosis and retrograde transport to the trans-Golgi network, as well as for regulation of lysosomal degradation.
messages: Early endosome
messages: Endoplasmic reticulum
messages: Endosome
messages: Expressed at high levels in the brain and pancreas. In the brain, expression is highest in the substantia nigra, locus coruleus and medulla oblongata.
messages: Inhibited by RTN3 and RTN4.
messages: Late endosome
messages: Lysosome
messages: Membrane raft
messages: Monomer. Interacts (via DXXLL motif) with GGA1, GGA2 and GGA3 (via their VHS domain); the interaction highly increases when BACE1 is phosphorylated at Ser-498 (PubMed:14567678, PubMed:15886016). Interacts with RTN1; RTN2; RTN3 and RTN4; the interaction leads to inhibition of amyloid precursor protein processing (PubMed:15286784, PubMed:16965550, PubMed:16979658). Interacts with SNX6 (PubMed:20354142). Interacts with PCSK9 (PubMed:18660751). Interacts with NAT8 and NAT8B (PubMed:19011241). Interacts with BIN1 (PubMed:27179792). Interacts (via extracellular domain) with ADAM10 (via extracellular domain) (By similarity). Interacts with SORL1; this interaction may affect binding with APP and hence reduce APP cleavage (PubMed:16407538). Interacts with NRDC AND NRG1 (By similarity).
messages: N-Glycosylated (PubMed:11083922, PubMed:17425515). Addition of a bisecting N-acetylglucosamine by MGAT3 blocks lysosomal targeting, further degradation and is required for maintaining stability under stress conditions (By similarity).
messages: Palmitoylation mediates lipid raft localization.
messages: Phosphorylation at Ser-498 is required for interaction with GGA1 and retrograded transport from endosomal compartments to the trans-Golgi network. Non-phosphorylated BACE1 enters a direct recycling route to the cell surface.
messages: Recycling endosome
messages: Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves at the N-terminus of the A-beta peptide sequence, between residues 671 and 672 of APP, leads to the generation and extracellular release of beta-cleaved soluble APP, and a corresponding cell-associated C-terminal fragment which is later released by gamma-secretase (PubMed:10656250, PubMed:10677483, PubMed:20354142). Cleaves CHL1 (By similarity).
messages: The transmembrane domain is necessary for its activity. It determines its late Golgi localization and access to its substrate, APP.
messages: Ubiquitinated at Lys-501, ubiquitination leads to lysosomal degradation (PubMed:27302062, PubMed:16033761, PubMed:20484053, PubMed:23109336). Monoubiquitinated and 'Lys-63'-linked polyubitinated (PubMed:20484053). Deubiquitnated by USP8; inhibits lysosomal degradation (PubMed:27302062).
messages: Up-regulated by the Ca(2+)-regulated transcription factor NFATC4.
messages: axon
messages: dendrite
messages: trans-Golgi network

9606:NPM2
gene id: 9606:NPM2
uniprot id: Q86SE8
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the nucleoplasmin family.
messages: Core histones chaperone involved in chromatin reprogramming, specially during fertilization and early embryonic development. Probably involved in sperm DNA decondensation during fertilization.
messages: Homopentamer, when bound to H2A-H2B dimers only. Homodecamer of two stacked pentamers, when bound to H2A-H2B dimers and H3-H4 tetramers simultaneously.
messages: Nucleus
messages: The acidic tract A2 mediates histone binding.

9606:POLM
gene id: 9606:POLM
uniprot id: Q9NP87
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the DNA polymerase type-X family.
messages: DPOLM has a reduced ability to distinguish dNTP and rNTP as substrates, and elongates them on DNA primer strand with a similar efficiency. It is able to polymerize nucleotides on RNA primer strands.
messages: Expressed in a number of tissues. Abundant in thymus.
messages: Gap-filling polymerase involved in repair of DNA double-strand breaks by non-homologous end joining (NHEJ). Participates in immunoglobulin (Ig) light chain gene rearrangement in V(D)J recombination.
messages: Nucleus

9606:ACBD4
gene id: 9606:ACBD4
uniprot id: Q8NC06
names: Function
messages: Binds medium- and long-chain acyl-CoA esters and may function as an intracellular carrier of acyl-CoA esters.

9606:HMGXB3
gene id: 9606:HMGXB3
uniprot id: Q12766
names: Subcellular Location Annotation
messages: Nucleus

9606:GPR174
gene id: 9606:GPR174
uniprot id: Q9BXC1
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Putative receptor for purines coupled to G-proteins.

9606:GTDC1
gene id: 9606:GTDC1
uniprot id: Q4AE62
names: Similarity
names: Tissue Specificity
messages: Belongs to the glycosyltransferase group 1 family. Glycosyltransferase 4 subfamily.
messages: Ubiquitous. Expressed at high levels in the lung, brain, spleen, testis, placenta. ovary, pancreas, spleen and peripheral blood leukocytes. Expressed at low level in the colon, small intestine, kidney, skeletal muscle and thymus. Expressed at high level in colon adenocarcinoma.

9606:GABRB3
gene id: 9606:GABRB3
uniprot id: B2RCW8
uniprot id: P28472
uniprot id: X5DQY4
names: Caution
names: Disease Annotation
names: Function
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the ligand-gated ion channel (TC 1.A.9) family.
messages: Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRB3 sub-subfamily.
messages: Cell membrane
messages: Cytoplasmic vesicle membrane
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry.
messages: GABRB3 variants may be associated with insomnia, a condition of inability to initiate or maintain sleep [MIM:137192].
messages: Heteropentamer, formed by a combination of alpha, beta, gamma, delta and rho chains (PubMed:22243422, PubMed:18281286, PubMed:18514161, PubMed:24909990). Can form functional homopentamers (in vitro) (PubMed:22303015). Interacts with UBQLN1 (By similarity). May interact with KIF21B (By similarity). Identified in a complex of 720 kDa composed of LHFPL4, NLGN2, GABRA1, GABRB2, GABRG2 and GABRB3 (By similarity). Interacts with LHFPL4 (By similarity). Interacts with GIT1; this interaction is required for synaptic GABRB3 surface stability and inhibitory synapse strength (By similarity).
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: Ligand-gated chloride channel which is a component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the brain (PubMed:18514161, PubMed:22303015, PubMed:26950270, PubMed:22243422, PubMed:24909990). Plays an important role in the formation of functional inhibitory GABAergic synapses in addition to mediating synaptic inhibition as a GABA-gated ion channel (PubMed:25489750). The gamma2 subunit is necessary but not sufficient for a rapid formation of active synaptic contacts and the synaptogenic effect of this subunit is influenced by the type of alpha and beta subunits present in the receptor pentamer (By similarity). The alpha1/beta3/gamma2 receptor exhibits synaptogenic activity (PubMed:25489750). The alpha2/beta3/gamma2 receptor shows very little or no synaptogenic activity (By similarity). Functions also as histamine receptor and mediates cellular responses to histamine (PubMed:18281286). Plays an important role in somatosensation and in the production of antinociception (By similarity).
messages: Membrane
messages: Postsynaptic cell membrane
messages: Synaptic cell membrane
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:TNFRSF17
gene id: 9606:TNFRSF17
uniprot id: Q02223
names: Disease Annotation
names: Function
names: Miscellaneous
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: A chromosomal aberration involving TNFRSF17 is found in a form of T-cell acute lymphoblastic leukemia (T-ALL). Translocation t(4;16)(q26;p13) with IL2.
messages: Associates with TRAF1, TRAF2, TRAF3, TRAF5 and TRAF6.
messages: Cell membrane
messages: Endomembrane system
messages: Expressed in mature B-cells, but not in T-cells or monocytes.
messages: Observed only in some CD19+ cell.
messages: Receptor for TNFSF13B/BLyS/BAFF and TNFSF13/APRIL. Promotes B-cell survival and plays a role in the regulation of humoral immunity. Activates NF-kappa-B and JNK.

9606:SLC35F4
gene id: 9606:SLC35F4
uniprot id: A4IF30
uniprot id: G3V4Z9
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the SLC35F solute transporter family.
messages: Membrane
messages: Putative solute transporter.

9606:SPON2
gene id: 9606:SPON2
uniprot id: Q9BUD6
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cell adhesion protein that promotes adhesion and outgrowth of hippocampal embryonic neurons. Binds directly to bacteria and their components and functions as an opsonin for macrophage phagocytosis of bacteria. Essential in the initiation of the innate immune response and represents a unique pattern-recognition molecule in the ECM for microbial pathogens (By similarity). Binds bacterial lipopolysaccharide (LPS).
messages: Expressed in normal lung tissue but not in lung carcinoma cell lines.
messages: Monomer. Interacts with integrin.
messages: extracellular matrix

9606:TXNDC12
gene id: 9606:TXNDC12
uniprot id: O95881
names: Function
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Endoplasmic reticulum lumen
messages: Protein-disulfide reductase of the endoplasmic reticulum that promotes disulfide bond formation in client proteins through its thiol-disulfide oxidase activity.
messages: Widely expressed.

9606:DEDD2
gene id: 9606:DEDD2
uniprot id: Q8WXF8
names: Domain
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Expressed in most tissues. High levels were found in liver, kidney, heart, ovary, spleen, testes, skeletal muscle and peripheral blood leukocytes. Expression was absent or low in colon and small intestine. Expression is relatively high in the tumor cell lines chronic myologenous leukemia K-562 and the colorectal adenocarcinoma SW480. Expression is moderate in the cervical carcinoma HeLa, the Burkitt's lymphoma Raji, the lung carcinoma A-549, and the melanoma G-361. In contrast, two leukemia cell lines, HL-60 (promyelocytic leukemia) and MOLT-4 (lymphoblastic leukemia), show relatively low levels.
messages: Interactions with CASP8 and CASP10 are mediated by the DED domain.
messages: Interacts with CASP8, CASP10 and GTF3C3. Homodimerizes and heterodimerizes with DEDD.
messages: May play a critical role in death receptor-induced apoptosis and may target CASP8 and CASP10 to the nucleus. May regulate degradation of intermediate filaments during apoptosis. May play a role in the general transcription machinery in the nucleus and might be an important regulator of the activity of GTF3C3.
messages: nucleolus

9606:PARP14
gene id: 9606:PARP14
uniprot id: Q460N5
names: Caution
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: ADP-ribosyltransferase that mediates mono-ADP-ribosylation of glutamate residues on target proteins (PubMed:16061477, PubMed:27796300, PubMed:18851833, PubMed:25043379). In contrast to PARP1 and PARP2, it is not able to mediate poly-ADP-ribosylation (PubMed:25043379). Has been shown to catalyze the mono-ADP-ribosylation of STAT1 at 'Glu-657' and 'Glu-705', thus decreasing STAT1 phosphorylation which negatively regulates pro-inflammatory cytokine production in macrophages in response to IFNG stimulation (PubMed:27796300). However, the role of ADP-ribosylation in the prevention of STAT1 phosphorylation has been called into question and it has been suggested that the inhibition of phosphorylation may be the result of sumoylation of STAT1 'Lys-703' (PubMed:29858569). Mono-ADP-ribosylates STAT6; enhancing STAT6-dependent transcription (PubMed:27796300). In macrophages, positively regulates MRC1 expression in response to IL4 stimulation by promoting STAT6 phosphorylation (PubMed:27796300). Mono-ADP-ribosylates PARP9 (PubMed:27796300).
messages: Auto-ADP-ribosylated.
messages: Belongs to the ARTD/PARP family.
messages: Cytoplasm
messages: Expressed in macrophages.
messages: Interacts with STAT6 (By similarity). Interacts with PARP10 (PubMed:23473667). Interacts with PARP9 in IFNG-stimulated macrophages; the interaction prevents PARP14-mediated STAT1 and STAT6 ADP-riboslylation (PubMed:27796300).
messages: Nucleus
messages: The role of PARP14-mediated ADP-ribosylation of STAT1 in the prevention of STAT1 phosphorylation has been called into question and it has been suggested that the inhibition of phosphorylation may be the result of sumoylation of STAT1 'Lys-703'.
messages: Up-regulated by IFNG in macrophages. Down-regulated by IL4 in macrophages.

9606:LCORL
gene id: 9606:LCORL
uniprot id: Q8N3X6
names: Caution
names: Function
names: Subcellular Location Annotation
messages: A report observed N-glycosylation at Asn-493 (PubMed:19139490). However, as the protein is predicted to act as a DNA-binding transcription activator, additional evidence is required to confirm this result.
messages: May act as transcription activator that binds DNA elements with the sequence 5'-CCCTATCGATCGATCTCTACCT-3'. May play a role in spermatogenesis (By similarity).
messages: Nucleus

9606:RNF8
gene id: 9606:RNF8
uniprot id: O76064
names: Caution
names: Developmental Stage
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts (via FHA domain) with phosphorylated human herpesvirus 1 ICP0 protein; leading to RNF8 degradation by the proteasome.
messages: According to a well-established model, RNF8 initiate H2A 'Lys-63'-linked ubiquitination leading to recruitment of RNF168 to amplify H2A 'Lys-63'-linked ubiquitination (PubMed:19203578, PubMed:19203579). However, other data suggest that RNF168 is the priming ubiquitin ligase by mediating monoubiquitination of 'Lys-13' and 'Lys-15' of nucleosomal histone H2A (H2AK13Ub and H2AK15Ub respectively) (PubMed:22980979). These data suggest that RNF168 might be recruited to DSBs sites in a RNF8-dependent manner by binding to non-histone proteins ubiquitinated via 'Lys-63'-linked and initiates monoubiquitination of H2A, which is then amplified by RNF8 (PubMed:22980979). Additional evidence is however required to confirm these data.
messages: Autoubiquitinated through 'Lys-48' and 'Lys-63' of ubiquitin. 'Lys-63' polyubiquitination is mediated by UBE2N. 'Lys-29'-type polyubiquitination is also observed, but it doesn't require its own functional RING-type zinc finger.
messages: Belongs to the RNF8 family.
messages: Cytoplasm
messages: E3 ubiquitin-protein ligase that plays a key role in DNA damage signaling via 2 distinct roles: by mediating the 'Lys-63'-linked ubiquitination of histones H2A and H2AX and promoting the recruitment of DNA repair proteins at double-strand breaks (DSBs) sites, and by catalyzing 'Lys-48'-linked ubiquitination to remove target proteins from DNA damage sites. Following DNA DSBs, it is recruited to the sites of damage by ATM-phosphorylated MDC1 and catalyzes the 'Lys-63'-linked ubiquitination of histones H2A and H2AX, thereby promoting the formation of TP53BP1 and BRCA1 ionizing radiation-induced foci (IRIF). Also controls the recruitment of UIMC1-BRCC3 (RAP80-BRCC36) and PAXIP1/PTIP to DNA damage sites. Also recruited at DNA interstrand cross-links (ICLs) sites and catalyzes 'Lys-63'-linked ubiquitination of histones H2A and H2AX, leading to recruitment of FAAP20/C1orf86 and Fanconi anemia (FA) complex, followed by interstrand cross-link repair. H2A ubiquitination also mediates the ATM-dependent transcriptional silencing at regions flanking DSBs in cis, a mechanism to avoid collision between transcription and repair intermediates. Promotes the formation of 'Lys-63'-linked polyubiquitin chains via interactions with the specific ubiquitin-conjugating UBE2N/UBC13 and ubiquitinates non-histone substrates such as PCNA. Substrates that are polyubiquitinated at 'Lys-63' are usually not targeted for degradation. Also catalyzes the formation of 'Lys-48'-linked polyubiquitin chains via interaction with the ubiquitin-conjugating UBE2L6/UBCH8, leading to degradation of substrate proteins such as CHEK2, JMJD2A/KDM4A and KU80/XRCC5: it is still unclear how the preference toward 'Lys-48'- versus 'Lys-63'-linked ubiquitination is regulated but it could be due to RNF8 ability to interact with specific E2 specific ligases. For instance, interaction with phosphorylated HERC2 promotes the association between RNF8 and UBE2N/UBC13 and favors the specific formation of 'Lys-63'-linked ubiquiti…
messages: Homodimer. Forms a E2-E3 ubiquitin ligase complex composed of the RNF8 homodimer and a E2 heterodimer of UBE2N and UBE2V2. Interacts with class III E2s, including UBE2E1, UBE2E2, and UBE2E3 and with UBE2N. Interacts with RXRA. Interacts (via FHA domain) with ATM-phosphorylated MDC1. Interacts (via FHA domain) with 'Thr-4827' phosphorylated HERC2 (via C-terminus). Interacts with PIWIL1; leading to sequester RNF8 in the cytoplasm (By similarity). Interacts with WRAP53/TCAB1 (PubMed:25512560).
messages: Low levels at the G1-S boundary increase in intensity during S phase and until the end of the G2 phase. Abruptly decreases in late mitosis (at protein level). Barely detectable in anaphase.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Midbody
messages: Nucleus
messages: The FHA domain specifically recognizes and binds ATM-phosphorylated MDC1 and 'Thr-4827' phosphorylated HERC2 (PubMed:18001824). This domain is required for proper recruitment to DNA damage sites after UV irradiation, ionizing radiation, or treatment with an alkylating agent (PubMed:23233665).
messages: Ubiquitous. In fetal tissues, highest expression in brain, thymus and liver. In adult tissues, highest levels in brain and testis, lowest levels in peripheral blood cells.
messages: telomere

9606:HEPN1
gene id: 9606:HEPN1
uniprot id: Q6WQI6
names: Caution
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Cytoplasm
messages: Expressed in liver. Expression is either down-regulated or lost in hepatocellular carcinomas (HCC).
messages: Product of a dubious CDS prediction. Encoded by the 3'-UTR of HEPACAM.

9606:GCNT2
gene id: 9606:GCNT2
uniprot id: Q8N0V5
names: Developmental Stage
names: Disease Annotation
names: Function
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the glycosyltransferase 14 family.
messages: Branching enzyme that converts linear into branched poly-N-acetyllactosaminoglycans. Introduces the blood group I antigen during embryonic development. It is closely associated with the development and maturation of erythroid cells.
messages: Determines the expression of the blood group I antigen in erythrocytes.
messages: Expressed in lens epithelium cells.
messages: Expressed in reticulocytes.
messages: Expression increases dramatically during development and oncogenesis.
messages: GCNT2 is involved in determining the blood group I system (Ii) [MIM:110800]. The i (fetal) and I (adult) antigens are determined by linear and branched poly-N-acetyllactosaminoglycans, respectively. A replacement during development of i by I is dependent on the appearance of a beta-1,6-N-acetylglucosaminyltransferase, the I-branching enzyme. The expression of the blood group I antigen in erythrocytes is determined by isoform C of GCNT2.
messages: Golgi apparatus membrane
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:TMEM131L
gene id: 9606:TMEM131L
uniprot id: A2VDJ0
names: Developmental Stage
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the TMEM131 family.
messages: Cell membrane
messages: Cytoplasm
messages: During intrathymic development, transcript levels strongly increase from pro-DN1 thymocytes to DN3a cells, in which they peak, and drop immediately after beta-selection in their DN3b successors. The subcellular location of the protein also varies, from punctate cytoplasmic structures in DN1 and DN2 cells to large crescent-shaped membrane structures in DN3 cells, which preferentially localize in cell-to-cell contact zones.
messages: Endoplasmic reticulum
messages: Expressed in thymocytes.
messages: Membrane-associated form that antagonizes canonical Wnt signaling by triggering lysosome-dependent degradation of Wnt-activated LRP6. Regulates thymocyte proliferation.

9606:FRRS1L
gene id: 9606:FRRS1L
uniprot id: Q9P0K9
names: Caution
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cell membrane
messages: Component of the outer core of AMPAR complex. AMPAR complex consists of an inner core made of 4 pore-forming GluA/GRIA proteins (GRIA1, GRIA2, GRIA3 and GRIA4) and 4 major auxiliary subunits arranged in a twofold symmetry. One of the two pairs of distinct binding sites is occupied either by CNIH2, CNIH3 or CACNG2, CACNG3. The other harbors CACNG2, CACNG3, CACNG4, CACNG8 or GSG1L. This inner core of AMPAR complex is complemented by outer core constituents binding directly to the GluA/GRIA proteins at sites distinct from the interaction sites of the inner core constituents. Outer core constituents include at least PRRT1, PRRT2, CKAMP44/SHISA9, FRRS1L and NRN1. The proteins of the inner and outer core serve as a platform for other, more peripherally associated AMPAR constituents. Alone or in combination, these auxiliary subunits control the gating and pharmacology of the AMPAR complex and profoundly impact their biogenesis and protein processing (By similarity).
messages: Expressed in adult and fetal brain. Very weak expression in medulla, spinal cord and in adult ovary.
messages: Important modulator of glutamate signaling pathway.
messages: Named FRRS1L by HGNC because it shares limited sequence similarity with FRRS1. However, sequence similarities lie outside of the reductase region, suggesting it has no oxidoreductase activity.
messages: Synapse
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:FECH
gene id: 9606:FECH
uniprot id: P22830
uniprot id: Q7KZA3
names: Activity Regulation
names: Cofactor
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the ferrochelatase family.
messages: Binds 1 [2Fe-2S] cluster.
messages: Catalyzes the ferrous insertion into protoporphyrin IX.
messages: Homodimer (PubMed:17261801, PubMed:30765471). Interacts with PGRMC1; the interaction results in decreased FECH activity (PubMed:27599036). Interacts with ABCB10 and SLC25A37; this interaction forms an oligomeric complex (By similarity). Forms a complex with ABCB7 and ABCB10, where a dimeric FECH bridges ABCB7 and ABCB10 homodimers; this complex may be required for cellular iron homeostasis, mitochondrial function and heme biosynthesis (PubMed:30765471). Interacts with ABCB7 and ABCB10 (PubMed:30765471).
messages: Inhibited by nitric oxide (NO). The 2Fe-2S cluster could act as a NO sensor.
messages: Mitochondrion inner membrane
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:PRDM14
gene id: 9606:PRDM14
uniprot id: Q9GZV8
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the class V-like SAM-binding methyltransferase superfamily.
messages: Expressed in embryonic stem cells. Tends to be overexpressed in breast cancer (at protein level).
messages: Interacts with CBFA2T2.
messages: Nucleus
messages: The first 5 zinc fingers, but not the last one, are required for DNA-binding and transcriptional activity.
messages: Transcription factor that has both positive and negative roles on transcription. Required for the maintenance of embryonic stem cell identity and the reacquisition of pluripotency in somatic cells. May play an essential role in germ cell development at 2 levels: the reacquisition of potential pluripotency, including SOX2 up-regulation, and successful epigenetic reprogramming, characterized by EHMT1 repression. Its association with CBFA2T2 is required for the functions in pluripotency and germ cell formation (By similarity). Directly up-regulates the expression of pluripotency gene POU5F1 through its proximal enhancer. Binds to the DNA consensus sequence 5'-GGTC[TC]CTAA-3'.

9606:NFKBIZ
gene id: 9606:NFKBIZ
uniprot id: Q9BYH8
names: Function
names: Induction
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: By TNF, IL1/interleukin-1 and bacterial lipopolysaccharides (LPS).
messages: Expressed at high levels in peripheral blood leukocytes and lung, at moderate levels in liver, placenta, and at low levels in spleen, kidney, skeletal muscle and heart.
messages: Interacts with NFKB1/p50 (PubMed:16513645). Interacts with RELA (PubMed:16513645). Interacts with AKIRIN2 (By similarity).
messages: Involved in regulation of NF-kappa-B transcription factor complexes (PubMed:16513645, PubMed:16622025). Inhibits NF-kappa-B activity without affecting its nuclear translocation upon stimulation (PubMed:16513645). Inhibits DNA-binding of RELA and NFKB1/p50, and of the NF-kappa-B p65-p50 heterodimer and the NF-kappa-B p50-p50 homodimer (PubMed:16513645). Seems also to activate NF-kappa-B-mediated transcription (PubMed:16622025). In vitro, upon association with NFKB1/p50 has transcriptional activation activity and, together with NFKB1/p50 and RELA, is recruited to LCN2 promoters (PubMed:16622025). Promotes transcription of LCN2 and DEFB4 (PubMed:16622025). Is recruited to IL-6 promoters and activates IL-6 but decreases TNF-alpha production in response to LPS (By similarity). Seems to be involved in the induction of inflammatory genes activated through TLR/IL-1 receptor signaling (By similarity). Involved in the induction of T helper 17 cells (Th17) differentiation upon recognition of antigen by T cell antigen receptor (TCR) (By similarity).
messages: Nucleus

9606:PSME3IP1
gene id: 9606:PSME3IP1
uniprot id: Q9GZU8
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: Interacts (via C-terminus) with both free and 20S proteasome-bound forms of the proteasome activator complex subunit PSME3; the interaction is direct.
messages: Nucleus
messages: Phosphorylation by CK2 stabilizes the interaction with PSME3.
messages: Promotes the association of the proteasome activator complex subunit PSME3 with the 20S proteasome and regulates its activity. Inhibits PSME3-mediated degradation of some proteasome substrates, probably by affecting their diffusion rate into the catalytic chamber of the proteasome. Also inhibits the interaction of PSME3 with COIL, inhibits accumulation of PSME3 in Cajal bodies and positively regulates the number of Cajal bodies in the nucleus.

9606:F2RL1
gene id: 9606:F2RL1
uniprot id: P55085
names: Activity Regulation
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: A proteolytic cleavage generates a new N-terminus that functions as a tethered ligand (PubMed:10831593, PubMed:19864598, PubMed:9020112, PubMed:10805786, PubMed:16478888). Activating serine proteases include trypsin, mast cell tryptase, coagulation factors VII and Xa, myeloblastin/PRTN3 and membrane-type serine protease 1/ST14 (PubMed:10831593, PubMed:19864598, PubMed:9020112, PubMed:10805786, PubMed:16478888, PubMed:23202369). Subsequent cleavage by serine proteases, including neutrophil elastase and cathepsin G, leads to receptor deactivation (PubMed:12594060). At least in part, implicated proteases are also shown to activate the receptor; the glycosylation status of the receptor is thought to contribute to the difference (PubMed:12171601). In addition to conventional trypsin-like proteases activated by other proteases and glycosidases derived from bacteria, fungi and insects (PubMed:11447194, PubMed:11441110, PubMed:17404307, PubMed:18474671, PubMed:19864598). Activated by serine protease allergens such as dust mite Der p3 and Der p9 and mold Pen c13 (PubMed:11441110, PubMed:17404307). Activated by P.gingivalis arginine-specific (trypsin-like) cysteine proteinases called gingipains (PubMed:11447194). Activated by S.griseus exogenous chitinase (PubMed:18474671). Activated by A.alternata aspartate protease; the cleavage generates non-conventional processed forms (PubMed:19864598).
messages: Activated upon interaction by mucunain, a cowhage (Mucuna pruriens) plant cysteine proteinase.
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Interacts with TLR4, COPS5 and TMED2. Interacts with GNAQ, GNA11, GNA12, GNA13 and GNA14 (By similarity).
messages: Monoubiquitinated by CBL at the plasma membrane and in early endosomes; not required for receptor endocytosis but for translocation to late endosomes or lysosomes. Deubiquitination involves STAMBP and USP8; required for lysosomal trafficking and receptor degradation.
messages: Multiple phosphorylated on serine and threonine residues in the cytoplasmic region upon receptor activation; required for receptor desensitization and recruitment of beta-arrestin.
messages: N-glycosylated and sialylated.
messages: Receptor for trypsin and trypsin-like enzymes coupled to G proteins (PubMed:28445455). Its function is mediated through the activation of several signaling pathways including phospholipase C (PLC), intracellular calcium, mitogen-activated protein kinase (MAPK), I-kappaB kinase/NF-kappaB and Rho (PubMed:28445455). Can also be transactivated by cleaved F2R/PAR1. Involved in modulation of inflammatory responses and regulation of innate and adaptive immunity, and acts as a sensor for proteolytic enzymes generated during infection. Generally is promoting inflammation. Can signal synergistically with TLR4 and probably TLR2 in inflammatory responses and modulates TLR3 signaling. Has a protective role in establishing the endothelial barrier; the activity involves coagulation factor X. Regulates endothelial cell barrier integrity during neutrophil extravasation, probably following proteolytic cleavage by PRTN3 (PubMed:23202369). Proposed to have a bronchoprotective role in airway epithelium, but also shown to compromise the airway epithelial barrier by interrupting E-cadherin adhesion (PubMed:10086357). Involved in the regulation of vascular tone; activation results in hypotension presumably mediated by vasodilation. Associates with a subset of G proteins alpha subunits such as GNAQ, GNA11, GNA14, GNA12 and GNA13, but probably not with G(o)-alpha, G(i) subunit alpha-1 and G(i) subunit alpha-2. However, according to PubMed:21627585 can signal through G(i) subunit alpha. Believed to be a class B receptor which internalizes as a complex with arrestin and traffic with it to endosomal vesicles, presumably as desensitized receptor, for extended periods of time. Mediates inhibition of TNF-alpha stimulated JNK phosphorylation via coupling to GNAQ and GNA11; the function involves dissociation of RIPK1 and TRADD from TNFR1. Mediates phosphorylation of nuclear factor NF-kappa-B RELA subunit at 'Ser-536'; the function involves IKBKB and is predominantly independent of G proteins. Involv…
messages: Synthetic PAR agonist peptides (APs) that mimic the first six amino acids of the newly formed N-terminus activate the native, uncleaved receptor nonenzymatically by binding directly to the corresponding second extracellular loop to mediate signaling.
messages: Widely expressed in tissues with especially high levels in pancreas, liver, kidney, small intestine, and colon (PubMed:7556175, PubMed:8615752). Moderate expression is detected in many organs, but none in brain or skeletal muscle (PubMed:7556175, PubMed:8615752). Expressed in endothelial cells (PubMed:23202369).

9606:AIMP2
gene id: 9606:AIMP2
uniprot id: A8MU58
uniprot id: Q13155
names: Disease Annotation
names: Function
names: Miscellaneous
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: Accumulates in brains affected by autosomal-recessive juvenile parkinsonism, idiopathic Parkinson disease and diffuse Lewy body disease.
messages: Nucleus
messages: Part of the multisynthetase complex (MSC), a multisubunit complex that groups tRNA ligases for Arg (RARS1), Asp (DARS1), Gln (QARS1), Ile (IARS1), Leu (LARS1), Lys (KARS1), Met (MARS1) the bifunctional ligase for Glu and Pro (EPRS1) and the auxiliary subunits AIMP1/p43, AIMP2/p38 and EEF1E1/p18 (PubMed:24312579, PubMed:19131329, PubMed:19289464). Interacts (via N-terminus) with KARS1 (PubMed:9878398, PubMed:15220430, PubMed:18029264, PubMed:23159739, PubMed:26074468). Interacts with EPRS1 (PubMed:26472928). Forms a linear complex that contains MARS1, EEF1E1, EPRS1 and AIMP2 that is at the core of the multisubunit complex (PubMed:26472928). Binds FUBP1 (via C-terminus). Interacts in both its unphosphorylated and phosphorylated forms with p53/TP53 (via N-terminus) in the nucleus following UV irradiation. Interacts (via N-terminus) with PRKN/parkin (via first RING-type domain) (PubMed:16135753). Interacts with TARS3 (PubMed:24312579).
messages: Phosphorylated on serine residues in response to UV irradiation.
messages: Required for assembly and stability of the aminoacyl-tRNA synthase complex (PubMed:19131329). Mediates ubiquitination and degradation of FUBP1, a transcriptional activator of MYC, leading to MYC down-regulation which is required for aveolar type II cell differentiation. Blocks MDM2-mediated ubiquitination and degradation of p53/TP53. Functions as a proapoptotic factor.
messages: The disease may be caused by variants affecting the gene represented in this entry.
messages: Ubiquitinated by PRKN, leading to its degradation by the proteasome. Mutant PRKN fails to ubiquitinate AIMP2 efficiently, allowing its accumulation which may contribute to neurodegeneration associated with Parkinson disease.
messages: cytosol

9606:SAT1
gene id: 9606:SAT1
uniprot id: P21673
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the acetyltransferase family.
messages: Enzyme which catalyzes the acetylation of polyamines (PubMed:15283699, PubMed:16455797, PubMed:17516632). Substrate specificity: norspermidine = spermidine >> spermine > N(1)-acetylspermine (PubMed:17516632). This highly regulated enzyme allows a fine attenuation of the intracellular concentration of polyamines (PubMed:16455797). Also involved in the regulation of polyamine transport out of cells (PubMed:16455797). Also acts on 1,3-diaminopropane and 1,5-diaminopentane (PubMed:16455797, PubMed:17516632).
messages: Homodimer.
messages: Overexpression of SAT1 and the consequent putrescine accumulation might play a role in the pathogenesis of keratosis follicularis spinulosa decalvans.
messages: cytosol

9606:CT45A6
gene id: 9606:CT45A6
uniprot id: P0DMU7
uniprot id: P0DMU8
uniprot id: P0DMV0
names: Similarity
names: Tissue Specificity
messages: Belongs to the CT45 family.
messages: Testis specific. Expressed in cancer cell lines.

9606:NDUFA11
gene id: 9606:NDUFA11
uniprot id: Q86Y39
names: Disease Annotation
names: Function
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone.
messages: Belongs to the complex I NDUFA11 subunit family.
messages: Complex I is composed of 45 different subunits.
messages: Erroneous CDS prediction.
messages: Mitochondrion inner membrane
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:ABTB2
gene id: 9606:ABTB2
uniprot id: Q8N961
names: Function
messages: May be involved in the initiation of hepatocyte growth.

9606:AP2A2
gene id: 9606:AP2A2
uniprot id: O94973
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Adaptor protein complex 2 (AP-2) is a heterotetramer composed of two large adaptins (alpha-type subunit AP2A1 or AP2A2 and beta-type subunit AP2B1), a medium adaptin (mu-type subunit AP2M1) and a small adaptin (sigma-type subunit AP2S1). Binds EPN1, EPS15, AMPH, SNAP91 and BIN1 (By similarity). Interacts with HIP1 (PubMed:11532990). Interacts with DGKD (By similarity). Interacts with DENND1A, DENND1B and DENND1C (By similarity). Interacts with FCHO1 and DAB2 (PubMed:22484487). Interacts with ATAT1; this interaction is required for efficient alpha-tubulin acetylation by ATAT1 (PubMed:24097348). Interacts with KIAA1107 (PubMed:29262337). Together with AP2B1 and AP2M1, it interacts with ADAM10; this interaction facilitates ADAM10 endocytosis from the plasma membrane during long-term potentiation in hippocampal neurons (PubMed:23676497). Interacts with CLN3 (via dileucine motif) (PubMed:15598649). Interacts with ABCB11; this interaction regulates cell membrane expression of ABCB11 through its internalization in a clathrin-dependent manner and its subsequent degradation (PubMed:22262466).
messages: Belongs to the adaptor complexes large subunit family.
messages: Cell membrane
messages: Component of the adaptor protein complex 2 (AP-2). Adaptor protein complexes function in protein transport via transport vesicles in different membrane traffic pathways. Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation. AP-2 is involved in clathrin-dependent endocytosis in which cargo proteins are incorporated into vesicles surrounded by clathrin (clathrin-coated vesicles, CCVs) which are destined for fusion with the early endosome. The clathrin lattice serves as a mechanical scaffold but is itself unable to bind directly to membrane components. Clathrin-associated adaptor protein (AP) complexes which can bind directly to both the clathrin lattice and to the lipid and protein components of membranes are considered to be the major clathrin adaptors contributing the CCV formation. AP-2 also serves as a cargo receptor to selectively sort the membrane proteins involved in receptor-mediated endocytosis. AP-2 seems to play a role in the recycling of synaptic vesicle membranes from the presynaptic surface. AP-2 recognizes Y-X-X-[FILMV] (Y-X-X-Phi) and [ED]-X-X-X-L-[LI] endocytosis signal motifs within the cytosolic tails of transmembrane cargo molecules. AP-2 may also play a role in maintaining normal post-endocytic trafficking through the ARF6-regulated, non-clathrin pathway. During long-term potentiation in hippocampal neurons, AP-2 is responsible for the endocytosis of ADAM10 (PubMed:23676497). The AP-2 alpha subunit binds polyphosphoinositide-containing lipids, positioning AP-2 on the membrane. The AP-2 alpha subunit acts via its C-terminal appendage domain as a scaffolding platform for endocytic accessory proteins. The AP-2 alpha and AP-2 sigma subunits are thought to contribute to the recognition of the [ED]-X-X-X-L-[LI] motif (By similarity).
messages: Expressed in the brain (at protein level).
messages: coated pit

9606:SLC27A6
gene id: 9606:SLC27A6
uniprot id: B2R8P6
uniprot id: Q9Y2P4
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the ATP-dependent AMP-binding enzyme family.
messages: Cell membrane
messages: Mediates the import of long-chain fatty acids (LCFA) into the cell by facilitating their transport at the plasma membrane (PubMed:12556534). Also functions as an acyl-CoA ligase catalyzing the ATP-dependent formation of fatty acyl-CoA using LCFA and very-long-chain fatty acids (VLCFA) as substrates (By similarity). Plays a pivotal role in regulating available LCFA substrates from exogenous sources in tissues undergoing high levels of beta-oxidation such as the heart (PubMed:12556534).
messages: Strongly expressed in heart and localizes to cardiac myocytes (PubMed:12556534). Expressed at moderate levels in placenta, testis, and adrenal glands. Expressed at very low levels in kidney, bladder and uterus.
messages: sarcolemma

9606:CCER2
gene id: 9606:CCER2
uniprot id: I3L3R5
names: Caution
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Despite its name, does not contain a real coiled coil domain region: predicted coiled coil regions are the result of the Glu-rich region.
messages: Expressed at higher levels in fetal brain and skeletal muscle. Lower expression is detected in fetal kidney, liver, spleen, thymus, heart and lung.
messages: Secreted

9606:SLC37A1
gene id: 9606:SLC37A1
uniprot id: P57057
names: Activity Regulation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the major facilitator superfamily. Organophosphate:Pi antiporter (OPA) (TC 2.A.1.4) family.
messages: Endoplasmic reticulum membrane
messages: Expressed in numerous tissues, with highest expression in pancreas, kidney, bone marrow, spleen, liver, small intestine, as well as in fetal brain, liver and spleen.
messages: Inhibited by vanadate but not by chlorogenic acid.
messages: Inorganic phosphate and glucose-6-phosphate antiporter. May transport cytoplasmic glucose-6-phosphate into the lumen of the endoplasmic reticulum and translocate inorganic phosphate into the opposite direction. Independent of a lumenal glucose-6-phosphatase. May not play a role in homeostatic regulation of blood glucose levels.

9606:PALD1
gene id: 9606:PALD1
uniprot id: Q9ULE6
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the paladin family.
messages: Expressed in endothelial cells, and in certain larger vessels, in mural cells. In the brain, possibly expressed in microglia. Expressed in peripheral blood mononuclear cells (at protein level).
messages: cytosol

9606:AHSG
gene id: 9606:AHSG
uniprot id: P02765
names: Disease Annotation
names: Function
names: PTM
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Alpha-2-HS glycoprotein derives from this precursor, when the connecting peptide is cleaved off. The two chains A and B are held together by a single disulfide bond.
messages: Belongs to the fetuin family.
messages: O- and N-glycosylated. O-glycosylated with core 1 or possibly core 8 glycans. N-glycan at Asn-156: Hex5HexNAc4; N-glycan heterogeneity at Asn-176: Hex5HexNAc4 (major) and Hex6HexNAc5 (minor).
messages: Phosphorylated by FAM20C in the extracellular medium.
messages: Promotes endocytosis, possesses opsonic properties and influences the mineral phase of bone. Shows affinity for calcium and barium ions.
messages: Secreted
messages: Synthesized in liver and selectively concentrated in bone matrix. Secreted in plasma. It is also found in dentin in much higher quantities than other plasma proteins.
messages: The disease may be caused by variants affecting the gene represented in this entry.
messages: There are two common alleles, AHSG*1 and AHSG*2. AHSG*1 has Thr-248/Thr-256; AHSG*2 has Met-248/Ser-256.

9606:ONECUT2
gene id: 9606:ONECUT2
uniprot id: O95948
names: Caution
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the CUT homeobox family.
messages: It is uncertain whether Met-1 or Met-20 is the initiator.
messages: Nucleus
messages: Transcriptional activator. Activates the transcription of a number of liver genes such as HNF3B.

9606:BUD13
gene id: 9606:BUD13
uniprot id: Q9BRD0
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the CWC26 family.
messages: Involved in pre-mRNA splicing as component of the activated spliceosome. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable).
messages: Nucleus
messages: Part of the activated spliceosome B/catalytic step 1 spliceosome, one of the forms of the spliceosome which has a well-formed active site but still cannot catalyze the branching reaction and is composed of at least 52 proteins, the U2, U5 and U6 snRNAs and the pre-mRNA. Component of the minor spliceosome, which splices U12-type introns (PubMed:33509932).

9606:RNFT1
gene id: 9606:RNFT1
uniprot id: Q5M7Z0
names: Function
names: Induction
names: Miscellaneous
names: Subcellular Location Annotation
names: Tissue Specificity
messages: E3 ubiquitin-protein ligase that acts in the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway, which targets misfolded proteins that accumulate in the endoplasmic reticulum (ER) for ubiquitination and subsequent proteasome-mediated degradation. Protects cells from ER stress-induced apoptosis.
messages: Endoplasmic reticulum membrane
messages: Expressed at highest levels in testis, lower levels in heart, liver, lung, and kidney (PubMed:17074343). Not detected in brain, ovary, and uterus (PubMed:17074343). Down-regulated in testis from patients with maturation arrest (MA) or Sertoli cell-only syndrome (SCOS) (PubMed:17074343). Ubiquitously expressed with high expression in testis (PubMed:27485036).
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Up-regulated by endoplasmic reticulum (ER) stress triggered by thapsigargin or tunicamycin.

9606:KCNAB2
gene id: 9606:KCNAB2
uniprot id: B2R776
uniprot id: Q13303
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the shaker potassium channel beta subunit family.
messages: Cell membrane
messages: Cytoplasm
messages: Cytoplasmic potassium channel subunit that modulates the characteristics of the channel-forming alpha-subunits (PubMed:7649300, PubMed:11825900). Contributes to the regulation of nerve signaling, and prevents neuronal hyperexcitability (By similarity). Promotes expression of the pore-forming alpha subunits at the cell membrane, and thereby increases channel activity (By similarity). Promotes potassium channel closure via a mechanism that does not involve physical obstruction of the channel pore (PubMed:7649300, PubMed:11825900). Promotes KCNA4 channel closure (PubMed:7649300, PubMed:11825900). Modulates the functional properties of KCNA5 (By similarity). Enhances KCNB2 channel activity (By similarity). Binds NADPH and has NADPH-dependent aldoketoreductase activity (By similarity). Has broad substrate specificity and can catalyze the reduction of methylglyoxal, 9,10-phenanthrenequinone, prostaglandin J2, 4-nitrobenzaldehyde, 4-nitroacetophenone and 4-oxo-trans-2-nonenal (in vitro) (By similarity).
messages: Detected in myelinated nerve fibers in the spinal cord, in the juxtaparanodal region of the nodes of Ranvier, but also in the paranodal region (PubMed:11086297). Detected in hippocampus (at protein level) (PubMed:21357749). Detected in hippocampus (PubMed:7649300).
messages: Homotetramer (By similarity). Interaction with tetrameric potassium channel alpha subunits gives rise to a heterooctamer (By similarity). Identified in potassium channel complexes containing KCNA1, KCNA2, KCNA4, KCNA5, KCNA6, KCNAB1 and KCNAB2 (By similarity). Interacts with KCNA1 (PubMed:11086297). Interacts with KCNA2 (PubMed:11086297). Interacts with KCNA4 and KCND3 (By similarity). Interacts with KCNA5 (By similarity). Interacts with KCNB2 (By similarity). Interacts (in unphosphorylated form) with MAPRE1 (By similarity). Forms a ternary complex with SQSTM1 and PRKCZ (By similarity).
messages: In contrast to KCNAB1, the shorter N-terminal domain of KCNAB2 cannot mediate closure of delayed rectifier potassium channels by physically obstructing the pore.
messages: Membrane
messages: Phosphorylated by PRKCZ; may be regulated by incorporation in a complex composed of PRKCZ and SQSTM1.
messages: axon
messages: cytoskeleton
messages: synaptosome

9606:SNX10
gene id: 9606:SNX10
uniprot id: B4DJM0
uniprot id: Q8N5Z3
uniprot id: Q9Y5X0
names: Disease Annotation
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the sorting nexin family.
messages: Cytoplasm
messages: Endosome membrane
messages: Interacts with ATP6V1D; may play a role in ciliogenesis.
messages: Membrane
messages: Probable phosphoinositide-binding protein involved in protein sorting and membrane trafficking in endosomes. Plays a role in cilium biogenesis through regulation of the transport and the localization of proteins to the cilium. Required for the localization to the cilium of V-ATPase subunit ATP6V1D and ATP6V0D1, and RAB8A. Involved in osteoclast differentiation and therefore bone resorption.
messages: The PX domain mediates interaction with membranes enriched in phosphatidylinositol 3-phosphate.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: centrosome

9606:PRSS53
gene id: 9606:PRSS53
uniprot id: Q2L4Q9
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the peptidase S1 family.
messages: In vitro can degrade the fibrinogen alpha chain of as well as pro-urokinase-type plasminogen activator.
messages: Predominantly detected in testis, liver, heart and ovary, as well as in several tumor cell lines.
messages: Secreted

9606:PPP2CA
gene id: 9606:PPP2CA
uniprot id: B3KUN1
uniprot id: P67775
names: Cofactor
names: Disease Annotation
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the PPP phosphatase family.
messages: Belongs to the PPP phosphatase family. PP-1 subfamily.
messages: Binds 2 manganese ions per subunit.
messages: Catalytically inactive, shows enhanced binding to IGBP1, and does not interact with the scaffolding subunit PPP2R1A.
messages: Cytoplasm
messages: Nucleus
messages: PP2A consists of a common heterodimeric core enzyme, composed of PPP2CA a 36 kDa catalytic subunit (subunit C) and PPP2R1A a 65 kDa constant regulatory subunit (PR65 or subunit A), that associates with a variety of regulatory subunits (PubMed:17055435, PubMed:18394995, PubMed:30595372). Proteins that associate with the core dimer include three families of regulatory subunits B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56 families), the 48 kDa variable regulatory subunit, viral proteins, and cell signaling molecules (PubMed:18394995, PubMed:30595372). Interacts with NXN; the interaction is direct (By similarity). Interacts with KCTD20 (By similarity). Interacts with BTBD10 (By similarity). Interacts with SGO1 and SGO2 (PubMed:16580887, PubMed:16541025, PubMed:17485487). Interacts with TP53 (PubMed:17245430). Interacts with AXIN1; the interaction dephosphorylates AXIN1 (PubMed:9920888). Interacts with PIM3; this interaction promotes dephosphorylation, ubiquitination and proteasomal degradation of PIM3 (PubMed:12473674). Interacts with RAF1 (PubMed:10801873). Interaction with IGBP1 protects unassembled PPP2CA from degradative ubiquitination (PubMed:9647778, PubMed:19818709, PubMed:20092282). Interacts with GSK3B (via C2 domain) (PubMed:20080667). Interacts with MFHAS1; retains PPP2CA into the cytoplasm and excludes it from the nucleus (PubMed:28609714). Interacts with PABIR1/FAM122A (PubMed:27588481). Interacts with ADCY8; interaction is phosphatase activity-dependent; antagonizes interaction between ADCY8 and calmodulin (PubMed:16258073). Interacts with CRTC3 (when phosphorylated at 'Ser-391') (PubMed:30611118). Interacts with SPRY2; the interaction is inhibited by TESK1 interaction with SPRY2, possibly by vesicular sequestration of SPRY2 (PubMed:17974561). Interacts with TRAF3IP3 (PubMed:30115741). Interacts with AMBRA1 (via PxP motifs); enhancing interaction between PPP2CA and MYC or FOXO3 (PubMed:25438055, PubMed:30513302). Forms a complex with AMBRA1 a…
messages: PP2A is the major phosphatase for microtubule-associated proteins (MAPs) (PubMed:22613722). PP2A can modulate the activity of phosphorylase B kinase casein kinase 2, mitogen-stimulated S6 kinase, and MAP-2 kinase (PubMed:22613722). Cooperates with SGO2 to protect centromeric cohesin from separase-mediated cleavage in oocytes specifically during meiosis I (By similarity). Can dephosphorylate SV40 large T antigen and p53/TP53 (PubMed:17245430). Activates RAF1 by dephosphorylating it at 'Ser-259' (PubMed:10801873). Mediates dephosphorylation of WEE1, preventing its ubiquitin-mediated proteolysis, increasing WEE1 protein levels, and promoting the G2/M checkpoint (PubMed:33108758). Mediates dephosphorylation of MYC; promoting its ubiquitin-mediated proteolysis: interaction with AMBRA1 enhances interaction between PPP2CA and MYC (PubMed:25438055). Mediates dephosphorylation of FOXO3; promoting its stabilization: interaction with AMBRA1 enhances interaction between PPP2CA and FOXO3 (PubMed:30513302). Catalyzes dephosphorylation of the pyrin domain of NLRP3, promoting assembly of the NLRP3 inflammasome (By similarity).
messages: Phosphorylation of either threonine (by autophosphorylation-activated protein kinase) or tyrosine results in inactivation of the phosphatase. Auto-dephosphorylation has been suggested as a mechanism for reactivation.
messages: Polyubiquitinated, leading to its degradation by the proteasome.
messages: Reversibly methyl esterified on Leu-309 by leucine carboxyl methyltransferase 1 (LCMT1) and protein phosphatase methylesterase 1 (PPME1). Carboxyl methylation influences the affinity of the catalytic subunit for the different regulatory subunits, thereby modulating the PP2A holoenzyme's substrate specificity, enzyme activity and cellular localization.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: centromere
messages: spindle pole

9606:HBG2
gene id: 9606:HBG2
uniprot id: D9YZU9
uniprot id: P69892
names: Developmental Stage
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Acetylation of Gly-2 converts Hb F to the minor Hb F1.
messages: Belongs to the globin family.
messages: Expressed until four or five weeks after birth.
messages: Gamma chains make up the fetal hemoglobin F, in combination with alpha chains.
messages: Heterotetramer of two alpha chains and two gamma chains in fetal hemoglobin (Hb F).
messages: Red blood cells.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:ZNG1C
gene id: 9606:ZNG1C
uniprot id: A0A0A6YYH9
uniprot id: Q5JTY5
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the SIMIBI class G3E GTPase family. ZNG1 subfamily.
messages: Nucleus
messages: Zinc chaperone that directly transfers zinc cofactor to target metalloproteins, thereby activating them. Catalyzes zinc insertion into the active site of methionine aminopeptidase METAP1, which function to cleave the initiator methionine from polypeptides during or after protein translation. Mechanistically, the N-terminal psi-PxLVp motif binds to the C6H2-type zinc finger of inactive form of METAP1. After formation of the docked complex, zinc is transferred from the CXCC motif in the GTPase domain of ZNG1C to the zinc binding site in the peptidase domain of METAP1 in a process requiring GTP hydrolysis. GTP/GDP exchange is required for release of active METAP1.

9606:UBXN7
gene id: 9606:UBXN7
uniprot id: O94888
names: Domain
names: Function
names: Sequence Caution
names: Subcellular Location Annotation
names: Subunit
messages: Interacts with neddylated CUL2, ubiquitinated HIF1A, and VCP/p97.
messages: Nucleus
messages: The UBA domain is required for binding ubiquitinated-protein substrates.
messages: The UBX domain mediates interaction with VCP/p97.
messages: The UIM (ubiquitin-interacting motif) is required to engage the NEDD8 modification on cullins.
messages: Ubiquitin-binding adapter that links a subset of NEDD8-associated cullin ring ligases (CRLs) to the segregase VCP/p97, to regulate turnover of their ubiquitination substrates.
messages: Unlikely isoform. Aberrant splice sites.

9606:DLG4
gene id: 9606:DLG4
uniprot id: P78352
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the MAGUK family.
messages: Brain.
messages: Cell membrane
messages: Cytoplasm
messages: Interacts through its PDZ domains with ANO2 and NETO1 (By similarity). Interacts through its first two PDZ domains with GRIN2A, GRIN2B, GRIN2C, GRIN2D (By similarity). Interacts with ASIC3 (By similarity). Interacts with SEMA4C (By similarity). Interacts with CXADR (By similarity). Interacts with KCND2 (By similarity). Interacts with SYNGAP1 (By similarity). Interacts with LRRC4 and LRRC4B (By similarity). Interacts with ERBB4 (PubMed:10725395). Interacts with KCNA1, KCNA2, KCNA3 and KCNA4 (PubMed:7477295). Interacts through its first PDZ domain with GRIK2, KCNA4 and CRIPT (PubMed:11744724). Interacts through its second PDZ domain with the PDZ domain of NOS1 or the C-terminus of CAPON (By similarity). Interacts through its third PDZ domain with NLGN1 and CRIPT, and probably with NLGN2 and NLGN3 (PubMed:9278515). Interacts through its guanylate kinase-like domain with KIF13B (PubMed:10859302). Interacts through its guanylate kinase-like domain with DLGAP1/GKAP, DLGAP2, DLGAP3, DLGAP4, MAP1A, BEGAIN and SIPA1L1 (By similarity). Isoform 2 interacts through an L27 domain with HGS/HRS and the first L27 domain of CASK (PubMed:12151521). Interacts with ADR1B and ANKS1B (By similarity). May interact with HTR2A (By similarity). Interacts with ADAM22 (PubMed:27066583). Interacts with KLHL17 and LGI1 (By similarity). Interacts with FRMPD4 (via C-terminus) (PubMed:19118189). Interacts with LRFN1, LRFN2 and LRFN4 (PubMed:16630835). Interacts (via N-terminal tandem pair of PDZ domains) with GPER1 (via C-terminus tail motif); the interaction is direct and induces the increase of GPER1 protein levels residing at the plasma membrane surface in a estradiol-independent manner (By similarity). Interacts (via N-terminus tandem pair of PDZ domains) with NOS1 (via N-terminal domain) (By similarity). Interacts with SHANK3 (By similarity). Interacts with KCNJ4 (By similarity). Interacts with GPR85 (PubMed:25780553). Interacts with CACNG2 and MPP2 (via the SH3-Guanylate kinase-like sub-modul…
messages: Palmitoylated (PubMed:26701913). Palmitoylation is required for targeting to postsynaptic density, plasma membrane and synapses (By similarity). Palmitoylation by ZDHHC2 occurs when the synaptic activity decreases and induces DLG4 synaptic clustering (By similarity). Palmitoylation by ZDHHC15 regulates trafficking to the postsynaptic density and function in synaptogenesis (By similarity). Palmitoylation may play a role in glutamate receptor GRIA1 synapse clustering (By similarity). Depalmitoylated by ABHD17A and ABHD17B and to a lesser extent by ABHD17C, ABHD12, ABHD13, LYPLA1 and LYPLA2 (PubMed:26701913). Undergoes rapid synaptic palmitoylation/depalmitoylation cycles during neuronal development which slow down in mature neurons (By similarity).
messages: Postsynaptic density
messages: Postsynaptic scaffolding protein that plays a critical role in synaptogenesis and synaptic plasticity by providing a platform for the postsynaptic clustering of crucial synaptic proteins. Interacts with the cytoplasmic tail of NMDA receptor subunits and shaker-type potassium channels. Required for synaptic plasticity associated with NMDA receptor signaling. Overexpression or depletion of DLG4 changes the ratio of excitatory to inhibitory synapses in hippocampal neurons. May reduce the amplitude of ASIC3 acid-evoked currents by retaining the channel intracellularly. May regulate the intracellular trafficking of ADR1B. Also regulates AMPA-type glutamate receptor (AMPAR) immobilization at postsynaptic density keeping the channels in an activated state in the presence of glutamate and preventing synaptic depression (By similarity). Under basal conditions, cooperates with FYN to stabilize palmitoyltransferase ZDHHC5 at the synaptic membrane through FYN-mediated phosphorylation of ZDHHC5 and its subsequent inhibition of association with endocytic proteins (PubMed:26334723).
messages: Presynapse
messages: Synapse
messages: The L27 domain near the N-terminus of isoform 2 is required for HGS/HRS-dependent targeting to postsynaptic density.
messages: The PDZ domain 3 mediates interaction with ADR1B.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitinated by MDM2 in response to NMDA receptor activation, leading to proteasome-mediated degradation of DLG4 which is required for AMPA receptor endocytosis.
messages: axon
messages: dendrite
messages: dendritic spine

9606:IL1RAP
gene id: 9606:IL1RAP
uniprot id: A8K6K4
uniprot id: Q9NPH3
names: Domain
names: Function
names: Induction
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Associates with secreted ligand-bound IL1R2 and increases the affinity of secreted IL1R2 for IL1B; this complex formation may be the dominant mechanism for neutralization of IL1B by secreted/soluble receptors (PubMed:12530978). Enhances the ability of secreted IL1R1 to inhibit IL-33 signaling (By similarity).
messages: Belongs to the interleukin-1 receptor family.
messages: Cell membrane
messages: Coreceptor for IL1RL2 in the IL-36 signaling system (By similarity). Coreceptor with IL1R1 in the IL-1 signaling system. Associates with IL1R1 bound to IL1B to form the high affinity interleukin-1 receptor complex which mediates interleukin-1-dependent activation of NF-kappa-B and other pathways. Signaling involves the recruitment of adapter molecules such as TOLLIP, MYD88, and IRAK1 or IRAK2 via the respective TIR domains of the receptor/coreceptor subunits. Recruits TOLLIP to the signaling complex. Does not bind to interleukin-1 alone; binding of IL1RN to IL1R1, prevents its association with IL1R1 to form a signaling complex. The cellular response is modulated through a non-signaling association with the membrane IL1R2 decoy receptor. Coreceptor for IL1RL1 in the IL-33 signaling system. Can bidirectionally induce pre- and postsynaptic differentiation of neurons by trans-synaptically binding to PTPRD (By similarity). May play a role in IL1B-mediated costimulation of IFNG production from T-helper 1 (Th1) cells (Probable).
messages: Detected in liver, skin, placenta, thymus and lung. Isoform 4 is predominantly expressed in brain. Overexpressed on candidate chronic myeloid leukemia (CML) stem cells, hematopoietic stem cells and mononuclear cells of patients with acute myeloid leukemia (AML). Overexpressed in patients with chronic obstructive pulmonary disease (COPD). Expressed in T-helper 1 (Th1) and T-helper 2 (Th2) cell subsets (PubMed:10653850).
messages: Isoform 1 is down-regulated by phorbol ester treatment. Isoform 2 is induced by phorbol ester treatment.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Secreted
messages: The TIR domain mediates NAD(+) hydrolase (NADase) activity. Self-association of TIR domains is required for NADase activity.
messages: The interleukin-36 receptor complex is a heterodimer of IL1RL2 and IL1RAP; the association is inhibited by IL36RN (By similarity). The interleukin-1 receptor complex is a heterodimer of IL1R1 and IL1RAP. Associates with IL1R2 to form a non-signaling interleukin-1 receptor complex. Isoform 4 interacts with IL1R1 in an interleukin-1-dependent manner. Interacts with IL-33-bound IL1RL1 to form the minimal interleukin-33 signaling complex with a 1:1:1 stoichiometry. Interacts with KIT (independently of stimulation with KITLG/SCF). A mast cell-specific KITLG/SCF-induced interleukin-33 signaling complex contains IL1RL1, IL1RAP, KIT and MYD88 (By similarity). Interacts (via the first immunoglobilin domain) with PTPRD (via the third immunoglobilin domain); induces pre- and postsynaptic differentiation of neurons (By similarity).
messages: Unable to mediate canonical IL-1 signaling (PubMed:19481478). Required for Src phosphorylation by IL1B. May be involved in IL1B-potentiated NMDA-induced calcium influx in neurons (By similarity).

9606:COPB2
gene id: 9606:COPB2
uniprot id: P35606
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the WD repeat COPB2 family.
messages: COPI-coated vesicle membrane
messages: Golgi apparatus membrane
messages: Oligomeric complex that consists of at least the alpha, beta, beta', gamma, delta, epsilon and zeta subunits. Probably interacts with PEX11A. Interacts with SCYL1 (By similarity). Interacts with JAGN1 (PubMed:25129144).
messages: The coatomer is a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Golgi network. Coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins. In mammals, the coatomer can only be recruited by membranes associated to ADP-ribosylation factors (ARFs), which are small GTP-binding proteins; the complex also influences the Golgi structural integrity, as well as the processing, activity, and endocytic recycling of LDL receptors.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The disease may be caused by variants affecting the gene represented in this entry.
messages: This coatomer complex protein, essential for Golgi budding and vesicular trafficking, is a selective binding protein (RACK) for protein kinase C, epsilon type. It binds to Golgi membranes in a GTP-dependent manner (By similarity).
messages: cytosol

9606:MYMX
gene id: 9606:MYMX
uniprot id: A0A1B0GTQ4
names: Disease Annotation
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the MYMX family.
messages: Cell membrane
messages: Interacts with MYMK.
messages: Myoblast-specific protein that mediates myoblast fusion, an essential step for the formation of multi-nucleated muscle fibers (PubMed:28569745, PubMed:35642635). Involved in membrane fusion downstream of the lipid mixing step mediated by MYMK (By similarity). Acts by generating membrane stresses via its extracellular C-terminus, leading to drive fusion pore formation. Acts independently of MYMK (By similarity). Involved in skeletal muscle regeneration in response to injury by mediating the fusion of satellite cells, a population of muscle stem cells, with injured myofibers (By similarity).
messages: The AxLyCxL motif is required for myoblast fusion.
messages: The disease may be caused by variants affecting the gene represented in this entry.

9606:FANCL
gene id: 9606:FANCL
uniprot id: Q9NW38
names: Caution
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: Although PubMed:12724401 reports that it contains a PHD-type zinc finger, it contains a RING-type zinc finger. Moreover, PHD-type zinc fingers do not have any ubiquitin ligase activity.
messages: Cytoplasm
messages: Interacts with GGN (By similarity). Belongs to the multisubunit FA complex composed of FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL/PHF9 and FANCM (PubMed:12973351, PubMed:15502827, PubMed:16116422, PubMed:22343915). The complex is not found in FA patients. In complex with FANCF, FANCA and FANCG, but not with FANCC, nor FANCE, interacts with HES1; this interaction may be essential for the stability and nuclear localization of FA core complex proteins (PubMed:18550849). Interacts with FANCI (PubMed:21775430). Directly interacts (via the RING-type zinc finger) with UBE2T and UBE2W (PubMed:16916645, PubMed:17938197, PubMed:19111657, PubMed:21775430, PubMed:24389026).
messages: Nucleus
messages: The RING-type zinc finger domain is monoubiquitinated in the presence of UBE2T and UBE2W.
messages: The UBC-RWD region (URD) region mediates interaction with FANCI and FANCD2.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitin ligase protein that mediates monoubiquitination of FANCD2 in the presence of UBE2T, a key step in the DNA damage pathway (PubMed:12973351, PubMed:16916645, PubMed:17938197, PubMed:19111657, PubMed:24389026). Also mediates monoubiquitination of FANCI (PubMed:19589784). May stimulate the ubiquitin release from UBE2W. May be required for proper primordial germ cell proliferation in the embryonic stage, whereas it is probably not needed for spermatogonial proliferation after birth.

9606:TIMM17B
gene id: 9606:TIMM17B
uniprot id: O60830
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the Tim17/Tim22/Tim23 family.
messages: Component of the TIM23 complex at least composed of TIMM23, TIMM17 (TIMM17A or TIMM17B) and TIMM50. The complex interacts with the TIMM44 component of the PAM complex and with DNAJC15.
messages: Essential component of the TIM23 complex, a complex that mediates the translocation of transit peptide-containing proteins across the mitochondrial inner membrane.
messages: Expression is abundant in heart and skeletal muscle, intermediate in brain, and weak in pancreas, placenta, kidney and liver.
messages: Forms one disulfide bond.
messages: Mitochondrion inner membrane

9606:HDAC5
gene id: 9606:HDAC5
uniprot id: Q9UQL6
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the histone deacetylase family. HD type 2 subfamily.
messages: Cytoplasm
messages: Interacts with AHRR, BAHD1, BCOR, HDAC7, HDAC9, CTBP1, MEF2C, NCOR2, NRIP1, PHB2 and a 14-3-3 chaperone protein. Interacts with BCL6, DDIT3/CHOP, GRK5, KDM5B and MYOCD. Interacts with EP300 in the presence of TFAP2C. Interacts with ANKRA2. Interacts with CUL7 (as part of the 3M complex); negatively regulated by ANKRA2. Interacts with ZBTB7B; the interaction allows the recruitment of HDAC4 on CD8 loci for deacetylation and possible inhibition of CD8 genes expression (By similarity). Interacts with RARA (PubMed:28167758).
messages: Nucleus
messages: Phosphorylated by AMPK, CaMK1, SIK1 and PRKD1 at Ser-259 and Ser-498. The phosphorylation is required for the export to the cytoplasm and inhibition. Phosphorylated by the PKC kinases PKN1 and PKN2, impairing nuclear import. Phosphorylated by GRK5, leading to nuclear export of HDAC5 and allowing MEF2-mediated transcription (By similarity).
messages: Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Involved in muscle maturation by repressing transcription of myocyte enhancer MEF2C. During muscle differentiation, it shuttles into the cytoplasm, allowing the expression of myocyte enhancer factors. Involved in the MTA1-mediated epigenetic regulation of ESR1 expression in breast cancer. Serves as a corepressor of RARA and causes its deacetylation (PubMed:28167758). In association with RARA, plays a role in the repression of microRNA-10a and thereby in the inflammatory response (PubMed:28167758).
messages: The nuclear export sequence mediates the shuttling between the nucleus and the cytoplasm.
messages: Ubiquitinated. Polyubiquitination however does not lead to its degradation.
messages: Ubiquitous.

9606:BTNL9
gene id: 9606:BTNL9
uniprot id: Q6UXG8
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the immunoglobulin superfamily. BTN/MOG family.
messages: Membrane

9606:OPN5
gene id: 9606:OPN5
uniprot id: Q6U736
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor 1 family. Opsin subfamily.
messages: Cell membrane
messages: Detected in brain and retina and cell lines derived from neural retina.
messages: G-protein coupled receptor which selectively activates G(i) type G proteins via ultraviolet A (UVA) light-mediated activation in the retina (By similarity). Preferentially binds the chromophore 11-cis retinal and is a bistable protein that displays emission peaks at 380 nm (UVA light) and 470 nm (blue light) (PubMed:22043319). Required for the light-response in the inner plexiform layer, and contributes to the regulation of the light-response in the nerve fiber layer, via phosphorylated DAT/SLC6A3 dopamine uptake (By similarity). Involved in local corneal and retinal circadian rhythm photoentrainment via modulation of the UVA light-induced phase-shift of the retina clock (By similarity). Acts as a circadian photoreceptor in the outer ear, via modulation of circadian clock-gene expression in response to violet light during the light-to-dark transition phase and night phase of the circadian cycle (By similarity). Required in the retina to negatively regulate hyaloid vessel regression during postnatal development via light-dependent OPN5-SLC32A1-DRD2-VEGFR2 signaling (By similarity). Involved in the light-dependent regulation of retina and vitreous compartment dopamine levels (By similarity).
messages: It is uncertain whether Cys-315 or Cys-316 is palmitoylated.

9606:HNRNPUL1
gene id: 9606:HNRNPUL1
uniprot id: Q9BUJ2
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: Acts as a basic transcriptional regulator. Represses basic transcription driven by several virus and cellular promoters. When associated with BRD7, activates transcription of glucocorticoid-responsive promoter in the absence of ligand-stimulation. Also plays a role in mRNA processing and transport. Binds avidly to poly(G) and poly(C) RNA homopolymers in vitro.
messages: Interacts with the adenovirus type 5 (Ad5) E1B-55 kDa, BRD7, PRMT2, TP53 and NXF1. Associates with histones and BRD7.
messages: Its methylation is enhanced in the late phase of adenoviral infection.
messages: May be due to intron retention.
messages: Methylated.
messages: Nucleus
messages: The RGG-box domain is methylated.

9606:SEMA6A
gene id: 9606:SEMA6A
uniprot id: A0A0A0MQU6
uniprot id: Q9H2E6
names: Caution
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Acts as a receptor for P.sordellii toxin TcsL in the in the vascular endothelium.
messages: (Microbial infection) Interacts with P.sordellii toxin TcsL; semaphorins SEMA6A and SEMA6B constitute the major host receptors for TcsL in the vascular endothelium.
messages: Active as a homodimer or oligomer (By similarity). The SEMA6A homodimer interacts with a PLXNA2 homodimer, giving rise to a heterotetramer (By similarity). Interacts with EVL (PubMed:10993894).
messages: Belongs to the semaphorin family.
messages: Cell membrane
messages: Cell surface receptor for PLXNA2 that plays an important role in cell-cell signaling. Required for normal granule cell migration in the developing cerebellum. Promotes reorganization of the actin cytoskeleton and plays an important role in axon guidance in the developing central nervous system. Can act as repulsive axon guidance cue. Has repulsive action towards migrating granular neurons. May play a role in channeling sympathetic axons into the sympathetic chains and controlling the temporal sequence of sympathetic target innervation.
messages: Lacks conserved residue(s) required for the propagation of feature annotation.

9606:CACFD1
gene id: 9606:CACFD1
uniprot id: Q9UGQ2
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the calcium channel flower family.
messages: Membrane

9606:ZNF473
gene id: 9606:ZNF473
uniprot id: Q8WTR7
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: Interacts with the SLBP/pre-mRNA complex but not with SLBP alone. Interacts with LSM11 in a U7 snRNP-dependent manner.
messages: Involved in histone 3'-end pre-mRNA processing by associating with U7 snRNP and interacting with SLBP/pre-mRNA complex. Increases histone 3'-end pre-mRNA processing but has no effect on U7 snRNP levels, when overexpressed. Required for cell cycle progression from G1 to S phases.
messages: Nucleus
messages: The C2H2-type zinc finger 2 to 6 are necessary and sufficient for discrete Cajal bodies localization. The C2H2-type zinc finger 5 to 10 are necessary and sufficient for interaction with LSM11. The C2H2-type zinc finger 2 to 8 are necessary for interaction with the SLBP/RNA complex in the histone pre-mRNAs. The C2H2-type zinc finger 2 to 10 confer activity in histone pre-mRNA processing.

9606:COX7A2
gene id: 9606:COX7A2
uniprot id: H0UI06
uniprot id: P14406
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the cytochrome c oxidase VIIa family.
messages: Component of the cytochrome c oxidase (complex IV, CIV), a multisubunit enzyme composed of 14 subunits. The complex is composed of a catalytic core of 3 subunits MT-CO1, MT-CO2 and MT-CO3, encoded in the mitochondrial DNA, and 11 supernumerary subunits COX4I1 (or COX4I2), COX5A, COX5B, COX6A1 (or COX6A2), COX6B1 (or COX6B2), COX6C, COX7A2 (or COX7A1), COX7B, COX7C, COX8A and NDUFA4, which are encoded in the nuclear genome (PubMed:30030519). The complex exists as a monomer or a dimer and forms supercomplexes (SCs) in the inner mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), resulting in different assemblies (supercomplex SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)) (PubMed:28844695). Interacts with PET100 (PubMed:22356826).
messages: Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix.
messages: Mitochondrion inner membrane

9606:CCNA2
gene id: 9606:CCNA2
uniprot id: P20248
names: Developmental Stage
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Interacts with human cytomegalovirus protein UL32.
messages: Accumulates steadily during G2 and is abruptly destroyed at mitosis. Not detected during the G1 phase of the cell cycle. It accumulates during the DNA synthesis/S phase and disappears as cells progress into mitosis, between prophase and metaphase (at protein level).
messages: Belongs to the cyclin family. Cyclin AB subfamily.
messages: Cyclin which controls both the G1/S and the G2/M transition phases of the cell cycle. Functions through the formation of specific serine/threonine protein kinase holoenzyme complexes with the cyclin-dependent protein kinases CDK1 or CDK2. The cyclin subunit confers the substrate specificity of these complexes and differentially interacts with and activates CDK1 and CDK2 throughout the cell cycle.
messages: Cytoplasm
messages: Interacts with the CDK1 and CDK2 protein kinases to form serine/threonine kinase holoenzyme complexes (PubMed:1312467, PubMed:7630397, PubMed:8684460, PubMed:8756328). Interacts with CDK1 (hyperphosphorylated form in G1 and underphosphorylated forms in S and G2) (PubMed:1312467). Interacts with CDK2; the interaction increases from G1 to G2 (PubMed:1312467). Interacts (associated with CDK2 but not with CDK1) with SCAPER; regulates the activity of CCNA2/CDK2 by transiently maintaining CCNA2 in the cytoplasm (PubMed:17698606). Forms a ternary complex with CDK2 and CDKN1B; CDKN1B inhibits the kinase activity of CDK2 through conformational rearrangements (PubMed:8684460). Interacts with INCA1 (PubMed:21540187).
messages: Nucleus
messages: Polyubiquitinated via 'Lys-11'-linked ubiquitin by the anaphase-promoting complex (APC/C), leading to its degradation by the proteasome. Deubiquitinated and stabilized by USP37 enables entry into S phase.

9606:CHRNG
gene id: 9606:CHRNG
uniprot id: A0A6F7YAP6
uniprot id: P07510
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
messages: Belongs to the ligand-gated ion channel (TC 1.A.9) family.
messages: Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Gamma/CHRNG sub-subfamily.
messages: Cell membrane
messages: Membrane
messages: Pentamer of two alpha chains, and one each of the beta, delta, and gamma (in immature muscle) or epsilon (in mature muscle) chains.
messages: Postsynaptic cell membrane
messages: Synaptic cell membrane
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:PTK2
gene id: 9606:PTK2
uniprot id: Q05397
uniprot id: Q59GM6
uniprot id: Q59GN8
uniprot id: Q658W2
names: Activity Regulation
names: Developmental Stage
names: Disease Annotation
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Aberrant PTK2/FAK1 expression may play a role in cancer cell proliferation, migration and invasion, in tumor formation and metastasis. PTK2/FAK1 overexpression is seen in many types of cancer.
messages: Belongs to the protein kinase superfamily. Tyr protein kinase family. FAK subfamily.
messages: Cell membrane
messages: Cytoplasm
messages: Detected in B and T-lymphocytes. Isoform 1 and isoform 6 are detected in lung fibroblasts (at protein level). Ubiquitous. Expressed in epithelial cells (at protein level) (PubMed:31630787).
messages: Detected in cultured cells, immediately after seeding and before formation of focal adhesions (at protein level).
messages: Interacts (via first Pro-rich region) with CAS family members (via SH3 domain), including BCAR1, BCAR3, and CASS4. Interacts with NEDD9 (via SH3 domain) (PubMed:9360983). Interacts with GIT1. Interacts with SORBS1. Interacts with ARHGEF28. Interacts with SHB. Part of a complex composed of THSD1, PTK2/FAK1, TLN1 and VCL (PubMed:29069646). Interacts with PXN and TLN1. Interacts with STAT1. Interacts with DCC. Interacts with WASL. Interacts with ARHGEF7. Interacts with GRB2 and GRB7 (By similarity). Component of a complex that contains at least FER, CTTN and PTK2/FAK1. Interacts with BMX. Interacts with TGFB1I1. Interacts with STEAP4. Interacts with ZFYVE21. Interacts with ESR1. Interacts with PIK3R1 or PIK3R2. Interacts with SRC, FGR, FLT4 and RET. Interacts with EPHA2 in resting cells; activation of EPHA2 recruits PTPN11, leading to dephosphorylation of PTK2/FAK1 and dissociation of the complex. Interacts with EPHA1 (kinase activity-dependent). Interacts with CD4; this interaction requires the presence of HIV-1 gp120. Interacts with PIAS1. Interacts with ARHGAP26 and SHC1. Interacts with RB1CC1; this inhibits PTK2/FAK1 activity and activation of downstream signaling pathways. Interacts with P53/TP53 and MDM2. Interacts with LPXN (via LD motif 3). Interacts with MISP. Interacts with CIB1 isoform 2. Interacts with CD36. Interacts with EMP2; regulates PTK2 activation and localization (PubMed:19494199). Interacts with DSCAM (By similarity). Interacts with AMBRA1 (By similarity). Interacts (when tyrosine-phosphorylated) with tensin TNS1; the interaction is increased by phosphorylation of TNS1 (PubMed:20798394).
messages: Isoform 6 (FRNK) does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling. Its enhanced expression can attenuate the nuclear accumulation of LPXN and limit its ability to enhance serum response factor (SRF)-dependent gene transcription.
messages: Non-receptor protein-tyrosine kinase that plays an essential role in regulating cell migration, adhesion, spreading, reorganization of the actin cytoskeleton, formation and disassembly of focal adhesions and cell protrusions, cell cycle progression, cell proliferation and apoptosis. Required for early embryonic development and placenta development. Required for embryonic angiogenesis, normal cardiomyocyte migration and proliferation, and normal heart development. Regulates axon growth and neuronal cell migration, axon branching and synapse formation; required for normal development of the nervous system. Plays a role in osteogenesis and differentiation of osteoblasts. Functions in integrin signal transduction, but also in signaling downstream of numerous growth factor receptors, G-protein coupled receptors (GPCR), EPHA2, netrin receptors and LDL receptors. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascade. Promotes activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling cascade. Promotes localized and transient activation of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), and thereby modulates the activity of Rho family GTPases. Signaling via CAS family members mediates activation of RAC1. Phosphorylates NEDD9 following integrin stimulation (PubMed:9360983). Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ACTN1, ARHGEF7, GRB7, RET and WASL. Promotes phosphorylation of PXN and STAT1; most likely PXN and STAT1 are phosphorylated by a SRC family kinase th…
messages: Nucleus
messages: Phosphorylated on tyrosine residues upon activation, e.g. upon integrin signaling. Tyr-397 is the major autophosphorylation site, but other kinases can also phosphorylate this residue. Phosphorylation at Tyr-397 promotes interaction with SRC and SRC family members, leading to phosphorylation at Tyr-576, Tyr-577 and at additional tyrosine residues. FGR promotes phosphorylation at Tyr-397 and Tyr-576. FER promotes phosphorylation at Tyr-577, Tyr-861 and Tyr-925, even when cells are not adherent. Tyr-397, Tyr-576 and Ser-722 are phosphorylated only when cells are adherent. Phosphorylation at Tyr-397 is important for interaction with BMX, PIK3R1 and SHC1. Phosphorylation at Tyr-925 is important for interaction with GRB2. Dephosphorylated by PTPN11; PTPN11 is recruited to PTK2 via EPHA2 (tyrosine phosphorylated). Microtubule-induced dephosphorylation at Tyr-397 is crucial for the induction of focal adhesion disassembly; this dephosphorylation could be catalyzed by PTPN11 and regulated by ZFYVE21. Phosphorylation on tyrosine residues is enhanced by NTN1 (By similarity).
messages: Produced by alternative promoter usage.
messages: Subject to autoinhibition, mediated by interactions between the FERM domain and the kinase domain. Activated by autophosphorylation at Tyr-397. This promotes interaction with SRC and phosphorylation at Tyr-576 and Tyr-577 in the kinase activation loop. Phosphorylation at Tyr-576 and Tyr-577 is required for maximal kinase activity. Inhibited by TAC544, TAE226, PF-573,228 and PF-562,271.
messages: Sumoylated; this enhances autophosphorylation.
messages: The C-terminal region is the site of focal adhesion targeting (FAT) sequence which mediates the localization of FAK1 to focal adhesions.
messages: The Pro-rich regions interact with the SH3 domain of CAS family members, such as BCAR1 and NEDD9, and with the GTPase activating protein ARHGAP26.
messages: cell cortex
messages: centrosome
messages: cilium basal body
messages: cytoskeleton
messages: focal adhesion
messages: perinuclear region

9606:TSFM
gene id: 9606:TSFM
uniprot id: E5KS95
uniprot id: P43897
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Associates with the EF-Tu.GDP complex and induces the exchange of GDP to GTP. It remains bound to the aminoacyl-tRNA.EF-Tu.GTP complex up to the GTP hydrolysis stage on the ribosome.
messages: Belongs to the EF-Ts family.
messages: Expressed in all tissues, with the highest levels of expression in skeletal muscle, liver and kidney.
messages: Mitochondrion
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:ERBB2
gene id: 9606:ERBB2
uniprot id: J3QLU9
uniprot id: P04626
uniprot id: X5DNK3
names: Activity Regulation
names: Disease Annotation
names: Function
names: Miscellaneous
names: PTM
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Activated by dimerization. Not activated by EGF, TGF-alpha and amphiregulin. Interaction with PTK6 increases its intrinsic kinase activity.
messages: Autophosphorylated. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit (Probable). Ligand-binding increases phosphorylation on tyrosine residues (PubMed:27134172, PubMed:33497358). Signaling via SEMA4C promotes phosphorylation at Tyr-1248 (PubMed:17554007). Dephosphorylated by PTPN12 (PubMed:27134172).
messages: Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily.
messages: Cell membrane
messages: Chromosomal aberrations involving ERBB2 may be a cause gastric cancer. Deletions within 17q12 region producing fusion transcripts with CDK12, leading to CDK12-ERBB2 fusion leading to truncated CDK12 protein not in-frame with ERBB2.
messages: Cytoplasm
messages: Early endosome
messages: Expressed in a variety of tumor tissues including primary breast tumors and tumors from small bowel, esophagus, kidney and mouth.
messages: Homodimer (PubMed:21454582). Heterodimer with EGFR, ERBB3 and ERBB4 (PubMed:10358079, PubMed:15093539, PubMed:21190959, PubMed:16978839). Part of a complex with EGFR and either PIK3C2A or PIK3C2B. May interact with PIK3C2B when phosphorylated on Tyr-1196 (PubMed:10805725). Interacts with PLXNB1 (PubMed:15210733). Interacts (when phosphorylated on Tyr-1248) with MEMO1 (PubMed:15156151). Interacts with MUC1; the interaction is enhanced by heregulin (HRG) (PubMed:12939402). Interacts (when phosphorylated on Tyr-1139) with GRB7 (via SH2 domain) (PubMed:12975581). Interacts (when phosphorylated on Tyr-1248) with ERBIN (PubMed:12444095). Interacts with KPNB1, RANBP2, EEA1, CRM1 and CLTC (PubMed:16314522). Interacts with PTK6 (PubMed:18719096). Interacts with RPA194 and ACTB (PubMed:21555369). Interacts with PRKCABP, SRC and MYOC (By similarity). Interacts (preferentially with the tyrosine phosphorylated form) with CPNE3; this interaction occurs at the cell membrane and is increased in a growth factor heregulin-dependent manner (PubMed:20010870). Interacts with HSP90AA1 and HSP90AB1 in an ATP-dependent manner; the interaction suppresses ERBB2 kinase activity (PubMed:26517842). Interacts with SORL1; this interaction regulates ERBB2 subcellular distribution by promoting its recycling after internalization from endosomes back to the plasma membrane, hence stimulates ERBB2-mediated signaling (PubMed:31138794). Interacts with SH3BGRL (PubMed:32381043).
messages: In the nucleus is involved in transcriptional regulation. Associates with the 5'-TCAAATTC-3' sequence in the PTGS2/COX-2 promoter and activates its transcription. Implicated in transcriptional activation of CDKN1A; the function involves STAT3 and SRC. Involved in the transcription of rRNA genes by RNA Pol I and enhances protein synthesis and cell growth.
messages: Membrane
messages: Nucleus
messages: Produced by alternative initiation at Met-611 of isoform 1.
messages: Produced by alternative initiation at Met-687 of isoform 1.
messages: Produced by alternative splicing of isoform 1.
messages: Protein tyrosine kinase that is part of several cell surface receptor complexes, but that apparently needs a coreceptor for ligand binding. Essential component of a neuregulin-receptor complex, although neuregulins do not interact with it alone. GP30 is a potential ligand for this receptor. Regulates outgrowth and stabilization of peripheral microtubules (MTs). Upon ERBB2 activation, the MEMO1-RHOA-DIAPH1 signaling pathway elicits the phosphorylation and thus the inhibition of GSK3B at cell membrane. This prevents the phosphorylation of APC and CLASP2, allowing its association with the cell membrane. In turn, membrane-bound APC allows the localization of MACF1 to the cell membrane, which is required for microtubule capture and stabilization.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The gene represented in this entry is involved in disease pathogenesis.
messages: The protein represented in this entry is involved in disease pathogenesis.
messages: There are four alleles due to the variations in positions 654 and 655. Allele B1 (Ile-654/Ile-655) has a frequency of 0.782; allele B2 (Ile-654/Val-655) has a frequency of 0.206; allele B3 (Val-654/Val-655) has a frequency of 0.012.
messages: perinuclear region
messages: ruffle membrane

9606:TCTN1
gene id: 9606:TCTN1
uniprot id: A0A087X1J4
uniprot id: A8MW34
uniprot id: B4DIB9
uniprot id: Q05BR9
uniprot id: Q2MV58
names: Disease Annotation
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the tectonic family.
messages: Component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes. Regulator of Hedgehog (Hh), required for both activation and inhibition of the Hh pathway in the patterning of the neural tube. During neural tube development, it is required for formation of the most ventral cell types and for full Hh pathway activation. Functions in Hh signal transduction to fully activate the pathway in the presence of high Hh levels and to repress the pathway in the absence of Hh signals. Modulates Hh signal transduction downstream of SMO and RAB23 (By similarity).
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Part of the tectonic-like complex (also named B9 complex).
messages: Secreted
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: cilium basal body

9606:ABLIM3
gene id: 9606:ABLIM3
uniprot id: A0A0C4DGA7
uniprot id: O94929
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cytoplasm
messages: Directly interacts with F-actin and ABRA.
messages: Expressed predominantly in heart and brain.
messages: May act as scaffold protein. May stimulate ABRA activity and ABRA-dependent SRF transcriptional activity.

9606:TMPPE
gene id: 9606:TMPPE
uniprot id: Q6ZT21
names: Cofactor
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the metallophosphoesterase superfamily. LOC643853 family.
messages: Binds 2 divalent metal cations.
messages: Membrane

9606:TPR
gene id: 9606:TPR
uniprot id: P12270
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: A chromosomal aberration involving TPR has been found in papillary thyroid carcinomas (PTCs). Intrachromosomal rearrangement that links the 5'-end of the TPR gene to the protein kinase domain of NTRK1 forms the fusion protein TRK-T1. TRK-T1 is a 55 kDa protein reacting with antibodies against the carboxy terminus of the NTRK1 protein.
messages: Belongs to the TPR family.
messages: Component of the nuclear pore complex (NPC), a complex required for the trafficking across the nuclear envelope. Functions as a scaffolding element in the nuclear phase of the NPC essential for normal nucleocytoplasmic transport of proteins and mRNAs, plays a role in the establishment of nuclear-peripheral chromatin compartmentalization in interphase, and in the mitotic spindle checkpoint signaling during mitosis. Involved in the quality control and retention of unspliced mRNAs in the nucleus; in association with NUP153, regulates the nuclear export of unspliced mRNA species bearing constitutive transport element (CTE) in a NXF1- and KHDRBS1-independent manner. Negatively regulates both the association of CTE-containing mRNA with large polyribosomes and translation initiation. Does not play any role in Rev response element (RRE)-mediated export of unspliced mRNAs. Implicated in nuclear export of mRNAs transcribed from heat shock gene promoters; associates both with chromatin in the HSP70 promoter and with mRNAs transcribed from this promoter under stress-induced conditions. Modulates the nucleocytoplasmic transport of activated MAPK1/ERK2 and huntingtin/HTT and may serve as a docking site for the XPO1/CRM1-mediated nuclear export complex. According to some authors, plays a limited role in the regulation of nuclear protein export (PubMed:22253824, PubMed:11952838). Also plays a role as a structural and functional element of the perinuclear chromatin distribution; involved in the formation and/or maintenance of NPC-associated perinuclear heterochromatin exclusion zones (HEZs). Finally, acts as a spatial regulator of the spindle-assembly checkpoint (SAC) response ensuring a timely and effective recruitment of spindle checkpoint proteins like MAD1L1 and MAD2L1 to unattached kinetochore during the metaphase-anaphase transition before chromosome congression. Its N-terminus is involved in activation of oncogenic kinases.
messages: Cytoplasm
messages: Expressed in esophagus, ovary, liver, skin, smooth muscles, cerebrum and fetal cerebellum (at protein level). Highest in testis, lung, thymus, spleen and brain, lower levels in heart, liver and kidney.
messages: Interacts with IFI204 (via C-terminal region). Interacts with IFI203 (By similarity). Homodimer. Part of the nuclear pore complex (NPC). Associates with the XPO1/CRM1-mediated nuclear export complex, the Importin alpha/Importin beta receptor and the dynein 1 complex. Interacts (via C-terminal domain) with the KPNB1; the interaction occurs in a RanGTP-dependent manner. Interacts (via C-terminal regionand phosphorylated form) with MAPK1/ERK2 (via phosphorylated form); the interaction requires dimerization of MAPK1/ERK2 and increases following EGF stimulation. Interacts with MAPK3/ERK1; the interaction increases following EGF stimulation. Interacts (via coiled coil region) with NUP153; the interaction is direct. Interacts with HSF1; the interaction increases in a stress-responsive manner and stimulates export of stress-induced HSP70 mRNA. Interacts with huntingtin/HTT; the interaction is inhibited by aggregated huntingtin/HTT forms with expanded polyglutamine stretch. Interacts with MAD1L1 (via N-terminal region), MAD2L1, and TTK; the interactions occurs in a microtubule-independent manner. Interacts (via middle region) with DYNLL1. Interacts with DCTN1, dynein, NUP153 and tubulin. Interacts with MTA1.
messages: Involved in tumorigenic rearrangements with the MET.
messages: Nucleus
messages: Nucleus envelope
messages: Nucleus membrane
messages: Phosphorylated. Phosphorylation occurs on serine and threonine residues (comprised in the C-terminal region) by MAPK1/ERK2 and stabilizes the interaction between these two proteins.
messages: Proteolytically degraded after poliovirus (PV) infection; degradation is restricted to its unfolded C-terminal tail domain whereas its coiled-coil domain containing NCP- and NUP153-binding domains withstand degradation.
messages: The N-terminal domain mediates intranuclear attachment to the nuclear pore complex. The C-terminal domain mediates its nuclear import.
messages: kinetochore
messages: nuclear pore complex
messages: spindle

9606:GPS2
gene id: 9606:GPS2
uniprot id: Q13227
names: Function
names: Induction
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts (via coiled coil domain) with hepatitis C virus (HCV) NS5A.
messages: (Microbial infection) Required for efficient replication of hepatitis C virus (HCV) by promoting the interaction between VAPA and HCV virus protein NS5A.
messages: Component of the N-Cor repressor complex, at least composed of NCOR1, NCOR2, HDAC3, TBL1X, TBL1R, CORO2A and GPS2 (PubMed:11931768, PubMed:19858209, PubMed:21240272). Interacts (when sumoylated at Lys-71) with TBL1X; leading to protect GPS2 from degradation by the proteasome (PubMed:24943844, PubMed:21240272). Interacts with UBE2N; leading to inhibit UBE2N/Ubc13 activity (By similarity). Interacts with TRAF1 (By similarity). Interacts with TRAF2 (By similarity). Interacts with TRAF6 (By similarity). Interacts with PPARG (when in the liganded conformation) (By similarity). Interacts with (sumoylated) NR1H2; interaction with sumoylated NR1H2 and NR5A2 onto hepatic acute phase protein promoters prevents N-Cor corepressor complex dissociation (PubMed:20159957). Interacts with (sumoylated) NR5A2; interaction with sumoylated NR1H2 and NR5A2 onto hepatic acute phase protein promoters prevents N-Cor corepressor complex dissociation (PubMed:20159957). Interacts with NR1H3 (PubMed:19481530). Interacts with RFX4 (By similarity). Interacts with ANKRD26 (PubMed:22666460).
messages: Down-regulated in liposarcoma (PubMed:27460081). Down-regulated in macrophages of patients with adipose tissue inflammation and type-2 diabetes (PubMed:27270589).
messages: Key regulator of inflammation, lipid metabolism and mitochondrion homeostasis that acts by inhibiting the activity of the ubiquitin-conjugating enzyme UBE2N/Ubc13, thereby inhibiting 'Lys-63'-linked ubiquitination (By similarity). In the nucleus, can both acts as a corepressor and coactivator of transcription, depending on the context (PubMed:24943844). Acts as a transcription coactivator in adipocytes by promoting the recruitment of PPARG to promoters: acts by inhibiting the activity of the ubiquitin-conjugating enzyme UBE2N/Ubc13, leading to stabilization of KDM4A and subsequent histone H3 'Lys-9' (H3K9) demethylation (By similarity). Promotes cholesterol efflux by acting as a transcription coactivator (PubMed:19481530). Acts as a regulator of B-cell development by inhibiting UBE2N/Ubc13, thereby restricting the activation of Toll-like receptors (TLRs) and B-cell antigen receptors (BCRs) signaling pathways (By similarity). Acts as a key mediator of mitochondrial stress response: in response to mitochondrial depolarization, relocates from the mitochondria to the nucleus following desumoylation and specifically promotes expression of nuclear-encoded mitochondrial genes (PubMed:29499132). Promotes transcription of nuclear-encoded mitochondrial genes by inhibiting UBE2N/Ubc13 (PubMed:29499132). Can also act as a corepressor as part of the N-Cor repressor complex by repressing active PPARG (PubMed:19858209, PubMed:24943844). Plays an anti-inflammatory role in macrophages and is required for insulin sensitivity by acting as a corepressor (By similarity). Plays an anti-inflammatory role during the hepatic acute phase response by interacting with sumoylated NR1H2 and NR5A2 proteins, thereby preventing N-Cor corepressor complex dissociation (PubMed:20159957). In the cytosol, also plays a non-transcriptional role by regulating insulin signaling and pro-inflammatory pathways (By similarity). In the cytoplasm, acts as a negative regulator of inflammation by inhibiting the pro…
messages: Methylated at Arg-312 and Arg-323 by PRMT6. Methylation at Arg-323 protects from degradation by the proteasome.
messages: Mitochondrion
messages: Nucleus
messages: Sumoylation regulates its subcellular location (PubMed:24943844). Sumoylation at Lys-45 and Lys-71 regulates the shuttling between the cytoplasm and the nucleus (PubMed:24943844). Sumoylation at Lys-71 is required for interaction with TBL1X (By similarity). Sumoylated at Lys-45 and Lys-71 in mitochondrion (By similarity). Desumoylation by SENP1 leads to relocation from the mitochondria to the nucleus (By similarity).
messages: Ubiquitinated at the C-terminus by SIAH2; leading to its degradation by the proteasome. Interaction with TBL1X and methylation at Arg-323 protect GPS2 against ubiquitination and degradation.
messages: Widely expressed.
messages: cytosol

9606:NDEL1
gene id: 9606:NDEL1
uniprot id: A6NIZ0
uniprot id: Q9GZM8
names: Caution
names: Developmental Stage
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the nudE family.
messages: Expressed in brain, heart, kidney, liver, lung, pancreas, placenta and skeletal muscle.
messages: Expression peaks in mitosis.
messages: Interacts with PLEKHM1 (via N- and C-terminus) (By similarity). Interacts with YWHAE. Interacts directly with NEFL and indirectly with NEFH. Interacts with microtubules (By similarity). Self-associates. Interacts with DISC1, dynein, dynactin, tubulin gamma, KATNA1, KATNB1, PAFAH1B1, PCM1 and PCNT. Interacts (via C-terminus) with CENPF. Interacts with ZNF365.
messages: Palmitoylation at Cys-273 reduces affinity for dynein.
messages: Phosphorylated in mitosis. Can be phosphorylated by CDK1, CDK5 and MAPK1. Phosphorylation by CDK5 promotes interaction with KATNA1 and YWHAE.
messages: Required for organization of the cellular microtubule array and microtubule anchoring at the centrosome. May regulate microtubule organization at least in part by targeting the microtubule severing protein KATNA1 to the centrosome. Also positively regulates the activity of the minus-end directed microtubule motor protein dynein. May enhance dynein-mediated microtubule sliding by targeting dynein to the microtubule plus ends. Required for several dynein- and microtubule-dependent processes such as the maintenance of Golgi integrity, the centripetal motion of secretory vesicles and the coupling of the nucleus and centrosome. Also required during brain development for the migration of newly formed neurons from the ventricular/subventricular zone toward the cortical plate. Plays a role, together with DISC1, in the regulation of neurite outgrowth. Required for mitosis in some cell types but appears to be dispensible for mitosis in cortical neuronal progenitors, which instead requires NDE1. Facilitates the polymerization of neurofilaments from the individual subunits NEFH and NEFL. Positively regulates lysosome peripheral distribution and ruffled border formation in osteoclasts (By similarity).
messages: Was originally thought to function as an oligopeptidase (NUDEL-oligopeptidase or endooligopeptidase A) which could regulate peptide levels relevant to brain function.
messages: centrosome
messages: cytoskeleton
messages: kinetochore
messages: spindle

9606:RNASE2
gene id: 9606:RNASE2
uniprot id: P10153
uniprot id: W0UV60
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: A particular signal processing and glycosylation pattern may differentiate the UpI2 RNase, found specifically in pregnant women urine, from other nonsecretory RNases.
messages: Belongs to the pancreatic ribonuclease family.
messages: Cytoplasmic granule
messages: Interacts with and forms a tight 1:1 complex with RNH1. Dimerization of two such complexes may occur.
messages: Liver, lung, spleen, leukocytes and body fluids.
messages: Lysosome
messages: The N-terminal region is necessary for mediating chemotactic activity.
messages: This is a non-secretory ribonuclease. It is a pyrimidine specific nuclease with a slight preference for U. Cytotoxin and helminthotoxin. Selectively chemotactic for dendritic cells. Possesses a wide variety of biological activities.

9606:PDPK1
gene id: 9606:PDPK1
uniprot id: O15530
names: Activity Regulation
names: Domain
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Appears to be expressed ubiquitously. The Tyr-9 phosphorylated form is markedly increased in diseased tissue compared with normal tissue from lung, liver, colon and breast.
messages: Autophosphorylated; autophosphorylation is inhibited by the apoptotic C-terminus cleavage product of PKN2.
messages: Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PDPK1 subfamily.
messages: Cell membrane
messages: Cytoplasm
messages: Homodimer in its autoinhibited state. Active as monomer. Interacts with NPRL2, PPARG, PAK1, PTK2B, GRB14, PKN1 (via C-terminus), STRAP and IKKB. The Tyr-9 phosphorylated form interacts with SRC, RASA1 and CRK (via their SH2 domains). Interacts with SGK3 in a phosphorylation-dependent manner. The tyrosine-phosphorylated form interacts with PTPN6. The Ser-241 phosphorylated form interacts with YWHAH and YWHAQ. Binds INSR in response to insulin. Interacts (via PH domain) with SMAD3, SMAD4 and SMAD7. Interacts with PKN2; the interaction stimulates PDPK1 autophosphorylation, its PI(3,4,5)P3-dependent kinase activity toward 'Ser-473' of AKT1 but also activates its kinase activity toward PRKCD and PRKCZ.
messages: Homodimerization regulates its activity by maintaining the kinase in an autoinhibitory conformation. NPRL2 down-regulates its activity by interfering with tyrosine phosphorylation at the Tyr-9, Tyr-373 and Tyr-376 residues. The 14-3-3 protein YWHAQ acts as a negative regulator by association with the residues surrounding the Ser-241 residue. STRAP positively regulates its activity by enhancing its autophosphorylation and by stimulating its dissociation from YWHAQ. SMAD2, SMAD3, SMAD4 and SMAD7 also positively regulate its activity by stimulating its dissociation from YWHAQ. Activated by phosphorylation on Tyr-9, Tyr-373 and Tyr-376 by INSR in response to insulin.
messages: Monoubiquitinated in the kinase domain, deubiquitinated by USP4.
messages: Nucleus
messages: Phosphorylation on Ser-241 in the activation loop is required for full activity. PDPK1 itself can autophosphorylate Ser-241, leading to its own activation. Autophosphorylation is inhibited by the apoptotic C-terminus cleavage product of PKN2 (By similarity). Tyr-9 phosphorylation is critical for stabilization of both PDPK1 and the PDPK1/SRC complex via HSP90-mediated protection of PDPK1 degradation. Angiotensin II stimulates the tyrosine phosphorylation of PDPK1 in vascular smooth muscle in a calcium- and SRC-dependent manner. Phosphorylated on Tyr-9, Tyr-373 and Tyr-376 by INSR in response to insulin. Palmitate negatively regulates autophosphorylation at Ser-241 and palmitate-induced phosphorylation at Ser-529 and Ser-501 by PKC/PRKCQ negatively regulates its ability to phosphorylate PKB/AKT1. Phosphorylation at Thr-354 by MELK partially inhibits kinase activity, the inhibition is cooperatively enhanced by phosphorylation at Ser-394 and Ser-398 by MAP3K5.
messages: Serine/threonine kinase which acts as a master kinase, phosphorylating and activating a subgroup of the AGC family of protein kinases. Its targets include: protein kinase B (PKB/AKT1, PKB/AKT2, PKB/AKT3), p70 ribosomal protein S6 kinase (RPS6KB1), p90 ribosomal protein S6 kinase (RPS6KA1, RPS6KA2 and RPS6KA3), cyclic AMP-dependent protein kinase (PRKACA), protein kinase C (PRKCD and PRKCZ), serum and glucocorticoid-inducible kinase (SGK1, SGK2 and SGK3), p21-activated kinase-1 (PAK1), protein kinase PKN (PKN1 and PKN2). Plays a central role in the transduction of signals from insulin by providing the activating phosphorylation to PKB/AKT1, thus propagating the signal to downstream targets controlling cell proliferation and survival, as well as glucose and amino acid uptake and storage. Negatively regulates the TGF-beta-induced signaling by: modulating the association of SMAD3 and SMAD7 with TGF-beta receptor, phosphorylating SMAD2, SMAD3, SMAD4 and SMAD7, preventing the nuclear translocation of SMAD3 and SMAD4 and the translocation of SMAD7 from the nucleus to the cytoplasm in response to TGF-beta. Activates PPARG transcriptional activity and promotes adipocyte differentiation. Activates the NF-kappa-B pathway via phosphorylation of IKKB. The tyrosine phosphorylated form is crucial for the regulation of focal adhesions by angiotensin II. Controls proliferation, survival, and growth of developing pancreatic cells. Participates in the regulation of Ca(2+) entry and Ca(2+)-activated K(+) channels of mast cells. Essential for the motility of vascular endothelial cells (ECs) and is involved in the regulation of their chemotaxis. Plays a critical role in cardiac homeostasis by serving as a dual effector for cell survival and beta-adrenergic response. Plays an important role during thymocyte development by regulating the expression of key nutrient receptors on the surface of pre-T cells and mediating Notch-induced cell growth and proliferative responses. Provides negative …
messages: Stimulated by insulin, and the oxidants hydrogen peroxide and peroxovanadate.
messages: The PH domain plays a pivotal role in the localization and nuclear import of PDPK1 and is also essential for its homodimerization.
messages: The PIF-pocket is a small lobe in the catalytic domain required by the enzyme for the binding to the hydrophobic motif of its substrates. It is an allosteric regulatory site that can accommodate small compounds acting as allosteric inhibitors.
messages: focal adhesion

9606:SUMO1
gene id: 9606:SUMO1
uniprot id: P63165
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Interacts (via N-terminus) with Hantaan hantavirus nucleoprotein.
messages: (Microbial infection) Interacts (via N-terminus) with Tula hantavirus nucleoprotein.
messages: (Microbial infection) Interacts with Epstein-barr virus BGLF4.
messages: Belongs to the ubiquitin family. SUMO subfamily.
messages: Cell membrane
messages: Cleavage of precursor form by SENP1 or SENP2 is necessary for function.
messages: Covalently attached to KCNB1; UBE2I increases cross-linking with KCNB1 and PIAS1 decreases cross-links with KCNB1 (PubMed:19223394, PubMed:15931224). Interacts with SAE2, RANBP2, PIAS1 and PIAS2 (PubMed:10961991, PubMed:15608651, PubMed:15660128, PubMed:16204249, PubMed:15931224). Interacts with PRKN (PubMed:16955485). Covalently attached to a number of proteins such as IKFZ1, PML, RANGAP1, HIPK2, SP100, p53, p73-alpha, MDM2, JUN, DNMT3B and TDG (PubMed:10961991, PubMed:15931224, PubMed:15959518, PubMed:17099698). Also interacts with HIF1A, HIPK2, HIPK3, CHD3, EXOSC9, RAD51 and RAD52 (PubMed:10961991, PubMed:12565818). Interacts with USP25 (via ts SIM domain); the interaction weakly sumoylates USP25 (PubMed:18538659). Interacts with SIMC1, CASP8AP2, RNF111 and SOBP (via SIM domains) (PubMed:23086935). Interacts with BHLHE40/DEC1 (PubMed:21829689). Interacts with RWDD3 (PubMed:17956732). Interacts with UBE2I/UBC9 and this interaction is enhanced in the presence of RWDD3 (PubMed:12924945, PubMed:17956732). Interacts with MTA1 (PubMed:21965678). Interacts with SENP2 (PubMed:15296745). Interacts with HINT1 (By similarity).
messages: Cytoplasm
messages: Nucleus
messages: Nucleus membrane
messages: Nucleus speckle
messages: PML body
messages: Polymeric SUMO1 chains undergo polyubiquitination by RNF4.
messages: The disease is caused by variants affecting the gene represented in this entry. A chromosomal aberration involving SUMO1 is the cause of OFC10. Translocation t(2;8)(q33.1;q24.3). The breakpoint occurred in the SUMO1 gene and resulted in haploinsufficiency confirmed by protein assays.
messages: Ubiquitin-like protein that can be covalently attached to proteins as a monomer or a lysine-linked polymer. Covalent attachment via an isopeptide bond to its substrates requires prior activation by the E1 complex SAE1-SAE2 and linkage to the E2 enzyme UBE2I, and can be promoted by E3 ligases such as PIAS1-4, RANBP2 or CBX4. This post-translational modification on lysine residues of proteins plays a crucial role in a number of cellular processes such as nuclear transport, DNA replication and repair, mitosis and signal transduction. Involved for instance in targeting RANGAP1 to the nuclear pore complex protein RANBP2. Covalently attached to the voltage-gated potassium channel KCNB1; this modulates the gating characteristics of KCNB1 (PubMed:19223394). Polymeric SUMO1 chains are also susceptible to polyubiquitination which functions as a signal for proteasomal degradation of modified proteins. May also regulate a network of genes involved in palate development. Covalently attached to ZFHX3 (PubMed:24651376).

9606:TCF7L1
gene id: 9606:TCF7L1
uniprot id: Q9HCS4
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the TCF/LEF family.
messages: Binds the armadillo repeat of CTNNB1 and forms a stable complex (By similarity). Interacts with DAZAP2 (PubMed:19304756).
messages: Detected in hair follicles and skin keratinocytes, and at lower levels in stomach epithelium.
messages: Nucleus
messages: Participates in the Wnt signaling pathway. Binds to DNA and acts as a repressor in the absence of CTNNB1, and as an activator in its presence. Necessary for the terminal differentiation of epidermal cells, the formation of keratohyalin granules and the development of the barrier function of the epidermis (By similarity). Down-regulates NQO1, leading to increased mitomycin c resistance.
messages: The putative Groucho interaction domain between the N-terminal CTNNB1 binding domain and the HMG-box is necessary for repression of the transactivation mediated by TCF7L1 and CTNNB1.

9606:STIM1
gene id: 9606:STIM1
uniprot id: G0XQ39
uniprot id: Q13586
names: Disease Annotation
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cell membrane
messages: Endoplasmic reticulum membrane
messages: Glycosylation is required for cell surface expression.
messages: Membrane
messages: Monomer in the presence of Ca(2+); it oligomerizes in absence of Ca(2+) (PubMed:18854159). Forms homooligomers and heterooligomers with STIM2 (PubMed:11463338, PubMed:11983428, PubMed:18854159, PubMed:22451904, PubMed:24351972, PubMed:24069340). Interacts (via the transmembrane region and the SOAR/CAD domain) with SPPL3; the interaction promotes the binding of STIM1 to ORAI1 (PubMed:25384971). Interacts with ORAI1 (PubMed:17905723, PubMed:19249086, PubMed:27185316, PubMed:24351972, PubMed:28219928, PubMed:30481768). Interacts with MAPRE1; probably required for targeting to the growing microtubule plus ends (PubMed:19632184). Interacts with CRACR2A/EFCAB4B; the interaction is direct and takes place in absence of Ca(2+) (PubMed:20418871). Forms a complex with CRACR2A/EFCAB4B and ORAI1 at low concentration of Ca(2+), the complex dissociates at elevated Ca(2+) concentrations (PubMed:20418871). Interacts with SARAF, promoting a slow inactivation of STIM1-dependent SOCE activity, possibly by facilitating the deoligomerization of STIM1 (PubMed:22464749, PubMed:30481768). Interacts with EFHB; the interaction takes place upon Ca(2+)-store depletion and inhibits the association with SARAF (PubMed:30481768). Interacts with ASPH (isoform 8) (PubMed:22586105). Interacts with SLC35G1; intracellular Ca(2+)-dependent. May interact with ATP1A1, ATP2A2, ATP2B1, ATP2B4, KPNB1 and XPO1; through SLC35G1 (PubMed:22084111). Interacts with TMEM203 (PubMed:25996873). Interacts with STIMATE, promoting STIM1 conformational switch (PubMed:26322679). Interacts with TMEM178A (By similarity). Interacts with CASQ1 (via C-terminal end and preferentially with the monomeric form); this interaction increases in response to a depletion of intracellular Ca(2+), decreases both STIM1 aggregation and clustering, interaction of STIM1 with ORAI1 and store-operated Ca(2+) entry (SOCE) activity (PubMed:27185316). Interacts with ADCY8 (PubMed:22494970).
messages: Phosphorylated predominantly on Ser residues.
messages: Plays a role in mediating store-operated Ca(2+) entry (SOCE), a Ca(2+) influx following depletion of intracellular Ca(2+) stores (PubMed:15866891, PubMed:16005298, PubMed:16208375, PubMed:16537481, PubMed:16733527, PubMed:16766533, PubMed:16807233, PubMed:18854159, PubMed:19249086, PubMed:22464749, PubMed:24069340, PubMed:24351972, PubMed:24591628, PubMed:26322679, PubMed:25326555, PubMed:28219928). Acts as Ca(2+) sensor in the endoplasmic reticulum via its EF-hand domain. Upon Ca(2+) depletion, translocates from the endoplasmic reticulum to the plasma membrane where it activates the Ca(2+) release-activated Ca(2+) (CRAC) channel subunit ORAI1 (PubMed:16208375, PubMed:16537481). Involved in enamel formation (PubMed:24621671). Activated following interaction with STIMATE, leading to promote STIM1 conformational switch (PubMed:26322679).
messages: Sarcoplasmic reticulum
messages: The STIM1 Orai1-activating region/CRAC-activating domain (SOAR/CAD) mediates interaction with ORAI1 to activate the channel.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The microtubule tip localization signal (MtLS) motif; mediates interaction with MAPRE1 and targeting to the growing microtubule plus ends.
messages: Transfection of STIM1 into cells derived from a rhabdoid tumor and from a rhabdomyosarcoma that do not express detectable levels of STIM1 can induce cell death, suggesting a possible role in the control of rhabdomyosarcomas and rhabdoid tumors.
messages: Ubiquitously expressed in various human primary cells and tumor cell lines.
messages: cytoskeleton

9606:DEFB116
gene id: 9606:DEFB116
uniprot id: Q30KQ4
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the beta-defensin family.
messages: Has antibacterial activity.
messages: Secreted

9606:USP49
gene id: 9606:USP49
uniprot id: Q70CQ1
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the peptidase C19 family.
messages: Component of a complex with RUVBL1 and PSMC5.
messages: Nucleus
messages: Specifically deubiquitinates histone H2B at 'Lys-120' (H2BK120Ub). H2BK120Ub is a specific tag for epigenetic transcriptional activation and acts as a regulator of mRNA splicing. Deubiquitination is required for efficient cotranscriptional splicing of a large set of exons.

9606:SPATA31D1
gene id: 9606:SPATA31D1
uniprot id: Q6ZQQ2
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the SPATA31 family.
messages: May play a role in spermatogenesis.
messages: Membrane

9606:KCNH4
gene id: 9606:KCNH4
uniprot id: Q9UQ05
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the potassium channel family. H (Eag) (TC 1.A.1.20) subfamily. Kv12.3/KCNH4 sub-subfamily.
messages: Detected only in brain, in particular in the telencephalon. Detected in putamen and caudate nucleus, and at lower levels in cerebral cortex, occipital and hippocampus.
messages: Membrane
messages: Pore-forming (alpha) subunit of voltage-gated potassium channel. Elicits an outward current, but shows no inactivation. Channel properties may be modulated by cAMP and subunit assembly.
messages: The potassium channel is probably composed of a homo- or heterotetrameric complex of pore-forming alpha subunits that can associate with modulating beta subunits.
messages: The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.

9606:KPRP
gene id: 9606:KPRP
uniprot id: Q5T749
names: Developmental Stage
names: Induction
names: Subcellular Location Annotation
names: Tissue Specificity
messages: By calcium and in psoriatic lesions.
messages: Cytoplasm
messages: Expressed in the periderm of fetal skin from 16th week gestational age and in the granular and horny layers of the epidermis at 24th week gestational age and thereafter (at protein level).
messages: Expressed in the upper layer of epidermis and psoriasis (at protein level). Expressed in the upper layer of epidermis and psoriasis.

9606:GIMAP7
gene id: 9606:GIMAP7
uniprot id: A0A090N8P8
uniprot id: Q8NHV1
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. AIG1/Toc34/Toc159-like paraseptin GTPase family. IAN subfamily.
messages: Cytoplasm
messages: Endoplasmic reticulum
messages: Golgi apparatus
messages: Lipid droplet
messages: Monomer in the presence of bound GDP and in the absence of bound nucleotide. Homodimer in the presence of bound GTP. Heterodimer with GIMAP2.
messages: Most abundantly expressed in spleen, lymph nodes, and fetal kidney, but also present in the heart and the small intestine. Lower expression levels are found in lung, kidney, liver, and thyroid, salivary, and mammary glands. Also detected in the thymus (PubMed:15474311). Detected in T-cells (PubMed:23454188).
messages: The dimer has GTPase activity; the active site contains residues from both subunits.

9606:SLC25A52
gene id: 9606:SLC25A52
uniprot id: I3L0B8
uniprot id: Q3SY17
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the mitochondrial carrier (TC 2.A.29) family.
messages: Membrane
messages: Mitochondrial membrane carrier protein that mediates the import of NAD(+) into mitochondria (PubMed:32906142). Compared to SLC25A51, SLC25A52-mediated transport is not essential for the import of NAD(+) in mitochondria (PubMed:32906142). The transport mechanism, uniport or antiport, its electrogenicity and substrate selectivity, remain to be elucidated.
messages: Mitochondrion inner membrane

9606:SLC10A7
gene id: 9606:SLC10A7
uniprot id: Q0GE19
names: Developmental Stage
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the bile acid:sodium symporter (BASS) (TC 2.A.28) family.
messages: Cell membrane
messages: Detected in the heart and vertebrae in embryos at 8 weeks of gestation (Carnegie stage 16), and in the long-bone cartilage at 9 weeks (Carnegie stages 19).
messages: Endoplasmic reticulum membrane
messages: Golgi apparatus membrane
messages: Involved in teeth and skeletal development. Has an essential role in the biosynthesis and trafficking of glycosaminoglycans and glycoproteins, to produce a proper functioning extracellular matrix. Required for extracellular matrix mineralization (PubMed:30082715, PubMed:29878199). Also involved in the regulation of cellular calcium homeostasis (PubMed:30082715, PubMed:31191616). Does not show transport activity towards bile acids or steroid sulfates (including taurocholate, cholate, chenodeoxycholate, estrone-3-sulfate, dehydroepiandrosterone sulfate (DHEAS) and pregnenolone sulfate).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Widely expressed (PubMed:15932064, PubMed:17628207). Expressed at high levels in liver and at lower levels in prostate, placenta, kidney, heart, lung, thymus and spleen (PubMed:15932064, PubMed:17628207). Strongly expressed in testis and also detected in brain, ovary, colon and small intestine (PubMed:17628207). Weakly expressed in testis and not detected in brain, ovary, colon or small intestine (PubMed:15932064). Isoform 1: Expressed in liver, testis and placenta (PubMed:17628207). Isoform 4: Expressed in liver, testis and placenta (PubMed:17628207).

9606:ZNF20
gene id: 9606:ZNF20
uniprot id: P17024
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:YAP1
gene id: 9606:YAP1
uniprot id: P46937
names: Disease Annotation
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Activates the C-terminal fragment (CTF) of ERBB4 (isoform 3).
messages: Belongs to the YAP1 family.
messages: Binds to the SH3 domain of the YES kinase. Binds to WBP1 and WBP2 (PubMed:9202023). Binds, in vitro, through the WW1 domain, to neural isoforms of ENAH that contain the PPSY motif (By similarity). The phosphorylated form interacts with YWHAB (PubMed:17974916). Interacts (via WW domains) with LATS1 (via PPxY motif 2) (PubMed:18158288). Interacts with LATS2 (PubMed:18158288). Interacts with TEAD1, TEAD2, TEAD3 and TEAD4 (PubMed:18579750, PubMed:20123905, PubMed:20123908). Interacts with TP73 (PubMed:18280240). Interacts with RUNX1 (PubMed:18280240). Interacts with HCK (PubMed:17535448). Interacts (via WW domains) with PTPN14 (via PPxY motif 2); this interaction leads to the cytoplasmic sequestration of YAP1 and inhibits its transcriptional coactivator activity (PubMed:22525271). Interacts (when phosphorylated at Ser-127) with SMAD2, SMAD3 and WWTR1 (By similarity). Interacts with PRRG2 (via cytoplasmic domain) (PubMed:17502622). Interacts (via WW domains) with PRRG4 (via cytoplasmic domain) (PubMed:23873930). Interacts (phosphorylated) with CLDN18; the interaction sequesters YAP1 away from the nucleus and thereby restricts transcription of YAP1 target genes (By similarity). Interacts with SMAD1 (PubMed:21685363).
messages: Cell junction
messages: Cytoplasm
messages: Highest expression in ovary and placenta, lowest in skeletal muscle and brain.
messages: Increased expression seen in some liver and prostate cancers. Isoforms lacking the transactivation domain found in striatal neurons of patients with Huntington disease (at protein level).
messages: Interacts (via WW domain 1) with isoform 3 of ERBB4 (via PPxY motif 2).
messages: Nucleus
messages: Phosphorylated by LATS1 and LATS2; leading to cytoplasmic translocation and inactivation (PubMed:18158288, PubMed:20048001). Phosphorylated by ABL1; leading to YAP1 stabilization, enhanced interaction with TP73 and recruitment onto proapoptotic genes; in response to DNA damage (PubMed:18280240). Phosphorylation at Ser-400 and Ser-403 by CK1 is triggered by previous phosphorylation at Ser-397 by LATS proteins and leads to YAP1 ubiquitination by SCF(beta-TRCP) E3 ubiquitin ligase and subsequent degradation (PubMed:20048001). Phosphorylated at Thr-119, Ser-138, Thr-154, Ser-367 and Thr-412 by MAPK8/JNK1 and MAPK9/JNK2, which is required for the regulation of apoptosis by YAP1 (PubMed:21364637).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The first coiled-coil region mediates most of the interaction with TEAD transcription factors.
messages: Transcriptional regulator which can act both as a coactivator and a corepressor and is the critical downstream regulatory target in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis (PubMed:17974916, PubMed:18280240, PubMed:18579750, PubMed:21364637, PubMed:30447097). The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ (PubMed:18158288). Plays a key role in tissue tension and 3D tissue shape by regulating cortical actomyosin network formation. Acts via ARHGAP18, a Rho GTPase activating protein that suppresses F-actin polymerization (PubMed:25778702). Plays a key role in controlling cell proliferation in response to cell contact. Phosphorylation of YAP1 by LATS1/2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration (PubMed:18158288). The presence of TEAD transcription factors are required for it to stimulate gene expression, cell growth, anchorage-independent growth, and epithelial mesenchymal transition (EMT) induction (PubMed:18579750). Suppresses ciliogenesis via acting as a transcriptional corepressor of the TEAD4 target genes AURKA and PLK1 (PubMed:25849865). In conjunction with WWTR1, involved in the regulation of TGFB1-dependent SMAD2 and SMAD3 nuclear accumulation (By similarity).
messages: Ubiquitinated by SCF(beta-TRCP) E3 ubiquitin ligase.

9606:TFAP2A
gene id: 9606:TFAP2A
uniprot id: P05549
names: Disease Annotation
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the AP-2 family.
messages: Binds DNA as a dimer. Can form homodimers or heterodimers with other AP-2 family members. Interacts with WWOX. Interacts with CITED4. Interacts with UBE2I. Interacts with RALBP1 in a complex also containing EPN1 and NUMB during interphase and mitosis. Interacts with KCTD1; this interaction represses transcription activation. Interacts (via C-terminus) with CITED2 (via C-terminus); the interaction stimulates TFAP2A-transcriptional activation. Interacts (via N-terminus) with EP300 (via N-terminus); the interaction requires CITED2. Interacts with KCTD15; this interaction inhibits TFAP2A transcriptional activation.
messages: May be an aberrantly processed form with no significant distribution in vivo.
messages: Nucleus
messages: Sequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to regulate transcription of selected genes. AP-2 factors bind to the consensus sequence 5'-GCCNNNGGC-3' and activate genes involved in a large spectrum of important biological functions including proper eye, face, body wall, limb and neural tube development. They also suppress a number of genes including MCAM/MUC18, C/EBP alpha and MYC. AP-2-alpha is the only AP-2 protein required for early morphogenesis of the lens vesicle. Together with the CITED2 coactivator, stimulates the PITX2 P1 promoter transcription activation. Associates with chromatin to the PITX2 P1 promoter region.
messages: Sumoylated on Lys-10; which inhibits transcriptional activity.
messages: The PPxY motif mediates interaction with WWOX.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:OR5B3
gene id: 9606:OR5B3
uniprot id: A0A126GVH3
uniprot id: Q8NH48
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Membrane
messages: Odorant receptor.

9606:ALG5
gene id: 9606:ALG5
uniprot id: Q9Y673
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the glycosyltransferase 2 family.
messages: Endoplasmic reticulum membrane
messages: Expressed in pancreas, placenta, liver, heart, brain, kidney, skeletal muscle, and lung.
messages: Required for the assembly of lipid-linked oligosaccharides in kidney epithelial cells, and protein N-glycosylation. Required for polycystin-1 (PKD1) glycosylation and maturation.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:OR4A16
gene id: 9606:OR4A16
uniprot id: A0A126GW87
uniprot id: Q8NH70
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Membrane
messages: Odorant receptor.

9606:CXCL12
gene id: 9606:CXCL12
uniprot id: P48061
names: Developmental Stage
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts with molluscum contagiosum virus protein MC148.
messages: Belongs to the intercrine alpha (chemokine CxC) family.
messages: Chemoattractant active on T-lymphocytes and monocytes but not neutrophils. Activates the C-X-C chemokine receptor CXCR4 to induce a rapid and transient rise in the level of intracellular calcium ions and chemotaxis. SDF-1-beta(3-72) and SDF-1-alpha(3-67) show a reduced chemotactic activity. Binding to cell surface proteoglycans seems to inhibit formation of SDF-1-alpha(3-67) and thus to preserve activity on local sites. Also binds to atypical chemokine receptor ACKR3, which activates the beta-arrestin pathway and acts as a scavenger receptor for SDF-1. Binds to the allosteric site (site 2) of integrins and activates integrins ITGAV:ITGB3, ITGA4:ITGB1 and ITGA5:ITGB1 in a CXCR4-independent manner (PubMed:29301984). Acts as a positive regulator of monocyte migration and a negative regulator of monocyte adhesion via the LYN kinase. Stimulates migration of monocytes and T-lymphocytes through its receptors, CXCR4 and ACKR3, and decreases monocyte adherence to surfaces coated with ICAM-1, a ligand for beta-2 integrins. SDF1A/CXCR4 signaling axis inhibits beta-2 integrin LFA-1 mediated adhesion of monocytes to ICAM-1 through LYN kinase. Inhibits CXCR4-mediated infection by T-cell line-adapted HIV-1. Plays a protective role after myocardial infarction. Induces down-regulation and internalization of ACKR3 expressed in various cells. Has several critical functions during embryonic development; required for B-cell lymphopoiesis, myelopoiesis in bone marrow and heart ventricular septum formation. Stimulates the proliferation of bone marrow-derived B-cell progenitors in the presence of IL7 as well as growth of stromal cell-dependent pre-B-cells (By similarity).
messages: Isoform Alpha and isoform Beta are ubiquitously expressed, with highest levels detected in liver, pancreas and spleen. Isoform Gamma is mainly expressed in heart, with weak expression detected in several other tissues. Isoform Delta, isoform Epsilon and isoform Theta have highest expression levels in pancreas, with lower levels detected in heart, kidney, liver and spleen.
messages: Isoform Alpha is ubiquitously expressed in fetal tissues. Isoform Beta and isoform Delta have more limited expression patterns, with highest levels detected in fetal spleen and fetal liver, respectively. Isoform Gamma and isoform Theta are weakly detected in fetal kidney.
messages: Monomer or homodimer; in equilibrium. Dimer formation is induced by non acidic pH and the presence of multivalent anions, and by binding to CXCR4 or heparin. Monomeric form is required for full chemotactic activity and resistance to ischemia/reperfusion injury, whereas the dimeric form acts as a partial agonist of CXCR4, stimulating Ca2+ mobilization but with no chemotactic activity and instead acts as a selective antagonist that blocks chemotaxis induced by the monomeric form. Interacts with the N-terminus of ACKR3. Interacts with integrin subunit ITGB3 (via the allosteric site (site 2)) (PubMed:29301984). Interacts with TNFAIP6 (via Link domain).
messages: Processed forms SDF-1-beta(3-72) and SDF-1-alpha(3-67) are produced after secretion by proteolytic cleavage of isoforms Beta and Alpha, respectively. The N-terminal processing is probably achieved by DPP4. Isoform Alpha is first cleaved at the C-terminus to yield a SDF-1-alpha(1-67) intermediate before being processed at the N-terminus. The C-terminal processing of isoform Alpha is reduced by binding to heparin and, probably, cell surface proteoglycans.
messages: Secreted

9606:LYSMD3
gene id: 9606:LYSMD3
uniprot id: Q7Z3D4
names: Function
names: Induction
names: Subcellular Location Annotation
messages: Cell membrane
messages: Essential for Golgi structural integrity.
messages: Golgi apparatus
messages: Up-regulated by Golgi stress-inducing agent nigericin.

9606:SLC29A2
gene id: 9606:SLC29A2
uniprot id: Q14542
uniprot id: Q96FB2
names: Caution
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Apical cell membrane
messages: Basolateral cell membrane
messages: Belongs to the SLC29A/ENT transporter (TC 2.A.57) family.
messages: Bidirectional uniporter involved in the facilitative transport of nucleosides and nucleobases, and contributes to maintaining their cellular homeostasis (PubMed:9396714, PubMed:9478986, PubMed:12527552, PubMed:10722669, PubMed:12590919, PubMed:21795683, PubMed:16214850). Functions as a Na(+)-independent, passive transporter (PubMed:9478986). Involved in the transport of nucleosides such as inosine, adenosine, uridine, thymidine, cytidine and guanosine (PubMed:9396714, PubMed:9478986, PubMed:12527552, PubMed:10722669, PubMed:12590919, PubMed:21795683, PubMed:16214850). Also able to transport purine nucleobases (hypoxanthine, adenine, guanine) and pyrimidine nucleobases (thymine, uracil) (PubMed:21795683, PubMed:16214850). Involved in nucleoside transport at basolateral membrane of kidney cells, allowing liver absorption of nucleoside metabolites (PubMed:12527552). Mediates apical nucleoside uptake into Sertoli cells, thereby regulating the transport of nucleosides in testis across the blood-testis-barrier (PubMed:23639800). Mediates both the influx and efflux of hypoxanthine in skeletal muscle microvascular endothelial cells to control the amount of intracellular hypoxanthine available for xanthine oxidase-mediated ROS production (By similarity).
messages: Glycosylated.
messages: Highly expressed in skeletal muscle (PubMed:9478986). Expressed in liver, lung, placenta, brain, heart, kidney and ovarian tissues (PubMed:9478986). Expressed in testis at the blood-brain-barrier (PubMed:23639800).
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Membrane
messages: Non functional nucleoside transporter protein for adenosine or thymidine tranport. Does not express on cell membrane.
messages: The nuclear function of SLC29A2/ENT2 is unclear. A study reported that under proliferative conditions, two SLC29A2/ENT2 nuclear isoforms recruited SLC29A2/ENT2 to the nuclear envelope in order to translocate nucleosides into the nucleus for incorporation into DNA during replication (PubMed:27271752). However, the physiological existence of these isoforms has yet to be proven.
messages: Transport activity is insensitive to nanomolar concentrations of the inhibitor nitrobenzylmercaptopurine riboside (NBMPR) (PubMed:9396714, PubMed:9478986, PubMed:10722669, PubMed:12590919, PubMed:21795683). Inhibited by higher concentrations of NBMPR (1uM-10uM) (PubMed:9396714, PubMed:9478986, PubMed:10722669, PubMed:12590919).

9606:NNMT
gene id: 9606:NNMT
uniprot id: B0YJ53
uniprot id: P40261
names: Activity Regulation
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the class I-like SAM-binding methyltransferase superfamily. NNMT/PNMT/TEMT family.
messages: Catalyzes the N-methylation of nicotinamide using the universal methyl donor S-adenosyl-L-methionine to form N1-methylnicotinamide and S-adenosyl-L-homocysteine, a predominant nicotinamide/vitamin B3 clearance pathway (PubMed:8182091, PubMed:21823666, PubMed:23455543). Plays a central role in regulating cellular methylation potential, by consuming S-adenosyl-L-methionine and limiting its availability for other methyltransferases. Actively mediates genome-wide epigenetic and transcriptional changes through hypomethylation of repressive chromatin marks, such as H3K27me3 (PubMed:26571212, PubMed:23455543, PubMed:31043742). In a developmental context, contributes to low levels of the repressive histone marks that characterize pluripotent embryonic stem cell pre-implantation state (PubMed:26571212). Acts as a metabolic regulator primarily on white adipose tissue energy expenditure as well as hepatic gluconeogenesis and cholesterol biosynthesis. In white adipocytes, regulates polyamine flux by consuming S-adenosyl-L-methionine which provides for propylamine group in polyamine biosynthesis, whereas by consuming nicotinamide controls NAD(+) levels through the salvage pathway (By similarity). Via its product N1-methylnicotinamide regulates protein acetylation in hepatocytes, by repressing the ubiquitination and increasing the stability of SIRT1 deacetylase (By similarity). Can also N-methylate other pyridines structurally related to nicotinamide and play a role in xenobiotic detoxification (PubMed:30044909).
messages: Cytoplasm
messages: Deiminated by PADI1 and PADI2.
messages: Inactivated by deimination on Arg-132.
messages: Monomer.
messages: Predominantly expressed in the liver. A lower expression is seen in the kidney, lung, skeletal muscle, placenta and heart. Not detected in the brain or pancreas.
messages: Prominently expressed in the stroma of high-grade serous carcinomas (PubMed:31043742). In tumorigenesis, regulates the epigenetic reprograming of cancer cells associated with increased cell migration and metastasis (PubMed:23455543, PubMed:31043742).

9606:DENND2D
gene id: 9606:DENND2D
uniprot id: Q9H6A0
names: Function
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Cytoplasm
messages: Guanine nucleotide exchange factor (GEF) which may activate RAB9A and RAB9B. Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form.
messages: In bronchial mucosa, mainly expressed in ciliated and basal epithelial cells and weakly in alveolar cells (at protein level). Tends to be down-regulated in lung cancers, immortalized bronchial epithelial cell lines and precancerous lesions.

9606:CCR6
gene id: 9606:CCR6
uniprot id: P51684
names: Caution
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor 1 family.
messages: By IL2/interleukin-2.
messages: Cell membrane
messages: Cell surface
messages: It is uncertain whether Met-1 or Met-6 is the initiator.
messages: Receptor for the C-C type chemokine CCL20 (PubMed:9169459). Binds to CCL20 and subsequently transduces a signal by increasing the intracellular calcium ion levels (PubMed:20068036). Although CCL20 is its major ligand it can also act as a receptor for non-chemokine ligands such as beta-defensins (PubMed:25585877). Binds to defensin DEFB1 leading to increase in intracellular calcium ions and cAMP levels. Its binding to DEFB1 is essential for the function of DEFB1 in regulating sperm motility and bactericidal activity (PubMed:25122636). Binds to defensins DEFB4 and DEFB4A/B and mediates their chemotactic effects (PubMed:20068036). The ligand-receptor pair CCL20-CCR6 is responsible for the chemotaxis of dendritic cells (DC), effector/ memory T-cells and B-cells and plays an important role at skin and mucosal surfaces under homeostatic and inflammatory conditions, as well as in pathology, including cancer and various autoimmune diseases. CCR6-mediated signals are essential for immune responses to microbes in the intestinal mucosa and in the modulation of inflammatory responses initiated by tissue insult and trauma (PubMed:21376174). CCR6 is essential for the recruitment of both the pro-inflammatory IL17 producing helper T-cells (Th17) and the regulatory T-cells (Treg) to sites of inflammation. Required for the normal migration of Th17 cells in Peyers-patches and other related tissue sites of the intestine and plays a role in regulating effector T-cell balance and distribution in inflamed intestine. Plays an important role in the coordination of early thymocyte precursor migration events important for normal subsequent thymocyte precursor development, but is not required for the formation of normal thymic natural regulatory T-cells (nTregs). Required for optimal differentiation of DN2 and DN3 thymocyte precursors. Essential for B-cell localization in the subepithelial dome of Peyers-patches and for efficient B-cell isotype switching to IgA in the Peyers-patches. Essential…
messages: Sperm. Mainly localized in the tail and in the postacrosomal region but is also found in the midpiece and basal region in a small percentage of sperm cells. Reduced levels found in the sperms of asthenozoospermia and leukocytospermia patients (at protein level). Spleen, lymph nodes, appendix, and fetal liver. Expressed in lymphocytes, T-cells and B-cells but not in natural killer cells, monocytes or granulocytes.

9606:ZIC1
gene id: 9606:ZIC1
uniprot id: Q15915
names: Disease Annotation
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acts as a transcriptional activator. Involved in neurogenesis. Plays important roles in the early stage of organogenesis of the CNS, as well as during dorsal spinal cord development and maturation of the cerebellum. Involved in the spatial distribution of mossy fiber (MF) neurons within the pontine gray nucleus (PGN). Plays a role in the regulation of MF axon pathway choice. Promotes MF migration towards ipsilaterally-located cerebellar territories. May have a role in shear flow mechanotransduction in osteocytes. Retains nuclear GLI1 and GLI3 in the cytoplasm. Binds to the minimal GLI-consensus sequence 5'-TGGGTGGTC-3' (By similarity).
messages: Belongs to the GLI C2H2-type zinc-finger protein family.
messages: CNS. A high level expression is seen in the cerebellum. Detected in the nuclei of the cerebellar granule cell lineage from the progenitor cells of the external germinal layer to the postmigrated cells of the internal granular layer. Detected in medulloblastoma (26/29 cases), but not present in all other tumors examined.
messages: Cytoplasm
messages: Interacts (via the C2H2-type domains 3, 4 and 5) with MDFIC (via the C2H2-type domains 3, 4 and 5). Interacts with GLI1; the interaction enhances transcription activation. Interacts with GLI2. Interacts with GLI3; the interaction enhances transcription activation (By similarity).
messages: Nucleus
messages: The C2H2-type 3, 4 and 5 zinc finger domains are necessary for transcription activation.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:MED9
gene id: 9606:MED9
uniprot id: Q9NWA0
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the Mediator complex subunit 9 family.
messages: Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors.
messages: Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP.
messages: Nucleus

9606:RNF225
gene id: 9606:RNF225
uniprot id: M0QZC1
names: Subcellular Location Annotation
messages: Membrane

9606:CATSPER4
gene id: 9606:CATSPER4
uniprot id: Q7RTX7
names: Activity Regulation
names: Caution
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the cation channel sperm-associated (TC 1.A.1.19) family.
messages: Component of the CatSper complex or CatSpermasome composed of the core pore-forming members CATSPER1, CATSPER2, CATSPER3 and CATSPER4 as well as auxiliary members CATSPERB, CATSPERG, CATSPERD, CATSPERE, CATSPERZ, C2CD6/CATSPERT, TMEM249, TMEM262 and EFCAB9 (By similarity). HSPA1 may be an additional auxiliary complex member (By similarity). The core complex members CATSPER1, CATSPER2, CATSPER3 and CATSPER4 form a heterotetrameric channel. The auxiliary CATSPERB, CATSPERG, CATSPERD and CATSPERE subunits form a pavilion-like structure over the pore which stabilizes the complex through interactions with CATSPER4, CATSPER3, CATSPER1 and CATSPER2 respectively (By similarity). TMEM262/CATSPERH interacts with CATSPERB, further stabilizing the complex. C2CD6/CATSPERT interacts at least with CATSPERD and is required for targeting the CatSper complex in the flagellar membrane (By similarity).
messages: In mouse, Slco6c1 is an additional auxiliary subunit of the CatSper complex. It is unclear if the related SLCO6A1 protein performs the same role in non-rodent species.
messages: Testis-specific.
messages: The CatSper calcium channel is indirectly activated by extracellular progesterone and prostaglandins following the sequence: progesterone > PGF1-alpha = PGE1 > PGA1 > PGE2 >> PGD2 (PubMed:21412338, PubMed:21412339, PubMed:26989199). The CatSper calcium channel is directly inhibited by endocannabinoid 2-arachidonoylglycerol (2AG) (PubMed:26989199). Indirect activation by progesterone takes place via the following mechanism: progesterone binds and activates the acylglycerol lipase ABHD2, which in turn mediates hydrolysis of 2AG inhibitor, relieving inhibition of the CatSper channel (PubMed:26989199). The primary effect of progesterone activation is to shift voltage dependence towards more physiological, negative membrane potentials; it is not mediated by metabotropic receptors and second messengers (PubMed:21412338, PubMed:21412339). Sperm capacitation enhances the effect of progesterone by providing additional negative shift. Also activated by the elevation of intracellular pH (PubMed:21412338, PubMed:21412339).
messages: Voltage-gated calcium channel that plays a central role in calcium-dependent physiological responses essential for successful fertilization, such as sperm hyperactivation, acrosome reaction and chemotaxis towards the oocyte.
messages: flagellum membrane

9606:PITPNB
gene id: 9606:PITPNB
uniprot id: P48739
names: Activity Regulation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the PtdIns transfer protein family. PI transfer class I subfamily.
messages: Catalyzes the transfer of phosphatidylinositol and phosphatidylcholine between membranes (PubMed:10531358, PubMed:18636990, PubMed:20332109). Also catalyzes the transfer of sphingomyelin (By similarity). Required for COPI-mediated retrograde transport from the Golgi to the endoplasmic reticulum; phosphatidylinositol and phosphatidylcholine transfer activity is essential for this function (PubMed:20332109).
messages: Constitutive phosphorylation of Ser-262 has no effect on phospholipid transfer activity but is required for Golgi targeting.
messages: Endoplasmic reticulum membrane
messages: Golgi apparatus
messages: Golgi apparatus membrane
messages: Phosphatidylinositol transfer activity is inhibited by N-ethylmaleimide.
messages: Widely expressed in various tissues including brain.

9606:FKBP11
gene id: 9606:FKBP11
uniprot id: Q9NYL4
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the FKBP-type PPIase family.
messages: Interacts with IFITM5.
messages: Membrane
messages: PPIases accelerate the folding of proteins during protein synthesis.

9606:MRPL18
gene id: 9606:MRPL18
uniprot id: Q9H0U6
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the universal ribosomal protein uL18 family.
messages: Component of the mitochondrial large ribosomal subunit (mt-LSU) (PubMed:28892042, PubMed:25278503). Mature mammalian 55S mitochondrial ribosomes consist of a small (28S) and a large (39S) subunit. The 28S small subunit contains a 12S ribosomal RNA (12S mt-rRNA) and 30 different proteins. The 39S large subunit contains a 16S rRNA (16S mt-rRNA), a copy of mitochondrial valine transfer RNA (mt-tRNA(Val)), which plays an integral structural role, and 52 different proteins.
messages: Mitochondrion
messages: Together with thiosulfate sulfurtransferase (TST), acts as a mitochondrial import factor for the cytosolic 5S rRNA. The precursor form shows RNA chaperone activity; is able to fold the 5S rRNA into an import-competent conformation that is recognized by rhodanese (TST). Both the cytoplasmic and mitochondrial forms are able to bind to the helix IV-loop D in the gamma domain of the 5S rRNA.

9606:ZNF668
gene id: 9606:ZNF668
uniprot id: Q96K58
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: May be involved in transcriptional regulation. May play a role in DNA repair process.
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:MIA3
gene id: 9606:MIA3
uniprot id: Q5JRA6
names: Disease Annotation
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Although 2 transmembrane domains are predicted, PubMed:19269366 showed that it only contains one transmembrane domain. The other predicted transmembrane region is probably a hairpin-type region embedded into the membrane, which does not cross the membrane. It is unclear which of the 2 predicted transmembrane regions is the transmembrane or the hairpin-type region.
messages: Belongs to the MIA/OTOR family. Tango1 subfamily.
messages: Broadly expressed, except in bone marrow and peripheral blood mononuclear cells. Down-regulated in melanoma tissue.
messages: Endoplasmic reticulum membrane
messages: Interacts with MIA2 (PubMed:21525241). Interacts (via SH3 domain) with COL7A1 (PubMed:19269366). Interacts with the COPII coat subunits SEC23A, SEC23B and maybe SEC24C (PubMed:19269366, PubMed:27551091, PubMed:28442536). May interact with APOB and MIA2 (PubMed:27138255). Isoform 1 and isoform 4 interact with SEC16A (PubMed:28442536).
messages: Plays a role in the transport of cargos that are too large to fit into COPII-coated vesicles and require specific mechanisms to be incorporated into membrane-bound carriers and exported from the endoplasmic reticulum. This protein is required for collagen VII (COL7A1) secretion by loading COL7A1 into transport carriers. It may participate in cargo loading of COL7A1 at endoplasmic reticulum exit sites by binding to COPII coat subunits Sec23/24 and guiding SH3-bound COL7A1 into a growing carrier. Does not play a role in global protein secretion and is apparently specific to COL7A1 cargo loading. However, it may participate in secretion of other proteins in cells that do not secrete COL7A1. It is also specifically required for the secretion of lipoproteins by participating in their export from the endoplasmic reticulum (PubMed:27138255, PubMed:19269366). Required for correct assembly of COPII coat components at endoplasmic reticulum exit sites (ERES) and for the localization of SEC16A and membrane-bound ER-resident complexes consisting of MIA2 and PREB/SEC12 to ERES (PubMed:28442536).
messages: The disease may be caused by variants affecting the gene represented in this entry.
messages: The proline-rich domain (PRD) contains repeated PPP motifs. A single PPP motif is necessary and sufficient to mediate interaction with the COPII coat subunits SEC23A and SEC23B.

9606:EDEM1
gene id: 9606:EDEM1
uniprot id: Q92611
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the glycosyl hydrolase 47 family.
messages: Endoplasmic reticulum membrane
messages: Extracts misfolded glycoproteins, but not glycoproteins undergoing productive folding, from the calnexin cycle. It is directly involved in endoplasmic reticulum-associated degradation (ERAD) and targets misfolded glycoproteins for degradation in an N-glycan-independent manner, probably by forming a complex with SEL1L. It has low mannosidase activity, catalyzing mannose trimming from Man8GlcNAc2 to Man7GlcNAc2.
messages: Interacts with DNAJC10 (By similarity). Interacts with DERL2 and DERL3. Binds to SEL1L.

9606:KIF12
gene id: 9606:KIF12
uniprot id: Q96FN5
names: Disease Annotation
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family.
messages: Expressed in fetal liver, adult brain and pancreatic islet as well as in kidney tumors, uterus cancer and pancreatic cancer.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: cytoskeleton

9606:LAMA2
gene id: 9606:LAMA2
uniprot id: P24043
uniprot id: Q59H37
names: Caution
names: Disease Annotation
names: Domain
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components.
messages: Domains VI, IV and G are globular.
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: Laminin is a complex glycoprotein, consisting of three different polypeptide chains (alpha, beta, gamma), which are bound to each other by disulfide bonds into a cross-shaped molecule comprising one long and three short arms with globules at each end. Alpha-2 is a subunit of laminin-2 (laminin-211 or merosin), laminin-4 (laminin-221 or S-merosin) and laminin-12 (laminin-213). Interacts with FBLN1, FBLN2 and NID2.
messages: Membrane
messages: Placenta, striated muscle, peripheral nerve, cardiac muscle, pancreas, lung, spleen, kidney, adrenal gland, skin, testis, meninges, choroid plexus, and some other regions of the brain; not in liver, thymus and bone.
messages: The alpha-helical domains I and II are thought to interact with other laminin chains to form a coiled coil structure.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: basement membrane

9606:DDX60L
gene id: 9606:DDX60L
uniprot id: Q5H9U9
names: Similarity
messages: Belongs to the helicase family.

9606:PMM2
gene id: 9606:PMM2
uniprot id: A0A0S2Z4J6
uniprot id: O15305
uniprot id: Q59F02
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the eukaryotic PMM family.
messages: Cytoplasm
messages: Homodimer.
messages: Involved in the synthesis of the GDP-mannose and dolichol-phosphate-mannose required for a number of critical mannosyl transfer reactions.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:APOC1
gene id: 9606:APOC1
uniprot id: P02654
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Apolipoprotein C-I is present in acidic (APOC1A) and basic (APOC1B) forms in P.paniscus, P.abelii and P.troglodytes and perhaps also in baboons and macaques. The two genes for ApoC-I arose through a duplication process that occurred after the divergence of New World monkeys from the human lineage. In human, the acidic form has become a pseudogene sometime between the divergence of bonobos and chimpanzees from the human lineage and the appearance of the Denisovans. Pseudogenization resulted when the codon for the penultimate amino acid in the signal sequence was changed to a stop codon.
messages: Belongs to the apolipoprotein C1 family.
messages: Inhibitor of lipoprotein binding to the low density lipoprotein (LDL) receptor, LDL receptor-related protein, and very low density lipoprotein (VLDL) receptor. Associates with high density lipoproteins (HDL) and the triacylglycerol-rich lipoproteins in the plasma and makes up about 10% of the protein of the VLDL and 2% of that of HDL. Appears to interfere directly with fatty acid uptake and is also the major plasma inhibitor of cholesteryl ester transfer protein (CETP). Binds free fatty acids and reduces their intracellular esterification. Modulates the interaction of APOE with beta-migrating VLDL and inhibits binding of beta-VLDL to the LDL receptor-related protein.
messages: Secreted
messages: Synthesized mainly in liver and to a minor degree in intestine. Also found in the lung and spleen.

9606:HTRA4
gene id: 9606:HTRA4
uniprot id: P83105
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the peptidase S1C family.
messages: Secreted
messages: Serine protease.

9606:SLC38A11
gene id: 9606:SLC38A11
uniprot id: Q08AI6
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the amino acid/polyamine transporter 2 family.
messages: Membrane
messages: Putative sodium-dependent amino acid/proton antiporter.

9606:MT1G
gene id: 9606:MT1G
uniprot id: P13640
names: Domain
names: Function
names: Similarity
names: Subunit
messages: Belongs to the metallothionein superfamily. Type 1 family.
messages: Class I metallothioneins contain 2 metal-binding domains: four divalent ions are chelated within cluster A of the alpha domain and are coordinated via cysteinyl thiolate bridges to 11 cysteine ligands. Cluster B, the corresponding region within the beta domain, can ligate three divalent ions to 9 cysteines.
messages: Metallothioneins have a high content of cysteine residues that bind various heavy metals; these proteins are transcriptionally regulated by both heavy metals and glucocorticoids.
messages: Monomer.

9606:SDF2
gene id: 9606:SDF2
uniprot id: Q99470
names: Subcellular Location Annotation
messages: Secreted

9606:NPLOC4
gene id: 9606:NPLOC4
uniprot id: Q8TAT6
names: Domain
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the NPL4 family.
messages: Binds ubiquitinated proteins via its RanBP2-type zinc finger.
messages: Endoplasmic reticulum
messages: Expressed at highest levels in brain, heart, skeletal muscle, kidney and fetal liver.
messages: Heterodimer with UFD1 (PubMed:11574150, PubMed:26471729). The heterodimer binds ubiquitinated proteins (By similarity). The heterodimer binds to VCP and inhibits Golgi membrane fusion (PubMed:11574150, PubMed:26471729). Interacts with ZFAND2B; probably through VCP (PubMed:24160817).
messages: May be due to an intron retention.
messages: Nucleus
messages: The ternary complex containing UFD1, VCP and NPLOC4 binds ubiquitinated proteins and is necessary for the export of misfolded proteins from the ER to the cytoplasm, where they are degraded by the proteasome. The NPLOC4-UFD1-VCP complex regulates spindle disassembly at the end of mitosis and is necessary for the formation of a closed nuclear envelope (By similarity). Acts as a negative regulator of type I interferon production via the complex formed with VCP and UFD1, which binds to RIGI and recruits RNF125 to promote ubiquitination and degradation of RIGI (PubMed:26471729).
messages: cytosol

9606:BOD1L1
gene id: 9606:BOD1L1
uniprot id: Q8NFC6
names: Function
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the BOD1 family.
messages: Chromosome
messages: Component of the fork protection machinery required to protect stalled/damaged replication forks from uncontrolled DNA2-dependent resection. Acts by stabilizing RAD51 at stalled replication forks and protecting RAD51 nucleofilaments from the antirecombinogenic activities of FBH1 and BLM (PubMed:26166705, PubMed:29937342). Does not regulate spindle orientation (PubMed:26166705).
messages: Contaminating sequence. Potential poly-A sequence.
messages: Interacts (via COMPASS-Shg1 domain) with SETD1A at stalled replication forks; this interaction mediates FANCD2-dependent nucleosome remodeling at reversed forks protecting them from nucleolytic degradation.

9606:INO80B
gene id: 9606:INO80B
uniprot id: Q9C086
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Component of the chromatin remodeling INO80 complex; specifically part of a complex module associated with the helicase ATP-binding and the helicase C-terminal domain of INO80. Interacts with RP9.
messages: Induces growth and cell cycle arrests at the G1 phase of the cell cycle.
messages: Nucleus
messages: Proposed core component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair.
messages: nucleolus

9606:EPHA1
gene id: 9606:EPHA1
uniprot id: P21709
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily.
messages: Cell membrane
messages: Homodimer. Forms a signaling complex with LCK; PTK2B/PYK2 and PI3-kinase upon activation by EFNA1; regulates T-lymphocytes migration. Interacts (via SAM domain) with ILK (via ANK repeats); stimulated by EFNA1 but independent of the kinase activity of EPHA1. Interacts (kinase activity-dependent) with PTK2/FAK1.
messages: Overexpressed in several carcinomas.
messages: Phosphorylated. Autophosphorylation is stimulated by its ligand EFNA1.
messages: Receptor tyrosine kinase which binds promiscuously membrane-bound ephrin-A family ligands residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Binds with a low affinity EFNA3 and EFNA4 and with a high affinity to EFNA1 which most probably constitutes its cognate/functional ligand. Upon activation by EFNA1 induces cell attachment to the extracellular matrix inhibiting cell spreading and motility through regulation of ILK and downstream RHOA and RAC. Also plays a role in angiogenesis and regulates cell proliferation. May play a role in apoptosis.
messages: Ubiquitinated.

9606:KHSRP
gene id: 9606:KHSRP
uniprot id: Q92945
names: Domain
names: Function
names: PTM
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Aberrant splicing.
messages: Belongs to the KHSRP family.
messages: Binds to the dendritic targeting element and may play a role in mRNA trafficking (By similarity). Part of a ternary complex that binds to the downstream control sequence (DCS) of the pre-mRNA. Mediates exon inclusion in transcripts that are subject to tissue-specific alternative splicing. May interact with single-stranded DNA from the far-upstream element (FUSE). May activate gene expression. Also involved in degradation of inherently unstable mRNAs that contain AU-rich elements (AREs) in their 3'-UTR, possibly by recruiting degradation machinery to ARE-containing mRNAs.
messages: Cytoplasm
messages: Detected in neural and non-neural cell lines.
messages: KH domains KH 3 and KH 4 behave as independent binding modules and can interact with different regions of the AU-rich RNA targets of degradation.
messages: Nucleus
messages: Part of a ternary complex containing FUBP2, PTBP1, PTBP2 and HNRPH1 (PubMed:11003644). Interacts with PARN (PubMed:15175153). Interacts with PQBP1 (PubMed:21933836).
messages: Phosphorylation at Ser-193 leads to the unfolding of the unstable KH domain 1, creating a site for 14-3-3 YWHAZ binding, which promotes nuclear localization and impairs the RNA degradation function.

9606:FGFRL1
gene id: 9606:FGFRL1
uniprot id: Q8N441
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Expressed preferentially in cartilaginous tissues and pancreas. Highly expressed in the liver, kidney, heart, brain and skeletal muscle. Weakly expressed in the lung, small intestine and spleen.
messages: Has a negative effect on cell proliferation.
messages: Interacts with FGF2 with a low affinity.
messages: Membrane

9606:KIF25
gene id: 9606:KIF25
uniprot id: Q9UIL4
names: Caution
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family.
messages: Homotetramer.
messages: In contrast to the ortholog protein in primates, human KIF25 protein is shorter at the N-terminus. While the kinesin motor domain is intact, it is unknown whether the absence of the N-terminus affects the microtubule-dependent motor activity.
messages: Minus-end microtubule-dependent motor protein (By similarity). Acts as a negative regulator of centrosome separation required to prevent premature centrosome separation during interphase (PubMed:28263957). Required to maintain a centered nucleus to ensure that the spindle is stably oriented at the onset of mitosis (PubMed:28263957). May also act as a negative regulator of amino acid starvation-induced autophagy (PubMed:22354037).
messages: centrosome

9606:CPD
gene id: 9606:CPD
uniprot id: O75976
names: Cofactor
names: Domain
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the peptidase M14 family.
messages: Binds 2 Zn(2+) ions per subunit.
messages: Cell membrane
messages: Highly expressed in placenta, pancreas and hepatoma cells. Lower levels found in skeletal muscle, heart and colon carcinoma and melanoma cell lines.
messages: There are 3 carboxypeptidase-like domains. Only the first two domains seem to have kept a catalytic activity.

9606:LGALS1
gene id: 9606:LGALS1
uniprot id: P09382
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cytoplasm
messages: Expressed in placenta, maternal decidua and fetal membranes. Within placenta, expressed in trophoblasts, stromal cells, villous endothelium, syncytiotrophoblast apical membrane and villous stroma. Within fetal membranes, expressed in amnion, chorioamniotic mesenchyma and chorion (at protein level). Expressed in cardiac, smooth, and skeletal muscle, neurons, thymus, kidney and hematopoietic cells.
messages: Homodimer. Binds LGALS3BP. Interacts with CD2, CD3, CD4, CD6, CD7, CD43, ALCAM and CD45. Interacts with laminin (via poly-N-acetyllactosamine). Interacts with SUSD2. Interacts with cargo receptor TMED10; the interaction mediates the translocation from the cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) and thereby secretion (PubMed:32272059).
messages: Lectin that binds beta-galactoside and a wide array of complex carbohydrates. Plays a role in regulating apoptosis, cell proliferation and cell differentiation. Inhibits CD45 protein phosphatase activity and therefore the dephosphorylation of Lyn kinase. Strong inducer of T-cell apoptosis.
messages: Secreted
messages: extracellular matrix

9606:NFYA
gene id: 9606:NFYA
uniprot id: P23511
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the NFYA/HAP2 subunit family.
messages: Component of the sequence-specific heterotrimeric transcription factor (NF-Y) which specifically recognizes a 5'-CCAAT-3' box motif found in the promoters of its target genes. NF-Y can function as both an activator and a repressor, depending on its interacting cofactors. NF-YA positively regulates the transcription of the core clock component BMAL1.
messages: Heterotrimeric transcription factor composed of three components, NF-YA, NF-YB and NF-YC. NF-YB and NF-YC must interact and dimerize for NF-YA association and DNA binding. Interacts with SP1; the interaction is inhibited by glycosylation of SP1. Interacts with ZHX1. Interacts (via N-terminus) with ZHX2 (via homeobox domain). Interacts with ZFX3.
messages: Nucleus

9606:TRIM8
gene id: 9606:TRIM8
uniprot id: Q9BZR9
names: Disease Annotation
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the TRIM/RBCC family.
messages: Cytoplasm
messages: E3 ubiquitin-protein ligase that participates in multiple biological processes including cell survival, differentiation, apoptosis, and in particular, the innate immune response (PubMed:27981609, PubMed:28747347). Participates in the activation of interferon-gamma signaling by promoting proteasomal degradation of the repressor SOCS1 (PubMed:12163497). Plays a positive role in the TNFalpha and IL-1beta signaling pathways. Mechanistically, induces the 'Lys-63'-linked polyubiquitination of MAP3K7/TAK1 component leading to the activation of NF-kappa-B (PubMed:22084099, PubMed:23152791, PubMed:27981609, PubMed:34871740). Modulates also STAT3 activity through negative regulation of PIAS3, either by degradation of PIAS3 through the ubiquitin-proteasome pathway or exclusion of PIAS3 from the nucleus (PubMed:20516148). Negatively regulates TLR3/4-mediated innate immune response by catalyzing 'Lys-6'- and 'Lys-33'-linked polyubiquitination of TICAM1 and thereby disrupting the TICAM1-TBK1 interaction (PubMed:28747347).
messages: Homodimer. Interacts with SOCS1 (via) SH2 domain and SOCS box (PubMed:12163497). Interacts with HSP90AB1; prevents nucleus translocation of phosphorylated STAT3 and HSP90AB1. Interacts with MAP3K7/TAK1 (PubMed:22084099). Interacts with PIAS3 (PubMed:20516148). Interacts with TICAM1 (PubMed:28747347). Interacts with TRIM15; this interaction prevents TRIM8 cytoplasmic translocation (PubMed:34871740).
messages: Nucleus
messages: The coiled coil domain is required for homodimerization.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The region immediately C-terminal to the RING motif is sufficient to mediate the interaction with SOCS1.
messages: Widely expressed. Expressed in glomerular podocytes of kidneys.
messages: nuclear body

9606:GOLGA8B
gene id: 9606:GOLGA8B
uniprot id: A8MQT2
names: Caution
names: Domain
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: A family of highly similar proteins (GOLGA8A, GOLGA8B, GOLGA8C, GOLGA8D, GOLGA8E, GOLGA8F, GOLGA8G) are encoded by a repeated region on chromosome 15q11-15q13. Our sequences are in agreement with HGNC nomenclature.
messages: Antibodies against GM88 are present in serum from a patient with Sjoegren syndrome. Sera from patients with Sjoegren syndrome often contain antibodies that react with normal components of the Golgi complex.
messages: Belongs to the GOLGA8 family.
messages: Extended rod-like protein with coiled-coil domains.
messages: Golgi stack membrane
messages: Highly expressed in brain, heart and kidney. Detected at lower levels in liver, thymus, spleen, lung and peripheral blood leukocytes.
messages: May be involved in maintaining Golgi structure.

9606:DVL2
gene id: 9606:DVL2
uniprot id: O14641
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the DSH family.
messages: Cell membrane
messages: Cytoplasmic vesicle
messages: Interacts through its PDZ domain with the C-terminal regions of VANGL1 and VANGL2. Interacts with Rac. Interacts with ARRB1; the interaction is enhanced by phosphorylation of DVL1 (By similarity). Can form large oligomers (via DIX domain). Interacts (via DIX domain) with DIXDC1 (via DIX domain). Interacts (via DEP domain) with AP2M1 and the AP-2 complex (By similarity). Interacts with DACT1 and FAM105B/otulin. Interacts with DCDC2. Interacts (when phosphorylated) with FOXK1 and FOXK2; the interaction induces DVL2 nuclear translocation (PubMed:25805136). Interacts with MAPK15 (By similarity). Interacts with PKD1 (via extracellular domain) (PubMed:27214281). Interacts with LMBR1L (By similarity).
messages: Nucleus
messages: Phosphorylated by CSNK1D (PubMed:21422228, PubMed:9192851). WNT3A induces DVL2 phosphorylation by CSNK1E and MARK kinases (PubMed:25805136).
messages: Plays a role in the signal transduction pathways mediated by multiple Wnt genes. Participates both in canonical and non-canonical Wnt signaling by binding to the cytoplasmic C-terminus of frizzled family members and transducing the Wnt signal to down-stream effectors. Promotes internalization and degradation of frizzled proteins upon Wnt signaling.
messages: The DIX domain mediates homooligomerization.
messages: cytosol

9606:NCOA1
gene id: 9606:NCOA1
uniprot id: Q15788
names: Disease Annotation
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: A chromosomal aberration involving NCOA1 is a cause of rhabdomyosarcoma. Translocation t(2;2)(q35;p23) with PAX3 generates the NCOA1-PAX3 oncogene consisting of the N-terminus part of PAX3 and the C-terminus part of NCOA1. The fusion protein acts as a transcriptional activator. Rhabdomyosarcoma is the most common soft tissue carcinoma in childhood, representing 5-8% of all malignancies in children.
messages: Belongs to the SRC/p160 nuclear receptor coactivator family.
messages: Contains 7 Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs. LXXLL motifs 3, 4 and 5 are essential for the association with nuclear receptors. LXXLL motif 7, which is not present in isoform 2, increases the affinity for steroid receptors in vitro.
messages: Interacts with PPARA; the interaction is direct (PubMed:11698662). Interacts with PPARG; the interaction is direct (PubMed:11698662, PubMed:9744270). Interacts with ESRRG; the interaction is direct (PubMed:11864604). Interacts with STAT5A (via FDL motif) (PubMed:12954634). Interacts with STAT5B (via FDL motif) (PubMed:12954634). Interacts with STAT6 (via LXXLL motif) (PubMed:12138096). Interacts (via LXXLL 1, 2 and 3 motifs) with RORC (via AF-2 motif) (By similarity). Interacts with ASXL1 (PubMed:16606617). Interacts with the methyltransferase CARM1 (By similarity). Interacts with COPS5 (PubMed:10722692). Interacts with the histone acetyltransferase CREBBP (By similarity). Interacts with DDX5 (PubMed:11250900). Interacts with the histone acetyltransferase EP300 (By similarity). Interacts with ESR1 (PubMed:7481822). Interacts with GCCR (PubMed:7481822). Interacts with the basal transcription factor GTF2B (PubMed:8754792). Interacts with NCOA6 (PubMed:10567404). Interacts with NCOA2 (PubMed:10594042). Interacts with NR3C1 (PubMed:12917342). Interacts with NR4A1/Nur77 (PubMed:18690216). Interacts with NR4A3 (By similarity). Interacts with PCAF (PubMed:9296499). Interacts with PGR (PubMed:7481822). Interacts with PRMT2 (PubMed:12039952). Interacts with PRMT6 (PubMed:20047962). Interacts with PSMB9 (PubMed:16957778). Interacts with RXRA, the interaction is ligand-dependent (PubMed:19786558, PubMed:7481822). Interacts with STAT3 following IL-6 stimulation (PubMed:11773079). Interacts with TRA (PubMed:7481822). Interacts with TRIP4 (PubMed:25219498). Interacts with TTLL5/STAMP (PubMed:17116691). Interacts with UBE2L3; they functionally interact to regulate progesterone receptor transcriptional activity (PubMed:15367689). Interacts with VDR (PubMed:28698609).
messages: Major form. Contains a domain at its C-terminus (1241-1399) that is able to mediate transactivation.
messages: Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Involved in the coactivation of different nuclear receptors, such as for steroids (PGR, GR and ER), retinoids (RXRs), thyroid hormone (TRs) and prostanoids (PPARs). Also involved in coactivation mediated by STAT3, STAT5A, STAT5B and STAT6 transcription factors. Displays histone acetyltransferase activity toward H3 and H4; the relevance of such activity remains however unclear. Plays a central role in creating multisubunit coactivator complexes that act via remodeling of chromatin, and possibly acts by participating in both chromatin remodeling and recruitment of general transcription factors. Required with NCOA2 to control energy balance between white and brown adipose tissues. Required for mediating steroid hormone response. Isoform 2 has a higher thyroid hormone-dependent transactivation activity than isoform 1 and isoform 3.
messages: Nucleus
messages: Sumoylated; sumoylation increases its interaction with PGR and prolongs its retention in the nucleus. It does not prevent its ubiquitination and does not exert a clear effect on the stability of the protein.
messages: The C-terminal (1107-1441) part mediates the histone acetyltransferase (HAT) activity.
messages: Ubiquitinated; leading to proteasome-mediated degradation. Ubiquitination and sumoylation take place at different sites.
messages: Widely expressed.

9606:PTPRC
gene id: 9606:PTPRC
uniprot id: P08575
names: Caution
names: Developmental Stage
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Acts as a receptor for human cytomegalovirus protein UL11 and mediates binding of UL11 to T-cells, leading to reduced induction of tyrosine phosphorylation of multiple signaling proteins upon T-cell receptor stimulation and impaired T-cell proliferation.
messages: (Microbial infection) Interacts with human cytomegalovirus protein UL11; the interaction is required for binding of UL11 to T-cells.
messages: Belongs to the protein-tyrosine phosphatase family. Receptor class 1/6 subfamily.
messages: Binds GANAB and PRKCSH (By similarity). Interacts with SKAP1 (PubMed:11909961). Interacts with DPP4; the interaction is enhanced in an interleukin-12-dependent manner in activated lymphocytes (PubMed:12676959).
messages: Cell membrane
messages: Disease susceptibility may be associated with variants affecting the gene represented in this entry.
messages: Heavily N- and O-glycosylated.
messages: Isoform 1: Detected in thymocytes. Isoform 2: Detected in thymocytes. Isoform 3: Detected in thymocytes. Isoform 4: Not detected in thymocytes. Isoform 5: Detected in thymocytes. Isoform 6: Not detected in thymocytes. Isoform 7: Detected in thymocytes. Isoform 8: Not detected in thymocytes.
messages: Isoform 1: During T-cell development, expressed at the CD3-CD4-CD8- and CD3+CD4+CD8- stages but barely detectable at the CD3-CD4+CD8+ stage. Isoform 2: During T-cell development, expressed at low levels at the CD3-CD4-CD8- and CD3-CD4+CD8- stages but up-regulated at the CD3+CD4+CD8+ and CD3+CD4+CD8- stages. Isoform 3: During T-cell development, expressed at the CD3-CD4-CD8- and CD3+CD4+CD8- stages but barely detectable at the CD3-CD4+CD8+ stage. Isoform 5: During T-cell development, expressed at the CD3-CD4-CD8- and CD3+CD4+CD8- stages but barely detectable at the CD3-CD4+CD8+ stage. Isoform 7: Consistently expressed at high levels at all stages of T-cell development.
messages: It is uncertain whether Met-1 or Met-3 is the initiator.
messages: Membrane raft
messages: Protein tyrosine-protein phosphatase required for T-cell activation through the antigen receptor. Acts as a positive regulator of T-cell coactivation upon binding to DPP4. The first PTPase domain has enzymatic activity, while the second one seems to affect the substrate specificity of the first one. Upon T-cell activation, recruits and dephosphorylates SKAP1 and FYN. Dephosphorylates LYN, and thereby modulates LYN activity (By similarity).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The first PTPase domain interacts with SKAP1.

9606:ARHGEF4
gene id: 9606:ARHGEF4
uniprot id: Q9NR80
names: Domain
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acts as guanine nucleotide exchange factor (GEF) for RHOA, RAC1 and CDC42 GTPases. Binding of APC may activate RAC1 GEF activity. The APC-ARHGEF4 complex seems to be involved in cell migration as well as in E-cadherin-mediated cell-cell adhesion. Required for MMP9 up-regulation via the JNK signaling pathway in colorectal tumor cells. Involved in tumor angiogenesis and may play a role in intestinal adenoma formation and tumor progression.
messages: Cytoplasm
messages: Expressed at high levels in the brain, skeletal muscle and testis and at low levels in the kidney, lung, small intestine, ovary and prostate. Expression is aberrantly enhanced in most colorectal tumors.
messages: In an autoinhibited form the SH3 domain binds intramolecularly to the DH domain, thus blocking the Rac-binding site.
messages: Isoform 3 interacts with RHOA and RAC1, and (via ABR domain) with APC. Found in a complex consisting of ARHGEF4, APC and CTNNB1.
messages: ruffle membrane

9606:ALDH7A1
gene id: 9606:ALDH7A1
uniprot id: P49419
names: Disease Annotation
names: Function
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Aberrant splicing.
messages: Abundant in hepatoma cells and fetal cochlea, ovary, eye, heart, adrenal gland, liver and kidney. Low levels present in adult peripheral blood leukocytes and fetal brain, thymus, spleen, skeletal muscle, lung and tongue.
messages: Belongs to the aldehyde dehydrogenase family.
messages: Homotetramer.
messages: Mitochondrion
messages: Multifunctional enzyme mediating important protective effects. Metabolizes betaine aldehyde to betaine, an important cellular osmolyte and methyl donor. Protects cells from oxidative stress by metabolizing a number of lipid peroxidation-derived aldehydes. Involved in lysine catabolism.
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: cytosol

9606:RHCG
gene id: 9606:RHCG
uniprot id: Q9UBD6
names: Developmental Stage
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Ammonium transporter involved in the maintenance of acid-base homeostasis. Transports ammonium and its related derivative methylammonium across the plasma membrane of epithelial cells likely contributing to renal transepithelial ammonia transport and ammonia metabolism. Postulated to primarily mediate an electroneutral bidirectional transport of NH3 ammonia species according to a mechanism that implies interaction of an NH4(+) ion with acidic residues of the pore entry followed by dissociation of NH4(+) into NH3 and H(+). As a result NH3 transits through the central pore and is protonated on the extracellular side reforming NH4(+) (PubMed:11062476, PubMed:14761968, PubMed:15929723, PubMed:16477434, PubMed:16580862, PubMed:24077989). May act as a CO2 channel providing for renal acid secretion (PubMed:24077989).
messages: Apical cell membrane
messages: Belongs to the ammonium transporter (TC 2.A.49) family. Rh subfamily.
messages: Cell membrane
messages: Expressed in brain, testis, placenta, pancreas, esophagus and prostate. Expressed in squamous epithelial tissues (at protein level). Expressed in kidney.
messages: Homotrimer.
messages: N-glycosylated.
messages: Specifically expressed in fetal kidney.

9606:LPCAT1
gene id: 9606:LPCAT1
uniprot id: Q8NF37
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the 1-acyl-sn-glycerol-3-phosphate acyltransferase family.
messages: Cell membrane
messages: Endoplasmic reticulum membrane
messages: Erythrocytes.
messages: Exhibits acyltransferase activity (PubMed:21498505, PubMed:18156367). Exhibits acetyltransferase activity (By similarity). Activity is calcium-independent (By similarity). Catalyzes the conversion of lysophosphatidylcholine (1-acyl-sn-glycero-3-phosphocholine or LPC) into phosphatidylcholine (1,2-diacyl-sn-glycero-3-phosphocholine or PC) (PubMed:21498505, PubMed:18156367). Catalyzes the conversion 1-acyl-sn-glycerol-3-phosphate (lysophosphatidic acid or LPA) into 1,2-diacyl-sn-glycerol-3-phosphate (phosphatidic acid or PA) by incorporating an acyl moiety at the sn-2 position of the glycerol backbone (By similarity). Displays a clear preference for saturated fatty acyl-CoAs, and 1-myristoyl or 1-palmitoyl LPC as acyl donors and acceptors, respectively (By similarity). Involved in platelet-activating factor (PAF) biosynthesis by catalyzing the conversion of the PAF precursor, 1-O-alkyl-sn-glycero-3-phosphocholine (lyso-PAF) into 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (PAF) (By similarity). May synthesize phosphatidylcholine in pulmonary surfactant, thereby playing a pivotal role in respiratory physiology (By similarity). Involved in the regulation of lipid droplet number and size (PubMed:25491198).
messages: Golgi apparatus membrane
messages: Lipid droplet
messages: The HXXXXD motif is essential for acyltransferase activity and may constitute the binding site for the phosphate moiety of the glycerol-3-phosphocholine.
messages: The di-lysine motif may confer endoplasmic reticulum localization.

9606:ACTA2
gene id: 9606:ACTA2
uniprot id: D2JYH4
uniprot id: P62736
names: Disease Annotation
names: Function
names: Induction
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Monomeric actin is cross-linked by V.cholerae toxins RtxA and VgrG1 in case of infection: bacterial toxins mediate the cross-link between Lys-52 of one monomer and Glu-272 of another actin monomer, resulting in formation of highly toxic actin oligomers that cause cell rounding (PubMed:19015515). The toxin can be highly efficient at very low concentrations by acting on formin homology family proteins: toxic actin oligomers bind with high affinity to formins and adversely affect both nucleation and elongation abilities of formins, causing their potent inhibition in both profilin-dependent and independent manners (PubMed:26228148).
messages: ACTA2 mutations predispose patients to a variety of diffuse and diverse vascular diseases, premature onset coronary artery disease (CAD), premature ischemic strokes and Moyamoya disease.
messages: Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
messages: Belongs to the actin family.
messages: In vertebrates 3 main groups of actin isoforms, alpha, beta and gamma have been identified. The alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. The beta and gamma actins coexist in most cell types as components of the cytoskeleton and as mediators of internal cell motility.
messages: Methylated at His-75 by SETD3.
messages: Monomethylation at Lys-86 (K84me1) regulates actin-myosin interaction and actomyosin-dependent processes. Demethylation by ALKBH4 is required for maintaining actomyosin dynamics supporting normal cleavage furrow ingression during cytokinesis and cell migration.
messages: N-terminal cleavage of acetylated cysteine of intermediate muscle actin by ACTMAP.
messages: Oxidation of Met-46 and Met-49 by MICALs (MICAL1, MICAL2 or MICAL3) to form methionine sulfoxide promotes actin filament depolymerization. MICAL1 and MICAL2 produce the (R)-S-oxide form. The (R)-S-oxide form is reverted by MSRB1 and MSRB2, which promotes actin repolymerization.
messages: Polymerization of globular actin (G-actin) leads to a structural filament (F-actin) in the form of a two-stranded helix. Each actin can bind to 4 others.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Up-regulated in response to enterovirus 71 (EV71) infection.
messages: cytoskeleton

9606:CRISPLD2
gene id: 9606:CRISPLD2
uniprot id: Q9H0B8
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the CRISP family.
messages: Binds to heparin, dermatan sulfate and chondroitin sulfate.
messages: Promotes matrix assembly.
messages: Secreted

9606:SFI1
gene id: 9606:SFI1
uniprot id: A8K8P3
names: Caution
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the SFI1 family.
messages: CETN2-binding regions contains a conserved Trp residue in their C-terminal ends, which seems critical for interaction with CETN2.
messages: Interacts with CETN2 (via C-terminus).
messages: It is uncertain whether Met-1 or Met-24 is the initiator.
messages: Plays a role in the dynamic structure of centrosome-associated contractile fibers via its interaction with CETN2.
messages: centriole

9606:HELZ2
gene id: 9606:HELZ2
uniprot id: Q9BYK8
names: Caution
names: Domain
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the DNA2/NAM7 helicase family.
messages: Contains 5 Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs. These motifs are not required for interaction with PPARG.
messages: Expressed in various tissues including heart, pancreas, skeletal muscle, colon, spleen, liver, kidney, lung, peripheral blood and placenta.
messages: Helicase that acts as a transcriptional coactivator for a number of nuclear receptors including PPARA, PPARG, THRA, THRB and RXRA.
messages: Interacts with PPARA (via DNA-binding domain) and PPARG; the interaction stimulates the transcriptional activity of PPARA and PPARG. Interacts with THRAP3; the interaction is direct and HELZ2 and THRAP3 synergistically enhance the transcriptional activity of PPARG. It is probably part of the peroxisome proliferator activated receptor alpha interacting complex (PRIC).
messages: More abundantly expressed than isoform 2.
messages: Nucleus
messages: PubMed:12189208 experiments have been carried out partly in rat and partly in human.

9606:CDS1
gene id: 9606:CDS1
uniprot id: Q92903
names: Activity Regulation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the CDS family.
messages: Catalyzes the conversion of phosphatidic acid (PA) to CDP-diacylglycerol (CDP-DAG), an essential intermediate in the synthesis of phosphatidylglycerol, cardiolipin and phosphatidylinositol (PubMed:9407135, PubMed:25375833). Exhibits almost no acyl chain preference for PA, showing no discrimination for the sn-1/sn-2 acyl chain composition of PAs (PubMed:25375833). Plays an important role in regulating the growth of lipid droplets which are storage organelles at the center of lipid and energy homeostasis (PubMed:26946540, PubMed:31548309). Positively regulates the differentiation and development of adipocytes (By similarity).
messages: Endoplasmic reticulum membrane
messages: Expressed in adult tissues such as placenta, brain, small intestine, ovary, testis and prostate. Highly expressed in fetal kidney, lung and brain. Lower level in fetal liver.
messages: Homodimer (By similarity). Interacts with FOS; this interaction may enhance catalytic activity (By similarity).
messages: Inhibited by its anionic phospholipid end products, with phosphatidylinositol-(4,5)- bisphosphate showing the strongest inhibition.

9606:KIF13A
gene id: 9606:KIF13A
uniprot id: Q9H1H9
names: Developmental Stage
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family.
messages: Endosome membrane
messages: Expressed at very low level in most fetal tissues, but at higher levels in skeletal muscle and lung.
messages: Golgi apparatus membrane
messages: Interacts with AP2B1 (By similarity). Interacts with ZFYVE26. Interacts with AP1G1 and AP1G2.
messages: Midbody
messages: Plus end-directed microtubule-dependent motor protein involved in intracellular transport and regulating various processes such as mannose-6-phosphate receptor (M6PR) transport to the plasma membrane, endosomal sorting during melanosome biogenesis and cytokinesis. Mediates the transport of M6PR-containing vesicles from trans-Golgi network to the plasma membrane via direct interaction with the AP-1 complex. During melanosome maturation, required for delivering melanogenic enzymes from recycling endosomes to nascent melanosomes by creating peripheral recycling endosomal subdomains in melanocytes. Also required for the abcission step in cytokinesis: mediates translocation of ZFYVE26, and possibly TTC19, to the midbody during cytokinesis.
messages: Widely expressed, with highest levels in heart, brain and skeletal muscle.
messages: centrosome

9606:GPHN
gene id: 9606:GPHN
uniprot id: Q9NQX3
names: Activity Regulation
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Cell membrane
messages: Has also a catalytic activity and catalyzes two steps in the biosynthesis of the molybdenum cofactor. In the first step, molybdopterin is adenylated. Subsequently, molybdate is inserted into adenylated molybdopterin and AMP is released.
messages: Homotrimer, homodimer and homooligomer (PubMed:26613940). Interacts with GABARAP (By similarity). Interacts with SRGAP2 (via SH3 domain) (By similarity). Interacts with GABRA3 (PubMed:26613940). Interacts with GLRB (PubMed:26613940, PubMed:12684523). GABRA3 and GLRB occupy overlapping binding sites (By similarity). Interacts with ARHGAP32; IQSEC3, INSYN1 and INSYN2A (By similarity).
messages: In the C-terminal section; belongs to the MoeA family.
messages: In the N-terminal section; belongs to the MoaB/Mog family.
messages: Inhibited by copper and tungsten.
messages: Microtubule-associated protein involved in membrane protein-cytoskeleton interactions. It is thought to anchor the inhibitory glycine receptor (GLYR) to subsynaptic microtubules (By similarity). Acts as a major instructive molecule at inhibitory synapses, where it also clusters GABA type A receptors (PubMed:25025157, PubMed:26613940).
messages: Palmitoylated (PubMed:25025157). Palmitoylation is stimulated by GABA type A receptors activity (By similarity). Palmitoylation by ZDHHC12 regulates clustering at synapses (PubMed:25025157).
messages: Postsynaptic cell membrane
messages: Postsynaptic density
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: cytoskeleton
messages: cytosol
messages: dendrite

9606:DUXA
gene id: 9606:DUXA
uniprot id: A6NLW8
names: Developmental Stage
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the paired homeobox family.
messages: Expressed in embryonic stem cells.
messages: Expressed in single blastomeres from 8-cell stage embryos.
messages: Nucleus
messages: Transcription factor that acts as repressor.

9606:DUS1L
gene id: 9606:DUS1L
uniprot id: Q6P1R4
names: Function
names: Similarity
messages: Belongs to the Dus family. Dus1 subfamily.
messages: Catalyzes the synthesis of dihydrouridine, a modified base found in the D-loop of most tRNAs.

9606:WBP2NL
gene id: 9606:WBP2NL
uniprot id: Q6ICG8
names: Function
names: Tissue Specificity
messages: Expressed in testis.
messages: May play a role in meiotic resumption and pronuclear formation, mediated by a WW domain-signaling pathway during fertilization.

9606:UTP20
gene id: 9606:UTP20
uniprot id: O75691
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the UTP20 family.
messages: Expressed in appendix, brain, colon, fetal liver, heart, ovary, pancreas, placenta, prostate, skeletal muscle, small intestine, spleen, testis and thymus.
messages: Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3 (PubMed:34516797). Interacts with FBL and PPP1R26 (PubMed:16053918, PubMed:17498821).
messages: Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome. Involved in 18S pre-rRNA processing. Associates with U3 snoRNA.
messages: nucleolus

9606:BTG1
gene id: 9606:BTG1
uniprot id: P62324
uniprot id: Q6IBC8
names: Developmental Stage
names: Disease Annotation
names: Function
names: Similarity
names: Subunit
messages: A chromosomal aberration involving BTG1 may be a cause of a form of B-cell chronic lymphocytic leukemia. Translocation t(8;12)(q24;q22) with MYC.
messages: Anti-proliferative protein.
messages: Belongs to the BTG family.
messages: Interacts with CNOT7 and CNOT8.
messages: Its expression is associated with the early G1 phase of the cell cycle.

9606:RGL4
gene id: 9606:RGL4
uniprot id: Q8IZJ4
names: Subcellular Location Annotation
messages: Cytoplasmic vesicle

9606:SLC16A14
gene id: 9606:SLC16A14
uniprot id: Q7RTX9
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the major facilitator superfamily. Monocarboxylate porter (TC 2.A.1.13) family.
messages: Cell membrane
messages: Proton-linked monocarboxylate transporter. May catalyze the transport of monocarboxylates across the plasma membrane.

9606:ZNF607
gene id: 9606:ZNF607
uniprot id: Q96SK3
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:DNAJC16
gene id: 9606:DNAJC16
uniprot id: Q9Y2G8
names: Function
names: Subcellular Location Annotation
messages: Endoplasmic reticulum membrane
messages: Plays an important role in regulating the size of autophagosomes during the formation process.

9606:UBE2G1
gene id: 9606:UBE2G1
uniprot id: P62253
names: Function
names: PTM
names: Similarity
names: Tissue Specificity
messages: Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-48'-, as well as 'Lys-63'-linked polyubiquitination. May be involved in degradation of muscle-specific proteins. Mediates polyubiquitination of CYP3A4.
messages: Autoubiquitinated in vitro.
messages: Belongs to the ubiquitin-conjugating enzyme family.
messages: Widely expressed, mainly in skeletal muscle.

9606:PRSS23
gene id: 9606:PRSS23
uniprot id: O95084
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the peptidase S1 family.
messages: Secreted

9606:GPR39
gene id: 9606:GPR39
uniprot id: O43194
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Expressed in many tissues, including the stomach, intestine and hypothalamus.
messages: Zn(2+) acts as an agonist. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated mainly through G(q)-alpha and G(12)/G(13) proteins. Involved in regulation of body weight, gastrointestinal mobility, hormone secretion and cell death (By similarity).

9606:SAA2-SAA4
gene id: 9606:SAA2-SAA4
uniprot id: A0A096LPE2
names: Similarity
messages: Belongs to the SAA family.

9606:JKAMP
gene id: 9606:JKAMP
uniprot id: Q9P055
names: Function
names: Induction
names: Miscellaneous
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: Basal expression under nonstress conditions; expression increases transiently after endoplasmic reticulum (ER) stress.
messages: Elevated expression in medulloblastomas (PubMed:12800201). Patients with cancer had 2 to 12-fold higher frequencies of antibodies against this antigen (PubMed:12800201).
messages: Endoplasmic reticulum membrane
messages: Interacts with RNF5 and MAPK8, but not with MAPK9. Binding to MAPK8 occurs before and after exposure to stress, such as UV irradiation. After exposure to stress, interacts with phosphorylated MAPK8. Competes with DUSP10 for MAPK8 binding. Associates with multiple components of the proteasome and with ERAD regulatory proteins including AMFR/GP78, CANX, PSMC1, PSMC2, PSMC3/TBP1, PSMC5, PSMC6, PSMD8, SEC61-ALPHA and UFD1 (By similarity). Interacts with DERL1 (in the presence of misfolded protein CFTR(F508del)) (PubMed:18784250).
messages: Regulates the duration of MAPK8 activity in response to various stress stimuli (By similarity). Facilitates degradation of misfolded endoplasmic reticulum (ER) proteins through the recruitment of components of the proteasome and endoplasmic reticulum-associated degradation (ERAD) system (PubMed:18784250).
messages: Ubiquitinated by RNF5 via 'Lys-63'-linked ubiquitin linkage in a UBE2N-dependent manner. Ubiquitination decreases association with components of the proteasome and ERAD.

9606:DMBX1
gene id: 9606:DMBX1
uniprot id: Q8NFW5
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the paired homeobox family.
messages: Functions as a transcriptional repressor. May repress OTX2-mediated transactivation by forming a heterodimer with OTX2 on the P3C (5'-TAATCCGATTA-3') sequence. Required for brain development (By similarity).
messages: Homodimer or heterodimer. Forms heterodimers with OTX2 (By similarity).
messages: Nucleus

9606:PI4KB
gene id: 9606:PI4KB
uniprot id: A0A0B4J1S8
uniprot id: Q9UBF8
names: Activity Regulation
names: Developmental Stage
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Activated by Aichi virus protein 3A, this activation is sensitized by ACBD3.
messages: (Microbial infection) Interacts with Aichi virus protein 3A. Part of a complex Aichi virus protein 3A/ACBD3/PI4KB that allows the synthesis of PI4P at the viral RNA replication sites.
messages: (Microbial infection) Plays an essential role in Aichi virus RNA replication (PubMed:22124328, PubMed:27989622, PubMed:22258260). Recruited by ACBD3 at the viral replication sites (PubMed:22124328, PubMed:27989622).
messages: (Microbial infection) Required for cellular spike-mediated entry of human coronavirus SARS-CoV.
messages: Belongs to the PI3/PI4-kinase family. Type III PI4K subfamily.
messages: Endomembrane system
messages: Expressed in 11-week old fetal inner ear.
messages: Golgi apparatus
messages: Golgi apparatus membrane
messages: Inhibited by wortmannin and adenosine (PubMed:11277933). Increased kinase activity upon interaction with NCS1/FREQ (By similarity).
messages: Interacts with ARF1 and ARF3 in the Golgi complex, but not with ARF4, ARF5 or ARF6 (PubMed:17555535). Interacts with NCS1/FREQ in a calcium-independent manner. Interacts with CALN1/CABP8 and CALN2/CABP7; in a calcium-dependent manner; this interaction competes with NCS1/FREQ binding (By similarity). Interacts with ACBD3 (PubMed:23572552, PubMed:27009356, PubMed:27989622, PubMed:22124328, PubMed:22258260). Interacts with ARMH3, YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ, YWHAZ and SFN (PubMed:23572552). Interacts with GGA2 (via VHS domain); the interaction is important for PI4KB location at the Golgi apparatus membrane (PubMed:28289207). Interacts with ATG9A (PubMed:30917996).
messages: Mitochondrion outer membrane
messages: Phosphorylates phosphatidylinositol (PI) in the first committed step in the production of the second messenger inositol-1,4,5,-trisphosphate (PIP). May regulate Golgi disintegration/reorganization during mitosis, possibly via its phosphorylation. Involved in Golgi-to-plasma membrane trafficking (By similarity) (PubMed:10559940, PubMed:11277933, PubMed:12749687, PubMed:9405935). May play an important role in the inner ear development.
messages: Rough endoplasmic reticulum membrane
messages: The disease may be caused by variants affecting the gene represented in this entry.
messages: Widely expressed with highest levels in heart, skeletal muscle, pancreas, testis and ovary. Weakly expressed in liver (PubMed:9020160, PubMed:9405935, PubMed:9405938). Expressed in the innear ear in the epithelium of the spinal organ of corti.
messages: perinuclear region

9606:PPP1R10
gene id: 9606:PPP1R10
uniprot id: Q2L6I0
uniprot id: Q96QC0
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Component of the PTW/PP1 phosphatase complex, composed of PPP1R10/PNUTS, TOX4, WDR82, and PPP1CA or PPP1CB or PPP1CC. Interacts with PPP1CC. Interacts with PPP1CA, WDR82 and TOX4 (By similarity).
messages: Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.
messages: Nucleus
messages: Phosphorylated on Ser-398 by PKA within the region necessary for interaction with PPP1CA.
messages: Scaffold protein which mediates the formation of the PTW/PP1 phosphatase complex by providing a binding platform to each component of the complex. The PTW/PP1 phosphatase complex plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase. Mediates interaction of WDR82 and PPP1CA. Inhibitor of PPP1CA and PPP1CC phosphatase activities. Has inhibitory activity on PPP1CA only when phosphorylated. Binds to mRNA, single-stranded DNA (ssDNA), poly(A) and poly(G) homopolymers (By similarity).
messages: Scaffold protein which mediates the formation of the PTW/PP1 phosphatase complex by providing a binding platform to each component of the complex. The PTW/PP1 phosphatase complex plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase. Mediates interaction of WDR82 and PPP1CA. Inhibitor of PPP1CA and PPP1CC phosphatase activities. Has inhibitory activity on PPP1CA only when phosphorylated. Binds to mRNA, single-stranded DNA (ssDNA), poly(A) and poly(G) homopolymers.

9606:KIF17
gene id: 9606:KIF17
uniprot id: A0A0A0MRS8
uniprot id: Q9P2E2
names: Caution
names: Function
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family.
messages: Cloning artifact.
messages: Contaminating sequence. Sequence of unknown origin in the N-terminal part.
messages: Dendrite-specific motor protein which, in association with the Apba1-containing complex (LIN-10-LIN-2-LIN-7 complex), transports vesicles containing N-methyl-D-aspartate (NMDA) receptor subunit NR2B along microtubules.
messages: Homodimer (By similarity). Interacts with APBA1 (via PDZ domain); the interaction is direct and is required for association of KIF17 with the cargo that is to be transported (By similarity). Interacts with IFT B complex components IFT52 and IFT57 (By similarity). Interacts with IFT70B (By similarity). Interacts with PIWIL1 (By similarity). Interacts with TBATA (By similarity).
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: cilium
messages: cytoskeleton
messages: dendrite

9606:GRB7
gene id: 9606:GRB7
uniprot id: A0A0S2Z4F6
uniprot id: Q14451
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Adapter protein that interacts with the cytoplasmic domain of numerous receptor kinases and modulates down-stream signaling. Promotes activation of down-stream protein kinases, including STAT3, AKT1, MAPK1 and/or MAPK3. Promotes activation of HRAS. Plays a role in signal transduction in response to EGF. Plays a role in the regulation of cell proliferation and cell migration. Plays a role in the assembly and stability of RNA stress granules. Binds to the 5'UTR of target mRNA molecules and represses translation of target mRNA species, when not phosphorylated. Phosphorylation impairs RNA binding and promotes stress granule disassembly during recovery after cellular stress (By similarity).
messages: Belongs to the GRB7/10/14 family.
messages: Cell membrane
messages: Cell projection
messages: Cytoplasm
messages: Cytoplasmic granule
messages: Homodimer. Interacts (via SH2 domain) with EGFR, ERBB2, ERBB3 (when phosphorylated), ERBB4 (when phosphorylated), EPHB1, INSR, FGFR1, PDGFRA (tyrosine phosphorylated) and PDGFRB (tyrosine phosphorylated). Interacts with SHC1. Interacts with RND1. Interacts (when tyrosine phosphorylated) with FHL2 and HAX1 (By similarity). Interacts (via SH2 domain) with RET and PTK2/FAK1. Interacts (when not phosphorylated) with ELAVL1. In stressed cells, but not in normal cells, part of a complex that contains at least GRB7, PTK2/FAK1, STAU1, ELAVL1 and TIA1. Interacts (via SH2 domain) with KIT (phosphorylated). Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated) (By similarity).
messages: Phosphorylated on serine and threonine residues in response to heregulin. Phosphorylated on tyrosine residues by TEK/TIE2. Phosphorylated on tyrosine residues in response to NTN1 signaling. Phosphorylation promotes stress granule disassembly during recovery after cellular stress (By similarity). Phosphorylated on tyrosine residues by PTK2/FAK1, and possibly also other kinases. Phosphorylation is enhanced by activation of receptor kinases. Tyrosine phosphorylation is essential for activation of down-stream protein kinases.
messages: The PH domain mediates interaction with membranes containing phosphoinositides.
messages: focal adhesion

9606:PRH2
gene id: 9606:PRH2
uniprot id: P02810
names: Function
names: PTM
names: Polymorphism
names: Subcellular Location Annotation
messages: An hexuronic acid was shown to be linked to Ser-33 in about 40% of the polypeptides. Neither the structure of the carbohydrate (whether glucuronic acid or an isomer of), nor the linkage (whether a glycoside or an ester) has been definitely established.
messages: PRP's act as highly potent inhibitors of crystal growth of calcium phosphates. They provide a protective and reparative environment for dental enamel which is important for the integrity of the teeth.
messages: Proteolytically cleaved; PRP-2, PRP-1, PIF-S and Db-S yield PRP-4, PRP-3 (protein A), PIF-F and Db-F, respectively.
messages: Secreted
messages: Sequence shown is that of allele PRH1-PIF, which is the most frequent allele (68% of the population). The PRH1-DB allele (about 16% of the population) has an insertion of 21 repeated amino acids compared to the PRH1-PIF allele. Allele PRH2-2, also known as PR-2, allele PRH2-1 is also known as PR-1 or protein C, and allele PRH2-3 as PR-1'. In contrast to all other PRH1 and PRH2 alleles, the PRH1-PA allele (16%) is not proteolytically cleaved.

9606:SPC25
gene id: 9606:SPC25
uniprot id: Q9HBM1
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Acts as a component of the essential kinetochore-associated NDC80 complex, which is required for chromosome segregation and spindle checkpoint activity (PubMed:14699129, PubMed:14738735). Required for kinetochore integrity and the organization of stable microtubule binding sites in the outer plate of the kinetochore (PubMed:14738735, PubMed:14699129). The NDC80 complex synergistically enhances the affinity of the SKA1 complex for microtubules and may allow the NDC80 complex to track depolymerizing microtubules (PubMed:23085020).
messages: Belongs to the SPC25 family.
messages: Component of the NDC80 complex, which consists of NDC80/HEC1, CDCA1, SPBC24 and SPBC25. The NDC80 complex is formed by two subcomplexes composed of NDC80/HEC1-CDCA1 and SPBC24-SPBC25. Each subcomplex is formed by parallel interactions through the coiled-coil domains of individual subunits. Formation of a tetrameric complex is mediated by interactions between the C-terminal regions of both subunits of the NDC80/HEC1-CDCA1 subcomplex and the N-terminal regions of both subunits of the SPBC24-SPBC25 complex. The tetrameric NDC80 complex has an elongated rod-like structure with globular domains at either end.
messages: Nucleus
messages: kinetochore

9606:FBXL3
gene id: 9606:FBXL3
uniprot id: Q9UKT7
names: Disease Annotation
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cytoplasm
messages: Nucleus
messages: Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXL3) composed of CUL1, SKP1, RBX1 and FBXL3 (By similarity). Interacts with CRY1 and CRY2 (phosphorylated) (PubMed:17463251). Interacts with HDAC3 (By similarity). Interacts with KDM8 (By similarity).
messages: Substrate-recognition component of the SCF(FBXL3) E3 ubiquitin ligase complex involved in circadian rhythm function. Plays a key role in the maintenance of both the speed and the robustness of the circadian clock oscillation (PubMed:17463251, PubMed:23452855, PubMed:27565346). The SCF(FBXL3) complex mainly acts in the nucleus and mediates ubiquitination and subsequent degradation of CRY1 and CRY2 (PubMed:17463251, PubMed:23452855, PubMed:27565346). Activity of the SCF(FBXL3) complex is counteracted by the SCF(FBXL21) complex (PubMed:23452855).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Undergoes autophagy-mediated degradation in the liver in a time-dependent manner.
messages: Widely expressed.

9606:CRYL1
gene id: 9606:CRYL1
uniprot id: Q9Y2S2
uniprot id: V9HWG2
names: Activity Regulation
names: Function
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the 3-hydroxyacyl-CoA dehydrogenase family.
messages: Cytoplasm
messages: Has high L-gulonate 3-dehydrogenase activity. It also exhibits low dehydrogenase activity toward L-3-hydroxybutyrate (HBA) and L-threonate.
messages: Homodimer.
messages: Inhibited by malonate.
messages: Unknown reasons.
messages: Widely expressed, with highest levels in liver and kidney.

9606:TAS2R31
gene id: 9606:TAS2R31
uniprot id: P59538
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor T2R family.
messages: Expressed in subsets of taste receptor cells of the tongue and exclusively in gustducin-positive cells.
messages: Membrane
messages: Most taste cells may be activated by a limited number of bitter compounds; individual taste cells can discriminate among bitter stimuli.
messages: Receptor that may play a role in the perception of bitterness and is gustducin-linked. May play a role in sensing the chemical composition of the gastrointestinal content. The activity of this receptor may stimulate alpha gustducin, mediate PLC-beta-2 activation and lead to the gating of TRPM5 (By similarity). Activated by the sulfonyl amide sweeteners saccharin and acesulfame K.

9606:MPHOSPH8
gene id: 9606:MPHOSPH8
uniprot id: Q99549
names: Domain
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: Chromosome
messages: Heterochromatin component that specifically recognizes and binds methylated 'Lys-9' of histone H3 (H3K9me) and promotes recruitment of proteins that mediate epigenetic repression (PubMed:20871592, PubMed:26022416). Mediates recruitment of the HUSH complex to H3K9me3 sites: the HUSH complex is recruited to genomic loci rich in H3K9me3 and is required to maintain transcriptional silencing by promoting recruitment of SETDB1, a histone methyltransferase that mediates further deposition of H3K9me3, as well as MORC2 (PubMed:26022416, PubMed:28581500). Binds H3K9me and promotes DNA methylation by recruiting DNMT3A to target CpG sites; these can be situated within the coding region of the gene (PubMed:20871592). Mediates down-regulation of CDH1 expression (PubMed:20871592). Also represses L1 retrotransposons in collaboration with MORC2 and, probably, SETDB1, the silencing is dependent of repressive epigenetic modifications, such as H3K9me3 mark. Silencing events often occur within introns of transcriptionally active genes, and lead to the down-regulation of host gene expression (PubMed:29211708). The HUSH complex is also involved in the silencing of unintegrated retroviral DNA by being recruited by ZNF638: some part of the retroviral DNA formed immediately after infection remains unintegrated in the host genome and is transcriptionally repressed (PubMed:30487602).
messages: Homodimer (PubMed:21419134, PubMed:22022377, PubMed:22086334). Interacts (via chromo domain) with histone H3K9me3 (PubMed:20871592). Has the highest affinity for H3K9me3, and lesser affinity for H3K9me2 and H3K9me1 (PubMed:20871592). Component of the HUSH complex; at least composed of TASOR, PPHLN1 and MPHOSPH8 (PubMed:26022416). Interacts with DNMT3, EHMT1 and SETDB1 (PubMed:20871592, PubMed:22086334). Interacts with MORC2; the interaction associateS MORC2 with the HUSH complex which recruits MORC2 to heterochromatic loci (PubMed:28581500). Interacts with ZNF638; leading to recruitment of the HUSH complex to unintegrated retroviral DNA (PubMed:30487602). Interacts with TASOR (By similarity). Interacts with humanin (PubMed:23532874).
messages: Nucleus
messages: Phosphorylated in M (mitotic) phase. Phosphorylation by CDK1 promotes dissociation from chromatin.
messages: The chromo domain mediates interaction with methylated 'Lys-9' of histone H3 (H3K9me), with the highest affinity for the trimethylated form (H3K9me3).

9606:CAMK1
gene id: 9606:CAMK1
uniprot id: B0YIY3
uniprot id: Q14012
names: Activity Regulation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Activated by Ca(2+)/calmodulin. Binding of calmodulin results in conformational change that relieves intrasteric autoinhibition and allows phosphorylation of Thr-177 within the activation loop by CaMKK1 or CaMKK2. Phosphorylation of Thr-177 results in several fold increase in total activity. Unlike CaMK4, is unable to exhibit autonomous activity after Ca(2+)/calmodulin activation.
messages: Belongs to the protein kinase superfamily.
messages: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily.
messages: Calcium/calmodulin-dependent protein kinase that operates in the calcium-triggered CaMKK-CaMK1 signaling cascade and, upon calcium influx, regulates transcription activators activity, cell cycle, hormone production, cell differentiation, actin filament organization and neurite outgrowth. Recognizes the substrate consensus sequence [MVLIF]-x-R-x(2)-[ST]-x(3)-[MVLIF]. Regulates axonal extension and growth cone motility in hippocampal and cerebellar nerve cells. Upon NMDA receptor-mediated Ca(2+) elevation, promotes dendritic growth in hippocampal neurons and is essential in synapses for full long-term potentiation (LTP) and ERK2-dependent translational activation. Downstream of NMDA receptors, promotes the formation of spines and synapses in hippocampal neurons by phosphorylating ARHGEF7/BETAPIX on 'Ser-694', which results in the enhancement of ARHGEF7 activity and activation of RAC1. Promotes neuronal differentiation and neurite outgrowth by activation and phosphorylation of MARK2 on 'Ser-91', 'Ser-92', 'Ser-93' and 'Ser-294'. Promotes nuclear export of HDAC5 and binding to 14-3-3 by phosphorylation of 'Ser-259' and 'Ser-498' in the regulation of muscle cell differentiation. Regulates NUMB-mediated endocytosis by phosphorylation of NUMB on 'Ser-276' and 'Ser-295'. Involved in the regulation of basal and estrogen-stimulated migration of medulloblastoma cells through ARHGEF7/BETAPIX phosphorylation (By similarity). Is required for proper activation of cyclin-D1/CDK4 complex during G1 progression in diploid fibroblasts. Plays a role in K(+) and ANG2-mediated regulation of the aldosterone synthase (CYP11B2) to produce aldosterone in the adrenal cortex. Phosphorylates EIF4G3/eIF4GII. In vitro phosphorylates CREB1, ATF1, CFTR, MYL9 and SYN1/synapsin I.
messages: Cytoplasm
messages: Monomer. Interacts with XPO1 (By similarity). Interacts with MARK2, ARHGEF7/BETAPIX and GIT1.
messages: Nucleus
messages: Phosphorylated by CaMKK1 and CaMKK2 on Thr-177.
messages: Polybiquitinated by the E3 ubiquitin-protein ligase complex SCF(FBXL12), leading to proteasomal degradation.
messages: The autoinhibitory domain overlaps with the calmodulin binding region and interacts in the inactive folded state with the catalytic domain as a pseudosubstrate.
messages: Widely expressed. Expressed in cells of the zona glomerulosa of the adrenal cortex.

9606:CCL24
gene id: 9606:CCL24
uniprot id: O00175
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Activated monocytes and activated T lymphocytes.
messages: Belongs to the intercrine beta (chemokine CC) family.
messages: Chemotactic for resting T-lymphocytes, and eosinophils (PubMed:9104803, PubMed:9365122). Has lower chemotactic activity for neutrophils but none for monocytes and activated lymphocytes (PubMed:9104803, PubMed:9365122). Is a strong suppressor of colony formation by a multipotential hematopoietic progenitor cell line (PubMed:9104803, PubMed:9365122). Binds to CCR3 (PubMed:9104803, PubMed:9365122).
messages: N-glycosylated.
messages: Secreted

9606:FIGNL2
gene id: 9606:FIGNL2
uniprot id: A6NMB9
names: Similarity
messages: Belongs to the AAA ATPase family.

9606:ATRN
gene id: 9606:ATRN
uniprot id: B4DZ36
uniprot id: O75882
names: Caution
names: Function
names: Induction
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Activation of peripheral blood leukocytes with phytohemagglutinin induces strong expression of the membrane isoform followed by the release of the secreted isoform.
messages: Cell membrane
messages: Heavily glycosylated.
messages: Involved in the initial immune cell clustering during inflammatory response and may regulate chemotactic activity of chemokines. May play a role in melanocortin signaling pathways that regulate energy homeostasis and hair color. Low-affinity receptor for agouti (By similarity). Has a critical role in normal myelination in the central nervous system (By similarity).
messages: Isoform 2 is detected in plasma (at protein level). Expressed and secreted by activated T-lymphocytes. Expressed at low to moderate levels in peripheral blood leukocytes, spleen, lymph node, tonsil, bone marrow and fetal liver. At very low levels found in thymus. Isoform 2 is the major isoform in peripheral blood leukocytes.
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: Monomer and homotrimer.
messages: Secreted
messages: Was originally (PubMed:7539799, PubMed:9736737) thought to have dipeptidase activity but it was shown later to lack that activity.

9606:ABCA7
gene id: 9606:ABCA7
uniprot id: B3KUJ3
uniprot id: Q8IZY2
names: Activity Regulation
names: Caution
names: Developmental Stage
names: Disease Annotation
names: Function
names: Induction
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: ATPase activity is decreased by cholesterol and ceramide. ATPase activity is stimulated by phosphatidylserine, phosphatidylcholine and sphingomyelin, but phosphatidylserine is more effective.
messages: Belongs to the ABC transporter superfamily. ABCA family.
messages: Catalyzes the translocation of specific phospholipids from the cytoplasmic to the extracellular/lumenal leaflet of membrane coupled to the hydrolysis of ATP (PubMed:24097981). Transports preferentially phosphatidylserine over phosphatidylcholine (PubMed:24097981). Plays a role in lipid homeostasis and macrophage-mediated phagocytosis (PubMed:14592415, PubMed:12917409, PubMed:12925201, PubMed:14570867). Binds APOA1 and may function in apolipoprotein-mediated phospholipid efflux from cells (PubMed:12917409, PubMed:14570867, PubMed:14592415). May also mediate cholesterol efflux (PubMed:14570867). May regulate cellular ceramide homeostasis during keratinocyte differentiation (PubMed:12925201). Involved in lipid raft organization and CD1D localization on thymocytes and antigen-presenting cells, which plays an important role in natural killer T-cell development and activation (By similarity). Plays a role in phagocytosis of apoptotic cells by macrophages (By similarity). Macrophage phagocytosis is stimulated by APOA1 or APOA2, probably by stabilization of ABCA7 (By similarity). Also involved in phagocytic clearance of amyloid-beta by microglia cells and macrophages (By similarity). Further limits amyloid-beta production by playing a role in the regulation of amyloid-beta A4 precursor protein (APP) endocytosis and/or processing (PubMed:26260791). Amyloid-beta is the main component of amyloid plaques found in the brains of Alzheimer patients (PubMed:26260791).
messages: Cell membrane
messages: Cytoplasm
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry.
messages: Early endosome membrane
messages: Endoplasmic reticulum
messages: Expressed in fetal tissues. Strongly expressed in fetal liver.
messages: Expressed in leukocytes (at protein level) (PubMed:10873640). Widely expressed (PubMed:10873640). Highly expressed in myelo-lymphatic tissues including peripheral leukocytes, thymus, spleen and bone marrow (PubMed:10873640, PubMed:11435699). Expressed in the hippocampus and the cerebellum (PubMed:27472885). Isoform 2: Abundant in lymph node, spleen, thymus and trachea (PubMed:14592415). Isoform 1: Strongly expressed in brain and bone marrow (PubMed:14592415).
messages: Golgi apparatus membrane
messages: Inactive for apoA-I-mediated lipid release.
messages: Membrane
messages: N-glycosylated.
messages: There are conflicting results concerning the role of ABCA7 in lipid transport. ABCA7 was described to play a role in apolipoprotein-mediated phospholipid and cholesterol efflux when expressed in HEK293 cells (PubMed:12917409, PubMed:27472885). However, another report shows that ABCA7 deficiency does not influence cholesterol and phospholipid efflux in mouse primary macrophages, but leads to lower serum HDL cholesterol levels and a reduction in fat mass in female mice (By similarity).
messages: Up-regulated in macrophages upon cholesterol uptake and inversely regulated upon cholesterol deloading from the cells (at protein level). Up-regulated in keratinocytes during terminal differentiation.
messages: phagocytic cup
messages: ruffle membrane

9606:TMEM95
gene id: 9606:TMEM95
uniprot id: Q3KNT9
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the TMEM95 family.
messages: Does not interact with sperm-egg fusion proteins IZUMO1 or IZUMO1R/JUNO.
messages: Sperm protein required for fusion of sperm with the egg membrane during fertilization.
messages: acrosome membrane

9606:USP46
gene id: 9606:USP46
uniprot id: P62068
names: Activity Regulation
names: Function
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Activated by interaction with WDR48.
messages: Belongs to the peptidase C19 family. USP12/USP46 subfamily.
messages: Broadly expressed.
messages: Deubiquitinating enzyme that plays a role in behavior, possibly by regulating GABA action. May act by mediating the deubiquitination of GAD1/GAD67 (By similarity). Has almost no deubiquitinating activity by itself and requires the interaction with WDR48 to have a high activity (PubMed:19075014, PubMed:26388029). Not involved in deubiquitination of monoubiquitinated FANCD2 (PubMed:19075014).
messages: Interacts with WDR48 (PubMed:19075014, PubMed:26388029). Interacts with WDR20 (PubMed:20147737).

9606:MRPL16
gene id: 9606:MRPL16
uniprot id: Q9NX20
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the universal ribosomal protein uL16 family.
messages: Component of the mitochondrial large ribosomal subunit (mt-LSU) (PubMed:28892042, PubMed:25838379, PubMed:25278503). Mature mammalian 55S mitochondrial ribosomes consist of a small (28S) and a large (39S) subunit. The 28S small subunit contains a 12S ribosomal RNA (12S mt-rRNA) and 30 different proteins. The 39S large subunit contains a 16S rRNA (16S mt-rRNA), a copy of mitochondrial valine transfer RNA (mt-tRNA(Val)), which plays an integral structural role, and 52 different proteins.
messages: Mitochondrion

9606:ST18
gene id: 9606:ST18
uniprot id: O60284
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the MYT1 family.
messages: Detected at low levels in heart, liver, kidney, skeletal muscle, pancreas, testis, ovary and prostate. Detected at even lower levels in mammary epithelial cells and breast cancer cells.
messages: Nucleus
messages: Repressor that binds to DNA sequences containing a bipartite element consisting of a direct repeat of the sequence 5'-AAAGTTT-3' separated by 2-9 nucleotides. Represses basal transcription activity from target promoters (By similarity). Inhibits colony formation in cultured breast cancer cells.

9606:SLC4A4
gene id: 9606:SLC4A4
uniprot id: A5JJ20
uniprot id: Q9Y6R1
names: Caution
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Basolateral cell membrane
messages: Belongs to the anion exchanger (TC 2.A.31) family.
messages: Cell membrane
messages: Electrogenic sodium/bicarbonate cotransporter with a Na(+):HCO3(-) stoichiometry varying from 1:2 to 1:3. May regulate bicarbonate influx/efflux at the basolateral membrane of cells and regulate intracellular pH.
messages: Expressed in the corneal endothelium cells (at protein level). Expressed in pancreas and to a lower extent in heart, skeletal muscle, liver, parotid salivary glands, prostate, colon, stomach, thyroid, brain and spinal chord.
messages: Homodimer (PubMed:29500354). Interacts with CA2/carbonic anhydrase 2 and CA4/carbonic anhydrase 4 which may regulate transporter activity (PubMed:12411514, PubMed:14567693, PubMed:15218065, PubMed:15563508). Isoform 1 but not isoform 2 interacts with AHCYL1 (via PEST domain when phosphorylated); the interaction increases SLC4A4 isoform 1 activity (PubMed:16769890). Interacts with AHCYL2 (By similarity).
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: Lateral cell membrane
messages: Loss of interaction with and stimulation by CA4 is the cause of retinitis pigmentosa type 17 (RP17).
messages: Membrane
messages: N-glycosylated. May not be necessary for the transporter basic functions.
messages: Phosphorylation of Ser-1026 by PKA increases the binding of CA2 and changes the Na(+):HCO3(-) stoichiometry of the transporter from 3:1 to 2:1 (PubMed:11744745, PubMed:12411514, PubMed:12730338). Phosphorylated in presence of STK39 and dephosphorylated in presence of PP1 phosphatase; phosphorylation seems to inhibit SLC4A4 activity (By similarity).
messages: Specifically expressed in kidney at the level of proximal tubules.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:RIBC2
gene id: 9606:RIBC2
uniprot id: Q9H4K1
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the RIB43A family.
messages: Expressed in airway epithelial cells.
messages: Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating.
messages: cilium axoneme

9606:CLMN
gene id: 9606:CLMN
uniprot id: Q96JQ2
names: Sequence Caution
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Chimeric cDNA.
messages: Membrane
messages: Widely expressed at intermediate level.

9606:KRTAP10-3
gene id: 9606:KRTAP10-3
uniprot id: P60369
names: Function
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Belongs to the KRTAP type 10 family.
messages: In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.
messages: Interacts with hair keratins.
messages: Restricted to a narrow region of the hair fiber cuticle, lying approximately 20 cell layers above the apex of the dermal papilla of the hair root; not detected in any other tissues.

9606:LCE3B
gene id: 9606:LCE3B
uniprot id: Q5TA77
names: Function
names: Similarity
names: Tissue Specificity
messages: A structural component of the cornified envelope of the stratum corneum involved in innate cutaneous host defense (Probable). Possesses defensin-like antimicrobial activity against a broad spectrum of Gram-positive and Gram-negative bacteria, both aerobic and anaerobic species. Upon inflammation, may regulate skin barrier repair by shaping cutaneous microbiota composition and immune response to bacterial antigens (PubMed:28634035).
messages: Belongs to the LCE family.
messages: Skin-specific. Expression was readily detected in adult trunk skin, adult arm skin, fetal skin, penal skin, vulva, esophagus and tongue. Not expressed in the cervix, rectum, lung, colon, or placenta.

9606:NUDT22
gene id: 9606:NUDT22
uniprot id: Q9BRQ3
names: Function
names: Similarity
messages: Belongs to the Nudix hydrolase family.
messages: Hydrolyzes UDP-glucose to glucose 1-phosphate and UMP and UDP-galactose to galactose 1-phosphate and UMP. Preferred substrate is UDP-glucose.

9606:CHST4
gene id: 9606:CHST4
uniprot id: Q8NCG5
names: Function
names: Induction
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the sulfotransferase 1 family. Gal/GlcNAc/GalNAc subfamily.
messages: Golgi apparatus membrane
messages: May serve as an anti-inflammatory target.
messages: Monomer.
messages: Specifically expressed in HEV. Weakly expressed in spleen. Not expressed in other tissues. Expressed in colonic mucinous adenocarcinoma.
messages: Sulfotransferase involved in SELL/L-selectin ligand biosynthesis pathway. Catalyzes the transfer of the sulfate group from 3'-phospho-5'-adenylyl sulfate (PAPS) onto the hydroxyl group at C-6 position of the non-reducing N-acetylglucosamine (GlcNAc) residue within O-linked mucin-type glycans. Contributes to generate sialyl 6-sulfo Lewis X determinant (also known as MECA-79 epitope) for SELL recognition, a prerequisite for continuous lymphocyte homing into peripheral lymph nodes and antigen immune surveillance (PubMed:11439191, PubMed:12107080, PubMed:10330415, PubMed:11726653). Transfers the sulfate group primarily on core 2 GlcNAcbeta1-6(Galbeta1-3)GalNAcalphaSer/Thr and extended core 1 GlcNAcbeta1-3Galbeta1-3GalNAcalphaSer/Thr based O-linked glycans on CD34 and GLYCAM1 peripheral node addressins (PNAds) expressed on the lumenal side of high endothelial venules (HEVs) (PubMed:11439191). The recognition of PNAds by SELL initiates a multistep process comprising tethering and rolling of blood lymphocytes on HEVs against the blood flow, followed by chemokine signaling, integrin-mediated lymphocyte adhesion onto endothelial cells and lymphocyte transendothelial migration. Modulates rolling velocity and differential T and B lymphocyte recruitment into peripheral lymph nodes, with a major role in B lymphocyte homing. Might be redundant in sulfation of MADCAM1 and lymphocyte trafficking to mesenteric lymph nodes (By similarity). Can also sulfonate core 3 GlcNAcbeta1-3GalNAc-R based glycans as well as GlcNAcbeta1-3Galbeta1-Glc, GlcNAcbeta1-6ManOMe and GlcNAcbeta1-2Man oligosaccharides, which might be ectopically expressed during tumorigenesis (PubMed:12107080, PubMed:11439191, PubMed:11726653).
messages: Upon cytokine activation, it is expressed at low level.

9606:MYRIP
gene id: 9606:MYRIP
uniprot id: Q8NFW9
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Binds MYO5A, MYO7A and F-actin (By similarity). Binds RAB27A that has been activated by GTP-binding via its N-terminus. Interacts with PRKAR2A. Interacts with components of the exocyst complex, including EXOC3 and EXOC4 (By similarity).
messages: Cytoplasm
messages: Detected in brain, skin, heart, adrenal medulla, pancreas, intestine, liver, kidney, muscle and testis.
messages: Rab effector protein involved in melanosome transport. Serves as link between melanosome-bound RAB27A and the motor proteins MYO5A and MYO7A. May link RAB27A-containing vesicles to actin filaments. Functions as a protein kinase A-anchoring protein (AKAP). May act as a scaffolding protein that links PKA to components of the exocytosis machinery, thus facilitating exocytosis, including insulin release (By similarity).
messages: perinuclear region
messages: secretory vesicle

9606:TUBB2B
gene id: 9606:TUBB2B
uniprot id: A0A384MEE3
uniprot id: Q9BVA1
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the tubulin family.
messages: Defects in TUBB2B may be involved in cerebellar ataxia, intellectual disability, and dysequilibrium syndrome (CAMRQ).
messages: Dimer of alpha and beta chains (PubMed:23001566, PubMed:28013290, PubMed:26732629). A typical microtubule is a hollow water-filled tube with an outer diameter of 25 nm and an inner diameter of 15 nM. Alpha-beta heterodimers associate head-to-tail to form protofilaments running lengthwise along the microtubule wall with the beta-tubulin subunit facing the microtubule plus end conferring a structural polarity. Microtubules usually have 13 protofilaments but different protofilament numbers can be found in some organisms and specialized cells.
messages: Dimer of alpha and beta chains. A typical microtubule is a hollow water-filled tube with an outer diameter of 25 nm and an inner diameter of 15 nM. Alpha-beta heterodimers associate head-to-tail to form protofilaments running lengthwise along the microtubule wall with the beta-tubulin subunit facing the microtubule plus end conferring a structural polarity. Microtubules usually have 13 protofilaments but different protofilament numbers can be found in some organisms and specialized cells.
messages: High expression in brain.
messages: Phosphorylated on Ser-172 by CDK1 during the cell cycle, from metaphase to telophase, but not in interphase. This phosphorylation inhibits tubulin incorporation into microtubules.
messages: Some glutamate residues at the C-terminus are monoglycylated but not polyglycylated due to the absence of functional TTLL10 in human. Monoglycylation is mainly limited to tubulin incorporated into cilia and flagella axonemes, which is required for their stability and maintenance. Flagella glycylation controls sperm motility. Both polyglutamylation and monoglycylation can coexist on the same protein on adjacent residues, and lowering glycylation levels increases polyglutamylation, and reciprocally.
messages: Some glutamate residues at the C-terminus are polyglutamylated, resulting in polyglutamate chains on the gamma-carboxyl group (PubMed:26875866). Polyglutamylation plays a key role in microtubule severing by spastin (SPAST). SPAST preferentially recognizes and acts on microtubules decorated with short polyglutamate tails: severing activity by SPAST increases as the number of glutamates per tubulin rises from one to eight, but decreases beyond this glutamylation threshold (PubMed:26875866). Glutamylation is also involved in cilia motility (By similarity).
messages: The MREI motif is common among all beta-tubulin isoforms and may be critical for tubulin autoregulation.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers (PubMed:23001566, PubMed:28013290, PubMed:26732629). Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin. Plays a critical role in proper axon guidance in both central and peripheral axon tracts (PubMed:23001566). Implicated in neuronal migration (PubMed:19465910).
messages: Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin.
messages: cytoskeleton

9606:SLC9A5
gene id: 9606:SLC9A5
uniprot id: Q14940
names: Activity Regulation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: ATP-depletion almost completely abolishes SLC9A5 activity. Inhibited by amiloride compounds.
messages: Belongs to the monovalent cation:proton antiporter 1 (CPA1) transporter (TC 2.A.36) family.
messages: Cell membrane
messages: Interacts with CHP1 and CHP2 (By similarity). Interacts with ARRB2; facilitates the endocytosis of SLC9A5 from the plasma membrane (PubMed:15699339, PubMed:21296876). Interacts with RACK1; this interaction positively regulates SLC9A5 activity and promotes SLC9A5 localization to focal adhesions (PubMed:24006492). Interacts with SCAMP2; this interaction regulates SLC9A5 cell-surface targeting and SLC9A5 activity (PubMed:19276089).
messages: Mainly expressed in brain (PubMed:7759094, PubMed:9933641). Expressed in neurons of the central and peripheral nervous system (PubMed:21551074, PubMed:9933641). Expressed also in testis, spleen, and skeletal muscle (PubMed:7759094).
messages: Phosphorylated by PRKAA2; promotes its accumulation at the cell surface (PubMed:24936055). Phosphorylated by CSNK2A1 in a manner favoring its beta-arrestin binding and endocytosis (PubMed:21296876).
messages: Plasma membrane Na(+)/H(+) antiporter. Mediates the electroneutral exchange of intracellular H(+) ions for extracellular Na(+) in 1:1 stoichiometry, thus regulating intracellular pH homeostasis, in particular in neural tissues (PubMed:9933641, PubMed:10692428, PubMed:19276089, PubMed:24936055). Acts as a negative regulator of dendritic spine growth (PubMed:21551074). Plays a role in postsynaptic remodeling and signaling (PubMed:24006492, PubMed:21551074). Can also contribute to organellar pH regulation, with consequences for receptor tyrosine kinase trafficking (PubMed:24936055).
messages: Recycling endosome membrane
messages: Synaptic cell membrane
messages: dendritic spine membrane
messages: focal adhesion

9606:RBX1
gene id: 9606:RBX1
uniprot id: P62877
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts with human adenovirus 5 protein E1A; this interaction inhibits RBX1-CUL1-dependent elongation reaction of ubiquitin chains by the SCF(FBW7) complex.
messages: Belongs to the RING-box family.
messages: Cytoplasm
messages: E3 ubiquitin ligase component of multiple cullin-RING-based E3 ubiquitin-protein ligase (CRLs) complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins, including proteins involved in cell cycle progression, signal transduction, transcription and transcription-coupled nucleotide excision repair (PubMed:10230407, PubMed:10579999, PubMed:15983046, PubMed:16678110, PubMed:19112177, PubMed:19679664, PubMed:23455478, PubMed:27565346, PubMed:29769719, PubMed:11961546, PubMed:22748924). CRLs complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins, ARIH1 mediating addition of the first ubiquitin on CRLs targets (PubMed:27565346). The functional specificity of the E3 ubiquitin-protein ligase complexes depends on the variable substrate recognition components. As a component of the CSA complex promotes the ubiquitination of ERCC6 resulting in proteasomal degradation. Recruits the E2 ubiquitin-conjugating enzyme CDC34 to the complex and brings it into close proximity to the substrate. Probably also stimulates CDC34 autoubiquitination. May be required for histone H3 and histone H4 ubiquitination in response to ultraviolet and for subsequent DNA repair. Promotes the neddylation of CUL1, CUL2, CUL4 and CUL4 via its interaction with UBE2M. Involved in the ubiquitination of KEAP1, ENC1 and KLHL41. In concert with ATF2 and CUL3, promotes degradation of KAT5 thereby attenuating its ability to acetylate and activate ATM. As part of a multisubunit complex composed of elongin BC complex (ELOB and ELOC), elongin A/ELOA, RBX1 and CUL5; polyubiquitinates monoubiquitinated POLR2A (PubMed:19920177).
messages: Nucleus
messages: Part of a SCF complex consisting of CUL1, RBX1, SKP1 and SKP2 (PubMed:10230406, PubMed:11961546). Part of a SCF-like complex consisting of CUL7, RBX1, SKP1 and FBXW8. Part of CBC(VHL) complexes with elongin BC complex (ELOB and ELOC), CUL2 or CUL5 and VHL (PubMed:10213691). Part of the CSA complex (DCX(ERCC8) complex), a DCX E3 ubiquitin-protein ligase complex containing ERCC8, RBX1, DDB1 and CUL4A; the CSA complex interacts with RNA polymerase II; upon UV irradiation it interacts with the COP9 signalosome and preferentially with the hyperphosphorylated form of RNA polymerase II (PubMed:12732143). Part of multisubunit E3 ubiquitin ligase complexes with elongin BC complex (ELOB and ELOC), CUL2 and MED8; elongin BC complex (ELOB and ELOC), CUL5 and MUF1 (PubMed:11384984, PubMed:12149480). Part of multisubunit complexes with elongin BC complex (ELOB and ELOC), SOCS1 or WSB1 and CUL5. Part of a multisubunit ubiquitin ligase complex consisting of elongin BC complex (ELOB and ELOC), elongin A/ELOA, RBX1 and CUL5 (PubMed:19920177). Interacts directly with CUL1 and probably also with CUL2, CUL3, CUL4A, CUL4B, CUL5 and CUL7 (PubMed:10230407, PubMed:12481031). Interacts with CDC34 (PubMed:22748924). Interacts with GLMN. GLMN competes for the binding site of the E2 ubiquitin-conjugating enzyme CDC34 and disrupts CDC34 binding (PubMed:22748924). Interacts with COPS6 (PubMed:11337588). Component of the DCX DET1-COP1 ubiquitin ligase complex at least composed of RBX1, DET1, DDB1, CUL4A and COP1 (PubMed:14739464). Part of an E3 ligase complex composed of RBX1, DDB1, DDB2 and CUL4A or CUL4B (PubMed:16678110). Interacts with UBE2M (PubMed:19250909). Part of a SCF complex consisting of CUL1, FBXO3, RBX1 and SKP1; this complex interacts with PML via FBXO3 (PubMed:18809579). Component of the SCF(Cyclin F) complex consisting of CUL1, RBX1, SKP1 and CCNF (PubMed:20596027). Identified in a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex together with HINT1 and CDC34 (PubMed:1911…
messages: The RING-type zinc finger domain is essential for ubiquitin ligase activity (PubMed:10230407). It coordinates an additional third zinc ion (PubMed:11961546, PubMed:22748924).
messages: Widely expressed.

9606:HS6ST3
gene id: 9606:HS6ST3
uniprot id: Q8IZP7
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: 6-O-sulfation enzyme which catalyzes the transfer of sulfate from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to position 6 of the N-sulfoglucosamine residue (GlcNS) of heparan sulfate.
messages: Belongs to the sulfotransferase 6 family.
messages: Membrane

9606:DUSP13A
gene id: 9606:DUSP13A
uniprot id: Q6B8I1
names: Activity Regulation
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily.
messages: Cytoplasm
messages: Inhibited by vanadate.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Monomer (PubMed:29106959). Interacts with MAP3K5/ASK1; may compete with AKT1 preventing MAP3K5/ASK1 phosphorylation by AKT1.
messages: Probable protein tyrosine phosphatase. Has phosphatase activity with synthetic substrates (PubMed:15252030, PubMed:29106959). Has a phosphatase activity-independent regulatory role in MAP3K5/ASK1-mediated apoptosis, preventing MAP3K5/ASK1 inhibition by AKT1. Shows no phosphatase activity on MAPK1/ERK2, MAPK8/JNK, MAPK14/p38 and MAP3K5/ASK1.
messages: Produced by alternative promoter usage.
messages: Skeletal muscle specific.

9606:TIMM23B
gene id: 9606:TIMM23B
uniprot id: Q5SRD1
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the Tim17/Tim22/Tim23 family.
messages: May participate in the translocation of transit peptide-containing proteins across the mitochondrial inner membrane. the PAM complex (By similarity).
messages: Mitochondrion inner membrane

9606:OR5H14
gene id: 9606:OR5H14
uniprot id: A6NHG9
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Odorant receptor.

9606:RNASE7
gene id: 9606:RNASE7
uniprot id: Q9H1E1
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the pancreatic ribonuclease family.
messages: Exhibits a potent RNase activity (PubMed:12244054, PubMed:12527768, PubMed:17150966). Has broad-spectrum antimicrobial activity against many pathogenic microorganisms including uropathogenic E.coli (UPEC), and remarkably potent activity (lethal dose of 90% < 30 nM) against a vancomycin resistant Enterococcus faecium (PubMed:12244054, PubMed:12527768, PubMed:25075772, PubMed:33818125, PubMed:17150966). Causes loss of bacterial membrane integrity (PubMed:17150966). Probably contributes to urinary tract sterility (PubMed:25075772). Bactericidal activity is independent of RNase activity (PubMed:17150966).
messages: Expressed in collecting ducts in kidney, and in apical uroepithelium in bladder (at protein level) (PubMed:25075772). Expressed in various epithelial tissues including skin, respiratory tract, genito-urinary tract and, at a low level, in the gut (PubMed:12244054). Expressed in liver, kidney, skeletal muscle and heart (PubMed:12527768).
messages: Secreted
messages: Up-regulated in response to the cytokines IL1B, IFNG and TNF (PubMed:12244054). Strongly up-regulated in response to the bacterium P.aeruginosa (PubMed:12244054). Moderately up-regulated in response to S.aureus, E.coli and S.pyogenes (PubMed:12244054). Up-regulated in kidney in response to infection (PubMed:25075772).

9606:CCL8
gene id: 9606:CCL8
uniprot id: P80075
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the intercrine beta (chemokine CC) family.
messages: By IFNG/IFN-gamma, mitogens and IL1/interleukin-1.
messages: Chemotactic factor that attracts monocytes, lymphocytes, basophils and eosinophils. May play a role in neoplasia and inflammatory host responses. This protein can bind heparin. The processed form MCP-2(6-76) does not show monocyte chemotactic activity, but inhibits the chemotactic effect most predominantly of CCL7, and also of CCL2 and CCL5 and CCL8.
messages: Highest expression found in the small intestine and peripheral blood cells. Intermediate levels seen in the heart, placenta, lung, skeletal muscle, thymus, colon, ovary, spinal cord and pancreas. Low levels seen in the brain, liver, spleen and prostate.
messages: Monomer or homodimer; in equilibrium.
messages: N-terminal processed form MCP-2(6-76) is produced by proteolytic cleavage after secretion from peripheral blood monocytes.
messages: Secreted

9606:OR4C15
gene id: 9606:OR4C15
uniprot id: A0A2C9F2M4
uniprot id: Q8NGM1
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Membrane
messages: Odorant receptor.

9606:ZNF256
gene id: 9606:ZNF256
uniprot id: Q9Y2P7
names: Domain
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: By GDNF/glial cell line-derived neurotrophic factor.
messages: Interacts with TRIM28.
messages: Nucleus
messages: The KRAB domain mediates interaction with TRIM28 and is required for transcriptional repressor activity.
messages: Transcriptional repressor that plays a role in cell proliferation. Requires TRIM28 for its activity.

9606:GRWD1
gene id: 9606:GRWD1
uniprot id: Q9BQ67
names: Function
names: Induction
names: Subcellular Location Annotation
names: Subunit
messages: Chromosome
messages: Histone binding-protein that regulates chromatin dynamics and minichromosome maintenance (MCM) loading at replication origins, possibly by promoting chromatin openness (PubMed:25990725).
messages: Induced by E2F transcription factors (PubMed:14990995).
messages: Interacts with METTL18 (PubMed:23349634). Interacts with CDT1; origin binding of GRWD1 is dependent on CDT1 (PubMed:25990725). Interacts with CDC6; origin binding of GRWD1 is dependent on CDC6 (PubMed:25990725). Binds to histone H2A-H2B and H3-H4 complexes (PubMed:25990725).
messages: Nucleus
messages: nucleolus

9606:KATNIP
gene id: 9606:KATNIP
uniprot id: O60303
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Interacts with microtubules. Interacts with 4 subunits of the katanin complex: KATNA1, KATNAL1, KATNB1 and KATNBL1.
messages: May influence the stability of microtubules (MT), possibly through interaction with the MT-severing katanin complex.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: cilium axoneme
messages: cilium basal body
messages: cytoskeleton

9606:FRMD8
gene id: 9606:FRMD8
uniprot id: Q9BZ67
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cell membrane
messages: Interacts with iRhom1/RHBDF1 and iRhom2/RHBDF2 (via cytoplasmic N-termini); this interaction leads to mutual protein stabilization (PubMed:29897333). Interacts with ADAM17; this interaction is indirect and mediated by iRhom proteins (PubMed:29897333, PubMed:29897336). Interacts with LRP6; this interaction affects LRP6-binding to AXIN1 (PubMed:19572019).
messages: Promotes the cell surface stability of iRhom1/RHBDF1 and iRhom2/RHBDF2 and prevents their degradation via the endolysosomal pathway. By acting on iRhoms, involved in ADAM17-mediated shedding of TNF, amphiregulin/AREG, HBEGF and TGFA from the cell surface (PubMed:29897333, PubMed:29897336). Negatively regulates Wnt signaling, possibly by antagonizing the recruitment of AXIN1 to LRP6 (PubMed:19572019).
messages: Widely expressed, with high expression in heart and spleen.
messages: cytosol

9606:CFAP69
gene id: 9606:CFAP69
uniprot id: A5D8W1
names: Disease Annotation
names: Function
names: Miscellaneous
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Cilium- and flagellum-associated protein (PubMed:29606301). In the olfactory epithelium, regulates the speed of activation and termination of the odor response and thus contributes to the robustness of olfactory transduction pathways (By similarity). Required for sperm flagellum assembly and stability (PubMed:29606301).
messages: Highly expressed in the testis, specifically in sperm (at protein level) (PubMed:29606301). Expressed in the brain, kidney, liver, lung, and intestine (PubMed:29606301).
messages: Incomplete sequence.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: cilium
messages: flagellum

9606:KCNK13
gene id: 9606:KCNK13
uniprot id: Q9HB14
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the two pore domain potassium channel (TC 1.A.1.8) family.
messages: Homodimer.
messages: Membrane
messages: Potassium channel displaying weak inward rectification in symmetrical K(+) solution.
messages: The current is enhanced by arachidonic acid and inhibited by halothane.

9606:SLC2A9
gene id: 9606:SLC2A9
uniprot id: Q9NRM0
names: Activity Regulation
names: Caution
names: Disease Annotation
names: Function
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Apical cell membrane
messages: Basolateral cell membrane
messages: Belongs to the major facilitator superfamily. Sugar transporter (TC 2.A.1.1) family. Glucose transporter subfamily.
messages: Cell membrane
messages: Extracellular glucose and urate accelerate urate efflux (PubMed:22647630, PubMed:18842065). Intracellular urate, glucose and fructose accelerate urate influx (PubMed:22647630).
messages: Genetic variations in SLC2A9 influence the variance in serum uric acid concentrations and define the serum uric acid concentration quantitative trait locus 2 (UAQTL2) [MIM:612076] with pronounced sex-specific effects. The proportion of the variance of serum uric acid concentrations explained by genotypes is about 1.2% in men and 6% in women, and the percentage accounted for by expression levels is 3.5% in men and 15% in women (PubMed:18327257, PubMed:18327256, PubMed:18842065). Excess serum accumulation of uric acid can lead to the development of gout (PubMed:18327257, PubMed:18327256).
messages: High-capacity urate transporter that was first described as a fructose and glucose transporter. Also described in the literature as high-affinity and low-capacity glucose and fructose transporter (PubMed:18327257, PubMed:17710649, PubMed:18842065). However, another group could not confirm transporter activity for glucose or fructose (PubMed:28083649).
messages: High-capacity urate transporter, which may play a role in the urate reabsorption by proximal tubules (PubMed:18327257, PubMed:28083649, PubMed:22647630, PubMed:18701466, PubMed:36749388). May have a residual high-affinity, low-capacity glucose and fructose transporter activity (PubMed:18842065, PubMed:18327257, PubMed:18701466). Transports urate at rates 45- to 60-fold faster than glucose (PubMed:18842065). Does not transport galactose (PubMed:28083649). May mediate small uptake of adenine but not of other nucleobases (PubMed:22647630).
messages: Most strongly expressed in basolateral membranes of proximal renal tubular cells, liver and placenta. Also detected in lung, blood leukocytes, heart skeletal muscle and chondrocytes from articular cartilage. Detected in kidney membrane (at protein level).
messages: No effect of extracellular urate, glucose or fructose on urate efflux. Intracellular urate and fructose slightly accelerate urate influx.
messages: Only detected in the apical membranes of polarized renal tubular cells and placenta. Detected in kidney membrane (at protein level).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:GNMT
gene id: 9606:GNMT
uniprot id: Q14749
uniprot id: V9HW60
names: Activity Regulation
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the class I-like SAM-binding methyltransferase superfamily. Glycine N-methyltransferase family.
messages: Catalyzes the methylation of glycine by using S-adenosylmethionine (AdoMet) to form N-methylglycine (sarcosine) with the concomitant production of S-adenosylhomocysteine (AdoHcy), a reaction regulated by the binding of 5-methyltetrahydrofolate. Plays an important role in the regulation of methyl group metabolism by regulating the ratio between S-adenosyl-L-methionine and S-adenosyl-L-homocysteine.
messages: Cytoplasm
messages: Expressed only in liver, pancreas, and prostate.
messages: Homotetramer.
messages: Inhibited by 5-methyltetrahydrofolate monoglutamate and by 5-methyltetrahydrofolate pentaglutamate, inhibition is much more effective by the pentaglutamate form than by the monoglutamate form. Two molecules of 5-methyltetrahydrofolate are bound per tetramer. The binding sites are localized between subunits. Inhibitor binding may preclude movements of the polypeptide chain that are necessary for enzyme activity.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:FAM72B
gene id: 9606:FAM72B
uniprot id: Q86X60
names: Miscellaneous
names: Similarity
messages: Belongs to the FAM72 family.
messages: Highly homologous to GCUD2 but localized to a distinct locus.

9606:VWA2
gene id: 9606:VWA2
uniprot id: Q5GFL6
names: Miscellaneous
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: A 55 kDa form is produced by proteolytic cleavage.
messages: Expression is generally absent in normal colon and other normal body tissues, but it is induced an average of 78-fold in Stage II, III, and IV colon cancers, as well as in colon adenomas and colon cancer cell lines.
messages: Forms monomers and multimers.
messages: May be used as a serological marker for colon neoplasia.
messages: Secreted

9606:SH3GL2
gene id: 9606:SH3GL2
uniprot id: Q7Z376
uniprot id: Q99962
names: Domain
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: An N-terminal amphipathic helix, the BAR domain and a second amphipathic helix inserted into helix 1 of the BAR domain (N-BAR domain) induce membrane curvature and bind curved membranes. The BAR domain dimer forms a rigid crescent shaped bundle of helices with the pair of second amphipathic helices protruding towards the membrane-binding surface.
messages: Belongs to the endophilin family.
messages: Brain, mostly in frontal cortex. Expressed at high level in fetal cerebellum.
messages: Cytoplasm
messages: Early endosome
messages: HeLa cells expressing the N-BAR domain of SH3GL2 show tubulation of the plasma membrane. The N-BAR domain binds liposomes and induces formation of tubules from liposomes. The N-terminal amphipathic helix is required for liposome binding. The second amphipathic helix enhances liposome tubulation.
messages: Implicated in synaptic vesicle endocytosis. May recruit other proteins to membranes with high curvature. Required for BDNF-dependent dendrite outgrowth. Cooperates with SH3GL2 to mediate BDNF-NTRK2 early endocytic trafficking and signaling from early endosomes.
messages: Membrane
messages: Monomer; in cytoplasm. Homodimer; when associated with membranes (By similarity). Interacts with OPHN1 (By similarity). Interacts with SYNJ1 (PubMed:10542231). Interacts with DNM1 (By similarity). Interacts with MAP4K3; the interaction appears to regulate MAP4K3-mediated JNK activation (By similarity). Interacts with PDCD6IP (PubMed:17350572). Interacts with ATXN2 (PubMed:18602463). Interacts with ADAM9 and ADAM15 cytoplasmic tails (PubMed:10531379). Interacts with BIN2 (PubMed:23285027). Interacts with TMEM108 (By similarity). Interacts with ADGRB2 (PubMed:28891236).
messages: Presynapse

9606:PC
gene id: 9606:PC
uniprot id: P11498
names: Cofactor
names: Disease Annotation
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: Acetylation of Lys-748 might play a role in catalytic activity regulation.
messages: Binds 1 Mn(2+) ion per subunit.
messages: Homotetramer (PubMed:18297087). Interacts (via the biotin carboxylation domain) with SIRT4 (PubMed:23438705).
messages: Mitochondrion matrix
messages: Pyruvate carboxylase catalyzes a 2-step reaction, involving the ATP-dependent carboxylation of the covalently attached biotin in the first step and the transfer of the carboxyl group to pyruvate in the second. Catalyzes in a tissue specific manner, the initial reactions of glucose (liver, kidney) and lipid (adipose tissue, liver, brain) synthesis from pyruvate.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:LRRN4CL
gene id: 9606:LRRN4CL
uniprot id: Q8ND94
names: Subcellular Location Annotation
messages: Membrane

9606:PRSS1
gene id: 9606:PRSS1
uniprot id: P07477
names: Caution
names: Cofactor
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the peptidase S1 family.
messages: Binds 1 Ca(2+) ion per subunit.
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry.
messages: Has activity against the synthetic substrates Boc-Phe-Ser-Arg-Mec, Boc-Leu-Thr-Arg-Mec, Boc-Gln-Ala-Arg-Mec and Boc-Val-Pro-Arg-Mec. The single-chain form is more active than the two-chain form against all of these substrates.
messages: Interacts with SERPINA1.
messages: Occurs in a single-chain form and a two-chain form, produced by proteolytic cleavage after Arg-122.
messages: Sulfation at Tyr-154 increases selectivity towards basic versus apolar residues at the P2' position of inhibitors that bind in a substrate-like fashion. Although the increase in selectivity is relatively small, it may facilitate digestion of a broader range of dietary proteins.
messages: Tyr-154 was proposed to be phosphorylated (PubMed:8683601) but it has been shown (PubMed:17087724) to be sulfated instead. Phosphate and sulfate groups are similar in mass and size, and this can lead to erroneous interpretation of the results.
messages: extracellular space

9606:SARDH
gene id: 9606:SARDH
uniprot id: A8K596
uniprot id: Q9UL12
names: Cofactor
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the GcvT family.
messages: Binds 1 FAD covalently per monomer.
messages: Catalyzes the last step of the oxidative degradation of choline to glycine. Converts sarcosine into glycine.
messages: Expressed in pancreas, liver and kidney.
messages: Mitochondrion matrix
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:OR9G1
gene id: 9606:OR9G1
uniprot id: Q8NH87
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Odorant receptor.

9606:NCAPG2
gene id: 9606:NCAPG2
uniprot id: Q86XI2
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Component of the condensin-2 complex, which contains the SMC2 and SMC4 heterodimer, and 3 non SMC subunits that probably regulate the complex: NCAPH2, NCAPD3 and NCAPG2.
messages: Nucleus
messages: Regulatory subunit of the condensin-2 complex, a complex which establishes mitotic chromosome architecture and is involved in physical rigidity of the chromatid axis.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:DAPL1
gene id: 9606:DAPL1
uniprot id: A0PJW8
names: Function
names: Tissue Specificity
messages: Expressed in hair follicle (at protein level).
messages: May play a role in the early stages of epithelial differentiation or in apoptosis.

9606:KRT75
gene id: 9606:KRT75
uniprot id: O95678
names: Disease Annotation
names: Function
names: Miscellaneous
names: Polymorphism
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Belongs to the intermediate filament family.
messages: Heterodimer of a type I and a type II keratin. May associate with KRT17.
messages: Highly expressed in hair follicles from scalp. Specifically expressed in the of the hair companion layer follicle, a single layered band of flat and vertically oriented cells between the cuboidal outer root sheath (ORS) cells and the inner root sheath (IRS) that stretches from the lowermost bulb region to the isthmus of the follicle. Also expressed in medullated hairs. In nails, it is almost exclusively present in the nail bed (at protein level).
messages: May be used as a marker of hair differentiation.
messages: Plays a central role in hair and nail formation. Essential component of keratin intermediate filaments in the companion layer of the hair follicle.
messages: The Thr-161 variant may increase risk to develop pseudofolliculitis barbae (PFB) [MIM:612318]. PFB is a common hair disorder characterized by a pustular foreign body inflammatory reaction that is induced by ingrown hairs of the facial and submental (barbea) regions after regular shaving. It occurs predominantly in black males, while it is rather rare and usually far less severe in Caucasian males.
messages: The disease may be caused by variants affecting the gene represented in this entry.
messages: There are two types of cytoskeletal and microfibrillar keratin, I (acidic) and II (neutral to basic) (40-55 and 56-70 kDa, respectively).

9606:C1QTNF3
gene id: 9606:C1QTNF3
uniprot id: Q9BXJ4
names: PTM
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Expressed in colon and small intestine.
messages: Glycosylated on Asn-70.
messages: Secreted

9606:ITGA3
gene id: 9606:ITGA3
uniprot id: A0A140VJM0
uniprot id: P26006
names: Biotechnology
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Integrin ITGA3:ITGB1 may act as a receptor for R.delemar CotH7 in alveolar epithelial cells, which may be an early step in pulmonary mucormycosis disease progression.
messages: Antibodies against integrin alpha-3 ITGA3 protects epithelial cells from invasion by the fungus R.delemar, a causative agent of mucormycosis, and could thus potentially be used to treat mucormycosis disease.
messages: Belongs to the integrin alpha chain family.
messages: Cell membrane
messages: Heterodimer of an alpha and a beta subunit. The alpha subunit is composed of a heavy and a light chain linked by a disulfide bond. Alpha-3 associates with beta-1. Interacts with HPS5. Interacts with FAP (seprase); the interaction occurs at the cell surface of invadopodia membrane in a collagen-dependent manner.
messages: Integrin alpha-3/beta-1 is a receptor for fibronectin, laminin, collagen, epiligrin, thrombospondin and CSPG4. Integrin alpha-3/beta-1 provides a docking site for FAP (seprase) at invadopodia plasma membranes in a collagen-dependent manner and hence may participate in the adhesion, formation of invadopodia and matrix degradation processes, promoting cell invasion. Alpha-3/beta-1 may mediate with LGALS3 the stimulation by CSPG4 of endothelial cells migration.
messages: Isoform 1 is widely expressed. Isoform 2 is expressed in brain and heart. In brain, both isoforms are exclusively expressed on vascular smooth muscle cells, whereas in heart isoform 1 is strongly expressed on vascular smooth muscle cells, isoform 2 is detected only on endothelial vein cells.
messages: Isoform 1, but not isoform 2, is phosphorylated on serine residues. Phosphorylation increases after phorbol 12-myristate 13-acetate stimulation.
messages: Membrane
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: filopodium membrane
messages: invadopodium membrane

9606:TAS2R1
gene id: 9606:TAS2R1
uniprot id: Q502V6
uniprot id: Q9NYW7
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor T2R family.
messages: Expressed in subsets of taste receptor cells of the tongue and palate epithelium and exclusively in gustducin-positive cells.
messages: Membrane
messages: Most taste cells may be activated by a limited number of bitter compounds; individual taste cells can discriminate among bitter stimuli.
messages: Receptor that may play a role in the perception of bitterness and is gustducin-linked. May play a role in sensing the chemical composition of the gastrointestinal content. The activity of this receptor may stimulate alpha gustducin, mediate PLC-beta-2 activation and lead to the gating of TRPM5.

9606:SLC22A2
gene id: 9606:SLC22A2
uniprot id: O15244
names: Activity Regulation
names: Caution
names: Domain
names: Function
names: Induction
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Apical cell membrane
messages: Basal cell membrane
messages: Basolateral cell membrane
messages: Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family.
messages: Contains one proline-rich sequence (Pro-Glu-Ser-Pro-Arg) that may be involved in tyrosine-protein kinase YES1 binding and is required for the activation of substrate transport.
messages: Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:9260930, PubMed:9687576). Functions as a Na(+)-independent, bidirectional uniporter (PubMed:9687576, PubMed:21128598). Cation cellular uptake or release is driven by the electrochemical potential, i.e. membrane potential and concentration gradient (PubMed:9260930, PubMed:9687576, PubMed:15212162). However, may also engage electroneutral cation exchange when saturating concentrations of cation substrates are reached (By similarity). Predominantly expressed at the basolateral membrane of hepatocytes and proximal tubules and involved in the uptake and disposition of cationic compounds by hepatic and renal clearance from the blood flow (PubMed:15783073). Implicated in monoamine neurotransmitters uptake such as histamine, dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, serotonin and tyramine, thereby supporting a physiological role in the central nervous system by regulating interstitial concentrations of neurotransmitters (PubMed:9687576, PubMed:16581093, PubMed:17460754). Also capable of transporting dopaminergic neuromodulators cyclo(his-pro), salsolinol and N-methyl-salsolinol, thereby involved in the maintenance of dopaminergic cell integrity in the central nervous system (PubMed:17460754). Mediates the bidirectional transport of acetylcholine (ACh) at the apical membrane of ciliated cell in airway epithelium, thereby playing a role in luminal release of ACh from bronchial epithelium (PubMed:15817714). Also transports guanidine and endogenous monoamines such as vitamin B1/thiamine, creatinine and N-1-methylnicotinamide (NMN) (PubMed:9260930, PubMed:12089365, PubMed:15212162, PubMed:17072098, PubMed:24961373). Mediates the uptake and efflux of quaternary ammonium compound choline (PubMed:9260930). Mediates the bidirectional transport of polyamine agmatine and the uptake of po…
messages: In contrast with isoform 1, not able to transport guanidine, creatinine, cimetidine and metformin.
messages: Mainly expressed in kidney, bone marrow and testis (PubMed:12089365). Expressed in colon, skeletal muscle, spinal cord, placenta and liver (PubMed:12089365).
messages: Mainly expressed in kidney, in the cortex and medulla (PubMed:9260930, PubMed:12089365, PubMed:11912245). Localized in testis, mostly to peritubular myoid cells and Leydig cells and also detected along the basal membrane of Sertoli cells (PubMed:12089365, PubMed:35307651). Expressed in brain, in neurons of the cerebral cortex and in various subcortical nuclei (PubMed:9260930, PubMed:12089365, PubMed:9687576). In the brain, also detected in the dopaminergic regions of the substantia nigra (PubMed:17460754). Expressed in tracheal and bronchial ciliated epithelium in the respiratory tract (PubMed:15817714). Also detected in secretory phase endometrium, in scattered stromal cells (PubMed:17393420). Expressed in spleen, placenta, small intestine and spinal cord (PubMed:9260930, PubMed:12089365). Weakly expressed in prostate, uterus and lung (PubMed:12089365).
messages: May be down-regulated in diabetic patients.
messages: Mediates the renal secretion of many clinically used cationic drugs (PubMed:12089365, PubMed:16272756). Transports drugs such as diabetes treatment medicine metformin, 1-methyl-4-phenylpyridinium (MPP(+)), famotidine, ranitidine, amantadine, acriflavine, amiloride, memantine, cimetidine, platinum-based drugs cisplatin and oxaliplatin, 3'-azido-3'-deoxythymidine (AZT) and tetraethylammonium (TEA) (PubMed:9260930, PubMed:12089365, PubMed:15496291, PubMed:16314463, PubMed:16272756, PubMed:16006492, PubMed:15783073, PubMed:16394027, PubMed:16951202, PubMed:16914559, PubMed:16581093, PubMed:24961373). Mediates the bidirectional transport of MPP(+) (PubMed:9260930, PubMed:12089365, PubMed:9687576). Metformin competitively inhibits OCT1-mediated thiamine uptake, leading to a decrease in hepatic steatosis (PubMed:24961373). Plays a predominant role in the anticancer activity of cisplatin and oxaliplatin and may contribute to antitumor specificity (PubMed:16951202, PubMed:16914559). Involved in cisplatin-induced nephrotoxicity (By similarity).
messages: Most authors have deduced a localization at the basolateral membrane of proximal tubules (PubMed:11912245). Other studies demonstrated a localization to the luminal membrane in the distal tubule (PubMed:9260930).
messages: Tyrosine phosphorylated by tyrosine-protein kinase YES1.
messages: Tyrosine phosphorylation of the transporter leads to activation of the transport activity (PubMed:26979622). TEA uptake is activated by tyrosine phosphorylation (PubMed:26979622). Inhibited by cGMP, most likely through a cGMP-binding protein that interacts with OCT2 (PubMed:12395288).

9606:TIGD3
gene id: 9606:TIGD3
uniprot id: Q6B0B8
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the tigger transposable element derived protein family.
messages: Nucleus

9606:C17orf78
gene id: 9606:C17orf78
uniprot id: Q8N4C9
names: Subcellular Location Annotation
messages: Membrane

9606:CASP14
gene id: 9606:CASP14
uniprot id: B2CIS9
uniprot id: P31944
names: Activity Regulation
names: Disease Annotation
names: Function
names: Induction
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the peptidase C14A family.
messages: Cytoplasm
messages: Expressed in bacteria requires high concentrations of kosmotropic salts to be activated (PubMed:15301553). The mature and the intermediate form differ in activity towards synthetic caspase substrates: the p17/p10 mature form but not the p20/p8 intermediate form is active on WEHD-MCA; p20/p8 is active on a number of other caspase substrates without any marked preference (VEID-AFC, DEVD-AFC, LEVD-AFC and LEHD-AFC) (PubMed:22825846).
messages: Expressed in keratinocytes of adult skin suprabasal layers (from spinous layers to the stratum granulosum and stratum corneum) (at protein level). Expressed in keratinocytes of hair shaft and sebaceous glands (at protein level). In psoriatic skin only expressed at very low levels (PubMed:11175259). The p17/10 mature form is expressed in epidermis stratum corneum, the p20/p8 intermediate form in epidermis upper granular cells of the stratum granulosum (PubMed:22825846).
messages: Heterodimer of a large and a small subunit, both processed from the precursor; the mature active form is a p17/p10 dimer and the intermediate form a p20/p8 dimer.
messages: In undifferentiated keratinocytes under postconfluency growth conditions (in vitro) (PubMed:11175259). By high glucose in retinal pigment epithelia cells (PubMed:25121097).
messages: Inhibited by caspase-1 inhibitor YVAD-FMK and the pan-caspase inhibitor VAD-FMK.
messages: Maturation by proteolytic processing appears to be a two-step process. The precursor is processed by KLK7 to yield the p20/p8 intermediate form which acts on the precursor to yield the p17/p10 mature form (PubMed:22825846). Initially, cleavage between Ile-152 and Lys-153 has been proposed to yield the large and small subunits of the active enzyme (PubMed:12200134).
messages: Non-apoptotic caspase involved in epidermal differentiation. Is the predominant caspase in epidermal stratum corneum (PubMed:15556625). Seems to play a role in keratinocyte differentiation and is required for cornification. Regulates maturation of the epidermis by proteolytically processing filaggrin (By similarity). In vitro has a preference for the substrate [WY]-X-X-D motif and is active on the synthetic caspase substrate WEHD-ACF (PubMed:16854378, PubMed:19960512). Involved in processing of prosaposin in the epidermis (By similarity). May be involved in retinal pigment epithelium cell barrier function (PubMed:25121097). Involved in DNA degradation in differentiated keratinocytes probably by cleaving DFFA/ICAD leading to liberation of DFFB/CAD (PubMed:24743736).
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:HSPB3
gene id: 9606:HSPB3
uniprot id: Q12988
uniprot id: Q6ICS9
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the small heat shock protein (HSP20) family.
messages: Cytoplasm
messages: Inhibitor of actin polymerization.
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:TM4SF18
gene id: 9606:TM4SF18
uniprot id: Q96CE8
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the L6 tetraspanin family.
messages: Membrane

9606:ZBED3
gene id: 9606:ZBED3
uniprot id: Q96IU2
names: Function
names: Induction
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acts as a positive regulator in the activation of the canonical Wnt/beta-catenin signaling pathway by stabilizing cytoplasmic beta-catenin (By similarity). Involved in transcription activation of Wnt target gene expression (By similarity). Plays a role in symmetric division of blastomeres in the early stages of embryogenesis via regulation of mitotic spindle central positioning and organization of the F-actin filament network (By similarity). Plays a role in regulating the distribution of cellular organelles, via modulation of cytoskeletal dynamics and cytoplasmic lattice formation (By similarity).
messages: Associates with the subcortical maternal complex (SCMC) composed of at least NLRP5, KHDC3L, OOEP, and TLE6 via interaction with NLRP5 and TLE6 (By similarity). Interacts with AXIN1; the interaction is direct, enhanced by protein kinase GSK3B and casein kinase CSNK1E activities and decreases GSK3B-induced beta-catenin serine and threonine phosphorylations (By similarity).
messages: Cytoplasm
messages: Induced in blood plasma by hyperglycemia (PubMed:24283382). Decreased in blood plasma by hyperinsulinemia (PubMed:24283382).
messages: Membrane
messages: Secreted
messages: Secreted in blood plasma, and expressed in skeletal muscle and adipose tissue (at protein level).

9606:SLFN13
gene id: 9606:SLFN13
uniprot id: Q68D06
names: Cofactor
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the Schlafen family. Subgroup III subfamily.
messages: Can also use Mn(2+).
messages: Cytoplasm
messages: Endoribonuclease that cleaves tRNAs and rRNAs (PubMed:29563550). Cleaves tRNAs 11 nucleotides from the 3'-terminus at the acceptor stem (PubMed:29563550). Does not act on tRNA(Sec) (PubMed:29563550). Able to restrict HIV-1 virus replication; ability to inhibit HIV-1 replication is dependent on endoribonuclease activity (PubMed:29563550).
messages: Shows a pseudo-dimeric U-pillow-shaped architecture of the SLFN13 N'-domain that may clamp base-paired RNAs.

9606:CHP1
gene id: 9606:CHP1
uniprot id: Q99653
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the calcineurin regulatory subunit family. CHP subfamily.
messages: Both N-myristoylation and calcium-mediated conformational changes are essential for its function in exocytic traffic (By similarity). N-myristoylation is required for its association with microtubules and interaction with GAPDH, but not for the constitutive association to membranes.
messages: Calcium-binding protein involved in different processes such as regulation of vesicular trafficking, plasma membrane Na(+)/H(+) exchanger and gene transcription. Involved in the constitutive exocytic membrane traffic. Mediates the association between microtubules and membrane-bound organelles of the endoplasmic reticulum and Golgi apparatus and is also required for the targeting and fusion of transcytotic vesicles (TCV) with the plasma membrane. Functions as an integral cofactor in cell pH regulation by controlling plasma membrane-type Na(+)/H(+) exchange activity. Affects the pH sensitivity of SLC9A1/NHE1 by increasing its sensitivity at acidic pH. Required for the stabilization and localization of SLC9A1/NHE1 at the plasma membrane. Inhibits serum- and GTPase-stimulated Na(+)/H(+) exchange. Plays a role as an inhibitor of ribosomal RNA transcription by repressing the nucleolar UBF1 transcriptional activity. May sequester UBF1 in the nucleoplasm and limit its translocation to the nucleolus. Associates to the ribosomal gene promoter. Acts as a negative regulator of the calcineurin/NFAT signaling pathway. Inhibits NFAT nuclear translocation and transcriptional activity by suppressing the calcium-dependent calcineurin phosphatase activity. Also negatively regulates the kinase activity of the apoptosis-induced kinase STK17B. Inhibits both STK17B auto- and substrate-phosphorylations in a calcium-dependent manner.
messages: Cell membrane
messages: Cytoplasm
messages: Endomembrane system
messages: Endoplasmic reticulum
messages: Endoplasmic reticulum-Golgi intermediate compartment
messages: Membrane
messages: Monomer. Interacts with STK17B; the interaction occurs in a calcium-independent manner and induces the translocation of CHP1 from the Golgi to the nucleus. Interacts with GAPDH; the interaction is direct, occurs in a N-myristoylation-dependent manner and facilitates the ability of CHP1 to bind microtubules. Interacts with KIF1B (via the C-terminal end of the kinesin-motor domain); the interaction occurs in a calcium-dependent manner. Associates (via C-terminal domain) with microtubules; the association occurs with polymerized microtubules during the cell cycle in a myristoylation- and calcium-independent manner and is enhanced by GAPDH (By similarity). Interacts with PPP3CA. Interacts with SLC9A1/NHE1 (via the C-terminal domain); the interaction occurs at the plasma membrane in a calcium-dependent manner and at a domain that is critical for growth factor stimulation of the exchanger (PubMed:8901634, PubMed:11350981, PubMed:15035633, PubMed:34108458, PubMed:35613257). Interacts with SLC9A3; increases SLC9A3 trafficking and activity at the plasma membrane (PubMed:35613257).
messages: Nucleus
messages: Phosphorylated; decreased phosphorylation is associated with an increase in SLC9A1/NHE1 Na(+)/H(+) exchange activity. Phosphorylation occurs in serum-dependent manner. The phosphorylation state may regulate the binding to SLC9A1/NHE1.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitously expressed. Has been found in fetal eye, lung, liver, muscle, heart, kidney, thymus and spleen.
messages: cytoskeleton

9606:IL5
gene id: 9606:IL5
uniprot id: P05113
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the IL-5 family.
messages: Homodimer; disulfide-linked (PubMed:8483502, PubMed:22528658). Interacts with IL5RA (PubMed:1495999, PubMed:22153509). Interacts with CSF2RB (PubMed:1495999).
messages: Homodimeric cytokine expressed predominantly by T-lymphocytes and NK cells that plays an important role in the survival, differentiation, and chemotaxis of eosinophils (PubMed:2653458, PubMed:9010276). Acts also on activated and resting B-cells to induce immunoglobulin production, growth, and differentiation (By similarity). Mechanistically, exerts its biological effects through a receptor composed of IL5RA subunit and the cytokine receptor common subunit beta/CSF2RB (PubMed:1495999, PubMed:22528658). Binding to the receptor leads to activation of various kinases including LYN, SYK and JAK2 and thereby propagates signals through the RAS-MAPK and JAK-STAT5 pathways respectively (PubMed:7613138).
messages: Secreted

9606:PNLIPRP1
gene id: 9606:PNLIPRP1
uniprot id: P54315
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the AB hydrolase superfamily. Lipase family.
messages: May function as inhibitor of dietary triglyceride digestion. Lacks detectable lipase activity towards triglycerides, diglycerides, phosphatidylcholine, galactolipids or cholesterol esters (in vitro) (By similarity).
messages: Pancreas.
messages: Secreted

9606:DNAH1
gene id: 9606:DNAH1
uniprot id: A0A140VJI6
uniprot id: Q9P2D7
names: Disease Annotation
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the dynein heavy chain family.
messages: Consists of at least two heavy chains and a number of intermediate and light chains.
messages: Dynein heavy chains probably consist of an N-terminal stem (which binds cargo and interacts with other dynein components), and the head or motor domain. The motor contains six tandemly-linked AAA domains in the head, which form a ring. A stalk-like structure (formed by two of the coiled coil domains) protrudes between AAA 4 and AAA 5 and terminates in a microtubule-binding site. A seventh domain may also contribute to this ring; it is not clear whether the N-terminus or the C-terminus forms this extra domain. There are four well-conserved and two non-conserved ATPase sites, one per AAA domain. Probably only one of these (within AAA 1) actually hydrolyzes ATP, the others may serve a regulatory function (By similarity).
messages: Expressed primarily in trachea and testis, 2 tissues containing axonemal structures. Also expressed in brain (PubMed:11175280).
messages: Force generating protein of cilia required for sperm flagellum motility. Produces force towards the minus ends of microtubules. Dynein has ATPase activity; the force-producing power stroke is thought to occur on release of ADP. Required in spermatozoa for the formation of the inner dynein arms and biogenesis of the axoneme (PubMed:24360805).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: cilium axoneme
messages: flagellum

9606:RBM12
gene id: 9606:RBM12
uniprot id: Q9NTZ6
names: Disease Annotation
names: Subcellular Location Annotation
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry.
messages: Nucleus

9606:IMP4
gene id: 9606:IMP4
uniprot id: E7ENR5
uniprot id: Q96G21
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Component of the 60-80S U3 small nucleolar ribonucleoprotein (U3 snoRNP). Required for the early cleavages during pre-18S ribosomal RNA processing (PubMed:12655004). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797).
messages: Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3 (PubMed:34516797). Component of a heterotrimeric complex containing IMP3, IMP4 and MPHOSPH10. Interacts with MPHOSPH10 (PubMed:12655004).
messages: nucleolus

9606:EIF2B5
gene id: 9606:EIF2B5
uniprot id: Q13144
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subunit
messages: Belongs to the eIF-2B gamma/epsilon subunits family.
messages: Catalyzes the exchange of eukaryotic initiation factor 2-bound GDP for GTP.
messages: Complex of five different subunits; alpha, beta, gamma, delta and epsilon. Interacts with RGS2.
messages: Phosphorylated at Ser-544 by DYRK2; this is required for subsequent phosphorylation by GSK3B (By similarity). Phosphorylated on serine and threonine residues by GSK3B; phosphorylation inhibits its function.
messages: Polyubiquitinated, probably by NEDD4.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:DEFB132
gene id: 9606:DEFB132
uniprot id: Q7Z7B7
names: Caution
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the beta-defensin family.
messages: Has antibacterial activity.
messages: Secreted
messages: Was termed (Ref.2) DEFB133.

9606:CLYBL
gene id: 9606:CLYBL
uniprot id: Q8N0X4
names: Caution
names: Cofactor
names: Function
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the HpcH/HpaI aldolase family. Citrate lyase beta subunit-like subfamily.
messages: Binds 1 Mg(2+) ion per subunit.
messages: Homotrimer.
messages: Mitochondrial citramalyl-CoA lyase indirectly involved in the vitamin B12 metabolism (PubMed:29056341). Converts citramalyl-CoA into acetyl-CoA and pyruvate in the C5-dicarboxylate catabolism pathway (PubMed:29056341). The C5-dicarboxylate catabolism pathway is required to detoxify itaconate, a vitamin B12-poisoning metabolite (PubMed:29056341). Also acts as a malate synthase in vitro, converting glyoxylate and acetyl-CoA to malate (PubMed:29056341, PubMed:24334609). Also displays malyl-CoA thioesterase activity (PubMed:29056341). Also acts as a beta-methylmalate synthase in vitro, by mediating conversion of glyoxylate and propionyl-CoA to beta-methylmalate (PubMed:24334609, PubMed:29056341). Also has very weak citramalate synthase activity in vitro (PubMed:24334609, PubMed:29056341).
messages: Mitochondrion
messages: The protein is absent in 2.7% of the human population due to a loss-of-function polymorphism (rs41281112) that changes Arg-259 to a premature stop codon, leading to loss of the protein product (PubMed:23754956, PubMed:24334609). This polymorphism is associated with reduction of circulating vitamin B12 (PubMed:23754956, PubMed:24334609). The reduction of circulating vitamin B12 is caused by accumulation of citramalyl-CoA, an intermediate in the C5-dicarboxylate metabolic pathway that includes itaconate (PubMed:29056341). Itaconate acting as a vitamin B12-poisoning metabolite that inactivates the mitochondrial methylglutaconyl-CoA hydratase (AUH) enzyme (PubMed:29056341).
messages: This organism lacks the other subunits that are necessary for ATP-independent citrate lyase activity. Even though this protein has clear similarity to citrate lyase beta subunit, it is expected to have a somewhat different enzyme activity.

9606:CA2
gene id: 9606:CA2
uniprot id: P00918
uniprot id: V9HW21
names: Activity Regulation
names: Cofactor
names: Disease Annotation
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Activated by X-ray, histamine, L-adrenaline, L- and D-phenylalanine, L- and D-histidine, L-His-OMe and beta-Ala-His (carnosine). Competitively inhibited by saccharin, thioxolone, coumarins, 667-coumate, celecoxib (Celebrex), valdecoxib (Bextra), SC-125, SC-560, diclofenac, acetate, azide, bromide, sulfonamide derivatives such as acetazolamide (AZA), methazolamide (MZA), ethoxzolamide (EZA), dichlorophenamide (DCP), brinzolamide, dansylamide, thiabendazole-5-sulfonamide, trifluoromethane sulfonamide and N-hydroxysulfamide, fructose-based sugar sulfamate RWJ-37497, and Foscarnet (phosphonoformate trisodium salt). Repressed strongly by hydrogen sulfide(HS) and weakly by nitrate (NO(3)). Esterase activity weakly reduced by cyanamide. N-hydroxyurea interfers with zinc binding and inhibit activity.
messages: Belongs to the alpha-carbonic anhydrase family.
messages: Catalyzes the reversible hydration of carbon dioxide (PubMed:1909891, PubMed:1910042, PubMed:1336460, PubMed:8485129, PubMed:8399159, PubMed:8218160, PubMed:8262987, PubMed:8451242, PubMed:7901850, PubMed:7761440, PubMed:8639494, PubMed:9265618, PubMed:17330962, PubMed:9398308, PubMed:11327835, PubMed:12056894, PubMed:17346964, PubMed:12171926, PubMed:15453828, PubMed:16214338, PubMed:15865431, PubMed:16106378, PubMed:15300855, PubMed:15667203, PubMed:18942852, PubMed:11831900, PubMed:17251017, PubMed:17314045, PubMed:18618712, PubMed:1336460, PubMed:11802772, PubMed:14736236, PubMed:16290146, PubMed:16759856, PubMed:16807956, PubMed:16686544, PubMed:17705204, PubMed:17127057, PubMed:17540563, PubMed:17588751, PubMed:18266323, PubMed:18024029, PubMed:18162396, PubMed:18374572, PubMed:18640037, PubMed:18481843, PubMed:19170619, PubMed:19186056, PubMed:19206230, PubMed:19778001, PubMed:19520834). Can also hydrate cyanamide to urea (PubMed:10550681, PubMed:11015219). Stimulates the chloride-bicarbonate exchange activity of SLC26A6 (PubMed:15990874). Essential for bone resorption and osteoclast differentiation (PubMed:15300855). Involved in the regulation of fluid secretion into the anterior chamber of the eye. Contributes to intracellular pH regulation in the duodenal upper villous epithelium during proton-coupled peptide absorption.
messages: Cell membrane
messages: Cytoplasm
messages: Interacts with SLC4A4 (PubMed:14567693, PubMed:15218065). Interaction with SLC4A7 regulates SLC4A7 transporter activity (PubMed:14736710). Interacts with SLC26A6 isoform 4 (via C-terminus cytoplasmic domain) (PubMed:15990874).
messages: Reversible hydration of carbon dioxide.
messages: Target of drugs used in treatments against glaucoma disorder and breast cancer.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Zinc. Can also use cobalt(II) with lower efficiency, but not copper(II), nickel(II) and manganese(II).

9606:SH3BP2
gene id: 9606:SH3BP2
uniprot id: P78314
names: Disease Annotation
names: Function
names: Miscellaneous
names: PTM
names: Tissue Specificity
messages: Binds differentially to the SH3 domains of certain proteins of signal transduction pathways. Binds to phosphatidylinositols; linking the hemopoietic tyrosine kinase fes to the cytoplasmic membrane in a phosphorylation dependent mechanism.
messages: Expressed in a variety of tissues including lung, liver, skeletal muscle, kidney and pancreas.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Phosphorylated. Phosphorylation at Tyr-448 may stimulate the activity of the LYN kinase (By similarity).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:TEKT5
gene id: 9606:TEKT5
uniprot id: Q96M29
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the tektin family.
messages: Interacts with TEKT3.
messages: May be a structural component of the sperm flagellum.
messages: flagellum

9606:ZNF45
gene id: 9606:ZNF45
uniprot id: Q02386
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:LUZP1
gene id: 9606:LUZP1
uniprot id: Q86V48
names: Subcellular Location Annotation
messages: Nucleus
messages: centrosome

9606:AGMAT
gene id: 9606:AGMAT
uniprot id: Q9BSE5
names: Caution
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the ureohydrolase superfamily. Arginase family.
messages: Highly expressed in liver and kidney. Also found in skeletal muscle, fetal liver, brain, testis, skin and the gastrointestinal tract. Within brain, expression is higher in the cerebral cortex with lower levels in the medulla and spinal cord.
messages: Hydrolyzes linear guanidino acids to form urea and the corresponding amines. Displays specificity for substrates having a negatively charged head group and short chains including taurocyamine, guanidino propanoic and butanoic acids. May protect cells by detoxifying potentially harmful amounts of guanidino acids. Metabolizes L-arginine with low efficiency.
messages: Initially proposed to function as agmatinase but this activity was not proved when using the purified enzyme. A recent study showed that it rather functions as a guanidino acid hydrolase.
messages: Mitochondrion

9606:LOC102724652
gene id: 9606:LOC102724652
uniprot id: A0A8C8KJZ9
uniprot id: P02489
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acetylation at Lys-70 may increase chaperone activity.
messages: Alpha-crystallin A 1-172 is found at nearly twofold higher levels in diabetic lenses than in age-matched control lenses.
messages: Belongs to the small heat shock protein (HSP20) family.
messages: Contributes to the transparency and refractive index of the lens (PubMed:18302245). In its oxidized form (absence of intramolecular disulfide bond), acts as a chaperone, preventing aggregation of various proteins under a wide range of stress conditions (PubMed:22120592, PubMed:31792453, PubMed:18199971, PubMed:19595763). Required for the correct formation of lens intermediate filaments as part of a complex composed of BFSP1, BFSP2 and CRYAA (PubMed:28935373).
messages: Cytoplasm
messages: Deamidation of Asn-101 in lens occurs mostly during the first 30 years of age, followed by a small additional amount of deamidation (approximately 5%) during the next approximately 38 years, resulting in a maximum of approximately 50% deamidation during the lifetime of the individual.
messages: Expressed in the eye lens (at protein level).
messages: Heteropolymer composed of three CRYAA and one CRYAB subunits (PubMed:20836128). Inter-subunit bridging via zinc ions enhances stability, which is crucial as there is no protein turn over in the lens (PubMed:22890888). Can also form homodimers and homotetramers (dimers of dimers) which serve as the building blocks of homooligomers (PubMed:17909943, PubMed:31792453, PubMed:23255486). Within homooligomers, the zinc-binding motif is created from residues of 3 different molecules. His-100 and Glu-102 from one molecule are ligands of the zinc ion, and His-107 and His-154 residues from additional molecules complete the site with tetrahedral coordination geometry (By similarity). Part of a complex required for lens intermediate filament formation composed of BFSP1, BFSP2 and CRYAA (PubMed:28935373).
messages: In young individuals and during the first approximately 30 years of life, less than half molecules contain an intramolecular disulfide bond (oxidized form), while in the remaining fraction the cysteines are in the free sulfhydryl form (reduced form). With aging, the amount of oxidized form increases up to 90% and it becomes a major constituent of high molecular weight aggregates, concomitant with an age-dependent loss of its chaperone activity. The reduced form is undetectable in cataractous lenses.
messages: Nucleus
messages: O-glycosylated; contains N-acetylglucosamine side chains.
messages: Phosphorylation on Ser-122 seems to be developmentally regulated. Absent in the first months of life, it appears during the first 12 years of human lifetime. The relative amount of phosphorylated form versus unphosphorylated form does not change over the lifetime of the individual.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Undergoes age-dependent proteolytical cleavage at the C-terminus. Alpha-crystallin A(1-172) is the most predominant form produced most rapidly during the first 12 years of age and after this age is present in approximately 50% of the lens molecules.

9606:MAPK10
gene id: 9606:MAPK10
uniprot id: A0A286YF97
uniprot id: F8W9R5
uniprot id: P53779
uniprot id: Q499Y8
names: Activity Regulation
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: A chromosomal aberration involving MAPK10 has been found in a single patient with pharmacoresistant epileptic encephalopathy. Translocation t(Y;4)(q11.2;q21) which causes MAPK10 truncation.
messages: Activated by threonine and tyrosine phosphorylation by two dual specificity kinases, MAP2K4 and MAP2K7. MAP2K7 phosphorylates MAPK10 on Thr-221 causing a conformational change and a large increase in Vmax. MAP2K4 then phosphorylates Tyr-223 resulting in a further increase in Vmax. Inhibited by dual specificity phosphatases, such as DUSP1. Inhibited by HDAC9.
messages: Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.
messages: Cytoplasm
messages: Dually phosphorylated on Thr-221 and Tyr-223 by MAP2K4 and MAP2K7, which activates the enzyme. MAP2K7 shows a strong preference for Thr-221 while MAP2K4 phosphorylates Tyr-223 preferentially. Weakly autophosphorylated on threonine and tyrosine residues in vitro.
messages: Interacts with MAPKBP1 (By similarity). Interacts with MAPK8IP1/JIP-1 and MAPK8IP3/JIP-3/JSAP1 (By similarity). Interacts with SPAG9/MAPK8IP4/JIP4 (PubMed:15693750). Interacts with HDAC9 (PubMed:16611996). Interacts with ARRB2; the interaction enhances MAPK10 activation by MAP3K5 (PubMed:18435604). Interacts with SARM1 (By similarity). Interacts with JUND; interaction is inhibited in the presence of MEN1 (PubMed:22327296).
messages: Membrane
messages: Mitochondrion
messages: Nucleus
messages: Palmitoylation regulates subcellular location and axonal development.
messages: Responds to activation by environmental stress and pro-inflammatory cytokines by phosphorylating a number of transcription factors, and thus regulates transcriptional activity.
messages: Serine/threonine-protein kinase involved in various processes such as neuronal proliferation, differentiation, migration and programmed cell death. Extracellular stimuli such as pro-inflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK10/JNK3. In turn, MAPK10/JNK3 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. Plays regulatory roles in the signaling pathways during neuronal apoptosis. Phosphorylates the neuronal microtubule regulator STMN2. Acts in the regulation of the amyloid-beta precursor protein/APP signaling during neuronal differentiation by phosphorylating APP. Participates also in neurite growth in spiral ganglion neurons. Phosphorylates the CLOCK-BMAL1 heterodimer and plays a role in the photic regulation of the circadian clock (PubMed:22441692). Phosphorylates JUND and this phosphorylation is inhibited in the presence of MEN1 (PubMed:22327296).
messages: Specific to a subset of neurons in the nervous system. Present in the hippocampus and areas, cerebellum, striatum, brain stem, and weakly in the spinal cord. Very weak expression in testis and kidney.
messages: The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.

9606:PDZD4
gene id: 9606:PDZD4
uniprot id: Q76G19
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Brain-specific. Expressed in fetal and adult brain. Up-regulated in synovial carcinomas.
messages: cell cortex

9606:MTHFR
gene id: 9606:MTHFR
uniprot id: P42898
uniprot id: Q59GJ6
names: Activity Regulation
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Polymorphism
names: Similarity
names: Subunit
messages: Allosterically regulated by S-adenosylmethionine (SAM).
messages: Belongs to the methylenetetrahydrofolate reductase family.
messages: Catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cosubstrate for homocysteine remethylation to methionine (PubMed:29891918). Represents a key regulatory connection between the folate and methionine cycles (Probable).
messages: Contains a serine-rich phosphorylation region at the N-terminal and an eukaryote-only S-adenosylmethionine (SAM)-binding domain at the C-terminal. Through asymmetric homodimerization, the two regions are positioned next to each other and N-terminal phosphorylation increases sensitivity to SAM binding and inhibition.
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry.
messages: Genetic variation in MTHFR influences susceptibility to occlusive vascular disease, neural tube defects (NTD), colon cancer and acute leukemia.
messages: Homodimer.
messages: Phosphorylation of an N-terminal serine-rich phosphorylation region increases sensitivity to S-adenosylmethionine and inhibition.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:MAGEC2
gene id: 9606:MAGEC2
uniprot id: Q9UBF1
names: Developmental Stage
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cytoplasm
messages: Interacts with TRIM28 and UBE2H.
messages: Not expressed in normal tissues, except in germ cells in the seminiferous tubules and in Purkinje cells of the cerebellum. Expressed in various tumors, including melanoma, lymphoma, as well as pancreatic cancer, mammary gland cancer, non-small cell lung cancer and liver cancer. In hepatocellular carcinoma, there is an inverse correlation between tumor differentiation and protein expression, i.e. the lower the differentiation, the higher percentage of expression.
messages: Nucleus
messages: Proposed to enhance ubiquitin ligase activity of RING-type zinc finger-containing E3 ubiquitin-protein ligases. In vitro enhances ubiquitin ligase activity of TRIM28 and stimulates p53/TP53 ubiquitination in presence of Ubl-conjugating enzyme UBE2H leading to p53/TP53 degradation. Proposed to act through recruitment and/or stabilization of the Ubl-conjugating enzymes (E2) at the E3:substrate complex.
messages: Strongly expressed in spermatogonia and primary spermatocytes. At later stages of maturation, expression gradually decreases and becomes undetectable in mature spermatids.

9606:ACTG1
gene id: 9606:ACTG1
uniprot id: P63261
names: Disease Annotation
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Monomeric actin is cross-linked by V.cholerae toxins RtxA and VgrG1 in case of infection: bacterial toxins mediate the cross-link between Lys-50 of one monomer and Glu-270 of another actin monomer, resulting in formation of highly toxic actin oligomers that cause cell rounding (PubMed:19015515). The toxin can be highly efficient at very low concentrations by acting on formin homology family proteins: toxic actin oligomers bind with high affinity to formins and adversely affect both nucleation and elongation abilities of formins, causing their potent inhibition in both profilin-dependent and independent manners (PubMed:26228148).
messages: Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
messages: Belongs to the actin family.
messages: Defects in ACTG1 has been found in a patient with isolated coloboma, a defect of the eye characterized by the absence of ocular structures due to abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure). Isolated colobomas may be associated with an abnormally small eye (microphthalmia) or small cornea.
messages: In vertebrates 3 main groups of actin isoforms, alpha, beta and gamma have been identified. The alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. The beta and gamma actins coexist in most cell types as components of the cytoskeleton and as mediators of internal cell motility.
messages: Methylated at His-73 by SETD3.
messages: Monomethylation at Lys-84 (K84me1) regulates actin-myosin interaction and actomyosin-dependent processes. Demethylation by ALKBH4 is required for maintaining actomyosin dynamics supporting normal cleavage furrow ingression during cytokinesis and cell migration.
messages: N-terminal acetylation by NAA80 affects actin filament depolymerization and elongation, including elongation driven by formins (PubMed:29581253). In contrast, filament nucleation by the Arp2/3 complex is not affected (PubMed:29581253).
messages: N-terminal cleavage of acetylated methionine of immature cytoplasmic actin by ACTMAP.
messages: Oxidation of Met-44 and Met-47 by MICALs (MICAL1, MICAL2 or MICAL3) to form methionine sulfoxide promotes actin filament depolymerization. MICAL1 and MICAL2 produce the (R)-S-oxide form. The (R)-S-oxide form is reverted by MSRB1 and MSRB2, which promote actin repolymerization.
messages: Polymerization of globular actin (G-actin) leads to a structural filament (F-actin) in the form of a two-stranded helix. Each actin can bind to 4 others. Interacts with TWF1, CAPZB, cofilin and profilin (PubMed:28493397).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: cytoskeleton

9606:BCCIP
gene id: 9606:BCCIP
uniprot id: Q9P287
names: Developmental Stage
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the BCP1 family.
messages: During interphase, required for microtubule organizing and anchoring activities. During mitosis, required for the organization and stabilization of the spindle pole (PubMed:28394342). Isoform 2/alpha is particularly important for the regulation of microtubule anchoring, microtubule stability, spindle architecture and spindle orientation, compared to isoform 1/beta (PubMed:28394342). May promote cell cycle arrest by enhancing the inhibition of CDK2 activity by CDKN1A. May be required for repair of DNA damage by homologous recombination in conjunction with BRCA2. May not be involved in non-homologous end joining (NHEJ).
messages: Expressed at high levels in testis and skeletal muscle and at lower levels in brain, heart, kidney, liver, lung, ovary, pancreas, placenta, and spleen.
messages: HT1080 cells that constitutively express low levels of BCCIP display increased levels of spontaneous single-stranded DNA and double-strand breaks.
messages: Interacts with BRCA2, CDKN1A and MTDH/LYRIC (PubMed:10878006, PubMed:11313963, PubMed:14726710, PubMed:15713648, PubMed:18440304). Isoform 2/alpha, but not isoform 1/beta, interacts with DCTN1/p150-glued and ACTR1A/ARP1 (PubMed:28394342). Both isoform 1 and isoform 2 interact with alpha-, beta- and gamma-tubulins (PubMed:28394342). Interacts with TENT5C; the interaction has no effect on TENT5C poly(A) polymerase function (PubMed:28931820).
messages: Isoform 1 is expressed throughout the cell cycle. Isoform 2 is expressed following mitosis and peaks in the G1/S phase of the cell cycle.
messages: Nucleus
messages: centriole
messages: centrosome
messages: spindle pole

9606:MAP7D2
gene id: 9606:MAP7D2
uniprot id: A0A0K1JRJ6
uniprot id: A0A0K1JS24
uniprot id: A0A0M4F6E1
uniprot id: A0A0M4FLI9
uniprot id: Q96T17
names: Similarity
messages: Belongs to the MAP7 family.

9606:BCL6
gene id: 9606:BCL6
uniprot id: P41182
names: Disease Annotation
names: Domain
names: Function
names: Induction
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: A chromosomal aberration involving BCL6 may be a cause of a form of B-cell leukemia. Translocation t(3;11)(q27;q23) with POU2AF1/OBF1.
messages: A chromosomal aberration involving BCL6 may be a cause of lymphoma. Translocation t(3;4)(q27;p11) with ARHH/TTF.
messages: Acetylated at Lys-379 by EP300 which inhibits the interaction with NuRD complex and the transcriptional repressor function. Deacetylated by HDAC- and SIR2-dependent pathways.
messages: Chromosomal aberrations involving BCL6 are a cause of B-cell non-Hodgkin lymphomas (B-cell NHL), including diffuse large B-cell lymphoma and follicular lymphoma. Approximately 40% of diffuse large B-cell lymphomas and 5 to 10% of follicular lymphomas are associated with chromosomal translocations that deregulate expression of BCL6 by juxtaposing heterologous promoters to the BCL6 coding domain (PubMed:10469447, PubMed:10753856, PubMed:12414651, PubMed:11821949). Translocation t(3;14)(q27;q32). Translocation t(3;22)(q27;q11) with immunoglobulin gene regions (PubMed:11821949). Translocation t(3;7)(q27;p12) with IKZF1 gene 5'non-coding region (PubMed:10753856). Translocation t(3;6)(q27;p21) with Histone H4 (PubMed:12414651). Translocation t(3;16)(q27;p11) with IL21R. Translocation t(3;13)(q27;q14) with LCP1 (PubMed:10469447).
messages: Down-regulated during maturation of dendritic cells by selective stimuli such as bacterial lipopolysaccharides (LPS), CD40LG and zymosan. Protein levels decreases upon genotoxic stress in a dose- and time-dependent way.
messages: Expressed in germinal center T- and B-cells and in primary immature dendritic cells.
messages: Homodimer. Interacts (via BTB domain) with the corepressors BCOR, NCOR1 and SMRT/NCOR2; the interactions are direct. Forms preferably ternary complexes with BCOR and SMRT/NCOR2 on target gene promoters but, on enhancer elements, interacts with SMRT/NCOR2 and HDAC3 to repress proximal gene expression. Interacts with histone deacetylases HDAC2, HDAC5 and HDAC9 (via the catalytic domain). Interacts with ZBTB7 and BCL6B. Interacts with SCF(FBXO11) complex; the interaction is independent of phosphorylation and promotes ubiquitination. Interacts (when phosphorylated) with PIN1; the interaction is required for BCL6 degradation upon genotoxic stress. Interacts with ZBTB17; inhibits ZBTB17 transcriptional activity. Interacts with CTBP1, autoinhibits its transcriptional expression. Interacts with NOTCH1 NCID and SIRT1; leads to a epigenetic repression of selective NOTCH1-target genes. Interacts (nor via BTB domain neither acetylated) with the NuRD complex components CHD4, HDAC1, MBD3 and MTA3; the interaction with MTA3 inhibits BCL6 acetylation and is required for BCL6 transpriptional repression.
messages: Nucleus
messages: Phosphorylated by MAPK1 in response to antigen receptor activation at Ser-333 and Ser-343. Phosphorylated by ATM in response to genotoxic stress. Phosphorylation induces its degradation by ubiquitin/proteasome pathway.
messages: Polyubiquitinated (PubMed:9649500, PubMed:22113614, PubMed:30190310). Polyubiquitinated by SCF(FBXO11), leading to its degradation by the proteasome (PubMed:22113614). Ubiquitinated by the SCF(FBXL17) complex, leading to its degradation by the proteasome: ubiquitination by the SCF(FBXL17) complex takes place when aberrant BTB domain dimers are formed (PubMed:30190310).
messages: The BTB domain mediates homodimerization. Its dimer interface mediates peptide binding such as to corepressors BCOR and NCOR2 (PubMed:18212045). Interaction with corepressors through the BTB domain is needed to facilitate the rapid proliferation and survival of GC B-cells but is not involved in the T(FH) formation and BCL6-mediated suppression of T(H)2 and T(H)17 differentiationrequired for GC formation (By similarity).
messages: Transcriptional repressor mainly required for germinal center (GC) formation and antibody affinity maturation which has different mechanisms of action specific to the lineage and biological functions. Forms complexes with different corepressors and histone deacetylases to repress the transcriptional expression of different subsets of target genes. Represses its target genes by binding directly to the DNA sequence 5'-TTCCTAGAA-3' (BCL6-binding site) or indirectly by repressing the transcriptional activity of transcription factors. In GC B-cells, represses genes that function in differentiation, inflammation, apoptosis and cell cycle control, also autoregulates its transcriptional expression and up-regulates, indirectly, the expression of some genes important for GC reactions, such as AICDA, through the repression of microRNAs expression, like miR155. An important function is to allow GC B-cells to proliferate very rapidly in response to T-cell dependent antigens and tolerate the physiological DNA breaks required for immunglobulin class switch recombination and somatic hypermutation without inducing a p53/TP53-dependent apoptotic response. In follicular helper CD4(+) T-cells (T(FH) cells), promotes the expression of T(FH)-related genes but inhibits the differentiation of T(H)1, T(H)2 and T(H)17 cells. Also required for the establishment and maintenance of immunological memory for both T- and B-cells. Suppresses macrophage proliferation through competition with STAT5 for STAT-binding motifs binding on certain target genes, such as CCL2 and CCND2. In response to genotoxic stress, controls cell cycle arrest in GC B-cells in both p53/TP53-dependedent and -independent manners. Besides, also controls neurogenesis through the alteration of the composition of NOTCH-dependent transcriptional complexes at selective NOTCH targets, such as HES5, including the recruitment of the deacetylase SIRT1 and resulting in an epigenetic silencing leading to neuronal differentiation.

9606:PSMA8
gene id: 9606:PSMA8
uniprot id: A0A087WYS6
uniprot id: Q4G1B8
uniprot id: Q8TAA3
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the peptidase T1A family.
messages: Component of the outer alpha-ring of the 20S proteasome core which is composed of 28 subunits that are arranged in four stacked rings, resulting in a barrel-shaped structure. The catalytic chamber with the active sites is on the inside of the barrel. Interacts with canonical subunits of the spermatoproteasome, including proteasome activators PSME4 (also called PA200) and PSME3 (also called PA28-gamma). Interacts with proteasome-interacting proteins chaperones, ubiquitin ligases and ubiquitin specific proteases. Interacts with meiotic proteins cyclin dependent kinase CDK1 and the ATPase TRIP13 as well as proteins of the synaptonemal complex SIX6OS1 and SYCE3.
messages: Component of the spermatoproteasome, a proteasome specifically found in testis that promotes acetylation-dependent degradation of histones, thereby participating actively to the exchange of histones during spermatogenesis. The proteasome is a protein complex that degrades unneeded or damaged proteins by proteolysis, a chemical reaction that breaks peptide bonds. Required for 20S core proteasome assembly, essential for the degradation of meiotic proteins RAD51 and RPA1 at late prophase I and the progression of meiosis I during spermatogenesis. Localizes to the synaptonemal complex, a 'zipper'-like structure that holds homologous chromosome pairs in synapsis during meiotic prophase I.
messages: Nucleus

9606:HNRNPCL4
gene id: 9606:HNRNPCL4
uniprot id: B7ZW38
uniprot id: P0DMR1
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the RRM HNRPC family. RALY subfamily.
messages: Nucleus

9606:GJD2
gene id: 9606:GJD2
uniprot id: A0A654IE23
uniprot id: Q9UKL4
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: A connexon is composed of a hexamer of connexins.
messages: Belongs to the connexin family.
messages: Belongs to the connexin family. Delta-type subfamily.
messages: Cell membrane
messages: Highly expressed in neurons.
messages: Membrane
messages: One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell.
messages: gap junction

9606:SNX33
gene id: 9606:SNX33
uniprot id: Q8WV41
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the sorting nexin family.
messages: Cytoplasmic vesicle membrane
messages: Detected in heart and pancreas.
messages: Homodimer (via BAR domain). Interacts with ADAM15. Interacts with FASLG. Interacts (via SH3 domain) with DNM1 and DNM2. Interacts with WASL. Interacts with FCHSD1 (via the F-BAR domain) (By similarity).
messages: Membrane
messages: Phosphorylated.
messages: Plays a role in the reorganization of the cytoskeleton, endocytosis and cellular vesicle trafficking via its interactions with membranes, WASL, DNM1 and DNM2. Acts both during interphase and at the end of mitotic cell divisions. Required for efficient progress through mitosis and cytokinesis. Required for normal formation of the cleavage furrow at the end of mitosis. Modulates endocytosis of cell-surface proteins, such as APP and PRNP; this then modulates the secretion of APP and PRNP peptides. Promotes membrane tubulation (in vitro). May promote the formation of macropinosomes.
messages: The PX and BAR domains mediate association with membranes and are required for membrane tubulation.
messages: cytosol

9606:ERCC5
gene id: 9606:ERCC5
uniprot id: P28715
names: Caution
names: Cofactor
names: Disease Annotation
names: Domain
names: Function
names: Induction
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: A paper describing an additional role for this protein in a base excision repair pathway that is not coupled to transcription has been retracted, because some of the experimental data were incorrect.
messages: Belongs to the XPG/RAD2 endonuclease family. XPG subfamily.
messages: Binds 2 magnesium ions per subunit. They probably participate in the reaction catalyzed by the enzyme. May bind an additional third magnesium ion after substrate binding.
messages: Both nuclear localization signals 1 and 2 act as a monopartite signal which binds to the high affinity site on KPNA2/importin-alpha.
messages: Both the spacer region (also known as the recognition (R) domain) and C-terminal domain are required for stable binding to the DNA repair bubble (PubMed:16246722). However, both domains are dispensable for incision of DNA bubble structures (PubMed:16246722, PubMed:32821917, PubMed:32522879).
messages: Chromosome
messages: Includes a cryptic exon found in intron 6.
messages: Induced by replication stress caused by DNA double-strand breaks (DBS).
messages: Monomer (PubMed:32522879). Homodimer (PubMed:32522879). Component of the homologous recombination repair (HR) complex composed of ERCC5/XPG, BRCA2, PALB2, DSS1 and RAD51 (PubMed:26833090). Within the complex, interacts with BRCA2 and PALB2 (PubMed:26833090). Interacts with RNA polymerase II (PubMed:16246722). Interacts (via C-terminus) with ERCC6/CSB; the interaction stimulates ERCC6/CSB binding to the DNA repair bubble and ERCC6/CSB ATPase activity (PubMed:16246722). May form a complex composed of RNA polymerase II, ERCC6/CSB and ERCC5/XPG which associates with the DNA repair bubble during transcription-coupled nucleotide excision repair (PubMed:16246722). Interacts with BRCA1; the interaction promotes the release of BRCA1 from DNA (PubMed:26833090). Interacts with PCNA (PubMed:9305916). Interacts with NTHL1; the interaction stimulates NTHL1 activity and NTHL1 binding to its DNA substrate (PubMed:9927729).
messages: Nucleus
messages: Single-stranded structure-specific DNA endonuclease involved in DNA excision repair (PubMed:8206890, PubMed:8090225, PubMed:8078765, PubMed:7651464, PubMed:32821917, PubMed:32522879). Makes the 3'incision in DNA nucleotide excision repair (NER) (PubMed:8090225, PubMed:8078765, PubMed:32821917, PubMed:32522879). Binds and bends DNA repair bubble substrate and breaks base stacking at the single-strand/double-strand DNA junction of the DNA bubble (PubMed:32522879). Plays a role in base excision repair (BER) by promoting the binding of DNA glycosylase NTHL1 to its substrate and increasing NTHL1 catalytic activity that removes oxidized pyrimidines from DNA (PubMed:9927729). Involved in transcription-coupled nucleotide excision repair (TCR) which allows RNA polymerase II-blocking lesions to be rapidly removed from the transcribed strand of active genes (PubMed:16246722). Functions during the initial step of TCR in cooperation with ERCC6/CSB to recognized stalled RNA polymerase II (PubMed:16246722). Also, stimulates ERCC6/CSB binding to the DNA repair bubble and ERCC6/CSB ATPase activity (PubMed:16246722). Required for DNA replication fork maintenance and preservation of genomic stability (PubMed:26833090, PubMed:32522879). Involved in homologous recombination repair (HRR) induced by DNA replication stress by recruiting RAD51, BRCA2, and PALB2 to the damaged DNA site (PubMed:26833090). During HRR, binds to the replication fork with high specificity and stabilizes it (PubMed:32522879). Also, acts upstream of HRR, to promote the release of BRCA1 from DNA (PubMed:26833090).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:BUB1B-PAK6
gene id: 9606:BUB1B-PAK6
uniprot id: Q9NQU5
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Autophosphorylated. Phosphorylated by MAP2K6//MAPKK6, leading to PAK6 activation.
messages: Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.
messages: Cytoplasm
messages: Interacts tightly with GTP-bound but not GDP-bound CDC42/p21 and RAC1 (By similarity). Interacts with the androgen receptor AR and the estrogen receptor ESR1. Interacts with IQGAP1 and PPM1B.
messages: Nucleus
messages: Selectively expressed in brain and testis, with lower levels in multiple tissues including prostate and breast.
messages: Serine/threonine protein kinase that plays a role in the regulation of gene transcription. The kinase activity is induced by various effectors including AR or MAP2K6/MAPKK6. Phosphorylates the DNA-binding domain of androgen receptor/AR and thereby inhibits AR-mediated transcription. Inhibits also ESR1-mediated transcription. May play a role in cytoskeleton regulation by interacting with IQGAP1. May protect cells from apoptosis through phosphorylation of BAD.

9606:ACLY
gene id: 9606:ACLY
uniprot id: P53396
uniprot id: Q4LE36
names: Activity Regulation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Acetylated at Lys-540, Lys-546 and Lys-554 by KAT2B/PCAF (PubMed:23932781). Acetylation is promoted by glucose and stabilizes the protein, probably by preventing ubiquitination at the same sites (PubMed:23932781). Acetylation promotes de novo lipid synthesis (PubMed:23932781). Deacetylated by SIRT2.
messages: Catalyzes the cleavage of citrate into oxaloacetate and acetyl-CoA, the latter serving as common substrate for de novo cholesterol and fatty acid synthesis.
messages: Homotetramer.
messages: ISGylated.
messages: In the C-terminal section; belongs to the succinate/malate CoA ligase alpha subunit family.
messages: In the N-terminal section; belongs to the succinate/malate CoA ligase beta subunit family.
messages: Phosphorylated by PKA and GSK3 in a sequential manner; phosphorylation results in activation of its activity (PubMed:10653665). Phosphorylation on Thr-447 and Ser-451 depends on the phosphorylation state of Ser-455 (By similarity). Phosphorylation on Ser-455 is decreased by prior phosphorylation on the other 2 residues (By similarity).
messages: Phosphorylation results in activation of its activity (PubMed:10653665). Glucose 6-phosphate, fructose 6-phosphate, fructose 2,6-bisphosphate, ribulose 5-phosphate, and fructose 1,6-bisphosphate also act as activators (PubMed:10653665).
messages: Ubiquitinated at Lys-540, Lys-546 and Lys-554 by the BCR(KLHL25) E3 ubiquitin ligase complex and UBR4, leading to its degradation (PubMed:23932781, PubMed:27664236, PubMed:34491895). Ubiquitination is probably inhibited by acetylation at same site (PubMed:23932781). BCR(KLHL25)-mediated degradation of ACLY promotes fatty acid oxidation and is required for differentiation of inducible regulatory T (iTreg) cells (PubMed:34491895).
messages: cytosol

9606:FAM180A
gene id: 9606:FAM180A
uniprot id: Q6UWF9
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the FAM180 family.
messages: Secreted

9606:CSPG4
gene id: 9606:CSPG4
uniprot id: Q6UVK1
names: Function
names: Miscellaneous
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts with C.difficile toxin TcdB, suggesting that it may act as a receptor for TcdB.
messages: Apical cell membrane
messages: Cell membrane
messages: Cell surface
messages: Detected in fibroblasts (at protein level) (PubMed:36213313). Detected in placenta (at protein level) (PubMed:32337544). Detected in malignant melanoma cells.
messages: Interacts with the first PDZ domain of MPDZ. Interacts with PRKCA. Binds TNC, laminin-1, COL5A1 and COL6A2. Interacts with PLG and angiostatin. Binds FGF2 and PDGFA. Interacts with GRIP1, GRIP2 and GRIA2. Forms a ternary complex with GRIP1 and GRIA2 (By similarity). Interacts with LGALS3 and the integrin composed of ITGB1 and ITGA3. Interacts with ITGA4 through its chondroitin sulfate glycosaminoglycan. Interacts with BCAR1, CDC42 and ACK1. Interacts with MMP16.
messages: O-glycosylated; contains glycosaminoglycan chondroitin sulfate which are required for proper localization and function in stress fiber formation (By similarity). Involved in interaction with MMP16 and ITGA4.
messages: Phosphorylation by PRKCA regulates its subcellular location and function in cell motility.
messages: Proteoglycan playing a role in cell proliferation and migration which stimulates endothelial cells motility during microvascular morphogenesis. May also inhibit neurite outgrowth and growth cone collapse during axon regeneration. Cell surface receptor for collagen alpha 2(VI) which may confer cells ability to migrate on that substrate. Binds through its extracellular N-terminus growth factors, extracellular matrix proteases modulating their activity. May regulate MPP16-dependent degradation and invasion of type I collagen participating in melanoma cells invasion properties. May modulate the plasminogen system by enhancing plasminogen activation and inhibiting angiostatin. Functions also as a signal transducing protein by binding through its cytoplasmic C-terminus scaffolding and signaling proteins. May promote retraction fiber formation and cell polarization through Rho GTPase activation. May stimulate alpha-4, beta-1 integrin-mediated adhesion and spreading by recruiting and activating a signaling cascade through CDC42, ACK1 and BCAR1. May activate FAK and ERK1/ERK2 signaling cascades.
messages: Valuable marker for several incompletely differentiated precursor cells.
messages: lamellipodium membrane

9606:RPL36
gene id: 9606:RPL36
uniprot id: Q9Y3U8
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the eukaryotic ribosomal protein eL36 family.
messages: Component of the large ribosomal subunit (PubMed:12962325, PubMed:23636399, PubMed:25901680, PubMed:25957688, PubMed:32669547).
messages: Component of the large ribosomal subunit (PubMed:12962325, PubMed:23636399, PubMed:25901680, PubMed:25957688, PubMed:32669547). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:12962325, PubMed:23636399, PubMed:25901680, PubMed:25957688, PubMed:32669547).
messages: Cytoplasm
messages: cytosol

9606:AP1M2
gene id: 9606:AP1M2
uniprot id: Q53GI5
uniprot id: Q9Y6Q5
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Adaptor protein complex 1 (AP-1) is a heterotetramer composed of two large adaptins (gamma-type subunit AP1G1 and beta-type subunit AP1B1), a medium adaptin (mu-type subunit AP1M1 or AP1M2) and a small adaptin (sigma-type subunit AP1S1 or AP1S2 or AP1S3). Interacts with P2X4 (By similarity).
messages: Belongs to the adaptor complexes medium subunit family.
messages: Golgi apparatus
messages: Phosphorylation of membrane-bound AP1M1/AP1M2 increases its affinity for sorting signals.
messages: Subunit of clathrin-associated adaptor protein complex 1 that plays a role in protein sorting in the trans-Golgi network (TGN) and endosomes. The AP complexes mediate the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules.
messages: clathrin-coated vesicle membrane

9606:CAT
gene id: 9606:CAT
uniprot id: A0A384P5Q0
uniprot id: P04040
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the catalase family.
messages: Catalyzes the degradation of hydrogen peroxide (H(2)O(2)) generated by peroxisomal oxidases to water and oxygen, thereby protecting cells from the toxic effects of hydrogen peroxide (PubMed:7882369). Promotes growth of cells including T-cells, B-cells, myeloid leukemia cells, melanoma cells, mastocytoma cells and normal and transformed fibroblast cells (PubMed:7882369).
messages: Homotetramer (PubMed:21976670, PubMed:10666617, PubMed:10656833). Interacts (via microbody targeting signal) with PEX5, monomeric form interacts with PEX5, leading to its translocation into peroxisomes (PubMed:21976670).
messages: Occurs in almost all aerobically respiring organisms and serves to protect cells from the toxic effects of hydrogen peroxide.
messages: Peroxisome
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:COPS5
gene id: 9606:COPS5
uniprot id: A0A024R7W9
uniprot id: Q92905
names: Domain
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the peptidase M67A family. CSN5 subfamily.
messages: Component of the CSN complex, composed of COPS1/GPS1, COPS2, COPS3, COPS4, COPS5, COPS6, COPS7 (COPS7A or COPS7B), COPS8 and COPS9 isoform 1 (PubMed:26456823). In the complex, it probably interacts directly with COPS1, COPS2, COPS4, COPS6 and COPS7 (COPS7A or COPS7B) and COPS9 isoform 1 (PubMed:26456823). Interacts with COPS9 isoform 2 (PubMed:23776465). The CSN complex interacts with the BRISC complex. Also exists as monomeric form. Interacts with TP53, MIF, JUN, UCHL1, NCOA1, HIF1A, CDKN1B, BCL3, GFER, PGR, LHCGR, SMAD4, SMAD7, ID1, ID3, ITGB2 and TOP2A. Part of a complex consisting of RANBP9, Ran, DYRK1B and COPS5. Interacts with IFIT3. Interacts with BRSK2. Interacts with ZDHHC16 (PubMed:17123647). Interacts with MINDY3 (PubMed:21499297). Interacts with FANK1; regulates the phosphorylation of JUN and the transcriptional activity of AP-1 (PubMed:20978819). Interacts with NUPR1; this interaction allows COPS5-dependent CDKN1B nuclear to cytoplasm translocation (PubMed:16300740).
messages: Nucleus
messages: Probable protease subunit of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of the SCF-type E3 ligase complexes, leading to decrease the Ubl ligase activity of SCF-type complexes such as SCF, CSA or DDB2. The complex is also involved in phosphorylation of p53/TP53, c-jun/JUN, IkappaBalpha/NFKBIA, ITPK1 and IRF8, possibly via its association with CK2 and PKD kinases. CSN-dependent phosphorylation of TP53 and JUN promotes and protects degradation by the Ubl system, respectively. In the complex, it probably acts as the catalytic center that mediates the cleavage of Nedd8 from cullins. It however has no metalloprotease activity by itself and requires the other subunits of the CSN complex. Interacts directly with a large number of proteins that are regulated by the CSN complex, confirming a key role in the complex. Promotes the proteasomal degradation of BRSK2.
messages: The CSN complex is associated with some 'Lys-63'-specific deubiquitination. Such activity is however not mediated by the core CSN complex but by the BRCC3/BRCC36 component of the BRISC complex.
messages: The JAMM motif is essential for the protease activity of the CSN complex resulting in deneddylation of cullins. It constitutes the catalytic center of the complex (By similarity).
messages: cytosol
messages: perinuclear region
messages: synaptic vesicle

9606:ARK2C
gene id: 9606:ARK2C
uniprot id: Q6ZSG1
names: Activity Regulation
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the Arkadia family.
messages: Binds free ubiquitin non-covalently via its RING-type zinc finger. Ubiquitin-binding leads to enhance the E3 ubiquitin-protein ligase activity by stabilizing the ubiquitin-conjugating enzyme E2 (donor ubiquitin) in the 'closed' conformation and activating ubiquitin transfer (PubMed:26656854).
messages: E3 ubiquitin-protein ligase that acts as a regulator of motor axon elongation. Required for efficient motor axon extension in the dorsal forelimb by enhancing the transcriptional responses of the SMAD1/SMAD5/SMAD8 effectors, which are activated downstream of BMP. Acts by mediating ubiquitination and degradation of SMAD inhibitors such as SMAD6, SMAD7, SKI and SNON isoform of SKIL.
messages: Monomer; binding to the ubiquitin-conjugating enzyme E2 does not trigger homodimerization (PubMed:26656854).
messages: Nucleus
messages: The RING-type zinc finger mediates the E3 ubiquitin-protein ligase activity and binds directly to free ubiquitin (PubMed:26656854). Non-covalent ubiquitin-binding stabilizes the ubiquitin-conjugating enzyme E2 (donor ubiquitin) in the 'closed' conformation and stimulates ubiquitin transfer (PubMed:26656854).

9606:TRPV5
gene id: 9606:TRPV5
uniprot id: A0A0A6YY98
uniprot id: Q9NQA5
names: Activity Regulation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Activated by WNK3.
messages: Apical cell membrane
messages: Belongs to the transient receptor (TC 1.A.4) family. TrpV subfamily. TRPV5 sub-subfamily.
messages: Cell membrane
messages: Constitutively active calcium selective cation channel thought to be involved in Ca(2+) reabsorption in kidney and intestine (PubMed:11549322, PubMed:18768590). Required for normal Ca(2+) reabsorption in the kidney distal convoluted tubules (By similarity). The channel is activated by low internal calcium level and the current exhibits an inward rectification (PubMed:11549322, PubMed:18768590). A Ca(2+)-dependent feedback regulation includes fast channel inactivation and slow current decay (By similarity). Heteromeric assembly with TRPV6 seems to modify channel properties. TRPV5-TRPV6 heteromultimeric concatemers exhibit voltage-dependent gating (By similarity).
messages: Expressed at high levels in kidney, small intestine and pancreas, and at lower levels in testis, prostate, placenta, brain, colon and rectum.
messages: Glycosylated.
messages: Homotetramer and probably heterotetramer with TRPV6. Interacts with TRPV6 (By similarity). Interacts with S100A10 and probably with the ANAX2-S100A10 heterotetramer. The interaction with S100A10 is required for the trafficking to the plasma membrane. Interacts with calmodulin. Interacts with BSPRY, which results in its inactivation.
messages: Membrane

9606:ATOH7
gene id: 9606:ATOH7
uniprot id: F1T0H4
uniprot id: Q8N100
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Forms a heterodimer with TCF3 isoform E47; interaction may be required for DNA-binding in certain situations.
messages: Nucleus
messages: Perikaryon
messages: The disease is caused by variants affecting the gene represented in this entry. A 6.5 kb deletion that spans a remote cis regulatory element 20 kb upstream from ATOH7 has been found in PHPVAR patients (PubMed:21441919).
messages: Transcription factor that binds to DNA at the consensus sequence 5'-CAG[GC]TG-3' (PubMed:31696227). Dimerization with TCF3 isoform E47 may be required in certain situations (PubMed:31696227). Binds to gene promoters and enhancer elements, and thereby regulates a transcriptional program of retinal ganglion cell (RGC) determinant genes (By similarity). Although the exact mechanism is not certain, retinal transcription regulation by ATOH7 has a role in RGC determination and survival, photoreceptor population development, targeting of RGC axons to the optic nerve and development of the retino-hypothalamic tract (By similarity). Binds to its own promoter and enhancer sequences, suggesting autoregulation of ATOH7 transcription (By similarity). Required for retinal circadian rhythm photoentrainment (By similarity). Plays a role in brainstem auditory signaling and binaural processing (By similarity).
messages: axon

9606:RSRP1
gene id: 9606:RSRP1
uniprot id: Q9BUV0
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the RSRP family.
messages: Expressed in brain (at protein level).
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Nucleus
messages: Phosphorylated. Phosphorylation at Ser-107 and Ser-109 mediates the interaction with spliceosome proteins.
messages: Probably acts as a spliceosomal factor that contributes to spliceosome assembly and regulates the isoform switching of proteins such as PARP6.

9606:KRTAP12-3
gene id: 9606:KRTAP12-3
uniprot id: P60328
names: Function
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Belongs to the KRTAP type 12 family.
messages: In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.
messages: Interacts with hair keratins.
messages: Restricted to a narrow region of the hair fiber cuticle, lying approximately 20 cell layers above the apex of the dermal papilla of the hair root; not detected in any other tissues.

9606:NEUROD1
gene id: 9606:NEUROD1
uniprot id: Q13562
names: Disease Annotation
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: Acts as a transcriptional activator: mediates transcriptional activation by binding to E box-containing promoter consensus core sequences 5'-CANNTG-3'. Associates with the p300/CBP transcription coactivator complex to stimulate transcription of the secretin gene as well as the gene encoding the cyclin-dependent kinase inhibitor CDKN1A. Contributes to the regulation of several cell differentiation pathways, like those that promote the formation of early retinal ganglion cells, inner ear sensory neurons, granule cells forming either the cerebellum or the dentate gyrus cell layer of the hippocampus, endocrine islet cells of the pancreas and enteroendocrine cells of the small intestine. Together with PAX6 or SIX3, is required for the regulation of amacrine cell fate specification. Also required for dendrite morphogenesis and maintenance in the cerebellar cortex. Associates with chromatin to enhancer regulatory elements in genes encoding key transcriptional regulators of neurogenesis (By similarity).
messages: Cytoplasm
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry.
messages: Efficient DNA-binding requires dimerization with another bHLH protein (By similarity). Heterodimer with TCF3/E47; the heterodimer is inhibited in presence of ID2, but not NR0B2, to E-box element (PubMed:14752053). Interacts with EP300; the interaction is inhibited by NR0B2 (PubMed:14752053). Interacts with RREB1 (PubMed:12482979). Interacts with ATOH8 (By similarity).
messages: Nucleus
messages: Phosphorylated. In islet cells, phosphorylated on Ser-274 upon glucose stimulation; which may be required for nuclear localization. In activated neurons, phosphorylated on Ser-335; which promotes dendritic growth. Phosphorylated by MAPK1; phosphorylation regulates heterodimerization and DNA-binding activities. Phosphorylation on Ser-266 and Ser-274 increases transactivation on the insulin promoter in glucose-stimulated insulinoma cells (By similarity).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:AGBL3
gene id: 9606:AGBL3
uniprot id: Q8NEM8
names: Cofactor
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the peptidase M14 family.
messages: Binds 1 zinc ion per subunit.
messages: Metallocarboxypeptidase that mediates deglutamylation of tubulin and non-tubulin target proteins. Catalyzes the removal of polyglutamate side chains present on the gamma-carboxyl group of glutamate residues within the C-terminal tail of tubulin protein. Specifically cleaves tubulin long-side-chains, while it is not able to remove the branching point glutamate. Also catalyzes the removal of polyglutamate residues from the carboxy-terminus of non-tubulin proteins such as MYLK. May catalyze the hydrolysis of aspartate from the carboxy-terminus of target proteins. Does not show detyrosinase or deglycylase activities from the carboxy-terminus of target proteins.
messages: Metallocarboxypeptidase that mediates tubulin deglutamylation.
messages: cytosol

9606:TMEM241
gene id: 9606:TMEM241
uniprot id: Q24JQ0
names: Induction
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the TMEM241 family.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Membrane
messages: Up-regulated by inducers of the unfolded protein response (UPR), including tunicamycin and thapsigargin.

9606:KRTAP5-1
gene id: 9606:KRTAP5-1
uniprot id: Q6L8H4
names: Function
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Belongs to the KRTAP type 5 family.
messages: Expressed in hair root but not in skin. Expressed also in lung, pancreas, ovary, testis.
messages: In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated protein (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.
messages: Interacts with hair keratins.

9606:THRAP3
gene id: 9606:THRAP3
uniprot id: Q9Y2W1
names: Function
names: PTM
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: ADP-ribosylation during genotoxic stress promotes accumulation in nuclear speckles.
messages: Associated with the large multiprotein complex TRAP (Mediator complex-like). Interacts with SFPQ; the interaction is dependent on SFPQ phosphorylation at 'Thr-687' and inhibits binding of SFPQ to an ESS1 exonic splicing silencer element-containing RNA. Interacts with NXF1. Component of the SNARP complex which consists at least of SNIP1, SNW1, THRAP3, BCLAF1 and PNN. Associated with spliced mRNP complexes. Interacts with HELZ2 and PPARG. Interacts with CLOCK and BMAL1 (By similarity). Component of a MACOM-like complex, named WTAP complex, composed of WTAP, ZC3H13, CBLL1, KIAA1429, RBM15, BCLAF1 and THRAP3.
messages: Belongs to the BCLAF1/THRAP3 family.
messages: Contaminating sequence. Potential poly-A sequence.
messages: Involved in pre-mRNA splicing. Remains associated with spliced mRNA after splicing which probably involves interactions with the exon junction complex (EJC). Can trigger mRNA decay which seems to be independent of nonsense-mediated decay involving premature stop codons (PTC) recognition. May be involved in nuclear mRNA decay. Involved in regulation of signal-induced alternative splicing. During splicing of PTPRC/CD45 is proposed to sequester phosphorylated SFPQ from PTPRC/CD45 pre-mRNA in resting T-cells. Involved in cyclin-D1/CCND1 mRNA stability probably by acting as component of the SNARP complex which associates with both the 3'end of the CCND1 gene and its mRNA. Involved in response to DNA damage. Is excluced from DNA damage sites in a manner that parallels transcription inhibition; the function may involve the SNARP complex. Initially thought to play a role in transcriptional coactivation through its association with the TRAP complex; however, it is not regarded as a stable Mediator complex subunit. Cooperatively with HELZ2, enhances the transcriptional activation mediated by PPARG, maybe through the stabilization of the PPARG binding to DNA in presence of ligand. May play a role in the terminal stage of adipocyte differentiation. Plays a role in the positive regulation of the circadian clock. Acts as a coactivator of the CLOCK-BMAL1 heterodimer and promotes its transcriptional activator activity and binding to circadian target genes (PubMed:24043798).
messages: Nucleus
messages: Nucleus speckle
messages: Ubiquitous.
messages: nucleoplasm

9606:NUBPL
gene id: 9606:NUBPL
uniprot id: B4DWB0
uniprot id: Q8TB37
uniprot id: X5D2R5
names: Cofactor
names: Disease Annotation
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the Mrp/NBP35 ATP-binding proteins family.
messages: Binds 1 [4Fe-4S] cluster.
messages: Highest expression in liver and kidney. expressed at significant levels in small intestine and brain (at protein level).
messages: May be due to exon skipping.
messages: Mitochondrion
messages: Required for the assembly of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I). May deliver of one or more Fe-S clusters to complex I subunits.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:FBXW12
gene id: 9606:FBXW12
uniprot id: Q6X9E4
names: Function
names: Subunit
names: Tissue Specificity
messages: Interacts with SKP1 (PubMed:26171402). Interacts with CUL1 (By similarity). Interacts with IL22RA1 (PubMed:26171402).
messages: Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex (PubMed:26171402). Promotes degradation of interleukin-22 receptor subunit IL22RA1 in resting and IL22-stimulated conditions by facilitating its ubiquitination (PubMed:26171402). Functions as a cell growth suppressor (PubMed:26171402).
messages: Ubiquitously expressed.

9606:CDC25B
gene id: 9606:CDC25B
uniprot id: B3KS38
uniprot id: B4DIG0
uniprot id: B4DQZ3
uniprot id: B4DRC3
uniprot id: E1YMX4
uniprot id: G8JLH2
uniprot id: P30305
uniprot id: Q6MZW8
names: Activity Regulation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the MPI phosphatase family.
messages: Functions as a dosage-dependent inducer in mitotic control. Tyrosine protein phosphatase required for progression of the cell cycle.
messages: Interacts with MAPK14 and 14-3-3 proteins.
messages: Phosphorylated by BRSK1 in vitro. Phosphorylated by CHEK1, which inhibits the activity of this protein. Phosphorylation at Ser-353 by AURKA might locally participate in the control of the onset of mitosis. Phosphorylation by MELK at Ser-169 promotes localization to the centrosome and the spindle poles during mitosis. Phosphorylation at Ser-323 and Ser-375 by MAPK14 is required for binding to 14-3-3 proteins.
messages: Stimulated by B-type cyclins.
messages: Tyrosine protein phosphatase which functions as a dosage-dependent inducer of mitotic progression. Required for G2/M phases of the cell cycle progression and abscission during cytokinesis in a ECT2-dependent manner. Directly dephosphorylates CDK1 and stimulates its kinase activity. The three isoforms seem to have a different level of activity.
messages: centrosome
messages: spindle pole

9606:MED28
gene id: 9606:MED28
uniprot id: Q9H204
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the Mediator complex subunit 28 family.
messages: Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. May be part of a complex containing NF2/merlin that participates in cellular signaling to the actin cytoskeleton downstream of tyrosine kinase signaling pathways.
messages: Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. Forms a ternary complex with NF2/merlin and GRB2. Binds to actin.
messages: Cytoplasm
messages: Membrane
messages: Nucleus
messages: Up-regulated by endothelial cells when exposed to tumor conditional media.
messages: Widely expressed. Highly expressed in vascular tissues such as placenta, testis and liver.

9606:SPATA13
gene id: 9606:SPATA13
uniprot id: Q96N96
names: Activity Regulation
names: Domain
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acts as guanine nucleotide exchange factor (GEF) for RHOA, RAC1 and CDC42 GTPases. Regulates cell migration and adhesion assembly and disassembly through a RAC1, PI3K, RHOA and AKT1-dependent mechanism. Increases both RAC1 and CDC42 activity, but decreases the amount of active RHOA. Required for MMP9 up-regulation via the JNK signaling pathway in colorectal tumor cells. Involved in tumor angiogenesis and may play a role in intestinal adenoma formation and tumor progression.
messages: Both the ABR and the SH3 domains contribute to maintaining the protein in an inhibited conformation by associating with the C-terminal tail. Binding of these domains to the C-terminal tail inhibits the activity of the protein by blocking a region that is required for its GEF activity.
messages: Cytoplasm
messages: Expressed at high levels in the placenta, spleen and kidney, at moderate levels in lung, small intestine, liver, brain and heart, and at low levels in skeletal muscle. Expression is aberrantly enhanced in most colorectal tumors.
messages: Interacts (via ABR and SH3 domain) with APC. The binding of APC enhances its GEF activity by relieving it from an autoinhibitory conformation, in which the ABR and SH3 domains are associated with the C-terminal tail. Interacts (via C-terminal tail) with PPP1R9B (via C-terminus). Interacts with RAC1.
messages: The C-terminal tail is required for its GEF activity.
messages: filopodium
messages: lamellipodium
messages: ruffle membrane

9606:PIGW
gene id: 9606:PIGW
uniprot id: Q7Z7B1
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the PIGW family.
messages: Endoplasmic reticulum membrane
messages: Required for the transport of GPI-anchored proteins to the plasma membrane (PubMed:24367057). Probable acetyltransferase, which acetylates the inositol ring of phosphatidylinositol during biosynthesis of GPI-anchor. Acetylation during GPI-anchor biosynthesis is not essential for the subsequent mannosylation and is usually removed soon after the attachment of GPIs to proteins (By similarity).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:GSTA2
gene id: 9606:GSTA2
uniprot id: A0A140VKE2
uniprot id: A8K987
uniprot id: P09210
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the GST superfamily. Alpha family.
messages: Catalyzes the conjugation of glutathione to a large variety of electrophilic compounds.
messages: Cytoplasm
messages: Homodimer or heterodimer of GSTA1 and GSTA2.
messages: Liver.

9606:SLC39A6
gene id: 9606:SLC39A6
uniprot id: Q13433
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Apical cell membrane
messages: Belongs to the ZIP transporter (TC 2.A.5) family.
messages: Cell membrane
messages: Cleaved on the N-terminus before locating to the plasma membrane.
messages: Highly expressed in the breast, prostate, placenta, kidney, pituitary and corpus callosum (PubMed:12839489). Weakly expressed in heart and intestine. Also highly expressed in cells derived from an adenocarcinoma of the cervix and lung carcinoma (PubMed:12839489).
messages: Interacts with SLC39A10; which triggers cells to undergo EMT and mitosis (PubMed:27274087). Found in a complex with SLC39A6, SLC39A10 and with the 'Ser-727' phosphorylated form of STAT3 throughout mitosis (PubMed:32797246). Found in a complex with SLC39A6, SLC39A10 and with NCAM1; this complex controls NCAM1 phosphorylation and integration into focal adhesion complexes during epithelial-to-mesenchymal transition (EMT) (By similarity). Found in a complex with SLC39A6, SLC39A10 and with GSK3B that controls NCAM1 phosphorylation (By similarity).
messages: Membrane raft
messages: N-glycosylated.
messages: Phosphorylated by ZAP70 in response to TCR stimulation leading to its activation.
messages: Up-regulated by estrogen in breast cancer cells lines (PubMed:2903103, PubMed:23919497). Decreased protein level in response to zinc treatment (PubMed:18272141). Increased upon T cell activation (PubMed:30552163). Induced by STAT3 (PubMed:23919497).
messages: Zinc-influx transporter which plays a role in zinc homeostasis and in the induction of epithelial-to-mesenchymal transition (EMT) (PubMed:27274087, PubMed:18272141, PubMed:21422171, PubMed:34394081, PubMed:23919497, PubMed:12839489). When associated with SLC39A10, the heterodimer formed by SLC39A10 and SLC39A6 mediates cellular zinc uptake to trigger cells to undergo epithelial- to-mesenchymal transition (EMT) (PubMed:27274087). The SLC39A10-SLC39A6 heterodimer also controls NCAM1 phosphorylation and its integration into focal adhesion complexes during EMT (By similarity). Zinc influx inactivates GSK3B, enabling unphosphorylated SNAI1 in the nucleus to down-regulate adherence genes such as CDH1, causing loss of cell adherence (PubMed:23919497). In addition, the SLC39A10-SLC39A6 heterodimer plays an essentiel role in initiating mitosis by importing zinc into cells to initiate a pathway resulting in the onset of mitosis (PubMed:32797246). Participates in the T-cell receptor signaling regulation by mediating cellular zinc uptake into activated lymphocytes (PubMed:30552163, PubMed:21422171, PubMed:34394081). Regulates the zinc influx necessary for proper meiotic progression to metaphase II (MII) that allows the oocyte-to-egg transition (PubMed:25143461).
messages: lamellipodium membrane

9606:PTPN4
gene id: 9606:PTPN4
uniprot id: P29074
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Interacts with attenuated rabies virus protein G; this interaction is required for virally-induced apoptosis.
messages: Belongs to the protein-tyrosine phosphatase family. Non-receptor class subfamily.
messages: Cell membrane
messages: Cleaved and activated by calpain I/CAPN1.
messages: Cytoplasm
messages: Highly phosphorylated on serine and threonine residues but not on tyrosines.
messages: Interacts with MAPK12 (via C-terminus); this interaction abolishes PTPN4 catalytic autoinhibition and thus activates the phosphatase activity.
messages: Phosphatase that plays a role in immunity, learning, synaptic plasticity or cell homeostasis (PubMed:25825441, PubMed:27246854). Regulates neuronal cell homeostasis by protecting neurons against apoptosis (PubMed:20086240). Negatively regulates TLR4-induced interferon beta production by dephosphorylating adapter TICAM2 and inhibiting subsequent TRAM-TRIF interaction (PubMed:25825441). Dephosphorylates also the immunoreceptor tyrosine-based activation motifs/ITAMs of the TCR zeta subunit and thereby negatively regulates TCR-mediated signaling pathway (By similarity). May act at junctions between the membrane and the cytoskeleton.
messages: cytoskeleton

9606:RPS27L
gene id: 9606:RPS27L
uniprot id: Q71UM5
names: Cofactor
names: Similarity
messages: Belongs to the eukaryotic ribosomal protein eS27 family.
messages: Binds 1 zinc ion per subunit.

9606:HS6ST2
gene id: 9606:HS6ST2
uniprot id: Q96MM7
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: 6-O-sulfation enzyme which catalyzes the transfer of sulfate from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to position 6 of the N-sulfoglucosamine residue (GlcNS) of heparan sulfate.
messages: Belongs to the sulfotransferase 6 family.
messages: Membrane
messages: The disease may be caused by variants affecting the gene represented in this entry.

9606:L2HGDH
gene id: 9606:L2HGDH
uniprot id: Q9H9P8
names: Disease Annotation
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the L2HGDH family.
messages: Mitochondrion
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Was named 'duranin' in honor of Marinus Duran, who first described L-2-hydroxyglutaric aciduria.
messages: Widely expressed. Highly expressed in brain, testis and muscle. Expressed to a lower extent in lymphocytes, fibroblasts, keratinocytes, placenta, bladder, small intestine, liver and bone marrow.

9606:ZNF622
gene id: 9606:ZNF622
uniprot id: Q969S3
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the REI1 family.
messages: Cytoplasm
messages: Expressed in lung, kidney, spleen, liver and brain with lowest expression in kidney.
messages: Homo- and heterodimer. Associates with pre-60S ribosomal particles (PubMed:32669547). Interacts with MELK and MYBL2 (PubMed:11802789, PubMed:12645566). Interacts with DNAJC21 (PubMed:27346687).
messages: Nucleus
messages: Phosphorylated by MELK. The phosphorylation may redirect the protein to the nucleus.
messages: Pre-60S-associated cytoplasmic factor involved in the cytoplasmic maturation of the 60S subunit.
messages: Ubiquitinated by HECTD1, leading to its degradation.

9606:KIAA0753
gene id: 9606:KIAA0753
uniprot id: Q2KHM9
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Interacts with CEP63 (PubMed:24613305). Interacts with WDR62 (PubMed:26297806). Forms a complex with OFD1 and CEP20/FOR20 (PubMed:26643951). Interacts with PCM1 (PubMed:26297806, PubMed:26643951).
messages: Involved in centriole duplication (PubMed:24613305, PubMed:26297806). Positively regulates CEP63 centrosomal localization (PubMed:24613305, PubMed:26297806). Required for WDR62 centrosomal localization and promotes the centrosomal localization of CDK2 (PubMed:24613305, PubMed:26297806). May play a role in cilium assembly.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The disease may be caused by variants affecting the gene represented in this entry.
messages: centriolar satellite
messages: centriole
messages: centrosome

9606:TOM1
gene id: 9606:TOM1
uniprot id: O60784
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Adapter protein that plays a role in the intracellular membrane trafficking of ubiquitinated proteins, thereby participating in autophagy, ubiquitination-dependent signaling and receptor recycling pathways (PubMed:14563850, PubMed:15047686, PubMed:23023224, PubMed:25588840, PubMed:26320582, PubMed:31371777). Acts as a MYO6/Myosin VI adapter protein that targets MYO6 to endocytic structures (PubMed:23023224). Together with MYO6, required for autophagosomal delivery of endocytic cargo, the maturation of autophagosomes and their fusion with lysosomes (PubMed:23023224). MYO6 links TOM1 with autophagy receptors, such as TAX1BP1; CALCOCO2/NDP52 and OPTN (PubMed:31371777). Binds to polyubiquitinated proteins via its GAT domain (PubMed:14563850). In a complex with TOLLIP, recruits ubiquitin-conjugated proteins onto early endosomes (PubMed:15047686). The Tom1-Tollip complex may regulate endosomal trafficking by linking polyubiquitinated proteins to clathrin (PubMed:14563850, PubMed:15047686). Mediates clathrin recruitment to early endosomes by ZFYVE16 (PubMed:15657082). Modulates binding of TOLLIP to phosphatidylinositol 3-phosphate (PtdIns(3)P) via binding competition; the association with TOLLIP may favor the release of TOLLIP from endosomal membranes, allowing TOLLIP to commit to cargo trafficking (PubMed:26320582). Acts as a phosphatidylinositol 5-phosphate (PtdIns(5)P) effector by binding to PtdIns(5)P, thereby regulating endosomal maturation (PubMed:25588840). PtdIns(5)P-dependent recruitment to signaling endosomes may block endosomal maturation (PubMed:25588840). Also inhibits Toll-like receptor (TLR) signaling and participates in immune receptor recycling (PubMed:15047686, PubMed:26320582).
messages: Belongs to the TOM1 family.
messages: Cytoplasm
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry.
messages: Early endosome membrane
messages: Endosome membrane
messages: Found in a complex with TOLLIP; interacts (via GAT domain) with TOLLIP (via N-terminus); the interactions leads to TOM1-recruitment to endosomes and inhibition of TOLLIP binding to PtdIns(3)P (PubMed:14563850, PubMed:15047686, PubMed:31263572, PubMed:26320582). Interacts (via GAT domain and the C-terminal part of the VHS domain) with UBC/ubiquitin (PubMed:14563850, PubMed:15047686, PubMed:16199040, PubMed:31263572). Interacts (via clathrin box and C-terminus) with clathrin heavy chain (PubMed:14563850, PubMed:15657082). Interacts with MYO6 (PubMed:23023224, PubMed:31371777). Interacts with TAX1BP1; CALCOCO2/NDP52 and OPTN; the interaction is indirect and is mediated by MYO6, which acts as a bridge between TOM1 and the three autophagy receptors (PubMed:31371777). Interacts (via C-terminus) with ZFYVE16 (via C-terminus); interaction is required to target TOM1 and clathrin to endosomes (PubMed:14613930, PubMed:15657082). Interacts with LRBA (PubMed:31263572).
messages: Monoubiquitinated.
messages: The GAT domain and the VHS domain are required for the interaction with polyubiquitinated proteins.
messages: The VHS domain binds to phosphatidylinositol monophosphates (PubMed:25588840). The KRKK motif within the VHS domain is required for binding to phosphatidylinositol monophosphates, with a preference for phosphatidylinositol 5-phosphate (PtdIns(5)P) (PubMed:25588840).
messages: Widely expressed. Highly expressed in skeletal muscle, heart, placenta and liver.

9606:PDGFRA
gene id: 9606:PDGFRA
uniprot id: P16234
names: Activity Regulation
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts with human cytomegalovirus/HHV-5 envelope glycoprotein B/gB. Interacts also with the trimeric complex gH-gL-gO. Trimer-PDGFRA interaction has an inhibitory effect on PDGFRA signaling (PubMed:33626330).
messages: A chromosomal aberration involving PDGFRA is found in some cases of hypereosinophilic syndrome. Interstitial chromosomal deletion del(4)(q12q12) causes the fusion of FIP1L1 and PDGFRA (FIP1L1-PDGFRA). Mutations that cause overexpression and/or constitutive activation of PDGFRA may be a cause of hypereosinophilic syndrome.
messages: Autophosphorylated on tyrosine residues upon ligand binding. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Phosphorylation at Tyr-731 and Tyr-742 is important for interaction with PIK3R1. Phosphorylation at Tyr-720 and Tyr-754 is important for interaction with PTPN11. Phosphorylation at Tyr-762 is important for interaction with CRK. Phosphorylation at Tyr-572 and Tyr-574 is important for interaction with SRC and SRC family members. Phosphorylation at Tyr-988 and Tyr-1018 is important for interaction with PLCG1.
messages: Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily.
messages: Cell membrane
messages: Detected in platelets (at protein level). Widely expressed. Detected in brain, fibroblasts, smooth muscle, heart, and embryo. Expressed in primary and metastatic colon tumors and in normal colon tissue.
messages: Golgi apparatus
messages: Interacts with homodimeric PDGFA, PDGFB and PDGFC, and with heterodimers formed by PDGFA and PDGFB. Monomer in the absence of bound ligand. Interaction with dimeric PDGFA, PDGFB and/or PDGFC leads to receptor dimerization, where both PDGFRA homodimers and heterodimers with PDGFRB are observed. Interacts (tyrosine phosphorylated) with SHB (via SH2 domain) (By similarity). Interacts (tyrosine phosphorylated) with SHF (via SH2 domain). Interacts (tyrosine phosphorylated) with SRC (via SH2 domain). Interacts (tyrosine phosphorylated) with PIK3R1. Interacts (tyrosine phosphorylated) with PLCG1 (via SH2 domain). Interacts (tyrosine phosphorylated) with CRK, GRB2 and GRB7.
messages: N-glycosylated.
messages: Present in an inactive conformation in the absence of bound ligand. Binding of PDGFA and/or PDGFB leads to dimerization and activation by autophosphorylation on tyrosine residues. Inhibited by imatinib, nilotinib and sorafenib.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The gene represented in this entry may be involved in disease pathogenesis. Mutations causing PDGFRA constitutive activation have been found in gastrointestinal stromal tumors lacking KIT mutations (PubMed:12522257).
messages: Tyrosine-protein kinase that acts as a cell-surface receptor for PDGFA, PDGFB and PDGFC and plays an essential role in the regulation of embryonic development, cell proliferation, survival and chemotaxis. Depending on the context, promotes or inhibits cell proliferation and cell migration. Plays an important role in the differentiation of bone marrow-derived mesenchymal stem cells. Required for normal skeleton development and cephalic closure during embryonic development. Required for normal development of the mucosa lining the gastrointestinal tract, and for recruitment of mesenchymal cells and normal development of intestinal villi. Plays a role in cell migration and chemotaxis in wound healing. Plays a role in platelet activation, secretion of agonists from platelet granules, and in thrombin-induced platelet aggregation. Binding of its cognate ligands - homodimeric PDGFA, homodimeric PDGFB, heterodimers formed by PDGFA and PDGFB or homodimeric PDGFC -leads to the activation of several signaling cascades; the response depends on the nature of the bound ligand and is modulated by the formation of heterodimers between PDGFRA and PDGFRB. Phosphorylates PIK3R1, PLCG1, and PTPN11. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate, mobilization of cytosolic Ca(2+) and the activation of protein kinase C. Phosphorylates PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, and thereby mediates activation of the AKT1 signaling pathway. Mediates activation of HRAS and of the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. Promotes activation of STAT family members STAT1, STAT3 and STAT5A and/or STAT5B. Receptor signaling is down-regulated by protein phosphatases that dephosphorylate the receptor and its down-stream effectors, and by rapid internalization of the activated receptor.
messages: Ubiquitinated, leading to its internalization and degradation.
messages: cilium

9606:ROCK2
gene id: 9606:ROCK2
uniprot id: A0A2P9DU05
uniprot id: O75116
uniprot id: Q14DU5
names: Activity Regulation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Activated by RHOA binding. Inhibited by Y-27632 (By similarity).
messages: Activated by RHOA binding. Inhibited by Y-27632.
messages: An interaction between Thr-414 and Asp-48 is essential for kinase activity and dimerization.
messages: Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family.
messages: Cell membrane
messages: Cleaved by granzyme B during apoptosis. This leads to constitutive activation of the kinase and membrane blebbing.
messages: Cytoplasm
messages: Expressed in the brain (at protein level).
messages: Homodimer (By similarity). Interacts with IRS1 (By similarity). Interacts with RAF1 (By similarity). Interacts with RHOA (activated by GTP), RHOB and RHOC (By similarity). Interacts with PPP1R12A (PubMed:10579722, PubMed:19131646). Interacts with EP300 (PubMed:16574662). Interacts with CHORDC1 (PubMed:20230755). Interacts with BRCA2 (PubMed:21084279). Interacts with NPM1; this interaction enhances ROCK2 activity (PubMed:17015463). Interacts with SORL1 (PubMed:21147781). Interacts with PJVK (By similarity).
messages: Homodimer.
messages: Membrane
messages: Nucleus
messages: Phosphorylation at Tyr-722 reduces its binding to RHOA and is crucial for focal adhesion dynamics. Dephosphorylation by PTPN11 stimulates its RHOA binding activity.
messages: Protein kinase which is a key regulator of actin cytoskeleton and cell polarity.
messages: Protein kinase which is a key regulator of actin cytoskeleton and cell polarity. Involved in regulation of smooth muscle contraction, actin cytoskeleton organization, stress fiber and focal adhesion formation, neurite retraction, cell adhesion and motility via phosphorylation of ADD1, BRCA2, CNN1, EZR, DPYSL2, EP300, MSN, MYL9/MLC2, NPM1, RDX, PPP1R12A and VIM. Phosphorylates SORL1 and IRF4. Acts as a negative regulator of VEGF-induced angiogenic endothelial cell activation. Positively regulates the activation of p42/MAPK1-p44/MAPK3 and of p90RSK/RPS6KA1 during myogenic differentiation. Plays an important role in the timely initiation of centrosome duplication. Inhibits keratinocyte terminal differentiation. May regulate closure of the eyelids and ventral body wall through organization of actomyosin bundles. Plays a critical role in the regulation of spine and synaptic properties in the hippocampus. Plays an important role in generating the circadian rhythm of the aortic myofilament Ca(2+) sensitivity and vascular contractility by modulating the myosin light chain phosphorylation.
messages: centrosome

9606:ANG
gene id: 9606:ANG
uniprot id: P03950
uniprot id: W0UV28
names: Caution
names: Developmental Stage
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the pancreatic ribonuclease family.
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry.
messages: Expressed predominantly in the liver. Also detected in endothelial cells and spinal cord neurons.
messages: Homodimer (PubMed:25372031). Interacts with and forms a tight 1:1 complex with RNH1. Dimerization of two such complexes may occur.
messages: It is uncertain whether Met-1 or Met-3 is the initiator.
messages: Low level expression in the developing fetus, increased in the neonate, and maximal in the adult.
messages: Nucleus
messages: Ribonuclease that cleaves tRNA within anticodon loops to produce tRNA-derived stress-induced fragments (tiRNAs) which inhibit protein synthesis and triggers the assembly of stress granules (SGs) (PubMed:1400510, PubMed:21855800). Binds to actin on the surface of endothelial cells; once bound, angiogenin is endocytosed and translocated to the nucleus (PubMed:8127865). Stimulates ribosomal RNA synthesis including that containing the initiation site sequences of 45S rRNA (PubMed:12051708). Angiogenin induces vascularization of normal and malignant tissues (PubMed:19354288). Angiogenic activity is regulated by interaction with RNH1 in vivo (PubMed:19354288).
messages: Secreted
messages: nucleolus
messages: secretory vesicle lumen

9606:SPAAR
gene id: 9606:SPAAR
uniprot id: A0A1B0GVQ0
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Highly expressed in lung, heart and skeletal muscle.
messages: Interacts with components of the lysosomal V-ATPase complex (PubMed:28024296). Interacts with ATP6V0A1 (PubMed:28024296). Interacts with ATP6V0A2 (PubMed:28024296).
messages: Late endosome membrane
messages: Lysosome membrane
messages: Negative regulator of amino acid sensing and mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels and amino acids (PubMed:28024296). Negatively regulates mTORC1 activation by inhibiting recruitment of mTORC1 to lysosomes upon stimulation with amino acids: acts by promoting the formation of a tightly bound supercomplex composed of the lysosomal V-ATPase, Ragulator and Rag GTPases, preventing recruitment of mTORC1 (PubMed:28024296). Acts as a regulator of muscle regeneration following injury by regulating mTORC1 activation (By similarity).

9606:IFI27L1
gene id: 9606:IFI27L1
uniprot id: Q96BM0
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the IFI6/IFI27 family.
messages: Membrane
messages: Not up-regulated by type-I interferon.
messages: Plays a role in the apoptotic process and has a pro-apoptotic activity.

9606:OR10AD1
gene id: 9606:OR10AD1
uniprot id: Q8NGE0
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Odorant receptor.

9606:BNC1
gene id: 9606:BNC1
uniprot id: Q01954
names: Disease Annotation
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cytoplasm
messages: In epidermis, primarily detected in cells of the basal or immediately suprabasal layers (at protein level) (PubMed:16891417). In hair follicles, mainly expressed in the outer root sheath (at protein level) (PubMed:8034748). Expressed in epidermis, testis and foreskin, and to a lower extent in thymus, spleen, mammary glands, placenta, brain and heart (PubMed:9687312). Expressed in the ovary, notably in oocytes (PubMed:30010909).
messages: Interacts with HSF2BP (via C-terminus).
messages: Nucleus
messages: Phosphorylation on Ser-537 and Ser-541 leads to cytoplasmic localization.
messages: The disease may be caused by variants affecting the gene represented in this entry.
messages: Transcriptional activator (By similarity). It is likely involved in the regulation of keratinocytes terminal differentiation in squamous epithelia and hair follicles (PubMed:8034748). Required for the maintenance of spermatogenesis (By similarity). It is involved in the positive regulation of oocyte maturation, probably acting through the control of BMP15 levels and regulation of AKT signaling cascade (PubMed:30010909). May also play a role in the early development of embryos (By similarity).
messages: nucleoplasm

9606:UBE2L3
gene id: 9606:UBE2L3
uniprot id: P68036
names: Caution
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the ubiquitin-conjugating enzyme family.
messages: Cytoplasm
messages: In contrast to other ubiquitin-conjugating enzymes E2, residues essential for lysine reactivity are absent: Pro and a His residues are present instead of an Asp and an Asp residues in positions 88 and 119, respectively.
messages: Interacts with PRKN; involved in ubiquitination and degradation of misfolded proteins. Interacts with UBE3A; used by the papilloma virus HPV-16 E6 protein to ubiquitinate p53/TP53. Interacts with CCNB1IP1, CBL, ZAP70, RNF19A, RNF19B and RNF144B. Interacts with ARIH1. Interacts with ARIH2 (via RING-type 1). Interacts with NCOA1; they functionally interact to regulate progesterone receptor transcriptional activity. May interact with NR3C1. Interacts with NDFIP1 (via N-terminus); the interaction mediates recruitment of UBE2L3 to ITCH and causes MAP3K7 ubiquitination (PubMed:25632008).
messages: Nucleus
messages: PubMed:10760570 reported that UBE2L1, UBE2L2 and UBE2L4 are most likely pseudogenes and the only expressed member of this subfamily seems to be UBE2L3.
messages: Ubiquitin-conjugating enzyme E2 that specifically acts with HECT-type and RBR family E3 ubiquitin-protein ligases. Does not function with most RING-containing E3 ubiquitin-protein ligases because it lacks intrinsic E3-independent reactivity with lysine: in contrast, it has activity with the RBR family E3 enzymes, such as PRKN, RNF31 and ARIH1, that function like RING-HECT hybrids. Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-11'-linked polyubiquitination. Involved in the selective degradation of short-lived and abnormal proteins. Down-regulated during the S-phase it is involved in progression through the cell cycle. Regulates nuclear hormone receptors transcriptional activity. May play a role in myelopoiesis.
messages: Ubiquitinated. The alteration of UBE2L3 protein levels during the S-phase of the cell cycle is due to ubiquitin-dependent proteasomal degradation. Autoubiquitinated in vitro (PubMed:22496338).
messages: Ubiquitous, with highest expression in testis.

9606:CPB2
gene id: 9606:CPB2
uniprot id: A0A087WSY5
uniprot id: Q96IY4
names: Activity Regulation
names: Cofactor
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the peptidase M14 family.
messages: Binds 1 zinc ion per subunit.
messages: Cleaves C-terminal arginine or lysine residues from biologically active peptides such as kinins or anaphylatoxins in the circulation thereby regulating their activities. Down-regulates fibrinolysis by removing C-terminal lysine residues from fibrin that has already been partially degraded by plasmin.
messages: N-glycosylated. N-glycan at Asn-108: Hex5HexNAc4.
messages: Plasma; synthesized in the liver.
messages: Secreted
messages: TAFI/CPB2 is unique among carboxypeptidases in that it spontaneously inactivates with a short half-life, a property that is crucial for its role in controlling blood clot lysis. The zymogen is stabilized by interactions with the activation peptide. Release of the activation peptide increases a dynamic flap mobility and in time this leads to conformational changes that disrupt the catalytic site and expose a cryptic thrombin-cleavage site present at Arg-324.

9606:SLC10A2
gene id: 9606:SLC10A2
uniprot id: Q12908
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the bile acid:sodium symporter (BASS) (TC 2.A.28) family.
messages: Mainly expressed in ileum and kidney, lower expression in cecum.
messages: Membrane
messages: Monomer and homodimer.
messages: Plays a critical role in the sodium-dependent reabsorption of bile acids from the lumen of the small intestine (PubMed:7592981, PubMed:9458785, PubMed:9856990). Transports various bile acids, unconjugated or conjugated, such as cholate and taurocholate (PubMed:7592981, PubMed:9458785, PubMed:9856990). Also responsible for bile acid transport in the renal proximal tubules, a salvage mechanism that helps conserve bile acids (Probable). Works collaboratively with the Na(+)-taurocholate cotransporting polypeptide (NTCP), the organic solute transporter (OST), and the bile salt export pump (BSEP), to ensure efficacious biological recycling of bile acids during enterohepatic circulation (PubMed:33222321).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:DLG3
gene id: 9606:DLG3
uniprot id: Q92796
names: Disease Annotation
names: Function
names: Similarity
names: Subunit
messages: Belongs to the MAGUK family.
messages: Interacts through its PDZ domains with NETO1, GRIN2B and SYNGAP1. Interacts through its guanylate kinase-like domain with DLGAP1, DLGAP2, DLGAP3 and DLGAP4. Interacts with FLTP/C1orf192 (By similarity). Interacts through its PDZ domains with APC. Interacts through its first two PDZ domains with ERBB4. Interacts through its third PDZ domain with NLGN1, and probably with NLGN2 and NLGN3. Interacts with FRMPD4 (via C-terminus). Interacts with LRFN1, LRFN2 and LRFN4. Interacts with DGKI (via PDZ-binding motif) (By similarity).
messages: Required for learning most likely through its role in synaptic plasticity following NMDA receptor signaling.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:MRPL39
gene id: 9606:MRPL39
uniprot id: Q9NYK5
names: Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the mitochondrion-specific ribosomal protein mL39 family.
messages: Component of the mitochondrial large ribosomal subunit (mt-LSU) (PubMed:28892042, PubMed:25838379, PubMed:25278503). Mature mammalian 55S mitochondrial ribosomes consist of a small (28S) and a large (39S) subunit. The 28S small subunit contains a 12S ribosomal RNA (12S mt-rRNA) and 30 different proteins. The 39S large subunit contains a 16S rRNA (16S mt-rRNA), a copy of mitochondrial valine transfer RNA (mt-tRNA(Val)), which plays an integral structural role, and 52 different proteins.
messages: Isoform 1 is ubiquitously expressed. Isoform 2 is heart-specific.
messages: It is uncertain whether Met-1 or Met-6 is the initiator.
messages: Mitochondrion
messages: Ref.1 indicates C21orf8 as a synonym for this orf, this is incorrect, C21orf8 is already assigned to another chromosome 21 region.

9606:CCNB2
gene id: 9606:CCNB2
uniprot id: O95067
names: Developmental Stage
names: Function
names: Similarity
names: Subunit
messages: Accumulates steadily during G2 and is abruptly destroyed at mitosis.
messages: Belongs to the cyclin family. Cyclin AB subfamily.
messages: Essential for the control of the cell cycle at the G2/M (mitosis) transition.
messages: Interacts with the CDK1 protein kinase to form a serine/threonine kinase holoenzyme complex also known as maturation promoting factor (MPF). The cyclin subunit imparts substrate specificity to the complex.

9606:OR5D14
gene id: 9606:OR5D14
uniprot id: Q8NGL3
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Odorant receptor.

9606:PPP1R16B
gene id: 9606:PPP1R16B
uniprot id: Q96T49
names: Function
names: Induction
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: Cell membrane
messages: Cell projection
messages: Inhibited by TGFB1 (Probable). Down-regulated by LPS (PubMed:21907835).
messages: Interacts with PPP1CA, PPP1CB and MSN. Interacts (via its fourth ankyrin repeat) with the mature dimeric form of RPSA/LAMR1 (PubMed:16263087, PubMed:18586956). Interacts with EEF1A1 (PubMed:26497934). Interacts with PTEN (PubMed:25007873). Interacts with ECE1 (By similarity).
messages: Nucleus
messages: Phosphorylated by PKA and, after PKA priming, by GSK3B. Phosphorylation by GSK3B reduces its association with PP1C and enhances PP1C activity. Dephosphorylation by its associated PP1C results in enhanced association with PP1C, but reduced PP1C activity (By similarity).
messages: Regulator of protein phosphatase 1 (PP1) that acts as a positive regulator of pulmonary endothelial cell (EC) barrier function (PubMed:18586956). Involved in the regulation of the PI3K/AKT signaling pathway, angiogenesis and endothelial cell proliferation (PubMed:25007873). Regulates angiogenesis and endothelial cell proliferation through the control of ECE1 dephosphorylation, trafficking and activity (By similarity). Protects the endothelial barrier from lipopolysaccharide (LPS)-induced vascular leakage (By similarity). Involved in the regulation of endothelial cell filopodia extension (By similarity). May be a downstream target for TGF-beta1 signaling cascade in endothelial cells (PubMed:16263087, PubMed:18586956). Involved in PKA-mediated moesin dephosphorylation which is important in EC barrier protection against thrombin stimulation (PubMed:18586956). Promotes the interaction of PPP1CA with RPSA/LAMR1 and in turn facilitates the dephosphorylation of RPSA/LAMR1 (PubMed:16263087). Involved in the dephosphorylation of EEF1A1 (PubMed:26497934).

9606:DNAJC1
gene id: 9606:DNAJC1
uniprot id: Q96KC8
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Endoplasmic reticulum membrane
messages: Interacts (via J domain) with HSPA5. Interacts (via cytosolic domain) with ribosomes (By similarity). Interacts (via SANT 2 domain) with SERPINA3; the interaction delays the formation of the covalent inhibitory complex SERPINA3-chymotrypsin, but does not alter the catalytic activity of SERPINA3. Interacts (via SANT 2 domain) with ITIH4 (via C-terminus); the interaction protects ITIH4 against in vitro cleavage by kallikrein.
messages: May modulate protein synthesis.
messages: Microsome membrane
messages: Nucleus membrane

9606:TRIM36
gene id: 9606:TRIM36
uniprot id: Q9NQ86
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the TRIM/RBCC family.
messages: Cytoplasm
messages: E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins. Involved in chromosome segregation and cell cycle regulation (PubMed:28087737). May play a role in the acrosome reaction and fertilization.
messages: Highly expressed in testis, prostate and brain (PubMed:15145053). Weakly expressed in kidney, lung and heart (PubMed:15145053). Expressed in fetal tissues (PubMed:28087737).
messages: Interacts with CENPH.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: acrosome
messages: cytoskeleton

9606:RPA4
gene id: 9606:RPA4
uniprot id: Q13156
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: As part of the alternative replication protein A complex, aRPA, binds single-stranded DNA and probably plays a role in DNA repair. Compared to the RPA2-containing, canonical RPA complex, may not support chromosomal DNA replication and cell cycle progression through S-phase. The aRPA may not promote efficient priming by DNA polymerase alpha but could support DNA polymerase delta synthesis in the presence of PCNA and replication factor C (RFC), the dual incision/excision reaction of nucleotide excision repair and RAD51-dependent strand exchange.
messages: Belongs to the replication factor A protein 2 family.
messages: Component of the aRPA, the alternative replication protein A complex, a trimeric complex similar to the replication protein A complex/RPA but where RPA1 and RPA3 are associated with RPA4 instead of RPA2. Interacts with RPA1 and RPA3.
messages: Nucleus
messages: Preferentially expressed in placental and colon mucosa. Widely expressed at intermediate or lower levels.

9606:TBC1D2
gene id: 9606:TBC1D2
uniprot id: Q9BYX2
names: Function
names: Miscellaneous
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: 'Armus' means hinge, linker in Latin and ancient Greek.
messages: Acts as GTPase-activating protein for RAB7A. Signal effector acting as a linker between RAC1 and RAB7A, leading to RAB7A inactivation and subsequent inhibition of cadherin degradation and reduced cell-cell adhesion.
messages: Cell junction
messages: Cytoplasm
messages: Cytoplasmic vesicle
messages: Expressed in a broad range of tissues, especially in kidney, liver, lung and placenta. Also expressed in keratinocytes and epithelia-containing organs. Isoform 2 is differentially expressed in prostate normal and cancer cells (at protein level).
messages: Interacts with activated RAC1 and CDH1.

9606:CYP4F22
gene id: 9606:CYP4F22
uniprot id: Q6NT55
names: Caution
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: A cytochrome P450 monooxygenase involved in epidermal ceramide biosynthesis. Hydroxylates the terminal carbon (omega-hydroxylation) of ultra-long-chain fatty acyls (C28-C36) prior to ceramide synthesis (PubMed:26056268). Contributes to the synthesis of three classes of omega-hydroxy-ultra-long chain fatty acylceramides having sphingosine, 6-hydroxysphingosine and phytosphingosine bases, all major lipid components that underlie the permeability barrier of the stratum corneum (PubMed:26056268). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase) (PubMed:26056268).
messages: A second transmembrane domain at positions 95-115 is predicted by three programs ESKW, MEMSAT and Phobius. However experimental evidence supports the presence of a single signal-anchor transmembrane domain at the N-terminus.
messages: Belongs to the cytochrome P450 family.
messages: Endoplasmic reticulum membrane
messages: Microsome membrane
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:ACY3
gene id: 9606:ACY3
uniprot id: Q96HD9
names: Cofactor
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Interacts with hepatitis C virus/HCV core protein.
messages: Apical cell membrane
messages: Belongs to the AspA/AstE family. Aspartoacylase subfamily.
messages: Binds 1 zinc ion per subunit.
messages: Cytoplasm
messages: Exists as a mixture of homodimers and homotetramer, both catalytically active.
messages: Plays an important role in deacetylating mercapturic acids in kidney proximal tubules. Also acts on N-acetyl-aromatic amino acids (By similarity).

9606:CNBP
gene id: 9606:CNBP
uniprot id: P62633
names: Disease Annotation
names: Function
names: Induction
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Arginine methylation by PRMT1 in the Arg/Gly-rich region impedes RNA binding.
messages: Associates with the 40S ribosomal subunit, the 80S ribosome and with polysomes.
messages: Binds G-rich elements in target mRNA coding sequences (PubMed:28329689). Prevents G-quadruplex structure formation in vitro, suggesting a role in supporting translation by resolving stable structures on mRNAs (PubMed:28329689).
messages: Binds to RNA.
messages: Cytoplasm
messages: Endoplasmic reticulum
messages: Expressed in the liver, kidney, spleen, testis, lung, muscle and adrenal glands.
messages: Nucleus
messages: Single-stranded DNA-binding protein that preferentially binds to the sterol regulatory element (SRE) sequence 5'-GTGCGGTG-3', and thereby mediates transcriptional repression (PubMed:2562787). Has a role as transactivator of the Myc promoter (By similarity). Binds single-stranded RNA in a sequence-specific manner (By similarity).
messages: The disease is caused by variants affecting the gene represented in this entry. The causative mutation is a CCTG expansion (mean approximately 5000 repeats) located in intron 1 of the CNBP gene.
messages: Transcriptionally up-regulated by sterol treatment.

9606:ZNF793
gene id: 9606:ZNF793
uniprot id: Q6ZN11
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:DUSP2
gene id: 9606:DUSP2
uniprot id: Q05923
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily.
messages: By mitogens.
messages: Dephosphorylates both phosphorylated Thr and Tyr residues in MAPK1, and dephosphorylation of phosphotyrosine is slightly faster than that of phosphothreonine (PubMed:8107850). Can dephosphorylate MAPK1 (By similarity).
messages: Expressed in hematopoietic tissues.
messages: Interacts with MAPK14; this interaction does not lead to catalytic activation of DUSP2 and dephosphrylation of MAPK14.
messages: Nucleus

9606:INCA1
gene id: 9606:INCA1
uniprot id: Q0VD86
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the INCA family.
messages: Binds to CDK2-bound cyclins and inhibits the kinase activity of CDK2; binding to cyclins is critical for its function as CDK inhibitor (PubMed:21540187). Inhibits cell growth and cell proliferation and may play a role in cell cycle control (By similarity). Required for ING5-mediated regulation of S-phase progression, enhancement of Fas-induced apoptosis and inhibition of cell growth (By similarity).
messages: By serum starvation.
messages: Cytoplasm
messages: Detected in testis, and at lower levels in ovary. Detected at very low levels in testis tumors (PubMed:15159402). Down-regulated in bone marrow cells in acute myeloid and lymphoid leukemia patients as compared with normal bone marrow cells (PubMed:21540187).
messages: Interacts with CCNA1 (PubMed:21540187, PubMed:15159402). Interacts with CCNA2, CCNB1 and CCNE1 (PubMed:21540187). Found in a complex with CCNA1 and CDK2 (PubMed:15159402). Interacts with ZNF16; the interaction inhibits INCA1 activity and induces the cell cycle process (PubMed:21874239). Interacts with SPACA9 (PubMed:18756329). Interacts with the CCNA1/CDK2 complex (PubMed:21540187). Interacts with ING5, DAZAP2, RNF26, USP15, SPOUT1, DPH7, TRIM26 and RAB5C (PubMed:21750715).
messages: Nucleus
messages: Phosphorylated when part of a complex with CCNA1 and CDK2. Strongly phosphorylated by CDK2 on its C-terminal region spanning amino acid 149-221. Less intensively phosphorylated by CDK2 on its first 75 amino acid residues.

9606:INO80E
gene id: 9606:INO80E
uniprot id: Q8NBZ0
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Component of the chromatin remodeling INO80 complex; specifically part of a complex module associated with the N-terminus of INO80.
messages: Nucleus
messages: Putative regulatory component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair.

9606:TPD52L1
gene id: 9606:TPD52L1
uniprot id: E9PPQ1
uniprot id: J3KNE7
uniprot id: Q16890
names: Similarity
names: Subunit
messages: Belongs to the TPD52 family.
messages: Forms a homodimer or heterodimer with other members of the family.

9606:SPNS3
gene id: 9606:SPNS3
uniprot id: Q6ZMD2
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the major facilitator superfamily. Spinster (TC 2.A.1.49) family.
messages: Membrane
messages: Sphingolipid transporter.

9606:AKT1S1
gene id: 9606:AKT1S1
uniprot id: Q96B36
names: Domain
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Associated component of the mechanistic target of rapamycin complex 1 (mTORC1), which contains core MTOR, MLST8 and RPTOR (PubMed:17510057, PubMed:17386266, PubMed:17277771, PubMed:29236692, PubMed:31601764). Dissociates from mTORC1 in response to insulin treatment (PubMed:17386266, PubMed:18372248). mTORC1 binds to and is inhibited by FKBP12-rapamycin (PubMed:31601764, PubMed:17277771). Interacts (via TOS motif) with RPTOR; interaction is direct (PubMed:17510057, PubMed:17517883, PubMed:17386266). The phosphorylated form interacts with 14-3-3 proteins (PubMed:12524439, PubMed:18372248).
messages: Negative regulator of the mechanistic target of rapamycin complex 1 (mTORC1), an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolecule biosynthesis to promote cellular biomass generation and growth (PubMed:17510057, PubMed:17386266, PubMed:17277771, PubMed:29236692). In absence of insulin and nutrients, AKT1S1 associates with the mTORC1 complex and directly inhibits mTORC1 activity by blocking the MTOR substrate-recruitment site (PubMed:29236692). In response to insulin and nutrients, AKT1S1 dissociates from mTORC1 (PubMed:17386266, PubMed:18372248). Its activity is dependent on its phosphorylation state and binding to 14-3-3 (PubMed:16174443, PubMed:18372248). May also play a role in nerve growth factor-mediated neuroprotection (By similarity).
messages: Phosphorylated by AKT1; phosphorylation takes place in response to insulin treatment and promotes AKT1S1 interaction with 14-3-3 proteins, leading to relieve its inhibitor activity (PubMed:12524439, PubMed:17386266). Phosphorylated by MTOR following mTORC1 activation, inhibiting AKT1S1 inhibitor activity: phosphorylation by MTOR probably serves as a feedback loop that relieves inhibition from AKT1S1 in response to mTORC1 inactivation (PubMed:17517883). Phosphorylation at Thr-246 by DYRK3 relieves inhibitory function on mTORC1 (PubMed:23415227).
messages: The TOS motif mediates interaction with RPTOR, leading to promote phosphorylation by mTORC1 complex.
messages: Widely expressed with highest levels of expression in liver and heart. Expressed at higher levels in cancer cell lines (e.g. A-549 and HeLa) than in normal cell lines (e.g. HEK293).
messages: cytosol

9606:HINFP
gene id: 9606:HINFP
uniprot id: Q9BQA5
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Binds MBD2 and a histone deacetylase complex. Interacts with NPAT.
messages: Nucleus
messages: Transcriptional repressor that binds to the consensus sequence 5'-CGGACGTT-3' and to the RB1 promoter. Transcriptional activator that promotes histone H4 gene transcription at the G1/S phase transition in conjunction with NPAT. Also activates transcription of the ATM and PRKDC genes. Autoregulates its expression by associating with its own promoter.
messages: Ubiquitinated. Ubiquitination may lead to proteasome-mediated degradation.
messages: Ubiquitous. Highly expressed in brain, heart, skeletal muscle, spleen, kidney, small intestine, placenta and liver.

9606:PVR
gene id: 9606:PVR
uniprot id: P15151
names: Domain
names: Function
names: Induction
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Acts as a receptor for Pseudorabies virus.
messages: (Microbial infection) Acts as a receptor for poliovirus. May play a role in axonal transport of poliovirus, by targeting virion-PVR-containing endocytic vesicles to the microtubular network through interaction with DYNLT1. This interaction would drive the virus-containing vesicle to the axonal retrograde transport.
messages: (Microbial infection) Interacts with human cytomegalovirus /HHV-5 UL141 protein.
messages: (Microbial infection) Interacts with poliovirus capsid proteins.
messages: (Microbial infection) Interacts with pseudorabies virus gD protein.
messages: (Microbial infection) Is prevented to reach cell surface upon infection by Human cytomegalovirus /HHV-5, presumably to escape immune recognition of infected cell by NK cells.
messages: Belongs to the nectin family.
messages: Can form trans-heterodimers with NECTIN3. The extracellular domain interacts with VTN, CD226 and CD96. The cytoplasmic domain interacts with DYNLT1. Binds with high affinity to TIGIT.
messages: Cell membrane
messages: Contains 1 copy of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases.
messages: Mediates NK cell adhesion and triggers NK cell effector functions. Binds two different NK cell receptors: CD96 and CD226. These interactions accumulates at the cell-cell contact site, leading to the formation of a mature immunological synapse between NK cell and target cell. This may trigger adhesion and secretion of lytic granules and IFN-gamma and activate cytotoxicity of activated NK cells. May also promote NK cell-target cell modular exchange, and PVR transfer to the NK cell. This transfer is more important in some tumor cells expressing a lot of PVR, and may trigger fratricide NK cell activation, providing tumors with a mechanism of immunoevasion. Plays a role in mediating tumor cell invasion and migration.
messages: N-glycosylated. N-glycan at Asn-120: Hex5HexNAc4.
messages: Phosphorylated by Src kinases on tyrosine residues in the ITIM motif upon ligation. Interaction with TIGIT is required for Phosphorylation.
messages: Secreted
messages: The V-type domain is necessary and sufficient for virus binding and uptake.
messages: Transcriptionally regulated by SHH.

9606:HEATR1
gene id: 9606:HEATR1
uniprot id: A2VDI1
uniprot id: B2RWN5
uniprot id: Q9H583
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the HEATR1/UTP10 family.
messages: Involved in nucleolar processing of pre-18S ribosomal RNA.
messages: Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3.
messages: Ribosome biogenesis factor. Involved in nucleolar processing of pre-18S ribosomal RNA. Required for optimal pre-ribosomal RNA transcription by RNA polymerase I (PubMed:17699751). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797).
messages: nucleolus

9606:PLIN5
gene id: 9606:PLIN5
uniprot id: Q00G26
names: Function
names: Induction
names: PTM
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the perilipin family.
messages: Cytoplasm
messages: Expressed in skeletal muscle, liver, heart and kidney.
messages: Homooligomer. Interacts with PNPLA2; prevents interaction of PNPLA2 with ABHD5. Interacts with ABHD5; targets ABHD5 to lipid droplets and promotes interaction of ABHD5 with PNPLA2. Interacts with LIPE (By similarity).
messages: Increased by endurance and sprint interval training.
messages: Lipid droplet
messages: Lipid droplet-associated protein that maintains the balance between lipogenesis and lipolysis and also regulates fatty acid oxidation in oxidative tissues. Recruits mitochondria to the surface of lipid droplets and is involved in lipid droplet homeostasis by regulating both the storage of fatty acids in the form of triglycerides and the release of fatty acids for mitochondrial fatty acid oxidation. In lipid droplet triacylglycerol hydrolysis, plays a role as a scaffolding protein for three major key lipolytic players: ABHD5, PNPLA2 and LIPE. Reduces the triacylglycerol hydrolase activity of PNPLA2 by recruiting and sequestering PNPLA2 to lipid droplets. Phosphorylation by PKA enables lipolysis probably by promoting release of ABHD5 from the perilipin scaffold and by facilitating interaction of ABHD5 with PNPLA2. Also increases lipolysis through interaction with LIPE and upon PKA-mediated phosphorylation of LIPE (By similarity).
messages: Mitochondrion
messages: Phosphorylated by PKA. Phosphorylated on serine in skeletal muscle at rest or upon lipolytic stimulation (By similarity).
messages: Probable cloning artifact.

9606:DEPDC7
gene id: 9606:DEPDC7
uniprot id: Q96QD5
names: Similarity
names: Tissue Specificity
messages: Belongs to the DEPDC7 family.
messages: Expressed in liver.

9606:PMF1
gene id: 9606:PMF1
uniprot id: Q6P1K2
names: Function
names: Induction
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: By polyamine analogs in analog-sensitive H157 cells.
messages: Component of the MIS12 complex composed of MIS12, DSN1, NSL1 and PMF1. Interacts with COPS7A. Interacts via its coiled-coil domain with the leucine-zipper domain of NFE2L2. The interaction with NFE2L2 is required for the transcriptional regulation of SSAT.
messages: Highest levels of expression in heart and skeletal muscle, with significant levels expressed in kidney and liver.
messages: Nucleus
messages: Part of the MIS12 complex which is required for normal chromosome alignment and segregation and kinetochore formation during mitosis. May act as a cotranscription partner of NFE2L2 involved in regulation of polyamine-induced transcription of SSAT.
messages: kinetochore

9606:PDGFC
gene id: 9606:PDGFC
uniprot id: Q9NRA1
names: Developmental Stage
names: Function
names: Induction
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: A lower molecular weight form (around 43 kDa) is present in patients with papillary thyroid carcinoma.
messages: Belongs to the PDGF/VEGF growth factor family.
messages: Cell membrane
messages: Cytoplasmic granule
messages: Expressed in the fallopian tube, vascular smooth muscle cells in kidney, breast and colon and in visceral smooth muscle of the gastrointestinal tract. Highly expressed in retinal pigment epithelia. Expressed in medulloblastoma. In the kidney, constitutively expressed in parietal epithelial cells of Bowman's capsule, tubular epithelial cells and in arterial endothelial cells (at protein level). Highly expressed in the platelets, prostate, testis and uterus. Higher expression is observed in uterine leiomyomata. Weaker expression in the spleen, thymus, heart, pancreas, liver, ovary cells and small intestine, and negligible expression in the colon and peripheral blood leukocytes.
messages: Growth factor that plays an essential role in the regulation of embryonic development, cell proliferation, cell migration, survival and chemotaxis. Potent mitogen and chemoattractant for cells of mesenchymal origin. Required for normal skeleton formation during embryonic development, especially for normal development of the craniofacial skeleton and for normal development of the palate. Required for normal skin morphogenesis during embryonic development. Plays an important role in wound healing, where it appears to be involved in three stages: inflammation, proliferation and remodeling. Plays an important role in angiogenesis and blood vessel development. Involved in fibrotic processes, in which transformation of interstitial fibroblasts into myofibroblasts plus collagen deposition occurs. The CUB domain has mitogenic activity in coronary artery smooth muscle cells, suggesting a role beyond the maintenance of the latency of the PDGF domain. In the nucleus, PDGFC seems to have additional function.
messages: Homodimer; disulfide-linked. Interacts with PDGFRA homodimers, and with heterodimers formed by PDGFRA and PDGFRB. Interacts (via CUB domain) with PLAT (via kringle domain).
messages: In the fetal kidney, detected in the developing mesangium, ureteric bud epithelium and the undifferentiated mesenchyme (at protein level).
messages: N-glycosylated.
messages: Nucleus
messages: Proteolytic removal of the N-terminal CUB domain releasing the core domain is necessary for unmasking the receptor-binding epitopes of the core domain. Cleavage after basic residues in the hinge region (region connecting the CUB and growth factor domains) gives rise to the receptor-binding form. Cleaved by PLAT and PLG.
messages: Secreted
messages: Sumoylated with SUMO1.
messages: Up-regulated by EWS-FLI1 chimeric transcription factor in tumor derived cells. Up-regulated in podocytes and interstitial cells after injury/activation of these cells. FGF2 activates PDGFC transcription via EGR1. Up-regulated by TGFB1 in concert with FGF2.
messages: cytosol

9606:FCN3
gene id: 9606:FCN3
uniprot id: O75636
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the ficolin lectin family.
messages: Homotrimer (PubMed:17215869). May form an octadecamer consisting of an elementary trimer unit. Does not interact with fibronectin, elastin or zymosan. Interacts with MASP1 and MASP2.
messages: Liver and lung. In liver it is produced by bile duct epithelial cells and hepatocytes. In lung it is produced by both ciliated bronchial epithelial cells and type II alveolar epithelial cells.
messages: May function in innate immunity through activation of the lectin complement pathway. Calcium-dependent and GlcNAc-binding lectin. Has affinity with GalNAc, GlcNAc, D-fucose, as mono/oligosaccharide and lipopolysaccharides from S.typhimurium and S.minnesota.
messages: Secreted
messages: The N-terminus is blocked.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:CNTD1
gene id: 9606:CNTD1
uniprot id: Q8N815
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Chromosome
messages: Cytoplasm
messages: Interacts with PRR19; this interaction promotes crossover formation. Interacts with RFC3 and RFC4; these interactions facilitate crossover formation. Interacts with CDC34; this interaction regulates the cell-cycle progression.
messages: Nucleus
messages: Plays a role in the different steps of crossover formation during meiotic recombination. Participates in the crossover differentiation step of crossover-specific recombination intermediates through its interaction with PRR19. In addition, stimulates crossover formation through the interactions with RFC3 and RFC4 and simultaneously regulates cell-cycle progression through interactions with CDC34 and subsequent ubiquitination of WEE1. May also participates in an active deselection process that destabilizes or removes excess pre-CO intermediates.

9606:CYP19A1
gene id: 9606:CYP19A1
uniprot id: A8K6W3
uniprot id: P11511
uniprot id: Q05CU4
uniprot id: Q8IYG4
uniprot id: Q8TCA4
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: A cytochrome P450 monooxygenase that catalyzes the conversion of C19 androgens, androst-4-ene-3,17-dione (androstenedione) and testosterone to the C18 estrogens, estrone and estradiol, respectively (PubMed:27702664, PubMed:2848247). Catalyzes three successive oxidations of C19 androgens: two conventional oxidations at C19 yielding 19-hydroxy and 19-oxo/19-aldehyde derivatives, followed by a third oxidative aromatization step that involves C1-beta hydrogen abstraction combined with cleavage of the C10-C19 bond to yield a phenolic A ring and formic acid (PubMed:20385561). Alternatively, the third oxidative reaction yields a 19-norsteroid and formic acid. Converts dihydrotestosterone to delta1,10-dehydro 19-nordihydrotestosterone and may play a role in homeostasis of this potent androgen (PubMed:22773874). Also displays 2-hydroxylase activity toward estrone (PubMed:22773874). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase) (PubMed:20385561, PubMed:22773874).
messages: Belongs to the cytochrome P450 family.
messages: Endoplasmic reticulum membrane
messages: Microsome membrane
messages: Phosphorylated in vitro by PKA and PKG/PRKG1. These phosphorylations inhibit the catalytic activity as measured by estrone synthesis from androstenedione (36% decrease for PKA and 30% for PKG/PRKG1).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Widely expressed, including in adult and fetal brain, placenta, skin fibroblasts, adipose tissue and gonads.

9606:LDHD
gene id: 9606:LDHD
uniprot id: Q86WU2
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the FAD-binding oxidoreductase/transferase type 4 family.
messages: Expressed moderately in heart and liver and at lower levels in skeletal muscle and kidney.
messages: Interacts with CSRP3.
messages: Involved in D-lactate, but not L-lactate catabolic process.
messages: Mitochondrion
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:MUC3A
gene id: 9606:MUC3A
uniprot id: Q02505
uniprot id: Q9H3Q6
names: Caution
names: Function
names: Miscellaneous
names: PTM
names: Sequence Caution
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Broad specificity; small intestine, colon, colonic tumors, heart, liver, thymus, prostate, pancreas and gall bladder.
messages: Highly O-glycosylated and probably also N-glycosylated.
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: Major glycoprotein component of a variety of mucus gels. Thought to provide a protective, lubricating barrier against particles and infectious agents at mucosal surfaces. May be involved in ligand binding and intracellular signaling.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Membrane
messages: Secreted
messages: This sequence is incomplete at 5' and 3' ends and extensively differs from that shown.

9606:PON3
gene id: 9606:PON3
uniprot id: Q15166
names: Cofactor
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the paraoxonase family.
messages: Binds 2 calcium ions per subunit.
messages: Has low activity towards the organophosphate paraxon and aromatic carboxylic acid esters. Rapidly hydrolyzes lactones such as statin prodrugs (e.g. lovastatin). Hydrolyzes aromatic lactones and 5- or 6-member ring lactones with aliphatic substituents but not simple lactones or those with polar substituents.
messages: Homodimer.
messages: The signal sequence is not cleaved.
messages: extracellular space

9606:PRSS33
gene id: 9606:PRSS33
uniprot id: Q8NF86
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the peptidase S1 family.
messages: Predominantly expressed in macrophages. Present in the spleen, small and large intestine, lung and brain (at protein level). Highly expressed in peripheral leukocytes, ovary, retina, spleen and stomach. Moderately expressed in thymus, uterus and platelets, as well as some brain tissues, such as thalamus and fetal brain.
messages: Secreted
messages: Serine protease that has amidolytic activity, cleaving its substrates before Arg residues.
messages: Up-regulated by phorbol myristate acetate (PMA).

9606:PDE4A
gene id: 9606:PDE4A
uniprot id: P27815
names: Activity Regulation
names: Cofactor
names: Developmental Stage
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the cyclic nucleotide phosphodiesterase family. PDE4 subfamily.
messages: Binds 2 divalent metal cations per subunit (PubMed:17727341, Ref.20). Site 2 has a preference for magnesium and/or manganese ions (By similarity).
messages: Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions.
messages: Efficiently hydrolyzes cAMP.
messages: Efficiently hydrolyzes cAMP. The phosphodiesterase activity is not affected by calcium, calmodulin or cyclic GMP (cGMP) levels. Does not hydrolyze cGMP.
messages: Expressed at high levels in the heart and small intestine. It is also found in the brain, kidney, spleen, colon, salivary gland, ovary and peripheral blood lymphocytes.
messages: Expressed in fetal brain.
messages: Expressed in lymphoid cell subsets including CD8-positive T cells and T-helper 2 cells. Expressed in dendritic cells.
messages: Expressed predominantly in skeletal muscle and brain and at lower levels in the testis. Found in specific neuronal subpopulations including cortical pyramidal neurons, horn neurons in the spinal cord and Purkinje cells in cerebellum (at protein level).
messages: Highly expressed in liver, stomach, testis, thyroid and adrenal glands and at a lower extent in placenta, kidney, pancreas, ovary, uterus and skin. Expressed in myeloid cell subsets including dendritic cells, monocytes, macrophages, eosinophils and mast cells. Expressed in natural killer cells. Expressed in bronchial smooth muscle.
messages: Hydrolyzes the second messenger 3',5'-cyclic AMP (cAMP), which is a key regulator of many important physiological processes.
messages: Inhibited by rolipram and cilomilast.
messages: Inhibited by rolipram, cilomilast, Ro 20-1724, roflumilast and denbufylline.
messages: Inhibited by rolipram.
messages: Interacts with LYN (via SH3 domain). Interacts with ARRB2.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. Probably represents a non-functional splice isoform.
messages: Membrane
messages: Phosphorylated at Ser-119 by PKA.
messages: Proteolytically cleaved by CASP3.
messages: cytosol
messages: perinuclear region
messages: ruffle membrane

9606:CCDC70
gene id: 9606:CCDC70
uniprot id: Q6NSX1
names: Caution
names: Subcellular Location Annotation
messages: It is uncertain whether Met-1 or Met-12 is the initiator.
messages: Mitochondrion

9606:SH3PXD2A
gene id: 9606:SH3PXD2A
uniprot id: Q5TCZ1
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Adapter protein involved in invadopodia and podosome formation, extracellular matrix degradation and invasiveness of some cancer cells. Binds matrix metalloproteinases (ADAMs), NADPH oxidases (NOXs) and phosphoinositides. Acts as an organizer protein that allows NOX1- or NOX3-dependent reactive oxygen species (ROS) generation and ROS localization. In association with ADAM12, mediates the neurotoxic effect of amyloid-beta peptide.
messages: Belongs to the SH3PXD2 family.
messages: Cytoplasm
messages: Found in several cancer cell lines, particularly invasive breast carcinomas and melanomas.
messages: Gene prediction based on similarity to mouse ortholog and partial transcript data.
messages: Interacts (via N-terminus) with CYBA (By similarity). Interacts with ADAM12, ADAM15 and ADAM19. Interacts with NOXO1. Interacts (via SH3 domains) with NOXA1. Interacts with FASLG.
messages: The PX domain is required for podosome localization because of its ability to bind phosphatidylinositol 3-phosphate (PtdIns(3)P) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) and, to a lesser extent, phosphatidylinositol 4-phosphate (PtdIns(4)P), phosphatidylinositol 5-phosphate (PtdIns(5)P), and phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). Binds to the third intramolecular SH3 domain (By similarity).
messages: The fifth SH3 domain mediates binding with ADAM12, ADAM15 and ADAM19.
messages: Tyrosine phosphorylated by SRC. Phosphorylation plays a regulatory role in the protein localization. The intramolecular interaction of the PX domain with the third SH3 domain maintains the protein in the cytoplasm and phosphorylation disrupts this interaction, resulting in the redistribution of the protein from cytoplasm to the perimembrane region. Phosphorylated on serine upon DNA damage, probably by ATM or ATR.
messages: podosome

9606:MRPS16
gene id: 9606:MRPS16
uniprot id: Q9Y3D3
names: Disease Annotation
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the bacterial ribosomal protein bS16 family.
messages: Component of the mitochondrial small ribosomal subunit (mt-SSU). Mature mammalian 55S mitochondrial ribosomes consist of a small (28S) and a large (39S) subunit. The 28S small subunit contains a 12S ribosomal RNA (12S mt-rRNA) and 30 different proteins. The 39S large subunit contains a 16S rRNA (16S mt-rRNA), a copy of mitochondrial valine transfer RNA (mt-tRNA(Val)), which plays an integral structural role, and 52 different proteins. bS16m has a zinc binding site.
messages: Mitochondrion
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:GARIN5B
gene id: 9606:GARIN5B
uniprot id: Q8N5Q1
names: Sequence Caution
names: Similarity
messages: Belongs to the GARIN family.
messages: Contaminating sequence. Potential poly-A sequence.

9606:HSD17B7
gene id: 9606:HSD17B7
uniprot id: P56937
names: Activity Regulation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the short-chain dehydrogenases/reductases (SDR) family. ERG27 subfamily.
messages: Bifunctional enzyme involved in steroid-hormone metabolism and cholesterol biosynthesis (PubMed:12574203, PubMed:12732193, PubMed:12829805, PubMed:20659585, PubMed:19772289, PubMed:11165030). Catalyzes the NADP(H)-dependent reduction of estrogens and androgens and regulates the biological potency of these steroids. Converts estrone (E1) to a more potent estrogen, 17beta-estradiol (E2) (PubMed:12574203, PubMed:12732193, PubMed:19772289). Converts dihydrotestosterone (DHT) to its inactive form 5a-androstane-3b,17b-diol (PubMed:12574203, PubMed:12732193, PubMed:19772289). Converts moderately progesterone to 3beta-hydroxypregn-4-ene-20-one, leading to its inactivation (PubMed:12574203, PubMed:12732193). Additionally, participates in the post-squalene cholesterol biosynthesis, as a 3-ketosteroid reductase (PubMed:12829805, PubMed:20659585, PubMed:11165030).
messages: Binds to the short form of prolactin receptor.
messages: Does not have enzymatic activities toward E1 and DHT.
messages: Endoplasmic reticulum membrane
messages: Estradiol 17-beta-dehydrogenase and dihydrotestosterone oxidoreductase activities are selectively inhibited by 4-methyl-4-aza-5alpha-androstane derivatives, such as 17beta-[(N-Heptyl)methylamino]-4-aza-5r-androstan-3-one and 17beta-(N-Decylformamido)-4-aza-5r-androstan-3-one.
messages: Expressed in eye ciliary epithelial cells and neuroendocrine cells.
messages: Highly expressed in adrenal gland, liver, lung and thymus. Expressed in breast, ovaries, pituitary gland, pregnant uterus, prostate, kidney, lymph node, small intestine, spinal cord and trachea. Weakly expressed in all other tissues tested.
messages: Phosphorylated.

9606:ZG16B
gene id: 9606:ZG16B
uniprot id: Q96DA0
names: Caution
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the jacalin lectin family.
messages: It is uncertain whether Met-1, Met-13 or Met-31 is the initiator.
messages: Secreted

9606:MED15
gene id: 9606:MED15
uniprot id: B7Z2H7
uniprot id: G3V1P5
uniprot id: Q6PKB8
uniprot id: Q96RN5
names: Function
names: Induction
names: PTM
names: Polymorphism
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the Mediator complex subunit 15 family.
messages: By 12-O-tetradecanoylphorbol-13-acetate (TPA).
messages: Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors.
messages: Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. Required for cholesterol-dependent gene regulation. Positively regulates the Nodal signaling pathway.
messages: Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP.
messages: Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. Interacts with SMAD2, SMAD3, SREBF1 and SREBF2. Interacts with WWTR1. Interacts with TRIM11.
messages: Cytoplasm
messages: Expressed in all tissues examined, including heart, brain, lung, spleen, thymus, pancreas, blood leukocyte and placenta. However, the level of expression varied, with highest expression in the placenta and peripheral blood and lowest in the pancreas and kidney.
messages: Nucleus
messages: Several sequencing errors.
messages: The poly-Gln region from amino acids 235-262 of PCQAP is polymorphic. There are from 15 to 18 repeats in the Italian population.
messages: Ubiquitinated by TRIM11, leading to proteasomal degradation.

9606:SLC7A10
gene id: 9606:SLC7A10
uniprot id: Q9NS82
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Associates with SLC3A2/4F2hc to form a functional heterodimeric complex that translocates small neutral L- and D-amino acids across the plasma membrane. Preferentially mediates exchange transport, but can also operate via facilitated diffusion (By similarity) (PubMed:10863037). Acts as a major transporter for glycine, L- and D-serine in the central nervous system. At the spinal cord and brainstem regulates glycine metabolism and glycinergic inhibitory neurotransmission by providing for glycine de novo synthesis from L-serine and glycine recycling from astrocytes to glycinergic motor neurons (By similarity). At Schaffer collateral-CA1 synapses mediates D-serine and glycine release that modulates post-synaptic activation of NMDA receptors and excitatory glutamatergic transmission (By similarity). May regulate D-serine release from mesenchymal progenitors located in developing subcutaneous adipose tissue, favoring white adipocyte over thermogenic beige adipocyte lineage commitment (By similarity).
messages: Belongs to the amino acid-polyamine-organocation (APC) superfamily.
messages: Cell membrane
messages: Disulfide-linked heterodimer with the amino acid transport protein SLC3A2/4F2hc.
messages: Expressed in brain, heart, kidney, liver, lung, pancreas, placenta, and skeletal muscle.

9606:DRD3
gene id: 9606:DRD3
uniprot id: A1A4V4
uniprot id: A8K8E4
uniprot id: E9PCM4
uniprot id: P35462
uniprot id: X5D2G4
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Brain.
messages: Cell membrane
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry. Glycine at position 9 results in gain of function and is associated with susceptibility to essential tremor.
messages: Disease susceptibility may be associated with variants affecting the gene represented in this entry. Glycine at position 9 results in gain of function and may be a risk factor for schizophrenia.
messages: Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase. Promotes cell proliferation.
messages: Interacts with CLIC6 (By similarity). Interacts with GRK4 (PubMed:19520868). Interacts with PALM (PubMed:16386234). Interacts with FLNA (via filamin repeat 21); increases PKA-mediated phosphorylation of FLNA (PubMed:26460884).
messages: Membrane
messages: Palmitoylated.
messages: Phosphorylated by GRK4 (GRK4-alpha and GRK4-gamma).

9606:GBGT1
gene id: 9606:GBGT1
uniprot id: J7Q0Z1
uniprot id: Q8N5D6
names: Caution
names: Cofactor
names: Domain
names: Function
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the glycosyltransferase 6 family.
messages: Binds 1 Mn(2+) ion per subunit.
messages: Common alleles GBGT1*01N.01 and GBGT1*01N.02 do not synthesize Forssman glycolipid antigen (FORS1). A rare allele encoding an arginine to glutamine change at residue 296 is associated with the ability to synthesize Forssman antigen, which is expressed in erythrocytes and is inheritable, thus defining a new histo-blood group FORS, also known as Apae. This variation might have arised as a consequence of the selective pressure exerted by microorganisms. For instance, the uropathogenic E.coli expressing prsG adhesin only binds and agglutinates FORS1-expressing erythrocytes. Thus, FORS1-positive individuals might be more susceptible to certain pathogens.
messages: Golgi apparatus membrane
messages: Has lost the ability to synthesize Forssman glycolipid antigen (FORS1/FG) (PubMed:10506200). Might have acquired an alternative function in glycosphingolipid metabolism, but it remains to be established. It appears to have drifted more slowly than confirmed pseudogenes in the glycosyltransferase 6 family, suggesting that it has remained under evolutionary pressure.
messages: Membrane
messages: The Forssman antigen (FORS1) is normally expressed on erythrocytes of some non-primate mammals. However, in rare cases it is expressed on human erythrocytes of histo-blood group FORS carriers.
messages: The conserved DXD motif is involved in cofactor binding. The manganese ion interacts with the beta-phosphate group of UDP and may also have a role in catalysis (By similarity).
messages: Widely expressed. Expressed at higher level in placenta, ovary and peripheral blood leukocyte, whereas it is weakly expressed in liver, thymus, and testis (PubMed:10506200). Expressed in bone marrow erythroid cells (PubMed:23255552).

9606:MINDY2
gene id: 9606:MINDY2
uniprot id: Q8NBR6
names: Function
names: Similarity
messages: Belongs to the MINDY deubiquitinase family. FAM63 subfamily.
messages: Hydrolase that can remove 'Lys-48'-linked conjugated ubiquitin from proteins (PubMed:27292798). Binds to polyubiquitin chains of different linkage types, including 'Lys-6', 'Lys-11', 'Lys-29', 'Lys-33', 'Lys-48' and 'Lys-63' (PubMed:28082312). May play a regulatory role at the level of protein turnover (PubMed:27292798).

9606:TPGS1
gene id: 9606:TPGS1
uniprot id: Q6ZTW0
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Part of the neuronal tubulin polyglutamylase complex which contains TPGS1, TPGS2, TTLL1, LRRC49 and NICN1 (Probable). Interacts with PCM1, CSTPP1 and LRRC49 (PubMed:34782749).
messages: Subunit of the tubulin polyglutamylase complex (TPGC). The complex mediates cilia and flagella polyglutamylation which is essential for their biogenesis and motility (Probable). May act in the targeting of the tubulin polyglutamylase complex. Required for the development of the spermatid flagellum (By similarity).
messages: axon
messages: centriolar satellite
messages: centrosome
messages: cilium axoneme
messages: cilium basal body
messages: dendrite
messages: flagellum axoneme
messages: flagellum basal body

9606:KBTBD6
gene id: 9606:KBTBD6
uniprot id: Q86V97
names: Domain
names: Function
names: Sequence Caution
names: Subcellular Location Annotation
names: Subunit
messages: As part of the CUL3(KBTBD6/7) E3 ubiquitin ligase complex functions as a substrate adapter for the RAC1 guanine exchange factor (GEF) TIAM1, mediating its 'Lys-48' ubiquitination and proteasomal degradation (PubMed:25684205). By controlling this ubiquitination, regulates RAC1 signal transduction and downstream biological processes including the organization of the cytoskeleton, cell migration and cell proliferation (PubMed:25684205). Ubiquitination of TIAM1 requires the membrane-associated protein GABARAP which may restrict locally the activity of the complex (PubMed:25684205).
messages: Core component of a BCR3 (BTB-CUL3-RBX1) E3 ubiquitin ligase complex, also named Cul3-RING ubiquitin ligase complex CUL3(KBTBD6/7), composed of CUL3, RBX1, KBTBD6 and KBTBD7 (PubMed:25684205). Interacts with GABARAP; the interaction is direct and is required for the ubiquitination of TIAM1 (PubMed:25684205). Interacts with GABARAPL1, GABARAPL2 and MAP1LC3B; the interaction is direct (PubMed:25684205).
messages: Cytoplasm
messages: Nucleus
messages: Probable cloning artifact.
messages: The ATG8 interaction motif (AIM) mediates interaction with proteins of the ATG8 family including GABARAP.
messages: The BTB domain is required for interaction with CUL3.
messages: The Kelch repeats mediate interaction with TIAM1, a CUL3(KBTBD6/7) E3 ubiquitin ligase substrate.

9606:ANO1
gene id: 9606:ANO1
uniprot id: Q5XXA6
uniprot id: Q9NW72
names: Activity Regulation
names: Caution
names: Developmental Stage
names: Disease Annotation
names: Domain
names: Function
names: Induction
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: ATP and calmodulin are essential for its activation. Channel activity is inhibited by CFTR protein and by chloride inhibitors such as niflumic acid (NFA) and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS). Activated by heat with activation seen at temperatures above 44 degrees Celsius (By similarity). Activated by BDNF in radial glial cells (By similarity).
messages: Apical cell membrane
messages: Belongs to the anoctamin family.
messages: By IL13 (PubMed:33026825). By IL4, likely as a result of IL4-induced cell proliferation (PubMed:31732694). By wounding in airway epithelial cells with levels decreasing significantly during the healing process (PubMed:31732694).
messages: Calcium-activated chloride channel (CaCC) (PubMed:20056604, PubMed:22178883, PubMed:21984732, PubMed:22946059, PubMed:32487539). Plays a role in transepithelial anion transport and smooth muscle contraction. Required for the normal functioning of the interstitial cells of Cajal (ICCs) which generate electrical pacemaker activity in gastrointestinal smooth muscles. Acts as a major contributor to basal and stimulated chloride conductance in airway epithelial cells and plays an important role in tracheal cartilage development. Required for CFTR activation by enhancing endoplasmic reticulum Ca(2+) store release and is also required for CFTR membrane expression (PubMed:28963502). Required for basal and ATP-dependent mucus secretion in airways and intestine, probably by controlling exocytosis of mucus-filled granules by providing Ca(2+) to an apical signaling compartment (By similarity). Contributes to airway mucus expression induced by interleukins IL3 and IL8 and by the asthma-associated protein CLCA1 and is required for expression of mucin MUC5AC (PubMed:33026825). However, was shown in another study not to be required for MUC5AC expression (PubMed:31732694). Plays a role in the propagation of Ca(2+) waves in Kolliker's organ in the cochlea and contributes to the refinement of auditory brainstem circuitries prior to hearing onset (By similarity). In vomeronasal sensory neurons, modulates spontaneous firing patterns in the absence of stimuli as well as the firing pattern of pheromone-evoked activity (By similarity). Responsible for calcium-activated chloride channel activity in type I taste cells of the vallate papillae (By similarity). Acts as a heat sensor in nociceptive neurons (By similarity). In dorsal root ganglion neurons, plays a role in mediating non-histaminergic Mas-related G-protein coupled receptor (MRGPR)-dependent itching, acting as a downstream effector of MRGPRs (By similarity). In the developing brain, required for the Ca(2+)-dependent process extensio…
messages: Calcium-activated chloride channel (CaCC). Contributes to calcium-activated chloride secretion in human sweat gland epithelial cells. Shows increased basal chloride permeability and decreased Ca(2+)-induced chloride permeability.
messages: Calcium-activated chloride channel (CaCC). Shows increased sensitivity to intracellular Ca(2+).
messages: Contains ten transmembrane regions, not eight as predicted.
messages: Expressed in nasal epithelial cells (at protein level) (PubMed:32487539). In the kidney, expressed in the collecting duct (at protein level) (PubMed:24913262). Broadly expressed with higher levels in liver, skeletal muscle and gastrointestinal muscles (PubMed:16906560, PubMed:15215166). Expressed in eccrine sweat glands (PubMed:25220078).
messages: Homodimer (PubMed:21056985, PubMed:28559167). Interacts with CFTR (PubMed:22178883, PubMed:28963502). Interacts with TRPV4 (By similarity).
messages: In airway epithelial cells, highly expressed during cell proliferation with levels decreasing as cell differentiation progresses (at protein level).
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: Membrane
messages: Presynapse
messages: The disease may be caused by variants affecting the gene represented in this entry.
messages: The region spanning the fifth and sixth transmembrane domains probably forms the pore-forming region.
messages: The term 'anoctamin' was coined because these channels are anion selective and are predicted to have eight (OCT) transmembrane segments. There is some dissatisfaction in the field with the Ano nomenclature because it is not certain that all the members of this family are anion channels or have the 8-transmembrane topology.

9606:EPSTI1
gene id: 9606:EPSTI1
uniprot id: Q96J88
names: Function
names: Induction
names: Sequence Caution
names: Tissue Specificity
messages: Highly expressed in placenta, small intestine, spleen, kidney, thymus, liver, salivary gland and testes. Weakly expressed in breast, skeletal muscle and colon. Highly expressed in breast cancer upon interaction between tumor cells and stromal cells in vitro. Expressed in blood mononuclear cells from patients with systemic lupus erythematosus (SLE).
messages: Intron retention. Authors have ignored retained intron when translating.
messages: Plays a role in M1 macrophage polarization and is required for the proper regulation of gene expression during M1 versus M2 macrophage differentiation (By similarity). Might play a role in RELA/p65 and STAT1 phosphorylation and nuclear localization upon activation of macrophages (By similarity).
messages: Up-regulated in breast carcinomas.

9606:STAT6
gene id: 9606:STAT6
uniprot id: A8K4S9
uniprot id: B4DQB3
uniprot id: P42226
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the transcription factor STAT family.
messages: Carries out a dual function: signal transduction and activation of transcription. Involved in IL4/interleukin-4- and IL3/interleukin-3-mediated signaling.
messages: Cytoplasm
messages: Forms a homodimer or a heterodimer with a related family member (By similarity). Interacts with NCOA1 via its C-terminal LXXLL motif.
messages: Mono-ADP-ribosylated by PARP14.
messages: Nucleus
messages: Tyrosine phosphorylated on Tyr-641 following stimulation by IL4/interleukin-4 (PubMed:27796300). Tyrosine phosphorylated following stimulation by IL3/interleukin-3 (By similarity). Dephosphorylation on tyrosine residues by PTPN2 negatively regulates the IL4/interleukin-4 mediated signaling (PubMed:17210636).

9606:OR52I1
gene id: 9606:OR52I1
uniprot id: Q8NGK6
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Odorant receptor.

9606:TAT
gene id: 9606:TAT
uniprot id: A0A140VKB7
uniprot id: P17735
names: Disease Annotation
names: Function
names: Similarity
names: Subunit
messages: Belongs to the class-I pyridoxal-phosphate-dependent aminotransferase family.
messages: Homodimer.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Transaminase involved in tyrosine breakdown. Converts tyrosine to p-hydroxyphenylpyruvate.
messages: Transaminase involved in tyrosine breakdown. Converts tyrosine to p-hydroxyphenylpyruvate. Can catalyze the reverse reaction, using glutamic acid, with 2-oxoglutarate as cosubstrate (in vitro). Has much lower affinity and transaminase activity towards phenylalanine.

9606:ITPR2
gene id: 9606:ITPR2
uniprot id: Q14571
names: Disease Annotation
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the InsP3 receptor family.
messages: Calcium appears to inhibit ligand binding to the receptor, most probably by interacting with a distinct calcium-binding protein which then inhibits the receptor.
messages: Endoplasmic reticulum membrane
messages: Homotetramer (By similarity). Interacts with CABP1 (PubMed:12032348). Interacts with BOK; regulates ITPR2 expression (By similarity). Interacts with BCL2L10 (PubMed:27995898). Interacts with TRPC4 (By similarity).
messages: Isoform Short is found in skeletal muscle and heart.
messages: Phosphorylation by cAMP-dependent PKA on Ser-937 increases calcium release.
messages: Receptor for inositol 1,4,5-trisphosphate, a second messenger that mediates the release of intracellular calcium. This release is regulated by cAMP both dependently and independently of PKA (By similarity).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The receptor contains a calcium channel in its C-terminal extremity. Its large N-terminal cytoplasmic region has the ligand-binding site in the N-terminus and modulatory sites in the middle portion immediately upstream of the channel region.

9606:RBMS1
gene id: 9606:RBMS1
uniprot id: P29558
names: Developmental Stage
names: Function
names: Miscellaneous
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Expressed at highest levels during the G1 to S transition of the cell cycle.
messages: Highest amounts are found in placenta, lung and heart.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Nucleus
messages: Single-stranded DNA binding protein that interacts with the region upstream of the MYC gene. Binds specifically to the DNA sequence motif 5'-[AT]CT[AT][AT]T-3'. Probably has a role in DNA replication.

9606:SETD2
gene id: 9606:SETD2
uniprot id: Q9BYW2
names: Activity Regulation
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Recruited to the promoters of adenovirus 12 E1A gene in case of infection, possibly leading to regulate its expression.
messages: Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. SET2 subfamily.
messages: Chromosome
messages: Contaminating sequence. Potential poly-A sequence.
messages: Histone methyltransferase that specifically trimethylates 'Lys-36' of histone H3 (H3K36me3) using dimethylated 'Lys-36' (H3K36me2) as substrate (PubMed:16118227, PubMed:19141475, PubMed:21526191, PubMed:21792193, PubMed:23043551, PubMed:27474439). It is capable of trimethylating unmethylated H3K36 (H3K36me0) in vitro (PubMed:19332550). Represents the main enzyme generating H3K36me3, a specific tag for epigenetic transcriptional activation (By similarity). Plays a role in chromatin structure modulation during elongation by coordinating recruitment of the FACT complex and by interacting with hyperphosphorylated POLR2A (PubMed:23325844). Acts as a key regulator of DNA mismatch repair in G1 and early S phase by generating H3K36me3, a mark required to recruit MSH6 subunit of the MutS alpha complex: early recruitment of the MutS alpha complex to chromatin to be replicated allows a quick identification of mismatch DNA to initiate the mismatch repair reaction (PubMed:23622243). Required for DNA double-strand break repair in response to DNA damage: acts by mediating formation of H3K36me3, promoting recruitment of RAD51 and DNA repair via homologous recombination (HR) (PubMed:24843002). Acts as a tumor suppressor (PubMed:24509477). H3K36me3 also plays an essential role in the maintenance of a heterochromatic state, by recruiting DNA methyltransferase DNMT3A (PubMed:27317772). H3K36me3 is also enhanced in intron-containing genes, suggesting that SETD2 recruitment is enhanced by splicing and that splicing is coupled to recruitment of elongating RNA polymerase (PubMed:21792193). Required during angiogenesis (By similarity). Required for endoderm development by promoting embryonic stem cell differentiation toward endoderm: acts by mediating formation of H3K36me3 in distal promoter regions of FGFR3, leading to regulate transcription initiation of FGFR3 (By similarity). In addition to histones, also mediates methylation of other proteins, such as tubulins and STAT1 (PubMed:27518565…
messages: May be automethylated.
messages: Nucleus
messages: Specifically inhibited by sinefungin derivatives. N-propyl sinefungin (Pr-SNF) interacts preferentially with SETD2.
messages: Specifically interacts with hyperphosphorylated C-terminal domain (CTD) of RNA polymerase II large subunit (POLR2A): binds to CTD heptad repeats doubly phosphorylated on 'Ser-2' and 'Ser-5' of each heptad (PubMed:16118227, PubMed:16314571). Interacts with HTT (PubMed:11461154, PubMed:9700202, PubMed:10958656). Interacts with IWS1 (PubMed:19141475). Interacts with p53/TP53; leading to regulate p53/TP53 target genes (PubMed:18585004). Component of a complex with HNRNPL (PubMed:19332550, PubMed:36537238). Interacts with TUBA1A; the interaction is independent on alpha-tubulin acetylation on 'Lys-40' (PubMed:27518565). Interacts with STAT1 (PubMed:28753426).
messages: The catalytic SET domain binds histone H3 (PubMed:27474439, PubMed:28256625). It is also able to bind oncogenic histone H3 K36M/I found in a number of cancer types, in which histone H3 'Lys-36' is replaced by a Met or an Ile residue. When binding the oncogenic variant histone H3 K36M/I, the SET domain undergoes dramatic conformational change to accommodate the histone H3 peptide, leading to sequester and inhibit SETD2 activity and block global H3K36 methylation (PubMed:27474439, PubMed:28256625).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The disease may be caused by variants affecting distinct genetic loci, including the gene represented in this entry.
messages: The disease may be caused by variants affecting the gene represented in this entry.
messages: The disease may be caused by variants affecting the gene represented in this entry. Defects of SETD2 are associated with loss of DNA methylation at non-promoter regions (PubMed:23792563). SETD2 defects lead to aberrant and reduced nucleosome compaction and chromatin association of key replication proteins, such as MCM7 and DNA polymerase delta, leading to hinder replication fork progression and prevent loading of RAD51 homologous recombination repair factor at DNA breaks (PubMed:25728682).
messages: The low charge region mediates the transcriptional activation activity.
messages: Ubiquitously expressed.

9606:POC1B
gene id: 9606:POC1B
uniprot id: Q8TC44
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the WD repeat POC1 family.
messages: Expressed in the retina.
messages: Interacts with POC1A (PubMed:23015594). Interacts with FAM161A (PubMed:25018096). Interacts with CEP44; the interaction is direct and recruits POC1B to centriolar microtubules (PubMed:32060285).
messages: Phosphorylated in mitotic cells that may be mediated by CDK1.
messages: Plays an important role in centriole assembly and/or stability and ciliogenesis (PubMed:20008567, PubMed:32060285). Involved in early steps of centriole duplication, as well as in the later steps of centriole length control (PubMed:19109428). Acts in concert with POC1A to ensure centriole integrity and proper mitotic spindle formation (PubMed:32060285). Required for primary cilia formation, ciliary length and also cell proliferation (PubMed:23015594). Required for retinal integrity (PubMed:25044745).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: centriole
messages: centrosome
messages: cilium basal body
messages: spindle pole

9606:SH2B2
gene id: 9606:SH2B2
uniprot id: O14492
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Adapter protein for several members of the tyrosine kinase receptor family. Involved in multiple signaling pathways. May be involved in coupling from immunoreceptor to Ras signaling. Acts as a negative regulator of cytokine signaling in collaboration with CBL. Binds to EPOR and suppresses EPO-induced STAT5 activation, possibly through a masking effect on STAT5 docking sites in EPOR. Suppresses PDGF-induced mitogenesis. May induce cytoskeletal reorganization via interaction with VAV3.
messages: Belongs to the SH2B adapter family.
messages: Cell membrane
messages: Cytoplasm
messages: Expressed in spleen, prostate, testis, uterus, small intestine and skeletal muscle. Among hematopoietic cell lines, expressed exclusively in B-cells. Not expressed in most tumor cell lines.
messages: Homodimer. Interacts with KIT/c-KIT, SHC1, EPOR, PDGFR, VAV1 and VAV3. Interacts (via N-terminal region) with SHC1. Interacts (via the phosphorylated C-terminus) with GRB2. Interacts (via its SH2 domain) with EPOR, INSR and KIT. Interacts with GRB2 after B-cell antigen receptor stimulation. Interacts (via PH domain) with VAV3. Interacts with NTRK1, NTRK2 and NTRK3 (phosphorylated); after stimulation of the receptor by its extracellular ligand and subsequent autophosphorylation of the receptor. Binds INSR, GRB2, ASB6 and CAP. Insulin stimulation leads to dissociation of CAP. Binds CBS only when SH2B2/APS has become phosphorylated. INSR binding does not depend on the phosphorylation of SH2B2/APS (By similarity).
messages: Tyrosine phosphorylated by JAK2, KIT and other kinases activated by B-cell receptor in response to stimulation with cytokines, IL3, IL5, PDGF, IGF1, IGF2, CSF2/GM-CSF and cross-linking of the B-cell receptor complex.

9606:POLR1G
gene id: 9606:POLR1G
uniprot id: O15446
names: Caution
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the eukaryotic RPA34 RNA polymerase subunit family.
messages: Chromosome
messages: Component of the RNA polymerase I (Pol I) complex consisting of at least 13 subunits. Interacts with TAF1A thereby associates with the SL1 complex. Interacts with UBTF. Interacts with POLR1E/PRAF1 through its N-terminal region (By similarity). Isoform 2 interacts with CD3E.
messages: DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase I which synthesizes ribosomal RNA precursors. Isoform 1 is involved in UBTF-activated transcription, presumably at a step following PIC formation.
messages: Has sharply different functional characteristics.
messages: Isoform 1 is phosphorylated on tyrosine residues in initiation-competent Pol I-beta complexes but not in Pol I-alpha complexes.
messages: Isoform 2 has been described as a component of preformed T-cell receptor (TCR) complex.
messages: Isoform 2 undergoes tyrosine phosphorylation upon T-cell receptor (TCR) stimulation. This phosphorylation has not been confirmed by other groups.
messages: It is in an antisense orientation to and overlaps the gene of the DNA repair enzyme ERCC1. This gene overlap is conserved in mouse, suggesting an important biological function.
messages: It is not known whether the so-called human ASE1 and human CAST proteins represent two sides of a single gene product with sharply different functional characteristics. Experiments done with the mouse homolog protein are in favor of an implication of this gene in rRNA transcription instead of T-cell receptor signaling.
messages: nucleolus

9606:PHF20
gene id: 9606:PHF20
uniprot id: Q9BVI0
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Antibodies against PHF20 are present in sera from patients with hepatocellular carcinoma, glioblastoma and childhood medulloblastula.
messages: Expressed in heart, kidney, liver, lung, pancreas, placenta, spleen and testis. Not expressed in brain, skeletal muscle, colon, ovary, prostate, small intestine and thymus. Expressed in colon and ovary cancer cell lines while it is not expressed in the respective normal tissues.
messages: Homodimer; disulfide-linked. Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1, WDR5 and RBBP5, as well as the facultative components BAP18, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, KAT8/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10. Component of the NSL complex at least composed of MOF/KAT8, KANSL1, KANSL2, KANSL3, MCRS1, PHF20, OGT1/OGT, WDR5 and HCFC1.
messages: Methyllysine-binding protein, component of the MOF histone acetyltransferase protein complex. Not required for maintaining the global histone H4 'Lys-16' acetylation (H4K16ac) levels or locus specific histone acetylation, but instead works downstream in transcriptional regulation of MOF target genes (By similarity). As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues. Contributes to methyllysine-dependent p53/TP53 stabilization and up-regulation after DNA damage.
messages: Nucleus
messages: The Tudor domain 1 doesn't bind dimethyl-lysine residues, due to an atypical and occluded aromatic cage.
messages: The Tudor domain 2 mediates reading of dimethyl-lysine residues.
messages: Ubiquitinated by TRIM26; leading to proteasomal degradation.

9606:ADGRG4
gene id: 9606:ADGRG4
uniprot id: Q8IZF6
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor 2 family. Adhesion G-protein coupled receptor (ADGR) subfamily.
messages: Detected in fetal retina. Highly expressed in normal enterochromaffin cells and in neuroendocrine carcinoma. Detected in normal liver; highly expressed in primary liver carcinoma.
messages: Membrane
messages: Orphan receptor.

9606:C19orf33
gene id: 9606:C19orf33
uniprot id: Q9GZP8
names: Subcellular Location Annotation
messages: Nucleus

9606:TVP23B
gene id: 9606:TVP23B
uniprot id: J3QL63
uniprot id: Q9NYZ1
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the TVP23 family.
messages: Membrane

9606:PRDM4
gene id: 9606:PRDM4
uniprot id: B3KPI0
uniprot id: Q9UKN5
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the class V-like SAM-binding methyltransferase superfamily.
messages: Expressed in many tissues. Highly expressed in ovary, testis, pancreas, brain, heart and prostate.
messages: May function as a transcription factor involved in cell differentiation.
messages: Nucleus

9606:DCAF4
gene id: 9606:DCAF4
uniprot id: Q8WV16
names: Function
names: Polymorphism
names: Subunit
messages: An intronic G-to-A transition (rs2535913) has been associated with leukocyte telomere length. The minor A allele is associated with shorter telomeres and lower expression in lymphoblastoid cells and in sun-exposed skin (PubMed:25624462).
messages: Interacts with DDB1 and CUL4A.
messages: May function as a substrate receptor for CUL4-DDB1 E3 ubiquitin-protein ligase complex.

9606:CYP2D6
gene id: 9606:CYP2D6
uniprot id: C1ID52
uniprot id: P10635
names: Function
names: Induction
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
messages: A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (PubMed:10681376). Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
messages: Belongs to the cytochrome P450 family.
messages: By pregnancy.
messages: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
messages: Endoplasmic reticulum membrane
messages: Genetic variations in CYP2D6 are the cause of poor drug metabolism CYP2D6-related [MIM:608902]. The CYP2D6 gene is highly polymorphic. CYP2D6 activity ranges widely within a population comprising ultrarapid (UM), extensive (EM), intermediate (IM) and poor (PM) metabolizer phenotypes. UM and PM are those most at risk for treatment failure or dose-dependent drug toxicity, respectively. Of the Caucasian populations of Europe and North America, 5%-10% are of the PM phenotype and are unable to metabolize the antihypersensitive drug debrisoquine and numerous other drugs. Different alleles are known, including CYP2D6*1 (PubMed:15768052), CYP2D6*2 (PubMed:25469868), CYP2D6*6B/6C (PubMed:7868129), CYP2D6*7 also known CYP2D6E (PubMed:7845481), CYP2D6*9 also known CYP2D6C (PubMed:1844820), CYP2D6*10 also known CYP2D6J (PubMed:8287064, PubMed:25469868), CYP2D6*12 (PubMed:8655150), CYP2D6*14 (PubMed:10064570), CYP2D6*17 also known CYP2D6Z (PubMed:8971426), CYP2D6*41B (PubMed:15768052), CYP2D6*45A (PubMed:15768052), CYP2D6*45B (PubMed:15768052), CYP2D6*46 (PubMed:15768052), CYP2D6*87 (PubMed:25469868), CYP2D6*88 (PubMed:25469868), CYP2D6*89 (PubMed:25469868), CYP2D6*90 (PubMed:25469868), CYP2D6*91 (PubMed:25469868), CYP2D6*93 (PubMed:25469868), C CYP2D6*94 (PubMed:25469868), CYP2D6*97 (PubMed:25469868) and CYP2D6*98 (PubMed:25469868). Isozymes CYP2D6.45 (Lys-155, Cys-296 and Thr-486) and CYP2D6.46 (His-26, Lys-155, Cys-296 and Thr-486) are functional (PubMed:15768052). The sequence shown is that of isozyme CYP2D6.1 corresponding to allele CYP2D6*1.
messages: Microsome membrane

9606:C10orf71
gene id: 9606:C10orf71
uniprot id: Q711Q0
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Expressed in the heart and skeletal muscle.
messages: Interacts with FHL2.
messages: Plays an important role in cardiomyocyte hypertrophy via activation of the calcineurin/NFAT signaling pathway.
messages: Z line

9606:PDCD2
gene id: 9606:PDCD2
uniprot id: Q16342
names: Function
names: PTM
names: Subcellular Location Annotation
names: Tissue Specificity
messages: May be a DNA-binding protein with a regulatory function. May play an important role in cell death and/or in regulation of cell proliferation.
messages: Nucleus
messages: Ubiquitinated by PRKN, promoting proteasomal degradation.
messages: Ubiquitous.

9606:A1CF
gene id: 9606:A1CF
uniprot id: B4E1E3
uniprot id: F8W9F8
uniprot id: Q9NQ94
names: Domain
names: Function
names: Miscellaneous
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cytoplasm
messages: Does not exhibit APOBEC1 complementation activity.
messages: Endoplasmic reticulum
messages: Essential component of the apolipoprotein B mRNA editing enzyme complex which is responsible for the postranscriptional editing of a CAA codon for Gln to a UAA codon for stop in APOB mRNA. Binds to APOB mRNA and is probably responsible for docking the catalytic subunit, APOBEC1, to the mRNA to allow it to deaminate its target cytosine. The complex also protects the edited APOB mRNA from nonsense-mediated decay.
messages: Major isoform found in 66-78% of cDNA clones.
messages: Minor isoform found in 2-3% of cDNA clones.
messages: Nucleus
messages: Part of the apolipoprotein B mRNA editing complex with APOBEC1 (PubMed:10781591, PubMed:10669759). Interacts with TNPO2; TNPO2 may be responsible for transport of A1CF into the nucleus (PubMed:12896982). Interacts with SYNCRIP (PubMed:11134005). Interacts with CELF2/CUGBP2 (PubMed:11577082). Interacts with RBM47 (PubMed:24916387).
messages: The RRM domains are necessary but not sufficient for binding to APOB mRNA. Additional residues in the pre-RRM and C-terminal regions are required for RNA-binding and for complementing APOBEC1 activity.
messages: Widely expressed with highest levels in brain, liver, pancreas, colon and spleen.

9606:GARIN5A
gene id: 9606:GARIN5A
uniprot id: Q6IPT2
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the GARIN family.
messages: Golgi apparatus
messages: Interacts (via N-terminus) with RAB2B (in GTP-bound form).
messages: RAB2B effector protein which promotes cytosolic DNA-induced innate immune responses. Regulates IFN responses against DNA viruses by regulating the CGAS-STING signaling axis.

9606:PFN3
gene id: 9606:PFN3
uniprot id: P60673
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the profilin family.
messages: Binds to actin and affects the structure of the cytoskeleton. Slightly reduces actin polymerization. Binds to poly-L-proline, phosphatidylinositol 3-phosphate (PtdIns(3)P), phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and phosphatidylinositol 4-phosphate (PtdIns(4)P). May be involved in spermatogenesis.
messages: Interacts with ACTRT3.
messages: Nucleus
messages: Testis specific.
messages: cytoskeleton

9606:FBXL16
gene id: 9606:FBXL16
uniprot id: Q8N461
names: Function
names: Subunit
messages: Interacts with SKP1 and CUL1.
messages: Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex.

9606:GCFC2
gene id: 9606:GCFC2
uniprot id: A4UHR0
uniprot id: B3KUM5
uniprot id: P16383
names: Caution
names: Function
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the GCF family.
messages: Contaminating sequence. The N-terminus matches the 2q37.3 region.
messages: Found in the Intron Large (IL) complex, a post-mRNA release spliceosomal complex containing the excised intron, U2, U5 and U6 snRNPs, and splicing factors (PubMed:24304693). Interacts with TFIP11 and DHX15 (PubMed:24304693).
messages: Involved in pre-mRNA splicing through regulating spliceosome C complex formation (PubMed:24304693). May play a role during late-stage splicing events and turnover of excised introns (PubMed:24304693).
messages: Was originally thought to be a DNA-binding transcriptional repressor. However, later work showed that the original sequence was a chimera and that the DNA-binding activity was derived from the incorrect N-terminal sequence.
messages: Widely expressed in tissues and cell lines.
messages: nucleolus
messages: nucleoplasm

9606:USP37
gene id: 9606:USP37
uniprot id: Q86T82
names: Developmental Stage
names: Domain
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the peptidase C19 family.
messages: Chromosome
messages: Deubiquitinase that plays a role in different processes including cell cycle regulation, DNA replication or DNA damage response (PubMed:26299517, PubMed:27296872, PubMed:31911859, PubMed:34509474). Antagonizes the anaphase-promoting complex (APC/C) during G1/S transition by mediating deubiquitination of cyclin-A (CCNA1 and CCNA2), thereby promoting S phase entry. Specifically mediates deubiquitination of 'Lys-11'-linked polyubiquitin chains, a specific ubiquitin-linkage type mediated by the APC/C complex. Phosphorylation at Ser-628 during G1/S phase maximizes the deubiquitinase activity, leading to prevent degradation of cyclin-A (CCNA1 and CCNA2) (PubMed:21596315). Plays an important role in the regulation of DNA replication by stabilizing the licensing factor CDT1 (PubMed:27296872). Plays also an essential role beyond S-phase entry to promote the efficiency and fidelity of replication by deubiquitinating checkpoint kinase 1/CHK1, promoting its stability (PubMed:34509474). Sustains the DNA damage response (DDR) by deubiquitinating and stabilizing the ATP-dependent DNA helicase BLM (PubMed:34606619). Mechanistically, DNA double-strand breaks (DSB) promotes ATM-mediated phosphorylation of USP37 and enhances the binding between USP37 and BLM (PubMed:34606619). Promotes cell migration by deubiquitinating and stabilizing the epithelial-mesenchymal transition (EMT)-inducing transcription factor SNAI (PubMed:31911859). Plays a role in the regulation of mitotic spindle assembly and mitotic progression by associating with chromatin-associated WAPL and stabilizing it through deubiquitination (PubMed:26299517).
messages: Expressed in brain and prostate.
messages: Induced by E2F transcription factors in G1.
messages: Induced in G1 phase, accumulates at G1/S transition, and degraded in late mitosis following ubiquitination and degradation by the APC(CDH1) complex.
messages: Interacts with FZR1/CDH1 (PubMed:21596315). Interacts with CDT1 (PubMed:27296872).
messages: Nucleus
messages: Phosphorylated at Ser-628 by CDK2 during G1/S phase but not during mitosis; phosphorylation at Ser-628 is required for deubiquitinase activity. Also polyubiquitinated during early G1 phase, without leading to degradation (PubMed:21596315). Phosphorylated at Ser-114 by ATM following DNA damage, which in turn increases its deubiquitination activity towards BLM (PubMed:34606619).
messages: Polyubiquitinated via 'Lys-11'-linked ubiquitin by the APC(CDH1) complex during late mitosis, leading to its degradation. Able to mediate auto-deubiquitination.
messages: The KEN box 3 is required for interaction with FZR1/CDH1 and is essential for APC(CDH1)-mediated ubiquitination.

9606:FATE1
gene id: 9606:FATE1
uniprot id: Q969F0
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Endoplasmic reticulum membrane
messages: Interacts with BIK and RNF183 (PubMed:26567849). Interacts with IMMT/MIC60and EMD (PubMed:27402544).
messages: Involved in the regulation of endoplasmic reticulum (ER)-mitochondria coupling. Negatively regulates the ER-mitochondria distance and Ca(2+) transfer from ER to mitochondria possibly implicating it in the regulation of apoptosis (PubMed:27402544). May collaborate with RNF183 to restrain BIK protein levels thus regulating apoptotic signaling (PubMed:26567849).
messages: Mitochondrion
messages: Mitochondrion outer membrane
messages: Testis-specific in fetus (aged from 6 to 11 weeks). In adult, expressed predominantly in testis, with some expression in lung, heart, kidney, adrenal gland and whole brain (PubMed:11694338). Highly expressed in certain types of cancer tissues such as hepatocellular carcinoma, colon and gastric cancer. Weakly expressed in normal pancreas (PubMed:12865919).

9606:DMRTC1B
gene id: 9606:DMRTC1B
uniprot id: Q5HYR2
names: Caution
names: Similarity
names: Tissue Specificity
messages: Although related to other DMRT proteins, it does not contain a canonical DM DNA-binding domain.
messages: Belongs to the DMRT family.
messages: Predominantly expressed in kidney, pancreas, ovary and testis. Detected in brain and in many other tissues.

9606:NFATC2IP
gene id: 9606:NFATC2IP
uniprot id: Q8NCF5
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: Cytoplasm
messages: In T-helper 2 (Th2) cells, regulates the magnitude of NFAT-driven transcription of a specific subset of cytokine genes, including IL3, IL4, IL5 and IL13, but not IL2. Recruits PRMT1 to the IL4 promoter; this leads to enhancement of histone H4 'Arg-3'-methylation and facilitates subsequent histone acetylation at the IL4 locus, thus promotes robust cytokine expression (By similarity). Down-regulates formation of poly-SUMO chains by UBE2I/UBC9 (By similarity).
messages: Interacts with NFATC2, TRAF1, TRAF2 and PRMT1. Interacts with UBE2I/UBC9 (By similarity).
messages: Methylation at the N-terminus by PRMT1 modulates interaction with the NFAT complex and results in augmented cytokine production.
messages: Nucleus

9606:NUP43
gene id: 9606:NUP43
uniprot id: Q8NFH3
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Component of the Nup107-160 subcomplex of the nuclear pore complex (NPC). The Nup107-160 subcomplex includes NUP160, NUP133, NUP107, NUP98, NUP85, NUP43, NUP37, SEH1 and SEC13.
messages: Component of the Nup107-160 subcomplex of the nuclear pore complex (NPC). The Nup107-160 subcomplex is required for the assembly of a functional NPC. The Nup107-160 subcomplex is also required for normal kinetochore microtubule attachment, mitotic progression and chromosome segregation.
messages: kinetochore
messages: nuclear pore complex

9606:LTV1
gene id: 9606:LTV1
uniprot id: Q96GA3
names: Disease Annotation
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the LTV1 family.
messages: Cytoplasm
messages: Expressed in the epidermis.
messages: The disease may be caused by variants affecting the gene represented in this entry.

9606:IGLON5
gene id: 9606:IGLON5
uniprot id: A6NGN9
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the immunoglobulin superfamily. IgLON family.
messages: Secreted

9606:CNIH3
gene id: 9606:CNIH3
uniprot id: Q8TBE1
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acts as an auxiliary subunit for AMPA-selective glutamate receptors (AMPARs). Found in a complex with GRIA1, GRIA2, GRIA3, GRIA4, CNIH2, CACNG2, CACNG3, CACNG4, CACNG5, CACNG7 and CACNG8 (By similarity).
messages: Belongs to the cornichon family.
messages: Expression is up-regulated in dorsolateral prefrontal cortex of patients with schizophrenia (postmortem brain study).
messages: Postsynaptic cell membrane
messages: Regulates the trafficking and gating properties of AMPA-selective glutamate receptors (AMPARs). Promotes their targeting to the cell membrane and synapses and modulates their gating properties by regulating their rates of activation, deactivation and desensitization.

9606:TLR10
gene id: 9606:TLR10
uniprot id: Q9BXR5
names: Caution
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the Toll-like receptor family.
messages: Binds MYD88 via their respective TIR domains (By similarity). Homodimer (Potential).
messages: Highly expressed in spleen, lymph node, thymus, tonsil and at lower levels in lung. Highly expressed in promyelocytic HL-60 cells and in B-cell lines.
messages: In some plant proteins and in human SARM1, the TIR domain has NAD(+) hydrolase (NADase) activity (By similarity). However, despite the presence of the catalytic Asp residue, the isolated TIR domain of human TLR4 lacks NADase activity (By similarity). Based on this, it is unlikely that Toll-like receptors have NADase activity.
messages: Membrane
messages: Participates in the innate immune response to microbial agents. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response (By similarity).

9606:RASSF7
gene id: 9606:RASSF7
uniprot id: Q02833
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: Interacts with MAP2K7 and GTP-bound NRAS.
messages: Negatively regulates stress-induced JNK activation and apoptosis by promoting MAP2K7 phosphorylation and inhibiting its ability to activate JNK. Following prolonged stress, anti-apoptotic effect stops because of degradation of RASSF7 protein via the ubiquitin-proteasome pathway. Required for the activation of AURKB and chromosomal congression during mitosis where it stimulates microtubule polymerization.
messages: Polyubiquitinated and degraded by the proteasome upon prolonged stress stimuli.
messages: centrosome

9606:RTF1
gene id: 9606:RTF1
uniprot id: Q92541
names: Caution
names: Domain
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Component of the PAF1 complex (PAF1C) which has multiple functions during transcription by RNA polymerase II and is implicated in regulation of development and maintenance of embryonic stem cell pluripotency. PAF1C associates with RNA polymerase II through interaction with POLR2A CTD non-phosphorylated and 'Ser-2'- and 'Ser-5'-phosphorylated forms and is involved in transcriptional elongation, acting both independently and synergistically with TCEA1 and in cooperation with the DSIF complex and HTATSF1. PAF1C is required for transcription of Hox and Wnt target genes. PAF1C is involved in hematopoiesis and stimulates transcriptional activity of KMT2A/MLL1; it promotes leukemogenesis through association with KMT2A/MLL1-rearranged oncoproteins, such as KMT2A/MLL1-MLLT3/AF9 and KMT2A/MLL1-MLLT1/ENL. PAF1C is involved in histone modifications such as ubiquitination of histone H2B and methylation on histone H3 'Lys-4' (H3K4me3). PAF1C recruits the RNF20/40 E3 ubiquitin-protein ligase complex and the E2 enzyme UBE2A or UBE2B to chromatin which mediate monoubiquitination of 'Lys-120' of histone H2B (H2BK120ub1); UB2A/B-mediated H2B ubiquitination is proposed to be coupled to transcription. PAF1C is involved in mRNA 3' end formation probably through association with cleavage and poly(A) factors. In case of infection by influenza A strain H3N2, PAF1C associates with viral NS1 protein, thereby regulating gene transcription. Binds single-stranded DNA. Required for maximal induction of heat-shock genes. Required for the trimethylation of histone H3 'Lys-4' (H3K4me3) on genes involved in stem cell pluripotency; this function is synergistic with CXXC1 indicative for an involvement of a SET1 complex (By similarity).
messages: Component of the PAF1 complex, which consists of CDC73, PAF1, LEO1, CTR9, RTF1 and SKIC8; the association of RTF1 appears to be less stable than that of other subunits. At least in HeLa cells a N-terminal shorter form of RTF1 is also found in the complex (PubMed:20178742). The PAF1 complex interacts with PHF5A (By similarity).
messages: It is uncertain whether Met-1 or Met-41 is the initiator.
messages: The Plus3 domain mediates single-stranded DNA-binding.
messages: nucleoplasm

9606:ZMYND8
gene id: 9606:ZMYND8
uniprot id: Q9ULU4
names: Developmental Stage
names: Disease Annotation
names: Domain
names: Function
names: Induction
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Chromatin reader that recognizes dual histone modifications such as histone H3.1 dimethylated at 'Lys-36' and histone H4 acetylated at 'Lys-16' (H3.1K36me2-H4K16ac) and histone H3 methylated at 'Lys-4' and histone H4 acetylated at 'Lys-14' (H3K4me1-H3K14ac) (PubMed:26655721, PubMed:31965980, PubMed:36064715, PubMed:27477906). May act as a transcriptional corepressor for KDM5D by recognizing the dual histone signature H3K4me1-H3K14ac (PubMed:27477906). May also act as a transcriptional corepressor for KDM5C and EZH2 (PubMed:33323928). Recognizes acetylated histone H4 and recruits the NuRD chromatin remodeling complex to damaged chromatin for transcriptional repression and double-strand break repair by homologous recombination (PubMed:30134174, PubMed:25593309, PubMed:27732854). Also activates transcription elongation by RNA polymerase II through recruiting the P-TEFb complex to target promoters (PubMed:30134174, PubMed:26655721). Localizes to H3.1K36me2-H4K16ac marks at all-trans-retinoic acid (ATRA)-responsive genes and positively regulates their expression (PubMed:26655721). Promotes neuronal differentiation by associating with regulatory regions within the MAPT gene, to enhance transcription of a protein-coding MAPT isoform and suppress the non-coding MAPT213 isoform (PubMed:36064715, PubMed:35916866, PubMed:30134174). Suppresses breast cancer, and prostate cancer cell invasion and metastasis (PubMed:27477906, PubMed:31965980, PubMed:33323928).
messages: Chromosome
messages: Cytoplasm
messages: Expressed in neurons (at protein level) (PubMed:36064715). Absent in astrocytes (at protein level) (PubMed:36064715). Expressed in all tissues examined with highest expression in brain, lung, pancreas, and placenta (PubMed:11003709, PubMed:35916866). Expressed in cutaneous T-cell lymphomas (CTCL) (PubMed:11149944).
messages: Highly expressed in fetal brain, with decreasing expression in postnatal stages.
messages: Induced by all-trans-retinoic acid (ATRA) (at protein level).
messages: Monomer and homodimer (PubMed:30134174). Interacts with NuRD subcomplexes containing GATAD2A (PubMed:27732854). Interacts with the histone deacetylase NuRD complex subunit CHD4; the interaction is direct, appears to occur with monomeric ZMYND8, and is increased following DNA damage (PubMed:30134174, PubMed:25593309, PubMed:36064715). Interacts (via N-terminus) with the P-TEFb complex subunit CCNT1 (via central region); the interaction is direct and the association appears to occur between homodimeric ZMYND8 and the activated form of the P-TEFb complex (PubMed:30134174). Interacts (via N-terminus) with DBN1 (via ADF-H domain); the interaction leads to sequestering of ZMYND8 in the cytoplasm (PubMed:28966017, PubMed:35916866). Interacts with the P-TEFb complex subunit CDK9; the association appears to occur between homodimeric ZMYND8 and the activated form of the P-TEFb complex (PubMed:30134174). Interacts with EZH2; the interaction is dependent on the presence of chromatin (PubMed:33323928, PubMed:36064715). Interacts (via MYND domain) with the NuRD complex subunit GATAD2A (PubMed:35916866, PubMed:27732854). Interacts with histone H3 (via N-terminus) that is both methylated at 'Lys-4' (H3K4me1) and acetylated at 'Lys-14' (H3K14ac), with histone H3 (via N-terminus) unmodified at 'Lys-4' (H3K4me0) and acetylated at 'Lys-14' (H3K14ac), and with histone H3 (via N-terminus) di-methylated at 'Lys-36' (H3K36me2) (PubMed:27477906, PubMed:25593309, PubMed:26655721, PubMed:31965980). Interacts (via Bromo domain) with histone H4 acetylated at 'Lys-16' (H4K16ac) (PubMed:25593309, PubMed:26655721, PubMed:31965980). Interacts with HDAC1 (PubMed:25593309, PubMed:36064715). Interacts with HDAC2 (PubMed:25593309). Interacts with KDM1A (PubMed:27477906, PubMed:25593309). Interacts with KDM5C (PubMed:33323928). Interacts with KDM5D (PubMed:27477906). Interacts in vitro with PRKCB (PubMed:11003709). Interacts with RNA polymerase II subunit POLR2A phosphorylated at 'Ser-5' (PubMed:2665572…
messages: Mutations in ZMYND8 may be the cause of syndromic intellectual disability with variable cardiovascular, ophthalmologic and minor skeletal anomalies.
messages: Nucleus
messages: The MYND-type zinc finger domain is required for localization to DNA damage sites.
messages: The PWWP domain is required for interaction with histone H3.1K36me2.
messages: The bromo domain is required for interaction with histone H4K16ac.
messages: The bromo domain is required for localization to DNA damage sites.

9606:AMIGO3
gene id: 9606:AMIGO3
uniprot id: Q86WK7
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the immunoglobulin superfamily. AMIGO family.
messages: Binds AMIGO1 or AMIGO2.
messages: May mediate heterophilic cell-cell interaction. May contribute to signal transduction through its intracellular domain (By similarity).
messages: Membrane

9606:PGLYRP2
gene id: 9606:PGLYRP2
uniprot id: Q96PD5
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the N-acetylmuramoyl-L-alanine amidase 2 family.
messages: Major isoform.
messages: May be due to an intron retention.
messages: May play a scavenger role by digesting biologically active peptidoglycan (PGN) into biologically inactive fragments. Has no direct bacteriolytic activity.
messages: Membrane
messages: Secreted
messages: Strongly expressed in liver and fetal liver, and secreted into serum. Expressed to a much lesser extent in transverse colon, lymph nodes, heart, thymus, pancreas, descending colon, stomach and testis. Isoform 2 is not detected in the liver or serum.

9606:ST13
gene id: 9606:ST13
uniprot id: A0A140VKA6
uniprot id: B4E0U6
uniprot id: P50502
uniprot id: Q0IJ56
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the FAM10 family.
messages: Cytoplasm
messages: Homotetramer. Interacts with HSC70 as well as DNAJ homologs and HSP90 (By similarity). Interacts (via the C-terminus 303- 319 AA) with GRK5.
messages: One HIP oligomer binds the ATPase domains of at least two HSC70 molecules dependent on activation of the HSC70 ATPase by HSP40. Stabilizes the ADP state of HSC70 that has a high affinity for substrate protein. Through its own chaperone activity, it may contribute to the interaction of HSC70 with various target proteins (By similarity).

9606:ZNF705B
gene id: 9606:ZNF705B
uniprot id: P0CI00
names: Caution
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: Could be the product of a pseudogene.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:PPP2R5A
gene id: 9606:PPP2R5A
uniprot id: Q15172
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the phosphatase 2A regulatory subunit B56 family.
messages: Cytoplasm
messages: Nucleus
messages: PP2A consists of a common heterodimeric core enzyme, composed of a 36 kDa catalytic subunit (subunit C) and a 65 kDa constant regulatory subunit (PR65 or subunit A), that associates with a variety of regulatory subunits. Proteins that associate with the core dimer include three families of regulatory subunits B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56 families), the 48 kDa variable regulatory subunit, viral proteins, and cell signaling molecules. Interacts with SGO1.
messages: Phosphorylated on serine residues.
messages: The B regulatory subunit might modulate substrate selectivity and catalytic activity, and also might direct the localization of the catalytic enzyme to a particular subcellular compartment.
messages: Widely expressed with the highest expression in heart and skeletal muscle.
messages: centromere

9606:PCP4
gene id: 9606:PCP4
uniprot id: P48539
names: Domain
names: Function
names: Similarity
names: Subunit
messages: Belongs to the PCP4 family.
messages: Binds to both calcium-free and calcium-bound calmodulin. The affinity for the calcium-bound form is 50-fold greater.
messages: Functions as a modulator of calcium-binding by calmodulin. Thereby, regulates calmodulin activity and the different processes it controls (PubMed:19106096, PubMed:23204517, PubMed:27876793). For instance, may play a role in neuronal differentiation through activation of calmodulin-dependent kinase signaling pathways (PubMed:21491429).
messages: Mostly intrinsically disordered, with residual structure localized to the IQ domain which mediates the interaction with calmodulin.

9606:OPRPN
gene id: 9606:OPRPN
uniprot id: Q99935
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Abundantly expressed in lacrimal gland where it found in the secretory endpieces. Also expressed at modest levels in the submandibular gland.
messages: Belongs to the PROL1/PROL3 family.
messages: Opiorphin is an endogenous inhibitor of neprilysin and aminopeptidase N. Inhibits the breakdown of substance P, Mca-BK2 and Met-enkephalin by neprilysin in vitro with IC(50) values of 29 uM, 33 uM and 33 uM respectively. Inhibits the breakdown of Ala-pNA by aminopeptidase N in vitro with an IC(50) of 65 uM. Has a potent analgesic effect when administered to rats by intravenous injection.
messages: Secreted

9606:BTBD8
gene id: 9606:BTBD8
uniprot id: Q5XKL5
names: Developmental Stage
names: Function
names: Miscellaneous
names: Sequence Caution
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Contaminating sequence. Premature poly-A sequence.
messages: Expressed mainly in fetal tissues.
messages: Highly expressed in fetal brain. Weakly expressed in adult brain and prostate.
messages: Interacts (via N-terminus) with adapter protein complex AP-2 subunits alpha (AP2A1) and beta (AP2B1).
messages: Involved in clathrin-mediated endocytosis at the synapse. Plays a role in neuronal development and in synaptic vesicle recycling in mature neurons, a process required for normal synaptic transmission.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Nucleus
messages: Presynapse
messages: Probable cloning artifact.
messages: axon
messages: clathrin-coated vesicle

9606:MEOX1
gene id: 9606:MEOX1
uniprot id: P50221
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
messages: Cytoplasm
messages: Mesodermal transcription factor that plays a key role in somitogenesis and is specifically required for sclerotome development. Required for maintenance of the sclerotome polarity and formation of the cranio-cervical joints (PubMed:23290072, PubMed:24073994). Binds specifically to the promoter of target genes and regulates their expression. Activates expression of NKX3-2 in the sclerotome. Activates expression of CDKN1A and CDKN2A in endothelial cells, acting as a regulator of vascular cell proliferation. While it activates CDKN1A in a DNA-dependent manner, it activates CDKN2A in a DNA-independent manner. Required for hematopoietic stem cell (HSCs) induction via its role in somitogenesis: specification of HSCs occurs via the deployment of a specific endothelial precursor population, which arises within a sub-compartment of the somite named endotome.
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:TSR1
gene id: 9606:TSR1
uniprot id: Q2NL82
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the TRAFAC class translation factor GTPase superfamily. Bms1-like GTPase family. TSR1 subfamily.
messages: Required during maturation of the 40S ribosomal subunit in the nucleolus.
messages: nucleolus

9606:DXO
gene id: 9606:DXO
uniprot id: A0A024RCW8
uniprot id: O77932
names: Cofactor
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the DXO/Dom3Z family.
messages: Binds 2 magnesium ions.
messages: Decapping enzyme for NAD-capped RNAs: specifically hydrolyzes the nicotinamide adenine dinucleotide (NAD) cap from a subset of RNAs by removing the entire NAD moiety from the 5'-end of an NAD-capped RNA (PubMed:28283058). The NAD-cap is present at the 5'-end of some RNAs and snoRNAs (PubMed:28283058). In contrast to the canonical 5'-end N7 methylguanosine (m7G) cap, the NAD cap promotes mRNA decay (PubMed:28283058). Preferentially acts on NAD-capped transcripts in response to environmental stress (PubMed:31101919). Also acts as a non-canonical decapping enzyme that removes the entire cap structure of m7G capped or incompletely capped RNAs and mediates their subsequent degradation (By similarity). Specifically degrades pre-mRNAs with a defective 5'-end m7G cap and is part of a pre-mRNA capping quality control (By similarity). Has decapping activity toward incomplete 5'-end m7G cap mRNAs such as unmethylated 5'-end-capped RNA (cap0), while it has no activity toward 2'-O-ribose methylated m7G cap (cap1) (PubMed:29601584). In contrast to canonical decapping enzymes DCP2 and NUDT16, which cleave the cap within the triphosphate linkage, the decapping activity releases the entire cap structure GpppN and a 5'-end monophosphate RNA (By similarity). Also has 5'-3' exoribonuclease activities: The 5'-end monophosphate RNA is then degraded by the 5'-3' exoribonuclease activity, enabling this enzyme to decap and degrade incompletely capped mRNAs (PubMed:29601584). Also possesses RNA 5'-pyrophosphohydrolase activity by hydrolyzing the 5'-end triphosphate to release pyrophosphates (By similarity). Exhibits decapping activity towards FAD-capped RNAs (PubMed:32374864). Exhibits decapping activity towards dpCoA-capped RNAs in vitro (By similarity).
messages: Decapping enzyme for NAD-capped RNAs: specifically hydrolyzes the nicotinamide adenine dinucleotide (NAD) cap from a subset of RNAs by removing the entire NAD moiety from the 5'-end of an NAD-capped RNA.
messages: Nucleus
messages: Ubiquitously expressed.

9606:DCAF12L2
gene id: 9606:DCAF12L2
uniprot id: Q5VW00
names: Similarity
messages: Belongs to the WD repeat DCAF12 family.

9606:INTS6
gene id: 9606:INTS6
uniprot id: Q9UL03
names: Function
names: Induction
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the Integrator subunit 6 family.
messages: Belongs to the multiprotein complex Integrator, at least composed of INTS1, INTS2, INTS3, INTS4, INTS5, INTS6, INTS7, INTS8, INTS9/RC74, INTS10, INTS11/CPSF3L and INTS12.
messages: Component of the Integrator (INT) complex, a complex involved in the small nuclear RNAs (snRNA) U1 and U2 transcription and in their 3'-box-dependent processing. The Integrator complex is associated with the C-terminal domain (CTD) of RNA polymerase II largest subunit (POLR2A) and is recruited to the U1 and U2 snRNAs genes (Probable). Mediates recruitment of cytoplasmic dynein to the nuclear envelope, probably as component of the INT complex (PubMed:23904267). May have a tumor suppressor role; an ectopic expression suppressing tumor cell growth (PubMed:15254679, PubMed:16239144).
messages: Contaminating sequence. Potential poly-A sequence.
messages: Frequently down-regulated in nonsmall cell lung carcinomas and prostate cancers. Down-regulation in prostate cancer is due to CpG hypermethylation of its promoter. However, some involvement in cancer is unclear.
messages: Nucleus
messages: Widely expressed. Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.

9606:LINGO1
gene id: 9606:LINGO1
uniprot id: Q96FE5
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cell membrane
messages: Expressed exclusively in the central nervous system. Highest level in the in amygdala, hippocampus, thalamus and cerebral cortex. In the rest of the brain a basal expression seems to be always present. Up-regulated in substantia nigra neurons from Parkinson disease patients.
messages: Functional component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors (PubMed:14966521, PubMed:15694321). Is also an important negative regulator of oligodentrocyte differentiation and axonal myelination (PubMed:15895088). Acts in conjunction with RTN4 and RTN4R in regulating neuronal precursor cell motility during cortical development (By similarity).
messages: Homotetramer (PubMed:17005555). Forms a ternary complex with RTN4R/NGFR and RTN4R/TNFRSF19 (PubMed:14966521, PubMed:15694321, PubMed:17005555). Interacts with NGRF and MYT1L (By similarity). Interacts with RTN4R (PubMed:19052207).
messages: N-glycosylated. Contains predominantly high-mannose glycans.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The intracellular domain of LINGO1 interacts with MYT1L.

9606:AR
gene id: 9606:AR
uniprot id: F1D8N5
uniprot id: P10275
names: Activity Regulation
names: Caution
names: Disease Annotation
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: AIM-100 (4-amino-5,6-biaryl-furo[2,3-d]pyrimidine) suppresses TNK2-mediated phosphorylation at Tyr-269. Inhibits the binding of the Tyr-269 phosphorylated form to androgen-responsive enhancers (AREs) and its transcriptional activity.
messages: Belongs to the nuclear hormone receptor family.
messages: Belongs to the nuclear hormone receptor family. NR3 subfamily.
messages: Binds DNA as a homodimer. Part of a ternary complex containing AR, EFCAB6/DJBP and PARK7. Interacts with HIPK3 and NR0B2 in the presence of androgen. The ligand binding domain interacts with KAT7/HBO1 in the presence of dihydrotestosterone. Interacts with EFCAB6/DJBP, PQBP1, RANBP9, RBAK, SPDEF, SRA1, TGFB1I1 and RREB1. Interacts with ZMIZ1/ZIMP10 and ZMIZ2/ZMIP7 which both enhance its transactivation activity. Interacts with SLC30A9 and RAD54L2/ARIP4. Interacts with MACROD1 (via macro domain) (PubMed:19022849). Interacts via the ligand-binding domain with LXXLL and FXXLF motifs from NCOA1, NCOA2, NCOA3, NCOA4 and MAGEA11. The AR N-terminal poly-Gln region binds Ran resulting in enhancement of AR-mediated transactivation. Ran-binding decreases as the poly-Gln length increases. Interacts with HIP1 (via coiled coil domain). Interacts (via ligand-binding domain) with TRIM68. Interacts with TNK2. Interacts with USP26. Interacts with RNF6. Interacts (regulated by RNF6 probably through polyubiquitination) with RNF14; regulates AR transcriptional activity. Interacts with PRMT2 and TRIM24. Interacts with RACK1. Interacts with RANBP10; this interaction enhances dihydrotestosterone-induced AR transcriptional activity. Interacts with PRPF6 in a hormone-independent way; this interaction enhances dihydrotestosterone-induced AR transcriptional activity. Interacts with STK4/MST1. Interacts with ZIPK/DAPK3. Interacts with LPXN. Interacts with MAK. Part of a complex containing AR, MAK and NCOA3. Interacts with CRY1. Interacts with CCAR1 and GATA2. Interacts with ZNF318 (By similarity). Interacts with BUD31 (PubMed:25091737). Interacts with ARID4A (PubMed:23487765). Interacts with ARID4B (By similarity). Interacts (via NR LBD domain) with ZBTB7A; the interaction is direct and androgen-dependent (PubMed:20812024). Interacts with NCOR1 (PubMed:20812024). Interacts with NCOR2 (PubMed:20812024). Interacts with CRY2 in a ligand-dependent manner (By similarity).
messages: Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain. In the presence of bound steroid the ligand-binding domain interacts with the N-terminal modulating domain, and thereby activates AR transcription factor activity. Agonist binding is required for dimerization and binding to target DNA. The transcription factor activity of the complex formed by ligand-activated AR and DNA is modulated by interactions with coactivator and corepressor proteins (PubMed:25091737). Interaction with RANBP9 is mediated by both the N-terminal domain and the DNA-binding domain. Interaction with EFCAB6/DJBP is mediated by the DNA-binding domain.
messages: Cytoplasm
messages: Defects in AR may play a role in metastatic prostate cancer. The mutated receptor stimulates prostate growth and metastases development despite of androgen ablation. This treatment can reduce primary and metastatic lesions probably by inducing apoptosis of tumor cells when they express the wild-type receptor.
messages: Expressed in basal and stromal cells of the prostate (at protein level).
messages: Had previously been shown to interact with PELP1. However this paper was retracted as cell-based data was viewed as unreliable.
messages: In the absence of ligand, steroid hormone receptors are thought to be weakly associated with nuclear components; hormone binding greatly increases receptor affinity. The hormone-receptor complex appears to recognize discrete DNA sequences upstream of transcriptional start sites.
messages: Lacks the C-terminal ligand-binding domain and may therefore constitutively activate the transcription of a specific set of genes independently of steroid hormones.
messages: Mainly expressed in heart and skeletal muscle.
messages: Minor isoform identified in prostate cancer cells.
messages: Minor isoform up-regulated in prostate cancer cells.
messages: Nucleus
messages: Palmitoylated by ZDHHC7 and ZDHHC21. Palmitoylation is required for plasma membrane targeting and for rapid intracellular signaling via ERK and AKT kinases and cAMP generation.
messages: Phosphorylated in prostate cancer cells in response to several growth factors including EGF. Phosphorylation is induced by c-Src kinase (CSK). Tyr-535 is one of the major phosphorylation sites and an increase in phosphorylation and Src kinase activity is associated with prostate cancer progression. Phosphorylation by TNK2 enhances the DNA-binding and transcriptional activity and may be responsible for androgen-independent progression of prostate cancer. Phosphorylation at Ser-83 by CDK9 regulates AR promoter selectivity and cell growth. Phosphorylation by PAK6 leads to AR-mediated transcription inhibition.
messages: Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues (PubMed:19022849). Transcription factor activity is modulated by bound coactivator and corepressor proteins like ZBTB7A that recruits NCOR1 and NCOR2 to the androgen response elements/ARE on target genes, negatively regulating androgen receptor signaling and androgen-induced cell proliferation (PubMed:20812024). Transcription activation is also down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3.
messages: Sumoylated on Lys-388 (major) and Lys-521. Ubiquitinated. Deubiquitinated by USP26. 'Lys-6' and 'Lys-27'-linked polyubiquitination by RNF6 modulates AR transcriptional activity and specificity.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The disease is caused by variants affecting the gene represented in this entry. Caused by trinucleotide CAG repeat expansion. In SMAX1 patients the number of Gln ranges from 38 to 62. Longer expansions result in earlier onset and more severe clinical manifestations of the disease.
messages: The level of tyrosine phosphorylation may serve as a diagnostic tool to predict patient outcome in response to hormone-ablation therapy. Inhibition of tyrosine phosphorylation may be an effective intervention target for hormone-refractory prostate cancer.
messages: The poly-Gln region of AR is highly polymorphic and the number of Gln varies in the population (from 17 to 26). A smaller size of the poly-Gln region may be associated with the development of prostate cancer. Long poly-Gln alleles (>23) may be associated with higher testosterone levels and severe clinical outcome in COVID-19 disease (PubMed:33647767).
messages: The poly-Gly region of AR is polymorphic and ranges from 24 to 31 Gly. A poly-Gly region shorter or equal to 23 may be associated with the development of androgenetic alopecia.
messages: Transcriptional activity is enhanced by binding to RANBP9.

9606:CILP2
gene id: 9606:CILP2
uniprot id: Q8IUL8
names: Function
names: PTM
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Expressed in articular chondrocytes but not in knee meniscal cartilage cells (PubMed:12746903). Localizes to the intermediate to deep zone of articular cartilage (PubMed:21880736).
messages: May be cleaved into 2 chains possibly by a furin-like protease upon or preceding secretion.
messages: May play a role in cartilage scaffolding.
messages: extracellular matrix

9606:ZNF729
gene id: 9606:ZNF729
uniprot id: A6NN14
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:ERMAP
gene id: 9606:ERMAP
uniprot id: A0A1C9HIH9
uniprot id: Q96PL5
names: Developmental Stage
names: Function
names: PTM
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the immunoglobulin superfamily. BTN/MOG family.
messages: Cell membrane
messages: Cytoplasm
messages: ERMAP is responsible for the Scianna/Radin blood group system which comprises seven different antigens (PubMed:12393480). The Sc1 and Sc2 antigens are resulting from a single variation in position 57; Arg-57 corresponds to the Sc2 antigen and Gly-57 to the Sc1 antigen. The Sc2 antigen is rare with an occurrence of less than 1% in the population while Sc1 is more frequent. Sc3 is not expressed by individuals homozygous for a null allele encoding a truncated protein lacking its extracellular part (Sc-3). The Sc4 antigen corresponding to the previously defined Radin blood group antigen (Rd) is due to a single variation in position 60; Ala-60 corresponds to Sc4/Rd(+), the antigenic form of the protein. Sc4 is found in less than 1% of the population. Sc5/STAR, Sc6/SCER and Sc7/SCAN antigens are due to single variations in positions 47, 81 and 35 respectively. Alloantibodies to the low frequency Sc2 and Sc4 antigens are the cause of hemolytic disease in the newborn (PubMed:15660834, PubMed:16371048).
messages: Expressed in erythroid-enriched bone marrow (at protein level). Highly expressed in bone marrow and to a lower extent in leukocytes, thymus, lymph node and spleen.
messages: Expressed in fetal liver blood cells (at protein level). Highly expressed in fetal liver.
messages: Glycosylated.
messages: Membrane
messages: Possible role as a cell-adhesion or receptor molecule of erythroid cells.

9606:GPR27
gene id: 9606:GPR27
uniprot id: Q9NS67
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Highly expressed as a 3.0 kb transcript in brain, ovary, testis, heart, prostate and peripheral Leukocytes. Lower levels in pancreas and small intestine. A 2.3 kb transcript was also found in peripheral Leukocytes. In brain regions, detected as a 3.0 kb transcript in all regions tested. Highest levels in the caudate nucleus, putamen, hippocampus and subthalamic nucleus. Lowest level in the cerebellum.
messages: Orphan receptor. Possible candidate for amine-like G-protein coupled receptor.

9606:EBF2
gene id: 9606:EBF2
uniprot id: B2RNT0
uniprot id: B7Z934
uniprot id: Q9HAK2
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the COE family.
messages: Forms either a homodimer or a heterodimer with a related family member (By similarity). Interacts with SIX1 (PubMed:27923061).
messages: Nucleus
messages: Transcription factor that, in osteoblasts, activates the decoy receptor for RANKL, TNFRSF11B, which in turn regulates osteoclast differentiation. Acts in synergy with the Wnt-responsive LEF1/CTNNB1 pathway. Recognizes variations of the palindromic sequence 5'-ATTCCCNNGGGAATT-3' (By similarity).

9606:IL17RA
gene id: 9606:IL17RA
uniprot id: Q96F46
names: Disease Annotation
names: Function
names: Miscellaneous
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts with SARS coronavirus-2/SARS-CoV-2 virus protein ORF8.
messages: (Microbial infection) Receptor for SARS coronavirus-2/SARS-CoV-2 virus protein ORF8, leading to IL17 pathway activation and an increased secretion of pro-inflammatory factors through activating NF-kappa-B signaling pathway.
messages: Cell membrane
messages: Forms heterodimers with IL17RC; the heterodimer binds IL17A and IL17F homodimers as well as the heterodimer formed by IL17A and IL17F (PubMed:16785495, PubMed:18684971, PubMed:32187518). Forms complexes with 2:1 binding stoichiometry: two receptor chains for one interleukin molecule (PubMed:32187518). IL17A homodimer preferentially drives the formation of IL17RA-IL17RC heterodimeric receptor complex, whereas IL17F homodimer forms predominantly complexes with IL17RC homodimer (PubMed:32187518). IL17A homodimer adopts an asymmetrical ternary structure with one IL17RA molecule, allowing for high affinity interactions of one IL17A monomer with one IL17RA molecule (via D1 and D2 domains), while disfavoring binding of a second IL17RA molecule on the other IL17A monomer (PubMed:23695682). IL17A-IL17F forms complexes with IL17RA-IL17RC, but with lower affinity when compared to IL17A homodimer (PubMed:32187518). IL17RA chain cannot distinguish between IL17A and IL17F molecules, potentially enabling the formation of topologically distinct complexes (PubMed:28827714). Interacts with TRAF3IP2 (PubMed:24120361). Forms heterodimers with IL17RE; the heterodimer binds IL17C (PubMed:21993848, PubMed:16785495, PubMed:18684971).
messages: Glycosylated.
messages: Receptor for IL17A and IL17F, major effector cytokines of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity. Receptor for IL17A (PubMed:17911633, PubMed:9367539). Receptor for IL17F (PubMed:19838198, PubMed:17911633). Binds to IL17A with higher affinity than to IL17F (PubMed:17911633). Binds IL17A and IL17F homodimers as part of a heterodimeric complex with IL17RC (PubMed:16785495). Also binds heterodimers formed by IL17A and IL17F as part of a heterodimeric complex with IL17RC (PubMed:18684971). Cytokine binding triggers homotypic interaction of IL17RA and IL17RC chains with TRAF3IP2 adapter, leading to TRAF6-mediated activation of NF-kappa-B and MAPkinase pathways, ultimately resulting in transcriptional activation of cytokines, chemokines, antimicrobial peptides and matrix metalloproteinases, with potential strong immune inflammation (PubMed:16785495, PubMed:24120361, PubMed:17911633, PubMed:18684971, PubMed:21350122). Involved in antimicrobial host defense primarily promoting neutrophil activation and recruitment at infection sites to destroy extracellular bacteria and fungi (By similarity). In secondary lymphoid organs, contributes to germinal center formation by regulating the chemotactic response of B cells to CXCL12 and CXCL13, enhancing retention of B cells within the germinal centers, B cell somatic hypermutation rate and selection toward plasma cells (By similarity). Plays a role in the maintenance of the integrity of epithelial barriers during homeostasis and pathogen infection. Stimulates the production of antimicrobial beta-defensins DEFB1, DEFB103A, and DEFB104A by mucosal epithelial cells, limiting the entry of microbes through the epithelial barriers (By similarity). Involved in antiviral host defense through various mechanisms. Enhances immunity against West Nile virus by promoting T cell cytotoxicity. Contributes to Influenza virus clearance by driving the differentiation of B-1a B cells, …
messages: Secreted
messages: Soluble isoform lacking the transmembrane segment.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Widely expressed.

9606:CD207
gene id: 9606:CD207
uniprot id: Q9UJ71
names: Disease Annotation
names: Domain
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Calcium-dependent lectin displaying mannose-binding specificity. Induces the formation of Birbeck granules (BGs); is a potent regulator of membrane superimposition and zippering. Binds to sulfated as well as mannosylated glycans, keratan sulfate (KS) and beta-glucans. Facilitates uptake of antigens and is involved in the routing and/or processing of antigen for presentation to T cells. Major receptor on primary Langerhans cells for Candida species, Saccharomyces species, and Malassezia furfur. Protects against human immunodeficiency virus-1 (HIV-1) infection. Binds to high-mannose structures present on the envelope glycoprotein which is followed by subsequent targeting of the virus to the Birbeck granules leading to its rapid degradation.
messages: Exclusively expressed by Langerhans cells. Expressed in astrocytoma and malignant ependymoma, but not in normal brain tissues.
messages: Homotrimer.
messages: Membrane
messages: The C-type lectin domain mediates dual recognition of both sulfated and mannosylated glycans.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:PCSK2
gene id: 9606:PCSK2
uniprot id: P16519
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the peptidase S8 family. Furin subfamily.
messages: Secreted
messages: Serine endopeptidase which is involved in the processing of hormone and other protein precursors at sites comprised of pairs of basic amino acid residues. Responsible for the release of glucagon from proglucagon in pancreatic A cells.
messages: secretory vesicle

9606:OR10Z1
gene id: 9606:OR10Z1
uniprot id: A0A126GV63
uniprot id: Q8NGY1
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Membrane
messages: Odorant receptor.

9606:GAB3
gene id: 9606:GAB3
uniprot id: Q8WWW8
names: PTM
names: Similarity
names: Subunit
messages: Belongs to the GAB family.
messages: Interacts with PIK3R/p85, SHP2 and GRAP2/MONA (By similarity). May interact with Grb2.
messages: Phosphorylated on tyrosine residue(s) after macrophage colony-stimulating factor (M-CSF) receptor stimulation.

9606:GPR52
gene id: 9606:GPR52
uniprot id: F2YGU0
uniprot id: Q9Y2T5
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Expressed in brain, especially in striatum.
messages: Gs-coupled receptor activated by antipsychotics reserpine leading to an increase in intracellular cAMP and its internalization (PubMed:24587241). May play a role in locomotor activity through modulation of dopamine, NMDA and ADORA2A-induced locomotor activity. These behavioral changes are accompanied by modulation of the dopamine receptor signaling pathway in striatum (PubMed:24587241). Modulates HTT level via cAMP-dependent but PKA independent mechanisms throught activation of RAB39B that translocates HTT to the endoplasmic reticulum, thus avoiding proteasome degradation (PubMed:25738228).

9606:TMEM207
gene id: 9606:TMEM207
uniprot id: Q6UWW9
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Expressed in some signet-ring cell carcinoma, especially those showing high invasion and metastatic activity (at protein level).
messages: Interacts with WWOX.
messages: Membrane

9606:PCDHGA2
gene id: 9606:PCDHGA2
uniprot id: Q9Y5H1
names: Function
names: Subcellular Location Annotation
messages: Cell membrane
messages: Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain.

9606:HIBCH
gene id: 9606:HIBCH
uniprot id: A0A140VJL0
uniprot id: Q6NVY1
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the enoyl-CoA hydratase/isomerase family.
messages: Highly expressed in liver and kidney, also detected in heart, muscle and brain (at protein level). Not detected in lung.
messages: Hydrolyzes 3-hydroxyisobutyryl-CoA (HIBYL-CoA), a saline catabolite. Has high activity toward isobutyryl-CoA. Could be an isobutyryl-CoA dehydrogenase that functions in valine catabolism. Also hydrolyzes 3-hydroxypropanoyl-CoA.
messages: Mitochondrion
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:EAF2
gene id: 9606:EAF2
uniprot id: B4DWJ3
uniprot id: Q96CJ1
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acts as a transcriptional transactivator of TCEA1 elongation activity (By similarity). Acts as a transcriptional transactivator of ELL and ELL2 elongation activities. Potent inducer of apoptosis in prostatic and non-prostatic cell lines. Inhibits prostate tumor growth in vivo.
messages: Belongs to the EAF family.
messages: By androgen.
messages: Expressed in heart, brain, placenta, lung, skeletal muscle, kidney, pancreas, spleen, prostate, testis, small intestine, colon, adrenal, bone marrow, lymph node, spinal gland, stomach, thyroid, trachea, thymus, liver and leukocytes.
messages: Isoform 1 and isoform 2 interact with TCEA1 (By similarity). Component of the super elongation complex (SEC), at least composed of EAF1, EAF2, CDK9, MLLT3/AF9, AFF (AFF1 or AFF4), the P-TEFb complex and ELL (ELL, ELL2 or ELL3). Interacts with ELL and ELL2.
messages: Nucleus speckle

9606:MMP11
gene id: 9606:MMP11
uniprot id: B3KQS8
uniprot id: P24347
names: Cofactor
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the peptidase M10A family.
messages: Binds 1 Ca(2+) ion per subunit.
messages: Binds 2 Zn(2+) ions per subunit.
messages: Can bind about 5 Ca(2+) ions per subunit.
messages: May play an important role in the progression of epithelial malignancies.
messages: Specifically expressed in stromal cells of breast carcinomas.
messages: The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.
messages: The precursor is cleaved by a furin endopeptidase.
messages: extracellular matrix

9606:TACSTD2
gene id: 9606:TACSTD2
uniprot id: P09758
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the EPCAM family.
messages: May function as a growth factor receptor.
messages: Membrane
messages: Placenta, pancreatic carcinoma cell lines.
messages: The N-terminus is blocked.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:SETX
gene id: 9606:SETX
uniprot id: Q7Z333
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the DNA2/NAM7 helicase family.
messages: Chromosome
messages: Cytoplasm
messages: Highly expressed in skeletal muscle. Expressed in heart, fibroblast, placenta and liver. Weakly expressed in brain and lung. Expressed in the cortex of the kidney (highly expressed in tubular epithelial cells but low expression in the glomerulus).
messages: Homodimer (PubMed:24244371). Interacts with PER2; the interaction inhibits termination of circadian target genes (By similarity). Interacts with CHD4, POLR2A, PRKDC and TRIM28 (PubMed:23149945). Does not interact with C14orf178 (PubMed:24244371). Interacts with UBE2I (PubMed:24105744). Interacts (via N-terminus domain) with EXOSC9 (via C-terminus region); the interaction enhances SETX sumoylation (PubMed:24105744). Interacts with NCL (via N-terminus domain) (PubMed:19515850). Interacts with PABPN1, PABPC1 and SF3B1 (PubMed:19515850). Interacts with SMN1/SMN2 and POLR2A; SMN1/SMN2 recruits SETX to POLR2A (PubMed:19515850, PubMed:26700805).
messages: Nucleus
messages: Probable RNA/DNA helicase involved in diverse aspects of RNA metabolism and genomic integrity. Plays a role in transcription regulation by its ability to modulate RNA Polymerase II (Pol II) binding to chromatin and through its interaction with proteins involved in transcription (PubMed:19515850, PubMed:21700224). Contributes to the mRNA splicing efficiency and splice site selection (PubMed:19515850). Required for the resolution of R-loop RNA-DNA hybrid formation at G-rich pause sites located downstream of the poly(A) site, allowing XRN2 recruitment and XRN2-mediated degradation of the downstream cleaved RNA and hence efficient RNA polymerase II (RNAp II) transcription termination (PubMed:19515850, PubMed:21700224, PubMed:26700805). Required for the 3' transcriptional termination of PER1 and CRY2, thus playing an important role in the circadian rhythm regulation (By similarity). Involved in DNA double-strand breaks damage response generated by oxidative stress (PubMed:17562789). In association with RRP45, targets the RNA exosome complex to sites of transcription-induced DNA damage (PubMed:24105744). Plays a role in the development and maturation of germ cells: essential for male meiosis, acting at the interface of transcription and meiotic recombination, and in the process of gene silencing during meiotic sex chromosome inactivation (MSCI) (By similarity). May be involved in telomeric stability through the regulation of telomere repeat-containing RNA (TERRA) transcription (PubMed:21112256). Plays a role in neurite outgrowth in hippocampal cells through FGF8-activated signaling pathways. Inhibits retinoic acid-induced apoptosis (PubMed:21576111).
messages: Sumoylated preferentially with SUMO2 or SUMO3 (PubMed:24105744, PubMed:24244371).
messages: The N-terminus domain is necessary for S/G2 nuclear foci localization (PubMed:23149945).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitinated.
messages: axon
messages: growth cone
messages: nucleolus
messages: nucleoplasm
messages: telomere

9606:PDF
gene id: 9606:PDF
uniprot id: Q9HBH1
names: Cofactor
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the polypeptide deformylase family.
messages: Binds 1 Co(2+) ion.
messages: Homodimer.
messages: Mitochondrion
messages: Removes the formyl group from the N-terminal Met of newly synthesized proteins.
messages: Ubiquitous.

9606:BORA
gene id: 9606:BORA
uniprot id: A0A087WV86
uniprot id: B5LMG6
uniprot id: Q6PGQ7
names: Function
names: PTM
names: Similarity
names: Subunit
messages: Belongs to the BORA family.
messages: Interacts with AURKA.
messages: Phosphorylated by AURKA.
messages: Required for the activation of AURKA at the onset of mitosis.

9606:CRTAC1
gene id: 9606:CRTAC1
uniprot id: Q9NQ79
names: Induction
names: Miscellaneous
names: PTM
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Expressed in the interterritorial matrix of articular deep zone cartilage (at protein level). Isoform 1 and isoform 2 are expressed in brain. Isoform 1 is detected in lung and chondrocytes. Detected in cartilage, bone, cultured chondrocytes and lung, and at low levels in heart. Not detected in osteoblasts.
messages: O-glycosylated.
messages: Shares an exon with the neighboring tail-to-tail oriented gene GOLGA7B.
messages: Up-regulated by BMP4 (at protein level). Up-regulated in mesenchymal stem cells undergoing chondrogenic differentiation and by BMP4.
messages: extracellular matrix

9606:NPIPA2
gene id: 9606:NPIPA2
uniprot id: A0A0B4J2F6
uniprot id: O15103
uniprot id: Q9UND3
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the NPIP family.
messages: May associate with the nuclear pore complex.
messages: Nucleus membrane
messages: Widely expressed.
messages: nuclear pore complex

9606:TRIM9
gene id: 9606:TRIM9
uniprot id: Q9C026
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Auto-ubiquitinated. Poly-ubiquitinated in cultured cells, whereas it is monoubiquitinated in vitro.
messages: Belongs to the TRIM/RBCC family.
messages: Brain. Highly expressed in the cerebral cortex (at protein level). Severely decreased in the affected brain areas in Parkinson disease and dementia with Lewy bodies.
messages: Cytoplasm
messages: E3 ubiquitin-protein ligase which ubiquitinates itself in cooperation with an E2 enzyme UBE2D2/UBC4 and serves as a targeting signal for proteasomal degradation. May play a role in regulation of neuronal functions and may also participate in the formation or breakdown of abnormal inclusions in neurodegenerative disorders. May act as a regulator of synaptic vesicle exocytosis by controlling the availability of SNAP25 for the SNARE complex formation.
messages: Interacts with SNAP25.
messages: May be due to a competing donor splice site, to exon inclusion and to intron retention.
messages: May be due to intron retention.
messages: Synapse
messages: The coiled coil domain mediates the interaction with the N-terminal t-SNARE domain of SNAP25.
messages: cytoskeleton
messages: dendrite
messages: synaptic vesicle

9606:SLU7
gene id: 9606:SLU7
uniprot id: O95391
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the SLU7 family.
messages: Component of pre-catalytic, catalytic and post-catalytic spliceosomes (PubMed:10197984, PubMed:28502770, PubMed:30705154). Associates with the spliceosome prior to recognition of the 3'-splice site for step II, probably during catalysis of step I (PubMed:10197984).
messages: Cytoplasm
messages: Nucleus
messages: Nucleus speckle
messages: Required for pre-mRNA splicing as component of the spliceosome (PubMed:10197984, PubMed:28502770, PubMed:30705154). Participates in the second catalytic step of pre-mRNA splicing, when the free hydroxyl group of exon I attacks the 3'-splice site to generate spliced mRNA and the excised lariat intron. Required for holding exon 1 properly in the spliceosome and for correct AG identification when more than one possible AG exists in 3'-splicing site region. May be involved in the activation of proximal AG. Probably also involved in alternative splicing regulation.
messages: The CCHC-type zinc finger is required to retain the protein within the nucleus and prevent its shuttle back to the cytoplasm via the CRM1 pathway.

9606:HP
gene id: 9606:HP
uniprot id: A0A0C4DGL8
uniprot id: P00738
names: Caution
names: Disease Annotation
names: Function
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Although homologous to serine proteases, it has lost all essential catalytic residues and has no enzymatic activity.
messages: As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of heme iron and to prevent kidney damage. Haptoglobin also acts as an antioxidant, has antibacterial activity and plays a role in modulating many aspects of the acute phase response. Hemoglobin/haptoglobin complexes are rapidly cleared by the macrophage CD163 scavenger receptor expressed on the surface of liver Kupfer cells through an endocytic lysosomal degradation pathway.
messages: As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of heme iron and to prevent kidney damage. Haptoglobin also acts as an antioxidant, has antibacterial activity, and plays a role in modulating many aspects of the acute phase response. Hemoglobin/haptoglobin complexes are rapidly cleared by the macrophage CD163 scavenger receptor expressed on the surface of liver Kupfer cells through an endocytic lysosomal degradation pathway.
messages: Belongs to the peptidase S1 family.
messages: Expressed by the liver and secreted in plasma.
messages: In human populations there are two major allelic forms, alpha-1 (1-1) with 83 residues and alpha-2 (2-2) with 142 residues. These alleles determine 3 possible genotypes, homozygous (1-1 or 2-2) and heterozygous (2-1), and 3 major phenotypes HP*1F/HP*1S and HP*2FS. The two main alleles of HP*1 are called HP*1F (fast) and HP*1S (slow). The alleles exhibit different oligomerization properties. In healthy males, but not in females, the Hp 2-2 phenotype is associated with higher serum iron, decreased antimicrobial and antioxidant capability, and less efficient clearance from the circulation, than Hp 1-1 and 2-1. The sequence displayed in this entry corresponds to allele alpha-2 (2-2).
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: Secreted
messages: Tetramer of two alpha and two beta chains; disulfide-linked (By similarity). The hemoglobin/haptoglobin complex is composed of a haptoglobin dimer bound to two hemoglobin alpha-beta dimers (By similarity). Interacts with CD163 (By similarity). Interacts with ERGIC3.
messages: Tetramer of two alpha and two beta chains; disulfide-linked (PubMed:6997877, PubMed:4573324). The hemoglobin/haptoglobin complex is composed of a haptoglobin dimer bound to two hemoglobin alpha-beta dimers (By similarity). Interacts with CD163 (By similarity). Interacts with ERGIC3 (PubMed:31142615).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The uncleaved form of allele alpha-2 (2-2), known as zonulin, plays a role in intestinal permeability, allowing intercellular tight junction disassembly, and controlling the equilibrium between tolerance and immunity to non-self antigens.

9606:ZNF224
gene id: 9606:ZNF224
uniprot id: Q9NZL3
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: Interacts with WT1. Interacts with DEPDC1A.
messages: May be involved in transcriptional regulation as a transcriptional repressor. The DEPDC1A-ZNF224 complex may play a critical role in bladder carcinogenesis by repressing the transcription of the A20 gene, leading to transport of NF-KB protein into the nucleus, resulting in suppression of apoptosis of bladder cancer cells.
messages: Nucleus
messages: Ubiquitous. Mainly expressed in fetal tissues.

9606:ACOX1
gene id: 9606:ACOX1
uniprot id: Q15067
names: Disease Annotation
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the acyl-CoA oxidase family.
messages: Homodimer (PubMed:32169171). Interacts with LONP2 (PubMed:18281296).
messages: Involved in the initial and rate-limiting step of peroxisomal beta-oxidation of straight-chain saturated and unsaturated very-long-chain fatty acids (PubMed:7876265, PubMed:15060085, PubMed:17458872, PubMed:17603022, PubMed:32169171, PubMed:33234382). Catalyzes the desaturation of fatty acyl-CoAs such as palmitoyl-CoA (hexadecanoyl-CoA) to 2-trans-enoyl-CoAs ((2E)-enoyl-CoAs) such as (2E)-hexadecenoyl-CoA, and donates electrons directly to molecular oxygen (O(2)), thereby producing hydrogen peroxide (H(2)O(2)) (PubMed:7876265, PubMed:17458872, PubMed:17603022).
messages: Is active against a much broader range of substrates and shows activity towards long-chain fatty acyl-CoAs.
messages: Isoform 1 and isoform 2 can reverse the Acox1 null phenotype in mouse which is characterized by severe microvesicular hepatic steatosis, sustained activation of PPARA, spontaneous massive peroxisome proliferation and eventual development of hepatocellular carcinomas. Isoform 2 is more effective in reversal of the phenotype than isoform 1 (PubMed:20195242).
messages: Peroxisome
messages: Shows highest activity against medium-chain fatty acyl-CoAs. Shows optimum activity with a chain length of 10 carbons (decanoyl-CoA) in vitro.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The gene represented in this entry is involved in disease pathogenesis.
messages: Widely expressed with highest levels of isoform 1 and isoform 2 detected in testis. Isoform 1 is expressed at higher levels than isoform 2 in liver and kidney while isoform 2 levels are higher in brain, lung, muscle, white adipose tissue and testis. Levels are almost equal in heart.

9606:AVPI1
gene id: 9606:AVPI1
uniprot id: Q5T686
names: Function
messages: May be involved in MAP kinase activation, epithelial sodium channel (ENaC) down-regulation and cell cycling.

9606:TSPAN17
gene id: 9606:TSPAN17
uniprot id: J3KNG2
uniprot id: Q96FV3
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the tetraspanin (TM4SF) family.
messages: Interacts with ADAM10.
messages: Membrane
messages: Regulates ADAM10 maturation.

9606:FRA10AC1
gene id: 9606:FRA10AC1
uniprot id: Q70Z53
names: Disease Annotation
names: Function
names: Polymorphism
names: Sequence Caution
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Chimeric cDNA.
messages: Expansion of a polymorphic CGG repeat within the 5'-UTR of FRA10AC1 results in expression of the folate-sensitive fragile site FRA10A. The number of the CGG repeats normally varies in the population from 8 to 14. In contrast, individuals cytogenetically expressing the fragile site have at least 200 CGG repeats (PubMed:15203205). No distinct phenotype has been associated with expression of FRA10A. Nevertheless, some studies have proposed that this fragile site expression might be associated with intellectual disability, tumorigenesis, or neurological disorders. However, these associations can be attributed to ascertainment bias.
messages: Interacts with ESS2.
messages: May be involved in pre-mRNA splicing.
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitously expressed with higher expression in brain, heart, skeletal muscle, kidney and liver.

9606:SLC15A1
gene id: 9606:SLC15A1
uniprot id: B2CQT6
uniprot id: P46059
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Apical cell membrane
messages: Belongs to the major facilitator superfamily. Proton-dependent oligopeptide transporter (POT/PTR) (TC 2.A.17) family.
messages: Electrogenic proton-coupled amino-acid transporter that transports oligopeptides of 2 to 4 amino acids with a preference for dipeptides. Transports neutral and monovalently charged peptides with a proton to peptide stoichiometry of 1:1 or 2:1 (PubMed:7896779, PubMed:9835627, PubMed:8914574, PubMed:15521010, PubMed:18367661, PubMed:19685173, PubMed:26320580) (By similarity). Primarily responsible for the absorption of dietary di- and tripeptides from the small intestinal lumen (By similarity). Mediates transepithelial transport of muramyl and N-formylated bacterial dipeptides contributing to recognition of pathogenic bacteria by the mucosal immune system (PubMed:9835627, PubMed:15521010).
messages: Expressed in small intestine.
messages: Interacts (via extracellular domain region) with trypsin.
messages: Membrane
messages: The extracellular domain (ECD) region specifically binds trypsin.

9606:RARRES2
gene id: 9606:RARRES2
uniprot id: A0A090N7U9
uniprot id: Q99969
names: Caution
names: Function
names: Induction
names: PTM
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Adipocyte-secreted protein (adipokine) that regulates adipogenesis, metabolism and inflammation through activation of the chemokine-like receptor 1 (CMKLR1). Acts also as a ligand for CMKLR2. Can also bind to C-C chemokine receptor-like 2 (CCRL2), but with a lower affinity than it does to CMKLR1 or CMKLR2 (PubMed:27716822). Positively regulates adipocyte differentiation, modulates the expression of adipocyte genes involved in lipid and glucose metabolism and might play a role in angiogenesis, a process essential for the expansion of white adipose tissue. Also acts as a pro-inflammatory adipokine, causing an increase in secretion of pro-inflammatory and prodiabetic adipokines, which further impair adipose tissue metabolic function and have negative systemic effects including impaired insulin sensitivity, altered glucose and lipid metabolism, and a decrease in vascular function in other tissues. Can have both pro- and anti-inflammatory properties depending on the modality of enzymatic cleavage by different classes of proteases. Acts as a chemotactic factor for leukocyte populations expressing CMKLR1, particularly immature plasmacytoid dendritic cells, but also immature myeloid DCs, macrophages and natural killer cells. Exerts an anti-inflammatory role by preventing TNF/TNFA-induced VCAM1 expression and monocytes adhesion in vascular endothelial cells. The effect is mediated via inhibiting activation of NF-kappa-B and CRK/p38 through stimulation of AKT1/NOS3 signaling and nitric oxide production. Its dual role in inflammation and metabolism might provide a link between chronic inflammation and obesity, as well as obesity-related disorders such as type 2 diabetes and cardiovascular disease. Exhibits an antimicrobial function in the skin.
messages: Expressed at the highest levels in placenta, liver, and white adipose tissue (WAT), and to a lesser extent in many other tissues such as lung, brown adipose tissue, heart, ovary, kidney, skeletal muscle and pancreas. Within WAT, expression is enriched in adipocytes as compared to the stromal vascular fraction. Expression and secretion increases dramatically with adipogenesis. Highly expressed in skin (basal and suprabasal layers of the epidermis, hair follicles and endothelial cells). Expression is elevated in numerous metabolic and inflammatory diseases including psoriasis, obesity, type 2 diabetes, metabolic syndrome and cardiovascular disease.
messages: Inhibited in psoriatic lesions. Activated by tazarotene in skin rafts and in the epidermis of psoriatic lesions.
messages: Secreted
messages: Secreted in an inactive precursor form, prochemerin, which is proteolytically processed by a variety of extracellular proteases to generate forms with differing levels of bioactivity. For example, the removal of six amino acids results in chemerin-157, which exhibits the highest activity, while removal of seven amino acids results in chemerin-156 which has slightly less activity. Some proteases are able to cleave at more than one site and chemerin forms may be sequentially processed by different enzymes to modulate activity levels. The coordinated expression and activity of chemerin-modifying enzymes is essential for regulating its bioactivation, inactivation and, consequently, biological function. Cathepsin G cleaves seven C-terminal amino acids from prochemerin (chemerin-156), elastase is able to cleave six (chemerin-157), eight (chemerin-155) or eleven (chemerin-152), plasmin cleaves five amino acids (chemerin-158), and tryptase cleaves five (chemerin-158) or eight (chemerin-155). Multiple cleavages might be required to fully activate chemerin, with an initial tryptase cleavage resulting in chemerin with low activity (chemerin-158), and a second cleavage by carboxypeptidase N or B producing highly active chemerin (chemerin-157).
messages: The sequence shown here is derived from an EMBL/GenBank/DDBJ whole genome shotgun (WGS) entry which is preliminary data.

9606:OR1E1
gene id: 9606:OR1E1
uniprot id: P30953
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Odorant receptor.

9606:CNOT1
gene id: 9606:CNOT1
uniprot id: A5YKK6
names: Developmental Stage
names: Disease Annotation
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the CNOT1 family.
messages: Component of the CCR4-NOT complex; distinct complexes seem to exist that differ in the participation of probably mutually exclusive catalytic subunits (PubMed:10637334, PubMed:16778766, PubMed:19558367, PubMed:22977175). In the complex, interacts directly with CNOT6, CNOT6L, CNOT7 or CNOT8 (PubMed:10637334, PubMed:16778766, PubMed:22977175). Interacts in a ligand-dependent fashion with ESR1 and RXRA (PubMed:16778766). Interacts with NANOS2, TOB1 and ZFP36 (PubMed:18377426, PubMed:21278420, PubMed:23644599). Interacts with TNRC6A, TNRC6B or TNRC6C; the interactions are direct (PubMed:21981923, PubMed:21984185). Interacts with YTHDF2; the interaction is direct and promotes recruitment of the CCR4-NOT complex to N6-methyladenosine (m6A)-containing mRNAs, leading to their deadenylation and subsequent degradation (PubMed:27558897). Interacts with EIF4ENIF1/4E-T (PubMed:26027925, PubMed:27342281, PubMed:32354837, PubMed:26489469).
messages: Contains Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs, a motif known to be important for the association with nuclear receptors.
messages: Expressed in embryonic stem (ES) cells.
messages: Nucleus
messages: P-body
messages: Scaffolding component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. Its scaffolding function implies its interaction with the catalytic complex module and diverse RNA-binding proteins mediating the complex recruitment to selected mRNA 3'UTRs. Involved in degradation of AU-rich element (ARE)-containing mRNAs probably via association with ZFP36. Mediates the recruitment of the CCR4-NOT complex to miRNA targets and to the RISC complex via association with TNRC6A, TNRC6B or TNRC6C. Acts as a transcriptional repressor. Represses the ligand-dependent transcriptional activation by nuclear receptors. Involved in the maintenance of embryonic stem (ES) cell identity.
messages: Strongly expressed in brain, heart, thymus, spleen, kidney, liver, placenta and lung. Weakly expressed in skeletal muscle and colon.
messages: The disease may be caused by variants affecting the gene represented in this entry.

9606:OXER1
gene id: 9606:OXER1
uniprot id: Q8TDS5
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Expressed in various tissues except brain. Expression is more intense in liver, kidney, peripheral leukocyte, lung, and spleen than in other tissues. Highly expressed in eosinophils, neutrophils, and lung macrophages.
messages: Receptor for eicosanoids and polyunsaturated fatty acids such as 5-oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-OXO-ETE), 5(S)-hydroperoxy-6E,8Z,11Z,14Z-eicosatetraenoic acid (5(S)-HPETE) and arachidonic acid. Seems to be coupled to the G(i)/G(o), families of heteromeric G proteins.

9606:LIMS1
gene id: 9606:LIMS1
uniprot id: P48059
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Adapter protein in a cytoplasmic complex linking beta-integrins to the actin cytoskeleton, bridges the complex to cell surface receptor tyrosine kinases and growth factor receptors. Involved in the regulation of cell survival, cell proliferation and cell differentiation.
messages: Cell membrane
messages: Expressed in most tissues except in the brain.
messages: Interacts (via LIM zinc-binding 5) with TGFB1I1 (By similarity). Interacts with integrin-linked protein kinase 1 (ILK) via the first LIM domain, and in competition with LIMS2. Part of the heterotrimeric IPP complex composed of integrin-linked kinase (ILK), LIMS1 or LIMS2, and PARVA. Interacts with SH3/SH2 adapter NCK2, thereby linking the complex to cell surface receptors.
messages: focal adhesion

9606:CLEC18A
gene id: 9606:CLEC18A
uniprot id: A5D8T8
names: Function
names: PTM
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Binds polysaccharides in a Ca(2+)-independent manner with a preferentially binding to fucoidan, beta-glucans and galactans (PubMed:26170455).
messages: Dectected in all cell lines tested and in peripheral blood cells.
messages: Endoplasmic reticulum
messages: Endosome
messages: Golgi apparatus
messages: N-glycosylated.
messages: Secreted

9606:TRMT1
gene id: 9606:TRMT1
uniprot id: Q9NXH9
names: Disease Annotation
names: Function
names: Similarity
messages: Belongs to the class I-like SAM-binding methyltransferase superfamily. Trm1 family.
messages: Dimethylates a single guanine residue at position 26 of most tRNAs using S-adenosyl-L-methionine as donor of the methyl groups.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:TPPP2
gene id: 9606:TPPP2
uniprot id: P59282
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the TPPP family.
messages: Expressed in spermatids (PubMed:23436708). Detected in liver cancer (at protein level) (PubMed:23436708).
messages: Probable regulator of microtubule dynamics required for sperm motility (Probable). In contrast to other members of the family, has no microtubule bundling activity (PubMed:17105200).
messages: cytosol
messages: flagellum

9606:IFI27L2
gene id: 9606:IFI27L2
uniprot id: Q9H2X8
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the IFI6/IFI27 family.
messages: Mitochondrion membrane
messages: Not up-regulated by type-I interferon.
messages: Plays a role in the apoptotic process and has a pro-apoptotic activity.

9606:MYO3B
gene id: 9606:MYO3B
uniprot id: B7ZM71
uniprot id: Q8WXR4
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.
messages: Expressed in retina, kidney and testis.
messages: In the C-terminal section; belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.
messages: In the N-terminal section; belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family.
messages: Interacts (via C-terminus) with ESPN. Interacts (via C-terminus) with ESPNL.
messages: Probable actin-based motor with a protein kinase activity. Required for normal cochlear hair bundle development and hearing. Plays an important role in the early steps of cochlear hair bundle morphogenesis. Influences the number and lengths of stereocilia to be produced and limits the growth of microvilli within the forming auditory hair bundles thereby contributing to the architecture of the hair bundle, including its staircase pattern. Involved in the elongation of actin in stereocilia tips by transporting the actin regulatory factor ESPN to the plus ends of actin filaments.
messages: cytoskeleton
messages: stereocilium

9606:SSX7
gene id: 9606:SSX7
uniprot id: Q7RTT5
names: Function
names: Similarity
names: Tissue Specificity
messages: Belongs to the SSX family.
messages: Could act as a modulator of transcription.
messages: Testis-specific. Expressed in a melanoma cell line.

9606:FAM47B
gene id: 9606:FAM47B
uniprot id: Q8NA70
names: Similarity
messages: Belongs to the FAM47 family.

9606:FBXW2
gene id: 9606:FBXW2
uniprot id: Q9UKT8
names: Function
names: Subunit
messages: Directly interacts with SKP1 and CUL1.
messages: Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex.

9606:ELOA
gene id: 9606:ELOA
uniprot id: Q14241
names: Caution
names: Domain
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: As part of a multisubunit complex composed of elongin BC complex (ELOB and ELOC), elongin A/ELOA, RBX1 and CUL5; polyubiquitinates monoubiquitinated POLR2A.
messages: Heterotrimer of an A (ELOA, ELOA2 or ELOA3P), ELOB and ELOC subunit (By similarity). Part of a multisubunit ubiquitin ligase complex consisting of elongin BC complex (ELOB and ELOC), elongin A/ELOA, RBX1 and CUL5 (PubMed:19920177). Interacts with ERCC6; the interaction is induced by DNA damaging agents or inhibitors of RNA polymerase II elongation (By similarity). Interacts (via BC-box) with CUL5 (By similarity).
messages: It is uncertain whether Met-1 or Met-27 is the initiator.
messages: Nucleus
messages: SIII, also known as elongin, is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites. Subunit A is transcriptionally active and its transcription activity is strongly enhanced by binding to the dimeric complex of the SIII regulatory subunits B and C (elongin BC complex).
messages: The BC-box, which mediates binding to the elongin BC complex, has the consensus sequence [APST]-L-x(3)-C-x(3)-[AILV].

9606:ALG1L2
gene id: 9606:ALG1L2
uniprot id: C9J202
names: Function
names: Similarity
messages: Belongs to the glycosyltransferase group 1 family.
messages: Putative glycosyltransferase.

9606:PLCB2
gene id: 9606:PLCB2
uniprot id: Q00722
uniprot id: Q59F77
names: Cofactor
names: Function
names: Miscellaneous
names: Subunit
messages: Binds 1 Ca(2+) ion per subunit.
messages: Interacts with RAC1 (PubMed:1644792). Forms a complex composed of at least WDR26, a G-beta:gamma unit, and PLCB2 (PubMed:23625927).
messages: The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes.
messages: The receptor-mediated activation of PLC-beta-2 is most effectively mediated by one G-protein alpha subunit, alpha-16.

9606:PAPOLA
gene id: 9606:PAPOLA
uniprot id: A0A0C4DGK1
uniprot id: P51003
names: Cofactor
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Acetylated in the C-terminus. Acetylation decreases interaction with NUDT21 and KPNB1, and inhibits nuclear localization through inhibiting binding to the importin alpha/beta complex (By similarity).
messages: Belongs to the poly(A) polymerase family.
messages: Binds 2 magnesium ions. Also active with manganese.
messages: Cytoplasm
messages: Hyperphosphorylation on multiple CDK2 consensus and non-consensus sites in the C-terminal Ser/Thr-rich region represses PAP activity in late M-phase. Phosphorylation/dephosphorylation may regulate the interaction between PAP and CPSF (By similarity).
messages: Monomer. Found in a complex with CPSF1, FIP1L1 and PAPOLA. Interacts with AHCYL1 and FIP1L1; the interaction with AHCYL1 seems to increase interaction with FIP1L1 (PubMed:19224921). Interacts with NUDT21; the interaction is diminished by acetylation. Interacts with KPNB1; the interaction promotes PAP nuclear import and is inhibited by acetylation of PAP (By similarity).
messages: Nucleus
messages: Polymerase that creates the 3'-poly(A) tail of mRNA's. Also required for the endoribonucleolytic cleavage reaction at some polyadenylation sites. May acquire specificity through interaction with a cleavage and polyadenylation specificity factor (CPSF) at its C-terminus.
messages: Polysumoylated. Varying sumoylation depending on tissue- and cell-type. Highly sumoylated in bladder and NIH 3T3 cells. Sumoylation is required for nuclear localization and enhances PAP stability. Desumoylated by SENP1. Inhibits polymerase activity (By similarity).

9606:NONO
gene id: 9606:NONO
uniprot id: A0A0S2Z4Z9
uniprot id: Q15233
names: Disease Annotation
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts with HIV-2 Capsid protein p24; interacts with high affinity (PubMed:30270045). Interacts with HIV-1 Capsid protein p24; interacts with low affinity (PubMed:30270045).
messages: A chromosomal aberration involving NONO may be a cause of papillary renal cell carcinoma (PRCC). Translocation t(X;X)(p11.2;q13.1) with TFE3.
messages: Chromosome
messages: DNA- and RNA binding protein, involved in several nuclear processes (PubMed:11525732, PubMed:12403470, PubMed:26571461). Binds the conventional octamer sequence in double-stranded DNA (PubMed:11525732, PubMed:12403470, PubMed:26571461). Also binds single-stranded DNA and RNA at a site independent of the duplex site (PubMed:11525732, PubMed:12403470, PubMed:26571461). Involved in pre-mRNA splicing, probably as a heterodimer with SFPQ (PubMed:11525732, PubMed:12403470, PubMed:26571461). Interacts with U5 snRNA, probably by binding to a purine-rich sequence located on the 3' side of U5 snRNA stem 1b (PubMed:12403470). Together with PSPC1, required for the formation of nuclear paraspeckles (PubMed:22416126). The SFPQ-NONO heteromer associated with MATR3 may play a role in nuclear retention of defective RNAs (PubMed:11525732). The SFPQ-NONO heteromer may be involved in DNA unwinding by modulating the function of topoisomerase I/TOP1 (PubMed:10858305). The SFPQ-NONO heteromer may be involved in DNA non-homologous end joining (NHEJ) required for double-strand break repair and V(D)J recombination and may stabilize paired DNA ends (PubMed:15590677). In vitro, the complex strongly stimulates DNA end joining, binds directly to the DNA substrates and cooperates with the Ku70/G22P1-Ku80/XRCC5 (Ku) dimer to establish a functional preligation complex (PubMed:15590677). NONO is involved in transcriptional regulation. The SFPQ-NONO-NR5A1 complex binds to the CYP17 promoter and regulates basal and cAMP-dependent transcriptional activity (PubMed:11897684). NONO binds to an enhancer element in long terminal repeats of endogenous intracisternal A particles (IAPs) and activates transcription (By similarity). Regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-BMAL1 heterodimer (By similarity). Important for the functional organization of GABAergic synapses (By similarity). Plays a specific and important role in the regulation of synaptic RNAs a…
messages: Heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. Also found in a number of breast tumor cell lines.
messages: Monomer and component of the SFPQ-NONO complex, which is probably a heterotetramer of two 52 kDa (NONO) and two 100 kDa (SFPQ) subunits (PubMed:8439294, PubMed:15590677). NONO is a component of spliceosome and U5.4/6 snRNP complexes (PubMed:12403470). Interacts with CPNE4 (via VWFA domain) (By similarity). Forms heterodimers with PSPC1; this involves formation of a coiled coil domain by helices from both proteins (PubMed:16148043, PubMed:22416126). Part of complex consisting of SFPQ, NONO and MATR3 (PubMed:11525732). Part of a complex consisting of SFPQ, NONO and NR5A1 (PubMed:11897684). Part of a complex consisting of SFPQ, NONO and TOP1 (PubMed:9756848). Interacts with SPI1 and SPIB (By similarity). Interacts with RNF43 (PubMed:18655028). Interacts with PER1 and PER2 (By similarity). Part of the HDP-RNP complex composed of at least HEXIM1, PRKDC, XRCC5, XRCC6, paraspeckle proteins (SFPQ, NONO, PSPC1, RBM14, and MATR3) and NEAT1 RNA (PubMed:28712728). Interacts (via second RRM domain) with WASL; the interaction is direct (PubMed:16767080). Component of a multiprotein complex with WASL and SFPQ (PubMed:16767080). Interacts with ERCC6 (PubMed:26030138). Interacts (via DNA-binding domain) with TET1 (By similarity).
messages: Nucleus
messages: Nucleus speckle
messages: The N-terminus is blocked.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: nucleolus

9606:TNFRSF11B
gene id: 9606:TNFRSF11B
uniprot id: O00300
names: Disease Annotation
names: Function
names: Induction
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acts as decoy receptor for TNFSF11/RANKL and thereby neutralizes its function in osteoclastogenesis. Inhibits the activation of osteoclasts and promotes osteoclast apoptosis in vitro. Bone homeostasis seems to depend on the local ratio between TNFSF11 and TNFRSF11B. May also play a role in preventing arterial calcification. May act as decoy receptor for TNFSF10/TRAIL and protect against apoptosis. TNFSF10/TRAIL binding blocks the inhibition of osteoclastogenesis.
messages: Highly expressed in adult lung, heart, kidney, liver, spleen, thymus, prostate, ovary, small intestine, thyroid, lymph node, trachea, adrenal gland, testis, and bone marrow. Detected at very low levels in brain, placenta and skeletal muscle. Highly expressed in fetal kidney, liver and lung.
messages: Homodimer. Interacts with TNFSF10 and TNFSF11.
messages: N-glycosylated. Contains sialic acid residues.
messages: Secreted
messages: The N-terminus is blocked.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Up-regulated by increasing calcium-concentration in the medium and estrogens. Down-regulated by glucocorticoids.

9606:SCP2
gene id: 9606:SCP2
uniprot id: A0A384NY87
uniprot id: B2R761
uniprot id: E9PLD1
uniprot id: P22307
uniprot id: Q59HG9
names: Disease Annotation
names: Function
names: Induction
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the thiolase-like superfamily. Thiolase family.
messages: Contains a putative mitochondrial transit peptide at positions 1-20.
messages: Cytoplasm
messages: Endoplasmic reticulum
messages: Expression at protein level is almost abolished in Zellweger syndrome. Cholesterol transfer from the endoplasmic reticulum to the plasma membrane was reduced in patient fibroblasts compared to controls.
messages: In the N-terminal section; belongs to the thiolase-like superfamily. Thiolase family.
messages: Interacts with PEX5; the interaction is essential for peroxisomal import.
messages: Liver, fibroblasts, and placenta.
messages: Mediates the transfer of all common phospholipids, cholesterol and gangliosides from the endoplasmic reticulum to the plasma membrane. May play a role in regulating steroidogenesis (PubMed:17157249, PubMed:8300590, PubMed:7642518). Stimulates the microsomal conversion of 7-dehydrocholesterol to cholesterol (By similarity). Also binds fatty acids and fatty acyl Coenzyme A (CoA) such as phytanoyl-CoA. Involved in the regulation phospholipid synthesis in endoplasmic reticulum enhancing the incorporation of exogenous fatty acid into glycerides. Seems to stimulate the rate-limiting step in phosphatidic acid formation mediated by GPAT3. Isoforms SCP2 and SCPx cooperate in peroxisomal oxidation of certain naturally occurring tetramethyl-branched fatty acyl-CoAs (By similarity).
messages: Mitochondrion
messages: Peroxisome
messages: Plays a crucial role in the peroxisomal oxidation of branched-chain fatty acids (PubMed:10706581). Catalyzes the last step of the peroxisomal beta-oxidation of branched chain fatty acids and the side chain of the bile acid intermediates di- and trihydroxycoprostanic acids (DHCA and THCA) (PubMed:10706581). Also active with medium and long straight chain 3-oxoacyl-CoAs. Stimulates the microsomal conversion of 7-dehydrocholesterol to cholesterol and transfers phosphatidylcholine and 7-dehydrocholesterol between membrances, in vitro (By similarity). Isoforms SCP2 and SCPx cooperate in peroxisomal oxidation of certain naturally occurring tetramethyl-branched fatty acyl-CoAs (By similarity).
messages: Produced by alternative splicing.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Up-regulated by 4-hydroxy-tamoxifen.
messages: preSCP2, a protein with a molecular mass of about 15 kDa, is processed into its mature form (SCP2) by proteolytic cleavage of a 20 residue leader sequence after translocation into peroxisomes.

9606:UBAP1
gene id: 9606:UBAP1
uniprot id: Q9NZ09
names: Caution
names: Disease Annotation
names: Domain
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: According to a report, can also be a component of ESCRT-I complexes containing VPS37B, VPS37C or VPS37D (PubMed:22405001). However, another publication showed that UBAP1 has specificity for complexes containing VPS37A and not VPS37 paralogs (PubMed:24284069).
messages: Component of an ESCRT-I complex (endosomal sorting complex required for transport I) which consists of TSG101, VPS28, VPS37A and UBAP1 in a 1:1:1:1 stoichiometry (PubMed:21757351, PubMed:24284069, PubMed:22405001, PubMed:31203368) (Probable). Interacts with PTPN23 (PubMed:21757351, PubMed:27839950). Interacts (via UBA domains) with ubiquitinated proteins (PubMed:22405001, PubMed:30929741).
messages: Component of the ESCRT-I complex, a regulator of vesicular trafficking process (PubMed:21757351, PubMed:22405001, PubMed:31203368). Binds to ubiquitinated cargo proteins and is required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies (MVBs) (PubMed:21757351, PubMed:22405001). Plays a role in the proteasomal degradation of ubiquitinated cell-surface proteins, such as EGFR and BST2 (PubMed:24284069, PubMed:22405001, PubMed:31203368).
messages: Endosome
messages: The UMA domain mediates association with the ESCRT-I complex.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitous. Highly expressed in heart, brain, placenta, lung, liver, skeletal muscle and pancreas.
messages: cytosol

9606:USP19
gene id: 9606:USP19
uniprot id: O94966
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the peptidase C19 family.
messages: Deubiquitinating enzyme that regulates the degradation of various proteins. Deubiquitinates and prevents proteasomal degradation of RNF123 which in turn stimulates CDKN1B ubiquitin-dependent degradation thereby playing a role in cell proliferation. Involved in decreased protein synthesis in atrophying skeletal muscle. Modulates transcription of major myofibrillar proteins. Also involved in turnover of endoplasmic-reticulum-associated degradation (ERAD) substrates. Regulates the stability of BIRC2/c-IAP1 and BIRC3/c-IAP2 by preventing their ubiquitination. Required for cells to mount an appropriate response to hypoxia and rescues HIF1A from degradation in a non-catalytic manner. Plays an important role in 17 beta-estradiol (E2)-inhibited myogenesis. Decreases the levels of ubiquitinated proteins during skeletal muscle formation and acts to repress myogenesis. Exhibits a preference towards 'Lys-63'-linked ubiquitin chains.
messages: Endoplasmic reticulum membrane
messages: Interacts with RNF123 (By similarity). Interacts with BIRC2/c-IAP1, BIRC3/c-IAP2 and XIAP/BIRC4. Interacts with HIF1A (via N-terminus).

9606:SLMAP
gene id: 9606:SLMAP
uniprot id: Q14BN4
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the SLMAP family.
messages: Homodimer. Interacts with myosin (By similarity).
messages: Incomplete sequence.
messages: May play a role during myoblast fusion.
messages: centrosome
messages: sarcolemma

9606:DRD4
gene id: 9606:DRD4
uniprot id: P21917
names: Activity Regulation
names: Function
names: PTM
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Dopamine receptor responsible for neuronal signaling in the mesolimbic system of the brain, an area of the brain that regulates emotion and complex behavior. Activated by dopamine, but also by epinephrine and norepinephrine, and by numerous synthetic agonists and drugs (PubMed:9003072, PubMed:16423344, PubMed:27659709, PubMed:29051383). Agonist binding triggers signaling via G proteins that inhibit adenylyl cyclase (PubMed:7512953, PubMed:7643093, PubMed:16423344, PubMed:27659709, PubMed:29051383). Modulates the circadian rhythm of contrast sensitivity by regulating the rhythmic expression of NPAS2 in the retinal ganglion cells (By similarity).
messages: Forms homo- and heterooligomers with DRD2. D4.7 allele exhibits higher affinity for homodimers compared to DRD2 heterodimers, while alleles D42. and 4.4 have similar affinities for both. The interaction with DRD2 may modulate agonist-induced downstream signaling (PubMed:21184734). Interacts with CLIC6 (By similarity). Interacts with GPRASP1 (PubMed:12142540). May interact with ADORA2A (PubMed:20836733). Interacts with KLHL12 (PubMed:18303015).
messages: Highly expressed in retina. Detected at much lower levels in brain, in amygdala, thalamus, hypothalamus, cerebellum and pituitary.
messages: Palmitoylated. Palmitoylation of the C-terminal Cys is important for normal expression at the cell membrane.
messages: Polyubiquitinated by the BCR(KLHL12) E3 ubiquitin ligase complex: polyubiquitination does not lead to degradation of DRD4 protein.
messages: Signaling in response to agonists such as dopamine, epinephrine and norepinephrine is modulated by Na(+); lower Na(+) levels result in higher receptor activity (in vitro).
messages: The number of repeats of 16 amino acids in the third cytoplasmic loop is highly polymorphic and varies among different alleles. Alleles corresponding in size to a 2 (D4.2), 3 (D4.3), 4 (D4.4), 5 (D4.5), 6 (D4.6), 7 (D4.7) and 9 (D4.9) repeats have been described. The sequence shown is that of allele D4.4. The polymorphic repeat sequence has little influence on DRD4-binding profiles and might not be essential for G protein interaction.

9606:RPS13
gene id: 9606:RPS13
uniprot id: P62277
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the universal ribosomal protein uS15 family.
messages: Component of the small ribosomal subunit. Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3 (PubMed:34516797).
messages: Component of the small ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797).
messages: Cytoplasm
messages: Ubiquitinated at Lys-27 by RNF14 and RNF25 in response to ribosome collisions (ribosome stalling).
messages: nucleolus

9606:AMDHD2
gene id: 9606:AMDHD2
uniprot id: Q9Y303
names: Cofactor
names: Function
names: Similarity
messages: Belongs to the metallo-dependent hydrolases superfamily. NagA family.
messages: Binds 1 divalent metal cation per subunit.
messages: Hydrolyzes the N-glycolyl group from N-glycolylglucosamine 6-phosphate (GlcNGc-6-P) in the N-glycolylneuraminic acid (Neu5Gc) degradation pathway. Although human is not able to catalyze formation of Neu5Gc due to the inactive CMAHP enzyme, Neu5Gc is present in food and must be degraded.

9606:ZNF579
gene id: 9606:ZNF579
uniprot id: Q8NAF0
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:IQCG
gene id: 9606:IQCG
uniprot id: Q9H095
uniprot id: Q9H5C8
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the DRC9 family.
messages: Component of the nexin-dynein regulatory complex (N-DRC) (By similarity). Interacts (via IQ domain) with CALM when calcium levels are low. Does not interact with CALM in the presence of Ca(2+). Interacts with the HSP70 proteins HSPA1L and HSPA8 (PubMed:24787902). May form a complex with CAMK4 and HSP70 (By similarity).
messages: Component of the nexin-dynein regulatory complex (N-DRC), a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes. Binds calmodulin when cellular Ca(2+) levels are low and thereby contributes to the regulation of calcium and calmodulin-dependent protein kinase IV (CAMK4) activity; contributes to the regulation of CAMK4 signaling cascades. Required for normal axoneme assembly in sperm flagella, normal sperm tail formation and for male fertility.
messages: Cytoplasm
messages: The IQ domain mediates interaction with calmodulin when cellular Ca(2+) levels are low.
messages: cilium
messages: cytoskeleton
messages: flagellum
messages: flagellum axoneme

9606:FAAP100
gene id: 9606:FAAP100
uniprot id: Q0VG06
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the multisubunit FA complex composed of FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL/PHF9, FANCM, FAAP24 and FAAP100. Forms a subcomplex with FANCB and FANCL.
messages: Nucleus
messages: Plays a role in Fanconi anemia-associated DNA damage response network. Regulates FANCD2 monoubiquitination and the stability of the FA core complex. Induces chromosomal instability as well as hypersensitivity to DNA cross-linking agents, when repressed.

9606:NUP37
gene id: 9606:NUP37
uniprot id: Q8NFH4
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Component of the Nup107-160 subcomplex of the nuclear pore complex (NPC). The Nup107-160 subcomplex includes NUP160, NUP133, NUP107, NUP98, NUP85, NUP43, NUP37, SEH1 and SEC13.
messages: Component of the Nup107-160 subcomplex of the nuclear pore complex (NPC). The Nup107-160 subcomplex is required for the assembly of a functional NPC. The Nup107-160 subcomplex is also required for normal kinetochore microtubule attachment, mitotic progression and chromosome segregation.
messages: The disease may be caused by variants affecting the gene represented in this entry.
messages: kinetochore
messages: nuclear pore complex

9606:VAX2
gene id: 9606:VAX2
uniprot id: F1T0K5
uniprot id: Q9UIW0
names: Developmental Stage
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the EMX homeobox family.
messages: Expressed in the ventral part of the optic vesicles at 7 week dpc.
messages: Nucleus
messages: Transcription factor that may function in dorsoventral specification of the forebrain. Regulates the expression of Wnt signaling antagonists including the expression of a truncated TCF7L2 isoform that cannot bind CTNNB1 and acts therefore as a potent dominant-negative Wnt antagonist. Plays a crucial role in eye development and, in particular, in the specification of the ventral optic vesicle (By similarity). May be a regulator of axial polarization in the retina.

9606:CD81
gene id: 9606:CD81
uniprot id: E9PJK1
uniprot id: P60033
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Acts as a receptor for hepatitis C virus (HCV) in hepatocytes. Association with CLDN1 and the CLDN1-CD81 receptor complex is essential for HCV entry into host cell.
messages: (Microbial infection) Involved in SAMHD1-dependent restriction of HIV-1 replication. May support early replication of both R5- and X4-tropic HIV-1 viruses in T cells, likely via proteasome-dependent degradation of SAMHD1.
messages: (Microbial infection) Plays a critical role in HCV attachment and/or cell entry by interacting with HCV E1/E2 glycoproteins heterodimer.
messages: (Microbial infection) Specifically required for Plasmodium falciparum infectivity of hepatocytes, controlling sporozoite entry into hepatocytes via the parasitophorous vacuole and subsequent parasite differentiation to exoerythrocytic forms.
messages: Basolateral cell membrane
messages: Belongs to the tetraspanin (TM4SF) family.
messages: Binds cholesterol in a cavity lined by the transmembrane spans.
messages: Cell membrane
messages: Expressed on B cells (at protein level) (PubMed:20237408). Expressed in hepatocytes (at protein level) (PubMed:12483205). Expressed in monocytes/macrophages (at protein level) (PubMed:12796480). Expressed on both naive and memory CD4-positive T cells (at protein level) (PubMed:22307619).
messages: Homodimer (PubMed:20375010). Part of a complex composed of CD19, CR2/CD21, CD81 and IFITM1/CD225 in the membrane of mature B cells. Interacts (via the second extracellular domain) with CD19; this interaction is initiated early during biosynthesis in the ER and enables trafficking of only properly folded CD19 (PubMed:16449649, PubMed:1383329). Part of a complex that includes MHC class II/HLA-DR molecules and IFITM1 (PubMed:8409388). Interacts with IFITM1 (PubMed:2398277, PubMed:26354436). Interacts with IFITM2 and IFITM3 (By similarity). Part of integrin-tetraspanin complex composed of CD9, CD81, beta-1 and beta-2 integrins in the membrane of monocyte/macrophages (PubMed:12796480). Interacts (via the second extracellular domain) with integrin ITGAV:ITGB3 (PubMed:27993971). Interacts with CD247/CD3 zeta, ICAM1 and CD9 at the immune synapse on T cell membrane (PubMed:23858057). Part of a GPCR-tetraspanin complex consisting at least of ADGRG1, CD81, possibly CD9, and GNA11 in which CD81 enhances the association of ADGRG1 with GNA11 (PubMed:15004227). Part of a complex composed of CD9, CD81, PTGFRN and IGSF8 (By similarity). Interacts directly with IGSF8 (PubMed:11504738). Interacts with CD53 and SCIMP (PubMed:21930792). Interacts with SAMHD1 (via its C-terminus) (PubMed:28871089). Interacts with glypican GPC3 and with the transcriptional repressor HHEX; binding to GPC3 decreases the availability of free CD81 for binding to HHEX, resulting in nuclear translocation of HHEX and transcriptional repression (By similarity). Interacts with CLDN1 (PubMed:20375010, PubMed:21516087). Interacts with CLDN6 and CLDN9 (PubMed:20375010).
messages: Likely constitutively palmitoylated at low levels. Protein palmitoylation is up-regulated upon coligation of BCR and CD9-C2R-CD81 complexes in lipid rafts.
messages: Membrane
messages: Not glycosylated.
messages: Structural component of specialized membrane microdomains known as tetraspanin-enriched microdomains (TERMs), which act as platforms for receptor clustering and signaling. Essential for trafficking and compartmentalization of CD19 receptor on the surface of activated B cells (PubMed:20237408, PubMed:27881302, PubMed:16449649). Upon initial encounter with microbial pathogens, enables the assembly of CD19-CR2/CD21 and B cell receptor (BCR) complexes at signaling TERMs, lowering the threshold dose of antigen required to trigger B cell clonal expansion and antibody production (PubMed:15161911, PubMed:20237408). In T cells, facilitates the localization of CD247/CD3 zeta at antigen-induced synapses with B cells, providing for costimulation and polarization toward T helper type 2 phenotype (PubMed:22307619, PubMed:23858057, PubMed:8766544). Present in MHC class II compartments, may also play a role in antigen presentation (PubMed:8409388, PubMed:8766544). Can act both as positive and negative regulator of homotypic or heterotypic cell-cell fusion processes. Positively regulates sperm-egg fusion and may be involved in acrosome reaction (By similarity). In myoblasts, associates with CD9 and PTGFRN and inhibits myotube fusion during muscle regeneration (By similarity). In macrophages, associates with CD9 and beta-1 and beta-2 integrins, and prevents macrophage fusion into multinucleated giant cells specialized in ingesting complement-opsonized large particles (PubMed:12796480). Also prevents the fusion of mononuclear cell progenitors into osteoclasts in charge of bone resorption (By similarity). May regulate the compartmentalization of enzymatic activities. In T cells, defines the subcellular localization of dNTPase SAMHD1 and permits its degradation by the proteasome, thereby controlling intracellular dNTP levels (PubMed:28871089). Also involved in cell adhesion and motility. Positively regulates integrin-mediated adhesion of macrophages, particularly relevant for the inflam…
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:MGAT4D
gene id: 9606:MGAT4D
uniprot id: A6NG13
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the glycosyltransferase 54 family.
messages: Endoplasmic reticulum membrane
messages: Expressed in testis. Poorly expressed in testis biopsies from men with impaired spermatogenesis.
messages: Golgi apparatus membrane
messages: May play a role in male spermatogenesis. In vitro acts as inhibitor of MGAT1 activity causing cell surface proteins to carry mainly high mannose N-glycans. The function is mediated by its lumenal domain and occurs specifically in the Golgi. A catalytic glucosyltransferase activity is not detected. May be involved in regulation of Sertoli-germ cell interactions during specific stages of spermatogenesis.
messages: May self-associate; specifically in the endoplasmic reticulum prior to its translocation to the Golgi. Interacts with MGAT1, MGAT3 and MAN2A2; may interact with MGTA1 specifically in the Golgi.

9606:FUT8
gene id: 9606:FUT8
uniprot id: A8K8P8
uniprot id: Q546E0
uniprot id: Q9BYC5
names: Disease Annotation
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the glycosyltransferase 23 family.
messages: Catalyzes the addition of fucose in alpha 1-6 linkage to the first GlcNAc residue, next to the peptide chains in N-glycans.
messages: Golgi stack membrane
messages: Membrane
messages: Seems to be only expressed in retina, inactive as a fucosyltransferase.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Tyrosine phosphorylated by PKDCC/VLK.

9606:PSMD3
gene id: 9606:PSMD3
uniprot id: O43242
names: Function
names: Similarity
names: Subunit
messages: Belongs to the proteasome subunit S3 family.
messages: Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits including PSMD3, a base containing 6 ATPases and few additional components (PubMed:27428775, PubMed:27342858). Interacts with UBQLN1 (via ubiquitin-like domain) (PubMed:15147878). Interacts with ERCC6 (PubMed:26030138).
messages: Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair.

9606:LY6G6F
gene id: 9606:LY6G6F
uniprot id: Q5SQ64
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: Cell membrane
messages: Homodimer; disulfide-linked. Interacts with GRB2 and GRB7 in a phosphorylation-dependent manner.
messages: May play a role in the downstream signal transduction pathways involving GRB2 and GRB7.
messages: N-glycosylated.

9606:CD63
gene id: 9606:CD63
uniprot id: P08962
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the tetraspanin (TM4SF) family.
messages: Cell membrane
messages: Cell surface
messages: Detected in platelets (at protein level). Dysplastic nevi, radial growth phase primary melanomas, hematopoietic cells, tissue macrophages.
messages: Functions as cell surface receptor for TIMP1 and plays a role in the activation of cellular signaling cascades. Plays a role in the activation of ITGB1 and integrin signaling, leading to the activation of AKT, FAK/PTK2 and MAP kinases. Promotes cell survival, reorganization of the actin cytoskeleton, cell adhesion, spreading and migration, via its role in the activation of AKT and FAK/PTK2. Plays a role in VEGFA signaling via its role in regulating the internalization of KDR/VEGFR2. Plays a role in intracellular vesicular transport processes, and is required for normal trafficking of the PMEL luminal domain that is essential for the development and maturation of melanocytes. Plays a role in the adhesion of leukocytes onto endothelial cells via its role in the regulation of SELP trafficking. May play a role in mast cell degranulation in response to Ms4a2/FceRI stimulation, but not in mast cell degranulation in response to other stimuli.
messages: Interacts with TIMP1 and ITGB1 and recruits TIMP1 to ITGB1 (PubMed:16917503, PubMed:24635319). Interacts with CD9. Identified in a complex with CD9 and ITGB3 (PubMed:19640571). Interacts with PMEL (PubMed:21962903). Interacts with KDR/VEGFR2; identified in a complex with ITGB1 and KDR/VEGFR2 and is required to recruit KDR to ITGB1 complexes (PubMed:23632027). Interacts with SYT7 (By similarity).
messages: Lack of expression of CD63 in platelets has been observed in a patient with Hermansky-Pudlak syndrome (HPS). Hermansky-Pudlak syndrome (HPS) is a genetically heterogeneous, rare, autosomal recessive disorder characterized by oculocutaneous albinism, bleeding due to platelet storage pool deficiency, and lysosomal storage defects. This syndrome results from defects of diverse cytoplasmic organelles including melanosomes, platelet dense granules and lysosomes. Ceroid storage in the lungs is associated with pulmonary fibrosis, a common cause of premature death in individuals with HPS.
messages: Late endosome membrane
messages: Lysosome membrane
messages: Melanosome
messages: Palmitoylated at a low, basal level in unstimulated platelets. The level of palmitoylation increases when platelets are activated by thrombin (in vitro).
messages: This antigen is associated with early stages of melanoma tumor progression.
messages: extracellular exosome
messages: multivesicular body

9606:AJM1
gene id: 9606:AJM1
uniprot id: C9J069
names: Function
names: Subcellular Location Annotation
messages: Apical cell membrane
messages: May be involved in the control of adherens junction integrity.
messages: adherens junction
messages: cilium

9606:CDYL2
gene id: 9606:CDYL2
uniprot id: Q8N8U2
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Interacts (via chromo domain) with histone H3K9me3.
messages: Nucleus
messages: Ubiquitously expressed.

9606:COPZ2
gene id: 9606:COPZ2
uniprot id: Q9P299
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the adaptor complexes small subunit family.
messages: COPI-coated vesicle membrane
messages: Cytoplasm
messages: Endoplasmic reticulum-Golgi intermediate compartment membrane
messages: Golgi apparatus membrane
messages: Oligomeric complex.
messages: The coatomer is a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Golgi network. Coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins. The zeta subunit may be involved in regulating the coat assembly and, hence, the rate of biosynthetic protein transport due to its association-dissociation properties with the coatomer complex.

9606:ARHGAP8
gene id: 9606:ARHGAP8
uniprot id: P85298
names: Function
names: Tissue Specificity
messages: GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state.
messages: Highly expressed in kidney and placenta. Also expressed in colon, skeletal muscle, small intestine, stomach, and testis. Not detected in brain, liver or spleen. Overexpressed in the majority of colorectal tumors examined.

9606:ZNF787
gene id: 9606:ZNF787
uniprot id: Q6DD87
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:G2E3
gene id: 9606:G2E3
uniprot id: Q7L622
names: Domain
names: Function
names: Induction
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Cytoplasm
messages: E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Essential in early embryonic development to prevent apoptotic death.
messages: Predominantly expressed in brain, liver, kidney, testes and ovary.
messages: Ubiquitin ligase activity is mediated by two distinct domains, PHD-type zinc fingers 2 and 3. The use of these distinct domains may allow ubiquitination of different targets by each domain. The HECT domain is catalytically inactive and does not contribute to this activity.
messages: Up-regulated approximately 4-fold in G2 when compared to S phase. Down-regulated approximately 3-fold by gamma-irradiation.
messages: nucleolus

9606:EGLN3
gene id: 9606:EGLN3
uniprot id: Q9H6Z9
names: Activity Regulation
names: Cofactor
names: Domain
names: Function
names: Induction
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Activated in cardiovascular cells and Hela cells following exposure to hypoxia. Inhibited by polynitrogen compounds probably by chelation to Fe(2+) ions.
messages: Binds 1 Fe(2+) ion per subunit.
messages: Cytoplasm
messages: Induced by hypoxia in a number of cells including neutrophils and certain cancer cell lines. Up-regulated 10-fold in pancreatic cancers.
messages: Interacts with BCL2 (via its BH4 domain); the interaction disrupts the BAX-BCL4 complex inhibiting the anti-apoptotic activity of BCL2 (PubMed:20849813). Interacts with WDR83; the interaction leads to almost complete elimination of HIF-mediated reporter activity (By similarity). Interacts with ADRB2; the interaction hydroxylates ADRB2 facilitating its ubiquitination by the VHL-E3 ligase complex (PubMed:19584355). Interacts with PAX2; the interaction targets PAX2 for destruction (PubMed:21575608). Interacts with PKM; the interaction hydroxylates PKM in hypoxia (PubMed:21620138, PubMed:21483450). Interacts with LIMD1, WTIP and AJUBA (PubMed:22286099).
messages: Nucleus
messages: Prolyl hydroxylase that mediates hydroxylation of proline residues in target proteins, such as PKM, TELO2, ATF4 and HIF1A (PubMed:19584355, PubMed:21620138, PubMed:21483450, PubMed:22797300, PubMed:20978507, PubMed:21575608). Target proteins are preferentially recognized via a LXXLAP motif. Cellular oxygen sensor that catalyzes, under normoxic conditions, the post-translational formation of 4-hydroxyproline in hypoxia-inducible factor (HIF) alpha proteins (PubMed:11595184, PubMed:12181324). Hydroxylates a specific proline found in each of the oxygen-dependent degradation (ODD) domains (N-terminal, NODD, and C-terminal, CODD) of HIF1A (PubMed:11595184, PubMed:12181324). Also hydroxylates HIF2A (PubMed:11595184, PubMed:12181324). Has a preference for the CODD site for both HIF1A and HIF2A (PubMed:11595184, PubMed:12181324). Hydroxylation on the NODD site by EGLN3 appears to require prior hydroxylation on the CODD site (PubMed:11595184, PubMed:12181324). Hydroxylated HIFs are then targeted for proteasomal degradation via the von Hippel-Lindau ubiquitination complex (PubMed:11595184, PubMed:12181324). Under hypoxic conditions, the hydroxylation reaction is attenuated allowing HIFs to escape degradation resulting in their translocation to the nucleus, heterodimerization with HIF1B, and increased expression of hypoxy-inducible genes (PubMed:11595184, PubMed:12181324). ELGN3 is the most important isozyme in limiting physiological activation of HIFs (particularly HIF2A) in hypoxia. Also hydroxylates PKM in hypoxia, limiting glycolysis (PubMed:21620138, PubMed:21483450). Under normoxia, hydroxylates and regulates the stability of ADRB2 (PubMed:19584355). Regulator of cardiomyocyte and neuronal apoptosis. In cardiomyocytes, inhibits the anti-apoptotic effect of BCL2 by disrupting the BAX-BCL2 complex (PubMed:20849813). In neurons, has a NGF-induced proapoptotic effect, probably through regulating CASP3 activity (PubMed:16098468). Also essential for hypoxic regulation of neutr…
messages: The Beta(2)beta(3) 'finger-like' loop domain is important for substrate (HIFs' CODD/NODD) selectivity.
messages: Ubiquitinated by SIAH1 and/or SIAH2 in response to the unfolded protein response (UPR), leading to its degradation.
messages: Widely expressed at low levels. Expressed at higher levels in adult heart (cardiac myocytes, aortic endothelial cells and coronary artery smooth muscle), lung and placenta, and in fetal spleen, heart and skeletal muscle. Also expressed in pancreas. Localized to pancreatic acini and islet cells.

9606:KCNK12
gene id: 9606:KCNK12
uniprot id: Q9HB15
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the two pore domain potassium channel (TC 1.A.1.8) family.
messages: Heterodimer.
messages: Membrane
messages: Probable potassium channel subunit. No channel activity observed in heterologous systems. May need to associate with another protein to form a functional channel (By similarity).

9606:SCNN1B
gene id: 9606:SCNN1B
uniprot id: B2R812
uniprot id: P51168
names: Activity Regulation
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Activated by WNK1, WNK2, WNK3 and WNK4.
messages: Apical cell membrane
messages: Belongs to the amiloride-sensitive sodium channel (TC 1.A.6) family. SCNN1B subfamily.
messages: Cytoplasmic vesicle membrane
messages: Detected in placenta, lung and kidney (PubMed:7762608). Expressed in kidney (at protein level) (PubMed:22207244).
messages: Heterotrimer containing an alpha/SCNN1A, a beta/SCNN1B and a gamma/SCNN1G subunit. An additional delta/SCNN1D subunit exists only in some organisms and can replace the alpha/SCNN1A subunit to form an alternative channel with specific properties (PubMed:7499195, PubMed:16423824). Interacts with NEDD4 (via WW domains) (PubMed:11244092, PubMed:12167593). Interacts with NEDD4L (via WW domains) (PubMed:11244092). Interacts with WWP1 (via WW domains) (PubMed:9169421). Interacts with WWP2 (via WW domains) (PubMed:9169421, PubMed:12167593). Interacts with the full-length immature form of PCSK9 (pro-PCSK9) (PubMed:22493497). Interacts (N-glycosylated) with BPIFA1; the interaction is direct and inhibits the proteolytic processing of SCNN1A and SCNN1G and the activation of ENaC (PubMed:24124190, PubMed:24043776).
messages: Membrane
messages: N-glycosylated. N-glycosylation is required for interaction with BPIFA1.
messages: Phosphorylated on serine and threonine residues. Aldosterone and insulin increase the basal level of phosphorylation.
messages: Sodium permeable non-voltage-sensitive ion channel inhibited by the diuretic amiloride. Mediates the electrodiffusion of the luminal sodium (and water, which follows osmotically) through the apical membrane of epithelial cells. Plays an essential role in electrolyte and blood pressure homeostasis, but also in airway surface liquid homeostasis, which is important for proper clearance of mucus. Controls the reabsorption of sodium in kidney, colon, lung and sweat glands. Also plays a role in taste perception.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The disease is caused by variants affecting the gene represented in this entry. The degree of channel function impairment differentially affects the renin-aldosterone system and urinary Na/K ratios, resulting in distinct genotype-phenotype relationships in PHA1 patients. Loss-of-function mutations are associated with a severe clinical course and age-dependent hyperactivation of the renin-aldosterone system. This feature is not observed in patients with missense mutations that reduce but do not eliminate channel function. Markedly reduced channel activity results in impaired linear growth and delayed puberty (PubMed:18634878).

9606:NOL8
gene id: 9606:NOL8
uniprot id: Q76FK4
names: Function
names: Induction
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Expressed in various diffuse-type gastric cancers. Detected at lower levels in skeletal muscle.
messages: Interacts with the GTP form of RRAGA, RRAGC and RRAGD. Interacts with NIP7. Interacts with DDX18; the interaction is RNA-dependent. Interacts with DDX47; the interaction is RNA-dependent.
messages: Phosphorylated.
messages: Plays an essential role in the survival of diffuse-type gastric cancer cells. Acts as a nucleolar anchoring protein for DDX47. May be involved in regulation of gene expression at the post-transcriptional level or in ribosome biogenesis in cancer cells.
messages: Up-regulated in diffuse-type gastric cancers.
messages: nucleolus

9606:RANBP6
gene id: 9606:RANBP6
uniprot id: B4DTX6
uniprot id: O60518
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the importin beta family.
messages: Cytoplasm
messages: May function in nuclear protein import as nuclear transport receptor.
messages: Nucleus

9606:NOS3
gene id: 9606:NOS3
uniprot id: A0S0A6
uniprot id: P29474
names: Activity Regulation
names: Cofactor
names: Disease Annotation
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the NOS family.
messages: Binds 1 FAD.
messages: Binds 1 FMN.
messages: Cell membrane
messages: Golgi apparatus
messages: Homodimer. Interacts with NOSIP and NOSTRIN (PubMed:11149895, PubMed:12446846). Interacts with HSP90AB1 (PubMed:23585225, PubMed:11149895, PubMed:12446846) (By similarity). Forms a complex with ASL, ASS1 and SLC7A1; the complex regulates cell-autonomous L-arginine synthesis and citrulline recycling while channeling extracellular L-arginine to nitric oxide synthesis pathway (By similarity).
messages: Lacks eNOS activity, dominant-negative form that may down-regulate eNOS activity by forming heterodimers with isoform 1.
messages: Lacks eNOS activity.
messages: Phosphorylation by AMPK at Ser-1177 in the presence of Ca(2+)-calmodulin (CaM) activates activity. In absence of Ca(2+)-calmodulin, AMPK also phosphorylates Thr-495, resulting in inhibition of activity (By similarity). Phosphorylation of Ser-114 by CDK5 reduces activity.
messages: Platelets, placenta, liver and kidney.
messages: Produces nitric oxide (NO) which is implicated in vascular smooth muscle relaxation through a cGMP-mediated signal transduction pathway (PubMed:1378832). NO mediates vascular endothelial growth factor (VEGF)-induced angiogenesis in coronary vessels and promotes blood clotting through the activation of platelets.
messages: Stimulated by calcium/calmodulin. Inhibited by NOSIP and NOSTRIN.
messages: Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the enzyme.
messages: Variation Asp-298 in NOS3 may be associated with susceptibility to coronary spasm.
messages: caveola
messages: cytoskeleton

9606:FTMT
gene id: 9606:FTMT
uniprot id: Q8N4E7
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the ferritin family.
messages: Catalyzes the oxidation of ferrous iron(II) to ferric iron(III) and stores iron in a soluble, non-toxic, readily available form (PubMed:11323407, PubMed:15201052). Important for iron homeostasis (PubMed:11323407, PubMed:15201052). Iron is taken up in the ferrous form and deposited as ferric hydroxides after oxidation (PubMed:11323407, PubMed:15201052).
messages: Detected in testis and erythroleukemia. Expression is very low or not detectable in brain, colon, heart, kidney, liver, lung, muscle, placental, spleen and small intestine.
messages: Homooligomer of 24 subunits. The functional molecule is roughly spherical and contains a central cavity into which the polymeric mineral iron core is deposited.
messages: Mitochondrion

9606:MAPK8IP3
gene id: 9606:MAPK8IP3
uniprot id: A0A087WYG2
uniprot id: B7ZMF3
uniprot id: E9PFH7
uniprot id: Q9UPT6
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the JIP scaffold family.
messages: Cytoplasm
messages: Cytoplasmic vesicle
messages: Forms homo- or heterooligomeric complexes. The central region of MAPK8IP3 interacts with the C-terminal of MAPK8IP2 but not MAPK8IP1. Binds specific components of the JNK signaling pathway namely MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3 to the N-terminal region, MAP2K4/MKK4 and MAP2K7/MKK7 to the central region and MAP3K11 to the C-terminal region. Binds the TPR motif-containing C-terminal of kinesin light chain, KLC1. Pre-assembled MAPK8IP1 scaffolding complexes are then transported as a cargo of kinesin, to the required subcellular location. Interacts with ROCK1 and this interaction is enhanced by ultraviolet-B (UVB) radiation. Interacts with SH3RF2 (By similarity). Interacts with NTRK2/TRKB and NTRK3/TRKC (By similarity).
messages: Golgi apparatus
messages: Phosphorylation by ROCK1 is crucial for the recruitment of JNK.
messages: The JNK-interacting protein (JIP) group of scaffold proteins selectively mediates JNK signaling by aggregating specific components of the MAPK cascade to form a functional JNK signaling module (PubMed:12189133). May function as a regulator of vesicle transport, through interactions with the JNK-signaling components and motor proteins (By similarity). Promotes neuronal axon elongation in a kinesin- and JNK-dependent manner. Activates cofilin at axon tips via local activation of JNK, thereby regulating filopodial dynamics and enhancing axon elongation. Its binding to kinesin heavy chains (KHC), promotes kinesin-1 motility along microtubules and is essential for axon elongation and regeneration. Regulates cortical neuronal migration by mediating NTRK2/TRKB anterograde axonal transport during brain development (By similarity). Acts as an adapter that bridges the interaction between NTRK2/TRKB and KLC1 and drives NTRK2/TRKB axonal but not dendritic anterograde transport, which is essential for subsequent BDNF-triggered signaling and filopodia formation (PubMed:21775604).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: axon
messages: dendrite
messages: growth cone
messages: perinuclear region

9606:LHCGR
gene id: 9606:LHCGR
uniprot id: P22888
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor 1 family. FSH/LSH/TSH subfamily.
messages: Cell membrane
messages: Gonadal and thyroid cells.
messages: Receptor for lutropin-choriogonadotropic hormone (PubMed:11847099). The activity of this receptor is mediated by G proteins which activate adenylate cyclase (PubMed:11847099).
messages: Sulfated.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:TMIGD2
gene id: 9606:TMIGD2
uniprot id: Q96BF3
names: Developmental Stage
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cell membrane
messages: May form homophilic interactions that could regulate cell-cell interaction. Interacts with CACNB2, DST, MIA and NCKIPSD. Interacts with HHLA2.
messages: N-glycosylated.
messages: Plays a role in cell-cell interaction, cell migration, and angiogenesis. Through interaction with HHLA2, costimulates T-cells in the context of TCR-mediated activation. Enhances T-cell proliferation and cytokine production via an AKT-dependent signaling cascade.
messages: Repetitive stimulation of naive T-cells, including with IL2 and antibodies against CD3 and CD28 or repetitive antigenic exposure, leads to progressive and irreversible loss of expression.
messages: Widely expressed, mainly by epithelial and endothelial cells, including bronchial epithelial cells of lung, breast glandular and lobular epithelia cells, urothelium of the bladder, skin epidermis, epithelium of gastrointestinal, rectum, endometrial glands of the uterus, ureter, fallopian tube epithelium, colonic epithelium, small bowl epithelium, stomach epithelium, including both chief and parietal cells, trophoblastic epithelium of placenta, and pancreatic acinar cells (at protein level). Consistently expressed in veins and arteries (at protein level). Not detected in thyroid, cerebellum, cerebral cortex and thymus (at protein level). Expressed in lymphoid organs, with highest levels in thymus, spleen, peripheral blood lymphocytes and liver. In the thymus, expressed in CD4+ and CD8+ single- and double-positive cells, but not in immature CD4- and CD8- double-negative cells (at protein level). In peripheral blood mononuclear cells, highly expressed on CD56+ or CD16+ natural killer cells and CD3+ T-cells(at protein level). Not detected on B-cells(at protein level). Expressed in tonsils (at protein level).

9606:SEC62
gene id: 9606:SEC62
uniprot id: Q99442
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the SEC62 family.
messages: Endoplasmic reticulum membrane
messages: Mediates post-translational transport of precursor polypeptides across endoplasmic reticulum (ER). Proposed to act as a targeting receptor for small presecretory proteins containing short and apolar signal peptides. Targets and properly positions newly synthesized presecretory proteins into the SEC61 channel-forming translocon complex, triggering channel opening for polypeptide translocation to the ER lumen.
messages: The ER translocon complex that consists of channel-forming core components SEC61A1, SEC61B and SEC61G and different auxiliary components such as SEC62 and SEC63. Interacts with SEC61B.

9606:SLC51B
gene id: 9606:SLC51B
uniprot id: Q86UW2
names: Disease Annotation
names: Domain
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the OST-beta family.
messages: Cell membrane
messages: Essential component of the Ost-alpha/Ost-beta complex, a heterodimer that acts as the intestinal basolateral transporter responsible for bile acid export from enterocytes into portal blood (PubMed:16317684). Modulates SLC51A glycosylation, membrane trafficking and stability activities (PubMed:16317684). The Ost-alpha/Ost-beta complex efficiently transports the major species of bile acids (taurocholate) (PubMed:16317684). Taurine conjugates are transported more efficiently across the basolateral membrane than glycine-conjugated bile acids (By similarity). Can also transport steroids such as estrone 3-sulfate and dehydroepiandrosterone 3-sulfate, therefore playing a role in the enterohepatic circulation of sterols (PubMed:16317684). Able to transport eicosanoids such as prostaglandin E2 (By similarity).
messages: Interacts with SLC51A. The Ost-alpha/Ost-beta complex is a heterodimer composed of alpha (SLC51A) and beta (SLC51B) subunit; induces the transport of SLC51A from the reticulum endoplasmic to the plasma membrane (By similarity).
messages: Positively regulated via NR1H4/FXR.
messages: The disease may be caused by variants affecting the gene represented in this entry.
messages: The transmembrane domain (TM) is the major site of interaction with SLC51A. The extracellular-membrane interface is absolutely required for transport activity. The intracellular-membrane interface is necessary for establishing the correct membrane orientation that is essential for the heterodimer Ost-alpha/Ost-beta complex formation and transport activity at the cell membrane surface (By similarity).
messages: Widely expressed with a high expression in ileum. Expressed in testis, colon, liver, small intestine, kidney, ovary and adrenal gland; and at low levels in heart, lung, brain, pituitary, thyroid gland, uterus, prostate, mammary gland and fat.

9606:COX8A
gene id: 9606:COX8A
uniprot id: P10176
uniprot id: Q53XN1
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the cytochrome c oxidase VIII family.
messages: Component of the cytochrome c oxidase (complex IV, CIV), a multisubunit enzyme composed of 14 subunits. The complex is composed of a catalytic core of 3 subunits MT-CO1, MT-CO2 and MT-CO3, encoded in the mitochondrial DNA, and 11 supernumerary subunits COX4I, COX5A, COX5B, COX6A, COX6B, COX6C, COX7A, COX7B, COX7C, COX8 and NDUFA4, which are encoded in the nuclear genome. The complex exists as a monomer or a dimer and forms supercomplexes (SCs) in the inner mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), resulting in different assemblies (supercomplex SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)).
messages: Component of the cytochrome c oxidase (complex IV, CIV), a multisubunit enzyme composed of 14 subunits. The complex is composed of a catalytic core of 3 subunits MT-CO1, MT-CO2 and MT-CO3, encoded in the mitochondrial DNA, and 11 supernumerary subunits COX4I1 (or COX4I2), COX5A, COX5B, COX6A1 (or COX6A2), COX6B1 (or COX6B2), COX6C, COX7A2 (or COX7A1), COX7B, COX7C, COX8A and NDUFA4, which are encoded in the nuclear genome (PubMed:30030519). The complex exists as a monomer or a dimer and forms supercomplexes (SCs) in the inner mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), resulting in different assemblies (supercomplex SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)) (PubMed:28844695).
messages: Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix.
messages: Membrane
messages: Mitochondrion inner membrane
messages: The disease may be caused by variants affecting the gene represented in this entry.
messages: Widely expressed.

9606:PDE4D
gene id: 9606:PDE4D
uniprot id: A0A140VJR0
uniprot id: Q08499
names: Activity Regulation
names: Cofactor
names: Disease Annotation
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Activated by phosphorylation at Ser-53. Mutagenesis of Ser-54 abolishes activation.
messages: Apical cell membrane
messages: Belongs to the cyclic nucleotide phosphodiesterase family. PDE4 subfamily.
messages: Binds 2 divalent metal cations per subunit (PubMed:15260978, PubMed:15576036). Site 2 has a preference for magnesium and/or manganese ions (By similarity).
messages: Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions.
messages: Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions.
messages: Cytoplasm
messages: Detected in brain, placenta, lung and kidney.
messages: Detected in brain.
messages: Detected in heart and skeletal muscle.
messages: Expressed in colonic epithelial cells (at protein level). Widespread; most abundant in skeletal muscle.
messages: Genetic variations in PDE4D might be associated with susceptibility to stroke. PubMed:17006457 states that association with stroke has to be considered with caution.
messages: Homodimer for the long isoforms. Isoforms with truncated N-termini are monomeric. Isoform 3 is part of a ternary complex containing PRKAR2A, PRKAR2B and AKAP9. Interacts with PDE4DIP. Identified in a complex composed of RYR1, PDE4D, PKA, FKBP1A and protein phosphatase 1 (PP1) (By similarity). Isoform 5, isoform N3 and isoform 12 bind RACK1 via their unique N-terminus. Binds ARRB2. Interacts (via N-terminal region) with SHANK2 (via proline-rich region); the interaction is increased in a PKA-dependent manner.
messages: Hydrolyzes the second messenger cAMP, which is a key regulator of many important physiological processes.
messages: Inhibited by rolipram. Activated by phosphatidic acid.
messages: Long isoforms that share a conserved PKA phosphorylation site in the N-terminus are activated by PKA through phosphorylation (By similarity). Isoform 3 and isoform 7 are activated by phosphorylation (in vitro), but not isoform 6. Isoform N3 and isoform 12 are phosphorylated on Ser-49, Ser-51, Ser-55 and Ser-59.
messages: Membrane
messages: Sumoylation of long isoforms by PIAS4 augments their activation by PKA phosphorylation and represses their inhibition by ERK phosphorylation.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: centrosome
messages: cytoskeleton

9606:GABRB2
gene id: 9606:GABRB2
uniprot id: P47870
names: Activity Regulation
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Allosterically activated by benzodiazepines (PubMed:29950725). Allosterically activated by the anesthetic etomidate (By similarity). Inhibited by the antagonist bicuculline (PubMed:29950725).
messages: Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRB2 sub-subfamily.
messages: Cell membrane
messages: Cytoplasmic vesicle membrane
messages: Glycosylated.
messages: Heteropentamer, formed by a combination of alpha, beta, gamma, delta and rho chains (PubMed:8264558, PubMed:29950725). Interacts with UBQLN1 (By similarity). Interacts with KCTD8, KCTD12 and KCTD16; this interaction determines the pharmacology and kinetics of the receptor response, the KCTD proteins markedly accelerating the GABA-B response, although to different extents (By similarity). May interact with KIF21B (By similarity). Identified in a complex of 720 kDa composed of LHFPL4, NLGN2, GABRA1, GABRB2, GABRG2 and GABRB3 (By similarity).
messages: Isoform 1 and isoform 2 show reduced expression in schizophrenic brain. Isoform 3 shows increased expression in schizophrenic and bipolar disorder brains while isoform 4 shows reduced expression.
messages: Ligand-gated chloride channel which is a component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the brain (PubMed:8264558, PubMed:19763268, PubMed:27789573, PubMed:29950725). Plays an important role in the formation of functional inhibitory GABAergic synapses in addition to mediating synaptic inhibition as a GABA-gated ion channel (PubMed:23909897, PubMed:25489750). The gamma2 subunit is necessary but not sufficient for a rapid formation of active synaptic contacts and the synaptogenic effect of this subunit is influenced by the type of alpha and beta subunits present in the receptor pentamer (By similarity). The alpha1/beta2/gamma2 receptor and the alpha2/beta2/gamma2 receptor exhibit synaptogenic activity (PubMed:23909897, PubMed:25489750). Functions also as histamine receptor and mediates cellular responses to histamine (By similarity).
messages: Postsynaptic cell membrane
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The extracellular domain contributes to synaptic contact formation.

9606:PALS1
gene id: 9606:PALS1
uniprot id: Q658X5
uniprot id: Q8N3R9
names: Domain
names: Function
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Acts as an interaction partner for human coronaviruses SARS-CoV and, probably, SARS-CoV-2 envelope protein E which results in delayed formation of tight junctions and disregulation of cell polarity.
messages: (Microbial infection) Interacts (via PDZ domain) with human coronaviruses SARS-CoV and, probably, SARS-CoV-2 envelope small membrane protein E (via C-terminus); this inhibits the interaction between PALS1 and CRB3.
messages: Apical cell membrane
messages: Belongs to the MAGUK family.
messages: Cell membrane
messages: Contaminating sequence. Potential poly-A sequence.
messages: Endomembrane system
messages: Endoplasmic reticulum-Golgi intermediate compartment
messages: Expressed at the outer limiting membrane in the retina (at protein level) (PubMed:15914641, PubMed:15558731, PubMed:16519681, PubMed:17584769). Expressed in T lymphocytes (at protein level) (PubMed:21479189). Expressed in the kidney (at protein level) (PubMed:17584769).
messages: Golgi apparatus
messages: Heterodimer with MPP1 (PubMed:17584769). Forms a heterotrimeric complex composed of PALS1, LIN7B and PATJ; the N-terminal L27 domain of PALS1 interacts with the L27 domain of PATJ and the C-terminal L27 domain of PALS1 interacts with the L27 domain of LIN7B (PubMed:22337881). Component of a complex composed of PALS1, CRB1 and MPP4 (PubMed:15914641). Component of a complex whose core is composed of ARHGAP17, AMOT, PALS1, PATJ and PARD3/PAR3 (PubMed:16678097). Component of a complex composed of PALS1, CRB1 and EPB41L5 (PubMed:17920587). Within the complex, interacts (via HOOK domain) with EPB41L5 (via FERM domain), and interacts with CRB1 (via intracellular domain) (PubMed:17920587). Component of a complex composed of PALS1, MPP3 and CRB1; PALS1 acts as a bridging protein between MPP3 (via guanylate kinase-like domain) and CRB1 (PubMed:16519681). Component of a complex composed of CRB3, PALS1 and PATJ (By similarity). Interacts (via PDZ domain) with PATJ (via N-terminus) (PubMed:12527193). Interacts with EZR (By similarity). Interacts (via PDZ domain) with CRB1 (via C-terminal ERLI motif) (PubMed:25385611, PubMed:25760605). While the PDZ domain is sufficient for interaction with CRB1, the adjacent SH3 and guanylate kinase-like domains are likely to contribute to a high affinity interaction (PubMed:25385611). Interacts with WWTR1/TAZ (via WW domain) (PubMed:21145499). Interacts with MPP7 (PubMed:16678097, PubMed:17332497). Interacts (via PDZ domain) with CRB3 (via C-terminus) (By similarity). Interacts with LIN7C (By similarity). Interacts with MPDZ (By similarity). Interacts with PARD6B (By similarity). Interacts with SC6A1 (By similarity). Interacts with CDH5; the interaction promotes PALS1 localization to cell junctions and is required for CDH5-mediated vascular lumen formation and endothelial cell (PubMed:27466317). Interacts with NPHP1 (via coiled coil and SH3 domains) (PubMed:19755384). Interacts with NPHP4 (PubMed:19755384). Interacts with CRB2 (By similarity).
messages: Perikaryon
messages: Plays a role in tight junction biogenesis and in the establishment of cell polarity in epithelial cells (PubMed:16678097, PubMed:25385611). Also involved in adherens junction biogenesis by ensuring correct localization of the exocyst complex protein EXOC4/SEC8 which allows trafficking of adherens junction structural component CDH1 to the cell surface (By similarity). Plays a role through its interaction with CDH5 in vascular lumen formation and endothelial membrane polarity (PubMed:27466317). Required during embryonic and postnatal retinal development (By similarity). Required for the maintenance of cerebellar progenitor cells in an undifferentiated proliferative state, preventing premature differentiation, and is required for cerebellar histogenesis, fissure formation, cerebellar layer organization and cortical development (By similarity). Plays a role in neuronal progenitor cell survival, potentially via promotion of mTOR signaling (By similarity). Plays a role in the radial and longitudinal extension of the myelin sheath in Schwann cells (By similarity). May modulate SC6A1/GAT1-mediated GABA uptake by stabilizing the transporter (By similarity). Plays a role in the T-cell receptor-mediated activation of NF-kappa-B (PubMed:21479189). Required for localization of EZR to the apical membrane of parietal cells and may play a role in the dynamic remodeling of the apical cytoskeleton (By similarity). Required for the normal polarized localization of the vesicular marker STX4 (By similarity). Required for the correct trafficking of the myelin proteins PMP22 and MAG (By similarity). Involved in promoting phosphorylation and cytoplasmic retention of transcriptional coactivators YAP1 and WWTR1/TAZ which leads to suppression of TGFB1-dependent transcription of target genes such as CCN2/CTGF, SERPINE1/PAI1, SNAI1/SNAIL1 and SMAD7 (By similarity).
messages: The L27 domain 1 functions in targeting to the tight junctions by binding to and stabilizing PATJ.
messages: The PDZ domain binds to the C-terminus of SC6A1.
messages: adherens junction
messages: axon
messages: tight junction

9606:TKT
gene id: 9606:TKT
uniprot id: P29401
names: Cofactor
names: Disease Annotation
names: Function
names: Similarity
names: Subunit
messages: Belongs to the transketolase family.
messages: Binds 1 Mg(2+) ion per subunit. Can also utilize other divalent metal cations, such as Ca(2+), Mn(2+) and Co(2+).
messages: Binds 1 thiamine pyrophosphate per subunit.
messages: Catalyzes the transfer of a two-carbon ketol group from a ketose donor to an aldose acceptor, via a covalent intermediate with the cofactor thiamine pyrophosphate.
messages: Homodimer.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:MTUS2
gene id: 9606:MTUS2
uniprot id: Q5JR59
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Binds microtubules. Together with MAPRE1 may target the microtubule depolymerase KIF2C to the plus-end of microtubules. May regulate the dynamics of microtubules at their growing distal tip.
messages: Detected in embryonic stem cells differentiating to cardiomyocytes.
messages: Homodimer. Interacts with KIF2C and MAPRE1; the interaction is direct and probably targets MTUS2 and KIF2C to microtubules.
messages: In the C-terminal section; belongs to the MTUS1 family.
messages: cytoskeleton

9606:DLAT
gene id: 9606:DLAT
uniprot id: P10515
uniprot id: Q86YI5
names: Cofactor
names: Disease Annotation
names: Function
names: PTM
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the 2-oxoacid dehydrogenase family.
messages: Binds 2 lipoyl cofactors covalently.
messages: Contaminating sequence. Sequence of unknown origin in the N-terminal part.
messages: Delipoylated at Lys-132 and Lys-259 by SIRT4, delipoylation decreases the PHD complex activity.
messages: Mitochondrion matrix
messages: Part of the multimeric pyruvate dehydrogenase complex that contains multiple copies of pyruvate dehydrogenase (subunits PDH1A and PDHB, E1), dihydrolipoamide acetyltransferase (DLAT, E2) and lipoamide dehydrogenase (DLD, E3) (PubMed:14638692). These subunits are bound to an inner core composed of about 48 DLAT and 12 PDHX molecules (PubMed:14638692, PubMed:20361979). Interacts with PDK2 and PDK3 (PubMed:15861126, PubMed:17532006, PubMed:17683942, PubMed:18387944). Interacts with SIRT4 (PubMed:25525879). Interacts with PDHB (PubMed:20160912).
messages: Primary biliary cirrhosis is a chronic, progressive cholestatic liver disease characterized by the presence of antimitochondrial autoantibodies in patients' serum. It manifests with inflammatory obliteration of intra-hepatic bile duct, leading to liver cell damage and cirrhosis. Patients with primary biliary cirrhosis show autoantibodies against the E2 component of pyruvate dehydrogenase complex.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.
messages: The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2).

9606:XCR1
gene id: 9606:XCR1
uniprot id: P46094
uniprot id: Q502V0
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Receptor for chemokines SCYC1 and SCYC2. Subsequently transduces a signal by increasing the intracellular calcium ions level. Receptor for XCL1/Lymphotactin.

9606:GPR180
gene id: 9606:GPR180
uniprot id: Q86V85
names: Subcellular Location Annotation
messages: Membrane

9606:G6PC3
gene id: 9606:G6PC3
uniprot id: Q9BUM1
names: Activity Regulation
names: Caution
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: According to PubMed:12370122, it has no hydrolytic activity.
messages: Belongs to the glucose-6-phosphatase family.
messages: Endoplasmic reticulum membrane
messages: Hydrolyzes glucose-6-phosphate to glucose in the endoplasmic reticulum. May form with the glucose-6-phosphate transporter (SLC37A4/G6PT) a ubiquitously expressed complex responsible for glucose production through glycogenolysis and gluconeogenesis. Probably required for normal neutrophil function.
messages: Inhibited by vanadate.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitously expressed. Highly expressed in skeletal muscle, at intermediate levels in heart, brain, placenta, kidney, colon, thymus, spleen and pancreas. Also detected in testis, prostate, ovary, liver, lung, small intestine and peripheral blood lymphocytes.

9606:RP1L1
gene id: 9606:RP1L1
uniprot id: Q8IWN7
names: Disease Annotation
names: Domain
names: Function
names: Miscellaneous
names: Polymorphism
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Interacts with RP1; has a synergistic effect with RP1 in photoreceptor differentiation.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Required for the differentiation of photoreceptor cells. Plays a role in the organization of outer segment of rod and cone photoreceptors (By similarity).
messages: Retinal-specific; expressed in photoreceptor.
messages: The C-terminal part contains a large repetitive region which contains an unusually high percentage of glutamine, glycine and above all glutamic acid residues.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The disease may be caused by variants affecting the gene represented in this entry.
messages: The exact length of RP1L1 is variable between individuals due to the presence of several length polymorphisms. The sequence shown here is that of allele RP1L1-1 and includes 3 repeats (from aa 1292-1342) with a length of 16 amino acids. The number of repeats is highly polymorphic and varies among different alleles, ranging from 3 to 8.
messages: cilium axoneme
messages: photoreceptor outer segment

9606:GGA2
gene id: 9606:GGA2
uniprot id: Q9UJY4
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the GGA protein family.
messages: Early endosome membrane
messages: Endosome membrane
messages: Monomer (Probable). Interacts with NECAP1, TSG101, UBC and AFTPH/aftiphilin. Interacts with CNST (By similarity). Interacts with GGA1 and GGA3 (PubMed:14638859). Binds to clathrin and activated ARFs, such as ARF1, ARF5 and ARF6 (PubMed:11301005, PubMed:11950392). Binds RABEP1 and RABGEF1 (PubMed:12505986). Interacts with the type-I membrane proteins LRP3, M6PR/CD-MPR, IGF2R/CI-MPR and BACE1 (PubMed:11390366, PubMed:11387475, PubMed:11886874, PubMed:14567678). Interacts (via N-terminal VHS domain) with SORL1/sorLA and SORT1 (via C-terminal cytosolic domain) (PubMed:11331584, PubMed:11390366, PubMed:11821067). Binds the accessory proteins CCDC91, P200, SYNRG, EPN4 and NECAP2 (PubMed:10814529, PubMed:12429846, PubMed:12808037, PubMed:14665628). Interacts with ADRA2B (PubMed:27901063). Interacts (via VHS domain) with PIK4B; the interaction is important for PIK4B location at the Golgi apparatus membrane (PubMed:28289207).
messages: Plays a role in protein sorting and trafficking between the trans-Golgi network (TGN) and endosomes. Mediates the ARF-dependent recruitment of clathrin to the TGN and binds ubiquitinated proteins and membrane cargo molecules with a cytosolic acidic cluster-dileucine (DXXLL) motif (PubMed:10747088). Mediates export of the GPCR receptor ADRA2B to the cell surface (PubMed:27901063). Regulates retrograde transport of phosphorylated form of BACE1 from endosomes to the trans-Golgi network (PubMed:15615712).
messages: The GAE domain binds accessory proteins regulating GGAs function.
messages: The GAT domain is responsible for interaction with ARF-GTP, UBC and RABEP1. Required for recruitment to the TGN it prevents ARF-GTP hydrolysis.
messages: The VHS domain functions as a recognition module for sorting signals composed of an acidic cluster followed by two leucines (DXXLL motif).
messages: The unstructured hinge region contains clathrin-binding but no autoinhibitory (DXXLL) motifs.
messages: Ubiquitinated.
messages: Ubiquitously expressed.
messages: trans-Golgi network membrane

9606:RNASET2
gene id: 9606:RNASET2
uniprot id: O00584
names: Activity Regulation
names: Disease Annotation
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the RNase T2 family.
messages: Endoplasmic reticulum lumen
messages: Inhibited by Zn(2+) and Cu(2+).
messages: Lysosome lumen
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Mitochondrion intermembrane space
messages: Ribonuclease that plays an essential role in innate immune response by recognizing and degrading RNAs from microbial pathogens that are subsequently sensed by TLR8 (PubMed:31778653). Cleaves preferentially single-stranded RNA molecules between purine and uridine residues, which critically contributes to the supply of catabolic uridine and the generation of purine-2',3'-cyclophosphate-terminated oligoribonucleotides (PubMed:31778653). In turn, RNase T2 degradation products promote the RNA-dependent activation of TLR8 (PubMed:31778653). Also plays a key role in degradation of mitochondrial RNA and processing of non-coding RNA imported from the cytosol into mitochondria (PubMed:28730546, PubMed:30184494). Participates as well in degradation of mitochondrion-associated cytosolic rRNAs (PubMed:30385512).
messages: Secreted
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitous. Higher expression levels observed in the temporal lobe and fetal brain.

9606:NT5C1B-RDH14
gene id: 9606:NT5C1B-RDH14
uniprot id: Q96P26
names: Activity Regulation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Activated by ADP.
messages: Belongs to the 5'-nucleotidase type 3 family.
messages: Catalyzes the hydrolysis of nucleotide monophosphates, releasing inorganic phosphate and the corresponding nucleoside, AMP is the major substrate.
messages: Cytoplasm
messages: Highly expressed in testis, placenta and pancreas. Detected at lower levels in heart, kidney, liver and lung.

9606:LEMD2
gene id: 9606:LEMD2
uniprot id: Q8NC56
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Interacts (via N-terminus) with LMNA isoform C (via C-terminus) (in vitro) (PubMed:16339967). Interacts (via LEM domain) with BANF1 (PubMed:32494070). Interacts (via C-terminus) with CHMP7 (PubMed:28242692). Interacts (via N-terminus) with tubulin; the interaction causes microtubule bundling and stabilization (in vitro) (PubMed:32494070).
messages: Nuclear lamina-associated inner nuclear membrane protein that is involved in nuclear structure organization, maintenance of nuclear envelope (NE) integrity and NE reformation after mitosis (PubMed:16339967, PubMed:17097643, PubMed:28242692, PubMed:32494070). Plays a role as transmembrane adapter for the endosomal sorting complexes required for transport (ESCRT), and is thereby involved in ESCRT-mediated NE reformation (PubMed:28242692, PubMed:32494070). Promotes ESCRT-mediated NE closure by recruiting CHMP7 and downstream ESCRT-III proteins IST1/CHMP8 and CHMP2A to the reforming NE during anaphase (PubMed:28242692). During nuclear reassembly, condenses into a liquid-like coating around microtubule spindles and coassembles with CHMP7 to form a macromolecular O-ring seal at the confluence between membranes, chromatin, and the spindle to facilitate early nuclear sealing (PubMed:32494070). Plays a role in the organization of heterochromatin associated with the NE and in the maintenance of NE organization under mechanical stress (By similarity). Required for embryonic development and involved in regulation of several signaling pathways such as MAPK and AKT (By similarity). Required for myoblast differentiation involving regulation of ERK signaling (By similarity). Essential for cardiac homeostasis and proper heart function (By similarity).
messages: Nucleus envelope
messages: Nucleus inner membrane
messages: Phosphorylated; strongly phosphorylated in mitosis compared to G1/S.
messages: The LEM domain is required for inner nuclear membrane (INM) localization and contains a BANF1 conserved binding motif which allows localization to chromatin (PubMed:16339967, PubMed:32494070). In late anaphase, as the reforming nuclear envelope (NE) surrounds the chromatin disk, both the LEM domain and the disordered regions are necessary for localization to the NE core (PubMed:32494070).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The disordered regions, also named low complexity domain, confer the ability to phase separate (PubMed:32494070). In late anaphase, as the reforming nuclear envelope (NE) surrounds the chromatin disk, both the LEM domain and the disordered regions are necessary for localization to the NE core (PubMed:32494070). During NE reformation, the proline-arginine-rich sequence within the disordered region binds microtubules, targeting LEM2 condensation to spindle microtubules traversing the nascent NE (PubMed:32494070).
messages: The winged-helix (WH) region (residues 395-503) activates the ESCRT-II/ESCRT-III hybrid protein CHMP7 to form co-oligomeric rings around spindle microtubules to facilitate early nuclear sealing.
messages: Ubiquitously expressed, including bone marrow, brain, kidney, colon, skeletal muscle, thymus, testis and uterus.
messages: spindle

9606:KLK8
gene id: 9606:KLK8
uniprot id: O60259
names: Activity Regulation
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the peptidase S1 family. Kallikrein subfamily.
messages: Cytoplasm
messages: Expressed at high levels in serum, ascites fluid and tumor cytosol of advanced stage ovarian cancer patients and may serve as a marker of ovarian cancer.
messages: Inhibited by a range of serine protease inhibitors including antipain, aprotinin, leupeptin, benzamidine and soybean trypsin inhibitor.
messages: Interacts with SPINK9.
messages: Isoform 1 is predominantly expressed in the pancreas. Isoform 2 is expressed in adult brain and hippocampus. Isoform 1 and isoform 2 are found in fetal brain and placenta. Detected in salivary gland, uterus, thymus, breast, testis and kidney but not in spleen, liver, lung or normal ovarian tissue. Displays an 11.5-fold increase in Alzheimer disease hippocampus compared to controls and is overexpressed in some ovarian carcinomas. Expressed at low levels in normal skin while high levels are found in psoriasis vulgaris, seborrheic keratosis, lichen planus and squamous cell carcinoma skin samples. Expressed in the keratinocytes.
messages: Produced as a result of a human-specific mutation which is not found in other primates.
messages: Secreted
messages: Serine protease which is capable of degrading a number of proteins such as casein, fibrinogen, kininogen, fibronectin and collagen type IV. Also cleaves L1CAM in response to increased neural activity. Induces neurite outgrowth and fasciculation of cultured hippocampal neurons. Plays a role in the formation and maturation of orphan and small synaptic boutons in the Schaffer-collateral pathway, regulates Schaffer-collateral long-term potentiation in the hippocampus and is required for memory acquisition and synaptic plasticity. Involved in skin desquamation and keratinocyte proliferation. Plays a role in the secondary phase of pathogenesis following spinal cord injury.

9606:B3GNT5
gene id: 9606:B3GNT5
uniprot id: Q9BYG0
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the glycosyltransferase 31 family.
messages: Beta-1,3-N-acetylglucosaminyltransferase that plays a key role in the synthesis of lacto- or neolacto-series carbohydrate chains on glycolipids, notably by participating in biosynthesis of HNK-1 and Lewis X carbohydrate structures. Has strong activity toward lactosylceramide (LacCer) and neolactotetraosylceramide (nLc(4)Cer; paragloboside), resulting in the synthesis of Lc(3)Cer and neolactopentaosylceramide (nLc(5)Cer), respectively. Probably plays a central role in regulating neolacto-series glycolipid synthesis during embryonic development.
messages: Golgi apparatus membrane
messages: Up-regulated by stimulation with retinoic acid and down-regulated with 12-O-tetradecanoylphorbol-13-acetate (TPA).
messages: Widely expressed. Highly expressed in lung, colon, placenta, testis, pituitary gland and cerebellum. Weakly expressed in brain, liver, spleen, lymph node and thymus.

9606:HOXB13
gene id: 9606:HOXB13
uniprot id: Q4KR72
uniprot id: Q92826
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the Abd-B homeobox family.
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry.
messages: Heterodimer with MEIS1 (PubMed:28473536). Heterodimer with MEIS2 (Ref.8).
messages: Nucleus
messages: Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. Binds preferentially to methylated DNA (PubMed:28473536).

9606:APOE
gene id: 9606:APOE
uniprot id: A0A0S2Z3D5
uniprot id: P02649
names: Disease Annotation
names: Function
names: Miscellaneous
names: PTM
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts with hepatitis C virus (HCV) envelope glycoprotein E2; this interaction is required for HCV infectivity and production.
messages: (Microbial infection) Through its interaction with HCV envelope glycoprotein E2, participates in the attachment of HCV to HSPGs and other receptors (LDLr, VLDLr, and SR-B1) on the cell surface and to the assembly, maturation and infectivity of HCV viral particles (PubMed:25122793, PubMed:29695434). This interaction is probably promoted via the up-regulation of cellular autophagy by the virus (PubMed:29695434).
messages: APOE exists as multiple glycosylated and sialylated glycoforms within cells and in plasma (PubMed:29516132). The extent of glycosylation and sialylation are tissue and context specific (PubMed:29516132). Plasma APOE undergoes desialylation and is less glycosylated and sialylated than the cellular form (PubMed:2498325, PubMed:19838169, PubMed:20511397, PubMed:23234360). Glycosylation is not required for proper expression and secretion (PubMed:2498325). O-glycosylated with core 1 or possibly core 8 glycans. Thr-307 and Ser-314 are minor glycosylation sites compared to Ser-308 (PubMed:19838169, PubMed:23234360).
messages: APOE is an apolipoprotein, a protein associating with lipid particles, that mainly functions in lipoprotein-mediated lipid transport between organs via the plasma and interstitial fluids (PubMed:6860692, PubMed:1911868, PubMed:14754908). APOE is a core component of plasma lipoproteins and is involved in their production, conversion and clearance (PubMed:6860692, PubMed:2762297, PubMed:1911868, PubMed:1917954, PubMed:9395455, PubMed:14754908, PubMed:23620513). Apolipoproteins are amphipathic molecules that interact both with lipids of the lipoprotein particle core and the aqueous environment of the plasma (PubMed:6860692, PubMed:2762297, PubMed:9395455). As such, APOE associates with chylomicrons, chylomicron remnants, very low density lipoproteins (VLDL) and intermediate density lipoproteins (IDL) but shows a preferential binding to high-density lipoproteins (HDL) (PubMed:6860692, PubMed:1911868). It also binds a wide range of cellular receptors including the LDL receptor/LDLR, the LDL receptor-related proteins LRP1, LRP2 and LRP8 and the very low-density lipoprotein receptor/VLDLR that mediate the cellular uptake of the APOE-containing lipoprotein particles (PubMed:2762297, PubMed:1917954, PubMed:7768901, PubMed:8939961, PubMed:12950167, PubMed:20030366, PubMed:2063194, PubMed:8756331, PubMed:20303980, PubMed:1530612, PubMed:7635945). Finally, APOE has also a heparin-binding activity and binds heparan-sulfate proteoglycans on the surface of cells, a property that supports the capture and the receptor-mediated uptake of APOE-containing lipoproteins by cells (PubMed:9395455, PubMed:9488694, PubMed:23676495, PubMed:7635945). A main function of APOE is to mediate lipoprotein clearance through the uptake of chylomicrons, VLDLs, and HDLs by hepatocytes (PubMed:1911868, PubMed:1917954, PubMed:9395455, PubMed:23676495, PubMed:29516132). APOE is also involved in the biosynthesis by the liver of VLDLs as well as their uptake by peripheral tissues ensuring the delivery of tri…
messages: Belongs to the apolipoprotein A1/A4/E family.
messages: Binds to and activates LILRB4 on acute myeloid leukemia (AML) cells which leads to suppression of T cell proliferation and promotion of AML cell migration and infiltration.
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry. The APOE*4 allele (APOE form E4) is genetically associated with the common late onset familial and sporadic forms of Alzheimer disease. Risk for AD increased from 20% to 90% and mean age at onset decreased from 84 to 68 years with increasing number of APOE*4 alleles in 42 families with late onset AD. Thus APOE*4 gene dose is a major risk factor for late onset AD and, in these families, homozygosity for APOE*4 was virtually sufficient to cause AD by age 80. The mechanism by which APOE*4 participates in pathogenesis is not known.
messages: Extracellular vesicle
messages: Glycated in plasma VLDL of normal subjects, and of hyperglycemic diabetic patients at a higher level (2-3 fold).
messages: Homotetramer (PubMed:8340399). May interact with ABCA1; functionally associated with ABCA1 in the biogenesis of HDLs (PubMed:14754908). May interact with APP/A4 amyloid-beta peptide; the interaction is extremely stable in vitro but its physiological significance is unclear (PubMed:8367470, PubMed:23620513). May interact with MAPT (PubMed:7972031). May interact with MAP2 (PubMed:7891887). In the cerebrospinal fluid, interacts with secreted SORL1 (PubMed:30448281). Interacts with PMEL; this allows the loading of PMEL luminal fragment on ILVs to induce fibril nucleation.
messages: Phosphorylated by FAM20C in the extracellular medium.
messages: Produced by several tissues and cell types and mainly found associated with lipid particles in the plasma, the interstitial fluid and lymph (PubMed:25173806). Mainly synthesized by liver hepatocytes (PubMed:25173806). Significant quantities are also produced in brain, mainly by astrocytes and glial cells in the cerebral cortex, but also by neurons in frontal cortex and hippocampus (PubMed:3115992, PubMed:10027417). It is also expressed by cells of the peripheral nervous system (PubMed:10027417, PubMed:25173806). Also expressed by adrenal gland, testis, ovary, skin, kidney, spleen and adipose tissue and macrophages in various tissues (PubMed:25173806).
messages: Secreted
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The disease is caused by variants affecting the gene represented in this entry. The vast majority of the patients are homozygous for APOE*2 alleles. More severe cases of HLPP3 have also been observed in individuals heterozygous for rare APOE variants. The influence of APOE on lipid levels is often suggested to have major implications for the risk of coronary artery disease (CAD). Individuals carrying the common APOE*4 variant are at higher risk of CAD.
messages: There are three common APOE alleles identified: APOE*2/APOE-epsilon2/E2, APOE*3/APOE-epsilon3/E3, and APOE*4/APOE-epsilon4/E4. The corresponding ApoE2, ApoE3 and ApoE4 isoforms differentially present Cys and Arg residues at positions 130 and 176. The most common allele in the human population is APOE*3 which sequence is the one displayed in that entry with a Cys at position 130 and an Arg at position 176. Common APOE variants influence lipoprotein metabolism in healthy individuals. Additional variants have been described and are described relative to the three common alleles. Allele APOE*4 is strongly associated with risk for severe COVID-19, increases susceptibility to SARS-CoV-2 infection in neurons and astrocytes (PubMed:33450186).
messages: Undergoes C-terminal proteolytic processing in neurons. C-terminally truncated APOE has a tendency to form neurotoxic intracellular neurofibrillary tangle-like inclusions in neurons.
messages: extracellular matrix
messages: extracellular space
messages: multivesicular body

9606:HSD17B10
gene id: 9606:HSD17B10
uniprot id: A0A0S2Z410
uniprot id: Q99714
names: Activity Regulation
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the short-chain dehydrogenases/reductases (SDR) family.
messages: Homotetramer (PubMed:15342248, PubMed:20077426, PubMed:25925575). Component of mitochondrial ribonuclease P, a complex composed of TRMT10C/MRPP1, HSD17B10/MRPP2 and PRORP/MRPP3 (PubMed:18984158, PubMed:25925575, PubMed:26950678, PubMed:28888424). Interacts with TRMT10C/MRPP1; forming the MRPP1-MRPP2 subcomplex of the mitochondrial ribonuclease P complex (PubMed:23042678, PubMed:29040705).
messages: In addition to mitochondrial dehydrogenase activity, moonlights as a component of mitochondrial ribonuclease P, a complex that cleaves tRNA molecules in their 5'-ends (PubMed:18984158, PubMed:24549042, PubMed:25925575, PubMed:26950678, PubMed:28888424). Together with TRMT10C/MRPP1, forms a subcomplex of the mitochondrial ribonuclease P, named MRPP1-MRPP2 subcomplex, which displays functions that are independent of the ribonuclease P activity (PubMed:23042678, PubMed:29040705). The MRPP1-MRPP2 subcomplex catalyzes the formation of N(1)-methylguanine and N(1)-methyladenine at position 9 (m1G9 and m1A9, respectively) in tRNAs; HSD17B10/MRPP2 acting as a non-catalytic subunit (PubMed:23042678, PubMed:25925575, PubMed:28888424). The MRPP1-MRPP2 subcomplex also acts as a tRNA maturation platform: following 5'-end cleavage by the mitochondrial ribonuclease P complex, the MRPP1-MRPP2 subcomplex enhances the efficiency of 3'-processing catalyzed by ELAC2, retains the tRNA product after ELAC2 processing and presents the nascent tRNA to the mitochondrial CCA tRNA nucleotidyltransferase TRNT1 enzyme (PubMed:29040705). Associates with mitochondrial DNA complexes at the nucleoids to initiate RNA processing and ribosome assembly.
messages: Mitochondrial dehydrogenase involved in pathways of fatty acid, branched-chain amino acid and steroid metabolism (PubMed:9553139, PubMed:10600649, PubMed:12917011, PubMed:20077426, PubMed:18996107, PubMed:19706438, PubMed:25925575, PubMed:26950678, PubMed:28888424). Acts as (S)-3-hydroxyacyl-CoA dehydrogenase in mitochondrial fatty acid beta-oxidation, a major degradation pathway of fatty acids. Catalyzes the third step in the beta-oxidation cycle, namely the reversible conversion of (S)-3-hydroxyacyl-CoA to 3-ketoacyl-CoA. Preferentially accepts straight medium- and short-chain acyl-CoA substrates with highest efficiency for (3S)-hydroxybutanoyl-CoA (PubMed:9553139, PubMed:10600649, PubMed:12917011, PubMed:25925575, PubMed:26950678). Acts as 3-hydroxy-2-methylbutyryl-CoA dehydrogenase in branched-chain amino acid catabolic pathway. Catalyzes the oxidation of 3-hydroxy-2-methylbutanoyl-CoA into 2-methyl-3-oxobutanoyl-CoA, a step in isoleucine degradation pathway (PubMed:20077426, PubMed:18996107, PubMed:19706438). Has hydroxysteroid dehydrogenase activity toward steroid hormones and bile acids. Catalyzes the oxidation of 3alpha-, 17beta-, 20beta- and 21-hydroxysteroids and 7alpha- and 7beta-hydroxy bile acids (PubMed:10600649, PubMed:12917011). Oxidizes allopregnanolone/brexanolone at the 3alpha-hydroxyl group, which is known to be critical for the activation of gamma-aminobutyric acid receptors (GABAARs) chloride channel (PubMed:19706438, PubMed:28888424). Has phospholipase C-like activity toward cardiolipin and its oxidized species. Likely oxidizes the 2'-hydroxyl in the head group of cardiolipin to form a ketone intermediate that undergoes nucleophilic attack by water and fragments into diacylglycerol, dihydroxyacetone and orthophosphate. Has higher affinity for cardiolipin with oxidized fatty acids and may degrade these species during the oxidative stress response to protect cells from apoptosis (PubMed:26338420). By interacting with intracellular amyloid-beta, …
messages: Mitochondrion
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The phospholipase C-like activity toward cardiolipin is inhibited by amyloid-beta peptide.
messages: Ubiquitously expressed in normal tissues but is overexpressed in neurons affected in AD.
messages: mitochondrion nucleoid

9606:SELENOS
gene id: 9606:SELENOS
uniprot id: Q6GYA4
uniprot id: Q9BQE4
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the selenoprotein S family.
messages: Cytoplasm
messages: Endoplasmic reticulum membrane
messages: Interacts with DERL1 and (via VIM motif) with VCP, suggesting that it forms a membrane complex with DERL1 that serves as a receptor for VCP. Also interacts with DERL2, DERL3 and SELENOK. The SELENOK-SELENOS complex interacts with VCP. Interacts with CCDC47 (By similarity).
messages: Involved in the degradation process of misfolded endoplasmic reticulum (ER) luminal proteins. Participates in the transfer of misfolded proteins from the ER to the cytosol, where they are destroyed by the proteasome in a ubiquitin-dependent manner. Probably acts by serving as a linker between DERL1, which mediates the retrotranslocation of misfolded proteins into the cytosol, and the ATPase complex VCP, which mediates the translocation and ubiquitination.
messages: Membrane
messages: Truncated SELENOS proteins produced by failed UGA/Sec decoding are ubiquitinated by the CRL2(KLHDC2) and CRL2(KLHDC3) complexes, which recognizes the glycine (Gly) at the C-terminus of truncated SELENOS proteins (PubMed:26138980, PubMed:30526872). Truncated SELENOS proteins produced by failed UGA/Sec decoding are also ubiquitinated by the CRL5(KLHDC1) complex (PubMed:32200094).

9606:REXO2
gene id: 9606:REXO2
uniprot id: Q9Y3B8
names: Activity Regulation
names: Developmental Stage
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: 3'-to-5'exoribonuclease that preferentially degrades DNA and RNA oligonucleotides composed of only two nucleotides (PubMed:31588022, PubMed:30926754, PubMed:32365187, PubMed:23741365). Binds and degrades longer oligonucleotides with a lower affinity (PubMed:31588022, PubMed:30926754, PubMed:32365187). Plays dual roles in mitochondria, scavenging nanoRNAs (small RNA oligonucleotides of <5 nucleotides) that are produced by the degradosome and clearing short RNAs that are generated by RNA processing (PubMed:31588022, PubMed:30926754, PubMed:32365187). Essential for correct initiation of mitochondrial transcription, degrading mitochondrial RNA dinucleotides to prevent RNA-primed transcription at non-canonical sites in the mitochondrial genome (PubMed:31588022). Essential for embryonic development (By similarity).
messages: 3'-to-5'exoribonuclease that preferentially degrades DNA and RNA oligonucleotides composed of only two nucleotides.
messages: Belongs to the oligoribonuclease family.
messages: Cytoplasm
messages: Expressed in fetal liver, lung and kidney.
messages: Highly expressed in the heart and at lower levels in the lymph nodes, brain, lung, liver, spleen and thymus.
messages: Homodimer (PubMed:31588022, PubMed:30926754, PubMed:32365187). Homotetramer (PubMed:23741365).
messages: Inhibited by adenosine 3',5'-bisphosphate.
messages: Mitochondrion
messages: Mitochondrion intermembrane space
messages: Mitochondrion matrix
messages: Nucleus

9606:GOT2
gene id: 9606:GOT2
uniprot id: P00505
names: Disease Annotation
names: Function
names: Induction
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the class-I pyridoxal-phosphate-dependent aminotransferase family.
messages: Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular NAD(H) redox balance. Is important for metabolite exchange between mitochondria and cytosol, and for amino acid metabolism. Facilitates cellular uptake of long-chain free fatty acids.
messages: Cell membrane
messages: Homodimer.
messages: In eukaryotes there are cytoplasmic, mitochondrial and chloroplastic isozymes.
messages: Mitochondrion matrix
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Up-regulated by long-time exposure to alcohol.

9606:RTL6
gene id: 9606:RTL6
uniprot id: Q6ICC9
names: Miscellaneous
names: Similarity
messages: Belongs to the LDOC1 family.
messages: RTL6 is one of at least 11 genes called Mar or Mart related to long terminal repeat retrotransposons. They do not correspond to functional retrotransposons, but rather to neofunctionalized retrotransposons genes.

9606:ZNF26
gene id: 9606:ZNF26
uniprot id: P17031
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:OR7G2
gene id: 9606:OR7G2
uniprot id: A0A126GW43
uniprot id: Q8NG99
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Membrane
messages: Odorant receptor.

9606:ZNF830
gene id: 9606:ZNF830
uniprot id: Q96NB3
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: Chromosome
messages: Component of the XAB2 complex, a multimeric protein complex composed of XAB2, PRPF19, AQR, ZNF830, ISY1, and PPIE; this complex binds preferentially to RNA. Interacts with XAB2 (PubMed:17981804). Identified in a pentameric intron-binding (IB) complex composed of AQR, XAB2, ISY1, ZNF830 and PPIE that is incorporated into the spliceosome as a preassembled complex (PubMed:25599396). The IB complex does not contain PRPF19 (PubMed:25599396).
messages: May play a role in pre-mRNA splicing as component of the spliceosome (PubMed:25599396). Acts as an important regulator of the cell cycle that participates in the maintenance of genome integrity. During cell cycle progression in embryonic fibroblast, prevents replication fork collapse, double-strand break formation and cell cycle checkpoint activation. Controls mitotic cell cycle progression and cell survival in rapidly proliferating intestinal epithelium and embryonic stem cells. During the embryo preimplantation, controls different aspects of M phase. During early oocyte growth, plays a role in oocyte survival by preventing chromosomal breaks formation, activation of TP63 and reduction of transcription (By similarity).
messages: Nucleus
messages: Nucleus speckle
messages: Phosphorylated in response to DNA damage by the cell cycle checkpoint kinases ATR/ATM.

9606:HTR3B
gene id: 9606:HTR3B
uniprot id: O95264
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the ligand-gated ion channel (TC 1.A.9) family. 5-hydroxytryptamine receptor (TC 1.A.9.2) subfamily. HTR3B sub-subfamily.
messages: Cell membrane
messages: Expressed in the brain cortex, in the caudate nucleus, the hippocampus, the thalamus and the amygdala. Detected in the kidney and testis as well as in monocytes of the spleen, small and large intestine, uterus, prostate, ovary and placenta.
messages: Forms homopentameric as well as heteropentameric serotonin-activated cation-selective channel complexes with HTR3A. The homomeric complex is not functional. Heteropentameric complexes display properties which resemble that of neuronal serotonin-activated channels in vivo.
messages: Forms serotonin (5-hydroxytryptamine/5-HT3)-activated cation-selective channel complexes, which when activated cause fast, depolarizing responses in neurons.
messages: N-glycosylation required for membrane localization.
messages: Postsynaptic cell membrane
messages: The HA-stretch region of HTR3B seems to confer increased conductance to HTR3A/HTR3B heteromers compared to that of HTR3A homomers.

9606:SLC2A8
gene id: 9606:SLC2A8
uniprot id: Q9NY64
names: Activity Regulation
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the major facilitator superfamily. Sugar transporter (TC 2.A.1.1) family. Glucose transporter subfamily.
messages: Cell membrane
messages: Cytoplasmic vesicle membrane
messages: Highly expressed in testis, but not in testicular carcinoma. Lower amounts present in most other tissues.
messages: In testis, down-regulated by estrogen.
messages: Inhibited by cytochalasin B.
messages: Insulin-regulated facilitative hexose transporter that mediates the transport of glucose and fructose (By similarity). Facilitates hepatic influx of dietary trehalose, which in turn inhibits glucose and fructose influx triggering a starvation signal and hepatic autophagy through activation of AMPK and ULK1 (PubMed:27922102). Also able to mediate the transport of dehydroascorbate.
messages: Interacts with AP2B1.

9606:GALNT16
gene id: 9606:GALNT16
uniprot id: Q68VJ8
uniprot id: Q8N428
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the glycosyltransferase 2 family. GalNAc-T subfamily.
messages: Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor.
messages: Golgi apparatus membrane
messages: Membrane
messages: The ricin B-type lectin domain binds to GalNAc and contributes to the glycopeptide specificity.
messages: There are two conserved domains in the glycosyltransferase region: the N-terminal domain (domain A, also called GT1 motif), which is probably involved in manganese coordination and substrate binding and the C-terminal domain (domain B, also called Gal/GalNAc-T motif), which is probably involved in catalytic reaction and UDP-Gal binding.

9606:ISCA2
gene id: 9606:ISCA2
uniprot id: Q86U28
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the HesB/IscA family.
messages: Involved in the maturation of mitochondrial 4Fe-4S proteins functioning late in the iron-sulfur cluster assembly pathway. May be involved in the binding of an intermediate of Fe/S cluster assembly.
messages: Mitochondrion
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:BRIX1
gene id: 9606:BRIX1
uniprot id: Q8TDN6
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the BRX1 family.
messages: Required for biogenesis of the 60S ribosomal subunit.
messages: nucleolus

9606:COL28A1
gene id: 9606:COL28A1
uniprot id: Q2UY09
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the VWA-containing collagen family.
messages: May act as a cell-binding protein.
messages: Trimer or homomer. Secreted as a 135 kDa monomer under reducing conditions and as a homotrimer under non-reducing conditions (By similarity).
messages: basement membrane

9606:IL17RC
gene id: 9606:IL17RC
uniprot id: Q8NAC3
names: Disease Annotation
names: Function
names: Induction
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: By HGF and VEGF.
messages: Cell membrane
messages: Does not bind IL17A or IL17F.
messages: Expressed in prostate, skeletal muscle, kidney and placenta (at protein level) (PubMed:11706037). Expressed in brain, cartilage, colon, heart, intestine, kidney, liver, lung, muscle, placenta, and prostate (PubMed:11706037). Also detected in thyroid, trachea and adrenal gland (PubMed:17911633). Low expression in thymus and leukocytes (PubMed:11706037).
messages: Homodimer; disulfide-linked (PubMed:32187518). Heterodimer with IL17RA (PubMed:16785495, PubMed:18684971). Heterodimerization with IL17RA is independent of the cytoplasmic tail (By similarity). Associates with non-glycosylated IL17RA constitutively (By similarity). Binding of IL17A and IL17F induces association with glycosylated IL17RA (By similarity). Forms complexes with 2:1 binding stoichiometry: two receptor chains for one interleukin molecule (PubMed:32187518, PubMed:28827714). IL17A homodimer preferentially drives the formation of IL17RA-IL17RC heterodimeric receptor complex, whereas IL17F homodimer forms predominantly complexes with IL17RC homodimer (PubMed:32187518). IL17A-IL17F forms complexes with IL17RA-IL17RC, but with lower affinity when compared to IL17A homodimer (PubMed:32187518). IL17RC chain cannot distinguish between IL17A and IL17F molecules, potentially enabling the formation of topologically distinct complexes (PubMed:28827714). Interacts (through SEFIR domain and extended downstream region) with TRAF3IP2/ACT1 (phosphorylated) (PubMed:24120361).
messages: Receptor for IL17A and IL17F, major effector cytokines of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity (By similarity). Receptor for IL17A and IL17F, major effector cytokines of innate and adaptive immune system involved in antimicrobial host defense and maintenance of tissue integrity. Receptor for IL17A and IL17F homodimers as part of a heterodimeric complex with IL17RA (PubMed:16785495). Receptor for the heterodimer formed by IL17A and IL17B as part of a heterodimeric complex with IL17RA (PubMed:18684971). Has also been shown to be the cognate receptor for IL17F and to bind IL17A with high affinity without the need for IL17RA (PubMed:17911633). Upon binding of IL17F homodimer triggers downstream activation of TRAF6 and NF-kappa-B signaling pathway (PubMed:16785495, PubMed:32187518). Induces transcriptional activation of IL33, a potent cytokine that stimulates group 2 innate lymphoid cells and adaptive T-helper 2 cells involved in pulmonary allergic response to fungi (By similarity). Promotes sympathetic innervation of peripheral organs by coordinating the communication between gamma-delta T cells and parenchymal cells. Stimulates sympathetic innervation of thermogenic adipose tissue by driving TGFB1 expression (By similarity). Binding of IL17A-IL17F to IL17RA-IL17RC heterodimeric receptor complex triggers homotypic interaction of IL17RA and IL17RC chains with TRAF3IP2 adapter through SEFIR domains. This leads to downstream TRAF6-mediated activation of NF-kappa-B and MAPkinase pathways ultimately resulting in transcriptional activation of cytokines, chemokines, antimicrobial peptides and matrix metalloproteinases, with potential strong immune inflammation (PubMed:18684971, PubMed:17911633). Primarily induces neutrophil activation and recruitment at infection and inflammatory sites (By similarity). Stimulates the production of antimicrobial beta-defensins DEFB1, DEFB103A, and DEFB104A by mucosal epithe…
messages: Receptor for both IL17A and IL17F.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:GBP5
gene id: 9606:GBP5
uniprot id: Q96PP8
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Antigenic tumor-specific truncated splice form.
messages: Belongs to the TRAFAC class dynamin-like GTPase superfamily. GB1/RHD3 GTPase family. GB1 subfamily.
messages: By IFNG in endothelial cells and in LPS-primed macrophages.
messages: Cytoplasm
messages: Cytoplasmic vesicle membrane
messages: Expressed in peripheral blood monocytes (at protein level).
messages: Golgi apparatus membrane
messages: Homodimer; homodimerizes upon GTP-binding (PubMed:20180847). GDP-bound form remains homodimeric (PubMed:20180847).
messages: Homodimer; homodimerizes upon GTP-binding (PubMed:20180847). GDP-bound is monomeric (PubMed:20180847).
messages: Homodimer; homodimerizes upon GTP-binding, forming a close face-to-face dimer (PubMed:20180847, PubMed:21151871, PubMed:33876762). Heterodimer with other family members, including GBP1, GBP2, GBP3 and GBP4 (PubMed:21151871). May also form tetramers (dimer of dimers) in the presence of GTP (PubMed:20180847). Interacts with NLRP3, possibly in its tetrameric form, and promotes PYCARD/ASC polymerization (PubMed:22461501).
messages: Interferon (IFN)-inducible GTPase that plays important roles in innate immunity against a diverse range of bacterial, viral and protozoan pathogens (By similarity). Hydrolyzes GTP, but in contrast to other family members, does not produce GMP (PubMed:20180847). Following infection, recruited to the pathogen-containing vacuoles or vacuole-escaped bacteria and acts as a positive regulator of inflammasome assembly by promoting the release of inflammasome ligands from bacteria (By similarity). Acts by promoting lysis of pathogen-containing vacuoles, releasing pathogens into the cytosol (By similarity). Following pathogen release in the cytosol, promotes recruitment of proteins that mediate bacterial cytolysis: this liberates ligands that are detected by inflammasomes, such as lipopolysaccharide (LPS) that activates the non-canonical CASP4/CASP11 inflammasome or double-stranded DNA (dsDNA) that activates the AIM2 inflammasome (By similarity). As an activator of NLRP3 inflammasome assembly: promotes selective NLRP3 inflammasome assembly in response to microbial and soluble, but not crystalline, agents (PubMed:22461501). Independently of its GTPase activity, acts as an inhibitor of various viruses infectivity, such as HIV-1, Zika and influenza A viruses, by inhibiting FURIN-mediated maturation of viral envelope proteins (PubMed:26996307, PubMed:31091448).
messages: Isoprenylation is required for proper subcellular location.

9606:SMIM7
gene id: 9606:SMIM7
uniprot id: B7WNH4
uniprot id: Q9BQ49
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the SMIM7 family.
messages: Membrane

9606:ARMC8
gene id: 9606:ARMC8
uniprot id: B7Z637
uniprot id: Q8IUR7
names: Function
names: Sequence Caution
names: Subcellular Location Annotation
names: Subunit
messages: Component of the CTLH E3 ubiquitin-protein ligase complex that selectively accepts ubiquitin from UBE2H and mediates ubiquitination and subsequent proteasomal degradation of the transcription factor HBP1.
messages: Cytoplasm
messages: Identified in the CTLH complex that contains GID4, RANBP9 and/or RANBP10, MKLN1, MAEA, RMND5A (or alternatively its paralog RMND5B), GID8, ARMC8, WDR26 and YPEL5 (PubMed:17467196, PubMed:29911972). Within this complex, MAEA, RMND5A (or alternatively its paralog RMND5B), GID8, WDR26, and RANBP9 and/or RANBP10 form the catalytic core, while GID4, MKLN1, ARMC8 and YPEL5 have ancillary roles (PubMed:29911972).
messages: Intron retention.
messages: Nucleus

9606:PRKAB2
gene id: 9606:PRKAB2
uniprot id: O43741
names: Function
names: PTM
names: Similarity
names: Subunit
messages: AMPK is a heterotrimer of an alpha catalytic subunit (PRKAA1 or PRKAA2), a beta (PRKAB1 or PRKAB2) and a gamma non-catalytic subunits (PRKAG1, PRKAG2 or PRKAG3).
messages: Belongs to the 5'-AMP-activated protein kinase beta subunit family.
messages: Non-catalytic subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Beta non-catalytic subunit acts as a scaffold on which the AMPK complex assembles, via its C-terminus that bridges alpha (PRKAA1 or PRKAA2) and gamma subunits (PRKAG1, PRKAG2 or PRKAG3).
messages: Phosphorylated when associated with the catalytic subunit (PRKAA1 or PRKAA2). Phosphorylated by ULK1 and ULK2; leading to negatively regulate AMPK activity and suggesting the existence of a regulatory feedback loop between ULK1, ULK2 and AMPK.

9606:PGR
gene id: 9606:PGR
uniprot id: P06401
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the nuclear hormone receptor family. NR3 subfamily.
messages: Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.
messages: Cytoplasm
messages: In reproductive tissues the expression of isoform A and isoform B varies as a consequence of developmental and hormonal status. Isoform A and isoform B are expressed in comparable levels in uterine glandular epithelium during the proliferative phase of the menstrual cycle. Expression of isoform B but not of isoform A persists in the glands during mid-secretory phase. In the stroma, isoform A is the predominant form throughout the cycle. Heterogeneous isoform expression between the glands of the endometrium basalis and functionalis is implying region-specific responses to hormonal stimuli.
messages: Increases mitochondrial membrane potential and cellular respiration upon stimulation by progesterone.
messages: Interacts with SMARD1 and UNC45A. Interacts with CUEDC2; the interaction promotes ubiquitination, decreases sumoylation, and represses transcriptional activity. Interacts with PIAS3; the interaction promotes sumoylation of PR in a hormone-dependent manner, inhibits DNA-binding, and alters nuclear export. Interacts with SP1; the interaction requires ligand-induced phosphorylation on Ser-345 by ERK1/2 MAPK. Interacts with PRMT2. Isoform A interacts with NCOR2. Isoform B (but not isoform A) interacts with NCOA2 and NCOA1. Isoform B (but not isoform A) interacts with KLF9. Interacts with GTF2B (PubMed:1517211).
messages: Ligand-dependent transdominant repressor of steroid hormone receptor transcriptional activity including repression of its isoform B, MR and ER. Transrepressional activity may involve recruitment of corepressor NCOR2.
messages: Mitochondrion outer membrane
messages: Nucleus
messages: Palmitoylated by ZDHHC7 and ZDHHC21. Palmitoylation is required for plasma membrane targeting and for rapid intracellular signaling via ERK and AKT kinases and cAMP generation.
messages: Phosphorylated on multiple serine sites. Several of these sites are hormone-dependent. Phosphorylation on Ser-294 occurs preferentially on isoform B, is highly hormone-dependent and modulates ubiquitination and sumoylation on Lys-388. Phosphorylation on Ser-102 and Ser-345 also requires induction by hormone. Basal phosphorylation on Ser-81, Ser-162, Ser-190 and Ser-400 is increased in response to progesterone and can be phosphorylated in vitro by the CDK2-A1 complex. Increased levels of phosphorylation on Ser-400 also in the presence of EGF, heregulin, IGF, PMA and FBS. Phosphorylation at this site by CDK2 is ligand-independent, and increases nuclear translocation and transcriptional activity. Phosphorylation at Ser-162 and Ser-294, but not at Ser-190, is impaired during the G(2)/M phase of the cell cycle. Phosphorylation on Ser-345 by ERK1/2 MAPK is required for interaction with SP1.
messages: Produced by alternative promoter usage.
messages: Produced by alternative splicing of isoform B.
messages: Sumoylation is hormone-dependent and represses transcriptional activity. Sumoylation on all three sites is enhanced by PIAS3. Desumoylated by SENP1. Sumoylation on Lys-388, the main site of sumoylation, is repressed by ubiquitination on the same site, and modulated by phosphorylation at Ser-294.
messages: The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Depending on the isoform, progesterone receptor functions as transcriptional activator or repressor.
messages: Transcriptional activator of several progesteron-dependent promoters in a variety of cell types. Involved in activation of SRC-dependent MAPK signaling on hormone stimulation.
messages: Ubiquitination is hormone-dependent and represses sumoylation on the same site. Promoted by MAPK-mediated phosphorylation on Ser-294.

9606:GANC
gene id: 9606:GANC
uniprot id: Q8TET4
names: Function
names: Similarity
messages: Belongs to the glycosyl hydrolase 31 family.
messages: Has alpha-glucosidase activity.

9606:RND1
gene id: 9606:RND1
uniprot id: Q92730
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the small GTPase superfamily. Rho family.
messages: Binds GRB7 and PLXNB1. Interacts with UBXD5. Interacts with PLXNA2.
messages: Cell membrane
messages: Lacks intrinsic GTPase activity. Has a low affinity for GDP, and constitutively binds GTP. Controls rearrangements of the actin cytoskeleton. Induces the Rac-dependent neuritic process formation in part by disruption of the cortical actin filaments. Causes the formation of many neuritic processes from the cell body with disruption of the cortical actin filaments.
messages: Mostly expressed in brain and liver.
messages: cytoskeleton

9606:FAM167B
gene id: 9606:FAM167B
uniprot id: Q9BTA0
names: Similarity
messages: Belongs to the FAM167 (SEC) family.

9606:FADD
gene id: 9606:FADD
uniprot id: Q13158
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Glycosylated at Arg-117 by enteropathogenic E.coli protein NleB1, C.rodentium protein NleB and S.typhimurium protein Ssek1: arginine GlcNAcylation prevents recruitment of caspase-8 or caspase-10 to the activated Fas (CD95) or TNFR-1 receptors.
messages: (Microbial infection) Interacts with human papillomavirus 16/HPV16 protein E6.
messages: (Microbial infection) Interacts with molluscum contagiosum virus proteins MC159L/v-CFLAR and MC160L.
messages: Apoptotic adaptor molecule that recruits caspase-8 or caspase-10 to the activated Fas (CD95) or TNFR-1 receptors (PubMed:7538907, PubMed:23955153, PubMed:19118384, PubMed:20935634, PubMed:16762833, PubMed:24025841). The resulting aggregate called the death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation (PubMed:7538907, PubMed:19118384, PubMed:20935634, PubMed:16762833). Active caspase-8 initiates the subsequent cascade of caspases mediating apoptosis (PubMed:16762833). Involved in interferon-mediated antiviral immune response, playing a role in the positive regulation of interferon signaling (PubMed:21109225).
messages: Can self-associate (PubMed:19118384, PubMed:20935634). Interacts with CFLAR, PEA15 and MBD4 (PubMed:10442631, PubMed:12702765). When phosphorylated, part of a complex containing HIPK3 and FAS (PubMed:11034606). May interact with MAVS/IPS1 (PubMed:16127453). Interacts with MOCV v-CFLAR protein and PIDD1 (PubMed:10825539). Interacts (via death domain) with FAS (via death domain) (PubMed:21109225, PubMed:16762833, PubMed:20935634). Interacts with CASP8 (PubMed:16762833). Interacts directly (via DED domain) with NOL3 (via CARD domain); inhibits death-inducing signaling complex (DISC) assembly by inhibiting the increase in FAS-FADD binding induced by FAS activation (By similarity). Interacts with RIPK1, TRADD and CASP8 (By similarity). Component of the AIM2 PANoptosome complex, a multiprotein complex that drives inflammatory cell death (PANoptosis) (By similarity). Interacts with stimulated TNFRSF10B (PubMed:18846110). Interacts with stimulated TNFRSF10B (By similarity).
messages: Contains a death domain involved in the binding of the corresponding domain within Fas receptor.
messages: Expressed in a wide variety of tissues, except for peripheral blood mononuclear leukocytes.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The interaction between the FAS and FADD death domains is crucial for the formation of the death-inducing signaling complex (DISC).

9606:PSG6
gene id: 9606:PSG6
uniprot id: Q00889
names: Developmental Stage
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the immunoglobulin superfamily. CEA family.
messages: PSBG are produced in high quantity during pregnancy.
messages: Secreted

9606:RSPH1
gene id: 9606:RSPH1
uniprot id: Q8WYR4
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Chromosome
messages: Component of the axonemal radial spoke 1 (RS1) and 2 (RS2) complexes, at least composed of spoke head proteins RSPH1, RSPH3, RSPH9 and the cilia-specific component RSPH4A or sperm-specific component RSPH6A, spoke stalk proteins RSPH14, DNAJB13, DYDC1, ROPN1L and NME5, and the RS1 complex-specific anchor protein IQUB (By similarity). Interacts with RSPH3B (By similarity). Interacts with RSPH4A (By similarity). Interacts with RSPH6A (By similarity).
messages: Cytoplasm
messages: Expressed in trachea, lungs, airway brushings, and testes.
messages: Functions as part of axonemal radial spoke complexes that play an important part in the motility of sperm and cilia.
messages: The disease is caused by variants affecting the gene represented in this entry. RSPH1 mutations result in a primary ciliary diskinesia phenotype with defects of the radial spokes and the axonemal central pair of microtubules (PubMed:23993197).
messages: cilium axoneme
messages: flagellum axoneme

9606:DUSP10
gene id: 9606:DUSP10
uniprot id: Q9Y6W6
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily.
messages: Cytoplasm
messages: Expressed in keratinocytes (at protein level) (PubMed:29043977). Detected in brain (PubMed:16806267).
messages: Monomer. Interacts with MAPK14.
messages: Nucleus
messages: Protein phosphatase involved in the inactivation of MAP kinases. Has a specificity for the MAPK11/MAPK12/MAPK13/MAPK14 subfamily. It preferably dephosphorylates p38.

9606:ST8SIA5
gene id: 9606:ST8SIA5
uniprot id: B7Z5F7
uniprot id: F5H8D1
uniprot id: O15466
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the glycosyltransferase 29 family.
messages: Expressed in fetal and adult brain, adult heart and skeletal muscle.
messages: Expressed in fetal and adult brain, not detected in adult heart and skeletal muscle.
messages: Golgi apparatus membrane
messages: Involved in the synthesis of gangliosides GD1c, GT1a, GQ1b, GP1c and GT3 from GD1a, GT1b, GM1b and GD3 respectively.
messages: Membrane

9606:PDP2
gene id: 9606:PDP2
uniprot id: Q9P2J9
names: Cofactor
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the PP2C family.
messages: Binds 2 magnesium ions per subunit.
messages: Catalyzes the dephosphorylation and concomitant reactivation of the alpha subunit of the E1 component of the pyruvate dehydrogenase complex.
messages: Heterodimer of a catalytic subunit and a FAD protein of unknown function.
messages: Mitochondrion matrix

9606:CERT1
gene id: 9606:CERT1
uniprot id: Q9Y5P4
names: Caution
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cytoplasm
messages: Endoplasmic reticulum
messages: Golgi apparatus
messages: Interacts with VAPA and VAPB. Interaction with VAPB is less efficient than with VAPA (PubMed:16895911). Interacts (via FFAT motif) with MOSPD2 (via MSP domain) (PubMed:29858488).
messages: Phosphorylation on Ser-132 decreases the affinity toward phosphatidylinositol 4-phosphate at Golgi membranes and reduces ceramide transfer activity. Inactivated by hyperphosphorylation of serine residues by CSNK1G2/CK1 that triggers dissociation from the Golgi complex, thus down-regulating ER-to-Golgi transport of ceramide and sphingomyelin synthesis.
messages: Shelters ceramides and diacylglycerol lipids inside its START domain and mediates the intracellular trafficking of ceramides and diacylglycerol lipids in a non-vesicular manner.
messages: The FFAT motif is required for interaction with VAPA, VAPB and MOSPD2.
messages: The PH domain targets the Golgi apparatus.
messages: The START domain recognizes ceramides and diacylglycerol lipids, interacts with membranes, and mediates the intermembrane transfer of ceramides and diacylglycerol lipids.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Was originally reported to have a protein kinase activity and to phosphorylate on Ser and Thr residues the Goodpasture autoantigen (in vitro).
messages: Widely expressed.

9606:PSMB7
gene id: 9606:PSMB7
uniprot id: E9KL30
uniprot id: Q99436
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts with HIV-1 Tat protein.
messages: Belongs to the peptidase T1B family.
messages: Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). Within the 20S core complex, PSMB7 displays a trypsin-like activity.
messages: Component of the proteasome complex.
messages: Component of the proteasome, a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity.
messages: Cytoplasm
messages: Expressed at a low level in colonic mucosa. Up-regulated in colorectal cancer tissues.
messages: Nucleus
messages: The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7.

9606:GPAT3
gene id: 9606:GPAT3
uniprot id: A0A024RDG5
uniprot id: Q53EU6
names: Activity Regulation
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the 1-acyl-sn-glycerol-3-phosphate acyltransferase family.
messages: Converts glycerol-3-phosphate to 1-acyl-sn-glycerol-3-phosphate (lysophosphatidic acid or LPA) by incorporating an acyl moiety at the sn-1 position of the glycerol backbone (PubMed:17170135). Also converts LPA into 1,2-diacyl-sn-glycerol-3-phosphate (phosphatidic acid or PA) by incorporating an acyl moiety at the sn-2 position of the glycerol backbone (PubMed:19318427). Protects cells against lipotoxicity (PubMed:30846318).
messages: Endoplasmic reticulum membrane
messages: Inhibited by N-ethylmaleimide (NEM).
messages: The HXXXXD motif is essential for acyltransferase activity and may constitute the binding site for the phosphate moiety of the glycerol-3-phosphate.
messages: Widely expressed. Expressed in liver, kidney, testis, brain, heart, skeletal muscle, thyroid, prostate, thymus and placenta. Also expressed lung and adipose tissue.

9606:PHLPP1
gene id: 9606:PHLPP1
uniprot id: O60346
names: Activity Regulation
names: Cofactor
names: Domain
names: Function
names: Sequence Caution
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Binds 2 manganese ions per subunit (By similarity). Mn(2+) is inhibitory below pH 8 and activating above pH 8 (PubMed:24892992).
messages: Cell membrane
messages: Contaminating sequence. Potential poly-A sequence.
messages: Cytoplasm
messages: In colorectal cancer tissue, expression is highest in the surface epithelium of normal colonic mucosa adjacent to the cancer tissue but is largely excluded from the crypt bases. Expression is lost or significantly decreased in 78% of tested tumors (at protein level). Ubiquitously expressed in non-cancerous tissues.
messages: Insensitive to okadaic acid (PubMed:15808505). Deubiquitination by WDR48-USP12 complex positively regulates PHLPP1 stability (PubMed:24145035).
messages: Interacts with the nucleotide free form of K-Ras (KRAS) via its LRR repeats (By similarity). Interacts with AKT2, AKT3, PRKCB isoform beta-II, STK4, RPS6KB1, RAF1 (PubMed:17386267, PubMed:18162466, PubMed:19732725, PubMed:21986499, PubMed:24530606). Isoform 1 (predominantly) and isoform 2 interact with BRAP (PubMed:25820252). Interacts with FKBP5; FKBP5 acts as a scaffold for PHLPP1 and Akt (PubMed:19732725). Interacts with SCRIB; SCRIB acts as a scaffold for PHLPP1 and Akt (PubMed:21701506). Interacts with NHERF1; NHERF1 scaffolds a heterotrimeric complex with PTEN at the plasma membrane (PubMed:21804599). Interacts with WDR48 and USP12 (PubMed:24145035).
messages: Membrane
messages: Nucleus
messages: Protein phosphatase involved in regulation of Akt and PKC signaling. Mediates dephosphorylation in the C-terminal domain hydrophobic motif of members of the AGC Ser/Thr protein kinase family; specifically acts on 'Ser-473' of AKT2 and AKT3, 'Ser-660' of PRKCB and 'Ser-657' of PRKCA (PubMed:15808505, PubMed:17386267, PubMed:18162466). Isoform 2 seems to have a major role in regulating Akt signaling in hippocampal neurons (By similarity). Akt regulates the balance between cell survival and apoptosis through a cascade that primarily alters the function of transcription factors that regulate pro- and antiapoptotic genes. Dephosphorylation of 'Ser-473' of Akt triggers apoptosis and suppression of tumor growth. Dephosphorylation of PRKCA and PRKCB leads to their destabilization and degradation (PubMed:18162466). Dephosphorylates STK4 on 'Thr-387' leading to STK4 activation and apoptosis (PubMed:20513427). Dephosphorylates RPS6KB1 and is involved in regulation of cap-dependent translation (PubMed:21986499). Inhibits cancer cell proliferation and may act as a tumor suppressor (PubMed:19079341). Dephosphorylates RAF1 inhibiting its kinase activity (PubMed:24530606). May act as a negative regulator of K-Ras signaling in membrane rafts (By similarity). Involved in the hippocampus-dependent long-term memory formation (By similarity). Involved in circadian control by regulating the consolidation of circadian periodicity after resetting (By similarity). Involved in development and function of regulatory T-cells (By similarity).
messages: The PH domain is required for interaction with PRKCB and its dephosphorylation.

9606:YY1AP1
gene id: 9606:YY1AP1
uniprot id: Q9H869
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Associates with the INO80 chromatin remodeling complex, which is responsible for transcriptional regulation, DNA repair, and replication (PubMed:27939641). Enhances transcription activation by YY1 (PubMed:14744866). Plays a role in cell cycle regulation (PubMed:17541814, PubMed:27939641).
messages: Cytoplasm
messages: Interacts with YY1. Interacts with MAD2L2. Interacts with INO80.
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitous. Detected in small intestine, skeletal muscle, lung, pancreas, brain, stomach, spleen, colon and heart. Detected at very low levels in healthy liver. Highly expressed in most liver carcinomas.
messages: nucleolus
messages: nucleoplasm

9606:POLR2G
gene id: 9606:POLR2G
uniprot id: P62487
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the eukaryotic RPB7/RPC8 RNA polymerase subunit family.
messages: Component of the RNA polymerase II (Pol II) complex consisting of 12 subunits. RPB4 and RPB7 form a subcomplex that protrudes from the 10-subunit Pol II core complex.
messages: DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB7 is part of a subcomplex with RPB4 that binds to a pocket formed by RPB1, RPB2 and RPB6 at the base of the clamp element. The RPB4-RPB7 subcomplex seems to lock the clamp via RPB7 in the closed conformation thus preventing double-stranded DNA to enter the active site cleft. The RPB4-RPB7 subcomplex binds single-stranded DNA and RNA (By similarity). Binds RNA.
messages: Nucleus

9606:UPF2
gene id: 9606:UPF2
uniprot id: Q9HAU5
names: Function
names: Sequence Caution
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cytoplasm
messages: Found in a post-splicing messenger ribonucleoprotein (mRNP) complex. Associates with the exon junction complex (EJC). Interacts with SMG1, EST1A, UPF1, UPF3A, UPF3B, EIF4A1 and EIF1.
messages: Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons by associating with the nuclear exon junction complex (EJC). Recruited by UPF3B associated with the EJC core at the cytoplasmic side of the nuclear envelope and the subsequent formation of an UPF1-UPF2-UPF3 surveillance complex (including UPF1 bound to release factors at the stalled ribosome) is believed to activate NMD. In cooperation with UPF3B stimulates both ATPase and RNA helicase activities of UPF1. Binds spliced mRNA.
messages: Probable cloning artifact.
messages: Ubiquitous.
messages: perinuclear region

9606:ACYP1
gene id: 9606:ACYP1
uniprot id: G3V2U7
uniprot id: P07311
names: Similarity
names: Tissue Specificity
messages: Belongs to the acylphosphatase family.
messages: Organ-common type isozyme is found in many different tissues.

9606:TARS2
gene id: 9606:TARS2
uniprot id: Q9BW92
uniprot id: U3KQG0
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the class-II aminoacyl-tRNA synthetase family.
messages: Catalyzes the attachment of threonine to tRNA(Thr) in a two-step reaction: threonine is first activated by ATP to form Thr-AMP and then transferred to the acceptor end of tRNA(Thr). Also edits incorrectly charged tRNA(Thr) via its editing domain.
messages: Homodimer.
messages: Mitochondrion matrix
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:SMCO3
gene id: 9606:SMCO3
uniprot id: A2RU48
names: Subcellular Location Annotation
messages: Membrane

9606:STX6
gene id: 9606:STX6
uniprot id: O43752
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the syntaxin family.
messages: Golgi apparatus membrane
messages: Identified in a complex containing STX6, STX12, VAMP4 and VTI1A (PubMed:17159904). Binds EEA1 (By similarity). Interacts with VPS45A (By similarity). Interacts with MARCHF2; the interaction promotes MARCHF2-mediated ubiquitination and degradation of CFTR (PubMed:23818989). Interacts with MARCHF3 (By similarity). Interacts with GOPC (PubMed:11384996). Interacts with BLTP3B (via C-terminal coiled-coil domain) (PubMed:20163565, PubMed:35499567). Interacts with BAIAP3; this interaction is increased in the presence of calcium (PubMed:28626000). Interacts with VPS13B (By similarity).
messages: Recycling endosome membrane
messages: SNARE promoting movement of transport vesicles to target membranes. Targets endosomes to the trans-Golgi network, and may therefore function in retrograde trafficking. Together with SNARE STX12, promotes movement of vesicles from endosomes to the cell membrane, and may therefore function in the endocytic recycling pathway.
messages: trans-Golgi network membrane

9606:GHRHR
gene id: 9606:GHRHR
uniprot id: A0A090N8Y6
uniprot id: Q02643
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor 2 family.
messages: Cell membrane
messages: Membrane
messages: Pituitary gland.
messages: Receptor for GRF, coupled to G proteins which activate adenylyl cyclase. Stimulates somatotroph cell growth, growth hormone gene transcription and growth hormone secretion.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:ATG4D
gene id: 9606:ATG4D
uniprot id: B4DGM8
uniprot id: Q86TL0
names: Activity Regulation
names: Caution
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: A paper describing ATG4D tissue expression has been retracted, due to concerns of image duplication in some of the figures.
messages: Belongs to the peptidase C54 family.
messages: Cleaved by CASP3 during apoptosis which leads to increased activity (PubMed:19549685, PubMed:22441018). The cleavage by CASP3 reveals a cryptic mitochondrial targeting sequence immediately downstream of their canonical caspase cleavage sites which leads to mitochondrial import of the protein (PubMed:19549685, PubMed:22441018).
messages: Cysteine protease that plays a key role in autophagy by mediating both proteolytic activation and delipidation of ATG8 family proteins (PubMed:21177865, PubMed:29458288, PubMed:30661429). The protease activity is required for proteolytic activation of ATG8 family proteins: cleaves the C-terminal amino acid of ATG8 proteins MAP1LC3 and GABARAPL2, to reveal a C-terminal glycine (PubMed:21177865). Exposure of the glycine at the C-terminus is essential for ATG8 proteins conjugation to phosphatidylethanolamine (PE) and insertion to membranes, which is necessary for autophagy (By similarity). In addition to the protease activity, also mediates delipidation of ATG8 family proteins (PubMed:29458288, PubMed:33909989). Catalyzes delipidation of PE-conjugated forms of ATG8 proteins during macroautophagy (PubMed:29458288, PubMed:33909989). Also involved in non-canonical autophagy, a parallel pathway involving conjugation of ATG8 proteins to single membranes at endolysosomal compartments, by catalyzing delipidation of ATG8 proteins conjugated to phosphatidylserine (PS) (PubMed:33909989). ATG4D plays a role in the autophagy-mediated neuronal homeostasis in the central nervous system (By similarity). Compared to other members of the family (ATG4A, ATG4B or ATG4C), constitutes the major protein for the delipidation activity, while it promotes weak proteolytic activation of ATG8 proteins (By similarity). Involved in phagophore growth during mitophagy independently of its protease activity and of ATG8 proteins: acts by regulating ATG9A trafficking to mitochondria and promoting phagophore-endoplasmic reticulum contacts during the lipid transfer phase of mitophagy (PubMed:33773106).
messages: Cysteine protease that plays a key role in autophagy by mediating both proteolytic activation and delipidation of ATG8 family proteins.
messages: Cytoplasm
messages: Inhibited by N-ethylmaleimide.
messages: Mitochondrion matrix
messages: Plays a role as an autophagy regulator that links mitochondrial dysfunction with apoptosis. The mitochondrial import of ATG4D during cellular stress and differentiation may play important roles in the regulation of mitochondrial physiology, ROS, mitophagy and cell viability.
messages: The cryptic mitochondrial transit peptide is revealed after cleavage by caspase upon oxidative stress and cell death (PubMed:22441018). It acts then as a functional transit peptide, and allows the import of the cleaved protein into the mitochondria (PubMed:22441018).
messages: Widely expressed in testis.

9606:USP16
gene id: 9606:USP16
uniprot id: Q9Y5T5
names: Disease Annotation
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: A chromosomal aberration involving USP16 is a cause of Chronic myelomonocytic leukemia. Inversion inv(21) (q21;q22) with RUNX1/AML1.
messages: Belongs to the peptidase C19 family. USP16 subfamily.
messages: Cytoplasm
messages: Homotetramer (PubMed:17914355). Associates with late pre-40S ribosomes (PubMed:32129764).
messages: Nucleus
messages: Phosphorylated at the onset of mitosis and dephosphorylated during the metaphase/anaphase transition. Phosphorylation by AURKB enhances the deubiquitinase activity.
messages: Present in all the tissues examined including fetal brain, lung, liver, kidney, and adult heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.
messages: Specifically deubiquitinates 'Lys-120' of histone H2A (H2AK119Ub), a specific tag for epigenetic transcriptional repression, thereby acting as a coactivator (PubMed:17914355). Deubiquitination of histone H2A is a prerequisite for subsequent phosphorylation at 'Ser-11' of histone H3 (H3S10ph), and is required for chromosome segregation when cells enter into mitosis (PubMed:17914355). In resting B- and T-lymphocytes, phosphorylation by AURKB leads to enhance its activity, thereby maintaining transcription in resting lymphocytes. Regulates Hox gene expression via histone H2A deubiquitination (PubMed:17914355). Prefers nucleosomal substrates (PubMed:17914355). Does not deubiquitinate histone H2B (PubMed:17914355). Also deubiquitinates non-histone proteins, such as ribosomal protein RPS27A: deubiquitination of monoubiquitinated RPS27A promotes maturation of the 40S ribosomal subunit (PubMed:32129764).
messages: The UBP-type zinc finger binds 3 zinc ions that form a pair of cross-braced ring fingers encapsulated within a third zinc finger in the primary structure. It recognizes the C-terminal tail of free ubiquitin.
messages: USP16 may contribute to somatic stem cell defects observed in Down syndrome. USP16 is triplicated in Down syndrome and its overexpression may contribute to proliferation defects in stem cells. Reduction of USP16 levels results in increased proliferation capacity of Down syndrome fibroblasts (PubMed:24025767).

9606:NSDHL
gene id: 9606:NSDHL
uniprot id: A0A384NPZ7
uniprot id: Q15738
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the 3-beta-HSD family.
messages: Brain, heart, liver, lung, kidney, skin and placenta.
messages: Catalyzes the NAD(P)(+)-dependent oxidative decarboxylation of the C4 methyl groups of 4-alpha-carboxysterols in post-squalene cholesterol biosynthesis (By similarity). Also plays a role in the regulation of the endocytic trafficking of EGFR (By similarity).
messages: Endoplasmic reticulum membrane
messages: Homodimer.
messages: Lipid droplet
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:FRG2C
gene id: 9606:FRG2C
uniprot id: A6NGY1
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the FRG2 family.
messages: Nucleus

9606:MIEN1
gene id: 9606:MIEN1
uniprot id: Q9BRT3
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Among normal tissues, present only in Leydig cells. Strongly up-regulated in breast cancers and in brain cancer distant metastasis (at protein level). Up-regulated in prostate cancer cells and in the higher grades of prostate adenocarcinoma (at protein level).
messages: Belongs to the SelWTH family.
messages: Cell membrane
messages: Increases cell migration by inducing filopodia formation at the leading edge of migrating cells. Plays a role in regulation of apoptosis, possibly through control of CASP3. May be involved in a redox-related process.
messages: Interacts with GPX1.
messages: Isoprenylation facilitates association with the plasma membrane and enhances the migratory phenotype of cells by inducing increased filopodia formation.
messages: cytosol

9606:SLC2A4
gene id: 9606:SLC2A4
uniprot id: P14672
names: Disease Annotation
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the major facilitator superfamily. Sugar transporter (TC 2.A.1.1) family. Glucose transporter subfamily.
messages: Cell membrane
messages: Endomembrane system
messages: Insulin-regulated facilitative glucose transporter, which plays a key role in removal of glucose from circulation. Response to insulin is regulated by its intracellular localization: in the absence of insulin, it is efficiently retained intracellularly within storage compartments in muscle and fat cells. Upon insulin stimulation, translocates from these compartments to the cell surface where it transports glucose from the extracellular milieu into the cell.
messages: Insulin-stimulated phosphorylation of TBC1D4 is required for GLUT4 translocation.
messages: Interacts with NDUFA9 (By similarity). Binds to DAXX (PubMed:11842083). Interacts via its N-terminus with SRFBP1 (PubMed:16647043). Interacts with TRARG1; the interaction is required for proper SLC2A4 recycling after insulin stimulation (By similarity).
messages: Palmitoylated (PubMed:28057756). Palmitoylation by ZDHHC7 controls the insulin-dependent translocation of GLUT4 to the plasma membrane (PubMed:28057756).
messages: Skeletal and cardiac muscles; brown and white fat.
messages: Sumoylated.
messages: The dileucine internalization motif is critical for intracellular sequestration.
messages: The disease may be caused by variants affecting the gene represented in this entry.
messages: perinuclear region

9606:ATP6V1C1
gene id: 9606:ATP6V1C1
uniprot id: A0A024R9I0
uniprot id: P21283
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the V-ATPase C subunit family.
messages: Subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons (PubMed:33065002). V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment (By similarity). Subunit C is necessary for the assembly of the catalytic sector of the enzyme and is likely to have a specific function in its catalytic activity (By similarity).
messages: Subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons. V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment. Subunit C is necessary for the assembly of the catalytic sector of the enzyme and is likely to have a specific function in its catalytic activity.
messages: Ubiquitous.
messages: V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex (PubMed:33065002). The V1 complex consists of three catalytic AB heterodimers that form a heterohexamer, three peripheral stalks each consisting of EG heterodimers, one central rotor including subunits D and F, and the regulatory subunits C and H (PubMed:33065002). The proton translocation complex V0 consists of the proton transport subunit a, a ring of proteolipid subunits c9c'', rotary subunit d, subunits e and f, and the accessory subunits ATP6AP1/Ac45 and ATP6AP2/PRR (PubMed:33065002).
messages: V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex. The V1 complex consists of three catalytic AB heterodimers that form a heterohexamer, three peripheral stalks each consisting of EG heterodimers, one central rotor including subunits D and F, and the regulatory subunits C and H. The proton translocation complex V0 consists of the proton transport subunit a, a ring of proteolipid subunits c9c'', rotary subunit d, subunits e and f, and two accessory subunits.
messages: clathrin-coated vesicle membrane
messages: synaptic vesicle membrane

9606:INTS14
gene id: 9606:INTS14
uniprot id: B4DWZ3
uniprot id: Q96SY0
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the INTS14 family.
messages: Nucleus
messages: Probable component of the Integrator (INT) complex, a complex involved in the small nuclear RNAs (snRNA) U1 and U2 transcription and in their 3'-box-dependent processing.
messages: Strongly expressed in numerous cancer cells compared with their non-cancerous counterparts (lung, prostate, colon, stomach and skin).

9606:SSBP4
gene id: 9606:SSBP4
uniprot id: Q9BWG4
names: Subcellular Location Annotation
messages: Nucleus

9606:ACOT9
gene id: 9606:ACOT9
uniprot id: Q9Y305
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Acyl-CoA thioesterases are a group of enzymes that catalyze the hydrolysis of acyl-CoAs to the free fatty acid and coenzyme A (CoASH), providing the potential to regulate intracellular levels of acyl-CoAs, free fatty acids and CoASH. Active on long chain acyl-CoAs.
messages: Belongs to the acyl coenzyme A hydrolase family.
messages: Interacts with NYAP1, NYAP2 and MYO16.
messages: Mitochondrion

9606:CPTP
gene id: 9606:CPTP
uniprot id: Q5TA50
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the GLTP family.
messages: Cell membrane
messages: Endosome membrane
messages: Mediates the intracellular transfer of ceramide-1-phosphate (C1P) between organelle membranes and the cell membrane. Required for normal structure of the Golgi stacks. Can bind phosphoceramides with a variety of aliphatic chains, but has a preference for lipids with saturated C16:0 or monounsaturated C18:1 aliphatic chains, and is inefficient with phosphoceramides containing lignoceryl (C24:0). Plays a role in the regulation of the cellular levels of ceramide-1-phosphate, and thereby contributes to the regulation of phospholipase PLA2G4A activity and the release of arachidonic acid. Has no activity with galactosylceramide, lactosylceramide, sphingomyelin, phosphatidylcholine, phosphatidic acid and ceramide. C1P transfer is stimulated by phosphatidylserine in C1P source vesicles (PubMed:28011644). Regulates autophagy, inflammasome mediated IL1B and IL18 processing, and pyroptosis, but not apoptosis (PubMed:29164996).
messages: Nucleus outer membrane
messages: Ubiquitous. Detected in heart, brain, placenta, lung, liver, skeletal muscle, kidney, pancreas, spleen, thymus, prostate, testis, ovary, small intestine, colon and peripheral blood leukocytes.
messages: cytosol
messages: trans-Golgi network membrane

9606:NBEA
gene id: 9606:NBEA
uniprot id: Q8NFP9
names: Disease Annotation
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the WD repeat neurobeachin family.
messages: Binds to type II regulatory subunits of protein kinase A and anchors/targets them to the membrane. May anchor the kinase to cytoskeletal and/or organelle-associated proteins (By similarity).
messages: Cytoplasm
messages: Interacts with RII subunit of PKA.
messages: Membrane
messages: Predominant in many brain structures. Also expressed at medium levels in spleen, thymus, prostate, testis and ovary. Low level expression is seen in heart, kidney, pancreas, skeletal muscle and intestine.
messages: RII-alpha binding site, predicted to form an amphipathic helix, could participate in protein-protein interactions with a complementary surface on the R-subunit dimer.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:HAPLN2
gene id: 9606:HAPLN2
uniprot id: Q9GZV7
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the HAPLN family.
messages: Expressed only in adult brain.
messages: Mediates a firm binding of versican V2 to hyaluronic acid. May play a pivotal role in the formation of the hyaluronan-associated matrix in the central nervous system (CNS) which facilitates neuronal conduction and general structural stabilization. Binds to hyaluronic acid (By similarity).
messages: extracellular matrix

9606:MEIS2
gene id: 9606:MEIS2
uniprot id: B3KPD8
uniprot id: B7Z6F6
uniprot id: O14770
names: Developmental Stage
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the TALE/MEIS homeobox family.
messages: Expressed in the proliferative zones of the fetal neocortex. Expressed at a very high level in the developing ganglionic eminence and at a more moderate level in the cortical plate.
messages: Expressed in various tissues. Expressed at high level in the lymphoid organs of hematopoietic tissues. Also expressed in some regions of the brain, such as the putamen.
messages: Involved in transcriptional regulation. Binds to HOX or PBX proteins to form dimers, or to a DNA-bound dimer of PBX and HOX proteins and thought to have a role in stabilization of the homeoprotein-DNA complex. Isoform 3 is required for the activity of a PDX1:PBX1b:MEIS2b complex in pancreatic acinar cells involved in the transcriptional activation of the ELA1 enhancer; the complex binds to the enhancer B element and cooperates with the transcription factor 1 complex (PTF1) bound to the enhancer A element; MEIS2 is not involved in complex DNA-binding. Probably in complex with PBX1, is involved in transcriptional regulation by KLF4. Isoform 3 and isoform 4 can bind to a EPHA8 promoter sequence containing the DNA motif 5'-CGGTCA-3'; in cooperation with a PBX protein (such as PBX2) is proposed to be involved in the transcriptional activation of EPHA8 in the developing midbrain. May be involved in regulation of myeloid differentiation. Can bind to the DNA sequence 5'-TGACAG-3'in the activator ACT sequence of the D(1A) dopamine receptor (DRD1) promoter and activate DRD1 transcription; isoform 5 cannot activate DRD1 transcription.
messages: Monomer and homodimer (PubMed:26550823). Heterodimer with HOXB13 (Ref.16). Isoform 2 interacts with TLX1. Isoform 3 interacts with HOXA13 and PBX1 isoform PBX1b. Isoform 4 interacts with SP1, SP3 and KLF4. Isoform 4 and isoform 5 interact with PBX1 isoform PBX1a; the interaction partially relieves MEIS2 autoinhibition. Isoform 3 also known as MEIS2b is part of a PDX1:PBX1b:Meis2B complex; Meis2B is recruited by PBX1b and can be replaced by isoform 4 in a small fraction of complexes. Can form trimeric complexes including HOXB8 and PBX2 or PBX3.
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: perinuclear region

9606:PAX1
gene id: 9606:PAX1
uniprot id: A0A087WXV5
uniprot id: P15863
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: This protein is a transcriptional activator. It may play a role in the formation of segmented structures of the embryo. May play an important role in the normal development of the vertebral column (By similarity).

9606:ATP5PF
gene id: 9606:ATP5PF
uniprot id: P18859
uniprot id: Q6IB54
uniprot id: Q6NZ59
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the eukaryotic ATPase subunit F6 family.
messages: F-type ATPases have 2 components, CF(1) - the catalytic core - and CF(0) - the membrane proton channel. CF(0) seems to have nine subunits: a, b, c, d, e, f, g, F6 and 8 (or A6L). Component of an ATP synthase complex composed of ATP5PB, ATP5MC1, ATP5F1E, ATP5PD, ATP5ME, ATP5PF, ATP5MF, MT-ATP6, MT-ATP8, ATP5F1A, ATP5F1B, ATP5F1D, ATP5F1C, ATP5PO, ATP5MG, ATP5MK and MP68 (By similarity).
messages: Membrane
messages: Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Part of the complex F(0) domain and the peripheric stalk, which acts as a stator to hold the catalytic alpha(3)beta(3) subcomplex and subunit a/ATP6 static relative to the rotary elements. Also involved in the restoration of oligomycin-sensitive ATPase activity to depleted F1-F0 complexes.
messages: Mitochondrion
messages: Mitochondrion inner membrane

9606:FAM133A
gene id: 9606:FAM133A
uniprot id: Q8N9E0
names: Similarity
messages: Belongs to the FAM133 family.

9606:SMOC2
gene id: 9606:SMOC2
uniprot id: Q9H3U7
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Binds various proteins from the extracellular matrix.
messages: Promotes matrix assembly and cell adhesiveness (By similarity). Can stimulate endothelial cell proliferation, migration, as well as angiogenesis.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: basement membrane

9606:SLC38A10
gene id: 9606:SLC38A10
uniprot id: Q9HBR0
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the amino acid/polyamine transporter 2 family.
messages: Facilitates bidirectional transport of amino acids. May act as a glutamate sensor that regulates glutamate-glutamine cycle and mTOR signaling in the brain. The transport mechanism remains to be elucidated.
messages: Membrane

9606:TRPM5
gene id: 9606:TRPM5
uniprot id: Q9NZQ8
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the transient receptor (TC 1.A.4) family. LTrpC subfamily. TRPM5 sub-subfamily.
messages: Cell membrane
messages: Strongly expressed in fetal brain, liver and kidney, and in adult prostate, testis, ovary, colon and peripheral blood leukocytes. Also expressed in a large proportion of Wilms' tumors and rhabdomyosarcomas. In monochromosomal cell lines shows exclusive paternal expression.
messages: Voltage-modulated Ca(2+)-activated, monovalent cation channel (VCAM) that mediates a transient membrane depolarization and plays a central role in taste transduction. Monovalent-specific, non-selective cation channel that mediates the transport of Na(+), K(+) and Cs(+) ions equally well. Activated directly by increases in intracellular Ca(2+), but is impermeable to it. Gating is voltage-dependent and displays rapid activation and deactivation kinetics upon channel stimulation even during sustained elevations in Ca(2+). Also activated by a fast intracellular Ca(2+) increase in response to inositol 1,4,5-triphosphate-producing receptor agonists. The channel is blocked by extracellular acidification. External acidification has 2 effects, a fast reversible block of the current and a slower irreversible enhancement of current inactivation. Is a highly temperature-sensitive, heat activated channel showing a steep increase of inward currents at temperatures between 15 and 35 degrees Celsius. Heat activation is due to a shift of the voltage-dependent activation curve to negative potentials. Activated by arachidonic acid in vitro. May be involved in perception of bitter, sweet and umami tastes. May also be involved in sensing semiochemicals.

9606:HES5
gene id: 9606:HES5
uniprot id: Q5TA89
names: Domain
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Expressed in fetal heart and brain tumors.
messages: Has a particular type of basic domain (presence of a helix-interrupting proline) that binds to the N-box (CACNAG), rather than the canonical E-box (CANNTG).
messages: Nucleus
messages: The C-terminal WRPW motif is a transcriptional repression domain necessary for the interaction with Groucho/TLE family members, transcriptional corepressors recruited to specific target DNA by Hairy-related proteins.
messages: Transcription repression requires formation of a complex with a corepressor protein of the Groucho/TLE family.
messages: Transcriptional repressor of genes that require a bHLH protein for their transcription. Plays an important role as neurogenesis negative regulator (By similarity).

9606:RPL32
gene id: 9606:RPL32
uniprot id: P62910
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the eukaryotic ribosomal protein eL32 family.
messages: Component of the large ribosomal subunit (PubMed:23636399, PubMed:32669547). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399, PubMed:32669547).
messages: Component of the large ribosomal subunit.
messages: Cytoplasm

9606:TNFRSF13C
gene id: 9606:TNFRSF13C
uniprot id: Q96RJ3
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Tissue Specificity
messages: B-cell receptor specific for TNFSF13B/TALL1/BAFF/BLyS. Promotes the survival of mature B-cells and the B-cell response.
messages: Highly expressed in spleen and lymph node, and in resting B-cells. Detected at lower levels in activated B-cells, resting CD4+ T-cells, in thymus and peripheral blood leukocytes.
messages: Membrane
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:SHOC2
gene id: 9606:SHOC2
uniprot id: Q9UQ13
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the SHOC2 family.
messages: Cytoplasm
messages: Interacts with M-Ras/MRAS, and RAF1 (PubMed:16630891, PubMed:25137548). Forms a multiprotein complex with Ras (M-Ras/MRAS), Raf (RAF1) and protein phosphatase 1 (PPP1CA, PPP1CB and PPP1CC) (PubMed:16630891, PubMed:25137548). Interacts with ERBIN; disrupts the interaction with RAF1 and Ras, leading to prevent activation of the Ras signaling pathway (PubMed:16301319). Specifically binds K-Ras/KRAS, M-Ras/MRAS and N-Ras/NRAS but not H-Ras/HRAS (PubMed:9674433). Interacts with LZTR1 (PubMed:30368668).
messages: Nucleus
messages: Regulatory subunit of protein phosphatase 1 (PP1c) that acts as a M-Ras/MRAS effector and participates in MAPK pathway activation. Upon M-Ras/MRAS activation, targets PP1c to specifically dephosphorylate the 'Ser-259' inhibitory site of RAF1 kinase and stimulate RAF1 activity at specialized signaling complexes.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:UPK3B
gene id: 9606:UPK3B
uniprot id: Q9BT76
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the uroplakin-3 family.
messages: Cell membrane
messages: Component of the asymmetric unit membrane (AUM); a highly specialized biomembrane elaborated by terminally differentiated urothelial cells. May play an important role in AUM-cytoskeleton interaction in terminally differentiated urothelial cells. It also contributes to the formation of urothelial glycocalyx which may play an important role in preventing bacterial adherence (By similarity).
messages: Heterodimer with uroplakin-1B (UPK1B).

9606:SMPDL3B
gene id: 9606:SMPDL3B
uniprot id: B4DW34
uniprot id: Q92485
names: Cofactor
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the acid sphingomyelinase family.
messages: Binds 2 Zn(2+) ions per subunit.
messages: Binds 2 Zn(2+) per subunit.
messages: Cell membrane
messages: Interacts with TLR4, TLR7, TLR8 and TLR9.
messages: Lipid-modulating phosphodiesterase (PubMed:26095358). Active on the surface of macrophages and dendritic cells and strongly influences macrophage lipid composition and membrane fluidity. Acts as a negative regulator of Toll-like receptor signaling (By similarity). Has in vitro phosphodiesterase activity, but the physiological substrate is unknown (PubMed:26095358). Lacks activity with phosphocholine-containing lipids, but can cleave CDP-choline, and can release phosphate from ATP and ADP (in vitro) (By similarity).
messages: N-glycosylated.
messages: Secreted

9606:MYBPC3
gene id: 9606:MYBPC3
uniprot id: Q14896
names: Disease Annotation
names: Function
names: PTM
names: Similarity
messages: Belongs to the immunoglobulin superfamily. MyBP family.
messages: MYBPC3 mutations may be involved in restrictive cardiomyopathy (RCM), a rare non-ischemic myocardial disease. RCM is characterized by restrictive ventricular-filling physiology in the presence of normal or reduced diastolic and/or systolic volumes (of 1 or both ventricles), biatrial enlargement, and normal ventricular wall thickness.
messages: Polyubiquitinated.
messages: Substrate for phosphorylation by PKA and PKC. Reversible phosphorylation appears to modulate contraction (By similarity).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Thick filament-associated protein located in the crossbridge region of vertebrate striated muscle a bands. In vitro it binds MHC, F-actin and native thin filaments, and modifies the activity of actin-activated myosin ATPase. It may modulate muscle contraction or may play a more structural role.

9606:THAP9
gene id: 9606:THAP9
uniprot id: Q9H5L6
names: Function
names: Miscellaneous
messages: Able to mediate mobilization of P-elements when transfected in Drosophila.
messages: Active transposase that specifically recognizes the bipartite 5'-TXXGGGX(A/T)-3' consensus motif and mediates transposition.

9606:RELN
gene id: 9606:RELN
uniprot id: P78509
names: Developmental Stage
names: Disease Annotation
names: Domain
names: Function
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: A polymorphic GGC triplet repeat located in the 5'-UTR region of RELN gene, which harbors in the normal population 8 to 10 repeats, is significantly increased in autistic patients to carry 4 to 23 additional repeats.
messages: Abundantly produced during brain ontogenesis by the Cajal-Retzius cells and other pioneer neurons located in the telencephalic marginal zone and by granule cells of the external granular layer of the cerebellum. In adult brain, preferentially expressed in GABAergic interneurons of prefrontal cortices, temporal cortex, hippocampus and glutamatergic granule cells of cerebellum. Expression is reduced to about 50% in patients with schizophrenia. Also expressed in fetal and adult liver.
messages: Belongs to the reelin family.
messages: Expressed in fetal and postnatal brain and liver. Expression in postnatal human brain is high in the cerebellum.
messages: Extracellular matrix serine protease that plays a role in layering of neurons in the cerebral cortex and cerebellum. Regulates microtubule function in neurons and neuronal migration. Affects migration of sympathetic preganglionic neurons in the spinal cord, where it seems to act as a barrier to neuronal migration. Enzymatic activity is important for the modulation of cell adhesion. Binding to the extracellular domains of lipoprotein receptors VLDLR and LRP8/APOER2 induces tyrosine phosphorylation of DAB1 and modulation of TAU phosphorylation (By similarity).
messages: Oligomer of disulfide-linked homodimers. Binds to the ectodomains of VLDLR and LRP8/APOER2 (By similarity).
messages: The basic C-terminal region is essential for secretion.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: extracellular matrix

9606:UNC119
gene id: 9606:UNC119
uniprot id: K7EN86
uniprot id: Q13432
names: Caution
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Abundantly expressed in retina, in photoreceptor synapses and inner segments. Expressed in a much lesser extent in several other tissues.
messages: According to some authors, acts by extracting target proteins from membranes (PubMed:21642972). According to a another report, rather acts by targeting proteins to membranes (PubMed:22085962).
messages: Adopts an immunoglobulin-like beta-sandwich fold forming a hydrophobic cavity that captures N-terminally myristoylated target peptides (PubMed:21642972). Phe residues within the hydrophobic beta sandwich are required for myristate binding (PubMed:22085962).
messages: Belongs to the PDE6D/unc-119 family.
messages: Defects in UNC119 may be a cause of cone-rod dystrophy. A mutation was found in a 57-year-old woman with late-onset cone-rod dystrophy: from 40 year old, the patient suffered from poor night vision, defective color vision and light-sensitivity. At 57 year old, she displayed reduced visual acuity, myopa, macular atrophy and pericentral ring scotomas. The disease was caused by a heterozygous mutation causing premature termination and truncated UNC119 protein with dominant-negative effect.
messages: Interacts with CABP4; in the absence of calcium (By similarity). Interacts with DNM1; leading to a decrease of DNM1 GTPase activity (By similarity). May interact with GTP-bound ARL1. Interacts with ARL2 and ARL3 (GTP-bound forms); this promotes the release of myyristoylated cargo proteins (PubMed:22960633, PubMed:30945270). Found in a complex with ARL3, RP2 and UNC119; RP2 induces hydrolysis of GTP ARL3 in the complex, leading to the release of UNC119. Interacts with NPHP3 (when myristoylated). Interacts with CYS1 (when myristoylated). Interacts with MACIR; interaction only takes place when UNC119 is not liganded with myristoylated proteins. Interacts with LCK; this interaction plays a crucial role in activation of LCK. Interacts with FYN. Interacts with RAB11A; in a cell cycle-dependent manner. Interacts with LYN (via SH2 and SH3 domains); leading to LYN activation. Found in a complex with ABL1, ABL2, CRK and UNC119; leading to the inhibition of CRK phosphorylation by ABL kinases. Interacts with CD44; leading to Shigella invasion. Interacts with KLHL18 (via kelch repeats) (PubMed:31696965). Interacts with PPP3CA, PPP3CB and PPP3CC (By similarity).
messages: Involved in synaptic functions in photoreceptor cells, the signal transduction in immune cells as a Src family kinase activator, endosome recycling, the uptake of bacteria and endocytosis, protein trafficking in sensory neurons and as lipid-binding chaperone with specificity for a diverse subset of myristoylated proteins. Specifically binds the myristoyl moiety of a subset of N-terminally myristoylated proteins and is required for their localization. Binds myristoylated GNAT1 and is required for G-protein localization and trafficking in sensory neurons. Probably plays a role in trafficking proteins in photoreceptor cells. Plays important roles in mediating Src family kinase signals for the completion of cytokinesis via RAB11A.
messages: Phosphorylation suppresses its interaction with KLHL18 and down-regulates its KLHL18-mediated degradation (PubMed:31696965). Phosphorylated more under light conditions than dark conditions (PubMed:31696965). Dephosphorylated by calcineurin (PubMed:31696965).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: centrosome
messages: spindle
messages: spindle pole

9606:PAM
gene id: 9606:PAM
uniprot id: A0A804HIQ0
uniprot id: P19021
names: Activity Regulation
names: Cofactor
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Bifunctional enzyme that catalyzes the post-translational modification of inactive peptidylglycine precursors to the corresponding bioactive alpha-amidated peptides, a terminal modification in biosynthesis of many neural and endocrine peptides (PubMed:12699694). Alpha-amidation involves two sequential reactions, both of which are catalyzed by separate catalytic domains of the enzyme. The first step, catalyzed by peptidyl alpha-hydroxylating monooxygenase (PHM) domain, is the copper-, ascorbate-, and O2- dependent stereospecific hydroxylation (with S stereochemistry) at the alpha-carbon (C-alpha) of the C-terminal glycine of the peptidylglycine substrate (PubMed:12699694). The second step, catalyzed by the peptidylglycine amidoglycolate lyase (PAL) domain, is the zinc-dependent cleavage of the N-C-alpha bond, producing the alpha-amidated peptide and glyoxylate (PubMed:12699694). Similarly, catalyzes the two-step conversion of an N-fatty acylglycine to a primary fatty acid amide and glyoxylate (By similarity).
messages: Binds 2 Cu(2+) ions per subunit.
messages: Binds one Zn(2+) ion per subunit.
messages: In the C-terminal section; belongs to the peptidyl-alpha-hydroxyglycine alpha-amidating lyase family.
messages: In the N-terminal section; belongs to the copper type II ascorbate-dependent monooxygenase family.
messages: Membrane
messages: Monomer. Interacts with RASSF9.
messages: PAM activity is inhibited by EDTA, phenylglyoxal and diethyl pyrocarbonate (PubMed:12699694). PAL activity is stimulated by cadmium and inhibited by mercury (By similarity).
messages: Secreted
messages: Soluble.
messages: secretory vesicle membrane

9606:PYDC5
gene id: 9606:PYDC5
uniprot id: W6CW81
names: Function
names: Induction
names: Subunit
names: Tissue Specificity
messages: Expressed in monocytic cell lines and primary macrophages but not in B or T cells.
messages: Functions as an inhibitor of DNA virus-induced activation of AIM2-like receptors (ALR) inflammasome through interaction with AIM2.
messages: Interacts with AIM2; disrupts assembly of the ALR inflammasome complex (PubMed:24531343). Interacts with IFI16 (PubMed:24531343). Interacts with NLRP3 (PubMed:24531343).
messages: Up-regulated in response to IFNB1 or virus infection.

9606:HOPX
gene id: 9606:HOPX
uniprot id: Q9BPY8
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Atypical homeodomain protein which does not bind DNA and is required to modulate cardiac growth and development. Acts via its interaction with SRF, thereby modulating the expression of SRF-dependent cardiac-specific genes and cardiac development. Prevents SRF-dependent transcription either by inhibiting SRF binding to DNA or by recruiting histone deacetylase (HDAC) proteins that prevent transcription by SRF. Overexpression causes cardiac hypertrophy (By similarity). May act as a tumor suppressor. Acts as a co-chaperone for HSPA1A and HSPA1B chaperone proteins and assists in chaperone-mediated protein refolding (PubMed:27708256).
messages: Cytoplasm
messages: Interacts with serum response factor (SRF). Component of a large complex containing histone deacetylases such as HDAC2 (By similarity). Interacts with the acetylated forms of HSPA1A and HSPA1B. Interacts with HSPA8 (PubMed:27708256).
messages: Nucleus
messages: Widely expressed. Expressed in the heart, brain, placenta, lung, skeletal and smooth muscles, uterus, urinary bladder, kidney and spleen. Down-regulated in some types of cancer such as lung cancer, choriocarcinoma, head and neck squamous cell carcinoma and oral squamous cell carcinoma.

9606:ZNF276
gene id: 9606:ZNF276
uniprot id: Q8N554
names: Function
names: Subcellular Location Annotation
messages: May be involved in transcriptional regulation.
messages: Nucleus
messages: kinetochore

9606:UFSP2
gene id: 9606:UFSP2
uniprot id: Q9NUQ7
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the peptidase C78 family.
messages: Cytoplasm
messages: Endoplasmic reticulum
messages: Expressed in brain.
messages: Interacts with DDRGK1 (By similarity). Interacts with TRIP4; deufmylates TRIP4 (PubMed:25219498).
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Thiol-dependent isopeptidase that recognizes and hydrolyzes the peptide bond at the C-terminal Gly of UFM1, a ubiquitin-like modifier protein bound to a number of target proteins (PubMed:25219498, PubMed:32160526). Does not hydrolyze SUMO1 or ISG15 ubiquitin-like proteins (PubMed:25219498). Through TRIP4 deufmylation may regulate intracellular nuclear receptors transactivation and thereby regulate cell proliferation and differentiation (PubMed:25219498).

9606:HLTF
gene id: 9606:HLTF
uniprot id: Q14527
names: Caution
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the SNF2/RAD54 helicase family. RAD16 subfamily.
messages: Cytoplasm
messages: Expressed in brain, heart, kidney, liver, lung, pancreas, placenta and skeletal muscle.
messages: Has both helicase and E3 ubiquitin ligase activities. Possesses intrinsic ATP-dependent nucleosome-remodeling activity; This activity may be required for transcriptional activation or repression of specific target promoters (By similarity). These may include the SERPINE1 and HIV-1 promoters and the SV40 enhancer, to which this protein can bind directly. Plays a role in error-free postreplication repair (PRR) of damaged DNA and maintains genomic stability through acting as a ubiquitin ligase for 'Lys-63'-linked polyubiquitination of chromatin-bound PCNA.
messages: In contrast with other SMARC proteins, there is currently no evidence that it associates with actin or actin-related proteins. It may rather act as a sequence-specific DNA binding ATPase, whose precise function remains to be fully characterized.
messages: Interacts with SP1 and SP3 independently of DNA; the interaction with these transcriptional factors may be required for basal transcription of target genes. Interacts with EGR1; the interaction requires prior binding to DNA and represses c-Rel via a DNA looping mechanism (By similarity). Interacts with GATA4 (By similarity). Interacts with PCNA; the interaction promotes polyubiquitination of PCNA through association with the UBE2B-RAD18 and UBE2V2-UBE2N ubiquitin ligase complexes. Interacts with RAD18, SHPRH, UBE2V2 and UBE2N.
messages: Nucleus
messages: Subject to frequent epigenetic inactivation by promoter methylation in colon cancer.
messages: nucleolus
messages: nucleoplasm

9606:PXK
gene id: 9606:PXK
uniprot id: Q7Z7A4
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the protein kinase superfamily.
messages: Binds to and modulates brain Na,K-ATPase subunits ATP1B1 and ATP1B3 and may thereby participate in the regulation of electrical excitability and synaptic transmission. May not display kinase activity.
messages: Cell membrane
messages: Cytoplasm
messages: The protein kinase domain is predicted to be catalytically inactive.
messages: Widely expressed in all tissues examined except in heart. Isoform 1 is expressed in high levels in the brain, skeletal muscle, spleen and testis. Isoform 7 expression has yet to be demonstrated.

9606:PRMT6
gene id: 9606:PRMT6
uniprot id: Q96LA8
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts with (and methylates) HIV-1 Tat, Rev and Nucleocapsid protein p7 (NC).
messages: (Microbial infection) Interacts with human cytomegalovirus protein UL69.
messages: Arginine methyltransferase that can catalyze the formation of both omega-N monomethylarginine (MMA) and asymmetrical dimethylarginine (aDMA), with a strong preference for the formation of aDMA (PubMed:17898714, PubMed:18077460, PubMed:18079182, PubMed:19405910, PubMed:30420520). Preferentially methylates arginyl residues present in a glycine and arginine-rich domain and displays preference for monomethylated substrates (PubMed:17898714, PubMed:18077460, PubMed:18079182, PubMed:19405910). Specifically mediates the asymmetric dimethylation of histone H3 'Arg-2' to form H3R2me2a (PubMed:17898714, PubMed:18079182, PubMed:18077460). H3R2me2a represents a specific tag for epigenetic transcriptional repression and is mutually exclusive with methylation on histone H3 'Lys-4' (H3K4me2 and H3K4me3) (PubMed:17898714, PubMed:18077460). Acts as a transcriptional repressor of various genes such as HOXA2, THBS1 and TP53 (PubMed:19509293). Repression of TP53 blocks cellular senescence (By similarity). Also methylates histone H2A and H4 'Arg-3' (H2AR3me and H4R3me, respectively). Acts as a regulator of DNA base excision during DNA repair by mediating the methylation of DNA polymerase beta (POLB), leading to the stimulation of its polymerase activity by enhancing DNA binding and processivity (PubMed:16600869). Methylates HMGA1 (PubMed:16157300, PubMed:16159886). Regulates alternative splicing events. Acts as a transcriptional coactivator of a number of steroid hormone receptors including ESR1, ESR2, PGR and NR3C1. Promotes fasting-induced transcriptional activation of the gluconeogenic program through methylation of the CRTC2 transcription coactivator (By similarity). May play a role in innate immunity against HIV-1 in case of infection by methylating and impairing the function of various HIV-1 proteins such as Tat, Rev and Nucleocapsid protein p7 (NC) (PubMed:17267505). Methylates GPS2, protecting GPS2 from ubiquitination and degradation (By similarity). Methylates SIRT7, inhibiting…
messages: Automethylation enhances its stability and antiretroviral activity.
messages: Belongs to the class I-like SAM-binding methyltransferase superfamily. Protein arginine N-methyltransferase family. PRMT6 subfamily.
messages: Highly expressed in kidney and testis.
messages: Interacts with EPB41L3 and NCOA1.
messages: Nucleus

9606:SLBP
gene id: 9606:SLBP
uniprot id: B3KSC5
uniprot id: B3KST9
uniprot id: B4DUW7
uniprot id: E7EUV9
uniprot id: Q14493
uniprot id: Q53XR2
names: Developmental Stage
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Amino acids 31-34, 96-99 and 241-244 are necessary for interaction with the Importin alpha/Importin beta receptor. The first 18 amino acids, amino acids 69-76 and 179-182 are necessary for interaction with TNPO3. Amino acids 31-34, 96-99 and 241-244 are necessary for nuclear localization.
messages: Belongs to the SLBP family.
messages: Cytoplasm
messages: Monomer (PubMed:22439849). SLBP/pre-mRNA complex interacts with ZNF473 (PubMed:11782445). Interacts with the Importin alpha/Importin beta receptor, LSM1, MIF4GD, TNPO3 and UPF1 (PubMed:15829567, PubMed:16086026, PubMed:18025107). Interaction with LSM1 occurs when histone mRNA is being rapidly degraded during the S phase (PubMed:18172165). Found in a ternary complex with ERI1 and the stem-loop structure of the 3' end of histone mRNA (PubMed:16912046). Associates with polyribosomes (PubMed:12588979). Identified in a histone pre-mRNA complex, at least composed of ERI1, LSM11, SLBP, SNRPB, SYNCRIP and YBX1 (By similarity). Binds in a cooperative manner with ERI1 to the mature 3'-end of histone mRNAs (By similarity).
messages: Nucleus
messages: Phosphorylated on Thr-61 and Thr-62 in the S-phase. Phosphorylation of Thr-62 by CDK1 primes phosphorylation of Thr-61 by CK2. Phosphorylation of Thr-62 is required for its degradation by the proteasome at the end of the S phase. Its degradation is not required for histone mRNA degradation at the end of the S phase. All the phosphorylated forms detected are present in the cytoplasm. Both unphosphorylated and phosphorylated forms bind the stem-loop structure of histone mRNAs. Phosphorylation at Thr-171 increases affinity for histone mRNAs.
messages: RNA-binding protein involved in the histone pre-mRNA processing (PubMed:8957003, PubMed:9049306, PubMed:12588979, PubMed:19155325). Binds the stem-loop structure of replication-dependent histone pre-mRNAs and contributes to efficient 3'-end processing by stabilizing the complex between histone pre-mRNA and U7 small nuclear ribonucleoprotein (snRNP), via the histone downstream element (HDE) (PubMed:8957003, PubMed:9049306, PubMed:12588979, PubMed:19155325). Plays an important role in targeting mature histone mRNA from the nucleus to the cytoplasm and to the translation machinery (PubMed:8957003, PubMed:9049306, PubMed:12588979, PubMed:19155325). Stabilizes mature histone mRNA and could be involved in cell-cycle regulation of histone gene expression (PubMed:8957003, PubMed:9049306, PubMed:12588979, PubMed:19155325). Involved in the mechanism by which growing oocytes accumulate histone proteins that support early embryogenesis (By similarity). Binds to the 5' side of the stem-loop structure of histone pre-mRNAs (By similarity).
messages: Regulated during the cell cycle: protein levels increase 10 to 20 fold in the late G1 and decrease at the S/G2 border.
messages: Ubiquitinated by the CRL2(FEM1A), CRL2(FEM1B) and CRL2(FEM1C) complexes, leading to its degradation.
messages: Widely expressed.

9606:JPT2
gene id: 9606:JPT2
uniprot id: Q9H910
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Involved in the endolysosomal trafficking of human coronavirus SARS-CoV-2.
messages: Belongs to the JUPITER family.
messages: Cytoplasm
messages: Expressed in liver, kidney, prostate, testis and uterus.
messages: Monomer (PubMed:33758062). Dimer (PubMed:33758062). Interacts with TPCN1 (PubMed:33758061).
messages: Nicotinic acid adenine dinucleotide phosphate (NAADP) binding protein required for NAADP-evoked intracellular calcium release (PubMed:33758061, PubMed:33758062). Confers NAADP-sensitivity to the two pore channels (TPCs) complex (PubMed:33758061). Enables NAADP to activate Ca(2+) release from the endoplasmic reticulum through ryanodine receptors (PubMed:33758062).
messages: Nucleus
messages: Up-regulated in squamous cell carcinoma (SCC) adenocarcinoma (AC), adenosquamous cell carcinoma (ASCC), bronchioalveolar carcinoma (BAC), breast and uterus tumors.

9606:ZNF18
gene id: 9606:ZNF18
uniprot id: B3KXT5
uniprot id: P17022
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:ADAM30
gene id: 9606:ADAM30
uniprot id: Q8TBZ7
uniprot id: Q9UKF2
names: Caution
names: Cofactor
names: Domain
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Binds 1 zinc ion per subunit.
messages: Expressed in brain neurons (at protein level) (PubMed:27333034). Expressed in testis (PubMed:10512762).
messages: Interacts with CTSD; this leads to activation of CTSD.
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: Late endosome membrane
messages: Membrane
messages: Plays a role in lysosomal amyloid precursor protein (APP) processing by cleaving and activating CTSD/cathepsin D which leads to APP degradation (PubMed:27333034).
messages: The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.

9606:RRAGD
gene id: 9606:RRAGD
uniprot id: Q9NQL2
names: Activity Regulation
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the GTR/RAG GTP-binding protein family.
messages: Cytoplasm
messages: Forms a heterodimer with RRAGA in a sequence-independent manner and RRAGB (PubMed:11073942, PubMed:14660641). Heterodimerization stabilizes RRAG proteins (PubMed:11073942, PubMed:14660641, PubMed:25561175, PubMed:25567906). The GDP-bound form of RRAGD (in complex with the GTP-bound form of RRAGA or RRAGB), interacts with RPTOR, thereby promoting recruitment of mTORC1 to the lysosomes (PubMed:18497260). Component of the lysosomal folliculin complex (LFC), composed of FLCN, FNIP1 (or FNIP2), RagA/RRAGA or RagB/RRAGB GDP-bound, RagC/RRAGC or RagD/RRAGD GTP-bound, and Ragulator (By similarity). Interacts with NOL8 (PubMed:14660641). Interacts with SH3BP4; the interaction with this negative regulator is most probably direct, preferentially occurs with the inactive GDP-bound form of RRAGD and is negatively regulated by amino acids (PubMed:22575674). The Rag heterodimer interacts with SLC38A9; the probable amino acid sensor (PubMed:25561175, PubMed:25567906). Interacts with SESN1, SESN2 and SESN3 (PubMed:25259925). The GDP-bound form interacts with TFEB (By similarity). The GDP-bound form interacts with TFE3 (PubMed:32612235).
messages: Guanine nucleotide-binding protein that plays a crucial role in the cellular response to amino acid availability through regulation of the mTORC1 signaling cascade (PubMed:20381137, PubMed:24095279, PubMed:34607910). Forms heterodimeric Rag complexes with RagA/RRAGA or RagB/RRAGB and cycles between an inactive GTP-bound and an active GDP-bound form: RagD/RRAGD is in its active form when GDP-bound RagD/RRAGD forms a complex with GTP-bound RagA/RRAGA (or RagB/RRAGB) and in an inactive form when GTP-bound RagD/RRAGD heterodimerizes with GDP-bound RagA/RRAGA (or RagB/RRAGB) (PubMed:24095279). In its active form, promotes the recruitment of mTORC1 to the lysosomes and its subsequent activation by the GTPase RHEB (PubMed:20381137, PubMed:24095279). This is a crucial step in the activation of the MTOR signaling cascade by amino acids (PubMed:20381137, PubMed:24095279). Also plays a central role in the non-canonical mTORC1 complex, which acts independently of RHEB and specifically mediates phosphorylation of MiT/TFE factors TFEB and TFE3: GDP-bound RagD/RRAGD mediates recruitment of MiT/TFE factors TFEB and TFE3 (PubMed:32612235).
messages: Lysosome membrane
messages: Nucleus
messages: The activation of RagD/RRAGD is mediated by a GTPase activating protein (GAP) (PubMed:24095279). In high-amino acid conditions, activated by GTPase activating protein FLCN that stimulates RRAGD GTPase activity to turn it into its active GDP-bound form (PubMed:24095279). In response to amino acid depletion, the GATOR1 complex inactivates RagC/RRAGC by securing the GTP-bound inactive form (By similarity).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:TSKU
gene id: 9606:TSKU
uniprot id: Q8WUA8
names: Function
names: Induction
names: Miscellaneous
names: Subcellular Location Annotation
names: Subunit
messages: By 17-beta-estradiol.
messages: Contributes to various developmental events and other processes such as wound healing and cholesterol homeostasis through its interactions with multiple signaling pathways. Wnt signaling inhibitor which competes with WNT2B for binding to Wnt receptor FZD4 and represses WNT2B-dependent development of the peripheral eye. Plays a role in regulating the hair cycle by controlling TGFB1 signaling. Required for the development of the anterior commissure in the brain by inhibiting neurite outgrowth. Essential for terminal differentiation of hippocampal neural stem cells. Plays a role in regulating bone elongation and bone mass by modulating growth plate chondrocyte function and overall body size. Required for development of the inner ear through its involvement in stereocilia formation in inner hair cells. Facilitates wound healing by inhibiting secretion of TGFB1 from macrophages which prevents myofibroblast differentiation, maintaining inflammatory cell quiescence. Plays a role in cholesterol homeostasis by reducing circulating high-density lipoprotein cholesterol, lowering cholesterol efflux capacity and decreasing cholesterol-to-bile acid conversion in the liver. In one study, shown to negatively regulate sympathetic innervation in brown fat, leading to reduced energy expenditure. In another study, shown not to affect brown fat thermogenic capacity, body weight gain or glucose homeostasis.
messages: Interacts with FZD4 (via FZ domain); competes with WNT2B for binding to FZD4, inhibiting Wnt signaling and repressing peripheral eye development (By similarity). Interacts with TGFB1; the interaction contributes to regulation of the hair cycle (By similarity). Interacts with netrin (By similarity). Interacts with CCN2 (PubMed:30232710).
messages: Secreted
messages: This factor is named 'Tsukushi' because its expression pattern in chick embryos is similar to the shape of the Japanese horsetail plant, tsukushi.

9606:ROM1
gene id: 9606:ROM1
uniprot id: Q03395
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the PRPH2/ROM1 family.
messages: Homodimer; disulfide-linked (PubMed:1610568). Forms a homotetramer (By similarity). Forms a heterotetramer with PRPH2 (By similarity). Homotetramer and heterotetramer core complexes go on to form higher order complexes by formation of intermolecular disulfide bonds (By similarity). Interacts with STX3 (By similarity). Interacts with SNAP25 (By similarity).
messages: Photoreceptor inner segment membrane
messages: Photoreceptor outer segment membrane
messages: Plays a role in rod outer segment (ROS) morphogenesis (By similarity). May play a role with PRPH2 in the maintenance of the structure of ROS curved disks (By similarity). Plays a role in the organization of the ROS and maintenance of ROS disk diameter (By similarity). Involved in the maintenance of the retina outer nuclear layer (By similarity).
messages: Retina photoreceptors (at protein level) (PubMed:1610568, PubMed:8504299). In rim region of ROS disks (PubMed:1610568).
messages: The disease may be caused by variants affecting distinct genetic loci, including the gene represented in this entry. A digenic form of retinitis pigmentosa 7 results from a mutation in the PRPH2 gene and a null mutation of the ROM1 gene has been reported (PubMed:8202715).

9606:ARMT1
gene id: 9606:ARMT1
uniprot id: B4DPT6
uniprot id: F5GZY1
uniprot id: Q9H993
names: Caution
names: Domain
names: Function
names: PTM
names: Similarity
messages: Automethylated.
messages: Belongs to the damage-control phosphatase family. Sugar phosphate phosphatase III subfamily.
messages: Has been reportedly associated with a protein carboxyl methyltransferase activity, but whether this protein indeed has such an activity remains to be determined (PubMed:25732820). It has been later shown to belong to a family of metal-dependent phosphatases implicated in metabolite damage-control (PubMed:27322068).
messages: Metal-dependent phosphatase that shows phosphatase activity against several substrates, including fructose-1-phosphate and fructose-6-phosphate (By similarity). Its preference for fructose-1-phosphate, a strong glycating agent that causes DNA damage rather than a canonical yeast metabolite, suggests a damage-control function in hexose phosphate metabolism (By similarity). Has also been shown to have O-methyltransferase activity that methylates glutamate residues of target proteins to form gamma-glutamyl methyl ester residues (PubMed:25732820). Possibly methylates PCNA, suggesting it is involved in the DNA damage response (PubMed:25732820).
messages: Metal-dependent phosphatase that shows phosphatase activity against several substrates, including fructose-1-phosphate and fructose-6-phosphate. Its preference for fructose-1-phosphate, a strong glycating agent that causes DNA damage rather than a canonical yeast metabolite, suggests a damage-control function in hexose phosphate metabolism. Has also been shown to have O-methyltransferase activity that methylates glutamate residues of target proteins to form gamma-glutamyl methyl ester residues. Possibly methylates PCNA, suggesting it is involved in the DNA damage response.
messages: Subfamily III proteins have a conserved RTxK motif about 40-50 residues from the C-terminus; the threonine may be replaced by serine or cysteine.

9606:ARHGAP11B
gene id: 9606:ARHGAP11B
uniprot id: Q3KRB8
names: Caution
names: Developmental Stage
names: Function
names: Miscellaneous
names: Subcellular Location Annotation
names: Subunit
messages: ARHGAP11B arose from partial duplication of ARHGAP11A on the human lineage after separation from the chimpanzee lineage, but before the divergence from Neandertals.
messages: Although it contains a Rho-GAP domains, does not have GTPase activator activity (PubMed:25721503, PubMed:27957544). The absence of GTPase activator activity is required to promote amplification of basal progenitors (PubMed:27957544). Restoring this activity abolishes ability to promote amplification of basal progenitors during neocortex development (PubMed:27957544).
messages: Hominin-specific protein that promotes development and evolutionary expansion of the brain neocortex (PubMed:25721503, PubMed:27957544, PubMed:30484771, PubMed:32554627, PubMed:33938018). Able to promote amplification of basal progenitors in the subventricular zone, producing more neurons during fetal corticogenesis, thereby playing a key role in neocortex expansion (PubMed:25721503). Promotes the proliferation of basal progenitors by inhibiting the mitochondrial permeability transition pore (mPTP): delays the opening of the mPTP via interaction with ADP:ATP translocase, thereby increasing mitochondrial Ca(2+) concentration and inducing glutamine catabolism, which is required for basal progenitor proliferation (PubMed:31883789). Does not possess GTPase activator activity: the absence of GTPase activator activity is required to promote amplification of basal progenitors during neocortex development (PubMed:25721503, PubMed:27957544).
messages: Interacts with ADP:ATP translocase components SLC25A4/ANT1 and SLC25A5/ANT2.
messages: Mitochondrion matrix
messages: Specifically expressed in radial glia cells of cortical neural stem and progenitor cells (NPCs) during neocortex development. Preferentially expressed in apical and basal radial glia (PubMed:25721503). Not detected in cortical neurons and cortical plate (PubMed:25721503).
messages: When expressed in embryonic mouse neocortex, promotes basal progenitor generation and self-renewal, and can increase cortical plate area and induce gyrification (PubMed:25721503, PubMed:33938018). Mice exhibit increased neocortical size and upper-layer neuron numbers persisting into adulthood (PubMed:33938018). Moreover, mice display altered neurobehaviour, characterized by an increased memory flexibility and a reduced anxiety level (PubMed:33938018). When expressed in the developing neocortex of the gyrencephalic ferret, strongly increases proliferative basal radial glia, a progenitor cell type thought to be instrumental for neocortical expansion, resulting in extension of the neurogenic period and an increase in upper-layer neurons (PubMed:30484771). As consequence, the postnatal ferret neocortex displays increased neuron density in the upper cortical layers and expands in both the radial and tangential dimensions (PubMed:30484771). Expression in fetal neocortex of the common marmoset increases the numbers of upper-layer neurons, promoting enlargement of the neocortex and inducing its folding (PubMed:32554627).

9606:GRHL1
gene id: 9606:GRHL1
uniprot id: Q9NZI5
names: Developmental Stage
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the grh/CP2 family. Grainyhead subfamily.
messages: Binds DNA as homodimer (PubMed:29309642). Homodimer, also forms heterodimers with GRHL2 or GRHL3 (PubMed:12175488, PubMed:12549979, PubMed:29309642, PubMed:35013237).
messages: Expressed in fetal liver and brain.
messages: Functions as transcription activator.
messages: GRHL genes (GRHL1, GRHL2 and GRHL3) show a paradoxical lack of redundancy despite their extensive sequence identity in the DNA-binding and protein dimerization domains and the fact that the core consensus DNA binding sites are identical. They have related but remarkably different functions during embryogenesis because of their differential spatiotemporal expression patterns during development.
messages: Isoform 1 is highly expressed in brain, pancreas, tonsil, placenta and kidney. Isoform 2 is highly expressed in brain and liver. Expressed at very low levels in non-steroidogenic cells.
messages: May function as a repressor in tissues where both isoform 1 and isoform 2 are expressed.
messages: Methylation at Arg-9 and Lys-116 may be involved in regulating transcriptional activation.
messages: Nucleus
messages: Transcription factor involved in epithelial development. Binds directly to the consensus DNA sequence 5'-AACCGGTT-3' (PubMed:12175488, PubMed:18288204, PubMed:29309642). Important regulator of DSG1 in the context of hair anchorage and epidermal differentiation, participates in the maintenance of the skin barrier. There is no genetic interaction with GRHL3, nor functional cooperativity due to diverse target gene selectivity during epithelia development (By similarity). May play a role in regulating glucose homeostasis and insulin signaling.

9606:RSPRY1
gene id: 9606:RSPRY1
uniprot id: Q96DX4
names: Disease Annotation
names: Subcellular Location Annotation
messages: Secreted
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:RAD51C
gene id: 9606:RAD51C
uniprot id: O43502
names: Disease Annotation
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the RecA family. RAD51 subfamily.
messages: Cytoplasm
messages: Essential for the homologous recombination (HR) pathway of DNA repair. Involved in the homologous recombination repair (HRR) pathway of double-stranded DNA breaks arising during DNA replication or induced by DNA-damaging agents. Part of the RAD51 paralog protein complexes BCDX2 and CX3 which act at different stages of the BRCA1-BRCA2-dependent HR pathway. Upon DNA damage, BCDX2 seems to act downstream of BRCA2 recruitment and upstream of RAD51 recruitment; CX3 seems to act downstream of RAD51 recruitment; both complexes bind predominantly to the intersection of the four duplex arms of the Holliday junction (HJ) and to junction of replication forks. The BCDX2 complex was originally reported to bind single-stranded DNA, single-stranded gaps in duplex DNA and specifically to nicks in duplex DNA. The BCDX2 subcomplex RAD51B:RAD51C exhibits single-stranded DNA-dependent ATPase activity suggesting an involvement in early stages of the HR pathway. Involved in RAD51 foci formation in response to DNA damage suggesting an involvement in early stages of HR probably in the invasion step. Has an early function in DNA repair in facilitating phosphorylation of the checkpoint kinase CHEK2 and thereby transduction of the damage signal, leading to cell cycle arrest and HR activation. Participates in branch migration and HJ resolution and thus is important for processing HR intermediates late in the DNA repair process; the function may be linked to the CX3 complex. Part of a PALB2-scaffolded HR complex containing BRCA2 and which is thought to play a role in DNA repair by HR. Protects RAD51 from ubiquitin-mediated degradation that is enhanced following DNA damage. Plays a role in regulating mitochondrial DNA copy number under conditions of oxidative stress in the presence of RAD51 and XRCC3. Contributes to DNA cross-link resistance, sister chromatid cohesion and genomic stability. Involved in maintaining centrosome number in mitosis.
messages: Expressed in a variety of tissues, with highest expression in testis, heart muscle, spleen and prostate.
messages: Mitochondrion
messages: Nucleus
messages: Part of the RAD51 paralog protein complexes BCDX2 and CX3; the complexes have a ring-like structure arranged into a flat disc around a central channel (PubMed:12427746, PubMed:11751635, PubMed:11751636, PubMed:11842112, PubMed:11842113, PubMed:14704354). The BCDX2 complex consits of RAD51B, RAD51C, RAD51D and XRCC2; the CX3 complex consists of RAD51C and XRCC3 (PubMed:11751635, PubMed:11842113, PubMed:14704354). The BCDX2 subcomplex RAD51B:RAD51C interacts with RAD51 (PubMed:12427746, PubMed:16395335). Interacts with SWSAP1; involved in homologous recombination repair (PubMed:21965664). Interacts directly with PALB2 which may serve as a scaffold for a HR complex containing PALB2, BRCA2, RAD51C, RAD51 and XRCC3 (PubMed:24141787). Interacts with HELQ (PubMed:24005041).
messages: Stress-induced increase in the mitochondrial levels is seen.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: perinuclear region

9606:TRAPPC13
gene id: 9606:TRAPPC13
uniprot id: A5PLN9
names: Miscellaneous
names: Sequence Caution
names: Similarity
names: Subunit
messages: Belongs to the TRAPPC13 family.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Part of the multisubunit TRAPP (transport protein particle) complex.
messages: Wrong choice of CDS.

9606:WDR18
gene id: 9606:WDR18
uniprot id: Q9BV38
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the WD repeat IPI3/WDR18 family.
messages: Component of the 5FMC complex, at least composed of PELP1, LAS1L, TEX10, WDR18 and SENP3; the complex interacts with methylated CHTOP and ZNF148. Interacts with NOL9. Component of the PELP1 complex, composed of at least PELP1, TEX10 and WDR18. The complex interacts with pre-60S ribosome particles (PubMed:21326211).
messages: Cytoplasm
messages: Dynein axonemal particle
messages: Functions as a component of the Five Friends of Methylated CHTOP (5FMC) complex; the 5FMC complex is recruited to ZNF148 by methylated CHTOP, leading to desumoylation of ZNF148 and subsequent transactivation of ZNF148 target genes (PubMed:22872859). Component of the PELP1 complex involved in the nucleolar steps of 28S rRNA maturation and the subsequent nucleoplasmic transit of the pre-60S ribosomal subunit (PubMed:21326211). May play a role during development (By similarity).
messages: nucleolus
messages: nucleoplasm

9606:FAM98A
gene id: 9606:FAM98A
uniprot id: B4DT23
uniprot id: I6L9E8
uniprot id: Q8NCA5
names: Function
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Belongs to the FAM98 family.
messages: Expressed strongly in colorectal cancer cells (PubMed:28040436). Expressed strongly in colorectal cancer tissues compared to wild-type colon samples (at protein level) (PubMed:28040436). Expressed strongly in colorectal cancer tissues compared to wild-type colon samples (PubMed:28040436).
messages: Interacts (via N- and C-terminus) with DDX1 (PubMed:28040436). Interacts (via N- and C-terminus) with C14orf166 (PubMed:28040436). Interacts with FAM98B (PubMed:28040436). Interacts with PLEKHM1 (via N- and C-terminus) (By similarity).
messages: Positively stimulates PRMT1-induced protein arginine methylation (PubMed:28040436). Involved in skeletal homeostasis (By similarity). Positively regulates lysosome peripheral distribution and ruffled border formation in osteoclasts (By similarity).

9606:ZIC3
gene id: 9606:ZIC3
uniprot id: O60481
names: Disease Annotation
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Acts as transcriptional activator. Required in the earliest stages in both axial midline development and left-right (LR) asymmetry specification. Binds to the minimal GLI-consensus sequence 5'-GGGTGGTC-3'.
messages: Belongs to the GLI C2H2-type zinc-finger protein family.
messages: Cytoplasm
messages: Interacts (via the C2H2-type domains 3, 4 and 5) with MDFIC (via the C2H2-type domains 3, 4 and 5); the interaction reduces its transcriptional activity (By similarity). Interacts with KPNA1 and KPNA6. Interacts (via C2H2-type domains 3, 4 and 5) with GLI3; the interaction enhances its transcriptional activity.
messages: Nucleus
messages: The C2H2-type 3, 4 and 5 zinc finger domains are necessary for transcription activation.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:ADGRL2
gene id: 9606:ADGRL2
uniprot id: A0A6I8PTT2
uniprot id: O95490
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor 2 family. Adhesion G-protein coupled receptor (ADGR) subfamily.
messages: Calcium-independent receptor of low affinity for alpha-latrotoxin, an excitatory neurotoxin present in black widow spider venom which triggers massive exocytosis from neurons and neuroendocrine cells. Receptor probably implicated in the regulation of exocytosis.
messages: Expressed very widely in all normal tissues tested. Expression is variable in tumor cell lines, apparently elevated in some lines and absent or markedly reduced in others.
messages: Forms a heterodimer, consisting of a large extracellular region non-covalently linked to a seven-transmembrane moiety.
messages: Membrane
messages: Proteolytically cleaved into 2 subunits, an extracellular subunit and a seven-transmembrane subunit.

9606:SPANXN1
gene id: 9606:SPANXN1
uniprot id: Q5VSR9
names: Similarity
messages: Belongs to the SPAN-X family.

9606:POF1B
gene id: 9606:POF1B
uniprot id: Q8WVV4
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Interacts with nonmuscle actin.
messages: Plays a key role in the organization of epithelial monolayers by regulating the actin cytoskeleton. May be involved in ovary development.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: tight junction

9606:SCUBE2
gene id: 9606:SCUBE2
uniprot id: B3KS09
uniprot id: Q9NQ36
names: Caution
names: Domain
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cell surface
messages: Expressed in a broad spectrum of adult tissues (PubMed:12270931).
messages: Forms homooligomers. Forms heterooligomers with SCUBE1. Forms heterooligomers with SCUBE3 (PubMed:33308444). Interacts with SHH via the cholesterol anchor of the dually lipid-modified SHH (ShhNp) (PubMed:19480626, PubMed:22902404). Interacts with PTCH1 (PubMed:19480626, PubMed:22902404). Interacts with VEGFR2 (PubMed:27834687).
messages: It is unclear how SCUBE2 binds the dilipidated SHH. According to a report, the SHH cholesterol-anchor, but not palmitate, seems to be both necessary and sufficient for SCUBE2-mediated SHH release from the cell membrane (PubMed:22902404). According to a second paper, palmitoylation accelerates the rate of SCUBE2-mediated release (PubMed:22677548). Cholesterol modification is sufficient for a heterologous protein to bind to SCUBE2 and to be secreted in a SCUBE2-dependent manner (PubMed:22902404).
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: Lipid-binding protein required for SHH long-range signaling by binding to the dually lipid-modified SHH (ShhNp) and by promoting ShhNp mobilization, solubilization and release from the cell membrane (PubMed:22902404, PubMed:22677548). Acts by enhancing the proteolytic processing (shedding) of the lipid-modified N- and C- terminal of ShhNp at the cell surface (PubMed:24522195). Synergizes with DISP1 to increase SHH secretion (PubMed:22902404). Probable cell surface coreceptor for VEGFR2 involved in VEGFR2-mediated angiogenesis (PubMed:27834687).
messages: N-glycosylated.
messages: Secreted
messages: The CUB domain is important for the interaction with the cholesterol-anchor of SHH. The CUB domain regulates protease recruitment and activation during SHH shedding.

9606:ABCD3
gene id: 9606:ABCD3
uniprot id: P28288
names: Caution
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the ABC transporter superfamily. ABCD family. Peroxisomal fatty acyl CoA transporter (TC 3.A.1.203) subfamily.
messages: Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that catalyzes the transport of long-chain fatty acids (LCFA)-CoA, dicarboxylic acids-CoA, long-branched-chain fatty acids-CoA and bile acids from the cytosol to the peroxisome lumen for beta-oxydation (PubMed:11248239, PubMed:25168382, PubMed:24333844, PubMed:29397936). Has fatty acyl-CoA thioesterase and ATPase activities (PubMed:29397936). Probably hydrolyzes fatty acyl-CoAs into free fatty acids prior to their ATP-dependent transport into peroxisomes (By similarity). Thus, play a role in regulation of LCFAs and energy metabolism namely, in the degradation and biosynthesis of fatty acids by beta-oxidation (PubMed:25944712, PubMed:24333844).
messages: Homodimers (PubMed:17609205). Can form heterodimers with ABCD1 and ABCD2 (PubMed:10777694, PubMed:10551832, PubMed:17609205). Dimerization is necessary to form an active transporter (PubMed:17609205). Interacts with PEX19; mediates the targeting of ABCD3 to peroxisomes (PubMed:10704444, PubMed:16344115, PubMed:17761678).
messages: Mutation in ABCD3 have been found in two individuals affected by Zellweger syndrome (PubMed:1301993). Later studies, however, showed unambiguously that a PEX1 defect was the underlying cause of the defect in peroxisome biogenesis in these patients (PubMed:9539740).
messages: Peroxisome membrane
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitinated by PEX2 during pexophagy in response to starvation, leading to its degradation.

9606:RPS6KA6
gene id: 9606:RPS6KA6
uniprot id: Q9UK32
names: Activity Regulation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. S6 kinase subfamily.
messages: Constitutively activated by phosphorylation at Ser-232, Ser-372, and Ser-389 in serum-starved cells. Does not require growth factor stimulation for significant kinase activity.
messages: Constitutively active serine/threonine-protein kinase that exhibits growth-factor-independent kinase activity and that may participate in p53/TP53-dependent cell growth arrest signaling and play an inhibitory role during embryogenesis.
messages: Forms a complex with MAPK3/ERK1 but not with MAPK9 or MAPK14 in serum-starved cells.
messages: Nucleus
messages: Phosphorylated at Ser-232, Ser-372, and Ser-389 in serum-starved cells.
messages: cytosol

9606:SIX3
gene id: 9606:SIX3
uniprot id: O95343
names: Developmental Stage
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the SIX/Sine oculis homeobox family.
messages: Expression is detected in Rathke's pouch and overlying ventral diencephalon at carnegie stage 17 and in the anterior and posterior lobes of the pituitary at carnegie stage 20. At fetal stage, expression is observed in the anterior pituitary, and the ventricular zones of the hypothalamus and telencephalic vesicles.
messages: Interacts with EYA4; translocates EYA4 from the cytoplasm to the nucleus and promotes activation of their target genes (By similarity). Interacts with MTA1 and HDAC2; represses its own transcription (By similarity). Interacts with MTA1; facilitates the binding of SIX3 to the core DNA motif of SIX3 promoter (By similarity). Interacts with EYA1; promotes EYA1 translocation to the nucleus (By similarity). Interacts with TLE1 and TLE5 (via Q domain); can act in combination with either TLE1 and/or TLE5 leading to transcriptional repression or activation, respectively. Interacts (via homeobox) with NR4A3; differentially regulates the transcriptional activities NR4A3. Interacts with GMNN. Interacts with TLE4.
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Transcriptional regulator which can act as both a transcriptional repressor and activator by binding a ATTA homeodomain core recognition sequence on these target genes. During forebrain development represses WNT1 expression allowing zona limitans intrathalamica formation and thereby ensuring proper anterio-posterior patterning of the diencephalon and formation of the rostral diencephalon. Acts as a direct upstream activator of SHH expression in the rostral diencephalon ventral midline and that in turn SHH maintains its expression. In addition, Six3 activity is required for the formation of the telencephalon. During postnatal stages of brain development is necessary for ependymal cell maturation by promoting the maturation of radial glia into ependymal cells through regulation of neuroblast proliferation and migration. Acts on the proliferation and differentiation of neural progenitor cells through activating transcription of CCND1 and CCND2. During early lens formation plays a role in lens induction and specification by activating directly PAX6 in the presumptive lens ectoderm. In turn PAX6 activates SIX3 resulting in activation of PDGFRA and CCND1 promoting cell proliferation. Also is required for the neuroretina development by directly suppressing WNT8B expression in the anterior neural plate territory. Its action during retina development and lens morphogenesis is TLE5 and TLE4-dependent manner. Furthermore, during eye development regulates several genes expression. Before and during early lens development represses the CRYGF promoter by binding a SIX repressor element. Directly activates RHO transcription, or cooperates with CRX or NRL. Six3 functions also in the formation of the proximodistal axis of the optic cup, and promotes the formation of optic vesicles-like structures. During pituitary development, acts in parallel or alternatively with HESX1 to control cell proliferation through Wnt/beta-catenin pathway (By similarity). Plays a role in eye development b…

9606:KCNMB3
gene id: 9606:KCNMB3
uniprot id: Q9NPA1
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the KCNMB (TC 8.A.14.1) family. KCNMB3 subfamily.
messages: Interacts with KCNMA1 tetramer. There are probably 4 molecules of KCMNB3 per KCNMA1 tetramer.
messages: Isoform 1, isoform 3 and isoform 4 are widely expressed. Isoform 2 is expressed placenta, pancreas, kidney and heart. Isoform 1 and isoform 3 are highly expressed in pancreas and testis.
messages: Isoform 4 cytoplasmic N-terminal domain participates in the partial inactivation of KCNMA1, possibly by binding to a receptor site.
messages: Membrane
messages: N-glycosylated.
messages: Regulatory subunit of the calcium activated potassium KCNMA1 (maxiK) channel. Modulates the calcium sensitivity and gating kinetics of KCNMA1, thereby contributing to KCNMA1 channel diversity. Alters the functional properties of the current expressed by the KCNMA1 channel. Isoform 2, isoform 3 and isoform 4 partially inactivate the current of KCNBMA. Isoform 4 induces a fast and incomplete inactivation of KCNMA1 channel that is detectable only at large depolarizations. In contrast, isoform 1 does not induce detectable inactivation of KCNMA1. Two or more subunits of KCNMB3 are required to block the KCNMA1 tetramer.
messages: The extracellular domain contains disulfide bond essential for the gating mechanism.
messages: The extracellular domain forms gates to block ion permeation, providing a mechanism by which current can be rapidly diminished upon cellular repolarization.

9606:ADM
gene id: 9606:ADM
uniprot id: P35318
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: AM and PAMP are potent hypotensive and vasodilatator agents. Numerous actions have been reported most related to the physiologic control of fluid and electrolyte homeostasis. In the kidney, am is diuretic and natriuretic, and both am and pamp inhibit aldosterone secretion by direct adrenal actions. In pituitary gland, both peptides at physiologically relevant doses inhibit basal ACTH secretion. Both peptides appear to act in brain and pituitary gland to facilitate the loss of plasma volume, actions which complement their hypotensive effects in blood vessels.
messages: Belongs to the adrenomedullin family.
messages: Highest levels found in pheochromocytoma and adrenal medulla. Also found in lung, ventricle and kidney tissues.
messages: Secreted

9606:SLC16A4
gene id: 9606:SLC16A4
uniprot id: O15374
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the major facilitator superfamily. Monocarboxylate porter (TC 2.A.1.13) family.
messages: Cell membrane
messages: Proton-linked monocarboxylate transporter. Catalyzes the rapid transport across the plasma membrane of many monocarboxylates such as lactate, pyruvate, branched-chain oxo acids derived from leucine, valine and isoleucine, and the ketone bodies acetoacetate, beta-hydroxybutyrate and acetate (By similarity).

9606:TANGO2
gene id: 9606:TANGO2
uniprot id: Q6ICL3
names: Caution
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the Tango2 family.
messages: Cytoplasm
messages: Golgi apparatus
messages: May be involved in lipid homeostasis.
messages: Mitochondrion
messages: Previous published data showed conflicting results on the intracellular location of TANGO2. Has been reported to be located in the Golgi apparatus (PubMed:26805781). However, another study was unable to detect Golgi localization (PubMed:32909282). Has been reported to be located in the mitochondrion by several recent studies (PubMed:32909282, PubMed:36961129, PubMed:35197517). However, no mitochondrial localization was detected in a study which reported that the protein is primarily cytoplasmic (PubMed:31276219).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:MAGI3
gene id: 9606:MAGI3
uniprot id: Q5TCQ9
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts with HTLV1 Tax protein, possibly affecting the transformation ability of Tax.
messages: (Microbial infection) Interacts with human papillomavirus/HPV type 16 and 18 E6 proteins.
messages: Acts as a scaffolding protein at cell-cell junctions, thereby regulating various cellular and signaling processes. Cooperates with PTEN to modulate the kinase activity of AKT1. Its interaction with PTPRB and tyrosine phosphorylated proteins suggests that it may link receptor tyrosine phosphatase with its substrates at the plasma membrane. In polarized epithelial cells, involved in efficient trafficking of TGFA to the cell surface. Regulates the ability of LPAR2 to activate ERK and RhoA pathways. Regulates the JNK signaling cascade via its interaction with FZD4 and VANGL2.
messages: Belongs to the MAGUK family.
messages: Cell membrane
messages: Interacts with ADRB1, FZD4, FZD7, PTPRB, TGFA and VANGL2. Interacts with unidentified tyrosine phosphorylated proteins (By similarity). Interacts with ADGRB1, LPAR2/EDG4, GRIN2B and PTEN. Does not interact with HTLV TAX2 or TAX3 proteins. Interacts with DLL1 (By similarity). Interacts with PRRG4 (via cytoplasmic domain) (PubMed:23873930).
messages: MAGI3 PDZ domains are used to design peptide ligands that bind and inhibit PDZ domains.
messages: Nucleus
messages: Ubiquitinated following interaction with HPV E6 protein, leading to its degradation by the proteasome. Degradation is independent of E6AP ubiquitin ligase complex.
messages: Widely expressed.
messages: tight junction

9606:THEM6
gene id: 9606:THEM6
uniprot id: Q8WUY1
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the THEM6 family.
messages: Secreted

9606:MRPL15
gene id: 9606:MRPL15
uniprot id: Q9P015
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the universal ribosomal protein uL15 family.
messages: Component of the mitochondrial large ribosomal subunit (mt-LSU) (PubMed:28892042, PubMed:25838379, PubMed:25278503). Mature mammalian 55S mitochondrial ribosomes consist of a small (28S) and a large (39S) subunit. The 28S small subunit contains a 12S ribosomal RNA (12S mt-rRNA) and 30 different proteins. The 39S large subunit contains a 16S rRNA (16S mt-rRNA), a copy of mitochondrial valine transfer RNA (mt-tRNA(Val)), which plays an integral structural role, and 52 different proteins.
messages: Mitochondrion

9606:SLC36A4
gene id: 9606:SLC36A4
uniprot id: Q6YBV0
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the amino acid/polyamine transporter 2 family.
messages: Expressed in retinal pigmented epithelial cells.
messages: Interacts with CRYBA1.
messages: Lysosome membrane
messages: Uniporter that mediates the transport of neutral amino acids like L-tryptophan, proline and alanine (PubMed:21097500). The transport activity is sodium ions-independent, electroneutral and therefore functions via facilitated diffusion (PubMed:21097500).

9606:ATP1A2
gene id: 9606:ATP1A2
uniprot id: A0A0S2Z3W6
uniprot id: P50993
names: Caution
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIC subfamily.
messages: Cell membrane
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: Membrane
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The sodium/potassium-transporting ATPase is composed of a catalytic alpha subunit, an auxiliary non-catalytic beta subunit and an additional regulatory subunit. Interacts with regulatory subunit FXYD1.
messages: This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates the electrochemical gradient of sodium and potassium, providing the energy for active transport of various nutrients.

9606:QRFP
gene id: 9606:QRFP
uniprot id: P83859
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the RFamide neuropeptide family.
messages: Expressed widely in the brain with highest expression levels in the cerebellum, medulla, pituitary, retina, vestibular nucleus, and white matter. Also expressed in the bladder, colon, coronary artery, parathyroid gland, prostate, testis, and thyroid.
messages: Ligand for the G-protein coupled receptor QRFPR/GPR103.
messages: Secreted
messages: Stimulates feeding behavior, metabolic rate and locomotor activity and increases blood pressure. May have orexigenic activity. May promote aldosterone secretion by the adrenal gland (By similarity).

9606:RBL2
gene id: 9606:RBL2
uniprot id: Q08999
names: Developmental Stage
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Interacts with JC virus small t antigen.
messages: Belongs to the retinoblastoma protein (RB) family.
messages: During G0 and early G1 phase of the cell cycle, phosphorylated on Ser-639 and on 5 sites within the domain B. Phosphorylation on Ser-672 in G1 leads to its ubiquitin-dependent proteolysis.
messages: G0-restricted expression.
messages: Interacts with AATF. Interacts with KMT5B, KMT5C and USP4 (By similarity). Component of the DREAM complex (also named LINC complex) at least composed of E2F4, E2F5, LIN9, LIN37, LIN52, LIN54, MYBL1, MYBL2, RBL1, RBL2, RBBP4, TFDP1 and TFDP2. The complex exists in quiescent cells where it represses cell cycle-dependent genes. It dissociates in S phase when LIN9, LIN37, LIN52 and LIN54 form a subcomplex that binds to MYBL2. Interacts with RINT1. Interacts with PML (isoform PML-1, isoform PML-2, isoform PML-3, isoform PML-4 and isoform PML-5). Interacts with RBBP9 (By similarity).
messages: Key regulator of entry into cell division. Directly involved in heterochromatin formation by maintaining overall chromatin structure and, in particular, that of constitutive heterochromatin by stabilizing histone methylation. Recruits and targets histone methyltransferases KMT5B and KMT5C, leading to epigenetic transcriptional repression. Controls histone H4 'Lys-20' trimethylation. Probably acts as a transcription repressor by recruiting chromatin-modifying enzymes to promoters. Potent inhibitor of E2F-mediated trans-activation, associates preferentially with E2F5. Binds to cyclins A and E. Binds to and may be involved in the transforming capacity of the adenovirus E1A protein. May act as a tumor suppressor.
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:FAT4
gene id: 9606:FAT4
uniprot id: A0A6Q8JR05
uniprot id: A0A7P0T1I0
uniprot id: B3KU84
uniprot id: Q6V0I7
uniprot id: X2GA70
names: Caution
names: Developmental Stage
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cadherins are calcium-dependent cell adhesion proteins. FAT4 plays a role in the maintenance of planar cell polarity as well as in inhibition of YAP1-mediated neuroprogenitor cell proliferation and differentiation (By similarity).
messages: Heterophilic interaction with DCHS1; this interaction affects their respective protein levels. Interacts (via cytoplasmic domain) with MPDZ. Forms a complex with PALS1 and MPDZ.
messages: In embryos at 9 weeks the strongest expression is detected in the apical neuroepithelium, with weaker staining being present in the subventricular zone and within the cortical plate.
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: Membrane
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Widely expressed. Expressed in fetal brain, infant brain, brain tumor and colorectal cancer.

9606:SUN5
gene id: 9606:SUN5
uniprot id: Q8TC36
names: Disease Annotation
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Golgi apparatus
messages: Highly glycosylated in the Golgi apparatus during spermiogenesis.
messages: Nucleus inner membrane
messages: Plays an essential role in anchoring sperm head to the tail. Is responsible for the attachment of the coupling apparatus to the sperm nuclear envelope.
messages: Probable homotrimer. Interacts with DNAJB13.
messages: Sperm (at protein level) (PubMed:27640305). Widely expressed (PubMed:12621555). Conflictingly shown to be specifically expressed in testis (PubMed:21711156).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:OPN1MW2
gene id: 9606:OPN1MW2
uniprot id: P04001
uniprot id: P0DN77
uniprot id: P0DN78
names: Caution
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor 1 family. Opsin subfamily.
messages: Cell membrane
messages: Medium-wave-sensitive opsin genes vary in number among individuals and, together with a single red pigment gene, reside in a head-to-tail tandem array within the X chromosome. In the GRCh38 reference genome assembly, there are 3 genes in tandem coding for identical proteins AC P04001, AC P0DN77 and P0DN78.
messages: Monomer. Homodimer. Homotetramer.
messages: N-glycosylated (PubMed:30948514). O-glycosylated (PubMed:30948514).
messages: N-glycosylated. O-glycosylated.
messages: Phosphorylated on some or all of the serine and threonine residues present in the C-terminal region.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The three color pigments are found in the cone photoreceptor cells.
messages: Visual pigments are the light-absorbing molecules that mediate vision. They consist of an apoprotein, opsin, covalently linked to cis-retinal.

9606:OR9Q1
gene id: 9606:OR9Q1
uniprot id: Q8NGQ5
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Odorant receptor.

9606:CTRL
gene id: 9606:CTRL
uniprot id: P40313
names: Similarity
messages: Belongs to the peptidase S1 family.

9606:GP5
gene id: 9606:GP5
uniprot id: P40197
names: Function
names: PTM
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Membrane
messages: Platelets and megakaryocytes.
messages: The GPIb-V-IX complex functions as the vWF receptor and mediates vWF-dependent platelet adhesion to blood vessels. The adhesion of platelets to injured vascular surfaces in the arterial circulation is a critical initiating event in hemostasis.
messages: The N-terminus is blocked.

9606:FSCN1
gene id: 9606:FSCN1
uniprot id: A0A384MEG1
uniprot id: B3KTA3
uniprot id: Q16658
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Actin-binding protein that contains 2 major actin binding sites (PubMed:21685497, PubMed:23184945). Organizes filamentous actin into parallel bundles (PubMed:20393565, PubMed:21685497, PubMed:23184945). Plays a role in the organization of actin filament bundles and the formation of microspikes, membrane ruffles, and stress fibers (PubMed:22155786). Important for the formation of a diverse set of cell protrusions, such as filopodia, and for cell motility and migration (PubMed:20393565, PubMed:21685497, PubMed:23184945). Mediates reorganization of the actin cytoskeleton and axon growth cone collapse in response to NGF (PubMed:22155786).
messages: Belongs to the fascin family.
messages: Cell junction
messages: Composed of four fascin beta-trefoil domains.
messages: Interacts with RUFY3 (via N-terminus); the interaction induces neuron axon development (By similarity). Interacts with NGFR (By similarity). Associates with CTNNB1 (By similarity). Interacts with PLXNB3 (PubMed:21706053).
messages: Phosphorylation at Ser-39 inhibits actin-binding (PubMed:8647875, PubMed:8999969). Phosphorylation is required for the reorganization of the actin cytoskeleton in response to NGF (PubMed:22155786).
messages: Ubiquitous.
messages: cell cortex
messages: cytoskeleton
messages: cytosol
messages: filopodium
messages: invadopodium
messages: microvillus
messages: stress fiber

9606:STT3A
gene id: 9606:STT3A
uniprot id: P46977
names: Disease Annotation
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the STT3 family.
messages: Catalytic subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophosphate to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains, the first step in protein N-glycosylation (PubMed:31831667, PubMed:34653363). N-glycosylation occurs cotranslationally and the complex associates with the Sec61 complex at the channel-forming translocon complex that mediates protein translocation across the endoplasmic reticulum (ER). All subunits are required for a maximal enzyme activity. This subunit contains the active site and the acceptor peptide and donor lipid-linked oligosaccharide (LLO) binding pockets (By similarity). STT3A is present in the majority of OST complexes and mediates cotranslational N-glycosylation of most sites on target proteins, while STT3B-containing complexes are required for efficient post-translational glycosylation and mediate glycosylation of sites that have been skipped by STT3A (PubMed:19167329).
messages: Component of the oligosaccharyltransferase (OST) complex (PubMed:31831667). OST exists in two different complex forms which contain common core subunits RPN1, RPN2, OST48, OST4, DAD1 and TMEM258, either STT3A or STT3B as catalytic subunits, and form-specific accessory subunits (PubMed:23606741, PubMed:25135935, PubMed:31831667). STT3A complex assembly occurs through the formation of 3 subcomplexes. Subcomplex 1 contains RPN1 and TMEM258, subcomplex 2 contains the STT3A-specific subunits STT3A, DC2/OSTC, and KCP2 as well as the core subunit OST4, and subcomplex 3 contains RPN2, DAD1, and OST48. The STT3A complex can form stable complexes with the Sec61 complex or with both the Sec61 and TRAP complexes (By similarity).
messages: Despite low primary sequence conservation between eukaryotic catalytic subunits and bacterial and archaeal single subunit OSTs (ssOST), structural comparison revealed several common motifs at spatially equivalent positions, like the DXD motif 1 on the external loop 1 and the DXD motif 2 on the external loop 2 involved in binding of the metal ion cofactor and the carboxamide group of the acceptor asparagine, the conserved Glu residue of the TIXE/SVSE motif on the external loop 5 involved in catalysis, as well as the WWDYG and the DK/MI motifs in the globular domain that define the binding pocket for the +2 Ser/Thr of the acceptor sequon. In bacterial ssOSTs, an Arg residue was found to interact with a negatively charged side chain at the -2 position of the sequon. This Arg is conserved in bacterial enzymes and correlates with an extended sequon requirement (Asp-X-Asn-X-Ser/Thr) for bacterial N-glycosylation.
messages: Endoplasmic reticulum
messages: Endoplasmic reticulum membrane
messages: Expressed at high levels in placenta, liver, muscle and pancreas, and at very low levels in brain, lung and kidney. Expressed in skin fibroblasts (at protein level).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:OR52N5
gene id: 9606:OR52N5
uniprot id: A0A126GVK9
uniprot id: Q8NH56
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Membrane
messages: Odorant receptor.

9606:NECAP1
gene id: 9606:NECAP1
uniprot id: Q8NC96
names: Disease Annotation
names: Domain
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the NECAP family.
messages: Cell membrane
messages: Interacts with AP1G1 and AP2A1 components of the adapter protein complexes AP-1 and AP-2. Interacts with the GAE domain proteins GGA1, GGA2 and GGA3 (By similarity).
messages: Involved in endocytosis.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: The WXXF motifs mediate binding of accessory proteins to the ear-domain of AP-1, GGAs and AP-2 through hydrophobic interactions. Selective binding to the GAE domains of AP-1 or to the alpha-ear domain of AP-2 is tuned by the acidic context surrounding the motif and the properties of the second residue of the motif itself. The WXXF motif 1, which is preceded by an acidic residue and has a glycine in second position mediates specific interaction with AP-1. The WXXF motif 2, which is followed by the C-terminal carboxyl group negative charge, allows specific interaction with AP-2 (By similarity).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: clathrin-coated vesicle membrane

9606:MAEL
gene id: 9606:MAEL
uniprot id: A0A140VJP0
uniprot id: E9JVC4
uniprot id: Q96JY0
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the maelstrom family.
messages: Cytoplasm
messages: Interacts with SMARCB1, SIN3B and DDX4. Interacts with piRNA-associated proteins TDRD1, PIWIL1 and PIWIL2 (By similarity). Interacts with TEX19 (By similarity).
messages: Nucleus
messages: Plays a central role during spermatogenesis by repressing transposable elements and preventing their mobilization, which is essential for the germline integrity. Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and governs the methylation and subsequent repression of transposons. Its association with piP-bodies suggests a participation in the secondary piRNAs metabolic process. Required for the localization of germ-cell factors to the meiotic nuage (By similarity).
messages: Plays a central role during spermatogenesis by repressing transposable elements and preventing their mobilization, which is essential for the germline integrity. Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and governs the methylation and subsequent repression of transposons. Its association with piP-bodies suggests a participation in the secondary piRNAs metabolic process. Required for the localization of germ-cell factors to the meiotic nuage.
messages: Testis-specific. Expressed in various cancer cell lines, probably due to demethylation of its promoter.

9606:C1orf21
gene id: 9606:C1orf21
uniprot id: Q9H246
names: Tissue Specificity
messages: Expressed in spleen, prostate, testis and uterus.

9606:CEP164
gene id: 9606:CEP164
uniprot id: Q9UPV0
names: Disease Annotation
names: Function
names: PTM
names: Sequence Caution
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Contaminating sequence. Potential poly-A sequence.
messages: Expressed in several cell lines.
messages: Interacts (via N-terminus) with ATRIP. Interacts with ATM, ATR and MDC1. Interacts with XPA (via N-terminus) upon UV irradiation. Interacts with CEP83, CCDC92, TTBK2, DVL3, NPHP3 and weakly with NPHP4. Interacts with DZIP1 (By similarity).
messages: Nucleus
messages: Phosphorylation at Ser-186 is induced upon DNA-damage caused by treatment with IR irradiation, UV irradiation, hydroxyurea or amphidicolin. Also MDC1-mediated chromatin remodeling is critical for DNA damage-induced phosphorylation.
messages: Plays a role in microtubule organization and/or maintenance for the formation of primary cilia (PC), a microtubule-based structure that protrudes from the surface of epithelial cells. Plays a critical role in G2/M checkpoint and nuclear divisions. A key player in the DNA damage-activated ATR/ATM signaling cascade since it is required for the proper phosphorylation of H2AX, RPA, CHEK2 and CHEK1. Plays a critical role in chromosome segregation, acting as a mediator required for the maintenance of genomic stability through modulation of MDC1, RPA and CHEK1.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: centriole

9606:PFDN5
gene id: 9606:PFDN5
uniprot id: Q99471
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the prefoldin subunit alpha family.
messages: Binds specifically to cytosolic chaperonin (c-CPN) and transfers target proteins to it. Binds to nascent polypeptide chain and promotes folding in an environment in which there are many competing pathways for nonnative proteins. Represses the transcriptional activity of MYC.
messages: Cytoplasm
messages: Does not repress transcription activity of MYC.
messages: Heterohexamer of two PFD-alpha type and four PFD-beta type subunits. Binds to MYC; interacts with its N-terminal domain.
messages: Highly expressed in pancreas and skeletal muscle and moderately in other tissues.
messages: Nucleus

9606:PLXNA1
gene id: 9606:PLXNA1
uniprot id: Q9UIW2
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the plexin family.
messages: Cell membrane
messages: Coreceptor for SEMA3A, SEMA3C, SEMA3F and SEMA6D. Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton. Plays a role in axon guidance, invasive growth and cell migration. Class 3 semaphorins bind to a complex composed of a neuropilin and a plexin. The plexin modulates the affinity of the complex for specific semaphorins, and its cytoplasmic domain is required for the activation of down-stream signaling events in the cytoplasm (By similarity).
messages: Detected in fetal brain, lung, liver and kidney.
messages: Interacts directly with NRP1 and NRP2. Interacts with FARP2, RND1 and KDR/VEGFR2. Binding of SEMA3A leads to dissociation of FARP2 (By similarity).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:DSG3
gene id: 9606:DSG3
uniprot id: P32926
names: Disease Annotation
names: Domain
names: Function
names: Miscellaneous
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cell membrane
messages: Component of intercellular desmosome junctions. Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion.
messages: Epidermis, tongue, tonsil, esophagus and carcinomas. Expressed in skin and mucosa (at protein level) (PubMed:30528827).
messages: Interacts with PKP2.
messages: Pemphigus vulgaris (PV) is a potentially lethal skin disease in which epidermal blisters occur as the result of the loss of cell-cell adhesion caused by the action of autoantibodies against desmoglein 3.
messages: The disease may be caused by variants affecting the gene represented in this entry.
messages: Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain.
messages: desmosome

9606:TGM5
gene id: 9606:TGM5
uniprot id: O43548
names: Cofactor
names: Disease Annotation
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the transglutaminase superfamily. Transglutaminase family.
messages: Binds 1 Ca(2+) ion per subunit.
messages: By 12-O-tetradecanoylphorbol-13-acetate (TPA) and calcium in NHEK cells.
messages: Catalyzes the cross-linking of proteins and the conjugation of polyamines to proteins. Contributes to the formation of the cornified cell envelope of keratinocytes.
messages: Cytoplasm
messages: Expressed in foreskin keratinocytes.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:PCDHB10
gene id: 9606:PCDHB10
uniprot id: Q9UN67
names: Function
names: Subcellular Location Annotation
messages: Cell membrane
messages: Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain.

9606:NTM
gene id: 9606:NTM
uniprot id: Q9P121
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the immunoglobulin superfamily. IgLON family.
messages: Cell membrane
messages: Neural cell adhesion molecule.

9606:SH3GL3
gene id: 9606:SH3GL3
uniprot id: Q99963
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: An N-terminal amphipathic helix, the BAR domain and a second amphipathic helix inserted into helix 1 of the BAR domain (N-BAR domain) induce membrane curvature and bind curved membranes.
messages: Belongs to the endophilin family.
messages: Brain and testis.
messages: Cytoplasm
messages: Early endosome membrane
messages: Implicated in endocytosis. May recruit other proteins to membranes with high curvature (By similarity).
messages: Interacts with ARC (By similarity). Interacts with DNM1, SGIP1 and SYNJ1. Interacts with the huntingtin exon 1 protein (HDEX1P) containing a glutamine repeat in the pathological range and promotes formation of insoluble polyglutamine-containing aggregates in vivo. Interacts with DYDC1. Interacts with FASLG. Interacts with ATXN2. Interacts with BIN2.

9606:TMEM127
gene id: 9606:TMEM127
uniprot id: O75204
names: Disease Annotation
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the TMEM127 family.
messages: Cell membrane
messages: Consistent with the observation that mTORC1 signaling regulates cell growth and size in many species, TMEM127 knockdown cells are larger and proliferate at higher rates compared to control cell lines. In contrast, cell proliferation is reduced in cells overexpressing TMEM127 (PubMed:20154675).
messages: Controls cell proliferation acting as a negative regulator of TOR signaling pathway mediated by mTORC1. May act as a tumor suppressor.
messages: Cytoplasm
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry.
messages: Widely expressed.

9606:CFAP298
gene id: 9606:CFAP298
uniprot id: P57076
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the CFAP298 family.
messages: Cytoplasm
messages: Interacts with ZMYND10.
messages: Plays a role in motile cilium function, possibly by acting on outer dynein arm assembly (PubMed:24094744). Seems to be important for initiation rather than maintenance of cilium motility (By similarity). Required for correct positioning of the cilium at the apical cell surface, suggesting an additional role in the planar cell polarity (PCP) pathway (By similarity). May suppress canonical Wnt signaling activity (By similarity).
messages: The disease is caused by variants affecting the gene represented in this entry. Cilia in nasal epithelia show the absence of both outer and inner dynein-arm components and complete paralysis.
messages: cilium basal body

9606:LEFTY2
gene id: 9606:LEFTY2
uniprot id: O00292
names: Developmental Stage
names: Disease Annotation
names: Function
names: PTM
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Authors have revised their sequence, but have not submitted the revised DNA sequence.
messages: Belongs to the TGF-beta family.
messages: Mesenchymal cells of the endometrial stroma.
messages: Required for left-right (L-R) asymmetry determination of organ systems in mammals. May play a role in endometrial bleeding.
messages: Secreted
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The processing of the protein may also occur at the second R-X-X-R site located at AA 132-135. Processing appears to be regulated in a cell-type specific manner.
messages: Transiently expressed before and during menstrual bleeding.

9606:CIDEB
gene id: 9606:CIDEB
uniprot id: Q9UHD4
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts (via N-terminus) with HCV non-structural protein 5A (via N-terminus); this interaction seems to regulate the association of HCV particles with ApoE.
messages: (Microbial infection) Involved in Hepatatis C virus (HCV) assembly and required for HCV entry into hepatocytes.
messages: Belongs to the CIDE family.
messages: COPI-coated vesicle
messages: Endoplasmic reticulum membrane
messages: Golgi apparatus
messages: Highly expressed in liver and small intestine and, at lower levels, in colon, kidney and spleen.
messages: Interacts with DFFA (PubMed:10619428). Interacts with DFFB; inhibited by DFFB (PubMed:10619428). Interacts with APOB. Interacts with PREB/SEC12; facilitating loading of SCAP-SREBP into COPII vesicles (By similarity).
messages: Lipid droplet
messages: Lipid transferase specifically expressed in hepatocytes, which promotes unilocular lipid droplet formation by mediating lipid droplet fusion (PubMed:35939579). Lipid droplet fusion promotes their enlargement, restricting lipolysis and favoring lipid storage (PubMed:35939579). Localizes on the lipid droplet surface, at focal contact sites between lipid droplets, and mediates atypical lipid droplet fusion by promoting directional net neutral lipid transfer from the smaller to larger lipid droplets (By similarity). The transfer direction may be driven by the internal pressure difference between the contacting lipid droplet pair (By similarity). Promotes lipid exchange and lipid droplet fusion in both small and large lipid droplet-containing hepatocytes (By similarity). In addition to its role in lipid droplet fusion, also involved in cytoplasmic vesicle biogenesis and transport (By similarity). Required for very-low-density lipoprotein (VLDL) lipidation and maturation (By similarity). Probably involved in the biogenesis of VLDL transport vesicles by forming a COPII vesicle coat and facilitating the formation of endoplasmic reticulum-derived large vesicles (By similarity). Also involved in sterol-regulated export of the SCAP-SREBP complex, composed of SCAP, SREBF1/SREBP1 and SREBF2/SREBP2, by promoting loading of SCAP-SREBP into COPII vesicles (By similarity). May also activate apoptosis (PubMed:10619428).

9606:CDC45
gene id: 9606:CDC45
uniprot id: O75419
names: Developmental Stage
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the CDC45 family.
messages: Chromosome
messages: Component of the CMG helicase complex, a hexameric ring of related MCM2-7 subunits stabilized by CDC45 and the tetrameric GINS complex (PubMed:34700328, PubMed:34694004, PubMed:32453425). Associated with ORC2. Interacts with HELB (PubMed:25933514).
messages: Nucleus
messages: Required for initiation of chromosomal DNA replication. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Transcript peaks at G1-S transition, but total protein remains constant throughout the cell cycle. Expressed in multiple tissues during embryogenesis, including neural crest-derived structures.
messages: Widely expressed, highest levels are found in adult testis and thymus and in fetal liver.

9606:ZNF679
gene id: 9606:ZNF679
uniprot id: Q8IYX0
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:H4C6
gene id: 9606:H4C6
uniprot id: B2R4R0
uniprot id: P62805
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Acetylation at Lys-6 (H4K5ac), Lys-9 (H4K8ac), Lys-13 (H4K12ac) and Lys-17 (H4K16ac) occurs in coding regions of the genome but not in heterochromatin.
messages: Belongs to the histone H4 family.
messages: Butyrylation of histones marks active promoters and competes with histone acetylation.
messages: Chromosomal aberrations involving HISTONE H4 is a cause of B-cell non-Hodgkin lymphomas (B-cell NHL). Translocation t(3;6)(q27;p21), with BCL6.
messages: Chromosome
messages: Citrullination at Arg-4 (H4R3ci) by PADI4 impairs methylation.
messages: Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
messages: Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.
messages: Glutarylation at Lys-92 (H4K91glu) destabilizes nucleosomes by promoting dissociation of the H2A-H2B dimers from nucleosomes.
messages: Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.
messages: Monomethylated, dimethylated or trimethylated at Lys-21 (H4K20me1, H4K20me2, H4K20me3) (PubMed:12086618, PubMed:15964846, PubMed:17967882). Monomethylation is performed by KMT5A/SET8 (PubMed:15964846). Dimethylation and trimethylation is performed by KMT5B and KMT5C and induces gene silencing (By similarity). Monomethylated at Lys-13 (H4K12me1) by N6AMT1; H4K12me1 modification is present at the promoters of numerous genes encoding cell cycle regulators (PubMed:31061526).
messages: Monomethylation and asymmetric dimethylation at Arg-4 (H4R3me1 and H4R3me2a, respectively) by PRMT1 favors acetylation at Lys-9 (H4K8ac) and Lys-13 (H4K12ac). Demethylation is performed by JMJD6. Symmetric dimethylation on Arg-4 (H4R3me2s) by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage.
messages: Nucleus
messages: Phosphorylated by PAK2 at Ser-48 (H4S47ph). This phosphorylation increases the association of H3.3-H4 with the histone chaperone HIRA, thus promoting nucleosome assembly of H3.3-H4 and inhibiting nucleosome assembly of H3.1-H4.
messages: Sumoylated, which is associated with transcriptional repression.
messages: The disease is caused by variants affecting the gene represented in this entry. TEBIVANED1 is caused by variants in H4C3.
messages: The disease is caused by variants affecting the gene represented in this entry. TEBIVANED2 is caused by variants in H4C11.
messages: The disease is caused by variants affecting the gene represented in this entry. TEBIVANED3 is caused by variants in H4C5.
messages: The disease is caused by variants affecting the gene represented in this entry. TEBIVANED4 is caused by variants in H4C9.
messages: The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA (By similarity). Found in a co-chaperone complex with DNJC9, MCM2 and histone H3.3-H4 dimers (PubMed:33857403). Within the complex, interacts with DNJC9 (via C-terminus); the interaction is direct (PubMed:33857403).
messages: The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.
messages: Ubiquitinated by the CUL4-DDB-RBX1 complex in response to ultraviolet irradiation. This may weaken the interaction between histones and DNA and facilitate DNA accessibility to repair proteins. Monoubiquitinated at Lys-92 of histone H4 (H4K91ub1) in response to DNA damage. The exact role of H4K91ub1 in DNA damage response is still unclear but it may function as a licensing signal for additional histone H4 post-translational modifications such as H4 Lys-21 methylation (H4K20me).
messages: Ufmylated; monofmylated by UFL1 at Lys-32 (H4K31Ufm1) in response to DNA damage.

9606:LRRK2
gene id: 9606:LRRK2
uniprot id: Q5S007
names: Activity Regulation
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Autophosphorylated (PubMed:28202711, PubMed:28720718, PubMed:29127255, PubMed:29212815, PubMed:30635421). Phosphorylation of Ser-910 and either Ser-935 or Ser-1444 facilitates interaction with YWHAG (PubMed:28202711). Phosphorylation of Ser-910 and/or Ser-935 facilitates interaction with SFN (PubMed:28202711).
messages: Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.
messages: Cytoplasmic vesicle
messages: Endoplasmic reticulum membrane
messages: Endosome
messages: Expressed in pyramidal neurons in all cortical laminae of the visual cortex, in neurons of the substantia nigra pars compacta and caudate putamen (at protein level). Expressed in neutrophils (at protein level) (PubMed:29127255). Expressed in the brain. Expressed throughout the adult brain, but at a lower level than in heart and liver. Also expressed in placenta, lung, skeletal muscle, kidney and pancreas. In the brain, expressed in the cerebellum, cerebral cortex, medulla, spinal cord occipital pole, frontal lobe, temporal lobe and putamen. Expression is particularly high in brain dopaminoceptive areas.
messages: Golgi apparatus membrane
messages: Homodimer (PubMed:22952686, PubMed:18230735, PubMed:30635421). Interacts with PRKN, PRDX3, and TPCN2 (PubMed:16352719, PubMed:21850687, PubMed:22012985). Interacts with VPS35 and RAB29 (PubMed:23395371). Interacts (via ROC domain) with SEC16A (PubMed:25201882). Interacts with APP; interaction promotes phosphorylation of 'Thr-743' of APP (PubMed:28720718). Interacts with MAPT (PubMed:26014385). Interacts with RAB8A, RAB10, and RAB12 (PubMed:26824392). Interacts with YWHAG; this interaction is dependent on phosphorylation of Ser-910 and either Ser-935 or Ser-1444 (PubMed:28202711). Interacts with SFN; this interaction is dependent on phosphorylation of Ser-910 and/or Ser-935 (PubMed:28202711).
messages: Kinase activity is regulated by the GTPase activity of the ROC domain (PubMed:29212815, PubMed:18230735). GTP-bound LLRK2 kinase activity is stimulated by RAB29 (PubMed:29212815). Inhibited by small molecule inhibitor MLi-2 (PubMed:26824392, PubMed:29127255).
messages: Lysosome
messages: Mitochondrion outer membrane
messages: Perikaryon
messages: Serine/threonine-protein kinase which phosphorylates a broad range of proteins involved in multiple processes such as neuronal plasticity, innate immunity, autophagy, and vesicle trafficking (PubMed:20949042, PubMed:22012985, PubMed:26824392, PubMed:27830463, PubMed:29125462, PubMed:28720718, PubMed:29127255, PubMed:30398148, PubMed:29212815, PubMed:30635421, PubMed:21850687, PubMed:23395371, PubMed:17114044, PubMed:24687852, PubMed:26014385, PubMed:25201882). Is a key regulator of RAB GTPases by regulating the GTP/GDP exchange and interaction partners of RABs through phosphorylation (PubMed:26824392, PubMed:28720718, PubMed:29127255, PubMed:30398148, PubMed:29212815, PubMed:29125462, PubMed:30635421). Phosphorylates RAB3A, RAB3B, RAB3C, RAB3D, RAB5A, RAB5B, RAB5C, RAB8A, RAB8B, RAB10, RAB12, RAB35, and RAB43 (PubMed:26824392, PubMed:28720718, PubMed:29127255, PubMed:30398148, PubMed:29212815, PubMed:29125462, PubMed:30635421, PubMed:23395371). Regulates the RAB3IP-catalyzed GDP/GTP exchange for RAB8A through the phosphorylation of 'Thr-72' on RAB8A (PubMed:26824392). Inhibits the interaction between RAB8A and GDI1 and/or GDI2 by phosphorylating 'Thr-72' on RAB8A (PubMed:26824392). Regulates primary ciliogenesis through phosphorylation of RAB8A and RAB10, which promotes SHH signaling in the brain (PubMed:29125462, PubMed:30398148). Together with RAB29, plays a role in the retrograde trafficking pathway for recycling proteins, such as mannose-6-phosphate receptor (M6PR), between lysosomes and the Golgi apparatus in a retromer-dependent manner (PubMed:23395371). Regulates neuronal process morphology in the intact central nervous system (CNS) (PubMed:17114044). Plays a role in synaptic vesicle trafficking (PubMed:24687852). Plays an important role in recruiting SEC16A to endoplasmic reticulum exit sites (ERES) and in regulating ER to Golgi vesicle-mediated transport and ERES organization (PubMed:25201882). Positively regulates autophagy through a calcium-dependent acti…
messages: The Roc domain mediates homodimerization and regulates kinase activity.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The seven-bladed WD repeat region is critical for synaptic vesicle trafficking and mediates interaction with multiple vesicle-associated presynaptic proteins (PubMed:24687852). It also mediates homodimerization and regulates kinase activity (PubMed:30635421).
messages: Ubiquitinated by TRIM1; undergoes 'Lys-48'-linked polyubiquitination leading to proteasomal degradation.
messages: axon
messages: cytoskeleton
messages: dendrite
messages: synaptic vesicle membrane

9606:RIT1
gene id: 9606:RIT1
uniprot id: Q92963
names: Activity Regulation
names: Disease Annotation
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Alternates between an inactive form bound to GDP and an active form bound to GTP.
messages: Belongs to the small GTPase superfamily. Ras family.
messages: Cell membrane
messages: Expressed in many tissues.
messages: Interacts with AFDN, the C-terminal domain of RALGDS and RLF, but not with RIN1 and PIK3CA. RLF binds exclusively to the active GTP-bound form. Strongly interacts with BRAF, but only weakly with RAF1. BARF and RAF1 association is dependent upon the GTP-bound state. Interacts with RGL3 (By similarity).
messages: Plays a crucial role in coupling NGF stimulation to the activation of both EPHB2 and MAPK14 signaling pathways and in NGF-dependent neuronal differentiation. Involved in ELK1 transactivation through the Ras-MAPK signaling cascade that mediates a wide variety of cellular functions, including cell proliferation, survival, and differentiation.
messages: Shows rapid uncatalyzed guanine nucleotide dissociation rates, which are much faster than those of most Ras subfamily members.
messages: Stimulation of the NGF and EGF receptor signaling pathways results in rapid and prolonged activation.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:TPP1
gene id: 9606:TPP1
uniprot id: O14773
names: Activity Regulation
names: Cofactor
names: Disease Annotation
names: Function
names: PTM
names: Sequence Caution
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Activated by autocatalytic proteolytical processing upon acidification (PubMed:11054422, PubMed:19038966, PubMed:19038967). N-glycosylation is required for processing and activity (PubMed:19038966, PubMed:19038967).
messages: Binds 1 Ca(2+) ion per subunit.
messages: Detected in all tissues examined with highest levels in heart and placenta and relatively similar levels in other tissues.
messages: Incorrectly indicated as originating from bovine.
messages: Inhibited by diisopropyl fluorophosphate (DFP).
messages: Lysosomal serine protease with tripeptidyl-peptidase I activity (PubMed:11054422, PubMed:19038966, PubMed:19038967). May act as a non-specific lysosomal peptidase which generates tripeptides from the breakdown products produced by lysosomal proteinases (PubMed:11054422, PubMed:19038966, PubMed:19038967). Requires substrates with an unsubstituted N-terminus (PubMed:19038966).
messages: Lysosome
messages: Melanosome
messages: Monomer (PubMed:19038967). Interacts with CLN5 (PubMed:19941651). Interacts with CLN3 (PubMed:17237713).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:WFIKKN1
gene id: 9606:WFIKKN1
uniprot id: Q96NZ8
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the WFIKKN family.
messages: Expressed in pancreas, kidney, liver, placenta, and lung.
messages: Protease-inhibitor that contains multiple distinct protease inhibitor domains. Probably has serine protease- and metalloprotease-inhibitor activity (By similarity).
messages: Secreted
messages: The second BPTI/Kunitz inhibitor domain is able to inhibit trypsin. It has however no activity toward chymotrypsin, elastase, plasmin, pancreatic kallikrein, lung tryptase, plasma kallikrein, thrombin, urokinase or tissue plasminogen activator.

9606:KMT5C
gene id: 9606:KMT5C
uniprot id: Q86Y97
names: Activity Regulation
names: Function
names: Miscellaneous
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. Suvar4-20 subfamily.
messages: Chromosome
messages: Histone methyltransferase that specifically methylates monomethylated 'Lys-20' (H4K20me1) and dimethylated 'Lys-20' (H4K20me2) of histone H4 to produce respectively dimethylated 'Lys-20' (H4K20me2) and trimethylated 'Lys-20' (H4K20me3) and thus regulates transcription and maintenance of genome integrity (PubMed:24396869, PubMed:28114273). In vitro also methylates unmodified 'Lys-20' (H4K20me0) of histone H4 and nucleosomes (PubMed:24396869). H4 'Lys-20' trimethylation represents a specific tag for epigenetic transcriptional repression. Mainly functions in pericentric heterochromatin regions, thereby playing a central role in the establishment of constitutive heterochromatin in these regions. KMT5C is targeted to histone H3 via its interaction with RB1 family proteins (RB1, RBL1 and RBL2) (By similarity). Facilitates TP53BP1 foci formation upon DNA damage and proficient non-homologous end-joining (NHEJ)-directed DNA repair by catalyzing the di- and trimethylation of 'Lys-20' of histone H4 (PubMed:28114273). May play a role in class switch reconbination by catalyzing the di- and trimethylation of 'Lys-20' of histone H4 (By similarity).
messages: Homodimer (By similarity). Interacts with HP1 proteins CBX1, CBX3 and CBX5. Interacts with RB1 family proteins RB1, RBL1 and RBL2 (By similarity).
messages: Inhibited by 6,7-Dichloro-N-cyclopentyl-4-(pyridin-4-yl)phthalazin-1-amine (A-196) with an IC(50) of 144 nM.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Nucleus
messages: Probable cloning artifact.

9606:H4C14
gene id: 9606:H4C14
uniprot id: B2R4R0
uniprot id: P62805
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Acetylation at Lys-6 (H4K5ac), Lys-9 (H4K8ac), Lys-13 (H4K12ac) and Lys-17 (H4K16ac) occurs in coding regions of the genome but not in heterochromatin.
messages: Belongs to the histone H4 family.
messages: Butyrylation of histones marks active promoters and competes with histone acetylation.
messages: Chromosomal aberrations involving HISTONE H4 is a cause of B-cell non-Hodgkin lymphomas (B-cell NHL). Translocation t(3;6)(q27;p21), with BCL6.
messages: Chromosome
messages: Citrullination at Arg-4 (H4R3ci) by PADI4 impairs methylation.
messages: Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
messages: Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.
messages: Glutarylation at Lys-92 (H4K91glu) destabilizes nucleosomes by promoting dissociation of the H2A-H2B dimers from nucleosomes.
messages: Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.
messages: Monomethylated, dimethylated or trimethylated at Lys-21 (H4K20me1, H4K20me2, H4K20me3) (PubMed:12086618, PubMed:15964846, PubMed:17967882). Monomethylation is performed by KMT5A/SET8 (PubMed:15964846). Dimethylation and trimethylation is performed by KMT5B and KMT5C and induces gene silencing (By similarity). Monomethylated at Lys-13 (H4K12me1) by N6AMT1; H4K12me1 modification is present at the promoters of numerous genes encoding cell cycle regulators (PubMed:31061526).
messages: Monomethylation and asymmetric dimethylation at Arg-4 (H4R3me1 and H4R3me2a, respectively) by PRMT1 favors acetylation at Lys-9 (H4K8ac) and Lys-13 (H4K12ac). Demethylation is performed by JMJD6. Symmetric dimethylation on Arg-4 (H4R3me2s) by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage.
messages: Nucleus
messages: Phosphorylated by PAK2 at Ser-48 (H4S47ph). This phosphorylation increases the association of H3.3-H4 with the histone chaperone HIRA, thus promoting nucleosome assembly of H3.3-H4 and inhibiting nucleosome assembly of H3.1-H4.
messages: Sumoylated, which is associated with transcriptional repression.
messages: The disease is caused by variants affecting the gene represented in this entry. TEBIVANED1 is caused by variants in H4C3.
messages: The disease is caused by variants affecting the gene represented in this entry. TEBIVANED2 is caused by variants in H4C11.
messages: The disease is caused by variants affecting the gene represented in this entry. TEBIVANED3 is caused by variants in H4C5.
messages: The disease is caused by variants affecting the gene represented in this entry. TEBIVANED4 is caused by variants in H4C9.
messages: The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA (By similarity). Found in a co-chaperone complex with DNJC9, MCM2 and histone H3.3-H4 dimers (PubMed:33857403). Within the complex, interacts with DNJC9 (via C-terminus); the interaction is direct (PubMed:33857403).
messages: The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.
messages: Ubiquitinated by the CUL4-DDB-RBX1 complex in response to ultraviolet irradiation. This may weaken the interaction between histones and DNA and facilitate DNA accessibility to repair proteins. Monoubiquitinated at Lys-92 of histone H4 (H4K91ub1) in response to DNA damage. The exact role of H4K91ub1 in DNA damage response is still unclear but it may function as a licensing signal for additional histone H4 post-translational modifications such as H4 Lys-21 methylation (H4K20me).
messages: Ufmylated; monofmylated by UFL1 at Lys-32 (H4K31Ufm1) in response to DNA damage.

9606:KIAA1586
gene id: 9606:KIAA1586
uniprot id: Q9HCI6
names: Domain
names: Function
names: Subunit
messages: Binds UBE2I/UBC9 and two SUMO2 molecules via its N-terminus. The most N-terminal region interacts with the SUMO2 chain that is covalently bound to the UBE2I/UBC9 active site, while the second region interacts with another SUMO2 that is non-covalently associated with the same UBE2I/UBC9 chain.
messages: E3 SUMO-protein ligase; facilitates UBE2I/UBC9-mediated SUMO2 modification of target proteins (PubMed:26524493).
messages: Interacts with UBE2I/UBC9 and SUMO2.

9606:C19orf25
gene id: 9606:C19orf25
uniprot id: Q9UFG5
names: Similarity
messages: Belongs to the UPF0449 family.

9606:LSM2
gene id: 9606:LSM2
uniprot id: Q9Y333
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the snRNP Sm proteins family.
messages: Component of the precatalytic spliceosome (spliceosome B complex) (PubMed:11991638, PubMed:28781166). Component of the U4/U6-U5 tri-snRNP complex, a building block of the precatalytic spliceosome (spliceosome B complex) (PubMed:10523320, PubMed:28781166, PubMed:26912367). The U4/U6-U5 tri-snRNP complex is composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39, plus LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8 (PubMed:26912367). LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8 form a heptameric, ring-shaped subcomplex (the LSM2-8 complex) that is part of the U4/U6-U5 tri-snRNP complex and the precatalytic spliceosome (PubMed:10523320, PubMed:26912367, PubMed:28781166).
messages: Nucleus
messages: Plays a role in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex that is involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex) (PubMed:28781166). The heptameric LSM2-8 complex binds specifically to the 3'-terminal U-tract of U6 snRNA (PubMed:10523320).

9606:MYO1F
gene id: 9606:MYO1F
uniprot id: O00160
uniprot id: Q4LE34
names: Caution
names: Disease Annotation
names: Function
names: Similarity
messages: Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.
messages: Defects in MYO1F has been found in a patient with a form of non-syndromic sensorineural hearing loss.
messages: Myosins are actin-based motor molecules with ATPase activity. Unconventional myosins serve in intracellular movements. Their highly divergent tails are presumed to bind to membranous compartments, which would be moved relative to actin filaments (By similarity).
messages: Represents an unconventional myosin. This protein should not be confused with the conventional myosin-1 (MYH1).

9606:FXYD5
gene id: 9606:FXYD5
uniprot id: F5H4X8
uniprot id: Q96DB9
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the FXYD family.
messages: Glycosylated.
messages: Involved in down-regulation of E-cadherin which results in reduced cell adhesion. Promotes metastasis.
messages: Membrane

9606:ZPBP2
gene id: 9606:ZPBP2
uniprot id: Q6X784
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the zona pellucida-binding protein Sp38 family.
messages: Expressed specifically in testis.
messages: Is implicated in sperm-oocyte interaction during fertilization.
messages: N-glycosylated.
messages: Secreted
messages: acrosome

9606:ALPI
gene id: 9606:ALPI
uniprot id: P09923
names: Cofactor
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Alkaline phosphatase that can hydrolyze various phosphate compounds.
messages: Belongs to the alkaline phosphatase family.
messages: Binds 1 Mg(2+) ion.
messages: Binds 2 Zn(2+) ions.
messages: Cell membrane
messages: Homodimer.
messages: In most mammals there are four different isozymes: placental (ALPP), germ cell (ALPG), intestinal (ALPI) and tissue non-specific (liver/bone/kidney) (ALPL/TNAP).

9606:TNFRSF10C
gene id: 9606:TNFRSF10C
uniprot id: O14798
names: Function
names: PTM
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Cell membrane
messages: Higher expression in normal tissues than in tumor cell lines. Highly expressed in peripheral blood lymphocytes, spleen, skeletal muscle, placenta, lung and heart.
messages: N-glycosylated and O-glycosylated.
messages: Receptor for the cytotoxic ligand TRAIL. Lacks a cytoplasmic death domain and hence is not capable of inducing apoptosis. May protect cells against TRAIL mediated apoptosis by competing with TRAIL-R1 and R2 for binding to the ligand.

9606:ANKRD23
gene id: 9606:ANKRD23
uniprot id: Q86SG2
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Interacts with titin/TTN and MYPN.
messages: Mainly expressed in heart, skeletal muscle and brown adipose tissues.
messages: May be involved in the energy metabolism. Could be a molecular link between myofibrillar stretch-induced signaling pathways and muscle gene expression.
messages: Nucleus

9606:PAFAH2
gene id: 9606:PAFAH2
uniprot id: Q99487
names: Activity Regulation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the serine esterase family.
messages: Broadly expressed in different tissues, but high in B- and T-lymphocytes. In brain, expression is restricted to amygdala and frontal cortex.
messages: Catalyzes the hydrolyze of the acetyl group at the sn-2 position of platelet-activating factor (PAF) and its analogs, leading to their inactivation (PubMed:9494101). Hydrolyzes propionyl and butyroyl moieties approximately half as effectively as PAF (By similarity). Also catalyzes transacetylation of the acetyl group from platelet-activating factor (PAF) to lysoplasmalogen and to sphingosine, producing plasmalogen analogs of PAF and N-acetylsphingosine (C2-ceramide) respectively. Has a marked selectivity for phospholipids with short acyl chains at the sn-2 position (By similarity).
messages: Cytoplasm
messages: Endoplasmic reticulum membrane
messages: Inhibited by phenylmethanesulfonyl fluoride, 3,4,dichloroisocoumarin, diisopropyl fluorophosphate (DFP) and diethyl p-nitrophenyl phosphate (DENP).
messages: Membrane
messages: Monomer.

9606:NAP1L2
gene id: 9606:NAP1L2
uniprot id: Q9ULW6
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Acidic protein which may be involved in interactions with other proteins or DNA.
messages: Belongs to the nucleosome assembly protein (NAP) family.
messages: Nucleus

9606:HIKESHI
gene id: 9606:HIKESHI
uniprot id: Q53FT3
names: Disease Annotation
names: Function
names: Induction
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: 'Hikeshi' is a traditional Japanese compound word used for a firefighter, smokejumper, or troubleshooter.
messages: Acts as a specific nuclear import carrier for HSP70 proteins following heat-shock stress: acts by mediating the nucleoporin-dependent translocation of ATP-bound HSP70 proteins into the nucleus. HSP70 proteins import is required to protect cells from heat shock damages. Does not translocate ADP-bound HSP70 proteins into the nucleus.
messages: Belongs to the OPI10 family.
messages: Cytoplasm
messages: Following heat-shock treatment.
messages: Forms an asymmetric homodimer; required for binding and nuclear import of HSP70 proteins (PubMed:25760597). Interacts with ATP-bound HSP70 proteins (PubMed:22541429). Interacts with NUP62 and NUP153 (via F-X-F-G repeats) (PubMed:22541429). Interacts with HSPA8 (PubMed:25760597).
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: cytosol

9606:EOGT
gene id: 9606:EOGT
uniprot id: Q5NDL2
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the glycosyltransferase 61 family.
messages: Catalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine or threonine residue in extracellular proteins resulting in their modification with a beta-linked N-acetylglucosamine (O-GlcNAc). Specifically glycosylates the Thr residue located between the fifth and sixth conserved cysteines of folded EGF-like domains.
messages: Endoplasmic reticulum lumen
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:ZNF597
gene id: 9606:ZNF597
uniprot id: Q96LX8
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: Imprinted. Promoter methylation of the paternal allele may restrict expression to the maternal allele in leukocytes.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:TMEM116
gene id: 9606:TMEM116
uniprot id: Q8NCL8
names: Subcellular Location Annotation
messages: Membrane

9606:GPBP1
gene id: 9606:GPBP1
uniprot id: D4PHA4
uniprot id: Q86WP2
names: Function
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the vasculin family.
messages: Contaminating sequence. Sequence of unknown origin in the N-terminal part.
messages: Cytoplasm
messages: Functions as a GC-rich promoter-specific transactivating transcription factor.
messages: Interacts with GTF2B, GTF2F2, RNA polymerase II and TBP.
messages: Nucleus
messages: Widely expressed. Some isoforms may be specifically expressed in veins and arteries (at protein level). Isoform 4 is widely expressed. Isoform 1, isoform 2 and isoform 3 may be specifically expressed in vascular smooth muscle cells.

9606:OR13J1
gene id: 9606:OR13J1
uniprot id: Q8NGT2
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Odorant receptor.

9606:SNURF
gene id: 9606:SNURF
uniprot id: P63162
uniprot id: Q9Y675
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the SNURF family.
messages: Belongs to the snRNP SmB/SmN family.
messages: Encoded on a bicistronic transcript that code for two proteins, SNRPN and SNURF.
messages: Encoded on a bicistronic transcript that code for two proteins, SNRPN and SNURF. In addition to the primary 1.6-kb bicistronic SNURF-SNRPN transcript, SNURF-only transcript is also detected.
messages: Expressed in brain and lymphoblasts.
messages: Expressed in heart, skeletal muscle and lymphoblasts (at protein level). Expressed in brain, pancreas, heart, liver, lung, kidney and skeletal muscle.
messages: Interacts with TDRD3.
messages: May be involved in tissue-specific alternative RNA processing events.
messages: Nucleus
messages: Patients with the autoimmune disease systemic lupus erythematosus (SLE) have autoantibodies directed against some of the individual snRNP polypeptides. The most common autoantigen is called Sm. N bears Sm epitopes.

9606:IRF8
gene id: 9606:IRF8
uniprot id: Q02556
names: Disease Annotation
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the IRF family.
messages: By IFNG/IFN-gamma. Negatively regulated by microRNA-155 (miR155).
messages: Cytoplasm
messages: Interacts (via C-terminus) with TRIM21 (via C-terminus). Interacts with the BATF-JUNB heterodimer. Interacts with BATF (via bZIP domain); the interaction is direct (By similarity). Interacts with COPS2. Interacts with SPI1 (PubMed:33951726).
messages: Nucleus
messages: Predominantly expressed in lymphoid tissues.
messages: Sumoylated with SUMO3. Desumoylated by SENP1.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Transcription factor that specifically binds to the upstream regulatory region of type I interferon (IFN) and IFN-inducible MHC class I genes (the interferon consensus sequence (ICS)) (PubMed:25122610). Can both act as a transcriptional activator or repressor (By similarity). Plays a negative regulatory role in cells of the immune system (By similarity). Involved in CD8(+) dendritic cell differentiation by forming a complex with the BATF-JUNB heterodimer in immune cells, leading to recognition of AICE sequence (5'-TGAnTCA/GAAA-3'), an immune-specific regulatory element, followed by cooperative binding of BATF and IRF8 and activation of genes (By similarity). Required for the development of plasmacytoid dendritic cells (pDCs), which produce most of the type I IFN in response to viral infection (By similarity). Positively regulates macroautophagy in dendritic cells (PubMed:29434592). Acts as a transcriptional repressor of osteoclast differentiation factors such as NFATC1 and EEIG1 (By similarity).
messages: Ubiquitinated (PubMed:25122610). Ubiquitination by TRIM21 in macrophages, a process that is strongly increased upon interferon gamma stimulation, leds to the enhanced transcriptional activity of target cytokine genes (By similarity). Ubiquitination leads to its degradation by the proteasome (PubMed:25122610).

9606:ASGR2
gene id: 9606:ASGR2
uniprot id: P07307
names: Function
names: Miscellaneous
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts with hepatitis E virus capsid protein ORF2.
messages: Calcium is required for ligand binding.
messages: Expressed exclusively in hepatic parenchymal cells.
messages: Mediates the endocytosis of plasma glycoproteins to which the terminal sialic acid residue on their complex carbohydrate moieties has been removed. The receptor recognizes terminal galactose and N-acetylgalactosamine units. After ligand binding to the receptor, the resulting complex is internalized and transported to a sorting organelle, where receptor and ligand are disassociated. The receptor then returns to the cell membrane surface.
messages: Membrane
messages: The functioning ligand-binding unit of this receptor is thought to be at least a dimer. Interacts with LASS2.

9606:NMUR2
gene id: 9606:NMUR2
uniprot id: Q9GZQ4
names: Caution
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: It is uncertain whether Met-1 or Met-4 is the initiator.
messages: Predominantly expressed in the CNS, particularly in the medulla oblongata, pontine reticular formation, spinal cord, and thalamus. High level in testis whereas lower levels are present in a variety of peripheral tissues including the gastrointestinal tract, genitourinary tract, liver, pancreas, adrenal gland, thyroid gland, lung, trachea, spleen and thymus.
messages: Receptor for the neuromedin-U and neuromedin-S neuropeptides.

9606:ANAPC15
gene id: 9606:ANAPC15
uniprot id: G5EA39
uniprot id: P60006
names: Function
names: Similarity
names: Subunit
messages: Belongs to the APC15 family.
messages: Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. In the complex, plays a role in the release of the mitotic checkpoint complex (MCC) from the APC/C: not required for APC/C activity itself, but promotes the turnover of CDC20 and MCC on the APC/C, thereby participating in the responsiveness of the spindle assembly checkpoint. Also required for degradation of CDC20.
messages: The mammalian APC/C is composed at least of 14 distinct subunits ANAPC1, ANAPC2, CDC27/APC3, ANAPC4, ANAPC5, CDC16/APC6, ANAPC7, CDC23/APC8, ANAPC10, ANAPC11, CDC26/APC12, ANAPC13, ANAPC15 and ANAPC16 that assemble into a complex of at least 19 chains with a combined molecular mass of around 1.2 MDa; APC/C interacts with FZR1 and FBXO5.

9606:WWP2
gene id: 9606:WWP2
uniprot id: O00308
names: Activity Regulation
names: Developmental Stage
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts with adenovirus type 2 PIII.
messages: A cysteine residue is required for ubiquitin-thioester formation.
messages: Activated by NDFIP1- and NDFIP2-binding.
messages: Autoubiquitinated. Ubiquitinated by the SCF(FBXL15) complex, leading to its degradation by the proteasome.
messages: Detected in heart, throughout the brain, placenta, lung, liver, muscle, kidney and pancreas. Also detected in spleen and peripheral blood leukocytes.
messages: E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Polyubiquitinates POU5F1 by 'Lys-63'-linked conjugation and promotes it to proteasomal degradation; in embryonic stem cells (ESCs) the ubiquitination is proposed to regulate POU5F1 protein level. Ubiquitinates EGR2 and promotes it to proteasomal degradation; in T-cells the ubiquitination inhibits activation-induced cell death. Ubiquitinates SLC11A2; the ubiquitination is enhanced by presence of NDFIP1 and NDFIP2. Ubiquitinates RPB1 and promotes it to proteasomal degradation.
messages: Highly expressed in undifferentiated embryonic stem cells and expression is reduced after embryoid body (EB) formation. Not detectable at day 13 of EB formation; low levels are again detected at day 18 of EB formation.
messages: Interacts with POU5F1, RBP1, EGR2 and SLC11A2 (By similarity). Interacts with SCNN1A, SCNN1B, SCNN1G, WBP1, WBP2 and ATN1. Interacts with ERBB4, NDFIP1 and NDFIP2. Interacts with ARRDC4 (PubMed:23236378). Interacts (via WW domains) with ARRDC1 (via PPxY motifs); ubiquitinates ARRDC1 (PubMed:22315426, PubMed:21191027). Interacts (via WW domains) with ARRDC2 and ARRDC3 (PubMed:21191027).
messages: Nucleus
messages: The C2 domain is involved in autoinhibition of the catalytic activity by interacting with the HECT domain.
messages: The WW domains mediate interaction with PPxY motif-containing proteins.

9606:SLC22A16
gene id: 9606:SLC22A16
uniprot id: Q86VW1
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family.
messages: Cell membrane
messages: Expressed in testis and epididymis (at protein level) (PubMed:12384147, PubMed:12089149, PubMed:15963465). Expressed in endometrium (at protein level); highly expressed during the normal secretory phase, but expression is significantly reduced in the proliferative phase (PubMed:17197897). Expressed at lower levels in adult tissues including bone marrow (at protein level) (PubMed:12372408, PubMed:12384147, PubMed:15963465). Expressed in hematopoietic cells, including CD34(+) leukocytes (PubMed:12384147). Expressed in fetal liver (at protein level), brain, lung, kidney, heart, skeletal muscle, spleen and thymus (PubMed:12372408, PubMed:12384147, PubMed:15963465). Expressed in leukemia cells (PubMed:12384147). Abundantly expressed in ovarian cancer clear-cell adenocarcinoma (PubMed:17581421).
messages: Facilitative organic cation transporter that mediates the transport of carnitine as well as the polyamine spermidine (PubMed:12089149, PubMed:20037140). Mediates the partially Na(+)-dependent bidirectional transport of carnitine (PubMed:12089149). May mediate L-carnitine secretion from testis epididymal epithelium into the lumen which is involved in the maturation of spermatozoa (PubMed:12089149).
messages: Involved in the uptake of clinically used drugs such as anticancer agents doxorubicin and bleomycin.

9606:ERP44
gene id: 9606:ERP44
uniprot id: Q9BS26
names: Function
names: Induction
names: Subcellular Location Annotation
names: Subunit
messages: Endoplasmic reticulum lumen
messages: Forms mixed disulfides with both ERO1A and ERO1B and cargo folding intermediates; the interactions with ERO1A and ERO1B result in their retention in the endoplasmic reticulum (PubMed:11847130, PubMed:29858230). Directly interacts with ITPR1 in a pH-, redox state- and calcium-dependent manner, but not with ITPR2 or ITPR3 (PubMed:15652484). The strength of this interaction inversely correlates with calcium concentration (By similarity).
messages: Mediates thiol-dependent retention in the early secretory pathway, forming mixed disulfides with substrate proteins through its conserved CRFS motif (PubMed:11847130, PubMed:14517240). Inhibits the calcium channel activity of ITPR1 (PubMed:15652484). May have a role in the control of oxidative protein folding in the endoplasmic reticulum (PubMed:11847130, PubMed:29858230, PubMed:14517240). Required to retain ERO1A and ERO1B in the endoplasmic reticulum (PubMed:11847130, PubMed:29858230).
messages: Up-regulated by inducers of the unfolded protein response (UPR), including tunicamycin and dithiothreitol.

9606:FKBP8
gene id: 9606:FKBP8
uniprot id: Q14318
names: Caution
names: Function
names: Miscellaneous
names: PTM
names: Sequence Caution
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts with hepatitis C/HCV protein NS5A.
messages: Binds the immunosuppressant FK506 only in its calmodulin/calcium activated form.
messages: Constitutively inactive PPiase, which becomes active when bound to calmodulin and calcium. Seems to act as a chaperone for BCL2, targets it to the mitochondria and modulates its phosphorylation state. The BCL2/FKBP8/calmodulin/calcium complex probably interferes with the binding of BCL2 to its targets. The active form of FKBP8 may therefore play a role in the regulation of apoptosis. Involved in the inhibition of viral infection by influenza A viruses (IAV) (PubMed:28169297).
messages: Homomultimers or heteromultimers (Potential). Forms heterodimer with calmodulin. When activated by calmodulin and calcium, interacts with the BH4 domain of BCL2 and weakly with BCL2L1/BCLX isoform Bcl-X(L). Does not bind and inhibit calcineurin. Interacts with ZFYVE27; may negatively regulate ZFYVE27 phosphorylation.
messages: Interacts with BCL2L1/BCLX.
messages: It is uncertain whether Met-1 or Met-58 is the initiator.
messages: Mitochondrion
messages: Mitochondrion membrane
messages: The first part of the cDNA maps to the same locus, but in opposite orientation.
messages: Ubiquitinated by PRKN during mitophagy, leading to its degradation and enhancement of mitophagy. Deubiquitinated by USP30.
messages: Widely expressed. Highest levels seen in the brain. Highly abundant in the retina.

9606:MATK
gene id: 9606:MATK
uniprot id: F1T0G6
uniprot id: P42679
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the protein kinase superfamily. Tyr protein kinase family.
messages: Belongs to the protein kinase superfamily. Tyr protein kinase family. CSK subfamily.
messages: Could play a significant role in the signal transduction of hematopoietic cells. May regulate tyrosine kinase activity of SRC-family members in brain by specifically phosphorylating their C-terminal regulatory tyrosine residue which acts as a negative regulatory site. It may play an inhibitory role in the control of T-cell proliferation.
messages: Cytoplasm
messages: Expressed in various myeloid cell lines, detected in brain and lung.
messages: Interacts with KIT.
messages: Membrane

9606:CT47A1
gene id: 9606:CT47A1
uniprot id: Q5JQC4
names: Tissue Specificity
messages: Strongly expressed in testis, low expression in placenta, and very low expression in brain.

9606:RNF125
gene id: 9606:RNF125
uniprot id: Q96EQ8
names: Disease Annotation
names: Domain
names: Function
names: Induction
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Autoubiquitinated, leading to its subsequent proteasomal degradation.
messages: Down-regulated by miR-15b (PubMed:26202983). Down-regulated in BRAFi resistant melanomas, leading to increased levels of JAK1 and possibly promoting BRAFi resistance.
messages: E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins, such as RIGI, MAVS/IPS1, IFIH1/MDA5, JAK1 and p53/TP53 (PubMed:15843525, PubMed:17460044, PubMed:17643463, PubMed:26027934, PubMed:26471729, PubMed:25591766, PubMed:27411375). Acts as a negative regulator of type I interferon production by mediating ubiquitination of RIGI at 'Lys-181', leading to RIGI degradation (PubMed:17460044, PubMed:26471729). Mediates ubiquitination and subsequent degradation of p53/TP53 (PubMed:25591766). Mediates ubiquitination and subsequent degradation of JAK1 (PubMed:26027934). Acts as a positive regulator of T-cell activation (PubMed:15843525).
messages: Golgi apparatus membrane
messages: Interacts with UBE2D1 (PubMed:27411375). Interacts with VCP/p97; leading to recruit RNF125 to RIGI and promote ubiquitination of RIGI (PubMed:26471729).
messages: Predominantly expressed in lymphoid tissues, including bone marrow, spleen and thymus. Also weakly expressed in other tissues. Predominant in the CD4(+) and CD8(+) T-cells, suggesting that it is preferentially confined to T-cells.
messages: The C2HC RNF-type zinc finger and the linker region stabilize the RING-type zinc finger, leading to promote binding of the RING-type zinc finger to the ubiquitin-conjugating enzyme E2 (donor ubiquitin) (PubMed:27411375).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:BIRC7
gene id: 9606:BIRC7
uniprot id: Q96CA5
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Apoptotic regulator capable of exerting proapoptotic and anti-apoptotic activities and plays crucial roles in apoptosis, cell proliferation, and cell cycle control (PubMed:11162435, PubMed:11024045, PubMed:11084335, PubMed:16729033, PubMed:17294084). Its anti-apoptotic activity is mediated through the inhibition of CASP3, CASP7 and CASP9, as well as by its E3 ubiquitin-protein ligase activity (PubMed:11024045, PubMed:16729033). As it is a weak caspase inhibitor, its anti-apoptotic activity is thought to be due to its ability to ubiquitinate DIABLO/SMAC targeting it for degradation thereby promoting cell survival (PubMed:16729033). May contribute to caspase inhibition, by blocking the ability of DIABLO/SMAC to disrupt XIAP/BIRC4-caspase interactions (PubMed:16729033). Protects against apoptosis induced by TNF or by chemical agents such as adriamycin, etoposide or staurosporine (PubMed:11162435, PubMed:11084335, PubMed:11865055). Suppression of apoptosis is mediated by activation of MAPK8/JNK1, and possibly also of MAPK9/JNK2 (PubMed:11865055). This activation depends on TAB1 and MAP3K7/TAK1 (PubMed:11865055). In vitro, inhibits CASP3 and proteolytic activation of pro-CASP9 (PubMed:11024045).
messages: Autoubiquitinated and undergoes proteasome-mediated degradation.
messages: Belongs to the IAP family.
messages: Binds to CASP9. Interaction with DIABLO/SMAC via the BIR domain disrupts binding to CASP9 and apoptotic suppressor activity. Interacts with TAB1. In vitro, interacts with CASP3 and CASP7 via its BIR domain.
messages: Blocks etoposide-induced apoptosis (PubMed:11162435, PubMed:11322947). Protects against natural killer (NK) cell-mediated killing (PubMed:18034418).
messages: Blocks staurosporine-induced apoptosis (PubMed:11322947). Promotes natural killer (NK) cell-mediated killing (PubMed:18034418).
messages: Cytoplasm
messages: Golgi apparatus
messages: Isoform 1 and isoform 2 are expressed at very low levels or not detectable in most adult tissues. Detected in adult heart, placenta, lung, lymph node, spleen and ovary, and in several carcinoma cell lines. Isoform 2 is detected in fetal kidney, heart and spleen, and at lower levels in adult brain, skeletal muscle and peripheral blood leukocytes.
messages: Nucleus
messages: The RING domain is essential for autoubiquitination.
messages: The truncated protein (tLivin) not only loses its anti-apoptotic effect but also acquires a pro-apoptotic effect.

9606:TCAP
gene id: 9606:TCAP
uniprot id: O15273
names: Disease Annotation
names: Function
names: Miscellaneous
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Heart and skeletal muscle.
messages: Interacts with MYOZ1, MYOZ2 and MYOZ3. Interacts with CSRP3. Interacts directly with the N-terminal Ig-like domains of 2 titin (TTN) molecules. Interacts with ANKRD2; the interaction is direct.
messages: Muscle assembly regulating factor. Mediates the antiparallel assembly of titin (TTN) molecules at the sarcomeric Z-disk.
messages: The C-terminal domain appears to be unstructured in solution. It may promote the assembly of higher-order TTN complexes.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: sarcomere

9606:OR2AG1
gene id: 9606:OR2AG1
uniprot id: A0A126GVD0
uniprot id: Q9H205
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Membrane
messages: Odorant receptor.

9606:ARSL
gene id: 9606:ARSL
uniprot id: A0A5F9ZHX8
uniprot id: A0A804HJF6
uniprot id: A1L484
uniprot id: B7Z1M0
uniprot id: B7Z6V4
uniprot id: F5GYY5
uniprot id: F5H324
uniprot id: P51690
names: Activity Regulation
names: Cofactor
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the sulfatase family.
messages: Binds 1 Ca(2+) ion per subunit.
messages: Exhibits arylsulfatase activity towards the artificial substrate 4-methylumbelliferyl sulfate (PubMed:7720070, PubMed:9497243). May be essential for the correct composition of cartilage and bone matrix during development (PubMed:7720070). Has no activity toward steroid sulfates (PubMed:7720070).
messages: Expressed in the pancreas, liver and kidney.
messages: Golgi stack
messages: Inhibited by millimolar concentrations of warfarin.
messages: N-glycosylated.
messages: The conversion to 3-oxoalanine (also known as C-formylglycine, FGly), of a serine or cysteine residue in prokaryotes and of a cysteine residue in eukaryotes, is critical for catalytic activity.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:PSMA4
gene id: 9606:PSMA4
uniprot id: H0YLC2
uniprot id: H0YN18
uniprot id: P25789
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Interaction with HTLV-1 TAX protein favors NFKB1 activation.
messages: Belongs to the peptidase T1A family.
messages: Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex).
messages: Cytoplasm
messages: Down-regulated by antioxidants BO-653 and probucol.
messages: Nucleus
messages: The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits.
messages: The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7.

9606:HACD2
gene id: 9606:HACD2
uniprot id: Q6Y1H2
names: Caution
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the very long-chain fatty acids dehydratase HACD family.
messages: Catalyzes the third of the very long-chain fatty acids (VLCFA) elongation four-step cycle (condensation, reduction, dehydration, and reduction). This endoplasmic reticulum-elongation process is characterized by the addition of two carbons to the lipid chain through each cycle. This enzyme catalyzes the dehydration of the 3-hydroxyacyl-CoA intermediate into trans-2,3-enoyl-CoA, within each cycle of elongation. Therefore, it participates in the production of various VLCFAs involved in multiple biological processes as precursors of membrane lipids and lipid mediators.
messages: Endoplasmic reticulum membrane
messages: Highly expressed in testis, spleen, prostate, colon and heart, followed by moderate expression in thymus, ovary, small intestine, peripheral blood leukocytes, liver, skeletal muscle and pancreas. Weakly detected in kidney, placenta, brain and lung.
messages: May interact with enzymes of the ELO family (including ELOVL1); with those enzymes that mediate condensation, the first of the four steps of the reaction cycle responsible for fatty acids elongation, may be part of a larger fatty acids elongase complex (PubMed:18554506). Interacts with BCAP31 (PubMed:15024066).
messages: Shares some similarity with tyrosine phosphatase proteins but it has probably no phosphatase activity.
messages: Turns over rapidly through degradation by the proteasome system.

9606:C8orf44-SGK3
gene id: 9606:C8orf44-SGK3
uniprot id: Q96BR1
names: Activity Regulation
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Activated by phosphorylation on Ser-486 by an unknown kinase (may be mTORC2 but not confirmed), transforming it into a substrate for PDPK1 which then phosphorylates it on Thr-320.
messages: Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family.
messages: Cytoplasmic vesicle
messages: Early endosome
messages: Expressed in most tissues with highest levels in pancreas, kidney liver, heart and brain and lower levels in lung, placenta and skeletal muscle. Expression is higher in ER-positive breast tumors than ER-negative breast tumors.
messages: Induced by estrogen/ER in breast cancer cells.
messages: Interacts with GSK3B and FLII. Interacts with PDPK1 in a phosphorylation-dependent manner.
messages: Recycling endosome
messages: Serine/threonine-protein kinase which is involved in the regulation of a wide variety of ion channels, membrane transporters, cell growth, proliferation, survival and migration. Up-regulates Na(+) channels: SCNN1A/ENAC and SCN5A, K(+) channels: KCNA3/KV1.3, KCNE1, KCNQ1 and KCNH2/HERG, epithelial Ca(2+) channels: TRPV5 and TRPV6, chloride channel: BSND, creatine transporter: SLC6A8, Na(+)/dicarboxylate cotransporter: SLC13A2/NADC1, Na(+)-dependent phosphate cotransporter: SLC34A2/NAPI-2B, amino acid transporters: SLC1A5/ASCT2 and SLC6A19, glutamate transporters: SLC1A3/EAAT1, SLC1A6/EAAT4 and SLC1A7/EAAT5, glutamate receptors: GRIA1/GLUR1 and GRIK2/GLUR6, Na(+)/H(+) exchanger: SLC9A3/NHE3, and the Na(+)/K(+) ATPase. Plays a role in the regulation of renal tubular phosphate transport and bone density. Phosphorylates NEDD4L and GSK3B. Positively regulates ER transcription activity through phosphorylation of FLII. Negatively regulates the function of ITCH/AIP4 via its phosphorylation and thereby prevents CXCR4 from being efficiently sorted to lysosomes.
messages: Two specific sites, one in the kinase domain (Thr-320) and the other in the C-terminal regulatory region (Ser-486), need to be phosphorylated for its full activation.

9606:RPL13A
gene id: 9606:RPL13A
uniprot id: A0A384ME37
uniprot id: P40429
uniprot id: Q8J015
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Associated with ribosomes but is not required for canonical ribosome function and has extra-ribosomal functions (PubMed:14567916, PubMed:17218275, PubMed:23636399, PubMed:32669547). Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes (PubMed:23071094). Upon interferon-gamma activation and subsequent phosphorylation dissociates from the ribosome and assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation (PubMed:23071094). In the GAIT complex interacts with m7G cap-bound eIF4G at or near the eIF3-binding site and blocks the recruitment of the 43S ribosomal complex (PubMed:23071094). Involved in methylation of rRNA (PubMed:17921318).
messages: Belongs to the universal ribosomal protein uL13 family.
messages: Citrullinated by PADI4.
messages: Component of the 60S ribosome (PubMed:14567916, PubMed:12962325, PubMed:23636399, PubMed:32669547). Component of the GAIT complex (PubMed:15479637). Interacts with EIF4G1 (PubMed:17218275).
messages: Cytoplasm
messages: Phosphorylation at Ser-77 upon interferon-gamma treatment in monocytes involves a DAPK1-DAPK3 kinase cascade and is causing release from the ribosome, association with the GAIT complex and subsequent involvement in transcript-selective translation inhibition.

9606:SRXN1
gene id: 9606:SRXN1
uniprot id: Q9BYN0
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the sulfiredoxin family.
messages: Contributes to oxidative stress resistance by reducing cysteine-sulfinic acid formed under exposure to oxidants in the peroxiredoxins PRDX1, PRDX2, PRDX3 and PRDX4 (PubMed:15448164, PubMed:15590625). Does not act on PRDX5 or PRDX6 (PubMed:15448164, PubMed:15590625). May catalyze the reduction in a multi-step process by acting both as a specific phosphotransferase and a thioltransferase (PubMed:15448164, PubMed:15590625).
messages: Cytoplasm
messages: Widely expressed with highest levels in kidney, lung, spleen and thymus.

9606:UEVLD
gene id: 9606:UEVLD
uniprot id: B4DIA9
uniprot id: Q8IX04
names: Function
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Belongs to the LDH/MDH superfamily.
messages: Colon, colon carcinoma cell lines, normal cervical epithelium, carcinomas of the uterine cervix and peripheral blood leukocytes.
messages: Homodimer.
messages: In the C-terminal section; belongs to the LDH/MDH superfamily.
messages: In the N-terminal section; belongs to the ubiquitin-conjugating enzyme family. UEV subfamily.
messages: Possible negative regulator of polyubiquitination.

9606:SLC9C1
gene id: 9606:SLC9C1
uniprot id: Q4G0N8
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the monovalent cation:proton antiporter 1 (CPA1) transporter (TC 2.A.36) family.
messages: Interacts with soluble adenylyl cyclase (sAC).
messages: Sperm-specific sodium/hydrogen exchanger involved in intracellular pH regulation of spermatozoa. Required for sperm motility and fertility. Involved in sperm cell hyperactivation, a step needed for sperm motility which is essential late in the preparation of sperm for fertilization. Required for the expression and bicarbonate regulation of the soluble adenylyl cyclase (sAC) (By similarity).
messages: The ion transport-like region is related to the membrane segments of voltage-gated ion channels. Its function is unknown (By similarity).
messages: flagellum membrane

9606:CAMK1G
gene id: 9606:CAMK1G
uniprot id: Q96NX5
names: Activity Regulation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Activated by Ca(2+)/calmodulin. Binding of calmodulin is thought to result in a conformational change and leads to activation through phosphorylation by CAMKK1 (By similarity).
messages: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily.
messages: Calcium/calmodulin-dependent protein kinase belonging to a proposed calcium-triggered signaling cascade. In vitro phosphorylates transcription factor CREB1 (By similarity).
messages: Cell membrane
messages: Cytoplasm
messages: Golgi apparatus membrane
messages: Mainly expressed in brain with small amounts in skeletal muscles, kidney, spleen and liver. Strongly expressed in forebrain neocortex, striatum and limbic system.
messages: May be prenylated on Cys-473.
messages: The autoinhibitory domain overlaps with the calmodulin binding region and interacts in the inactive folded state with the catalytic domain as a pseudosubstrate.

9606:CDRT15L2
gene id: 9606:CDRT15L2
uniprot id: A8MXV6
names: Subcellular Location Annotation
messages: Membrane

9606:MGA
gene id: 9606:MGA
uniprot id: Q8IWI9
names: Domain
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Functions as a dual-specificity transcription factor, regulating the expression of both MAX-network and T-box family target genes. Functions as a repressor or an activator. Binds to 5'-AATTTCACACCTAGGTGTGAAATT-3' core sequence and seems to regulate MYC-MAX target genes. Suppresses transcriptional activation by MYC and inhibits MYC-dependent cell transformation. Function activated by heterodimerization with MAX. This heterodimerization serves the dual function of both generating an E-box-binding heterodimer and simultaneously blocking interaction of a corepressor (By similarity).
messages: Interacts with MAX. Requires dimerization with MAX for E-box binding (By similarity). Component of some MLL1/MLL complex, at least composed of the core components KMT2A/MLL1, ASH2L, HCFC1/HCF1, WDR5 and RBBP5, as well as the facultative components BAP18, CHD8, E2F6, HSP70, INO80C, KANSL1, LAS1L, MAX, MCRS1, MGA, MYST1/MOF, PELP1, PHF20, PRP31, RING2, RUVB1/TIP49A, RUVB2/TIP49B, SENP3, TAF1, TAF4, TAF6, TAF7, TAF9 and TEX10. Interacts with ZMYND11.
messages: Nucleus
messages: Transcription repression is enhanced or dependent on the presence of the T-box DNA-binding domain.

9606:ITGA10
gene id: 9606:ITGA10
uniprot id: B4E282
uniprot id: O75578
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the integrin alpha chain family.
messages: Heterodimer of an alpha and a beta subunit. Alpha-10 associates with beta-1.
messages: Integrin alpha-10/beta-1 is a receptor for collagen.
messages: Membrane
messages: The integrin I-domain (insert) is a VWFA domain. Integrins with I-domains do not undergo protease cleavage.
messages: Widely expressed with highest expression in muscle and heart. Found in articular cartilage.

9606:KCNH3
gene id: 9606:KCNH3
uniprot id: Q9ULD8
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the potassium channel family. H (Eag) (TC 1.A.1.20) subfamily. Kv12.2/KCNH3 sub-subfamily.
messages: Detected only in brain, in particular in the telencephalon. Detected in the cerebral cortex, occipital pole, frontal and temporal lobe, putamen, amygdala, hippocampus and caudate nucleus.
messages: Membrane
messages: Pore-forming (alpha) subunit of voltage-gated potassium channel. Elicits an outward current with fast inactivation. Channel properties may be modulated by cAMP and subunit assembly.
messages: The potassium channel is probably composed of a homo- or heterotetrameric complex of pore-forming alpha subunits that can associate with modulating beta subunits.
messages: The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.

9606:FAM111A
gene id: 9606:FAM111A
uniprot id: Q96PZ2
names: Disease Annotation
names: Domain
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Interacts with SV40 virus large T antigen and this interaction is required for efficient viral replication and sustained viral gene expression in restrictive cell types.
messages: (Microbial infection) May directly function at replication forks, explaining why Simian virus 40 (SV40) interacts with FAM111A to overcome host range restriction.
messages: Autocatalytically cleaved; activating the protein (PubMed:32165630). Autocatalytic cleavage takes place in trans (PubMed:32165630).
messages: Belongs to the FAM111 family.
messages: Chromosome
messages: Cytoplasm
messages: Interacts (via PIP-box) with PCNA; then interaction is direct.
messages: Nucleus
messages: Regulated in a cell cycle dependent manner with the lowest expression during G0 or the quiescent phase and with peak expression during G2/M phase (at protein level).
messages: Single-stranded DNA-binding serine protease that mediates the proteolytic cleavage of covalent DNA-protein cross-links (DPCs) during DNA synthesis, thereby playing a key role in maintaining genomic integrity (PubMed:32165630). DPCs are highly toxic DNA lesions that interfere with essential chromatin transactions, such as replication and transcription, and which are induced by reactive agents, such as UV light or formaldehyde (PubMed:32165630). Protects replication fork from stalling by removing DPCs, such as covalently trapped topoisomerase 1 (TOP1) adducts on DNA lesion, or poly(ADP-ribose) polymerase 1 (PARP1)-DNA complexes trapped by PARP inhibitors (PubMed:32165630). Required for PCNA loading on replication sites (PubMed:24561620). Promotes S-phase entry and DNA synthesis (PubMed:24561620).
messages: The PIP-box mediates the interaction with PCNA.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:MYL12B
gene id: 9606:MYL12B
uniprot id: O14950
names: Function
names: Miscellaneous
names: PTM
names: Subunit
names: Tissue Specificity
messages: Myosin is a hexamer of 2 heavy chains and 4 light chains: interacts with myosin heavy chain MYO19.
messages: Myosin regulatory subunit that plays an important role in regulation of both smooth muscle and nonmuscle cell contractile activity via its phosphorylation. Phosphorylation triggers actin polymerization in vascular smooth muscle. Implicated in cytokinesis, receptor capping, and cell locomotion.
messages: Phosphorylation increases the actin-activated myosin ATPase activity and thereby regulates the contractile activity. It is required to generate the driving force in the migration of the cells but not necessary for localization of myosin-2 at the leading edge. Phosphorylation is reduced following epigallocatechin-3-O-gallate treatment.
messages: This chain binds calcium.
messages: Ubiquitously expressed in various hematopoietic cells.

9606:PATE3
gene id: 9606:PATE3
uniprot id: B3GLJ2
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the PATE family.
messages: Secreted
messages: Specifically expressed in prostate and testis.

9606:SUPT5H
gene id: 9606:SUPT5H
uniprot id: O00267
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the SPT5 family.
messages: Component of the DRB sensitivity-inducing factor complex (DSIF complex), which regulates mRNA processing and transcription elongation by RNA polymerase II. DSIF positively regulates mRNA capping by stimulating the mRNA guanylyltransferase activity of RNGTT/CAP1A. DSIF also acts cooperatively with the negative elongation factor complex (NELF complex) to enhance transcriptional pausing at sites proximal to the promoter. Transcriptional pausing may facilitate the assembly of an elongation competent RNA polymerase II complex. DSIF and NELF promote pausing by inhibition of the transcription elongation factor TFIIS/S-II. TFIIS/S-II binds to RNA polymerase II at transcription pause sites and stimulates the weak intrinsic nuclease activity of the enzyme. Cleavage of blocked transcripts by RNA polymerase II promotes the resumption of transcription from the new 3' terminus and may allow repeated attempts at transcription through natural pause sites. DSIF can also positively regulate transcriptional elongation and is required for the efficient activation of transcriptional elongation by the HIV-1 nuclear transcriptional activator, Tat. DSIF acts to suppress transcriptional pausing in transcripts derived from the HIV-1 LTR and blocks premature release of HIV-1 transcripts at terminator sequences.
messages: Interacts with SUPT4H1 to form DSIF. DSIF interacts with the positive transcription elongation factor b complex (P-TEFb complex), which is composed of CDK9 and cyclin-T (CCNT1 or CCNT2). DSIF interacts with RNA polymerase II, and this interaction is reduced by phosphorylation of the C-terminal domain (CTD) of POLR2A by P-TEFb. DSIF also interacts with the NELF complex, which is composed of NELFA, NELFB, NELFD and NELFE, and this interaction occurs following prior binding of DSIF to RNA polymerase II. DSIF also interacts with PRMT1/HRMT1L2, HTATSF1/TATSF1, RNGTT/CAP1A, PRMT5/SKB1, SUPT6H, and can interact with PIN1. Component of a complex which is at least composed of HTATSF1/Tat-SF1, the P-TEFb complex components CDK9 and CCNT1, RNA polymerase II, SUPT5H, and NCL/nucleolin. Interacts with MCM3AP isoform GANP (PubMed:23652018).
messages: Methylated by PRMT1/HRMT1L2 and PRMT5/SKB1. Methylation negatively regulates interaction with P-TEFb and RNA polymerase II.
messages: Nucleus
messages: Phosphorylated by CDK7 and CDK9. Phosphorylation by P-TEFb alleviates transcriptional pausing and can stimulate transcriptional elongation from the HIV-1 LTR. P-TEFb dependent phosphorylation is stimulated by the HIV-1 Tat protein. Phosphorylation may also stimulate interaction with PIN1. Bulk phosphorylation occurs predominantly in mitosis.
messages: Ubiquitously expressed.

9606:HKDC1
gene id: 9606:HKDC1
uniprot id: B3KT70
uniprot id: Q2TB90
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the hexokinase family.
messages: Catalyzes the phosphorylation of hexose to hexose 6-phosphate, although at very low level compared to other hexokinases (PubMed:30517626). Has low glucose phosphorylating activity compared to other hexokinases (PubMed:30517626). Involved in glucose homeostasis and hepatic lipid accumulation. Required to maintain whole-body glucose homeostasis during pregnancy; however additional evidences are required to confirm this role (By similarity).
messages: Cytoplasm
messages: Mitochondrion membrane
messages: Photoreceptor inner segment
messages: The disease may be caused by variants affecting the gene represented in this entry.
messages: Widely expressed (PubMed:27459389, PubMed:29401404). Highly expressed in the brush border, surface epithelium and the myenteric plexus of the small and large intestines; the acinar centrocytes and interlobular ducts of the pancreas; and the alveolar macrophages in the lungs (at protein level) (PubMed:29401404). Present at moderate level in the thyroid follicular epithelium (at protein level) (PubMed:29401404).

9606:NFKB2
gene id: 9606:NFKB2
uniprot id: Q00653
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: A chromosomal aberration involving NFKB2 is found in a case of B-cell non Hodgkin lymphoma (B-NHL). Translocation t(10;14)(q24;q32) with IGHA1. The resulting oncogene is also called Lyt-10C alpha variant.
messages: A chromosomal aberration involving NFKB2 is found in a cutaneous T-cell leukemia (C-TCL) cell line. This rearrangement produces the p80HT gene which codes for a truncated 80 kDa protein (p80HT).
messages: Component of the NF-kappa-B RelB-p52 complex. Homodimer; component of the NF-kappa-B p52-p52 complex. Component of the NF-kappa-B p65-p52 complex. Component of the NF-kappa-B p52-c-Rel complex. NFKB2/p52 interacts with NFKBIE. Component of a complex consisting of the NF-kappa-B p50-p50 homodimer and BCL3. Directly interacts with MEN1.
messages: Constitutive processing is tightly suppressed by its C-terminal processing inhibitory domain, named PID, which contains the death domain.
messages: Cytoplasm
messages: In B-cell leukemia (B-CLL) cell line, LB40 and EB308, can be found after heterogeneous chromosomal aberrations, such as internal deletions.
messages: NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. In a non-canonical activation pathway, the MAP3K14-activated CHUK/IKKA homodimer phosphorylates NFKB2/p100 associated with RelB, inducing its proteolytic processing to NFKB2/p52 and the formation of NF-kappa-B RelB-p52 complexes. The NF-kappa-B heterodimeric RelB-p52 complex is a transcriptional activator. The NF-kappa-B p52-p52 homodimer is a transcriptional repressor. NFKB2 appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins by p100 and generation of p52 by a cotranslational processing. The proteasome-mediated process ensures the production of both p52 and p100 and preserves their independent function. p52 binds to …
messages: Nucleus
messages: Subsequent to MAP3K14-dependent serine phosphorylation, p100 polyubiquitination occurs then triggering its proteasome-dependent processing.
messages: The C-terminus of p100 might be involved in cytoplasmic retention, inhibition of DNA-binding by p52 homodimers, and/or transcription activation.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The glycine-rich region (GRR) appears to be a critical element in the generation of p52.
messages: While translation occurs, the particular unfolded structure after the GRR repeat promotes the generation of p52 making it an acceptable substrate for the proteasome. This process is known as cotranslational processing. The processed form is active and the unprocessed form acts as an inhibitor (I kappa B-like), being able to form cytosolic complexes with NF-kappa B, trapping it in the cytoplasm. Complete folding of the region downstream of the GRR repeat precludes processing.

9606:HOXA5
gene id: 9606:HOXA5
uniprot id: P20719
names: Developmental Stage
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the Antp homeobox family.
messages: Expressed during embryogenesis and in adult kidney.
messages: Forms a DNA-binding heterodimer with transcription factor PBX1.
messages: Nucleus
messages: Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. Also binds to its own promoter. Binds specifically to the motif 5'-CYYNATTA[TG]Y-3'.

9606:CAPN12
gene id: 9606:CAPN12
uniprot id: Q6ZSI9
names: Function
names: Similarity
messages: Belongs to the peptidase C2 family.
messages: Calcium-regulated non-lysosomal thiol-protease.

9606:TMEM41A
gene id: 9606:TMEM41A
uniprot id: Q96HV5
names: Domain
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the TMEM41 family.
messages: Membrane
messages: The VTT domain was previously called the SNARE-assoc domain. As there is no evidence that this domain associates with SNARE proteins, it was renamed as VMP1, TMEM41, and TVP38 (VTT) domain.
messages: Unlikely isoform. Aberrant splice sites.

9606:PMAIP1
gene id: 9606:PMAIP1
uniprot id: Q13794
names: Domain
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the PMAIP1 family.
messages: Highly expressed in adult T-cell leukemia cell line.
messages: Interacts with MCL1 (PubMed:15694340, PubMed:17374615, PubMed:17389404). Interacts with BCL2A1 (Ref.11). Interacts with BAX (PubMed:15705586). Interacts with BCL2L10 (PubMed:23563182).
messages: Mitochondrion
messages: Promotes activation of caspases and apoptosis. Promotes mitochondrial membrane changes and efflux of apoptogenic proteins from the mitochondria. Contributes to p53/TP53-dependent apoptosis after radiation exposure. Promotes proteasomal degradation of MCL1. Competes with BAK1 for binding to MCL1 and can displace BAK1 from its binding site on MCL1 (By similarity). Competes with BIM/BCL2L11 for binding to MCL1 and can displace BIM/BCL2L11 from its binding site on MCL1.
messages: The BH3 motif is essential for pro-apoptotic activity.
messages: Up-regulated by p53/TP53, phorbol esters, double-stranded RNA, IFNB1/IFN-beta and viruses.

9606:STING1
gene id: 9606:STING1
uniprot id: J3QTB1
uniprot id: Q86WV6
uniprot id: V5V0K2
names: Activity Regulation
names: Disease Annotation
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Antiviral activity is antagonized by oncoproteins, such as papillomavirus (HPV) protein E7 and adenovirus early E1A protein (PubMed:26405230). Such oncoproteins prevent the ability to sense cytosolic DNA (PubMed:26405230).
messages: (Microbial infection) Deubiquitinated by Epstein-Barr virus BPLF1 on both 'Lys-48' and 'Lys-63'-linked ubiquitin chains; leading to inhibition of cGAS-STING signaling.
messages: (Microbial infection) Interacts with Chikungunya virus non-structural protein 1; this interaction results in inhibition of cGAS-STING signaling and increased levels of palmitoylated nsP1 and protein stabilization.
messages: (Microbial infection) Interacts with adenovirus early E1A protein.
messages: (Microbial infection) Interacts with herpes simplex virus 1 protein ICP34.5; this interaction inhibits the intracellular DNA sensing pathway.
messages: (Microbial infection) Interacts with human cytomegalovirus proteins UL94, UL42 and UL138; these interactions result in the inhibition of cGAS-STING signaling.
messages: (Microbial infection) Interacts with human papillomavirus (HPV) protein E7.
messages: (Microbial infection) Interacts with varivella virus protein 39; this interaction results in the inhibition of cGAS-STING signaling.
messages: Activated upon binding to the hydrolysis-resistant 2'3'-cG(s)A(s)MP, an analog of cGAMP, in which phosphodiester linkages are replaced by phosphothioate linkages (PubMed:25344812). Specifically inhibited by small-molecule H-151 (N-(4-ethylphenyl)-N'-1H-indol-3-yl-urea), which covalently binds Cys-91 and prevents palmitoylation and subsequent activation of STING1 (PubMed:29973723, PubMed:35045565). In contrast to mouse protein, not activated by anticancer molecule 5,6-dimethylxanthenone 4-acetic acid (DMXAA) (PubMed:26669264, PubMed:23910378, PubMed:25199835). Inhibited by compound 18 ([(3S,4S)-2-(4-tert-butyl-3-chlorophenyl)-3-(2,3-dihydro-1,4-benzodioxin-6-yl)-7-fluoro-1-oxo-1,2,3,4-tetrahydroisoquinolin-4-yl]acetate), a competitive inhibitor with slow dissociation kinetics and good oral bioavailability (PubMed:30655953).
messages: Belongs to the STING family.
messages: Cell membrane
messages: Endoplasmic reticulum membrane
messages: Endoplasmic reticulum-Golgi intermediate compartment membrane
messages: Facilitator of innate immune signaling that acts as a sensor of cytosolic DNA from bacteria and viruses and promotes the production of type I interferon (IFN-alpha and IFN-beta) (PubMed:18724357, PubMed:18818105, PubMed:19433799, PubMed:19776740, PubMed:23027953, PubMed:23910378, PubMed:23747010, PubMed:29973723, PubMed:30842659, PubMed:35045565, PubMed:27801882, PubMed:36808561). Innate immune response is triggered in response to non-CpG double-stranded DNA from viruses and bacteria delivered to the cytoplasm (PubMed:26300263). Acts by binding cyclic dinucleotides: recognizes and binds cyclic di-GMP (c-di-GMP), a second messenger produced by bacteria, and cyclic GMP-AMP (cGAMP), a messenger produced by CGAS in response to DNA virus in the cytosol (PubMed:21947006, PubMed:23258412, PubMed:23707065, PubMed:23722158, PubMed:26229117, PubMed:23910378, PubMed:23747010, PubMed:30842659). Upon binding of c-di-GMP or cGAMP, STING1 oligomerizes, translocates from the endoplasmic reticulum and is phosphorylated by TBK1 on the pLxIS motif, leading to recruitment and subsequent activation of the transcription factor IRF3 to induce expression of type I interferon and exert a potent anti-viral state (PubMed:22394562, PubMed:25636800, PubMed:29973723, PubMed:30842653, PubMed:35045565). In addition to promote the production of type I interferons, plays a direct role in autophagy (PubMed:30568238, PubMed:30842662). Following cGAMP-binding, STING1 buds from the endoplasmic reticulum into COPII vesicles, which then form the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) (PubMed:30842662). The ERGIC serves as the membrane source for WIPI2 recruitment and LC3 lipidation, leading to formation of autophagosomes that target cytosolic DNA or DNA viruses for degradation by the lysosome (PubMed:30842662). The autophagy- and interferon-inducing activities can be uncoupled and autophagy induction is independent of TBK1 phosphorylation (PubMed:30568238, PubMed:30842662). Autophagy…
messages: Golgi apparatus membrane
messages: Homodimer; forms a homodimer in absence of cyclic nucleotide (c-di-GMP or cGAMP); 'Lys-63'-linked ubiquitination at Lys-150 is required for homodimerization (PubMed:22579474, PubMed:22705373, PubMed:22728658, PubMed:22728660, PubMed:22728659, PubMed:19285439, PubMed:30842659). Homotetramer; in presence of cyclic nucleotide (c-di-GMP or cGAMP), forms tetramers and higher-order oligomers through side-by-side packing (Probable). Interacts (when phosphorylated) with IRF3; following activation and phosphorylation on the pLxIS motif by TBK1, recruits IRF3 (PubMed:22394562, PubMed:25636800, PubMed:28331227, PubMed:27302953). Interacts with RIGI, MAVS and SSR2 (PubMed:18818105, PubMed:18724357). Interacts with RNF5 and TRIM56 (PubMed:19285439, PubMed:21074459). Interacts with TBK1; when homodimer, leading to subsequent production of IFN-beta (PubMed:19416887). Interacts with IFIT1 and IFIT2 (PubMed:19416887). Interacts with TRIM29; this interaction induces STING1 ubiquitination and subsequent degradation (PubMed:29038422). Associates with the MHC-II complex (By similarity). Interacts with STEEP; the interaction is increased upon cGAMP binding and promotes STING1 translocation to COPII vesicles (PubMed:32690950). Interacts with SEC24A, SEC24B, and SEC24C; promoting translocation to COPII vesicles (PubMed:32690950, PubMed:30842662). Interacts (when ubiquitinated) with SQSTM1; leading to relocalization to autophagosomes (By similarity). Interacts with SURF4 (PubMed:29251827). Interacts with HNRNPA2B1 (PubMed:31320558). Interacts with ZDHHC1; ZDHHC1 constitutively interacts with STING1 and in presence of DNA viruses activates it by promoting its cGAMP-induced oligomerization and the recruitment of downstream signaling components (PubMed:25299331). Interacts with ZDHHC11; in presence of DNA viruses promotes the recruitment of IRF3 to STING1 (PubMed:28331227). Interacts with TOMM70 (PubMed:20628368). Interacts with isoform IFI16-beta of IFI16 (PubMed:30104205).
messages: In absence of cGAMP, the transmembrane and cytoplasmic regions interact to form an integrated, domain-swapped dimeric assembly (By similarity). In absence of cyclic nucleotide (c-di-GMP or cGAMP), the protein is autoinhibited by an intramolecular interaction between the cyclic dinucleotide-binding domain (CBD) and the C-terminal tail (CTT) (PubMed:22579474, PubMed:22705373, PubMed:22728658, PubMed:22728660, PubMed:22728659). Following cGAMP-binding, the cyclic dinucleotide-binding domain (CBD) is closed, leading to a 180 degrees rotation of the CBD domain relative to the transmembrane domain. This rotation is coupled to a conformational change in a loop on the side of the CBD dimer, which leads to the formation of the STING1 tetramer and higher-order oligomers through side-by-side packing (By similarity). The N-terminal part of the CBD region was initially though to contain a fifth transmembrane region (TM5) but is part of the folded, soluble CBD (PubMed:22579474, PubMed:22705373, PubMed:22728658, PubMed:22728660, PubMed:22728659).
messages: Mitochondrion outer membrane
messages: Palmitoylation takes place in the Golgi apparatus and creates a platform for the recruitment of TBK1.
messages: Phosphorylation by TBK1 leads to activation and production of IFN-beta (PubMed:18818105, PubMed:19433799, PubMed:25636800, PubMed:30842659, PubMed:30842653, PubMed:27302953). Following cyclic nucleotide (c-di-GMP or cGAMP)-binding, activation and translocation from the endoplasmic reticulum, STING1 is phosphorylated by TBK1 at Ser-366 in the pLxIS motif (PubMed:25636800, PubMed:32690950). The phosphorylated pLxIS motif constitutes an IRF3-binding motif, leading to recruitment of the transcription factor IRF3 to induce type-I interferons and other cytokines (PubMed:25636800). The phosphorylated pLxIS motif facilitates SENP2 recruitment during late phase of viral infection (By similarity). Phosphorylated on tyrosine residues upon MHC-II aggregation (By similarity). Dephosphorylation by PPP6C leads to inactivation and decreased production of IFN-beta (PubMed:32753499). Phosphorylation at Ser-358 is also required to activate IRF3 (PubMed:25636800).
messages: Sumoylated at Lys-338 by TRIM38 during the early phase of viral infection, promoting its stability by preventing its relocalization to autophagosomes and subsequent degradation. Desumoylated by SENP2 during the late phase of viral infection.
messages: The N-terminal domain interacts with glycerophospholipids and phospholipids.
messages: The cGAS-STING signaling pathway drives sterile inflammation leading to type I interferon immunopathology in severe COVID-19 disease caused by SARS-CoV-2 virus infection (PubMed:35045565). Tissue damages in the lung and skin lesions are caused by activation of the cGAS-STING signaling leading to aberrant inflammation (PubMed:35045565). Endothelial cell damage is also caused by activation of the cGAS-STING pathway: SARS-CoV-2 infection triggers mitochondrial DNA release into the cytosol (PubMed:35045565). Released mitochondrial DNA is then detected by CGAS, leading to activation of the cGAS-STING pathway, triggering type-I interferon production and autoinflammation (PubMed:35045565).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The pLxIS motif constitutes an IRF3-binding motif: following phosphorylation by TBK1, the phosphorylated pLxIS motif of STING1 recruits IRF3 (PubMed:25636800). IRF3 is then phosphorylated and activated by TBK1 to induce type-I interferons and other cytokines (PubMed:25636800).
messages: Ubiquitinated (PubMed:19285439, PubMed:19433799, PubMed:21074459, PubMed:25254379). Ubiquitinated via 'Lys-63'-linked ubiquitin chains in response to double-stranded DNA treatment, leading to relocalization to autophagosomes and subsequent degradation; this process is dependent on SQSTM1 (By similarity). 'Lys-63'-linked ubiquitination mediated by TRIM56 at Lys-150 promotes homodimerization and recruitment of the antiviral kinase TBK1 and subsequent production of IFN-beta (PubMed:21074459). 'Lys-48'-linked polyubiquitination at Lys-150 occurring after viral infection is mediated by RNF5 and leads to proteasomal degradation (PubMed:19285439). 'Lys-11'-linked polyubiquitination at Lys-150 by RNF26 leads to stabilize STING1: it protects STING1 from RNF5-mediated 'Lys-48'-linked polyubiquitination (PubMed:25254379). 'Lys-33'-linked and 'Lys-48'-linked deubiquitinated by USP20; leading to its stabilization and promotion of innate antiviral response (PubMed:27801882). 'Lys-48'-linked deubiquitinated by USP44; leading to its stabilization and promotion of innate antiviral response (PubMed:31968013). Deubiquitinated by USP13; leading to inhibition of innate antiviral response (PubMed:28534493).
messages: Ubiquitously expressed. Expressed in skin endothelial cells, alveolar type 2 pneumocytes, bronchial epithelium and alveolar macrophages.
messages: autophagosome membrane
messages: perinuclear region

9606:KLF7
gene id: 9606:KLF7
uniprot id: O75840
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: Interacts with FBXO38.
messages: Nucleus
messages: The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. In KLF7, the motif is inactive.
messages: The acidic N-terminal part may favor interaction with the basic domain of transcription factors.
messages: Transcriptional factor (PubMed:9774444, PubMed:16339272). Plays a critical role in neuronal morphogenesis and survival of sensory neurons (By similarity). Represses the corneal epithelium differentiation (PubMed:28916725). Acts also as a metabolic regulator, by modulating insulin sensitivity in pancreatic beta cells and skeletal muscle cells (PubMed:16339272). Inhibits transcriptional inducers of adipogenesis and has a repressive role in the expression of several adipokines, including leptin (PubMed:16339272).
messages: Widely expressed.

9606:FAF1
gene id: 9606:FAF1
uniprot id: Q9UNN5
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Interacts with CDT1 and ATPase VCP/p97 (PubMed:26842564). Interacts (via UBA domain) with FAS (via death domain) (PubMed:10462485). Interacts (via UBA domain) with NLRP12 (via DAPIN/PYRIN domain) (PubMed:21978668).
messages: Most abundant in testis, slightly less abundant in skeletal muscle and heart, followed by prostate, thymus, ovary, small intestine, and colon. Not detected in the peripheral blood leukocytes.
messages: Nucleus
messages: Ubiquitin-binding protein (PubMed:19722279). Required for the progression of DNA replication forks by targeting DNA replication licensing factor CDT1 for degradation (PubMed:26842564). Potentiates but cannot initiate FAS-induced apoptosis (By similarity).

9606:COL16A1
gene id: 9606:COL16A1
uniprot id: Q07092
names: Developmental Stage
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the fibril-associated collagens with interrupted helices (FACIT) family.
messages: Glycosylated.
messages: Homotrimer. Interacts with FBN1, fibronectin and integrins ITGA1/ITGB1 and ITGA2/ITGB1. Integrin ITGA1/ITGB1 binds to a unique site within COL16A1 located close to its C-terminal end between collagenous domains COL1-COL3.
messages: In papillary dermis, is a component of specialized fibrillin-1-containing microfibrils, whereas in territorial cartilage matrix, it is localized to a discrete population of thin, weakly banded collagen fibrils in association with other collagens (at protein level). In the placenta, where it is found in the amnion, a membranous tissue lining the amniotic cavity. Within the amnion, it is found in an acellular, relatively dense layer of a complex network of reticular fibers. Also located to a fibroblast layer beneath this dense layer. Exists in tissues in association with other types of collagen.
messages: Involved in mediating cell attachment and inducing integrin-mediated cellular reactions, such as cell spreading and alterations in cell morphology.
messages: Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.
messages: This sequence defines eighteen different domains, nine triple-helical domains (COL9 to COL1) and ten non-triple-helical domains (NC10 to NC1). The numerous interruptions in the triple helix may make this molecule either elastic or flexible.
messages: Transiently elevated expression during gestation, and decrease at term.
messages: extracellular matrix

9606:PTGES3L-AARSD1
gene id: 9606:PTGES3L-AARSD1
uniprot id: Q9BTE6
names: Cofactor
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
messages: Based on a readthrough transcript which may produce a PTGES3L-AARSD1 fusion protein.
messages: Belongs to the class-II aminoacyl-tRNA synthetase family. Alax-L subfamily.
messages: Binds 1 zinc ion per subunit.
messages: Cytoplasm
messages: Functions in trans to edit the amino acid moiety from incorrectly charged tRNA(Ala).

9606:OR5J2
gene id: 9606:OR5J2
uniprot id: A0A126GVP0
uniprot id: Q8NH18
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Membrane
messages: Odorant receptor.

9606:POTEB
gene id: 9606:POTEB
uniprot id: A0A0A6YYL3
names: Caution
names: Similarity
messages: Belongs to the POTE family.
messages: Maps to a duplicated region on chromosome 15; the gene is present in at least 3 almost identical copies.

9606:YTHDF2
gene id: 9606:YTHDF2
uniprot id: Q9Y5A9
names: Caution
names: Domain
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Promotes viral gene expression and replication of polyomavirus SV40: acts by binding to N6-methyladenosine (m6A)-containing viral RNAs (PubMed:29447282).
messages: (Microbial infection) Promotes viral gene expression and virion production of kaposis sarcoma-associated herpesvirus (KSHV) at some stage of the KSHV life cycle (in iSLK.219 and iSLK.BAC16 cells) (PubMed:29659627). Acts by binding to N6-methyladenosine (m6A)-containing viral RNAs (PubMed:29659627).
messages: Belongs to the YTHDF family. YTHDF2 subfamily.
messages: Following heat shock stress.
messages: Highly expressed in induced pluripotent stem cells (iPSCs) and down-regulated during neural differentiation.
messages: Interacts with CNOT1; interaction is direct and promotes recruitment of the CCR4-NOT complex (PubMed:27558897, PubMed:32492408). Interacts with YTHDF3 (PubMed:28106072). Interacts with RIDA/HRSP12; interaction leads to recruitment of the ribonuclease P/MRP complex (PubMed:30930054).
messages: Nucleus
messages: P-body
messages: Previous studies suggested the 3 different paralogs (YTHDF1, YTHDF2 and YTHDF3) have unique functions with limited redundancy (PubMed:26046440). However, later studies showed that YTHDF1, YTHDF2 and YTHDF3 paralogs have redundant functions to a profound extent and directly promote degradation of m6A-containing mRNAs (PubMed:32492408).
messages: Specifically recognizes and binds N6-methyladenosine (m6A)-containing RNAs, and regulates their stability (PubMed:24284625, PubMed:26046440, PubMed:26318451, PubMed:32492408). M6A is a modification present at internal sites of mRNAs and some non-coding RNAs and plays a role in mRNA stability and processing (PubMed:22575960, PubMed:24284625, PubMed:32492408, PubMed:25412658, PubMed:25412661). Acts as a regulator of mRNA stability by promoting degradation of m6A-containing mRNAs via interaction with the CCR4-NOT and ribonuclease P/MRP complexes, depending on the context (PubMed:24284625, PubMed:26046440, PubMed:27558897, PubMed:30930054, PubMed:32492408). The YTHDF paralogs (YTHDF1, YTHDF2 and YTHDF3) share m6A-containing mRNAs targets and act redundantly to mediate mRNA degradation and cellular differentiation (PubMed:28106072, PubMed:32492408). M6A-containing mRNAs containing a binding site for RIDA/HRSP12 (5'-GGUUC-3') are preferentially degraded by endoribonucleolytic cleavage: cooperative binding of RIDA/HRSP12 and YTHDF2 to transcripts leads to recruitment of the ribonuclease P/MRP complex (PubMed:30930054). Other m6A-containing mRNAs undergo deadenylation via direct interaction between YTHDF2 and CNOT1, leading to recruitment of the CCR4-NOT and subsequent deadenylation of m6A-containing mRNAs (PubMed:27558897). Required maternally to regulate oocyte maturation: probably acts by binding to m6A-containing mRNAs, thereby regulating maternal transcript dosage during oocyte maturation, which is essential for the competence of oocytes to sustain early zygotic development (By similarity). Also required during spermatogenesis: regulates spermagonial adhesion by promoting degradation of m6A-containing transcripts coding for matrix metallopeptidases (By similarity). Also involved in hematopoietic stem cells specification by binding to m6A-containing mRNAs, leading to promote their degradation (PubMed:30065315). Also acts as a regulator of neural development by promoting…
messages: Stress granule
messages: The disordered regions have the ability to interact with each other and to 'phase separate' into liquid droplets within the cytosol following binding to mRNAs containing multiple m6A-modified residues (PubMed:31292544). This leads to the partition of m6A-containing mRNAs into membraneless compartments, where mRNAs may be stored, degraded or used to transport mRNAs to dendritic arbors in neurons (PubMed:31292544).
messages: The role of YTHDF2 and N6-methyladenosine (m6A) in virus expression and replication is unclear (PubMed:29109479, PubMed:29447282, PubMed:29659627, PubMed:30559377). According to some reports, YTHDF2 promotes viral gene expression and replication of polyomavirus SV40 and herpesvirus (KSHV) by binding to N6-methyladenosine (m6A)-containing viral RNAs (PubMed:29447282, PubMed:29659627). Another report however suggests that YTHDF2 regulates virus expression and replication indirectly, via its ability to inhibit the type I interferon response, thereby promoting virus expression (PubMed:30559377). Indirect regulation via inhibition of type I interferon response might explain why contradictory results have been reported for its role in KSHV virus replication (PubMed:29109479, PubMed:29659627).
messages: Ubiquitinated by the SCF(SKP2) complex, leading to its degradation.
messages: cytosol

9606:TRIM7
gene id: 9606:TRIM7
uniprot id: Q9C029
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Promotes Zika virus replication by mediating envelope protein E ubiquitination.
messages: Auto-ubiquitinates via 'Lys-63'-linked polyubiquitination.
messages: Belongs to the TRIM/RBCC family.
messages: Cytoplasm
messages: E3 ubiquitin-protein ligase that have both tumor-promoting and tumor-suppressing activities and functions in several biological processes including innate immunity, regulation of ferroptosis as well as cell proliferation and migration (PubMed:25851810, PubMed:32853985, PubMed:34062120). Acts as an antiviral effector against multiple viruses by targeting specific viral proteins for ubiquitination and degradation including norovirus NTPase protein or SARS-CoV-2 NSP5 and NSP8 proteins (PubMed:34062120, PubMed:35982226). Mechanistically, recognizes the C-terminal glutamine-containing motif usually generated by viral proteases that process the polyproteins and trigger their ubiquitination and subsequent degradation (PubMed:35982226, PubMed:35867826, PubMed:35893676). Mediates 'Lys-63'-linked polyubiquitination and stabilization of the JUN coactivator RNF187 in response to growth factor signaling via the MEK/ERK pathway, thereby regulating JUN transactivation and cellular proliferation (PubMed:25851810). Promotes the TLR4-mediated signaling activation through its E3 ligase domain leading to production of pro-inflammatory cytokines and type I interferon (By similarity). Also plays a negative role in the regulation of exogenous cytosolic DNA virus-triggered immune response. Mechanistically, enhances the 'Lys-48'-linked ubiquitination of STING1 leading to its proteasome-dependent degradation (PubMed:32126128). Mediates the ubiquitination of the SIN3-HDAC chromatin remodeling complex component BRMS1 (PubMed:32853985). Modulates NCOA4-mediated ferritinophagy and ferroptosis in glioblastoma cells by ubiquitinating NCOA4, leading to its degradation (PubMed:36067704).
messages: Forms homodimers (PubMed:35893676). Interacts with GNIP2 (PubMed:14984203, PubMed:25851810). Interacts with GYG1 (PubMed:11916970, PubMed:14984203, PubMed:33989636). Interacts with RNF187 (via C-terminus) (PubMed:25851810).
messages: Golgi apparatus
messages: Nucleus
messages: Phosphorylated at Ser-107 by RPS6KA5/MSK1, which stimulates the ubiquitin ligase activity.
messages: Skeletal muscle and placenta, at lower levels in heart, brain and pancreas. Isoform 1 is widely expressed with high level in testis, kidney and heart.
messages: The B30.2 domain mediates interaction with GYG1.
messages: The coiled-coil region mediates homodimerization and heterodimerization.

9606:CRABP1
gene id: 9606:CRABP1
uniprot id: F1T0F7
uniprot id: P29762
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the calycin superfamily. Fatty-acid binding protein (FABP) family.
messages: Cytoplasm
messages: Cytosolic CRABPs may regulate the access of retinoic acid to the nuclear retinoic acid receptors.
messages: Forms a beta-barrel structure that accommodates hydrophobic ligands in its interior.

9606:TK2
gene id: 9606:TK2
uniprot id: A4IF54
uniprot id: A5PLM0
uniprot id: O00142
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the DCK/DGK family.
messages: Mitochondrion
messages: Monomer.
messages: Phosphorylates thymidine, deoxycytidine, and deoxyuridine in the mitochondrial matrix (PubMed:9989599, PubMed:11687801). In non-replicating cells, where cytosolic dNTP synthesis is down-regulated, mtDNA synthesis depends solely on TK2 and DGUOK (PubMed:9989599). Widely used as target of antiviral and chemotherapeutic agents (PubMed:9989599).
messages: Predominantly expressed in liver, pancreas, muscle, and brain.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:GAS2L1
gene id: 9606:GAS2L1
uniprot id: Q99501
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the GAS2 family.
messages: Interacts with MAPRE1.
messages: Involved in the cross-linking of microtubules and microfilaments (PubMed:12584248, PubMed:24706950). Regulates microtubule dynamics and stability by interacting with microtubule plus-end tracking proteins, such as MAPRE1, to regulate microtubule growth along actin stress fibers (PubMed:24706950).
messages: cytoskeleton
messages: stress fiber

9606:SPATA4
gene id: 9606:SPATA4
uniprot id: Q8NEY3
names: Function
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Highly expressed in testis, the expression is observed precisely in seminiferous tubules.
messages: May play a role in apoptosis regulation.
messages: Nucleus

9606:CLDN4
gene id: 9606:CLDN4
uniprot id: O14493
uniprot id: Q75L80
names: Caution
names: Developmental Stage
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Interacts (via both extracellular domains) with Clostridium perfringens enterotoxin CPE; the interaction may disrupt claudin assembly in tight junctions.
messages: Belongs to the claudin family.
messages: CLDN4 is located in the Williams-Beuren syndrome (WBS) critical region. WBS results from a hemizygous deletion of several genes on chromosome 7q11.23, thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region.
messages: Cell membrane
messages: Channel-forming tight junction protein that mediates paracellular chloride transport in the kidney. Plays a critical role in the paracellular reabsorption of filtered chloride in the kidney collecting ducts. Claudins play a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity.
messages: Directly interacts with TJP1/ZO-1 (PubMed:16236711). Interacts with TJP2/ZO-2 and TJP3/ZO-3 (By similarity). Interacts with EPHA2; phosphorylates CLDN4 and may regulate tight junctions (PubMed:16236711). Interacts with CLDN1 (PubMed:20375010). Interacts with CLDN8 (By similarity).
messages: Expressed in the lungs from 23 weeks of gestation till birth.
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: Membrane
messages: Phosphorylated. Phosphorylation by EPHA2 is stimulated by EFNA1 and alters interaction with TJP1.
messages: Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity.
messages: tight junction

9606:LAMP5
gene id: 9606:LAMP5
uniprot id: Q9UJQ1
names: Function
names: Induction
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Appears to be a novel specific biomarker for blastic plasmocytoid dendritic cells neoplasia.
messages: Belongs to the LAMP family.
messages: Cell membrane
messages: Cytoplasmic vesicle membrane
messages: Early endosome membrane
messages: Endoplasmic reticulum-Golgi intermediate compartment membrane
messages: Endosome membrane
messages: Expressed in plasmocytoid dendritic cells. Expressed in suprabasal skin keratinocytes and squamous cells (at protein level). Expressed in the brain and weakly in spleen and skin. Expressed in plasmocytoid dendritic cells.
messages: Glycosylated.
messages: Plays a role in short-term synaptic plasticity in a subset of GABAergic neurons in the brain.
messages: Recycling endosome
messages: Up-regulated upon CpG dinucleotides activation. Down-regulated upon activation by Toll-like receptor (TLR) ligands.
messages: dendrite
messages: growth cone membrane
messages: synaptic vesicle membrane

9606:RFX6
gene id: 9606:RFX6
uniprot id: Q8HWS3
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the RFX family.
messages: Expressed in pancreas (PubMed:25497100). Expressed in pancreatic beta-cells (insulin-positive cells) and alpha-cells (glucagon-positive cells) (at protein level). Specifically expressed in pancreas, small intestine and colon (PubMed:20148032). Expressed in endocrine cells in the islets (PubMed:25497100).
messages: Interacts with RFX3.
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Transcription factor required to direct islet cell differentiation during endocrine pancreas development. Specifically required for the differentiation of 4 of the 5 islet cell types and for the production of insulin (PubMed:20148032, PubMed:25497100). Not required for pancreatic PP (polypeptide-producing) cells differentiation. Acts downstream of NEUROG3 and regulates the transcription factors involved in beta-cell maturation and function, thereby restricting the expression of the beta-cell differentiation and specification genes, and thus the beta-cell fate choice. Activates transcription by forming a heterodimer with RFX3 and binding to the X-box in the promoter of target genes (PubMed:20148032). Involved in glucose-stimulated insulin secretion by promoting insulin and L-type calcium channel gene transcription (PubMed:25497100).

9606:PTGER4
gene id: 9606:PTGER4
uniprot id: A0PJF5
uniprot id: P35408
names: Caution
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: High in intestine and in peripheral blood mononuclear cells; low in lung, kidney, thymus, uterus, vasculature and brain. Not found in liver, heart, retina oe skeletal muscle.
messages: Interacts with FEM1A.
messages: Membrane
messages: Phosphorylation mediates agonist-mediated desensitization by promoting cytoplasmic retention.
messages: Receptor for prostaglandin E2 (PGE2). The activity of this receptor is mediated by G(s) proteins that stimulate adenylate cyclase. Has a relaxing effect on smooth muscle. May play an important role in regulating renal hemodynamics, intestinal epithelial transport, adrenal aldosterone secretion, and uterine function.
messages: Was originally designated as the EP2 subtype.

9606:RAB5A
gene id: 9606:RAB5A
uniprot id: P20339
names: Activity Regulation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Glycosylated on arginine residues by S.typhimurium protein Ssek3.
messages: Belongs to the small GTPase superfamily. Rab family.
messages: Cell membrane
messages: Cytoplasmic vesicle
messages: Early endosome membrane
messages: Endosome membrane
messages: Interacts with SGSM1 and SGSM3 (By similarity). Interacts with PIK3CB (By similarity). Interacts with GDI1; this promotes dissociation from membranes; phosphorylation at Ser-84 disrupts this interaction (PubMed:23815289, PubMed:29125462). Interacts with GDI2; phosphorylation at Ser-84 disrupts the interaction (PubMed:29125462). Interacts with EEA1 (PubMed:10491193, PubMed:20534488). Interacts with RIN1 and GAPVD1, which regulate its pathway, probably by acting as a GEF (PubMed:11703925, PubMed:16410077). Interacts with RINL. Interacts with ALS2CL, SUN2, ZFYVE20 and RUFY1 (PubMed:10818110, PubMed:11062261, PubMed:15388334, PubMed:14617813, PubMed:16034420). Interacts with RABEP1; one RABEP1 homodimer binds two RAB5A chains, but at opposite sides of the dimer (PubMed:15378032). Interacts with OCRL (PubMed:25869668). Interacts with INPP5F. May be a component of a complex composed of RAB5A, DYN2 and PIK3C3 (By similarity). Does not interact with BLOC-3 complex (heterodimer of HPS1 and HPS4) (By similarity). Interacts with CLN5 (PubMed:22431521). Interacts with APPL2 (By similarity). Interacts with F8A1/F8A2/F8A3 (By similarity). Found in a complex with F8A1/F8A2/F8A3, HTT and RAB5A; mediates the recruitment of HTT by RAB5A onto early endosomes (By similarity). Interacts with ATP9A (PubMed:36604604).
messages: Melanosome
messages: Membrane
messages: Phosphorylation of Ser-84 in the switch II region by LRRK2 prevents the association of RAB regulatory proteins, including RAB GDP dissociation inhibitors GDI1 and GDI2.
messages: Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP.
messages: Small GTPase which cycles between active GTP-bound and inactive GDP-bound states. In its active state, binds to a variety of effector proteins to regulate cellular responses such as of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Active GTP-bound form is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. RAB5A is required for the fusion of plasma membranes and early endosomes (PubMed:10818110, PubMed:14617813, PubMed:16410077, PubMed:15378032). Contributes to the regulation of filopodia extension (PubMed:14978216). Required for the exosomal release of SDCBP, CD63, PDCD6IP and syndecan (PubMed:22660413). Regulates maturation of apoptotic cell-containing phagosomes, probably downstream of DYN2 and PIK3C3 (By similarity).
messages: cytosol
messages: phagosome membrane
messages: ruffle

9606:RPTOR
gene id: 9606:RPTOR
uniprot id: Q8N122
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts with vaccinia virus protein F17; this interaction dysregulates mTOR.
messages: Acetylation at Lys-1097 by EP300/p300 in response to leucine metabolite acetyl-coA promotes its activity, leading to activation of the mTORC1 complex (PubMed:30197302, PubMed:32561715). Acetylation is decreased in response to fasting (By similarity).
messages: Belongs to the WD repeat RAPTOR family.
messages: Component of the mechanistic target of rapamycin complex 1 (mTORC1), an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolecule biosynthesis to promote cellular biomass generation and growth (PubMed:12150925, PubMed:12150926, PubMed:12747827, PubMed:24403073, PubMed:26588989, PubMed:32561715). In response to nutrients, growth factors or amino acids, mTORC1 is recruited to the lysosome membrane and promotes protein, lipid and nucleotide synthesis by phosphorylating several substrates, such as ribosomal protein S6 kinase (RPS6KB1 and RPS6KB2) and EIF4EBP1 (4E-BP1) (PubMed:12150925, PubMed:12150926, PubMed:12747827, PubMed:24403073, PubMed:26588989). In the same time, it inhibits catabolic pathways by phosphorylating the autophagy initiation components ULK1 and ATG13, as well as transcription factor TFEB, a master regulators of lysosomal biogenesis and autophagy (PubMed:12150925, PubMed:12150926, PubMed:12747827, PubMed:24403073, PubMed:32561715). The mTORC1 complex is inhibited in response to starvation and amino acid depletion (PubMed:12150925, PubMed:12150926, PubMed:12747827, PubMed:24403073). Within the mTORC1 complex, RPTOR acts both as a molecular adapter, which (1) mediates recruitment of mTORC1 to lysosomal membranes via interaction with small GTPases Rag (RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and/or RagD/RRAGD), and a (2) substrate-specific adapter, which promotes substrate specificity by binding to TOS motif-containing proteins and direct them towards the active site of the MTOR kinase domain for phosphorylation (PubMed:12747827, PubMed:24403073, PubMed:26588989). mTORC1 complex regulates many cellular processes, such as odontoblast and osteoclast differentiation or neuronal transmission (By similarity). mTORC1 complex in excitatory neuronal transmission is required for the prosocial behavior induced by the psychoactive substance lysergic acid diethylamide (LSD) (By similarity).
messages: Cytoplasm
messages: Cytoplasmic granule
messages: Highly expressed in skeletal muscle, and in a lesser extent in brain, lung, small intestine, kidney and placenta.
messages: Insulin-stimulated phosphorylation at Ser-863 by MTOR and MAPK8 regulates mTORC1 activity (PubMed:19864431). Phosphorylated at Ser-863 by NLK in response to stress, disrupting the interaction with small GTPases Rag (RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and/or RagD/RRAGD), thereby preventing lysosome recruitment and activation of the mTORC1 complex (PubMed:26588989). Osmotic stress also induces phosphorylation at Ser-696, Thr-706 and Ser-863 by MAPK8 (PubMed:19864431, PubMed:22493283). Ser-863 phosphorylation is required for phosphorylation at Ser-855 and Ser-859 (PubMed:19864431). In response to nutrient limitation, phosphorylated at Ser-722 and Ser-792 by AMPK; phosphorylation promotes interaction with 14-3-3 proteins, leading to negative regulation of the mTORC1 complex (PubMed:18439900). In response to growth factors, phosphorylated at Ser-719, Ser-721 and Ser-722 by RPS6KA1, which stimulates mTORC1 activity (PubMed:18722121, PubMed:18439900). Phosphorylation at Ser-791 by PKA downstream of cAMP inhibits the mTORC1 complex (PubMed:31112131). Phosphorylated at Ser-877 by TBK1, leading to negative regulation of the mTORC1 complex (PubMed:31530866).
messages: Lysosome membrane
messages: Part of the mechanistic target of rapamycin complex 1 (mTORC1) which contains MTOR, MLST8 and RPTOR (PubMed:12408816, PubMed:24403073, PubMed:25940091, PubMed:27909983, PubMed:29236692, PubMed:31601764, PubMed:31601708, PubMed:36697823). mTORC1 associates with AKT1S1/PRAS40, which inhibits its activity (PubMed:17386266, PubMed:31601764). mTORC1 associates with DEPTOR, which regulates its activity (PubMed:34519269, PubMed:34519268). mTORC1 binds to and is inhibited by FKBP12-rapamycin (PubMed:12408816, PubMed:15066126). Forms a complex with MTOR under both leucine-rich and -poor conditions (PubMed:12408816, PubMed:25940091, PubMed:31601764, PubMed:31601708). Interacts with (via TOS motifs) EIF4EBP1 and RPS6KB1; interaction is independent of its association with MTOR (PubMed:12150925, PubMed:12150926, PubMed:12747827, PubMed:24403073). Binds preferentially to poorly or non-phosphorylated forms of EIF4EBP1, and this binding is critical to the ability of MTOR to catalyze phosphorylation (PubMed:12747827, PubMed:24403073). Interacts with ULK1 in a nutrient-dependent manner; the interaction is reduced during starvation (PubMed:19211835). Interacts with GTP-bound form of RagA/RRAGA or RagB/RRAGB and GDP-bound form of RagC/RRAGC or RagD/RRAGD, promoting recruitment of mTORC1 to the lysosomes (PubMed:31601764, PubMed:31601708). Interacts (when phosphorylated by AMPK) with 14-3-3 protein, leading to inhibition of its activity (PubMed:18439900). Interacts with SPAG5; SPAG5 competes with MTOR for RPTOR-binding, resulting in decreased mTORC1 formation (PubMed:23953116). Interacts with WAC; WAC positively regulates MTOR activity by promoting the assembly of the TTT complex composed of TELO2, TTI1 and TTI2 and the RUVBL complex composed of RUVBL1 and RUVBL2 into the TTT-RUVBL complex which leads to the dimerization of the mTORC1 complex and its subsequent activation (PubMed:26812014). Interacts with G3BP1 (PubMed:23953116). The complex formed with G3BP1 and SPAG5 is increased by o…
messages: Ubiquitinated, leading to its degradation by the proteasome (PubMed:34290272, PubMed:35927303). Deubiquitinated by OTUB1 via a non-catalytic mechanism (PubMed:35927303). Ubiquitinated by an E3 ubiquitin ligase complex containing VHL (PubMed:34290272).
messages: Widely expressed, with highest levels in nasal mucosa and pituitary and lowest in spleen.

9606:FBN3
gene id: 9606:FBN3
uniprot id: A0A494C0D8
uniprot id: A8KAY2
uniprot id: Q75N90
names: Caution
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the fibrillin family.
messages: Fibrillins are structural components of 10-12 nm extracellular calcium-binding microfibrils, which occur either in association with elastin or in elastin-free bundles. Fibrillin-containing microfibrils provide long-term force bearing structural support.
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: Predominantly expressed in connective tissues such as skeletal muscle, tendon, skin, perichondrium and periosteum. Highly expressed in fetal lung, brain, kidney. Expressed at low level in prostate, testis, mammary gland, uterus, ovary, placenta, bladder, adrenal gland, thyroid, fetal thymus, fetal liver, liver, fetal heart and heart.
messages: Probably forms intermolecular disulfide bonds either with other FBN3 molecules or with other components of the microfibrils.
messages: extracellular matrix

9606:COLEC10
gene id: 9606:COLEC10
uniprot id: Q9Y6Z7
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the COLEC10/COLEC11 family.
messages: Cytoplasm
messages: Golgi apparatus
messages: Highly expressed in liver, placenta and adrenal gland. Moderately expressed in small intestine, lung, stomach and prostate. Weakly expressed in trachea and spleen.
messages: Lectin that binds to various sugars: galactose > mannose = fucose > N-acetylglucosamine > N-acetylgalactosamine (PubMed:10224141). Acts as a chemoattractant, probably involved in the regulation of cell migration (PubMed:28301481).
messages: Secreted
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:CABP7
gene id: 9606:CABP7
uniprot id: Q86V35
names: Domain
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Cell membrane
messages: Interacts with PI4KB. This binding competes with FREQ/NCS1 binding in a calcium-dependent manner (By similarity).
messages: Negatively regulates Golgi-to-plasma membrane trafficking by interacting with PI4KB and inhibiting its activity.
messages: The C-terminal transmembrane domain (TMD) is necessary and sufficient for membrane targeting.
messages: perinuclear region
messages: trans-Golgi network membrane

9606:YIPF7
gene id: 9606:YIPF7
uniprot id: Q8N8F6
names: Caution
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the YIP1 family.
messages: Endoplasmic reticulum membrane
messages: It is uncertain whether Met-1 or Met-25 is the initiator.
messages: cis-Golgi network membrane
messages: trans-Golgi network membrane

9606:HINT2
gene id: 9606:HINT2
uniprot id: Q9BX68
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the HINT family.
messages: Exhibits adenosine 5'-monophosphoramidase activity, hydrolyzing purine nucleotide phosphoramidates with a single phosphate group such as adenosine 5'monophosphoramidate (AMP-NH2) to yield AMP and NH2 (PubMed:16762638, PubMed:31990367). Hydrolyzes adenosine 5'-O-p-nitrophenylphosphoramidate (AMP-pNA) (PubMed:16762638). Hydrolyzes fluorogenic purine nucleoside tryptamine phosphoramidates in vitro (PubMed:31990367). May be involved in steroid biosynthesis (PubMed:18653718). May play a role in apoptosis (PubMed:16762638).
messages: High expression in liver and pancreas. Expression is significantly down-regulated in hepatocellular carcinoma (HCC) patients.
messages: Mitochondrion

9606:TUBA8
gene id: 9606:TUBA8
uniprot id: Q9NY65
names: Disease Annotation
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the tubulin family.
messages: Dimer of alpha and beta chains. A typical microtubule is a hollow water-filled tube with an outer diameter of 25 nm and an inner diameter of 15 nM. Alpha-beta heterodimers associate head-to-tail to form protofilaments running lengthwise along the microtubule wall with the beta-tubulin subunit facing the microtubule plus end conferring a structural polarity. Microtubules usually have 13 protofilaments but different protofilament numbers can be found in some organisms and specialized cells.
messages: Preferentially expressed in heart, skeletal muscle and testis. Expressed at low levels in the developing brain. Expressed in megakaryocytes and platelets (PubMed:34704371).
messages: Some glutamate residues at the C-terminus are monoglycylated but not polyglycylated due to the absence of functional TTLL10 in human. Monoglycylation is mainly limited to tubulin incorporated into cilia and flagella axonemes, which is required for their stability and maintenance. Flagella glycylation controls sperm motility. Both polyglutamylation and monoglycylation can coexist on the same protein on adjacent residues, and lowering glycylation levels increases polyglutamylation, and reciprocally.
messages: Some glutamate residues at the C-terminus are polyglutamylated, resulting in polyglutamate chains on the gamma-carboxyl group (PubMed:26875866). Polyglutamylation plays a key role in microtubule severing by spastin (SPAST). SPAST preferentially recognizes and acts on microtubules decorated with short polyglutamate tails: severing activity by SPAST increases as the number of glutamates per tubulin rises from one to eight, but decreases beyond this glutamylation threshold (PubMed:26875866). Glutamylation is also involved in cilia motility (By similarity).
messages: The C-terminal phenylalanine residue is cleaved by KIAA0895L/MATCAP.
messages: The MREC motif may be critical for tubulin autoregulation.
messages: The disease may be caused by variants affecting the gene represented in this entry.
messages: This tubulin does not have a C-terminal tyrosine; however, its C-terminal phenylalanine residue can be cleaved.
messages: Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin.
messages: cytoskeleton

9606:OR6J1
gene id: 9606:OR6J1
uniprot id: Q8NGC5
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Odorant receptor.

9606:TTLL5
gene id: 9606:TTLL5
uniprot id: Q6EMB2
names: Disease Annotation
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Arg-186 is the main determinant for regioselectivity, which segregates between initiases and elongases in all tubulin--tyrosine ligase family. A glutamine residue at this position is found in elongases TTLL6, TTLL9, TTLL11, TTLL13, TTLL10 and favors glutamate-chain elongation, whereas an arginine residue is found in initiases TTLL2, TTLL4, TTLL5, TTLL3, TTLL8 and favors initiation.
messages: Belongs to the tubulin--tyrosine ligase family.
messages: Cytoplasm
messages: Expressed in the retina, found in the rod and cone photoreceptors (at protein level). Widely expressed with highest levels in heart and skeletal muscle and low levels in other tissues.
messages: Interacts with the transcriptional coactivators NCOA1/SRC-1 and NCOA2/TIF2.
messages: Nucleus
messages: Polyglutamylase which modifies tubulin, generating polyglutamate side chains on the gamma-carboxyl group of specific glutamate residues within the C-terminal tail of tubulin. Preferentially mediates ATP-dependent initiation step of the polyglutamylation reaction over the elongation step. Preferentially modifies the alpha-tubulin tail over a beta-tail (By similarity). Required for CCSAP localization to both polyglutamylated spindle and cilia microtubules (PubMed:22493317). Increases the effects of transcriptional coactivator NCOA2/TIF2 in glucocorticoid receptor-mediated repression and induction and in androgen receptor-mediated induction (PubMed:17116691).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The flexible c-MTBD (cationic microtubule binding domain) region mediates binding to microtubules. It is positively charged and becomes ordered when bound to microtubules: it interacts with a negatively charged patch on tubulin. The presence of positive charges in the c-MTBD region is essential for proper binding.
messages: cilium
messages: cilium basal body

9606:INTS3
gene id: 9606:INTS3
uniprot id: Q68E01
names: Function
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the Integrator subunit 3 family.
messages: Belongs to the multiprotein complex Integrator, at least composed of INTS1, INTS2, INTS3, INTS4, INTS5, INTS6, INTS7, INTS8, INTS9/RC74, INTS10, INTS11/CPSF3L and INTS12. Component of the SOSS complex, composed of SOSS-B (SOSS-B1/NABP2 or SOSS-B2/NABP1), SOSS-A/INTS3 and SOSS-C/INIP. SOSS complexes containing SOSS-B1/NABP2 are more abundant than complexes containing SOSS-B2/NABP1. Interacts with SOSS-B1/NABP2, SOSS-B2/NABP1 and SOSS-C/INIP; the interaction is direct. Interacts with NBN/NBS1.
messages: Component of the Integrator (INT) complex. The Integrator complex is involved in the small nuclear RNAs (snRNA) U1 and U2 transcription and in their 3'-box-dependent processing. The Integrator complex is associated with the C-terminal domain (CTD) of RNA polymerase II largest subunit (POLR2A) and is recruited to the U1 and U2 snRNAs genes (Probable). Mediates recruitment of cytoplasmic dynein to the nuclear envelope, probably as component of the INT complex (PubMed:23904267).
messages: Component of the SOSS complex, a multiprotein complex that functions downstream of the MRN complex to promote DNA repair and G2/M checkpoint. The SOSS complex associates with single-stranded DNA at DNA lesions and influences diverse endpoints in the cellular DNA damage response including cell-cycle checkpoint activation, recombinational repair and maintenance of genomic stability. The SOSS complex is required for efficient homologous recombination-dependent repair of double-strand breaks (DSBs) and ATM-dependent signaling pathways. In the SOSS complex, it is required for the assembly of the complex and for stabilization of the complex at DNA damage sites.
messages: Cytoplasm
messages: Intron retention.
messages: Nucleus

9606:KRTAP21-2
gene id: 9606:KRTAP21-2
uniprot id: Q3LI59
names: Function
names: Subunit
messages: In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.
messages: Interacts with hair keratins.

9606:TNRC6A
gene id: 9606:TNRC6A
uniprot id: Q8NDV7
names: Disease Annotation
names: Function
names: Induction
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Antibodies against TNRC6A are found in sera from patients with Sjoegren syndrome (SS), ataxia and sensor neuropathy diseases that developed autoantibodies against protein of the GWB structure. Autoantibodies were mapped to the GW-rich mid-part, the non-GW-rich region and the C-terminus of the protein.
messages: Belongs to the GW182 family.
messages: By exogenous short interfering RNA (siRNA).
messages: Interacts with AGO2 (PubMed:16284623, PubMed:16284622, PubMed:18690212, PubMed:19304925, PubMed:19324964, PubMed:19383768). Interacts with AGO1, AGO3 and AGO4 (PubMed:19324964, PubMed:19383768). Interacts with CNOT1; the interaction is direct and mediates the association with the CCR4-NOT complex (PubMed:21981923). Interacts with ZC3H12A (PubMed:26134560). Interacts with SND1 (PubMed:28546213). Interacts with GARRE1 (PubMed:29395067).
messages: P-body
messages: Plays a role in RNA-mediated gene silencing by both micro-RNAs (miRNAs) and short interfering RNAs (siRNAs). Required for miRNA-dependent repression of translation and for siRNA-dependent endonucleolytic cleavage of complementary mRNAs by argonaute family proteins. As a scaffolding protein, associates with argonaute proteins bound to partially complementary mRNAs, and can simultaneously recruit CCR4-NOT and PAN deadenylase complexes.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitous.

9606:OGDHL
gene id: 9606:OGDHL
uniprot id: Q9ULD0
names: Disease Annotation
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: 2-oxoglutarate dehydrogenase (E1-like) component of the 2-oxoglutarate dehydrogenase multienzyme complex (OGDHC) which mediates the decarboxylation of alpha-ketoglutarate in the tricarboxylic acid cycle. The OGDHC complex catalyzes the overall conversion of 2-oxoglutarate to succinyl-CoA and CO(2) while reducing NAD(+) to NADH (By similarity). The OGDHC complex is mainly active in the mitochondrion (By similarity). Involved in the inhibition of cell proliferation and in apoptosis (PubMed:23152800, PubMed:31175094).
messages: Belongs to the alpha-ketoglutarate dehydrogenase family.
messages: Expressed in the brain and the liver.
messages: Mitochondrion matrix
messages: Post-transcriptionally repressed by microRNA miR-214 in cancer cells.
messages: The OGDHC complex comprises multiple copies of three catalytic enzyme components, the 2-oxoglutarate dehydrogenase (OGDH/E1), the dihydrolipoamide dehydrogenase (DLST/E2) and the dihydrolipoamide dehydrogenase (DLD/E3). OGDHL/E1-like isoenzyme may replace OGDH in the OGDHC complex in the brain. The presence of either ODGH/E1 or ODGHL/E1-like isoenzyme in the complex may depend on its tissular distribution.
messages: The disease may be caused by variants affecting the gene represented in this entry.

9606:CNOT6L
gene id: 9606:CNOT6L
uniprot id: B4E0K8
uniprot id: Q96LI5
names: Activity Regulation
names: Cofactor
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the CCR4/nocturin family.
messages: Binds 2 magnesium ions, but the ions interact each with only 1 or 2 residues.
messages: Component of the CCR4-NOT complex; distinct complexes seem to exist that differ in the participation of probably mutually exclusive catalytic subunits; the complex contains two deadenylase subunits, CNOT6 or CNOT6L, and CNOT7 or CNOT8 (PubMed:17452450, PubMed:18377426, PubMed:19558367). Interacts with CNOT1, CNOT3, CNOT7, CNOT8 and CNOT9 (PubMed:17452450). Interacts with TOB1 (PubMed:18377426). Interacts with NANOS2 (By similarity). Interacts with ZFP36 (By similarity). Interacts with ZFP36L2 (PubMed:34611029). Interacts with RBM46 (By similarity).
messages: Cytoplasm
messages: Depletion of CNOT6L causes cell growth defect.
messages: Has 3'-5' poly(A) exoribonuclease activity for synthetic poly(A) RNA substrate. Catalytic component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. May be involved in the deadenylation-dependent degradation of mRNAs through the 3'-UTR AU-rich element-mediated mechanism. Involved in deadenylation-dependent degradation of CDKN1B mRNA. Its mRNA deadenylase activity can be inhibited by TOB1. Mediates cell proliferation and cell survival and prevents cellular senescence.
messages: Highly expressed in placenta, skeletal muscle, pancreas, testis and leukocytes. Weakly expressed in heart, spleen and thymus.
messages: Inhibited by free AMP, and with lesser efficiency also by CMP, GMP, UMP, ATP and neomycin.
messages: Nucleus

9606:DNASE1L2
gene id: 9606:DNASE1L2
uniprot id: Q92874
names: Function
names: Induction
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the DNase I family.
messages: Cytoplasm
messages: Divalent cation-dependent acid DNA endonuclease involved in the breakdown of the nucleus during corneocyte formation of epidermal keratinocytes. May play an immune role by eliminating harmful DNA released into the extracellular environment by damaged epidermal cells.
messages: Preferentially expressed in the skin and up-regulated during keratinocytes differentiation. Highly abundant (at protein level) in the stratum granulosum.
messages: Secreted
messages: Specifically expressed in peripheral blood leukocytes.
messages: Up-regulated by inflammatory cytokines.

9606:HSP90AA1
gene id: 9606:HSP90AA1
uniprot id: K9JA46
uniprot id: P07900
uniprot id: Q86SX1
names: Activity Regulation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Interacts with N.meningitidis serogroup B adhesin A (nadA). Interaction is stabilized by ADP and 17-AAG (17-N-allylamino-17-demethoxygeldanamycin) and inhibited by ATP. Decreasing HSP90 levels increases adhesion and entry of bacterial into human Chang cells; increasing its levels leads to decreased adhseion and invasion.
messages: (Microbial infection) Interacts with herpes simplex virus 1 protein US11; this interaction inhibits TBK1-induced interferon production.
messages: (Microbial infection) Seems to interfere with N.meningitidis NadA-mediated invasion of human cells. Decreasing HSP90 levels increases adhesion and entry of E.coli expressing NadA into human Chang cells; increasing its levels leads to decreased adhesion and invasion.
messages: Belongs to the heat shock protein 90 family.
messages: Cell membrane
messages: Cytoplasm
messages: Homodimer (PubMed:7588731, PubMed:8289821, PubMed:18400751, PubMed:29127155). Identified in NR3C1/GCR steroid receptor-chaperone complexes formed at least by NR3C1, HSP90AA1 and a variety of proteins containing TPR repeats such as FKBP4, FKBP5, PPID, PPP5C or STIP1 (PubMed:15383005, PubMed:9195923). Forms a complex containing HSP90AA1, TSC1 and TSC2; TSC1 is required to recruit TCS2 to the complex (PubMed:29127155). The closed form interacts (via the middle domain and TPR repeat-binding motif) with co-chaperone TSC1 (via C-terminus) (PubMed:29127155). Interacts with TOM34 (PubMed:9660753). Interacts with TERT; the interaction, together with PTGES3, is required for correct assembly and stabilization of the TERT holoenzyme complex (PubMed:11274138, PubMed:9817749). Interacts with CHORDC1 and DNAJC7 (PubMed:12853476, PubMed:19875381). Interacts with STUB1 and UBE2N; may couple the chaperone and ubiquitination systems (PubMed:16307917, PubMed:27353360). Interacts (via TPR repeat-binding motif) with PPP5C (via TPR repeats); the interaction is direct and activates PPP5C phosphatase activity (PubMed:15383005, PubMed:15577939, PubMed:16531226, PubMed:27353360). Following LPS binding, may form a complex with CXCR4, GDF5 and HSPA8 (PubMed:11276205). Interacts with KSR1 (PubMed:10409742). Interacts with co-chaperone CDC37 (via C-terminus); the interaction inhibits HSP90AA1 ATPase activity (PubMed:23569206, PubMed:27353360). May interact with NWD1 (PubMed:24681825). Interacts with FNIP1 and FNIP2; the interaction inhibits HSP90AA1 ATPase activity (PubMed:17028174, PubMed:27353360). Interacts with co-chaperone AHSA1 (phosphorylated on 'Tyr-223'); the interaction activates HSP90AA1 ATPase activity and results in the dissociation of TSC1 from HSP90AA1 (PubMed:12604615, PubMed:27353360, PubMed:29127155). Interacts with FLCN in the presence of FNIP1 (PubMed:27353360). Interacts with HSP70, STIP1 and PTGES3 (PubMed:27353360). Interacts with SMYD3; this interaction enhances SMYD3 hist…
messages: ISGylated.
messages: In the resting state, through the dimerization of its C-terminal domain, HSP90 forms a homodimer which is defined as the open conformation (PubMed:18400751). Upon ATP-binding, the N-terminal domain undergoes significant conformational changes and comes in contact to form an active closed conformation (PubMed:18400751). After HSP90 finishes its chaperoning tasks of assisting the proper folding, stabilization and activation of client proteins under the active state, ATP molecule is hydrolyzed to ADP which then dissociates from HSP90 and directs the protein back to the resting state (PubMed:18400751). Co-chaperone TSC1 promotes ATP binding and inhibits HSP90AA1 ATPase activity (PubMed:29127155). Binding to phosphorylated AHSA1 promotes HSP90AA1 ATPase activity (PubMed:29127155). Inhibited by geldanamycin, Ganetespib (STA-9090) and SNX-2112 (PubMed:29127155, PubMed:12526792).
messages: Melanosome
messages: Mitochondrion
messages: Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity which is essential for its chaperone activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function (PubMed:11274138, PubMed:15577939, PubMed:15937123, PubMed:27353360, PubMed:29127155, PubMed:12526792). Engages with a range of client protein classes via its interaction with various co-chaperone proteins or complexes, that act as adapters, simultaneously able to interact with the specific client and the central chaperone itself (PubMed:29127155). Recruitment of ATP and co-chaperone followed by client protein forms a functional chaperone. After the completion of the chaperoning process, properly folded client protein and co-chaperone leave HSP90 in an ADP-bound partially open conformation and finally, ADP is released from HSP90 which acquires an open conformation for the next cycle (PubMed:27295069, PubMed:26991466). Plays a critical role in mitochondrial import, delivers preproteins to the mitochondrial import receptor TOMM70 (PubMed:12526792). Apart from its chaperone activity, it also plays a role in the regulation of the transcription machinery. HSP90 and its co-chaperones modulate transcription at least at three different levels (PubMed:25973397). In the first place, they alter the steady-state levels of certain transcription factors in response to various physiological cues(PubMed:25973397). Second, they modulate the activity of certain epigenetic modifiers, such as histone deacetylases or DNA methyl transferases, and thereby respond to the change in the environment (PubMed:25973397). Third, they participate in the eviction of h…
messages: Nucleus
messages: S-nitrosylated; negatively regulates the ATPase activity and the activation of eNOS by HSP90AA1.
messages: The TPR repeat-binding motif mediates interaction with TPR repeat-containing proteins like the co-chaperone STUB1.
messages: Ubiquitinated via 'Lys-63'-linked polyubiquitination by HECTD1. Ubiquitination promotes translocation into the cytoplasm away from the membrane and secretory pathways.

9606:PPP3R2
gene id: 9606:PPP3R2
uniprot id: Q96LZ3
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the calcineurin regulatory subunit family.
messages: Forms a complex composed of a calmodulin-dependent catalytic subunit (also known as calcineurin A) and a regulatory Ca(2+)-binding subunit (also known as calcineurin B). There are three catalytic subunits, each encoded by a separate gene (PPP3CA, PPP3CB, and PPP3CC) and two regulatory subunits which are also encoded by separate genes (PPP3R1 and PPP3R2) (By similarity). Interacts with SPATA33 (via PQIIIT motif) (PubMed:34446558).
messages: Mitochondrion
messages: Regulatory subunit of calcineurin, a calcium-dependent, calmodulin stimulated protein phosphatase. Confers calcium sensitivity.
messages: Testis-specific.
messages: This protein has four functional calcium-binding sites.

9606:ALLC
gene id: 9606:ALLC
uniprot id: Q8N6M5
names: Function
names: Polymorphism
names: Similarity
messages: Belongs to the allantoicase family.
messages: Product of a polymorphic gene which also produces a longer 410-residue protein due to a polymorphism which affects Met-1, resulting in a longer protein starting at an upstream Met.
messages: The function of this enzyme is unclear as allantoicase activity is not known to exist in mammals.

9606:PRAMEF8
gene id: 9606:PRAMEF8
uniprot id: Q5VWM4
names: Similarity
messages: Belongs to the PRAME family.

9606:ZHX1
gene id: 9606:ZHX1
uniprot id: Q9UKY1
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acts as a transcriptional repressor. Increases DNMT3B-mediated repressive transcriptional activity when DNMT3B is tethered to DNA. May link molecule between DNMT3B and other co-repressor proteins.
messages: Belongs to the ZHX family.
messages: Forms homodimers. Heterodimer (via HD1 domain) with ZHX2 (via HD1 domain). Also forms a heterodimer with ZHX3 which is a prerequisite for repressor activity. Interacts with ATF7IP and NFYA. Interacts (via homeobox domains) with DNMT3B (via PWWP domain).
messages: Nucleus
messages: Ubiquitously expressed. Expressed in podocytes.

9606:APOBEC1
gene id: 9606:APOBEC1
uniprot id: P41238
names: Cofactor
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the cytidine and deoxycytidylate deaminase family.
messages: Binds 1 Zn(2+) ion per subunit.
messages: Cytidine deaminase catalyzing the cytidine to uridine postranscriptional editing of a variety of mRNAs (PubMed:30844405). Form complexes with cofactors that confer differential editing activity and selectivity. Responsible for the postranscriptional editing of a CAA codon for Gln to a UAA codon for stop in the apolipoprotein B mRNA (PubMed:24916387). Also involved in CGA (Arg) to UGA (Stop) editing in the NF1 mRNA (PubMed:11727199). May also play a role in the epigenetic regulation of gene expression by participating in DNA demethylation (By similarity).
messages: Cytoplasm
messages: Expressed exclusively in the small intestine.
messages: Homodimer (PubMed:8078915). Interacts with A1CF; form an mRNA editing complex (PubMed:30844405). Interacts with RBM47; form an mRNA editing complex (PubMed:24916387, PubMed:30844405). Found in a complex with CELF2/CUGBP2 and A1CF. Interacts with HNRPAB (PubMed:8999813). Interacts with SYNCRIP (PubMed:11352648).
messages: Nucleus

9606:SLC22A17
gene id: 9606:SLC22A17
uniprot id: Q8WUG5
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family.
messages: Cell membrane
messages: Cell surface receptor for LCN2 (24p3) that plays a key role in iron homeostasis and transport. Able to bind iron-bound LCN2 (holo-24p3), followed by internalization of holo-24p3 and release of iron, thereby increasing intracellular iron concentration and leading to inhibition of apoptosis. Also binds iron-free LCN2 (apo-24p3), followed by internalization of apo-24p3 and its association with an intracellular siderophore, leading to iron chelation and iron transfer to the extracellular medium, thereby reducing intracellular iron concentration and resulting in apoptosis (By similarity).
messages: Expressed in brain.
messages: Expression is activated by RUNX3. Repressed by the oncoprotein BCR-ABL; BCR-ABL misregulates expression by inducing a switch in binding from RUNX3 to RUNX1, a repressor of 24p3R expression, through a Ras signaling pathway.
messages: Vacuole membrane

9606:FZD9
gene id: 9606:FZD9
uniprot id: O00144
names: Caution
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Authors show that FZD9 is responsible for the cellular phenotype found in neural progenitor cells (NPCs) derived from Williams syndrome patients namely increased apoptosis of neural progenitor cells (NPCs).
messages: Belongs to the G-protein coupled receptor Fz/Smo family.
messages: Cell membrane
messages: Expressed predominantly in adult and fetal brain, testis, eye, skeletal muscle and kidney. Moderately expressed in pancreas, thyroid, adrenal cortex, small intestine and stomach. Detected in fetal liver and kidney. Expressed in neural progenitor cells (PubMed:27509850).
messages: Has been first described as FZD3 in literature.
messages: Lys-Thr-X-X-X-Trp motif interacts with the PDZ domain of Dvl (Disheveled) family members and is involved in the activation of the Wnt/beta-catenin signaling pathway.
messages: Receptor for WNT2 that is coupled to the beta-catenin canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes (By similarity). Plays a role in neuromuscular junction (NMJ) assembly by negatively regulating the clustering of acetylcholine receptors (AChR) through the beta-catenin canonical signaling pathway (By similarity). May play a role in neural progenitor cells (NPCs) viability through the beta-catenin canonical signaling pathway by negatively regulating cell cycle arrest leading to inhibition of neuron apoptotic process (PubMed:27509850). During hippocampal development, regulates neuroblast proliferation and apoptotic cell death. Controls bone formation through non canonical Wnt signaling mediated via ISG15. Positively regulates bone regeneration through non canonical Wnt signaling (By similarity).
messages: The FZ domain is involved in binding with Wnt ligands.
messages: Ubiquitinated by ZNRF3, leading to its degradation by the proteasome.

9606:ARID1B
gene id: 9606:ARID1B
uniprot id: Q8NFD5
names: Disease Annotation
names: Function
names: Miscellaneous
names: Polymorphism
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Component of SWI/SNF chromatin remodeling complexes, in some of which it can be mutually exclusive with ARID1B/BAF250B (PubMed:12672490, PubMed:22952240, PubMed:26601204, PubMed:12200431, PubMed:11988099, PubMed:15170388). The canonical complex contains a catalytic subunit (either SMARCA4/BRG1/BAF190A or SMARCA2/BRM/BAF190B) and at least SMARCE1, ACTL6A/BAF53, SMARCC1/BAF155, SMARCC2/BAF170, and SMARCB1/SNF5/BAF47. Other subunits specific to each of the complexes may also be present permitting several possible combinations developmentally and tissue specific (PubMed:11734557, PubMed:22952240, PubMed:26601204). Component of the BAF (SWI/SNF-A) complex, which includes at least actin (ACTB), ARID1A/BAF250A, ARID1B/BAF250B, SMARCA2/BRM, SMARCA4/BRG1/BAF190A, ACTL6A/BAF53, ACTL6B/BAF53B, SMARCE1/BAF57, SMARCC1/BAF155, SMARCC2/BAF170, SMARCB1/SNF5/INI1, and one or more SMARCD1/BAF60A, SMARCD2/BAF60B, or SMARCD3/BAF60C (PubMed:18765789). In muscle cells, the BAF complex also contains DPF3. Component of neural progenitors-specific chromatin remodeling complex (npBAF complex) composed of at least, ARID1A/BAF250A or ARID1B/BAF250B, SMARCD1/BAF60A, SMARCD3/BAF60C, SMARCA2/BRM/BAF190B, SMARCA4/BRG1/BAF190A, SMARCB1/BAF47, SMARCC1/BAF155, SMARCE1/BAF57, SMARCC2/BAF170, PHF10/BAF45A, ACTL6A/BAF53A and actin. Component of neuron-specific chromatin remodeling complex (nBAF complex) composed of at least, ARID1A/BAF250A or ARID1B/BAF250B, SMARCD1/BAF60A, SMARCD3/BAF60C, SMARCA2/BRM/BAF190B, SMARCA4/BRG1/BAF190A, SMARCB1/BAF47, SMARCC1/BAF155, SMARCE1/BAF57, SMARCC2/BAF170, DPF1/BAF45B, DPF3/BAF45C, ACTL6B/BAF53B and actin (By similarity). Component of a SWI/SNF-like EBAFb complex, at least composed of SMARCA4/BRG1/BAF190A, SMARCB1/BAF47/SNF5, ACTL6A/BAF53A, SMARCE1/BAF57, SMARCD1/BAF60A, SMARCD2/BAF60B, SMARCC1/BAF155, SMARCC2/BAF170, ARID1B/BAF250B, MLLT1/ENL and actin (PubMed:12665591). Interacts through its C-terminus with SMARCA2/BRM/BAF190B and SMARCA4/BRG1/BAF190A (PubMed:12200…
messages: Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex). During neural development a switch from a stem/progenitor to a postmitotic chromatin remodeling mechanism occurs as neurons exit the cell cycle and become committed to their adult state. The transition from proliferating neural stem/progenitor cells to postmitotic neurons requires a switch in subunit composition of the npBAF and nBAF complexes. As neural progenitors exit mitosis and differentiate into neurons, npBAF complexes which contain ACTL6A/BAF53A and PHF10/BAF45A, are exchanged for homologous alternative ACTL6B/BAF53B and DPF1/BAF45B or DPF3/BAF45C subunits in neuron-specific complexes (nBAF). The npBAF complex is essential for the self-renewal/proliferative capacity of the multipotent neural stem cells. The nBAF complex along with CREST plays a role regulating the activity of genes essential for dendrite growth (By similarity). Binds DNA non-specifically (PubMed:14982958, PubMed:15170388).
messages: Nucleus
messages: Produced by alternative initiation at Met-84 of isoform 5.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The poly-Gln region is polymorphic and the number of Gln varies in the population (from 17 to 23).
messages: Widely expressed with high levels in heart, skeletal muscle and kidney.

9606:ZC3H7A
gene id: 9606:ZC3H7A
uniprot id: Q8IWR0
names: Function
names: Subcellular Location Annotation
messages: May be a specific regulator of miRNA biogenesis. Binds to microRNAs MIR7-1, MIR16-2 and MIR29A hairpins recognizing the 3'-ATA(A/T)-5' motif in the apical loop.
messages: Nucleus

9606:ERRFI1
gene id: 9606:ERRFI1
uniprot id: B3KTV8
uniprot id: I6S2Y9
uniprot id: Q9UJM3
names: Domain
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the MIG6 family.
messages: Cell membrane
messages: Cytoplasm
messages: Interacts with ERBB2 (By similarity). Interacts with EGFR.
messages: Levels are very low in quiescent cells. Up-regulated by mitogens.
messages: Membrane
messages: Negative regulator of EGFR signaling in skin morphogenesis. Acts as a negative regulator for several EGFR family members, including ERBB2, ERBB3 and ERBB4. Inhibits EGFR catalytic activity by interfering with its dimerization. Inhibits autophosphorylation of EGFR, ERBB2 and ERBB4. Important for normal keratinocyte proliferation and differentiation. Plays a role in modulating the response to steroid hormones in the uterus. Required for normal response to progesterone in the uterus and for fertility. Mediates epithelial estrogen responses in the uterus by regulating ESR1 levels and activation. Important for regulation of endometrium cell proliferation. Important for normal prenatal and perinatal lung development (By similarity).
messages: Nucleus
messages: The EGFR-binding region prevents binding of a cyclin-like activator to the EGFR kinase domain, and thereby keeps EGFR in an inactive conformation. Also maintains EGFR in an inactive conformation by preventing formation of an asymmetric homodimer.

9606:KIFC1
gene id: 9606:KIFC1
uniprot id: A0A024RCS7
uniprot id: Q9BW19
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family.
messages: Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. NCD subfamily.
messages: Binds NUBP1 and NUBP2. Interacts with PPP1R42 (By similarity).
messages: Early endosome
messages: HeLa cells lacking KIFC1 show multipolar mitotic spindles and a defect in chromosome congression and chromosome alignment during mitosis.
messages: Minus end-directed microtubule-dependent motor required for bipolar spindle formation (PubMed:15843429). May contribute to movement of early endocytic vesicles (By similarity). Regulates cilium formation and structure (By similarity).
messages: Nucleus
messages: centrosome
messages: spindle

9606:NDUFAF8
gene id: 9606:NDUFAF8
uniprot id: A1L188
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Interacts with NDUFAF5.
messages: Involved in the assembly of mitochondrial NADH:ubiquinone oxidoreductase complex (complex I, MT-ND1) (PubMed:27499296). Required to stabilize NDUFAF5 (PubMed:27499296).
messages: Mitochondrion
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:NNAT
gene id: 9606:NNAT
uniprot id: A0A3B3ITN5
uniprot id: Q16517
names: Developmental Stage
names: Function
names: Similarity
messages: Abundant in 18-24 week old fetal brain. Postnatally its expression decline and only minimal levels were present in adulthood.
messages: Belongs to the neuronatin family.
messages: May participate in the maintenance of segment identity in the hindbrain and pituitary development, and maturation or maintenance of the overall structure of the nervous system. May function as a regulatory subunit of ion channels.

9606:RANBP3
gene id: 9606:RANBP3
uniprot id: Q9H6Z4
names: Function
names: Sequence Caution
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Aberrant splicing.
messages: Acts as a cofactor for XPO1/CRM1-mediated nuclear export, perhaps as export complex scaffolding protein. Bound to XPO1/CRM1, stabilizes the XPO1/CRM1-cargo interaction. In the absence of Ran-bound GTP prevents binding of XPO1/CRM1 to the nuclear pore complex. Binds to CHC1/RCC1 and increases the guanine nucleotide exchange activity of CHC1/RCC1. Recruits XPO1/CRM1 to CHC1/RCC1 in a Ran-dependent manner. Negative regulator of TGF-beta signaling through interaction with the R-SMAD proteins, SMAD2 and SMAD3, and mediating their nuclear export.
messages: Cytoplasm
messages: Interacts with CHC1 in a Ran-stimulated manner. Interacts with XPO1. Interacts (via its C-terminal R domain) with SMAD2 (dephosphorylated form via its MH1 and MH2 domains); the interaction results in the nuclear export of SMAD2 and termination of the TGF-beta signaling. Interacts (via its C-terminal R domain) with SMAD3 (dephosphorylated form via its MH1 domain); the interaction results in the nuclear export of SMAD3 and termination of the TGF-beta signaling.
messages: Nucleus
messages: Widely expressed with high levels in testis and heart.

9606:MCL1
gene id: 9606:MCL1
uniprot id: A0A087WT64
uniprot id: C8YZ26
uniprot id: Q07820
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the Bcl-2 family.
messages: Cleaved by CASP3 during apoptosis. In intact cells cleavage occurs preferentially after Asp-127, yielding a pro-apoptotic 28 kDa C-terminal fragment.
messages: Cytoplasm
messages: Expression increases early during phorbol ester-induced differentiation along the monocyte/macrophage pathway in myeloid leukemia cell line ML-1. Rapidly up-regulated by CSF2 in ML-1 cells. Up-regulated by heat shock-induced differentiation. Expression increases early during retinoic acid-induced differentiation.
messages: Interacts with HIF3A (via C-terminus domain) (By similarity). Interacts with BAD, BOK, BIK and BMF (By similarity). Interacts with PMAIP1 (PubMed:17389404). Interacts with BBC3 (By similarity). Isoform 1 interacts with BAX, BAK1 and TPT1 (PubMed:10837489, PubMed:12149273, PubMed:15077116). Heterodimer of isoform 1 and isoform 2. Homodimers of isoform 1 or isoform 2 are not detected. Isoform 2 does not interact with pro-apoptotic BCL2-related proteins (PubMed:10837489). Interacts with RTL10/BOP (PubMed:23055042). Interacts with BCL2L11; may sequester BCL2L11 to prevent its pro-apoptotic activity (PubMed:10837489, PubMed:27013495, PubMed:17389404, PubMed:20562877). Interacts with GIMAP5 and HSPA8/HSC70; the interaction between HSPA8 and MCL1 is impaired in the absence of GIMAP5 (By similarity).
messages: Involved in the regulation of apoptosis versus cell survival, and in the maintenance of viability but not of proliferation. Mediates its effects by interactions with a number of other regulators of apoptosis. Isoform 1 inhibits apoptosis. Isoform 2 promotes apoptosis.
messages: Membrane
messages: Mitochondrion
messages: Phosphorylated on Ser-159, by GSK3, in response to IL3/interleukin-3 withdrawal. Phosphorylation at Ser-159 induces ubiquitination and proteasomal degradation, abrogating the anti-apoptotic activity. Treatment with taxol or okadaic acid induces phosphorylation on additional sites.
messages: Rapidly degraded in the absence of phosphorylation on Thr-163 in the PEST region.
messages: Ubiquitinated. Ubiquitination is induced by phosphorylation at Ser-159 (PubMed:16543145). Deubiquitinated by USP20; leading to increased stability (PubMed:35063767).
messages: nucleoplasm

9606:LXN
gene id: 9606:LXN
uniprot id: Q9BS40
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the protease inhibitor I47 (latexin) family.
messages: Cytoplasm
messages: Hardly reversible, non-competitive, and potent inhibitor of CPA1, CPA2 and CPA4. May play a role in inflammation.
messages: Highly expressed in heart, prostate, ovary, kidney, pancreas, and colon, moderate or low in other tissues including brain.

9606:ABI2
gene id: 9606:ABI2
uniprot id: A0A0C4DG21
uniprot id: A0A7D9NKC8
uniprot id: B7Z836
uniprot id: Q9NYB9
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts with human cytomegalovirus UL135.
messages: Belongs to the ABI family.
messages: Component of the WAVE complex composed of ABI2, CYFIP1 or CYFIP2, BRK1, NCKAP1 and WASF1/WAVE1. Within the complex, a heterodimer containing NCKAP1 and CYFIP1 interacts with a heterotrimer formed by WAVE1, ABI2 and BRK1. CYFIP2 binds to activated RAC1 which causes the complex to dissociate, releasing activated WASF1 (PubMed:21107423). Interacts (via SH3 domain) with ABL1 and ABL2 (PubMed:7590236, PubMed:8649853).
messages: Cytoplasm
messages: Nucleus
messages: Phosphorylated by ABL1.
messages: Regulator of actin cytoskeleton dynamics underlying cell motility and adhesion. Functions as a component of the WAVE complex, which activates actin nucleating machinery Arp2/3 to drive lamellipodia formation (PubMed:21107423). Acts as regulator and substrate of nonreceptor tyrosine kinases ABL1 and ABL2 involved in processes linked to cell growth and differentiation. Positively regulates ABL1-mediated phosphorylation of ENAH, which is required for proper polymerization of nucleated actin filaments at the leading edge (PubMed:7590236, PubMed:8649853, PubMed:10498863). Contributes to the regulation of actin assembly at the tips of neuron projections. In particular, controls dendritic spine morphogenesis and may promote dendritic spine specification toward large mushroom-type spines known as repositories of memory in the brain (By similarity). In hippocampal neurons, may mediate actin-dependent BDNF-NTRK2 early endocytic trafficking that triggers dendrite outgrowth (By similarity). Participates in ocular lens morphogenesis, likely by regulating lamellipodia-driven adherens junction formation at the epithelial cell-secondary lens fiber interface (By similarity). Also required for nascent adherens junction assembly in epithelial cells (PubMed:15572692).
messages: The SH3 domain is critical for binding to ABL1 and ABL2.
messages: Widely expressed. Abundant in testes, ovary, thymus, and colon, with lower but detectable levels in prostate, peripheral blood leukocytes, and spleen.
messages: adherens junction
messages: cytoskeleton
messages: filopodium
messages: lamellipodium

9606:PPP1R14B
gene id: 9606:PPP1R14B
uniprot id: Q96C90
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the PP1 inhibitor family.
messages: Cytoplasm
messages: Inhibitor of PPP1CA. Has over 50-fold higher inhibitory activity when phosphorylated (By similarity).
messages: Phosphorylated primarily on Thr-57 by PKC (in vitro). An unknown Ser is also phosphorylated by PKC (in vitro) (By similarity).
messages: Ubiquitous. Expressed at low levels.

9606:C4BPB
gene id: 9606:C4BPB
uniprot id: P20851
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Controls the classical pathway of complement activation. It binds as a cofactor to C3b/C4b inactivator (C3bINA), which then hydrolyzes the complement fragment C4b. It also accelerates the degradation of the C4bC2a complex (C3 convertase) by dissociating the complement fragment C2a. It also interacts with anticoagulant protein S and with serum amyloid P component. The beta chain binds protein S.
messages: Disulfide-linked complex of alpha and beta chains of 3 possible sorts: a 570 kDa complex of 7 alpha chains and 1 beta chain, a 530 kDa homoheptamer of alpha chains or a 500 kDa complex of 6 alpha chains and 1 beta chain. The central body of the alpha chain homomer supports tentacles, each with the binding site for C4b at the end.
messages: Secreted

9606:NEURL2
gene id: 9606:NEURL2
uniprot id: Q9BR09
names: Domain
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cytoplasm
messages: Expressed specifically in skeletal and cardiac muscles.
messages: Plays an important role in the process of myofiber differentiation and maturation. Probable substrate-recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex, which mediates the ubiquitination of proteins. Probably contributes to catalysis through recognition and positioning of the substrate and the ubiquitin-conjugating enzyme. During myogenesis, controls the ubiquitination and degradation of the specific pool of CTNNB1/beta-catenin located at the sarcolemma (By similarity).
messages: Probable component the ECS(NEURL2) E3 ubiquitin-protein ligase complex consisting of ELOB/Elongin B, ELOC/Elongin C, CUL5, RBX1 and NEURL2. Interacts with CTNNB1 (By similarity).
messages: The SOCS domain mediates the interaction with ELOB and ELOC, while the NHR domain may be involved in ubiquitination substrate binding.

9606:ZNF394
gene id: 9606:ZNF394
uniprot id: Q53GI3
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:KLK12
gene id: 9606:KLK12
uniprot id: Q9UKR0
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the peptidase S1 family. Kallikrein subfamily.
messages: Secreted

9606:SMAD3
gene id: 9606:SMAD3
uniprot id: P84022
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Interacts with SARS-CoV nucleoprotein.
messages: Acetylation in the nucleus by EP300 in the MH2 domain regulates positively its transcriptional activity and is enhanced by TGF-beta.
messages: Belongs to the dwarfin/SMAD family.
messages: Cytoplasm
messages: Monomer; in the absence of TGF-beta (PubMed:9670020). Homooligomer; in the presence of TGF-beta (PubMed:9670020). Heterotrimer; forms a heterotrimer in the presence of TGF-beta consisting of two molecules of C-terminally phosphorylated SMAD2 or SMAD3 and one of SMAD4 to form the transcriptionally active SMAD2/SMAD3-SMAD4 complex (PubMed:9670020, PubMed:11224571, PubMed:15799969, PubMed:15350224). Part of a complex consisting of MAGI2/ARIP1, ACVR2A, ACVR1B and SMAD3 (PubMed:9892009). Forms a complex with SMAD2 and TRIM33 upon addition of TGF-beta (PubMed:16751102). Found in a complex composed of SMAD3, RAN and XPO4; within the complex interacts directly with XPO4 (PubMed:16449645). Component of the multimeric complex SMAD3/SMAD4/JUN/FOS which forms at the AP1 promoter site; required for synergistic transcriptional activity in response to TGF-beta (PubMed:9732876, PubMed:10995748). Part of a ternary complex composed of SMAD3, ITCH/AIP4 and NEDD9/HEF1; within the complex NEDD9/HEF1 interacts (via N-terminus) with ITCH/AIP4; the complex mediates ubiquitination and proteasomal degradation of NEDD9/HEF1 (PubMed:15051726). Interacts with NEDD9; the interaction promotes NEDD9 ubiquitination and proteasomal degradation (PubMed:15051726). Interacts (via an N-terminal domain) with JUN (via its basic DNA binding and leucine zipper domains); this interaction is essential for DNA binding and cooperative transcriptional activity in response to TGF-beta (PubMed:9732876, PubMed:10995748). Identified in a complex that contains at least ZNF451, SMAD2, SMAD3 and SMAD4 (PubMed:24324267). Interacts with PPM1A; the interaction dephosphorylates SMAD3 in the C-terminal SXS motif leading to disruption of the SMAD2/3-SMAD4 complex, nuclear export and termination of TGF-beta signaling (PubMed:16751101). Interacts (via MH2 domain) with ZMIZ1 (via SP-RING-type domain); in the TGF-beta signaling pathway increases the activity of the SMAD3/SMAD4 transcriptional complex (PubMed:16777850). Interacts…
messages: Nucleus
messages: Phosphorylated on serine and threonine residues. Enhanced phosphorylation in the linker region on Thr-179, Ser-204 and Ser-208 on EGF and TGF-beta treatment. Ser-208 is the main site of MAPK-mediated phosphorylation. CDK-mediated phosphorylation occurs in a cell-cycle dependent manner and inhibits both the transcriptional activity and antiproliferative functions of SMAD3. This phosphorylation is inhibited by flavopiridol. Maximum phosphorylation at the G(1)/S junction. Also phosphorylated on serine residues in the C-terminal SXS motif by TGFBR1 and ACVR1. TGFBR1-mediated phosphorylation at these C-terminal sites is required for interaction with SMAD4, nuclear location and transactivational activity, and appears to be a prerequisite for the TGF-beta mediated phosphorylation in the linker region. Dephosphorylated in the C-terminal SXS motif by PPM1A. This dephosphorylation disrupts the interaction with SMAD4, promotes nuclear export and terminates TGF-beta-mediated signaling. Phosphorylation at Ser-418 by CSNK1G2/CK1 promotes ligand-dependent ubiquitination and subsequent proteasome degradation, thus inhibiting SMAD3-mediated TGF-beta responses. Phosphorylated by PDPK1.
messages: Poly-ADP-ribosylated by PARP1 and PARP2. ADP-ribosylation negatively regulates SMAD3 transcriptional responses during the course of TGF-beta signaling.
messages: Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases. Binds the TRE element in the promoter region of many genes that are regulated by TGF-beta and, on formation of the SMAD3/SMAD4 complex, activates transcription. Also can form a SMAD3/SMAD4/JUN/FOS complex at the AP-1/SMAD site to regulate TGF-beta-mediated transcription. Has an inhibitory effect on wound healing probably by modulating both growth and migration of primary keratinocytes and by altering the TGF-mediated chemotaxis of monocytes. This effect on wound healing appears to be hormone-sensitive. Regulator of chondrogenesis and osteogenesis and inhibits early healing of bone fractures. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator.
messages: The MH1 domain is required for DNA binding. Also binds zinc ions which are necessary for the DNA binding.
messages: The MH2 domain is required for both homomeric and heteromeric interactions and for transcriptional regulation. Sufficient for nuclear import.
messages: The disease is caused by variants affecting the gene represented in this entry. SMAD3 mutations have been reported to be also associated with thoracic aortic aneurysms and dissection (TAAD) (PubMed:21778426). This phenotype is distinguised from LDS3 by having aneurysms restricted to thoracic aorta. As individuals carrying these mutations also exhibit aneurysms of other arteries, including abdominal aorta, iliac, and/or intracranial arteries (PubMed:21778426), they have been classified as LDS3 by the OMIM resource.
messages: The disease may be caused by variants affecting the gene represented in this entry.
messages: The linker region is required for the TGFbeta-mediated transcriptional activity and acts synergistically with the MH2 domain.
messages: Ubiquitinated. Monoubiquitinated, leading to prevent DNA-binding (PubMed:21947082). Deubiquitination by USP15 alleviates inhibition and promotes activation of TGF-beta target genes (PubMed:21947082). Ubiquitinated by RNF111, leading to its degradation: only SMAD3 proteins that are 'in use' are targeted by RNF111, RNF111 playing a key role in activating SMAD3 and regulating its turnover (By similarity). Undergoes STUB1-mediated ubiquitination and degradation (PubMed:24613385).

9606:MYOF
gene id: 9606:MYOF
uniprot id: Q9NZM1
names: Cofactor
names: Disease Annotation
names: Domain
names: Function
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the ferlin family.
messages: Binds Ca(2+). The ions are bound to the C2 1 domain.
messages: Calcium/phospholipid-binding protein that plays a role in the plasmalemma repair mechanism of endothelial cells that permits rapid resealing of membranes disrupted by mechanical stress. Involved in endocytic recycling. Implicated in VEGF signal transduction by regulating the levels of the receptor KDR (By similarity).
messages: Cell membrane
messages: Contaminating sequence. Potential poly-A sequence.
messages: Cytoplasmic vesicle membrane
messages: Expressed in myoblast and endothelial cells (at protein level). Highly expressed in cardiac and skeletal muscles. Also present in lung, and at very low levels in kidney, placenta and brain.
messages: Interacts with DNM2 and KDR. Interacts with EHD1 (By similarity). Interacts with EHD2; the interaction is direct (PubMed:18502764). Interacts with RIPOR2 (PubMed:24687993).
messages: Nucleus membrane
messages: The C2 domain 1 associates with lipid membranes in a calcium-dependent manner.
messages: The disease may be caused by variants affecting the gene represented in this entry.

9606:CCR7
gene id: 9606:CCR7
uniprot id: A0N0Q0
uniprot id: J3KSS9
uniprot id: P32248
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor 1 family.
messages: By Epstein-Barr virus (EBV).
messages: Cell membrane
messages: Expressed in various lymphoid tissues and activated B- and T-lymphocytes, strongly up-regulated in B-cells infected with Epstein-Barr virus and T-cells infected with herpesvirus 6 or 7.
messages: Receptor for the MIP-3-beta chemokine. Probable mediator of EBV effects on B-lymphocytes or of normal lymphocyte functions.

9606:CACNA1S
gene id: 9606:CACNA1S
uniprot id: B1ALM3
uniprot id: Q13698
names: Activity Regulation
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family.
messages: Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family. CACNA1S subfamily.
messages: Channel activity is blocked by dihydropyridines (DHP), phenylalkylamines, and by benzothiazepines.
messages: Component of a calcium channel complex consisting of a pore-forming alpha subunit (CACNA1S) and the ancillary subunits CACNB1 or CACNB2, CACNG1 and CACNA2D1. The channel complex contains alpha, beta, gamma and delta subunits in a 1:1:1:1 ratio, i.e. it contains either CACNB1 or CACNB2 (By similarity). CACNA1S channel activity is modulated by the auxiliary subunits (CACNB1 or CACNB2, CACNG1 and CACNA2D1). Interacts with DYSF and JSRP1 (By similarity). Interacts with RYR1 (By similarity). Interacts with STAC, STAC2 and STAC3 (via their SH3 domains) (PubMed:29078335). Interacts with CALM (PubMed:19473981).
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry.
messages: Each of the four internal repeats contains five hydrophobic transmembrane segments (S1, S2, S3, S5, S6) and one positively charged transmembrane segment (S4). S4 segments probably represent the voltage-sensor and are characterized by a series of positively charged amino acids at every third position.
messages: Membrane
messages: Phosphorylated. Phosphorylation by PKA activates the calcium channel. Both the minor and major forms are phosphorylated in vitro by PKA. Phosphorylation at Ser-1575 is involved in beta-adrenergic-mediated regulation of the channel.
messages: Pore-forming, alpha-1S subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents in skeletal muscle. Calcium channels containing the alpha-1S subunit play an important role in excitation-contraction coupling in skeletal muscle via their interaction with RYR1, which triggers Ca(2+) release from the sarcoplasmic reticulum and ultimately results in muscle contraction. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group.
messages: Skeletal muscle specific.
messages: T-tubule
messages: The alpha-1S subunit is found in two isoforms in the skeletal muscle: a minor form of 212 kDa containing the complete amino acid sequence, and a major form of 190 kDa derived from the full-length form by post-translational proteolysis close to Phe-1690.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The loop between repeats II and III interacts with the ryanodine receptor, and is therefore important for calcium release from the endoplasmic reticulum necessary for muscle contraction.
messages: Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death.

9606:ADAM32
gene id: 9606:ADAM32
uniprot id: A0A140VJD9
uniprot id: B4DTC2
uniprot id: Q8TC27
names: Caution
names: Function
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: May play a role in sperm development and fertilization This is a non-catalytic metalloprotease-like protein.
messages: Membrane
messages: Testis specific.

9606:PDE10A
gene id: 9606:PDE10A
uniprot id: A0A1B1UZR0
uniprot id: Q9Y233
names: Activity Regulation
names: Cofactor
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Abundant in the putamen and caudate nucleus regions of brain and testis, moderately expressed in the thyroid gland, pituitary gland, thalamus and cerebellum.
messages: Belongs to the cyclic nucleotide phosphodiesterase family.
messages: Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions.
messages: Composed of a C-terminal catalytic domain containing two divalent metal sites and an N-terminal regulatory domain which contains one cyclic nucleotide-binding region.
messages: Homodimer.
messages: Inhibited by dipyridamole and moderately by IBMX. cGMP acts as an allosteric activator.
messages: Phosphorylated on Thr-16.
messages: Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides (PubMed:10373451, PubMed:10393245, PubMed:16330539, PubMed:27058447, PubMed:17389385). Can hydrolyze both cAMP and cGMP, but has higher affinity for cAMP and is more efficient with cAMP as substrate (PubMed:10373451, PubMed:10393245, PubMed:27058447, PubMed:17389385). May play a critical role in regulating cAMP and cGMP levels in the striatum, a region of the brain that contributes to the control of movement and cognition (PubMed:27058447).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The tandem GAF domains bind cAMP, and regulate enzyme activity. The binding of cAMP stimulates enzyme activity.
messages: cytosol

9606:WDR37
gene id: 9606:WDR37
uniprot id: Q9Y2I8
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Cytoplasm
messages: Forms homodimers (PubMed:34642815). Interacts with PACS1 (PubMed:34642815). Interacts with PACS2 (PubMed:34642815).
messages: Nucleus
messages: Required for normal ER Ca2+ handling in lymphocytes. Together with PACS1, it plays an essential role in stabilizing peripheral lymphocyte populations.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:FOXJ3
gene id: 9606:FOXJ3
uniprot id: Q9UPW0
names: Function
names: Subcellular Location Annotation
messages: Nucleus
messages: Transcriptional activator of MEF2C involved in the regulation of adult muscle fiber type identity and skeletal muscle regeneration (By similarity). Plays an important role in spermatogenesis (By similarity). Required for the survival of spermatogonia and participates in spermatocyte meiosis (By similarity).

9606:SSBP1
gene id: 9606:SSBP1
uniprot id: A4D1U3
uniprot id: B7Z268
uniprot id: Q04837
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Binds preferentially and cooperatively to pyrimidine rich single-stranded DNA (ss-DNA) (PubMed:21953457, PubMed:23290262, PubMed:31550240). In vitro, required to maintain the copy number of mitochondrial DNA (mtDNA) and plays a crucial role during mtDNA replication by stimulating the activity of the replisome components POLG and TWNK at the replication fork (PubMed:21953457, PubMed:12975372, PubMed:26446790, PubMed:15167897, PubMed:31550240). Promotes the activity of the gamma complex polymerase POLG, largely by organizing the template DNA and eliminating secondary structures to favor ss-DNA conformations that facilitate POLG activity (PubMed:26446790, PubMed:21953457, PubMed:31550240). In addition it is able to promote the 5'-3' unwinding activity of the mtDNA helicase TWNK (PubMed:12975372). May also function in mtDNA repair (PubMed:23290262).
messages: Expressed in retinal ganglion cells, photoreceptors, pigmented epithelium and fibroblasts (at protein level).
messages: Homotetramer (PubMed:23290262, PubMed:31550240). Interacts with MPG/AAG, through inhibition of its glycosylase activity it potentially prevents formation of DNA breaks in ssDNA, ensuring that base removal primarily occurs in dsDNA (PubMed:23290262). Interacts with POLDIP2 (PubMed:16428295). Interacts with PRIMPOL (PubMed:25550423).
messages: Mitochondrion
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: mitochondrion nucleoid

9606:INSL6
gene id: 9606:INSL6
uniprot id: Q9Y581
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the insulin family.
messages: May have a role in sperm development and fertilization.
messages: Secreted
messages: Testis specific.

9606:WEE2
gene id: 9606:WEE2
uniprot id: P0C1S8
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WEE1 subfamily.
messages: Expressed in oocytes (at protein level) (PubMed:29606300). May also be expressed in testis (PubMed:11029659).
messages: Nucleus
messages: Oocyte-specific protein tyrosine kinase that phosphorylates and inhibits CDK1/CDC2 and acts as a key regulator of meiosis during both prophase I and metaphase II (PubMed:29606300). Required to maintain meiotic arrest in oocytes during the germinal vesicle (GV) stage, a long period of quiescence at dictyate prophase I, by phosphorylating CDK1 at 'Tyr-15', leading to inhibit CDK1 activity and prevent meiotic reentry. Also required for metaphase II exit during egg activation by phosphorylating CDK1 at 'Tyr-15', to ensure exit from meiosis in oocytes and promote pronuclear formation (By similarity).
messages: Phosphorylated on serine residues (PubMed:29606300). Phosphorylation leads to increase its activity (By similarity).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:MAGEA11
gene id: 9606:MAGEA11
uniprot id: P43364
names: Function
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Acts as androgen receptor coregulator that increases androgen receptor activity by modulating the receptors interdomain interaction. May play a role in embryonal development and tumor transformation or aspects of tumor progression.
messages: Cytoplasm
messages: Expressed in tumors of several types, such as melanoma, head and neck squamous cell carcinoma, lung carcinoma and breast carcinoma. Expressed in testis, ovary, prostate, cancerous prostate, breast and adrenal tissue.
messages: Nucleus

9606:COL5A1
gene id: 9606:COL5A1
uniprot id: P20908
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the fibrillar collagen family.
messages: Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.
messages: Sulfated on 40% of tyrosines.
messages: The C-terminal propeptide, also known as COLFI domain, have crucial roles in tissue growth and repair by controlling both the intracellular assembly of procollagen molecules and the extracellular assembly of collagen fibrils. It binds a calcium ion which is essential for its function (By similarity).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Trimers of two alpha 1(V) and one alpha 2(V) chains in most tissues and trimers of one alpha 1(V), one alpha 2(V), and one alpha 3(V) chains in placenta. Interacts with CSPG4.
messages: Type V collagen is a member of group I collagen (fibrillar forming collagen). It is a minor connective tissue component of nearly ubiquitous distribution. Type V collagen binds to DNA, heparan sulfate, thrombospondin, heparin, and insulin.
messages: extracellular matrix

9606:ZNF544
gene id: 9606:ZNF544
uniprot id: Q6NX49
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:PARVA
gene id: 9606:PARVA
uniprot id: Q9NVD7
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the parvin family.
messages: Cell membrane
messages: Interacts with TGFB1I1 (By similarity). Interacts with LIMS1 (via LD motifs) (PubMed:11331308). Interacts with ARHGAP31 (PubMed:16860736). Interacts with the actin cytoskeleton (PubMed:11331308). Interacts (via C-terminus) with ILK (PubMed:11331308, PubMed:15284246, PubMed:15817463, PubMed:20005845). Interacts (via C-terminus) with TESK1 (via C-terminus); the interaction inhibits TESK1 kinase activity (PubMed:15817463). Interacts with PXN/PAXILLIN (via LD motif 4) (PubMed:15817463, PubMed:18508764, PubMed:18940607).
messages: Plays a role in sarcomere organization and in smooth muscle cell contraction. Required for normal development of the embryonic cardiovascular system, and for normal septation of the heart outflow tract. Plays a role in sprouting angiogenesis and is required for normal adhesion of vascular smooth muscle cells to endothelial cells during blood vessel development (By similarity). Plays a role in the reorganization of the actin cytoskeleton, formation of lamellipodia and ciliogenesis. Plays a role in the establishment of cell polarity, cell adhesion, cell spreading, and directed cell migration.
messages: Widely expressed, with highest levels in heart, skeletal muscle, kidney and liver.
messages: Z line
messages: cytoskeleton
messages: focal adhesion

9606:ZNF613
gene id: 9606:ZNF613
uniprot id: Q6PF04
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:PEBP4
gene id: 9606:PEBP4
uniprot id: Q96S96
names: Caution
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the phosphatidylethanolamine-binding protein family.
messages: It was previously reported that PEBP4 is a lysosomal protein which is highly expressed in tumor cells, and may promote cellular resistance to TNF-induced apoptosis. However the paper has since been retracted by the journal due to concerns of image manipulation.
messages: Promotes AKT phosphorylation, suggesting a possible role in the PI3K-AKT signaling pathway.
messages: Secreted

9606:ZNF253
gene id: 9606:ZNF253
uniprot id: O75346
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: Expressed in bone marrow and in monocytic and immature erythroid cell lines.
messages: May function as a transcription factor. Seem to have a transcriptional repression activity.
messages: Nucleus

9606:TTC39A
gene id: 9606:TTC39A
uniprot id: A0A0A0MRQ0
uniprot id: A0A140VJY6
uniprot id: A0A7P0T922
uniprot id: B7Z4W9
uniprot id: F6WE04
uniprot id: Q5SRH9
names: Similarity
messages: Belongs to the TTC39 family.

9606:ENPP4
gene id: 9606:ENPP4
uniprot id: Q9Y6X5
names: Cofactor
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the nucleotide pyrophosphatase/phosphodiesterase family.
messages: Binds 2 Zn(2+) ions per subunit.
messages: Cell membrane
messages: Expressed on the surface of vascular endothelia.
messages: Hydrolyzes extracellular Ap3A into AMP and ADP, and Ap4A into AMP and ATP. Ap3A and Ap4A are diadenosine polyphosphates thought to induce proliferation of vascular smooth muscle cells. Acts as a procoagulant, mediating platelet aggregation at the site of nascent thrombus via release of ADP from Ap3A and activation of ADP receptors.

9606:COL3A1
gene id: 9606:COL3A1
uniprot id: P02461
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the fibrillar collagen family.
messages: Collagen type III occurs in most soft connective tissues along with type I collagen. Involved in regulation of cortical development. Is the major ligand of ADGRG1 in the developing brain and binding to ADGRG1 inhibits neuronal migration and activates the RhoA pathway by coupling ADGRG1 to GNA13 and possibly GNA12.
messages: O-linked glycan consists of a Glc-Gal disaccharide bound to the oxygen atom of a post-translationally added hydroxyl group.
messages: Proline residues at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.
messages: The C-terminal propeptide, also known as COLFI domain, have crucial roles in tissue growth and repair by controlling both the intracellular assembly of procollagen molecules and the extracellular assembly of collagen fibrils. It binds a calcium ion which is essential for its function.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Trimers of identical alpha 1(III) chains. The chains are linked to each other by interchain disulfide bonds. Trimers are also cross-linked via hydroxylysines. Interacts with ADGRG1 (PubMed:28258187).
messages: extracellular matrix

9606:CNIH1
gene id: 9606:CNIH1
uniprot id: B2R4P1
uniprot id: O95406
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the cornichon family.
messages: Endoplasmic reticulum membrane
messages: Golgi apparatus membrane
messages: Highly expressed in heart, liver, skeletal muscle, pancreas, adrenal medulla and cortex, thyroid, testis, spleen, appendix, peripheral blood lymphocytes and bone marrow. Lower expression found in brain, placenta, lung, kidney, ovary, small intestine, stomach, lymph node, thymus and fetal liver. Expression is up-regulated in dorsolateral prefrontal cortex of patients with schizophrenia (postmortem brain study).
messages: Interacts with AREG immature precursor and with immature TGFA, i.e. with a prosegment and lacking full N-glycosylation, but not with the fully N-glycosylated form. In the Golgi apparatus, may form a complex with GORASP55 and transmembrane TGFA.
messages: Involved in the selective transport and maturation of TGF-alpha family proteins.
messages: Membrane

9606:LILRB1
gene id: 9606:LILRB1
uniprot id: Q8NHL6
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Binds PTPN6 when phosphorylated (PubMed:9285411). Binds FCER1A and FCGR1A (PubMed:9842885, PubMed:11907092). Interacts with human cytomegalovirus/HHV-5 protein UL18 (PubMed:10591185). Interacts with peptide-bound HLA-G-B2M complex (PubMed:16455647). Interacts with peptide-bound HLA-F-B2M complex but not with peptide-free HLA-F open conformer. It does not probe the peptide sequence directly (PubMed:28636952).
messages: Cell membrane
messages: Contains 4 copies of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases.
messages: Expressed in B cells, monocytes and various dendritic cell (DC) subsets including myeloid, plasmacytoid and tolerogenic DCs (at protein level) (PubMed:20448110, PubMed:9285411, PubMed:9842885, PubMed:24453251). Expressed in decidual macrophages (at protein level) (PubMed:19304799). Expressed in decidual NK cells (at protein level) (PubMed:29262349).
messages: May act as dominant negative regulator and block the interaction between membrane-associated isoforms and HLA-class I.
messages: Phosphorylated on tyrosine residues. Dephosphorylated by PTPN6.
messages: Receptor for class I MHC antigens. Recognizes a broad spectrum of HLA-A, HLA-B, HLA-C, HLA-G and HLA-F alleles (PubMed:16455647, PubMed:28636952). Receptor for H301/UL18, a human cytomegalovirus class I MHC homolog. Ligand binding results in inhibitory signals and down-regulation of the immune response. Engagement of LILRB1 present on natural killer cells or T-cells by class I MHC molecules protects the target cells from lysis. Interaction with HLA-B or HLA-E leads to inhibition of FCER1A signaling and serotonin release. Inhibits FCGR1A-mediated phosphorylation of cellular proteins and mobilization of intracellular calcium ions (PubMed:11907092, PubMed:9285411, PubMed:9842885). Recognizes HLA-G in complex with B2M/beta-2 microglobulin and a nonamer self-peptide (PubMed:16455647). Upon interaction with peptide-bound HLA-G-B2M complex, triggers secretion of growth-promoting factors by decidual NK cells (PubMed:29262349, PubMed:19304799). Reprograms B cells toward an immune suppressive phenotype (PubMed:24453251).
messages: Secreted

9606:GRID1
gene id: 9606:GRID1
uniprot id: A8KAN9
uniprot id: Q9ULK0
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family.
messages: Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. GRID1 subfamily.
messages: Cell membrane
messages: Dimer. Interacts (via extracellular N-terminal domain) with CBLN1 (via C1q domain), and more weakly with CBLN2.
messages: Membrane
messages: Postsynaptic cell membrane
messages: Receptor for glutamate that functions as a ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system.
messages: Receptor for glutamate. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. The postsynaptic actions of Glu are mediated by a variety of receptors that are named according to their selective agonists.

9606:ZNF41
gene id: 9606:ZNF41
uniprot id: P51814
names: Caution
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: A chromosomal aberration involving ZNF41 has been found in a patient with severe intellectual disability. Translocation t(X;7)(p11.3;q11.21).
messages: Although ZNF41 has been reported to be involved in X-linked intellectual disability (PubMed:14628291), its pathological role is questionable (PubMed:23871722).
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: Expressed in the heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:PLA2G4B
gene id: 9606:PLA2G4B
uniprot id: P0C869
names: Activity Regulation
names: Caution
names: Domain
names: Function
names: Miscellaneous
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Based on a naturally occurring readthrough transcript which produces a JMJD7-PLA2G4B fusion protein.
messages: Calcium-dependent phospholipase A1 and A2 and lysophospholipase that may play a role in membrane phospholipid remodeling.
messages: Calcium-dependent phospholipase A1 and A2 and lysophospholipase. Cleaves the ester bond of the fatty acyl group attached to the sn-1 or sn-2 position of diacyl phospholipids (phospholipase A1 and A2 activity, respectively), producing lysophospholipids that may be used in deacylation-reacylation cycles. Can further hydrolyze lysophospholipids enabling complete deacylation. Has no activity toward alkylacyl phospholipids.
messages: Calcium-dependent phospholipase A2 and lysophospholipase. Cleaves the ester bond of the fatty acyl group attached to the sn-2 position of phosphatidylethanolamines, producing lysophospholipids that may be used in deacylation-reacylation cycles. Hydrolyzes lysophosphatidylcholines with low efficiency but is inefficient toward phosphatidylcholines.
messages: Early endosome membrane
messages: Mitochondrion membrane
messages: Most tissues also express read-through transcripts from this gene into the upstream gene (JMJD7), some of which may encode fusion proteins.
messages: Stimulated by cytosolic Ca(2+).
messages: The N-terminal C2 domain associates with lipid membranes upon calcium binding. It modulates enzyme activity by presenting the active site to its substrate in response to elevations of cytosolic Ca(2+) (By similarity).
messages: Widely expressed. Expressed at higher level in brain, heart, liver, cerebellum and pancreas.
messages: cytosol

9606:PRSS16
gene id: 9606:PRSS16
uniprot id: F2Z2N5
uniprot id: Q9NQE7
names: Developmental Stage
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the peptidase S28 family.
messages: Cytoplasmic vesicle
messages: Expressed in fetal thymus.
messages: Expressed predominantly in cortical thymic epithelial cells.
messages: Protease that may play a role in T-cell development.

9606:MBD3L1
gene id: 9606:MBD3L1
uniprot id: Q8WWY6
names: Domain
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the MBD3L family.
messages: Does not bind methylated DNA.
messages: Highly expressed in testis. Detected at low levels in pancreas. Not detected in the other tissues tested.
messages: Nucleus
messages: The MBD3L proteins are encoded by strongly repeated regions of the 19p13 chromosome. The exact number of functional copies is unclear, and some of them may represent pseudogenes.
messages: The N-terminal half of the protein mediates transcription repression.
messages: Transcriptional repressor.

9606:EVPLL
gene id: 9606:EVPLL
uniprot id: A8MZ36
names: Similarity
messages: Belongs to the plakin or cytolinker family.

9606:DNLZ
gene id: 9606:DNLZ
uniprot id: Q5SXM8
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: May function as a co-chaperone towards HSPA9/mortalin which, by itself, is prone to self-aggregation.
messages: Mitochondrion
messages: Oligomerizes in a concentration-dependent fashion. Interacts with HSPA9.

9606:MKNK2
gene id: 9606:MKNK2
uniprot id: Q9HBH9
names: Activity Regulation
names: Cofactor
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.
messages: Binds 1 zinc ion per subunit.
messages: Cytoplasm
messages: Dual phosphorylation of Thr-244 and Thr-249 activates the kinase. Phosphorylation of Thr-379 activates the kinase. Phosphorylated upon arsenic trioxide As(2)O(3) treatment. Phosphorylated by MAPK1/ERK2, MAPK11 and MAPK14. Dephosphorylated by PP2A.
messages: Inhibited by CGP57380 and staurosporine. Activated by phosphorylation in a negative-feedback regulatory manner in response to chemotherapy (e.g. cytarabine) and thus impairs the generation of antileukemic responses.
messages: Monomer. Interacts with the C-terminal regions of EIF4G1 and EIF4G2; this interaction is promoted when MAPK pathways are repressed but repressed upon ERK proteins activation. Also binds to dephosphorylated MAPK3/ERK1 and MAPK1/ERK2. Isoform 1 interaction with phosphorylated MAPK3/ERK1 and MAPK1/ERK2 protects it from dephosphorylation and inactivation. Isoform 2 interacts with ESR2 and EIF4E in the nucleus.
messages: PML body
messages: Serine/threonine-protein kinase that phosphorylates SFPQ/PSF, HNRNPA1 and EIF4E. May play a role in the response to environmental stress and cytokines. Appears to regulate translation by phosphorylating EIF4E, thus increasing the affinity of this protein for the 7-methylguanosine-containing mRNA cap. Required for mediating PP2A-inhibition-induced EIF4E phosphorylation. Triggers EIF4E shuttling from cytoplasm to nucleus. Isoform 1 displays a high basal kinase activity, but isoform 2 exhibits a very low kinase activity. Acts as a mediator of the suppressive effects of IFNgamma on hematopoiesis. Negative regulator for signals that control generation of arsenic trioxide As(2)O(3)-dependent apoptosis and anti-leukemic responses. Involved in anti-apoptotic signaling in response to serum withdrawal.
messages: Ubiquitously expressed in all tissues examined. Isoform 2 is expressed at higher levels in the ovary than is isoform 1.

9606:SNCA
gene id: 9606:SNCA
uniprot id: H6UYS5
uniprot id: P37840
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acetylation at Met-1 seems to be important for proper folding and native oligomeric structure.
messages: Belongs to the synuclein family.
messages: Cytoplasm
messages: Genetic alterations of SNCA resulting in aberrant polymerization into fibrils, are associated with several neurodegenerative diseases (synucleinopathies). SNCA fibrillar aggregates represent the major non A-beta component of Alzheimer disease amyloid plaque, and a major component of Lewy body inclusions. They are also found within Lewy body (LB)-like intraneuronal inclusions, glial inclusions and axonal spheroids in neurodegeneration with brain iron accumulation type 1.
messages: Hallmark lesions of neurodegenerative synucleinopathies contain alpha-synuclein that is modified by nitration of tyrosine residues and possibly by dityrosine cross-linking to generated stable oligomers.
messages: Highly expressed in presynaptic terminals in the central nervous system. Expressed principally in brain.
messages: Membrane
messages: Neuronal protein that plays several roles in synaptic activity such as regulation of synaptic vesicle trafficking and subsequent neurotransmitter release (PubMed:28288128, PubMed:30404828, PubMed:20798282, PubMed:26442590). Participates as a monomer in synaptic vesicle exocytosis by enhancing vesicle priming, fusion and dilation of exocytotic fusion pores (PubMed:28288128, PubMed:30404828). Mechanistically, acts by increasing local Ca(2+) release from microdomains which is essential for the enhancement of ATP-induced exocytosis (PubMed:30404828). Acts also as a molecular chaperone in its multimeric membrane-bound state, assisting in the folding of synaptic fusion components called SNAREs (Soluble NSF Attachment Protein REceptors) at presynaptic plasma membrane in conjunction with cysteine string protein-alpha/DNAJC5 (PubMed:20798282). This chaperone activity is important to sustain normal SNARE-complex assembly during aging (PubMed:20798282). Also plays a role in the regulation of the dopamine neurotransmission by associating with the dopamine transporter (DAT1) and thereby modulating its activity (PubMed:26442590).
messages: Nucleus
messages: Phosphorylated, predominantly on serine residues. Phosphorylation by CK1 appears to occur on residues distinct from the residue phosphorylated by other kinases. Phosphorylation of Ser-129 is selective and extensive in synucleinopathy lesions. In vitro, phosphorylation at Ser-129 promoted insoluble fibril formation. Phosphorylated on Tyr-125 by a PTK2B-dependent pathway upon osmotic stress.
messages: Secreted
messages: Soluble monomer. Homotetramer (PubMed:21841800). A dynamic intracellular population of tetramers and monomers coexists normally and the tetramer plays an essential role in maintaining homeostasis (PubMed:21841800). Interacts with UCHL1 (By similarity). Interacts with phospholipase D and histones. Interacts (via N-terminus) with synphilin-1/SNCAIP; this interaction promotes formation of SNCA inclusions in the cytoplasm (PubMed:19762560). Interacts with CALM1 (PubMed:23607618). Interacts with STXBP1; this interaction controls SNCA self-replicating aggregation (PubMed:27597756). Interacts with SNARE components VAMP2 and SNAP25; these interactions allows SNARE complex assembly and integrity (PubMed:20798282). Interacts with RPH3A and RAB3A (PubMed:15207266). Interacts with SERF1A; this interaction promotes the aggregation of SNCA (PubMed:22854022, PubMed:31034892). Interacts with SEPTIN4 (By similarity).
messages: Synapse
messages: The 'non A-beta component of Alzheimer disease amyloid plaque' domain (NAC domain) is involved in fibrils formation. The middle hydrophobic region forms the core of the filaments. The C-terminus may regulate aggregation and determine the diameter of the filaments.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitinated. The predominant conjugate is the diubiquitinated form.
messages: axon

9606:TPM1
gene id: 9606:TPM1
uniprot id: A0A0K0K1I0
uniprot id: B7Z722
uniprot id: D9YZV4
uniprot id: D9YZV5
uniprot id: D9YZV7
uniprot id: F5H7S3
uniprot id: H0YK48
uniprot id: H7BYY1
uniprot id: O15513
uniprot id: P09493
names: Disease Annotation
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the tropomyosin family.
messages: Binds to actin filaments in muscle and non-muscle cells (PubMed:23170982). Plays a central role, in association with the troponin complex, in the calcium dependent regulation of vertebrate striated muscle contraction (PubMed:23170982). Smooth muscle contraction is regulated by interaction with caldesmon. In non-muscle cells is implicated in stabilizing cytoskeleton actin filaments.
messages: Detected in primary breast cancer tissues but undetectable in normal breast tissues in Sudanese patients. Isoform 1 is expressed in adult and fetal skeletal muscle and cardiac tissues, with higher expression levels in the cardiac tissues. Isoform 10 is expressed in adult and fetal cardiac tissues, but not in skeletal muscle.
messages: Homodimer (PubMed:23170982). Heterodimer of an alpha (TPM1, TPM3 or TPM4) and a beta (TPM2) chain (By similarity). Interacts with HRG (via the HRR domain); the interaction contributes to the antiangiogenic properties of the histidine/proline-rich region (HRR) of HRG (By similarity). Interacts (via N-terminus) with LMOD2 (via N-terminus) and TMOD1 (via N-terminus) (PubMed:26873245).
messages: Incomplete sequence.
messages: Phosphorylated at Ser-283 by DAPK1 in response to oxidative stress and this phosphorylation enhances stress fiber formation in endothelial cells.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The molecule is in a coiled coil structure that is formed by 2 polypeptide chains. The sequence exhibits a prominent seven-residues periodicity.
messages: cytoskeleton

9606:SPIN1
gene id: 9606:SPIN1
uniprot id: Q9Y657
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the SPIN/STSY family.
messages: Chromatin reader that specifically recognizes and binds histone H3 both trimethylated at 'Lys-4' and asymmetrically dimethylated at 'Arg-8' (H3K4me3 and H3R8me2a) and acts as an activator of Wnt signaling pathway downstream of PRMT2. In case of cancer, promotes cell cancer proliferation via activation of the Wnt signaling pathway (PubMed:24589551). Overexpression induces metaphase arrest and chromosomal instability. Localizes to active rDNA loci and promotes the expression of rRNA genes (PubMed:21960006). May play a role in cell-cycle regulation during the transition from gamete to embryo. Involved in oocyte meiotic resumption, a process that takes place before ovulation to resume meiosis of oocytes blocked in prophase I: may act by regulating maternal transcripts to control meiotic resumption.
messages: Highly expressed in ovarian cancer tissues.
messages: Homodimer; may form higher-order oligomers (PubMed:17082182). Interacts with TCF7L2/TCF4; the interaction is direct (PubMed:22258766, PubMed:24589551, PubMed:29061846). Interacts with HABP4 and SERBP1 (By similarity). Interacts with C11orf84/SPINDOC (PubMed:29061846).
messages: Nucleus
messages: Phosphorylated during oocyte meiotic maturation.
messages: The 3 tudor-like domains (also named Spin/Ssty repeats) specifically recognize and bind methylated histones (PubMed:23077255, PubMed:24589551). H3K4me3 and H3R8me2a are recognized by tudor-like domains 2 and 1, respectively (PubMed:24589551).
messages: nucleolus

9606:TAS2R7
gene id: 9606:TAS2R7
uniprot id: Q9NYW3
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor T2R family.
messages: Expressed in subsets of taste receptor cells of the tongue and palate epithelium and exclusively in gustducin-positive cells.
messages: Gustducin-coupled receptor implicated in the perception of bitter compounds in the oral cavity and the gastrointestinal tract. Signals through PLCB2 and the calcium-regulated cation channel TRPM5.
messages: Membrane
messages: Several bitter taste receptors are expressed in a single taste receptor cell.

9606:NDUFAF4
gene id: 9606:NDUFAF4
uniprot id: Q9P032
names: Disease Annotation
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Interacts with the vesicular stomatitis virus matrix protein/M; the interaction inhibits viral propagation.
messages: Belongs to the NDUFAF4 family.
messages: Binds calmodulin. Interacts with NDUFAF3.
messages: Expression is low in quiescent cells and is induced in exponentially proliferating cultures. Expression is also induced when prolactin is added to stationary cells. Induced by dietary differentiating agents such as butyrate and retinoic acid.
messages: Involved in the assembly of mitochondrial NADH:ubiquinone oxidoreductase complex (complex I) (PubMed:18179882, PubMed:28853723). May be involved in cell proliferation and survival of hormone-dependent tumor cells. May be a regulator of breast tumor cell invasion.
messages: Membrane
messages: Mitochondrion
messages: Phosphorylated on serine. Prolactin stimulate serine phosphorylation (By similarity).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:TRIM35
gene id: 9606:TRIM35
uniprot id: Q9UPQ4
names: Domain
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the TRIM/RBCC family.
messages: By TLR7 and TLR9 stimulation.
messages: Cytoplasm
messages: E3 ubiquitin-protein ligase that participates in multiple biological processes including cell death, glucose metabolism, and in particular, the innate immune response. Mediates 'Lys-63'-linked polyubiquitination of TRAF3 thereby promoting type I interferon production via RIG-I signaling pathway (PubMed:32562145). Can also catalyze 'Lys-48'-linked polyubiquitination and proteasomal degradation of viral proteins such as influenza virus PB2 (PubMed:32562145). Acts as a negative feedback regulator of TLR7- and TLR9-triggered signaling. Mechanistically, promotes the 'Lys-48'-linked ubiquitination of IRF7 and induces its degradation via a proteasome-dependent pathway (PubMed:25907537). Reduces FGFR1-dependent tyrosine phosphorylation of PKM, inhibiting PKM-dependent lactate production, glucose metabolism, and cell growth (PubMed:25263439).
messages: Interacts with PKM isoform M2, but not isoform M1; this interaction may compete with that between PKM and FGFR1, and hence reduces FGFR1-dependent tyrosine phosphorylation of PKM (PubMed:25263439). Interacts with IRF7; this interaction promotes IRF7 proteasomal degradation (PubMed:25907537). Interacts with TRAF3; this interaction promotes TRAF3 activation (PubMed:32562145).
messages: Nucleus
messages: The RING finger domain and the coiled-coil region are required for the apoptosis-inducing activity.

9606:PTP4A3
gene id: 9606:PTP4A3
uniprot id: O75365
names: Activity Regulation
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the protein-tyrosine phosphatase family.
messages: Cell membrane
messages: Early endosome
messages: Farnesylated. Farnesylation is required for membrane targeting (By similarity).
messages: Inhibited by sodium orthovanadate and peroxovanadium compounds, and by pentamidine.
messages: Interacts with tubulin.
messages: Mainly expressed in cardiomyocytes and skeletal muscle; also found in pancreas. Consistently overexpressed in colon cancer metastasis.
messages: Protein tyrosine phosphatase which stimulates progression from G1 into S phase during mitosis. Enhances cell proliferation, cell motility and invasive activity, and promotes cancer metastasis. May be involved in the progression of cardiac hypertrophy by inhibiting intracellular calcium mobilization in response to angiotensin II.
messages: Unstructured and inactive.

9606:PVALB
gene id: 9606:PVALB
uniprot id: P20472
names: Function
names: Similarity
messages: Belongs to the parvalbumin family.
messages: In muscle, parvalbumin is thought to be involved in relaxation after contraction. It binds two calcium ions.

9606:GLDC
gene id: 9606:GLDC
uniprot id: P23378
names: Activity Regulation
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the GcvP family.
messages: Homodimer (By similarity). Interacts with GCSH (By similarity). The glycine cleavage system is composed of four proteins: P (GLDC), T (GCST), L (DLD) and H (GCSH).
messages: Mitochondrion
messages: Stimulated by lipoic acid. Inhibited in presence of methylamine (By similarity).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The glycine cleavage system catalyzes the degradation of glycine. The P protein (GLDC) binds the alpha-amino group of glycine through its pyridoxal phosphate cofactor; CO(2) is released and the remaining methylamine moiety is then transferred to the lipoamide cofactor of the H protein (GCSH).

9606:LTBP3
gene id: 9606:LTBP3
uniprot id: B9EG76
uniprot id: Q8WYU6
uniprot id: Q9NS15
names: Caution
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the LTBP family.
messages: Contains hydroxylated asparagine residues.
messages: Forms part of the large latent transforming growth factor beta precursor complex; removal is essential for activation of complex. Interacts with EFEMP2 (PubMed:27339457).
messages: Isoform 2: Expressed prominently in heart, skeletal muscle, prostate, testis, small intestine and ovary (PubMed:12154076). Isoform 1: Strongly expressed in pancreas and liver (PubMed:12154076).
messages: Key regulator of transforming growth factor beta (TGFB1, TGFB2 and TGFB3) that controls TGF-beta activation by maintaining it in a latent state during storage in extracellular space. Associates specifically via disulfide bonds with the Latency-associated peptide (LAP), which is the regulatory chain of TGF-beta, and regulates integrin-dependent activation of TGF-beta.
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: Secreted
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Two intrachain disulfide bonds from the TB3 domain are rearranged upon TGFB1 binding, and form interchain bonds with TGFB1 propeptide, anchoring it to the extracellular matrix.
messages: extracellular matrix

9606:HEXIM2
gene id: 9606:HEXIM2
uniprot id: Q96MH2
names: Domain
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the HEXIM family.
messages: Homooligomer and heterooligomer with HEXIM1; probably dimeric (PubMed:15713661, PubMed:15994294). Core component of the 7SK RNP complex, at least composed of 7SK RNA, LARP7, MEPCE, HEXIM1 (or HEXIM2) and P-TEFb (composed of CDK9 and CCNT1/cyclin-T1) (PubMed:15713661, PubMed:15713662, PubMed:15994294). Interacts with CCNT2 (PubMed:19883659).
messages: Nucleus
messages: The coiled-coil domain mediates oligomerization.
messages: Transcriptional regulator which functions as a general RNA polymerase II transcription inhibitor (PubMed:15713661, PubMed:15713662). Core component of the 7SK RNP complex: in cooperation with 7SK snRNA sequesters P-TEFb in a large inactive 7SK snRNP complex preventing RNA polymerase II phosphorylation and subsequent transcriptional elongation (PubMed:15713661, PubMed:15713662).
messages: Ubiquitously expressed with higher expression in testis. HEXIM1 and HEXIM2 are differentially expressed.
messages: Up-regulated by HMBA (hexamethylene bisacetamide) (at protein level).

9606:NR5A1
gene id: 9606:NR5A1
uniprot id: F1D8R8
uniprot id: Q13285
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acetylation stimulates the transcriptional activity.
messages: Belongs to the nuclear hormone receptor family. NR5 subfamily.
messages: Binds DNA as a monomer. Interacts with NR0B2 and PPARGC1A (By similarity). Part of a complex consisting of SFPQ, NONO and NR5A1. Interacts with NCOA2. Interacts with DGKQ and CDK7. Binds to and activated by HIPK3.
messages: High expressed in the adrenal cortex, the ovary, the testis, and the spleen (PubMed:9177385).
messages: Nucleus
messages: Phosphorylated on Ser-203 by CDK7. This phosphorylation promotes transcriptional activity.
messages: Sumoylation reduces CDK7-mediated phosphorylation on Ser-203.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Transcriptional activator. Essential for sexual differentiation and formation of the primary steroidogenic tissues (PubMed:27378692). Binds to the Ad4 site found in the promoter region of steroidogenic P450 genes such as CYP11A, CYP11B and CYP21B. Also regulates the AMH/Muellerian inhibiting substance gene as well as the AHCH and STAR genes. 5'-YCAAGGYC-3' and 5'-RRAGGTCA-3' are the consensus sequences for the recognition by NR5A1 (PubMed:27378692). The SFPQ-NONO-NR5A1 complex binds to the CYP17 promoter and regulates basal and cAMP-dependent transcriptional activity. Binds phosphatidylcholine (By similarity). Binds phospholipids with a phosphatidylinositol (PI) headgroup, in particular PI(3,4)P2 and PI(3,4,5)P3. Activated by the phosphorylation of NR5A1 by HIPK3 leading to increased steroidogenic gene expression upon cAMP signaling pathway stimulation.

9606:STX1B
gene id: 9606:STX1B
uniprot id: P61266
names: Disease Annotation
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the syntaxin family.
messages: Interacts with OTOF. Interacts with SYT6 and SYT8; the interaction is Ca(2+)-dependent (By similarity).
messages: Membrane
messages: Nucleus
messages: Phosphorylated by CK2.
messages: Potentially involved in docking of synaptic vesicles at presynaptic active zones. May mediate Ca(2+)-regulation of exocytosis acrosomal reaction in sperm (By similarity).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The glycine-rich C-terminus serves as an unconventional nuclear localization signal.
messages: centrosome
messages: spindle

9606:RAP1A
gene id: 9606:RAP1A
uniprot id: P62834
names: Activity Regulation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Activated by guanine nucleotide-exchange factors (GEF) EPAC and EPAC2 in a cAMP-dependent manner, and GFR.
messages: Belongs to the small GTPase superfamily. Ras family.
messages: Cell junction
messages: Cell membrane
messages: Cytoplasm
messages: Early endosome
messages: Found in a complex, at least composed of ITGB1BP1, KRIT1 and RAP1A (PubMed:17916086). Interacts (active GTP-bound form preferentially) with KRIT1 (via C-terminus FERM domain); the interaction does not induce the opening conformation of KRIT1 (PubMed:17916086). In its GTP-bound form interacts with PLCE1 and RADIL (PubMed:11022048, PubMed:12444546, PubMed:17704304). Interacts with SGSM1, SGSM2 and SGSM3 (PubMed:17509819). Interacts (via GTP-bound active form) with RAPGEF2 (via Ras-associating domain) (PubMed:11359771, PubMed:10608844). Interacts with TBC1D21 (By similarity). Interacts with RAP1GDS1 (PubMed:20709748).
messages: Induces morphological reversion of a cell line transformed by a Ras oncogene. Counteracts the mitogenic function of Ras, at least partly because it can interact with Ras GAPs and RAF in a competitive manner. Together with ITGB1BP1, regulates KRIT1 localization to microtubules and membranes. Plays a role in nerve growth factor (NGF)-induced neurite outgrowth. Plays a role in the regulation of embryonic blood vessel formation. Involved in the establishment of basal endothelial barrier function. May be involved in the regulation of the vascular endothelial growth factor receptor KDR expression at endothelial cell-cell junctions.
messages: perinuclear region

9606:SLC25A27
gene id: 9606:SLC25A27
uniprot id: B4DHR4
uniprot id: O95847
names: Activity Regulation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the mitochondrial carrier (TC 2.A.29) family.
messages: Facilitates proton transport across the inner mitochondrial membrane and may dissipate excessive proton gradient associated with oxidative and metabolic stress at neuronal synapses. Regulates glutamate-induced proton conductance in astrocytes, shifting the energy metabolism toward aerobic glycolysis and lactate transfer to neurons for ATP synthesis. Can transport chloride ions with lower efficiency. The transport mechanism remains to be elucidated.
messages: Found in adult and fetal brain. Present in most of the brain tissues, with low levels in spinal chord, corpus callosum and substantia nigra.
messages: Homotetramer.
messages: Membrane
messages: Mitochondrion inner membrane
messages: Proton conductance is up-regulated by unsaturated long-chain fatty acids and inhibited by purine nucleotides ATP and ADP. The transport of chloride ions is partially inhibited by long-chain fatty acids.

9606:IPO13
gene id: 9606:IPO13
uniprot id: O94829
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the importin beta family.
messages: Cytoplasm
messages: Expressed in fetal brain, heart, intestine and kidney.
messages: Functions in nuclear protein import as nuclear transport receptor. Serves as receptor for nuclear localization signals (NLS) in cargo substrates. Is thought to mediate docking of the importin/substrate complex to the nuclear pore complex (NPC) through binding to nucleoporin and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to the importin, the importin/substrate complex dissociates and importin is re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus (By similarity). Mediates the nuclear import of UBC9, the RBM8A/MAGOH complex, PAX6 and probably other members of the paired homeobox family. Also mediates nuclear export of eIF-1A, and the cytoplasmic release of eIF-1A is triggered by the loading of import substrates onto IPO13.
messages: Interacts with UBC9, RAN, RBM8A, eIF-1A and PAX6.
messages: Nucleus

9606:KCNU1
gene id: 9606:KCNU1
uniprot id: A8MYU2
names: Disease Annotation
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the potassium channel family. Calcium-activated (TC 1.A.1.3) subfamily. KCa5.1/KCNU1 sub-subfamily.
messages: Cell membrane
messages: Homotetramer; which constitutes the calcium-activated potassium channel. May interact with LRRC52; this interaction may change channel gating properties, such as shifting gating to more negative potentials at a given pH.
messages: Testis-specific potassium channel activated by both intracellular pH and membrane voltage that mediates export of K(+). May represent the primary spermatozoan K(+) current. In contrast to KCNMA1/SLO1, it is not activated by Ca(2+) or Mg(2+). Critical for fertility. May play an important role in sperm osmoregulation required for the acquisition of normal morphology and motility when faced with osmotic challenges, such as those experienced after mixing with seminal fluid and entry into the vagina.
messages: Testis-specific.
messages: The C-terminal cytosolic region confers the pH-dependence.
messages: The RCK N-terminal domain mediates the homotetramerization, thereby promoting the assembly of monomers into functional potassium channel.
messages: The S4 segment, which is characterized by a series of positively charged amino acids at every third position, is part of the voltage-sensor.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The pore-forming domain (also referred as P region) is imbedded into the membrane, and forms the selectivity filter of the pore. It contains the signature sequence of potassium channels that displays selectivity to potassium (By similarity).

9606:PPCDC
gene id: 9606:PPCDC
uniprot id: Q96CD2
names: Cofactor
names: Function
names: Miscellaneous
names: Similarity
names: Subunit
messages: Belongs to the HFCD (homooligomeric flavin containing Cys decarboxylase) superfamily.
messages: Binds 1 FMN per subunit.
messages: Catalyzes the decarboxylation of the cysteine moiety of 4-phosphopantothenoylcysteine to form 4'-phosphopantotheine and this reaction forms part of the biosynthesis of coenzyme A.
messages: Homotrimer.
messages: The Met-1 codon is associated with a polymorphism (dbSNP:rs2304899) that replaces the initiation ATG codon by an ATA codon.

9606:CTAG2
gene id: 9606:CTAG2
uniprot id: O75638
names: Polymorphism
names: Similarity
names: Tissue Specificity
messages: At least three different alleles exist. The allele defined by Arg-6 and Glu-89 is associated with a risk of gastric cancer.
messages: Belongs to the CTAG/PCC1 family.
messages: Testis and very low level in placenta and in some uterus samples. Observed in 25-50% of tumor samples of melanomas, non-small-cell lung carcinomas, bladder, prostate and head and neck cancers.

9606:AADACL2
gene id: 9606:AADACL2
uniprot id: Q6P093
names: Miscellaneous
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the 'GDXG' lipolytic enzyme family.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Secreted
messages: Wrong choice of CDS.

9606:CNOT7
gene id: 9606:CNOT7
uniprot id: Q96IQ6
uniprot id: Q9UIV1
names: Cofactor
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the CAF1 family.
messages: Binds 2 divalent metal cations per subunit with RNAase activity being higher in presence of Mn(2+) than of Mg(2+) or Co(2+).
messages: Component of the CCR4-NOT complex; distinct complexes seem to exist that differ in the participation of probably mutually exclusive catalytic subunits; the complex contains two deadenylase subunits, CNOT6 or CNOT6L, and CNOT7 or CNOT8 (PubMed:19558367). In the complex, interacts directly with CNOT1 (PubMed:21336257). Interacts with AGO2 (By similarity). Interacts with TOB1; recruited by TOB1 to a ternary complex with CPEB3 which is required for mRNA deadenylation and decay (PubMed:21336257, PubMed:23236473, PubMed:19276069). Interacts with BTG1 (By similarity). Interacts with BTG2 (PubMed:23236473). Interacts with NANOS2 (By similarity). Interacts with ZFP36, ZFP36L1 and ZFP36L2; these interactions are inhibited in response to phorbol 12-myristate 13-acetate (PMA) treatment in a p38 MAPK-dependent manner (PubMed:25106868). Interacts with TARDBP (PubMed:30520513). Interacts with BTG4 (PubMed:32502391). Interacts with EIF4E; this interaction is increased by CNOT7 interaction with BTG4 (By similarity).
messages: Cytoplasmic ribonucleoprotein granule
messages: Has 3'-5' poly(A) exoribonuclease activity for synthetic poly(A) RNA substrate (PubMed:20634287, PubMed:31439799, PubMed:19276069). Its function seems to be partially redundant with that of CNOT8 (PubMed:19605561). Catalytic component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation (PubMed:20634287, PubMed:31439799, PubMed:19276069). During miRNA-mediated repression the complex seems also to act as translational repressor during translational initiation (PubMed:20065043). Additional complex functions may be a consequence of its influence on mRNA expression (PubMed:23236473, PubMed:19276069). Associates with members of the BTG family such as TOB1 and BTG2 and is required for their anti-proliferative activity (PubMed:23236473, PubMed:19276069).
messages: Nucleus
messages: P-body

9606:ORC3
gene id: 9606:ORC3
uniprot id: Q9UBD5
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the ORC3 family.
messages: Chromosome
messages: Component of ORC, a complex composed of at least 6 subunits: ORC1, ORC2, ORC3, ORC4, ORC5 and ORC6. ORC is regulated in a cell-cycle dependent manner. It is sequentially assembled at the exit from anaphase of mitosis and disassembled as cells enter S phase.
messages: Component of the origin recognition complex (ORC) that binds origins of replication. DNA-binding is ATP-dependent. The specific DNA sequences that define origins of replication have not been identified yet. ORC is required to assemble the pre-replication complex necessary to initiate DNA replication. Binds histone H3 and H4 trimethylation marks H3K9me3, H3K27me3 and H4K20me3.
messages: Multi-mono-ubiquitinated by OBI1; ubiquitination is important for efficient DNA replication origin site activation. Ubiquitination levels are low in mitotic and early G1-phAse cells and are induced in late G1-/early S-phase, peaking in S-phase and decrease toward the end of the cell cycle.
messages: Nucleus

9606:IL26
gene id: 9606:IL26
uniprot id: A0A7R8GUW8
uniprot id: Q9NPH9
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the IL-10 family.
messages: By Herpesvirus saimiri infection.
messages: Expressed in HVS transformed T-cells but not other T-cell lines or primary stimulated T-cells. Expressed in colonic T-cells including Th17 inflammatory T-cells; the expression is significantly increased in serum of patients with Crohn's disease (at protein level).
messages: Homodimer.
messages: Immune regulatory cytokine.
messages: May play a role in local mechanisms of mucosal immunity and seems to have a pro-inflammatory function. May play a role in inflammatory bowel disease. Activates STAT1 and STAT3, MAPK1/3 (ERK1/2), JUN and AKT. Induces expression of SOCS3, TNF-alpha and IL-8, secretion of IL-8 and IL-10 and surface expression of ICAM1. Decreases proliferation of intestinal epithelial cells. Is inhibited by heparin.
messages: Secreted

9606:OR13F1
gene id: 9606:OR13F1
uniprot id: Q8NGS4
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Odorant receptor.

9606:OVCH2
gene id: 9606:OVCH2
uniprot id: A0A087X1V8
names: Caution
messages: Lacks conserved residue(s) required for the propagation of feature annotation.

9606:PTPN1
gene id: 9606:PTPN1
uniprot id: A8K3M3
uniprot id: B4DSN5
uniprot id: P18031
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the protein-tyrosine phosphatase family. Non-receptor class 1 subfamily.
messages: Endoplasmic reticulum membrane
messages: Expressed in keratinocytes (at protein level).
messages: Interacts with EPHA3 (phosphorylated); dephosphorylates EPHA3 and may regulate its trafficking and function. Interacts with MET.
messages: Oxidized on Cys-215; the Cys-SOH formed in response to redox signaling reacts with the alpha-amido of the following residue to form a sulfenamide cross-link, triggering a conformational change that inhibits substrate binding and activity. The active site can be restored by reduction.
messages: S-nitrosylation of Cys-215 inactivates the enzyme activity.
messages: Ser-50 is the major site of phosphorylation as compared to Ser-242 and Ser-243. Activated by phosphorylation at Ser-50.
messages: Sulfhydration at Cys-215 following endoplasmic reticulum stress inactivates the enzyme activity, promoting EIF2AK3/PERK activity.
messages: Tyrosine-protein phosphatase which acts as a regulator of endoplasmic reticulum unfolded protein response. Mediates dephosphorylation of EIF2AK3/PERK; inactivating the protein kinase activity of EIF2AK3/PERK. May play an important role in CKII- and p60c-src-induced signal transduction cascades. May regulate the EFNA5-EPHA3 signaling pathway which modulates cell reorganization and cell-cell repulsion. May also regulate the hepatocyte growth factor receptor signaling pathway through dephosphorylation of MET.

9606:RSPO3
gene id: 9606:RSPO3
uniprot id: Q9BXY4
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Activator of the canonical Wnt signaling pathway by acting as a ligand for LGR4-6 receptors, which acts as a key regulator of angiogenesis. Upon binding to LGR4-6 (LGR4, LGR5 or LGR6), LGR4-6 associate with phosphorylated LRP6 and frizzled receptors that are activated by extracellular Wnt receptors, triggering the canonical Wnt signaling pathway to increase expression of target genes. Also regulates the canonical Wnt/beta-catenin-dependent pathway and non-canonical Wnt signaling by acting as an inhibitor of ZNRF3, an important regulator of the Wnt signaling pathway. Acts as a ligand for frizzled FZD8 and LRP6. May negatively regulate the TGF-beta pathway (PubMed:21727895, PubMed:21909076, PubMed:22615920). Acts as a key regulator of angiogenesis by controlling vascular stability and pruning: acts by activating the non-canonical Wnt signaling pathway in endothelial cells (By similarity) (PubMed:21727895, PubMed:21909076, PubMed:22615920). Can also amplify Wnt signaling pathway independently of LGR4-6 receptors, possibly by acting as a direct antagonistic ligand to RNF43 and ZNRF3 (PubMed:29769720).
messages: Belongs to the R-spondin family.
messages: Interacts with the extracellular domain of FZD8 and LRP6 (By similarity). It however does not form a ternary complex with FZD8 and LRP6 (By similarity). Interacts with WNT1 (By similarity). Binds heparin. Interacts with LGR4, LGR5 and LGR6 (PubMed:21727895, PubMed:21909076, PubMed:22615920).
messages: Secreted
messages: The FU repeats are required for activation and stabilization of beta-catenin.
messages: Ubiquitously expressed. Expressed at higher level in placenta, small intestine, fetal thymus and lymph node (PubMed:12463421). Highly expressed in endothelial cells (PubMed:26766444).

9606:FGF8
gene id: 9606:FGF8
uniprot id: A0A087X1S5
uniprot id: A1A515
uniprot id: P55075
names: Developmental Stage
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the heparin-binding growth factors family.
messages: In adults expression is restricted to the gonads.
messages: Monomer. Homodimer. Interacts with FGFR1, FGFR2, FGFR3 and FGFR4. Affinity between fibroblast growth factors (FGFs) and their receptors is increased by heparan sulfate glycosaminoglycans that function as coreceptors.
messages: Plays an important role in the regulation of embryonic development, cell proliferation, cell differentiation and cell migration. Required for normal brain, eye, ear and limb development during embryogenesis. Required for normal development of the gonadotropin-releasing hormone (GnRH) neuronal system (PubMed:16384934, PubMed:16597617, PubMed:8663044). Plays a role in neurite outgrowth in hippocampal cells (PubMed:21576111).
messages: Secreted
messages: The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry. The genetics of hypogonadotropic hypogonadism involves various modes of transmission. Oligogenic inheritance has been reported in some patients carrying mutations in FGF8 as well as in other HH-associated genes including FGFR1 (PubMed:23643382).
messages: The gene represented in this entry is involved in disease pathogenesis. Duplications encompassing the FGF8 locus have been found in unrelated families with isolated bilateral hypoplasia of the femoral and pelvic bone. The phenotype is most likely the result of position effects causing altered FGF8 expression rather than gene dosage.

9606:MSTN
gene id: 9606:MSTN
uniprot id: O14793
uniprot id: Q53S46
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Acts specifically as a negative regulator of skeletal muscle growth.
messages: Belongs to the TGF-beta family.
messages: Homodimer; disulfide-linked (PubMed:27625211). Interacts with WFIKKN2, leading to inhibit its activity (PubMed:12595574). Interacts with FST3 (PubMed:17878677).
messages: Homodimer; disulfide-linked. Interacts with WFIKKN2, leading to inhibit its activity. Interacts with FSTL3.
messages: Secreted
messages: Synthesized as large precursor molecule that undergoes proteolytic cleavage to generate an N-terminal propeptide and a disulfide linked C-terminal dimer, which is the biologically active molecule. The circulating form consists of a latent complex of the C-terminal dimer and other proteins, including its propeptide, which maintain the C-terminal dimer in a latent, inactive state. Ligand activation requires additional cleavage of the prodomain by a tolloid-like metalloproteinase.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:GPR65
gene id: 9606:GPR65
uniprot id: B5B0C2
uniprot id: Q8IYL9
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Predominantly expressed in thymus, spleen, lymph nodes, small intestine, lung, placenta and peripheral blood leukocytes.
messages: Receptor for the glycosphingolipid psychosine (PSY) and several related glycosphingolipids (PubMed:11309421). Plays a role in immune response by maintaining lysosome function and supporting phagocytosis-mediated intracellular bacteria clearance (PubMed:27287411). May have a role in activation-induced cell death or differentiation of T-cells (By similarity).

9606:CAPN7
gene id: 9606:CAPN7
uniprot id: Q7Z479
uniprot id: Q9Y6W3
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the peptidase C2 family.
messages: Calcium-regulated non-lysosomal thiol-protease.
messages: Nucleus
messages: Ubiquitous.

9606:FASTK
gene id: 9606:FASTK
uniprot id: A0A090N8I0
uniprot id: A0A090N8Z7
uniprot id: Q14296
names: Caution
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Autophosphorylated on serine/threonine residues. Activated by dephosphorylation.
messages: Belongs to the FAST protein kinase family.
messages: Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.
messages: Interacts with TIA1; the interactions leads to TIA1 phosphorylation (PubMed:7544399, PubMed:17135269). Interacts with TIAR (PubMed:7544399, PubMed:17135269).
messages: Mitochondrion matrix
messages: Phosphorylates the splicing regulator TIA1, thereby promoting the inclusion of FAS exon 6, which leads to an mRNA encoding a pro-apoptotic form of the receptor.
messages: Required for the biogenesis of some mitochondrial-encoded mRNAs, specifically stabilizes ND6 (NADH dehydrogenase complex subunit 6) mRNA, and regulates its levels.
messages: The RAP domain is essential for RNA-binding.
messages: The sequence shown here is derived from an EMBL/GenBank/DDBJ whole genome shotgun (WGS) entry which is preliminary data.

9606:COBLL1
gene id: 9606:COBLL1
uniprot id: Q53SF7
names: Sequence Caution
messages: Intron retention.

9606:INPP5F
gene id: 9606:INPP5F
uniprot id: Q9Y2H2
names: Caution
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Early endosome
messages: Homodimer (PubMed:25869669). Interacts with OCRL and RAB5A (PubMed:25869668). Interacts with INPP5B and INPP4A (PubMed:25869668). Interacts with STAT3; the interaction is independent of STAT3 'Tyr-705' phosphorylation status (PubMed:25476455).
messages: INPP5F has been initially described as an inositol polyphosphate 5-phosphatase.
messages: Inositol 4-phosphatase which mainly acts on phosphatidylinositol 4-phosphate. May be functionally linked to OCRL, which converts phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol, for a sequential dephosphorylation of phosphatidylinositol 4,5-bisphosphate at the 5 and 4 position of inositol, thus playing an important role in the endocytic recycling (PubMed:25869669). Regulator of TF:TFRC and integrins recycling pathway, is also involved in cell migration mechanisms (PubMed:25869669). Modulates AKT/GSK3B pathway by decreasing AKT and GSK3B phosphorylation (PubMed:17322895). Negatively regulates STAT3 signaling pathway through inhibition of STAT3 phosphorylation and translocation to the nucleus (PubMed:25476455). Functionally important modulator of cardiac myocyte size and of the cardiac response to stress (By similarity). May play a role as negative regulator of axon regeneration after central nervous system injuries (By similarity).
messages: Recycling endosome
messages: Ubiquitous (PubMed:11274189). Highly expressed in brain (PubMed:26203138).
messages: clathrin-coated pit

9606:MORF4L2
gene id: 9606:MORF4L2
uniprot id: Q15014
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Component of the NuA4 histone acetyltransferase complex which contains the catalytic subunit KAT5/TIP60 and the subunits EP400, TRRAP/PAF400, BRD8/SMAP, EPC1, DMAP1/DNMAP1, RUVBL1/TIP49, RUVBL2, ING3, actin, ACTL6A/BAF53A, MORF4L1/MRG15, MORF4L2/MRGX, MRGBP, YEATS4/GAS41 and VPS72/YL1. The NuA4 complex interacts with MYC and the adenovirus E1A protein. MORF4L1 may also participate in the formation of NuA4 related complexes which lack the KAT5/TIP60 catalytic subunit, but which include the SWI/SNF related protein SRCAP. Component of the MSIN3A histone deacetylase complex, which includes SIN3A, HDAC2, ARID4B, MORF4L1, RBBP4/RbAp48, and RBBP7/RbAp46. Interacts with MRFAP1 and RB1. May also interact with one or more as yet undefined members of the TLE (transducin-like enhancer of split) family of transcriptional repressors.
messages: Component of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histone H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair. The NuA4 complex ATPase and helicase activities seem to be, at least in part, contributed by the association of RUVBL1 and RUVBL2 with EP400. NuA4 may also play a direct role in DNA repair when directly recruited to sites of DNA damage. Also a component of the MSIN3A complex which acts to repress transcription by deacetylation of nucleosomal histones.
messages: Nucleus

9606:BTBD17
gene id: 9606:BTBD17
uniprot id: A6NE02
names: Subcellular Location Annotation
messages: Secreted

9606:FRYL
gene id: 9606:FRYL
uniprot id: O94915
names: Disease Annotation
names: Function
names: Similarity
names: Tissue Specificity
messages: A chromosomal aberration involving FRYL is found in treatment-related acute lymphoblastic leukemia (ALL). Translocation t(4;11)(p12;q23) that forms a KMT2A/MLL1-FRYL fusion protein.
messages: Belongs to the furry protein family.
messages: Plays a key role in maintaining the integrity of polarized cell extensions during morphogenesis, regulates the actin cytoskeleton and plays a key role in patterning sensory neuron dendritic fields by promoting avoidance between homologous dendrites as well as by limiting dendritic branching (By similarity). May function as a transcriptional activator.
messages: Widely expressed with higher expression in colon, placenta, brain and cells of lymphoid origin.

9606:PLD1
gene id: 9606:PLD1
uniprot id: Q13393
uniprot id: Q59EA4
names: Activity Regulation
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the phospholipase D family.
messages: Endoplasmic reticulum membrane
messages: Expressed abundantly in the pancreas and heart and at high levels in brain, placenta, spleen, uterus and small intestine.
messages: Function as phospholipase selective for phosphatidylcholine (PubMed:8530346, PubMed:9582313, PubMed:25936805). Implicated as a critical step in numerous cellular pathways, including signal transduction, membrane trafficking, and the regulation of mitosis. May be involved in the regulation of perinuclear intravesicular membrane traffic (By similarity).
messages: Golgi apparatus membrane
messages: Interacts with PIP5K1B.
messages: Late endosome membrane
messages: Stimulated by phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate, activated by the phosphokinase C-alpha, by the ADP-ribosylation factor-1 (ARF-1), and to a lesser extent by GTP-binding proteins: RHO A, RAC-1 and CDC42. Inhibited by oleate.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: perinuclear region

9606:NUP85
gene id: 9606:NUP85
uniprot id: J3KT10
uniprot id: Q9BW27
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the nucleoporin Nup85 family.
messages: Component of the nuclear pore complex (NPC) (PubMed:12196509). Component of the NPC Nup107-160 subcomplex, consisting of at least NUP107, NUP98/Nup96, NUP160, NUP133, NUP85, NUP37, NUP43 and SEC13 (PubMed:15146057). Interacts with NUP160, NUP133 and SEC13 (PubMed:12718872, PubMed:30179222). Interacts with NUP37, NUP107 and NUP43 (PubMed:15146057). Interacts with CCR2 (PubMed:15995708).
messages: Component of the nuclear pore complex (NPC).
messages: Cytoplasm
messages: Essential component of the nuclear pore complex (NPC) that seems to be required for NPC assembly and maintenance (PubMed:12718872). As part of the NPC Nup107-160 subcomplex plays a role in RNA export and in tethering NUP96/Nup98 and NUP153 to the nucleus (PubMed:12718872). The Nup107-160 complex seems to be required for spindle assembly during mitosis (PubMed:16807356). NUP85 is required for membrane clustering of CCL2-activated CCR2 (PubMed:15995708). Seems to be involved in CCR2-mediated chemotaxis of monocytes and may link activated CCR2 to the phosphatidyl-inositol 3-kinase-Rac-lammellipodium protrusion cascade (PubMed:15995708). Involved in nephrogenesis (PubMed:30179222).
messages: Functions as a component of the nuclear pore complex (NPC).
messages: Nucleus membrane
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: kinetochore
messages: nuclear pore complex
messages: spindle

9606:ARFIP2
gene id: 9606:ARFIP2
uniprot id: P53365
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Forms homodimers or heterodimers with ARFIP1 (PubMed:21239483). Interacts with RAC1 (PubMed:11346801). Specifically binds to GTP-bound ARF1 and ARF6, but binds to RAC1.GTP and RAC1.GDP with similar affinities. Interacts with ARL1 (PubMed:11303027, PubMed:22679020, PubMed:26507660). Interacts (via N-terminus) with IKBKB and IKBKG; these interactions inhibit activation of NF-kappa-B (PubMed:26296658).
messages: Golgi apparatus
messages: Plays a role in constitutive metalloproteinase (MMP) secretion from the trans Golgi network (PubMed:26507660). May have important functions during vesicle biogenesis at certain cargo subdomains, which could be predominantly utilized by secreted MMPs, such as MMP7 and MMP2 (PubMed:26507660). Also involved in autophagy by regulating the starvation-dependent trafficking of ATG9A vesicles which deliver the phosphatidylinositol 4-kinase beta (PI4KB) to the autophagosome initiation site (PubMed:31204568, PubMed:30917996). Involved in phagophore growth during mitophagy by regulating ATG9A trafficking to mitochondria (PubMed:33773106). In addition, plays a role in NF-kappa-B inhibition by interacting with IKBKB and IKBKG (PubMed:26296658).
messages: trans-Golgi network membrane

9606:NOC4L
gene id: 9606:NOC4L
uniprot id: Q9BVI4
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the CBF/MAK21 family.
messages: Nucleus membrane
messages: nucleolus

9606:ISG20
gene id: 9606:ISG20
uniprot id: Q96AZ6
names: Cofactor
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Associates with PML and SP100 in the PML NB complex. Associates with survival motor neuron protein (SMN)-containing macromolecular nuclear complexes and U1 and U2 snRNAs and U3 snoRNA.
messages: Belongs to the exonuclease superfamily.
messages: Binds 2 manganese ions per subunit.
messages: Cajal body
messages: Cytoplasm
messages: Highly expressed in peripheral blood leukocytes, spleen, thymus, colon and lung. Up regulated by E2 in estrogen receptor-positive breast cancer lines.
messages: Induced by interferons alpha and beta. Weaker induction was seen with interferon gamma. Increased expression was seen at the transcriptional level.
messages: Interferon-induced antiviral exoribonuclease that acts mainly on single-stranded RNA (PubMed:11401564, PubMed:12594219, PubMed:16033969). Exhibits antiviral activity against RNA viruses including hepatitis C virus (HCV), hepatitis A virus (HAV) and yellow fever virus (YFV) (PubMed:16514659, PubMed:21036379). Inhibition of several viruses such as chikungunya virus (CHIKV) does not involve the degradation of viral RNAs, but rather the inhibition of translation of viral proteins (By similarity). Exerts a translational control over a large panel of non-self RNA substrates while sparing endogenous transcripts. This activity correlates with the protein's ability to localize in cytoplasmic processing bodies (PubMed:31600344). May also act as master regulator of over hundred interferon stimulated genes leading to viral genome translation inhibition (By similarity). May play additional roles in the maturation of snRNAs and rRNAs, and in ribosome biogenesis (PubMed:16514659).
messages: Nucleus
messages: P-body
messages: nucleolus

9606:HNRNPAB
gene id: 9606:HNRNPAB
uniprot id: Q99729
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Binds single-stranded RNA. Has a high affinity for G-rich and U-rich regions of hnRNA. Also binds to APOB mRNA transcripts around the RNA editing site.
messages: Cytoplasm
messages: Dimethylation at Arg-322 is probably asymmetric.
messages: Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Interacts with APOBEC1.
messages: Nucleus
messages: Ubiquitous.

9606:TCIM
gene id: 9606:TCIM
uniprot id: Q9NR00
names: Function
names: Induction
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cytoplasm
messages: Induced by pro-inflammatory cytokines such as TNF and IL1B, via NF-kappaB signaling (PubMed:16730711, PubMed:19684084). Induced by cellular stresses such as heat shock, TPA, lipopolysaccharide and UV (PubMed:17603013). Induced by mitogens such as thrombin (PubMed:18959821).
messages: Monomer. Interacts with NOTCH2 (via ANK repeats), the interaction inhibits the nuclear translocation of NOTCH2 N2ICD (PubMed:25985737). Interacts (C-terminus) with CBY1 (C-terminus), TCIM competes with CTNNB1 for the interaction with CBY1 (PubMed:16424001).
messages: Nucleus
messages: Nucleus speckle
messages: Seems to be involved in the regulation of cell growth an differentiation, may play different and opposite roles depending on the tissue or cell type. May enhance the WNT-CTNNB1 pathway by relieving antagonistic activity of CBY1 (PubMed:16424001, PubMed:16730711). Enhances the proliferation of follicular dendritic cells (PubMed:16730711). Plays a role in the mitogen-activated MAPK2/3 signaling pathway, positively regulates G1-to-S-phase transition of the cell cycle (PubMed:18959821). In endothelial cells, enhances key inflammatory mediators and inflammatory response through the modulation of NF-kappaB transcriptional regulatory activity (PubMed:19684084). Involved in the regulation of heat shock response, seems to play a positive feedback with HSF1 to modulate heat-shock downstream gene expression (PubMed:17603013). Plays a role in the regulation of hematopoiesis even if the mechanisms are unknown (By similarity). In cancers such as thyroid or lung cancer, it has been described as promoter of cell proliferation, G1-to-S-phase transition and inhibitor of apoptosis (PubMed:15087392, PubMed:24941347). However, it negatively regulates self-renewal of liver cancer cells via suppresion of NOTCH2 signaling (PubMed:25985737).
messages: Ubiquitous. Expressed in thyroid papillary carcinoma. Expressed in liver, expression levels decrease in hepatocellular carcinoma (PubMed:25985737). Slightly detected in normal lung, its expression is highly induced in lung cancer cells (at protein level) (PubMed:24941347).
messages: nucleolus

9606:RGS19
gene id: 9606:RGS19
uniprot id: P49795
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Fatty acylated. Heavily palmitoylated in the cysteine string motif.
messages: Highest expression in lung. Placenta, liver and heart also express high levels of GAIP.
messages: Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form. Binds to G-alpha subfamily 1 members, with the order G(i)a3 > G(i)a1 > G(o)a >> G(z)a/G(i)a2. Activity on G(z)-alpha is inhibited by phosphorylation and palmitoylation of the G-protein.
messages: Interacts with GIPC PDZ domain. Interacts with GNAO1 (PubMed:34685729).
messages: Membrane
messages: Phosphorylated, mainly on serine residues.

9606:SMARCD2
gene id: 9606:SMARCD2
uniprot id: J3KMX2
uniprot id: Q92925
names: Disease Annotation
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the SMARCD family.
messages: Component of the multiprotein chromatin-remodeling complexes SWI/SNF: SWI/SNF-A (BAF), SWI/SNF-B (PBAF) and related complexes. The canonical complex contains a catalytic subunit (either SMARCA4/BRG1/BAF190A or SMARCA2/BRM/BAF190B), and at least SMARCE1, ACTL6A/BAF53, SMARCC1/BAF155, SMARCC2/BAF170, and SMARCB1/SNF5/BAF47. Other subunits specific to each of the complexes may also be present permitting several possible combinations developmentally and tissue specific (PubMed:22952240). Component of the BAF complex, which includes at least actin (ACTB), ARID1A/BAF250A, ARID1B/BAF250B, SMARCA2/BRM, SMARCA4/BRG1, ACTL6A/BAF53, ACTL6B/BAF53B, SMARCE1/BAF57, SMARCC1/BAF155, SMARCC2/BAF170, SMARCB1/SNF5/INI1, and one or more SMARCD1/BAF60A, SMARCD2/BAF60B, or SMARCD3/BAF60C (PubMed:18765789). In muscle cells, the BAF complex also contains DPF3. Component of the SWI/SNF-B (PBAF) chromatin remodeling complex, at least composed of SMARCA4/BRG1, SMARCB1/BAF47/SNF5, ACTL6A/BAF53A or ACTL6B/BAF53B, SMARCE1/BAF57, SMARCD1/BAF60A, SMARCD2/BAF60B, perhaps SMARCD3/BAF60C, SMARCC1/BAF155, SMARCC2/BAF170, PBRM1/BAF180, ARID2/BAF200 and actin (ACTB) (PubMed:22952240, PubMed:26601204). Interacts with UNKL (PubMed:20148946). Interacts with CEBPE (PubMed:28369036).
messages: Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Component of SWI/SNF chromatin remodeling complexes that carry out key enzymatic activities, changing chromatin structure by altering DNA-histone contacts within a nucleosome in an ATP-dependent manner (PubMed:22952240, PubMed:26601204). Critical regulator of myeloid differentiation, controlling granulocytopoiesis and the expression of genes involved in neutrophil granule formation (PubMed:28369036).
messages: Isoform 2 is expressed in the pancreas.
messages: Nucleus
messages: Produced by aberrant splicing sites.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitinated through a signaling process involving RAC1 and the RING finger protein UNKL.

9606:ARAP3
gene id: 9606:ARAP3
uniprot id: Q8WWN8
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: Cell membrane
messages: Cytoplasm
messages: Interacts (via SAM domain) with INPPL1/SHIP2.
messages: Phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating protein that modulates actin cytoskeleton remodeling by regulating ARF and RHO family members. Is activated by phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) binding. Can be activated by phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding, albeit with lower efficiency. Acts on ARF6, RAC1, RHOA and CDC42. Plays a role in the internalization of anthrax toxin.
messages: Tyrosine phosphorylated at a low basal level. PDGF treatment stimulates phosphorylation. Tyrosine phosphorylation is increased in cells that are in the process of becoming attached to a substrate and that start spreading and flattening (By similarity).
messages: cytoskeleton
messages: lamellipodium
messages: ruffle

9606:PHF5A
gene id: 9606:PHF5A
uniprot id: Q7RTV0
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the PHF5 family.
messages: Interacts (via N-terminus) with U2AF1 and SRSF5; acts to bridge the two. Interacts (via C-terminus) with EP400 and DDX1; acts to bridge the two (By similarity). Component of splicing factor SF3B complex which is composed of at least eight subunits; SF3B1, SF3B2, SF3B3, SF3B4, SF3B5, SF3B6, PHF5A and DDX42 (PubMed:12234937, PubMed:12738865, PubMed:27720643, PubMed:28541300). Within the SF3B complex interacts directly with SF3B1 and SF3B3 (PubMed:27720643). The SF3B complex composed of SF3B1, SF3B2, SF3B3, SF3B4, SF3B5, SF3B6 and PHF5A interacts with U2AF2 (PubMed:27720643). SF3B associates with the splicing factor SF3A and a 12S RNA unit to form the U2 small nuclear ribonucleoproteins complex (U2 snRNP) (PubMed:12234937). Component of the minor spliceosome, also called U12-type spliceosome, which splices U12-type introns. Within this complex, interacts with CRIPT (PubMed:15146077, PubMed:33509932). Interacts with the PAF1 complex (PAF1C) composed of CDC73, PAF1, LEO1, CTR9, RTF1 and SKIC8. Within the PAF1C interacts directly with CDC73 and SKIC8. Interacts with RNA polymerase II (By similarity).
messages: Involved with the PAF1 complex (PAF1C) in transcriptional elongation by RNA polymerase II, and in regulation of development and maintenance of embryonic stem cell (ESC) pluripotency. Required for maintenance of ESCs self-renewal and cellular reprogramming of stem cells. Maintains pluripotency by recruiting and stabilizing PAF1C on pluripotency genes loci, and by regulating the expression of the pluripotency genes. Regulates the deposition of elongation-associated histone modifications, including dimethylated histone H3 'Lys-79' (H3K79me2) and trimethylated histone H3 'Lys-36' (H3K36me3), on PAF1C targets, self-renewal and pluripotency genes. Regulates RNA polymerase II promoter-proximal pause release of the PAF1C targets and self-renewal genes, and the levels of elongating ('Ser-2' phosphorylated) RNA polymerase II in their gene bodies. Regulates muscle specification in adult stem cells by stabilizing PAF1C in chromatin to promote myogenic differentiation (By similarity). Involved in pre-mRNA splicing as a component of the splicing factor SF3B complex (PubMed:27720643, PubMed:28541300). SF3B complex is required for 'A' complex assembly formed by the stable binding of U2 snRNP to the branchpoint sequence (BPS) in pre-mRNA. Sequence independent binding of SF3A/SF3B complex upstream of the branch site is essential, it may anchor U2 snRNP to the pre-mRNA (PubMed:12234937). Acts as a transcriptional regulator by binding to the GJA1/Cx43 promoter and enhancing its up-regulation by ESR1/ER-alpha (By similarity). As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable).
messages: Nucleus
messages: Nucleus speckle

9606:MGLL
gene id: 9606:MGLL
uniprot id: Q99685
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the AB hydrolase superfamily. Monoacylglycerol lipase family.
messages: Converts monoacylglycerides to free fatty acids and glycerol (PubMed:19029917, PubMed:20079333, PubMed:21049984, PubMed:22969151, PubMed:24368842). Hydrolyzes the endocannabinoid 2-arachidonoylglycerol, and thereby contributes to the regulation of endocannabinoid signaling, nociperception and perception of pain (PubMed:19029917, PubMed:20079333, PubMed:21049984, PubMed:22969151, PubMed:24368842). Regulates the levels of fatty acids that serve as signaling molecules and promote cancer cell migration, invasion and tumor growth (PubMed:20079333).
messages: Detected in adipose tissue, lung, liver, kidney, brain and heart.
messages: Homodimer.
messages: Membrane
messages: Short-term inhibition causes analgesia, while long-term inhibition causes tolerance to endocannabinoids acting on brain cannabinoid receptor CNR1, and a reduction in brain cannabinoid receptor CNR1 activity.
messages: cytosol

9606:NOL3
gene id: 9606:NOL3
uniprot id: O60936
names: Disease Annotation
names: Domain
names: Function
names: Induction
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: CARD is critical for both extrinsic and intrinsic apoptotic pathways (By similarity). CARD domain mediates a protective effect against myocardial ischemia/reperfusion, oxidative stress and TNF-induced necrosis (PubMed:15004034). The C-terminal domain (amino acids 99 to 208) is involved in calcium binding and plays a protective role in calcium-mediated cell death (PubMed:15509781).
messages: Cytoplasm
messages: Functions as an apoptosis repressor that blocks multiple modes of cell death. Inhibits extrinsic apoptotic pathways through two different ways. Firstly by interacting with FAS and FADD upon FAS activation blocking death-inducing signaling complex (DISC) assembly (By similarity). Secondly by interacting with CASP8 in a mitochondria localization- and phosphorylation-dependent manner, limiting the amount of soluble CASP8 available for DISC-mediated activation (By similarity). Inhibits intrinsic apoptotic pathway in response to a wide range of stresses, through its interaction with BAX resulting in BAX inactivation, preventing mitochondrial dysfunction and release of pro-apoptotic factors (PubMed:15004034). Inhibits calcium-mediated cell death by functioning as a cytosolic calcium buffer, dissociating its interaction with CASP8 and maintaining calcium homeostasis (PubMed:15509781). Negatively regulates oxidative stress-induced apoptosis by phosphorylation-dependent suppression of the mitochondria-mediated intrinsic pathway, by blocking CASP2 activation and BAX translocation (By similarity). Negatively regulates hypoxia-induced apoptosis in part by inhibiting the release of cytochrome c from mitochondria in a caspase-independent manner (By similarity). Also inhibits TNF-induced necrosis by preventing TNF-signaling pathway through TNFRSF1A interaction abrogating the recruitment of RIPK1 to complex I (By similarity). Finally through its role as apoptosis repressor, promotes vascular remodeling through inhibition of apoptosis and stimulation of proliferation, in response to hypoxia (By similarity). Inhibits too myoblast differentiation through caspase inhibition (By similarity).
messages: Highly expressed in heart and skeletal muscle. Detected at low levels in placenta, liver, kidney and pancreas.
messages: May be involved in RNA splicing.
messages: Membrane
messages: Mitochondrion
messages: Oligomerizes (via CARD doamin). Interacts (via CARD domain) with CASP2; inhibits CASP2 activity in a phosphorylation-dependent manner. Interacts with CASP8; decreases CASP8 activity in a mitochondria localization- and phosphorylation-dependent manner and this interaction is dissociated by calcium. Interacts with TFPT; translocates NOL3 into the nucleus and negatively regulated TFPT-induced cell death (By similarity). Interacts directly (via CARD domain) with FAS and FADD (via DED domain); inhibits death-inducing signaling complex death-inducing signaling complex (DISC) assembly by inhibiting the increase in FAS-FADD binding induced by FAS activation (By similarity). Interacts (via CARD domain) with BAX (via a C-terminal 33 residues); inhibits BAX activation and translocation and consequently cytochrome c release from mitochondria. Interacts with PPM1G; may dephosphorylate NOL3 (By similarity). Interacts (via CARD domain) with BBC3 (via BH3 domain); preventing the association of BBC3 with BCL2 and resulting in activation of CASP8 (By similarity). Interacts (via CARD domain) with BAD(via BH3 domain); preventing the association of BAD with BCL2 (By similarity). Interacts directly (via CARD domain) with TNFRSF1A; inhibits TNF-signaling pathway (By similarity). Isoform 1 binds to SFRS9/SRp30C.
messages: Phosphorylation at Thr-149 is required for its antiapoptotic effect by blocking death-inducing signaling complex death-inducing signaling complex (DISC) activity through the control of interaction with CASP8. Phosphorylation at Thr-149 results in translocation to mitochondria and this translocation enables the binding to CASP8. Dephosphorylated at Thr-149 by calcineurin; doesn't inhibit the association between FADD and CASP8 and the consequent apoptosis.
messages: Polyubiquitinated by MDM2; promoting proteasomal-dependent degradation in response to apoptotic stimuli.
messages: Protein expression decreases in hearts failure patients (PubMed:16505176) and in response to oxidative stress (PubMed:17142452).
messages: Sarcoplasmic reticulum
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: nucleolus

9606:NT5DC4
gene id: 9606:NT5DC4
uniprot id: A0A8I5KQP2
uniprot id: A0A8I5KQQ4
names: Cofactor
names: Similarity
messages: Belongs to the 5'(3')-deoxyribonucleotidase family.
messages: Binds 1 Mg(2+) ion per subunit.

9606:ZNF133
gene id: 9606:ZNF133
uniprot id: P52736
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: May be involved in transcriptional regulation as a repressor.
messages: Nucleus
messages: Seems ubiquitous. Seen in the heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.

9606:ACRBP
gene id: 9606:ACRBP
uniprot id: A0A140VJD6
uniprot id: Q8NEB7
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acrosomal protein that maintains proacrosin (pro-ACR) as an enzymatically inactive zymogen in the acrosome. Involved also in the acrosome formation.
messages: Binds proacrosin (pro-ACR). Does not bind the mature form of ACR.
messages: Expression restricted to testis in normal tissue. Expressed in a wide spectrum of cancers, including bladder, breast, liver, lung and colon cancers.
messages: Phosphorylated on Tyr residues in capacitated sperm.
messages: Secreted
messages: Synthesized as a 60-kDa precursor, the 32-kDa mature form is post-translationally produced by the removal of the N-terminal half of the precursor during sperm maturation in the testis and/or epididymis.
messages: The N-terminus is blocked.
messages: acrosome

9606:SPRED3
gene id: 9606:SPRED3
uniprot id: Q2MJR0
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: Cell membrane
messages: Interacts with palmitoyltransferase ZDHHC17/HIP14; the interaction leads to palmitoylation of SPRED3.
messages: Palmitoylated by ZDHHC17/HIP14.
messages: Phosphorylated on tyrosine.
messages: Tyrosine kinase substrate that inhibits growth-factor-mediated activation of MAP kinase (By similarity). Inhibits fibroblast growth factor (FGF)-induced retinal lens fiber differentiation, probably by inhibiting FGF-mediated phosphorylation of ERK1/2 (By similarity). Inhibits TGFB-induced epithelial-to-mesenchymal transition in lens epithelial cells (By similarity).
messages: Ubiquitinated.

9606:MYH4
gene id: 9606:MYH4
uniprot id: Q9Y623
names: Caution
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.
messages: Limited proteolysis of myosin heavy chain produces 1 light meromyosin (LMM) and 1 heavy meromyosin (HMM). HMM can be further cleaved into 2 globular subfragments (S1) and 1 rod-shaped subfragment (S2).
messages: Muscle contraction.
messages: Muscle myosin is a hexameric protein that consists of 2 heavy chain subunits (MHC), 2 alkali light chain subunits (MLC) and 2 regulatory light chain subunits (MLC-2).
messages: Represents a conventional myosin. This protein should not be confused with the unconventional myosin-4 (MYO4).
messages: The rodlike tail sequence is highly repetitive, showing cycles of a 28-residue repeat pattern composed of 4 heptapeptides, characteristic for alpha-helical coiled coils.
messages: myofibril

9606:FOXO4
gene id: 9606:FOXO4
uniprot id: P98177
names: Disease Annotation
names: Function
names: PTM
names: Pharmaceutical
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: A chromosomal aberration involving FOXO4 is found in acute leukemias. Translocation t(X;11)(q13;q23) with KMT2A/MLL1. The result is a rogue activator protein.
messages: A constitutively active FOXO4 mutant where phosphorylation sites Thr-32, Ser-197 and Ser-262 have been mutated to alanine may have therapeutic potential in ERBB2/HER2-overexpressing cancers as it inhibits ERBB2-mediated cell survival, transformation and tumorigenicity.
messages: Acetylation by CREBBP/CBP, which is induced by peroxidase stress, inhibits transcriptional activity. Deacetylation by SIRT1 is NAD-dependent and stimulates transcriptional activity.
messages: Cytoplasm
messages: Heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. Isoform zeta is most abundant in the liver, kidney, and pancreas.
messages: Interacts with CREBBP/CBP, CTNNB1, MYOCD, SIRT1, SRF and YWHAZ. Acetylated by CREBBP/CBP and deacetylated by SIRT1. Binding of YWHAZ inhibits DNA-binding. Interacts with USP7; the interaction is enhanced in presence of hydrogen peroxide and occurs independently of TP53. Interacts with NLK, and this inhibits monoubiquitination and transcriptional activity. Interacts with FOXK1; the interaction inhibits MEF2C transactivation activity (By similarity).
messages: Monoubiquitinated; monoubiquitination is induced by oxidative stress and reduced by deacetylase inhibitors; results in its relocalization to the nucleus and its increased transcriptional activity. Deubiquitinated by USP7; deubiquitination is induced by oxidative stress; enhances its interaction with USP7 and consequently, deubiquitination; increases its translocation to the cytoplasm and inhibits its transcriptional activity. Hydrogene-peroxide-induced ubiquitination and USP7-mediated deubiquitination have no major effect on its protein stability.
messages: Nucleus
messages: Phosphorylation by PKB/AKT1 inhibits transcriptional activity and is responsible for cytoplasmic localization. May be phosphorylated at multiple sites by NLK.
messages: Transcription factor involved in the regulation of the insulin signaling pathway. Binds to insulin-response elements (IREs) and can activate transcription of IGFBP1. Down-regulates expression of HIF1A and suppresses hypoxia-induced transcriptional activation of HIF1A-modulated genes. Also involved in negative regulation of the cell cycle. Involved in increased proteasome activity in embryonic stem cells (ESCs) by activating expression of PSMD11 in ESCs, leading to enhanced assembly of the 26S proteasome, followed by higher proteasome activity.

9606:ELL
gene id: 9606:ELL
uniprot id: P55199
uniprot id: U3KQ90
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: A chromosomal aberration involving ELL is found in acute leukemias. Translocation t(11;19)(q23;p13.1) with KMT2A/MLL1. The result is a rogue activator protein.
messages: Belongs to the ELL/occludin family.
messages: Cajal body
messages: Component of the super elongation complex (SEC), at least composed of EAF1, EAF2, CDK9, MLLT3/AF9, AFF (AFF1 or AFF4), the P-TEFb complex and ELL (ELL, ELL2 or ELL3). Component of the little elongation complex (LEC), at least composed of ELL (ELL, ELL2 or ELL3), ZC3H8, ICE1 and ICE2. Interacts with AFF4; the interaction is direct. Interacts with EAF1 and EAF2. Interacts with ICE1 (via N-terminus domain). Interacts with ICE2. Interacts with USPL1 (PubMed:24413172).
messages: Elongation factor component of the super elongation complex (SEC), a complex required to increase the catalytic rate of RNA polymerase II transcription by suppressing transient pausing by the polymerase at multiple sites along the DNA. Elongation factor component of the little elongation complex (LEC), a complex required to regulate small nuclear RNA (snRNA) gene transcription by RNA polymerase II and III (PubMed:22195968, PubMed:23932780). Specifically required for stimulating the elongation step of RNA polymerase II- and III-dependent snRNA gene transcription (PubMed:23932780). ELL also plays an early role before its assembly into in the SEC complex by stabilizing RNA polymerase II recruitment/initiation and entry into the pause site. Required to stabilize the pre-initiation complex and early elongation.
messages: Expressed in all tissues tested. Highest levels found in placenta, skeletal muscle, testis and peripheral blood leukocytes.
messages: Nucleus
messages: Nucleus speckle

9606:ASCL1
gene id: 9606:ASCL1
uniprot id: P50553
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Efficient DNA binding requires dimerization with another bHLH protein. Forms a heterodimer with TCF3.
messages: Nucleus
messages: Transcription factor that plays a key role in neuronal differentiation: acts as a pioneer transcription factor, accessing closed chromatin to allow other factors to bind and activate neural pathways. Directly binds the E box motif (5'-CANNTG-3') on promoters and promotes transcription of neuronal genes. The combination of three transcription factors, ASCL1, POU3F2/BRN2 and MYT1L, is sufficient to reprogram fibroblasts and other somatic cells into induced neuronal (iN) cells in vitro. Plays a role at early stages of development of specific neural lineages in most regions of the CNS, and of several lineages in the PNS. Essential for the generation of olfactory and autonomic neurons. Acts synergistically with FOXN4 to specify the identity of V2b neurons rather than V2a from bipotential p2 progenitors during spinal cord neurogenesis, probably through DLL4-NOTCH signaling activation. Involved in the regulation of neuroendocrine cell development in the glandular stomach (By similarity).

9606:KCTD10
gene id: 9606:KCTD10
uniprot id: Q9H3F6
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the BACURD family.
messages: Homotetramer; forms a two-fold symmetric tetramer in solution (PubMed:28963344). Interacts with CUL3; interaction is direct and forms a 5:5 heterodecamer (PubMed:28963344). Component of the BCR(BACURD3) E3 ubiquitin ligase complex, at least composed of CUL3, KCTD10/BACURD3 and RBX1 (By similarity). Interacts with DNA polymerase delta subunit 2/POLD2 (By similarity). Interacts with PCNA (PubMed:19125419).
messages: Nucleus
messages: Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex. The BCR(BACURD3) E3 ubiquitin ligase complex mediates the ubiquitination of target proteins, leading to their degradation by the proteasome (By similarity).

9606:KRTAP9-3
gene id: 9606:KRTAP9-3
uniprot id: Q9BYQ3
names: Function
names: Similarity
names: Subunit
messages: Belongs to the KRTAP type 9 family.
messages: In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.
messages: Interacts with hair keratins.

9606:RCAN2
gene id: 9606:RCAN2
uniprot id: B2R612
uniprot id: Q14206
names: Function
names: Induction
names: Similarity
names: Tissue Specificity
messages: Belongs to the RCAN family.
messages: By thyroid hormone.
messages: Expressed in fibroblasts, heart, brain, liver, and skeletal muscle but not in placenta, lung, kidney and pancreas.
messages: Inhibits calcineurin-dependent transcriptional responses by binding to the catalytic domain of calcineurin A. Could play a role during central nervous system development.

9606:ISM1
gene id: 9606:ISM1
uniprot id: B1AKI9
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Acts as an angiogenesis inhibitor.
messages: Belongs to the isthmin family.
messages: Interacts with integrin ITGAV/ITGB5.
messages: Secreted
messages: The C-terminal AMOP domain plays an important role in the anti-angiogenic function of ISM1.

9606:RIMS2
gene id: 9606:RIMS2
uniprot id: Q9UQ26
names: Disease Annotation
names: Function
names: Miscellaneous
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cell membrane
messages: Interacts with RAB3A and RAB3B that have been activated by GTP-binding. Interacts with RAB3C, RAB3D and RAB26. Interacts with TSPOAP1 and RIMBP2. Interacts with PPFIA3 and PPFIA4. Interacts via its zinc finger with the first C2 domain of UNC13A. Forms a complex consisting of UNC13A, RIMS2 and RAB3A. Heterodimer with PCLO. Part of a ternary complex involving PCLO and EPAC2 (By similarity).
messages: May be due to an intron retention.
messages: Presynaptic cell membrane
messages: Rab effector involved in exocytosis. May act as scaffold protein. Plays a role in dendrite formation by melanocytes (PubMed:23999003).
messages: Synapse
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Widely expressed (PubMed:32470375). Expressed in melanocytes (PubMed:23999003). In fetal tissues, predominantly expressed in the brain (PubMed:32470375). In the retina, expressed in the outer plexiform layer (at protein level) (PubMed:32470375). In the cerebellum, expressed in Purkinje cells (at protein level) (PubMed:32470375). In the pancreas, expressed in Langerhans islets (at protein level) (PubMed:32470375).

9606:HINT1
gene id: 9606:HINT1
uniprot id: A0A384NPU2
uniprot id: P49773
names: Caution
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the HINT family.
messages: Cytoplasm
messages: Exhibits adenosine 5'-monophosphoramidase activity, hydrolyzing purine nucleotide phosphoramidates with a single phosphate group such as adenosine 5'monophosphoramidate (AMP-NH2) to yield AMP and NH2 (PubMed:15703176, PubMed:16835243, PubMed:17337452, PubMed:17217311, PubMed:23614568, PubMed:28691797, PubMed:29787766, PubMed:31990367, PubMed:22329685). Hydrolyzes adenosine 5'monophosphomorpholidate (AMP-morpholidate) and guanosine 5'monophosphomorpholidate (GMP-morpholidate) (PubMed:15703176, PubMed:16835243). Hydrolyzes lysyl-AMP (AMP-N-epsilon-(N-alpha-acetyl lysine methyl ester)) generated by lysine tRNA ligase, as well as Met-AMP, His-AMP and Asp-AMP, lysyl-GMP (GMP-N-epsilon-(N-alpha-acetyl lysine methyl ester)) and AMP-N-alanine methyl ester (PubMed:15703176, PubMed:22329685, PubMed:17337452). Hydrolyzes 3-indolepropionic acyl-adenylate, tryptamine adenosine phosphoramidate monoester and other fluorogenic purine nucleoside tryptamine phosphoramidates in vitro (PubMed:17337452, PubMed:23614568, PubMed:29787766, PubMed:17217311, PubMed:28691797, PubMed:31990367). Can also convert adenosine 5'-O-phosphorothioate and guanosine 5'-O-phosphorothioate to the corresponding nucleoside 5'-O-phosphates with concomitant release of hydrogen sulfide (PubMed:30772266). In addition, functions as scaffolding protein that modulates transcriptional activation by the LEF1/TCF1-CTNNB1 complex and by the complex formed with MITF and CTNNB1 (PubMed:16014379, PubMed:22647378). Modulates p53/TP53 levels and p53/TP53-mediated apoptosis (PubMed:16835243). Modulates proteasomal degradation of target proteins by the SCF (SKP2-CUL1-F-box protein) E3 ubiquitin-protein ligase complex (PubMed:19112177). Also exhibits SUMO-specific isopeptidase activity, deconjugating SUMO1 from RGS17 (PubMed:31088288). Deconjugates SUMO1 from RANGAP1 (By similarity).
messages: Homodimer. Interacts with CDK7. Interacts with RUVBL1 and RUVBL2 and is associated with the LEF1/TCF1-CTNNB1 complex and with a KAT5 histone acetyltransferase complex. Identified in a complex with MITF and CTNNB1. Interacts with CDC34 and RBX1, and is part of a SCF (SKP2-CUL1-F-box protein) E3 ubiquitin-protein ligase complex (PubMed:19112177). Interacts with SUMO1, SUMO2 and RGS17 (By similarity). Interacts with the Ten-1 ICD form of TENM1 (By similarity). Interacts with CALM1; interaction increases in the presence of calcium ions (By similarity).
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Was originally thought to be a protein kinase C inhibitor and to bind zinc in solution. Both seem to be incorrect.
messages: Widely expressed.

9606:KCTD20
gene id: 9606:KCTD20
uniprot id: Q7Z5Y7
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Cytoplasm
messages: Interacts with AKT1; AKT2 and AKT3 (By similarity). Associates with PP2CA (By similarity). Part of a complex containing MARK4 (PubMed:14676191).
messages: Promotes the phosphorylation of AKT family members.

9606:ATP6V1A
gene id: 9606:ATP6V1A
uniprot id: P38606
names: Activity Regulation
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts with Rabies virus protein M; this interaction promotes virion uncoating.
messages: (Microbial infection) Plays an important role in virion uncoating during Rabies virus replication after membrane fusion. Specifically, participates in the dissociation of incoming viral matrix M proteins uncoating through direct interaction.
messages: ATP hydrolysis occurs at the interface between the nucleotide-binding domains of subunits A and B (By similarity). ATP hydrolysis triggers a conformational change in the subunits D and F, which induces a shift of subunit d (By similarity). The c-ring is subsequently rotated and results in a continuous proton translocation across the membrane (By similarity).
messages: Belongs to the ATPase alpha/beta chains family.
messages: Catalytic subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons (PubMed:8463241). V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment (PubMed:32001091). In aerobic conditions, involved in intracellular iron homeostasis, thus triggering the activity of Fe(2+) prolyl hydroxylase (PHD) enzymes, and leading to HIF1A hydroxylation and subsequent proteasomal degradation (PubMed:28296633). May play a role in neurite development and synaptic connectivity (PubMed:29668857).
messages: Cytoplasm
messages: High expression in the skin.
messages: Lysosome
messages: Phosphorylation at Ser-384 by AMPK down-regulates its enzyme activity.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex (PubMed:33065002). The V1 complex consists of three catalytic AB heterodimers that form a heterohexamer, three peripheral stalks each consisting of EG heterodimers, one central rotor including subunits D and F, and the regulatory subunits C and H (PubMed:33065002). The proton translocation complex V0 consists of the proton transport subunit a, a ring of proteolipid subunits c9c'', rotary subunit d, subunits e and f, and the accessory subunits ATP6AP1/Ac45 and ATP6AP2/PRR (PubMed:33065002). Interacts with the V0 complex V-ATPase subunit a4 ATP6V0A4 (By similarity). Interacts with WFS1 (PubMed:23035048). Interacts with alpha-crystallin B chain/CRYAB and with MTOR, forming a ternary complex (PubMed:31786107).
messages: clathrin-coated vesicle membrane
messages: cytosol
messages: secretory vesicle

9606:SNAPC1
gene id: 9606:SNAPC1
uniprot id: Q16533
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Nucleus
messages: Part of the SNAPc complex composed of 5 subunits: SNAPC1, SNAPC2, SNAPC3, SNAPC4 and SNAPC5. SNAPC1 interacts with SNAPC3, SNAPC4 and TBP.
messages: Part of the SNAPc complex required for the transcription of both RNA polymerase II and III small-nuclear RNA genes. Binds to the proximal sequence element (PSE), a non-TATA-box basal promoter element common to these 2 types of genes. Recruits TBP and BRF2 to the U6 snRNA TATA box.

9606:ZACN
gene id: 9606:ZACN
uniprot id: Q401N2
names: Caution
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the ligand-gated ion channel (TC 1.A.9) family.
messages: Cell membrane
messages: Detected in pancreas, brain, liver, placenta, trachea, kidney, spinal cord, stomach and fetal brain. In the adult brain region expression is detected in the hippocampus, striatum, amygdala and thalamus.
messages: Glycosylated.
messages: It is uncertain whether Met-1 or Met-2 is the initiator.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: The mouse and rat orthologous proteins do not exist.
messages: Zinc-activated ligand-gated ion channel.

9606:RPLP1
gene id: 9606:RPLP1
uniprot id: P05386
names: Function
names: PTM
names: Similarity
names: Subunit
messages: Belongs to the eukaryotic ribosomal protein P1/P2 family.
messages: Heterodimer with RPLP2 at the lateral ribosomal stalk of the large ribosomal subunit.
messages: Plays an important role in the elongation step of protein synthesis.
messages: Ubiquitinated at Lys-92 and Lys-93 by RNF14 and RNF25 in response to ribosome collisions (ribosome stalling).

9606:PEDS1-UBE2V1
gene id: 9606:PEDS1-UBE2V1
uniprot id: A5PLL7
uniprot id: Q13404
names: Domain
names: Function
names: Induction
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the fatty acid desaturase CarF family.
messages: Belongs to the ubiquitin-conjugating enzyme family.
messages: Down-regulated during differentiation of cultured colon adenocarcinoma cells.
messages: Endoplasmic reticulum membrane
messages: Has no ubiquitin ligase activity on its own. The UBE2V1-UBE2N heterodimer catalyzes the synthesis of non-canonical poly-ubiquitin chains that are linked through Lys-63. This type of poly-ubiquitination activates IKK and does not seem to involve protein degradation by the proteasome. Plays a role in the activation of NF-kappa-B mediated by IL1B, TNF, TRAF6 and TRAF2. Mediates transcriptional activation of target genes. Plays a role in the control of progress through the cell cycle and differentiation. Plays a role in the error-free DNA repair pathway and contributes to the survival of cells after DNA damage. Promotes TRIM5 capsid-specific restriction activity and the UBE2V1-UBE2N heterodimer acts in concert with TRIM5 to generate 'Lys-63'-linked polyubiquitin chains which activate the MAP3K7/TAK1 complex which in turn results in the induction and expression of NF-kappa-B and MAPK-responsive inflammatory genes. Together with RNF135 and UBE2N, catalyzes the viral RNA-dependent 'Lys-63'-linked polyubiquitination of RIGI to activate the downstream signaling pathway that leads to interferon beta production (PubMed:31006531). UBE2V1-UBE2N together with TRAF3IP2 E3 ubiquitin ligase mediate 'Lys-63'-linked polyubiquitination of TRAF6, a component of IL17A-mediated signaling pathway.
messages: Heterodimer with UBE2N (PubMed:11057907, PubMed:16307917, PubMed:16893187). Interacts (UBE2V2-UBE2N heterodimer) with the E3 ligase STUB1 (via the U-box domain); the complex has a specific 'Lys-63'-linked polyubiquitination activity (PubMed:16307917). Interacts with TRAF6 (PubMed:11057907, PubMed:16307917).
messages: Highly expressed in thyroid, pancreas, spinal cord, lymph node, trachea, adrenal gland, bone marrow and pancreas. Detected at low levels in heart, breast, placenta, brain, liver, kidney, stomach and lung.
messages: Histidine box-1 and -2 together with other histidine residues are essential for catalytic activity.
messages: In human, PESD1 and UBE2V1 are adjacent genes which can produce independent proteins and can also be fused to form a PESD1-UBE2V1 hybrid protein.
messages: In human, PESD1/KUA and UBE2V1/UEV1 are adjacent genes which can produce independent proteins and can also be fused to form a PESD1-UBE2V1 hybrid protein.
messages: Nucleus
messages: Plasmanylethanolamine desaturase involved in plasmalogen biogenesis in the endoplasmic reticulum membrane (PubMed:31604315, PubMed:32209662, PubMed:33859415). Plasmalogens are glycerophospholipids with a hydrocarbon chain linked by a vinyl ether bond at the glycerol sn-1 position, and are involved in antioxidative and signaling mechanisms (PubMed:31604315).

9606:TIFA
gene id: 9606:TIFA
uniprot id: Q96CG3
names: Caution
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Adapter molecule that plays a key role in the activation of pro-inflammatory NF-kappa-B signaling following detection of bacterial pathogen-associated molecular pattern metabolites (PAMPs) (PubMed:12566447, PubMed:15492226, PubMed:26068852, PubMed:28877472, PubMed:28222186, PubMed:30111836). Promotes activation of an innate immune response by inducing the oligomerization and polyubiquitination of TRAF6, which leads to the activation of TAK1 and IKK through a proteasome-independent mechanism (PubMed:15492226, PubMed:26068852). TIFA-dependent innate immune response is triggered by ADP-D-glycero-beta-D-manno-heptose (ADP-Heptose), a potent PAMP present in all Gram-negative and some Gram-positive bacteria: ADP-Heptose is recognized by ALPK1, which phosphorylates TIFA at Thr-9, leading to TIFA homooligomerization and subsequent activation of pro-inflammatory NF-kappa-B signaling (PubMed:30111836).
messages: Belongs to the TIFA family.
messages: Cytoplasm
messages: D-glycero-beta-D-manno-heptose 1,7-bisphosphate (HBP) was initially thought to constitute the bacterial pathogen-associated molecular pattern metabolite (PAMP) triggering the ALPK1-TIFA innate immunune response (PubMed:26068852, PubMed:28877472, PubMed:28222186). It was however shown that ADP-D-glycero-beta-D-manno-heptose (ADP-Heptose) constitutes the main PAMP that activates the kinase activity of ALPK1, promoting phosphorylation of TIFA (PubMed:30111836).
messages: Homooligomer; homooligomerizes following phosphorylation at Thr-9 (PubMed:12566447, PubMed:22566686, PubMed:26068852, PubMed:26389808). Interacts with IRAK1, TRAF2 and TRAF6 (PubMed:12566447). Interacts with TIFAB; binding to TIFAB inhibits TRAF6 activation, possibly by inducing a conformational change in TIFA (PubMed:15047173). Interacts with ZCCHC11; binding to ZCCHC11 suppresses the TRAF6-dependent activation of NF-kappa-B (PubMed:16643855).
messages: Phosphorylated at Thr-9 following detection of ADP-D-glycero-beta-D-manno-heptose (ADP-Heptose) by ALPK1 (PubMed:30111836). Phosphorylation at Thr-9 by ALPK1 leads to the formation of an intermolecular binding between the FHA domain and phosphorylated Thr-9, promoting TIFA oligomerization and TIFA-mediated NF-kappa-B activation (PubMed:22566686, PubMed:30111836, PubMed:26389808).
messages: The FHA domain recognizes and binds phosphorylated Thr-9, promoting homooligomerization and subsequent activation of NF-kappa-B.

9606:SLC43A2
gene id: 9606:SLC43A2
uniprot id: Q8N370
names: Activity Regulation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Affinity and transport activity are regulated by a phosphorylation switch state at Ser-274 and Ser-297; increasing of affinity and amino acid transport activity via dephosphorylation at Ser-274 and phosphorylation at Ser-297.
messages: Basolateral cell membrane
messages: Belongs to the SLC43A transporter (TC 2.A.1.44) family.
messages: Cell membrane
messages: Dephosphorylation at Ser-274 and phosphorylation at Ser-297 increase affinity and amino acid transport activity (PubMed:30379325). Phosphorylation-dephosphorylation cycle is regulated by food-entrained diurnal rhythm and dietary proteins (By similarity).
messages: Detected in several tissues with higher expression in placenta, kidney and peripheral blood leukocytes (PubMed:15659399). In the kidney, is detected in epithelial cells of the distal tubule and collecting duct (PubMed:15659399). In the intestine, is expressed mainly in crypt cells of the intestinal microvilli and epithelial cells in the base of the villus (PubMed:15659399).
messages: Glycosylated.
messages: Uniporter that mediates the transport of the stereospecific L-phenylalanine, L-methionine and L-branched-chain amino acids, between the extracellular space and the cytoplasm and may control the transepithelial (re)absorption of neutral amino acid in kidney and small intestine (PubMed:30379325, PubMed:15659399). The transport activity is mediated through facilitated diffusion and is sodium ions-, chloride ions- and pH-independent (PubMed:15659399).

9606:ZNF286A
gene id: 9606:ZNF286A
uniprot id: Q9HBT8
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:GIPC1
gene id: 9606:GIPC1
uniprot id: A8K2I7
uniprot id: O14908
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the GIPC family.
messages: Cytoplasm
messages: Interacts with GLUT1 (C-terminus), ACTN1, KIF1B, MYO6, PLEKHG5, SDC4/syndecan-4 and SEMA4C/semaphorin-4C (By similarity). Interacts with RGS19 C-terminus. Interacts with HTLV-I Tax through the PDZ domain.
messages: May be involved in G protein-linked signaling.
messages: Membrane
messages: The disease may be caused by variants affecting the gene represented in this entry. GGC repeat expansions in the 5'-UTR ranging from 73 to 164 were reported in patients, compared with a normal range from 12 to 32 in unaffected individuals. Patient skeletal muscle showed similar protein levels to those of unaffected individuals.
messages: Widely expressed (PubMed:9770488). Expressed in skeletal muscle (at protein level) (PubMed:32413282).

9606:DERL2
gene id: 9606:DERL2
uniprot id: I3L3R8
uniprot id: Q9GZP9
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) In contrast to DERL1, it is not involved in the degradation of MHC class I heavy chains following infection by cytomegaloviruses.
messages: Belongs to the derlin family.
messages: Endoplasmic reticulum membrane
messages: Forms homo- and heterooligomers with DERL3 and, to a lesser extent, with DERL1 (PubMed:16186509). Interacts with the SEL1L/SYVN1 and VCP/SELENOS protein complexes (PubMed:16186509). Mediates association between VCP and EDEM1, as well as that between VCP and the misfolded glycoproteins (PubMed:16449189). Interacts with OS9 (PubMed:19084021). Interacts with SELENOK and SELENOS (PubMed:22016385). Interacts with the signal recognition particle/SRP and the SRP receptor; in the process of endoplasmic reticulum stress-induced pre-emptive quality control (PubMed:26565908). Interacts with CCDC47 (By similarity).
messages: Functional component of endoplasmic reticulum-associated degradation (ERAD) for misfolded lumenal glycoproteins, but not that of misfolded nonglycoproteins. May act by forming a channel that allows the retrotranslocation of misfolded glycoproteins into the cytosol where they are ubiquitinated and degraded by the proteasome. May mediate the interaction between VCP and misfolded glycoproteins (PubMed:16186509, PubMed:16449189). May also be involved in endoplasmic reticulum stress-induced pre-emptive quality control, a mechanism that selectively attenuates the translocation of newly synthesized proteins into the endoplasmic reticulum and reroutes them to the cytosol for proteasomal degradation (PubMed:26565908).
messages: Membrane
messages: Ubiquitous. Overexpressed in various hepatocarcinomas.
messages: Up-regulated in response to endoplasmic reticulum stress via the ERN1-XBP1 pathway of the unfolded protein response (UPR).

9606:ANTXRL
gene id: 9606:ANTXRL
uniprot id: A0A2U7XUX1
uniprot id: A6NF34
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the ATR family.
messages: Membrane

9606:ANKS6
gene id: 9606:ANKS6
uniprot id: Q68DC2
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: Cytoplasm
messages: Homooligomer (By similarity). Central component of a complex containing at least ANKS6, INVS, NEK8 and NPHP3 (PubMed:23793029). ANKS6 may organize complex assembly by linking INVS and NPHP3 to NEK8 and INVS may target the complex to the proximal ciliary axoneme (PubMed:23793029). Interacts (via SAM domain) with BICC1 (via KH domains) in an RNA-dependent manner (By similarity). Interacts (via SAM domain) with ANKS3 (via SAM domain) (PubMed:24998259).
messages: Hydroxylated at Asn-138, most probably by HIF1AN. This hydroxylation results in decreased NEK8-binding.
messages: Required for renal function.
messages: The SAM domain mediates interaction with the SAM domain of ANKS3.
messages: The ankyrin repeats are necessary and sufficient for NEK8-binding.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: cilium

9606:VIPR1
gene id: 9606:VIPR1
uniprot id: B4DNY6
uniprot id: P32241
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor 2 family.
messages: Cell membrane
messages: In lung, HT-29 colonic epithelial cells, Raji B-lymphoblasts. Lesser extent in brain, heart, kidney, liver and placenta. Not expressed in CD4+ or CD8+ T-cells. Expressed in the T-cell lines HARRIS, HuT 78, Jurkat and SUP-T1, but not in the T-cell lines Peer, MOLT-4, HSB and YT.
messages: Membrane
messages: This is a receptor for VIP. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. The affinity is VIP = PACAP-27 > PACAP-38.

9606:RPL24
gene id: 9606:RPL24
uniprot id: P83731
uniprot id: V9HW01
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the eukaryotic ribosomal protein eL24 family.
messages: Component of the large ribosomal subunit.
messages: Component of the large ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell.
messages: Cytoplasm
messages: Mono-ADP-ribosylation at Glu-4 by PARP16 inhibits polysome assembly and mRNA loading, thereby inhibiting protein translation.

9606:PHRF1
gene id: 9606:PHRF1
uniprot id: Q9P1Y6
names: Subunit
messages: Interacts with POLR2A (via the C-terminal domain).

9606:STK36
gene id: 9606:STK36
uniprot id: Q9NRP7
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.
messages: Cytoplasm
messages: Expressed at low levels in most fetal tissues, adult ovaries and at high levels in adult testis, where it is localized in germ cells (PubMed:10806483). Expressed in respiratory epithelial cells of the lung (PubMed:28543983).
messages: Interacts with GLI1, GLI2 and GLI3 (PubMed:10806483). Interacts with SPAG16 and KIF27.
messages: Nucleus
messages: Serine/threonine protein kinase which plays an important role in the sonic hedgehog (Shh) pathway by regulating the activity of GLI transcription factors (PubMed:10806483). Controls the activity of the transcriptional regulators GLI1, GLI2 and GLI3 by opposing the effect of SUFU and promoting their nuclear localization (PubMed:10806483). GLI2 requires an additional function of STK36 to become transcriptionally active, but the enzyme does not need to possess an active kinase catalytic site for this to occur (PubMed:10806483). Required for postnatal development, possibly by regulating the homeostasis of cerebral spinal fluid or ciliary function. Essential for construction of the central pair apparatus of motile cilia.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: cilium axoneme

9606:SGSH
gene id: 9606:SGSH
uniprot id: P51688
names: Cofactor
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the sulfatase family.
messages: Binds 1 Ca(2+) ion per subunit.
messages: Catalyzes a step in lysosomal heparan sulfate degradation.
messages: Lysosome
messages: The conversion to 3-oxoalanine (also known as C-formylglycine, FGly), of a serine or cysteine residue in prokaryotes and of a cysteine residue in eukaryotes, is critical for catalytic activity.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:H2AC6
gene id: 9606:H2AC6
uniprot id: Q93077
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the histone H2A family.
messages: Chromosome
messages: Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
messages: Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.
messages: Deiminated on Arg-4 in granulocytes upon calcium entry.
messages: Glutamine methylation at Gln-105 (H2AQ104me) by FBL is specifically dedicated to polymerase I. It is present at 35S ribosomal DNA locus and impairs binding of the FACT complex (PubMed:24352239).
messages: Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.
messages: Monoubiquitination of Lys-120 (H2AK119Ub) by RING1, TRIM37 and RNF2/RING2 complex gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. It is involved in the initiation of both imprinted and random X inactivation. Ubiquitinated H2A is enriched in inactive X chromosome chromatin. Ubiquitination of H2A functions downstream of methylation of 'Lys-27' of histone H3 (H3K27me). H2AK119Ub by RNF2/RING2 can also be induced by ultraviolet and may be involved in DNA repair. Monoubiquitination of Lys-120 (H2AK119Ub) by TRIM37 may promote transformation of cells in a number of breast cancers (PubMed:25470042). Following DNA double-strand breaks (DSBs), it is ubiquitinated through 'Lys-63' linkage of ubiquitin moieties by the E2 ligase UBE2N and the E3 ligases RNF8 and RNF168, leading to the recruitment of repair proteins to sites of DNA damage. Ubiquitination at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) in response to DNA damage is initiated by RNF168 that mediates monoubiquitination at these 2 sites, and 'Lys-63'-linked ubiquitin are then conjugated to monoubiquitin; RNF8 is able to extend 'Lys-63'-linked ubiquitin chains in vitro. Deubiquitinated by USP51 at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) after damaged DNA is repaired (PubMed:27083998). H2AK119Ub and ionizing radiation-induced 'Lys-63'-linked ubiquitination (H2AK13Ub and H2AK15Ub) are distinct events.
messages: Nucleus
messages: Phosphorylation on Ser-2 (H2AS1ph) is enhanced during mitosis. Phosphorylation on Ser-2 by RPS6KA5/MSK1 directly represses transcription. Acetylation of H3 inhibits Ser-2 phosphorylation by RPS6KA5/MSK1. Phosphorylation at Thr-121 (H2AT120ph) by DCAF1 is present in the regulatory region of many tumor suppresor genes and down-regulates their transcription.
messages: Symmetric dimethylation on Arg-4 by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage.
messages: The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.

9606:ST6GAL1
gene id: 9606:ST6GAL1
uniprot id: P15907
names: Activity Regulation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the glycosyltransferase 29 family.
messages: Golgi stack membrane
messages: Inhibited by CTP.
messages: Monomer and homodimer.
messages: N-glycosylated.
messages: Secreted
messages: The HB-6, CDW75, and CD76 differentiation antigens are cell-surface carbohydrate determinants generated by this enzyme.
messages: The soluble form derives from the membrane form by proteolytic processing.
messages: Transfers sialic acid from CMP-sialic acid to galactose-containing acceptor substrates.

9606:PEX7
gene id: 9606:PEX7
uniprot id: O00628
uniprot id: Q6FGN1
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the WD repeat peroxin-7 family.
messages: Interacts with PEX5; interaction only takes place when PEX7 is associated with cargo proteins (PubMed:11546814, PubMed:33389129, PubMed:25538232). Interacts with VWA8 (PubMed:30204880).
messages: Peroxisome matrix
messages: Receptor required for the peroxisomal import of proteins containing a C-terminal PTS2-type peroxisomal targeting signal (PubMed:9090381, PubMed:11931631, PubMed:22057399, PubMed:25538232). Specifically binds to cargo proteins containing a PTS2 peroxisomal targeting signal in the cytosol (PubMed:11931631, PubMed:22057399, PubMed:25538232). Cargo protein-binding triggers interaction with PEX5 and formation of a ternary complex composed of PEX5 and PEX7 along with PTS2-containing cargo proteins, which is tranlocated into peroxisomes by passing through the PEX13-PEX14 docking complex (PubMed:11546814, PubMed:25538232).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitous (PubMed:9090381). Highest expression in pancreas, skeletal muscle and heart (PubMed:9090381).
messages: cytosol

9606:CYP2U1
gene id: 9606:CYP2U1
uniprot id: Q7Z449
names: Developmental Stage
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: A cytochrome P450 monooxygenase involved in the metabolism of arachidonic acid and its conjugates (PubMed:14660610, PubMed:24563460). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase) (PubMed:14660610, PubMed:24563460). Acts as an omega and omega-1 hydroxylase for arachidonic acid and possibly for other long chain fatty acids. May modulate the arachidonic acid signaling pathway and play a role in other fatty acid signaling processes (PubMed:14660610, PubMed:24563460). May down-regulate the biological activities of N-arachidonoyl-serotonin, an endocannabinoid that has anti-nociceptive effects through inhibition of fatty acid amide hydrolase FAAH, TRPV1 receptor and T-type calcium channels. Catalyzes C-2 oxidation of the indole ring of N-arachidonoyl-serotonin forming a less active product 2-oxo-N-arachidonoyl-serotonin (PubMed:24563460).
messages: Belongs to the cytochrome P450 family.
messages: Endoplasmic reticulum membrane
messages: Expressed in fetal thymus.
messages: Microsome membrane
messages: Mitochondrion inner membrane
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Widely expressed with stronger expression in thymus, heart and cerebellum.

9606:NUTM2B
gene id: 9606:NUTM2B
uniprot id: A6NNL0
names: Similarity
messages: Belongs to the NUT family.

9606:PNPLA3
gene id: 9606:PNPLA3
uniprot id: Q9NST1
names: Activity Regulation
names: Disease Annotation
names: Function
names: Induction
names: Polymorphism
names: Subcellular Location Annotation
messages: By changes in energy balance: down-regulated following very low-calorie diet, whereas refeeding elevates the mRNA level.
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry.
messages: Lipid droplet
messages: Membrane
messages: Polymorphic variation at position 148 influences insulin secretion levels and obesity. In obese subjects the body mass index and waist are higher in carriers of the Ile-148 allele. The Ile-148 carriers also display decreased insulin secretion in response to oral glucose tolerance test. Met-148 allele carriers are seemingly more insulin resistant at a lower body mass index.
messages: Specifically catalyzes coenzyme A (CoA)-dependent acylation of 1-acyl-sn-glycerol 3-phosphate (2-lysophosphatidic acid/LPA) to generate phosphatidic acid (PA), an important metabolic intermediate and precursor for both triglycerides and glycerophospholipids. Does not esterify other lysophospholipids. Acyl donors are long chain (at least C16) fatty acyl-CoAs: arachidonoyl-CoA, linoleoyl-CoA, oleoyl-CoA and at a lesser extent palmitoyl-CoA (PubMed:22560221). Additionally possesses low triacylglycerol lipase and CoA-independent acylglycerol transacylase activities and thus may play a role in acyl-chain remodeling of triglycerides (PubMed:15364929, PubMed:20034933, PubMed:22560221). In vitro may express hydrolytic activity against glycerolipids triacylglycerol, diacylglycerol and monoacylglycerol, with a strong preference for oleic acid as the acyl moiety (PubMed:21878620). However, the triacylglycerol hydrolase activity is controversial and may be very low (PubMed:22560221). Possesses phospholipase A2 activity (PubMed:15364929).
messages: The triglyceride lipase activity is inhibited by BEL ((E)-6-(bromomethylene)-3-(1-naphthalenyl)-2H-tetrahydropyran-2-one), a suicide substrate inhibitor.

9606:HACL1
gene id: 9606:HACL1
uniprot id: B4DXR1
uniprot id: Q9UJ83
names: Cofactor
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the TPP enzyme family.
messages: Binds 1 Mg(2+) ion per subunit.
messages: Binds 1 thiamine pyrophosphate per subunit.
messages: Homotetramer.
messages: Peroxisomal 2-OH acyl-CoA lyase involved in the cleavage (C1 removal) reaction in the fatty acid alpha-oxydation in a thiamine pyrophosphate (TPP)-dependent manner (PubMed:28289220, PubMed:21708296, PubMed:10468558). Involved in the degradation of 3-methyl-branched fatty acids like phytanic acid and the shortening of 2-hydroxy long-chain fatty acids (PubMed:28289220, PubMed:21708296, PubMed:10468558). Plays a significant role in the biosynthesis of heptadecanal in the liver (By similarity).
messages: Peroxisome
messages: Widely expressed.

9606:POM121L12
gene id: 9606:POM121L12
uniprot id: Q8N7R1
names: Sequence Caution
names: Similarity
messages: Belongs to the POM121 family.
messages: Contaminating sequence.

9606:CDCA5
gene id: 9606:CDCA5
uniprot id: Q96FF9
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the sororin family.
messages: Chromosome
messages: Cytoplasm
messages: Interacts with the APC/C complex (By similarity). Interacts with the chromatin-bound cohesin complex; the interaction is indirect, occurs after DNA replication and requires acetylation of the cohesin component SMC3. Interacts (via the FGF motif) with PDS5A and PDS5B; the interaction is direct and prevents the interaction of PDS5A with WAPL.
messages: Named sororin after the Latin word 'soror', which means 'sister', because of its critical role in sister chromatid cohesion.
messages: Nucleus
messages: Phosphorylated. Phosphorylation, as cells enter mitosis, disrupts the interaction with PDS5A and relieves the inhibition of WAPL by CDCA5.
messages: Regulator of sister chromatid cohesion in mitosis stabilizing cohesin complex association with chromatin. May antagonize the action of WAPL which stimulates cohesin dissociation from chromatin. Cohesion ensures that chromosome partitioning is accurate in both meiotic and mitotic cells and plays an important role in DNA repair. Required for efficient DNA double-stranded break repair.
messages: The KEN box is required for the association with the APC/C complex.
messages: Ubiquitinated by the APC/C complex in G1, leading to its degradation.

9606:HDDC3
gene id: 9606:HDDC3
uniprot id: Q8N4P3
names: Function
names: Similarity
messages: Belongs to the MESH1 family.
messages: ppGpp hydrolyzing enzyme involved in starvation response.

9606:KPNA5
gene id: 9606:KPNA5
uniprot id: O15131
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts with ebolavirus protein VP24.
messages: Belongs to the importin alpha family.
messages: Consists of an N-terminal hydrophilic region, a hydrophobic central region composed of 10 repeats, and a short hydrophilic C-terminus. The N-terminal hydrophilic region contains the importin beta binding domain (IBB domain), which is sufficient for binding importin beta and essential for nuclear protein import.
messages: Cytoplasm
messages: Forms a complex with importin subunit beta-1.
messages: Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Docking of the importin/substrate complex to the nuclear pore complex (NPC) is mediated by KPNB1 through binding to nucleoporin FxFG repeats and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to importin-beta and the three components separate and importin-alpha and -beta are re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran from importin. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. Mediates nuclear import of STAT1 homodimers and STAT1/STAT2 heterodimers by recognizing non-classical NLSs of STAT1 and STAT2 through ARM repeats 8-9. Recognizes influenza A virus nucleoprotein through ARM repeat 7-9 In vitro, mediates the nuclear import of human cytomegalovirus UL84 by recognizing a non-classical NLS.
messages: Testis.
messages: The IBB domain is thought to act as an intrasteric autoregulatory sequence by interacting with the internal autoinhibitory NLS. Binding of KPNB1 probably overlaps the internal NLS and contributes to a high affinity for cytoplasmic NLS-containing cargo substrates. After dissociation of the importin/substrate complex in the nucleus the internal autohibitory NLS contributes to a low affinity for nuclear NLS-containing proteins (By similarity).
messages: The major and minor NLS binding sites are mainly involved in recognition of simple or bipartite NLS motifs. Structurally located within in a helical surface groove they contain several conserved Trp and Asn residues of the corresponding third helices (H3) of ARM repeats which mainly contribute to binding (By similarity).

9606:ARPIN-AP3S2
gene id: 9606:ARPIN-AP3S2
uniprot id: A0A0A6YYH1
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the Arpin family.
messages: Cytoplasmic vesicle membrane
messages: Membrane
messages: Part of the AP-3 complex, an adaptor-related complex which is not clathrin-associated. The complex is associated with the Golgi region as well as more peripheral structures. It facilitates the budding of vesicles from the Golgi membrane and may be directly involved in trafficking to lysosomes. In concert with the BLOC-1 complex, AP-3 is required to target cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals.

9606:DAZL
gene id: 9606:DAZL
uniprot id: A0A140VK77
uniprot id: Q92904
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the RRM DAZ family.
messages: Cytoplasm
messages: Homodimer and heterodimer. Multiple DAZL RRMs can bind to a single RNA containing multiple GUU triplets (By similarity). Forms a heterodimer with DAZ. Interacts with BOLL, DAZAP1 and DAZAP2. Interacts with PUM2.
messages: Nucleus
messages: RNA-binding protein, which is essential for gametogenesis in both males and females. Plays a central role during spermatogenesis. Acts by binding to the 3'-UTR of mRNA, specifically recognizing GUU triplets, and thereby regulating the translation of key transcripts (By similarity).
messages: Testis specific.
messages: The DAZ domain mediates the interaction with DAZAP1 and DAZAP2.

9606:SLC16A6
gene id: 9606:SLC16A6
uniprot id: O15403
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Basolateral cell membrane
messages: Belongs to the major facilitator superfamily. Monocarboxylate porter (TC 2.A.1.13) family.
messages: Forms functional complexes with BSG/CD147 or EMB/GP70 ancillary proteins.
messages: Monocarboxylate transporter selective for taurine. May associate with BSG/CD147 or EMB/GP70 ancillary proteins to mediate facilitative efflux or influx of taurine across the plasma membrane. The transport is pH- and sodium-independent. Rather low-affinity, is likely effective for taurine transport in tissues where taurine is present at high concentrations.

9606:CLEC5A
gene id: 9606:CLEC5A
uniprot id: Q9NY25
names: Function
names: Miscellaneous
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Critical macrophage receptor for dengue virus serotypes 1-4 (PubMed:18496526, PubMed:21566123). The binding of dengue virus to CLEC5A triggers signaling through the phosphorylation of TYROBP (PubMed:18496526). This interaction does not result in viral entry, but stimulates pro-inflammatory cytokine release (PubMed:18496526).
messages: (Microbial infection) Interacts with dengue virus envelope protein E (PubMed:18496526, PubMed:21566123).
messages: Acts as a key regulator of synovial injury and bone erosion during autoimmune joint inflammation when its activation leads to enhanced recruitment of inflammatory macrophages and neutrophils to the joints.
messages: Cell membrane
messages: Functions as a positive regulator of osteoclastogenesis (By similarity). Cell surface receptor that signals via TYROBP (PubMed:10449773). Regulates inflammatory responses (By similarity).
messages: Highly expressed in bone marrow with lower levels in synovium, lung and bronchus (PubMed:20212065). Expressed in peripheral blood monocytes and in the monocyte/macrophage cell lines U-937 and Mono-Mac-6, but not in cell lines of other origins (PubMed:10449773). Expression is down-regulated when monocytes differentiate into dendritic cells (PubMed:10449773).
messages: Monomer (PubMed:21566123). Homodimer (PubMed:21566123). The majority of CLEC5A is expressed as a monomeric form on macrophages (PubMed:21566123). Interacts with TYROBP/DAP12 (PubMed:10449773). The interaction with TYROBP is required for CLEC5A cell surface expression (PubMed:10449773). Interacts with HCST/DAP10 (By similarity). Forms a CLEC5A/TYROBP/HCST trimolecular complex depending almost solely on TYROBP (By similarity).
messages: N-glycosylated. Contains sialic acid residues.

9606:NELFE
gene id: 9606:NELFE
uniprot id: A0A1U9X830
uniprot id: P18615
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Binds to the HIV-1 TAR RNA which is located in the long terminal repeat (LTR) of HIV-1.
messages: (Microbial infection) The NELF complex is involved in HIV-1 latency possibly involving recruitment of PCF11 to paused RNA polymerase II.
messages: Belongs to the RRM NELF-E family.
messages: Chromosome
messages: Essential component of the NELF complex, a complex that negatively regulates the elongation of transcription by RNA polymerase II (PubMed:10199401, PubMed:27256882). The NELF complex, which acts via an association with the DSIF complex and causes transcriptional pausing, is counteracted by the P-TEFb kinase complex (PubMed:11940650, PubMed:12612062, PubMed:27256882). Provides the strongest RNA binding activity of the NELF complex and may initially recruit the NELF complex to RNA (PubMed:18303858, PubMed:27282391, PubMed:27256882).
messages: Nucleus
messages: Phosphorylated by the P-TEFb complex at sites next to its RNA recognition motif, promoting its release from chromatin.
messages: Poly-ADP-ribosylated by PARP1, thereby preventing RNA-binding and relieving transcription pausing.
messages: Sumoylated.
messages: The NELF complex is composed of NELFA, NELFB, NELFCD (isoform NELF-C or isoform NELF-D) and NELFE (PubMed:10199401, PubMed:27282391). Interacts with NELFB (By similarity).
messages: The RRM domain interacts with RNA, and is essential for NELF complex function. It is however not required for the NELF complex formation.
messages: Widely expressed. Expressed in heart, brain, lung, placenta, liver, skeletal muscle, kidney and pancreas.

9606:AK4
gene id: 9606:AK4
uniprot id: F8VS11
uniprot id: P27144
names: Caution
names: Domain
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the adenylate kinase family.
messages: Belongs to the adenylate kinase family. AK3 subfamily.
messages: By hypoxia (at protein level).
messages: Consists of three domains, a large central CORE domain and two small peripheral domains, NMPbind and LID, which undergo movements during catalysis. The LID domain closes over the site of phosphoryl transfer upon GTP/ATP binding. Assembling and dissambling the active center during each catalytic cycle provides an effective means to prevent GTP/ATP hydrolysis.
messages: Highly expressed in kidney, moderately expressed in heart and liver and weakly expressed in brain.
messages: Involved in maintaining the homeostasis of cellular nucleotides by catalyzing the interconversion of nucleoside phosphates (PubMed:19073142, PubMed:19766732, PubMed:23416111, PubMed:24767988). Efficiently phosphorylates AMP and dAMP using ATP as phosphate donor, but phosphorylates only AMP when using GTP as phosphate donor (PubMed:19073142, PubMed:19766732, PubMed:23416111). Also displays broad nucleoside diphosphate kinase activity (PubMed:19073142, PubMed:19766732, PubMed:23416111). Plays a role in controlling cellular ATP levels by regulating phosphorylation and activation of the energy sensor protein kinase AMPK (PubMed:24767988, PubMed:26980435). Plays a protective role in the cellular response to oxidative stress (PubMed:19130895, PubMed:23474458, PubMed:26980435).
messages: Mitochondrion matrix
messages: Monomer (Ref.17). Interacts with SLC25A5/ANT2 (PubMed:19130895).
messages: Some studies have failed to detect adenylate kinase activity (PubMed:11485571, PubMed:19130895). However, kinase activity has been demonstrated in a number of other studies (PubMed:19766732, PubMed:23416111).

9606:IGFL4
gene id: 9606:IGFL4
uniprot id: Q6B9Z1
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the IGFL family.
messages: Detected in the cerebellum.
messages: Secreted

9606:MYO1A
gene id: 9606:MYO1A
uniprot id: B2R643
uniprot id: Q9UBC5
names: Caution
names: Function
names: PTM
names: Similarity
messages: Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.
messages: Involved in directing the movement of organelles along actin filaments.
messages: MYO1A mutations have been reported to cause autosomal dominant non-syndromic hearing loss DFNA48 (PubMed:12736868). It was later shown that MYO1A is not associated with DFNA48 (PubMed:24616153).
messages: Phosphorylated by ALPK1.
messages: Represents an unconventional myosin. This protein should not be confused with the conventional myosin-1 (MYH1).

9606:ALKBH5
gene id: 9606:ALKBH5
uniprot id: Q6P6C2
names: Cofactor
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the alkB family.
messages: Binds 1 Fe(2+) ion per subunit.
messages: By hypoxia, directly activated by HIF1A. Expression is regulated by PRMT7.
messages: Dioxygenase that demethylates RNA by oxidative demethylation: specifically demethylates N(6)-methyladenosine (m6A) RNA, the most prevalent internal modification of messenger RNA (mRNA) in higher eukaryotes (PubMed:23177736, PubMed:24489119, PubMed:24616105, PubMed:24778178). Can also demethylate N(6)-methyladenosine in single-stranded DNA (in vitro) (PubMed:24616105). Requires molecular oxygen, alpha-ketoglutarate and iron (PubMed:21264265, PubMed:23177736, PubMed:24489119, PubMed:24616105, PubMed:24778178). Demethylation of m6A mRNA affects mRNA processing and export (PubMed:23177736). Required for the late meiotic and haploid phases of spermatogenesis by mediating m6A demethylation in spermatocytes and round spermatids: m6A demethylation of target transcripts is required for correct splicing and the production of longer 3'-UTR mRNAs in male germ cells (By similarity).
messages: Monomer.
messages: Nucleus speckle
messages: Widely expressed, with highest expression in lung, followed by testis, pancreas, spleen and ovary.

9606:ZNF200
gene id: 9606:ZNF200
uniprot id: P98182
names: Function
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Could have a role in spermatogenesis.
messages: Highly expressed in testis, weakly expressed in spleen, thymus, prostate, ovary, small intestine colon and peripheral blood leukocytes.
messages: Nucleus

9606:SSH1
gene id: 9606:SSH1
uniprot id: Q8WYL5
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the protein-tyrosine phosphatase family.
messages: Cleavage furrow
messages: Due to intron retention.
messages: Interacts with actin and this stimulates phosphatase activity. Also interacts with LIMK1 and with the 14-3-3 proteins YWHAB, YWHAG, YWHAQ, and YWHAZ. Interaction with 14-3-3 proteins inhibits phosphatase activity and also blocks recruitment to lamellipodia and stimulation by actin.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Midbody
messages: Phosphorylated. Inhibitory phosphorylation by PAK4 promotes binding to YWHAZ. Phosphorylation at Ser-978 is decreased by stimuli which promote actin reorganization and lamellipodia formation. Can be dephosphorylated and activated by PPP3CA/calcineurin A. Phosphorylation decreases immediately prior to telophase.
messages: Protein phosphatase which regulates actin filament dynamics. Dephosphorylates and activates the actin binding/depolymerizing factor cofilin, which subsequently binds to actin filaments and stimulates their disassembly. Inhibitory phosphorylation of cofilin is mediated by LIMK1, which may also be dephosphorylated and inactivated by this protein.
messages: Tyrosine phosphatase activity has not been demonstrated for this protein to date.
messages: cytoskeleton
messages: lamellipodium

9606:GALNT15
gene id: 9606:GALNT15
uniprot id: C9JGI4
uniprot id: Q8N3T1
names: Caution
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the glycosyltransferase 2 family. GalNAc-T subfamily.
messages: Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor. Although it displays a much weaker activity toward all substrates tested compared to GALNT2, it is able to transfer up to seven GalNAc residues to the Muc5AC peptide, suggesting that it can fill vicinal Thr/Ser residues in cooperation with other GALNT proteins. Prefers Muc1a as substrate.
messages: Golgi apparatus membrane
messages: Membrane
messages: The ricin B-type lectin domain binds to GalNAc and contributes to the glycopeptide specificity.
messages: There are two conserved domains in the glycosyltransferase region: the N-terminal domain (domain A, also called GT1 motif), which is probably involved in manganese coordination and substrate binding and the C-terminal domain (domain B, also called Gal/GalNAc-T motif), which is probably involved in catalytic reaction and UDP-Gal binding.
messages: Was originally termed Galnt15/pp-GaNTase 15.
messages: Widely expressed. Highly expressed in small intestine, placenta, spleen, cerebral cortex and ovary. Expressed at intermediate level in uterus, mammary gland, stomach, cerebellum and whole brain. Weakly expressed in fetal brain, bone marrow, thyroid gland, thymus, heart, skeletal muscle, lung, liver, colon, pancreas, kidney and testis. Not expressed in leukocyte. Expressed in both normal and osteoarthritic cartilage. Expressed at low level in chondrocytes in all zones of both normal and osteoarthritic cartilage.

9606:TAS2R42
gene id: 9606:TAS2R42
uniprot id: A0A0G2JPZ2
uniprot id: Q7RTR8
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor T2R family.
messages: Membrane
messages: Most taste cells may be activated by a limited number of bitter compounds; individual taste cells can discriminate among bitter stimuli.
messages: Receptor that may play a role in the perception of bitterness and is gustducin-linked. May play a role in sensing the chemical composition of the gastrointestinal content. The activity of this receptor may stimulate alpha gustducin, mediate PLC-beta-2 activation and lead to the gating of TRPM5 (By similarity).

9606:FTH1
gene id: 9606:FTH1
uniprot id: P02794
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the ferritin family.
messages: Cytoplasm
messages: Expressed in the liver.
messages: Oligomer of 24 subunits (PubMed:9159481). There are two types of subunits: L (light) chain and H (heavy) chain (PubMed:9159481). The major chain can be light or heavy, depending on the species and tissue type. In the human liver, the heavy chain is predominant (PubMed:9159481). The functional molecule forms a roughly spherical shell with a diameter of 12 nm and contains a central cavity into which the insoluble mineral iron core is deposited (PubMed:9159481).
messages: Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity (PubMed:9003196). Iron is taken up in the ferrous form and deposited as ferric hydroxides after oxidation (PubMed:9003196). Also plays a role in delivery of iron to cells (By similarity). Mediates iron uptake in capsule cells of the developing kidney (By similarity).
messages: The disease is caused by variants affecting the gene represented in this entry. In a Japanese family affected by HFE5, a single point mutation has been detected in the iron-responsive element (IRE) in the 5'-UTR of FTH1 mRNA. This mutation leads to an increased binding affinity for iron regulatory protein and thereby to the efficient suppression of mRNA translation.

9606:PRAMEF11
gene id: 9606:PRAMEF11
uniprot id: O60813
names: Similarity
messages: Belongs to the PRAME family.

9606:TPH2
gene id: 9606:TPH2
uniprot id: Q8IWU9
names: Disease Annotation
names: RNA Editing
names: Similarity
names: Tissue Specificity
messages: Belongs to the biopterin-dependent aromatic amino acid hydroxylase family.
messages: Brain specific.
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry.
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry. Naturally occurring variants of TPH2 with impaired enzyme activity could cause deficiency of serotonin production and result in an increased risk of developing behavioral disorders.
messages: Modulates the kinetic properties of both isoforms.

9606:ENG
gene id: 9606:ENG
uniprot id: P17813
names: Disease Annotation
names: Domain
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cell membrane
messages: Detected on umbilical veil endothelial cells (PubMed:10625079). Detected in placenta (at protein level) (PubMed:1692830). Detected on endothelial cells (PubMed:1692830).
messages: Homodimer; disulfide-linked (PubMed:8370410, PubMed:1326540, PubMed:21737454, PubMed:22347366, PubMed:28564608). Forms a heteromeric complex with the signaling receptors for transforming growth factor-beta: TGFBR1 and/or TGFBR2 (PubMed:1326540). It is able to bind TGFB1 and TGFB2 with high affinity, but not TGFB3 (PubMed:8370410, PubMed:1326540). Interacts with GDF2, forming a heterotetramer with a 2:2 stoichiometry (PubMed:21737454, PubMed:22347366, PubMed:28564608). Interacts with ACVRL1 (PubMed:22347366, PubMed:28564608). Can form a heteromeric complex with GDF2 and ACVRL1 (PubMed:28564608). Interacts with BMP10 (PubMed:21737454). Interacts with DYNLT4 (PubMed:16982625). Interacts with ARRB2 (PubMed:17540773).
messages: The N-terminal OR region is composed of two intertwined domains (OR1 and OR2) with a common, novel fold. Each contains 12 beta-strands that form a parallel beta-helix-like structure, plus a single alpha-helix. The OR1 region mediates interaction with GDF2.
messages: The ZP domain mediates dimerization.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Vascular endothelium glycoprotein that plays an important role in the regulation of angiogenesis (PubMed:21737454, PubMed:23300529). Required for normal structure and integrity of adult vasculature (PubMed:7894484). Regulates the migration of vascular endothelial cells (PubMed:17540773). Required for normal extraembryonic angiogenesis and for embryonic heart development (By similarity). May regulate endothelial cell shape changes in response to blood flow, which drive vascular remodeling and establishment of normal vascular morphology during angiogenesis (By similarity). May play a critical role in the binding of endothelial cells to integrins and/or other RGD receptors (PubMed:1692830). Acts as TGF-beta coreceptor and is involved in the TGF-beta/BMP signaling cascade that ultimately leads to the activation of SMAD transcription factors (PubMed:8370410, PubMed:21737454, PubMed:22347366, PubMed:23300529). Required for GDF2/BMP9 signaling through SMAD1 in endothelial cells and modulates TGFB1 signaling through SMAD3 (PubMed:21737454, PubMed:22347366, PubMed:23300529).

9606:MICU3
gene id: 9606:MICU3
uniprot id: Q86XE3
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the MICU1 family. MICU3 subfamily.
messages: Binds calcium.
messages: May play a role in mitochondrial calcium uptake.
messages: Membrane
messages: Mitochondrion

9606:CHIA
gene id: 9606:CHIA
uniprot id: A8K3T7
uniprot id: Q1M0P3
uniprot id: Q1M0P4
uniprot id: Q2VT96
uniprot id: Q9BZP6
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the glycosyl hydrolase 18 family. Chitinase class II subfamily.
messages: Cytoplasm
messages: Degrades chitin and chitotriose. May participate in the defense against nematodes, fungi and other pathogens. Plays a role in T-helper cell type 2 (Th2) immune response. Contributes to the response to IL-13 and inflammation in response to IL-13. Stimulates chemokine production by pulmonary epithelial cells. Protects lung epithelial cells against apoptosis and promotes phosphorylation of AKT1. Its function in the inflammatory response and in protecting cells against apoptosis is inhibited by allosamidin, suggesting that the function of this protein depends on carbohydrate binding.
messages: Detected in lung epithelial cells from asthma patients (at protein level). Highly expressed in stomach. Detected at lower levels in lung.
messages: Interacts with EGFR.
messages: Secreted
messages: Up-regulated in lung epithelial cells from asthma patients.

9606:GOLGA4
gene id: 9606:GOLGA4
uniprot id: Q13439
names: Domain
names: Function
names: Miscellaneous
names: Subcellular Location Annotation
names: Subunit
messages: Antibodies against GOLGA4 are present in sera from patients with Sjoegren syndrome. Sera from patients with Sjoegren syndrome often contain antibodies that react with normal components of the Golgi complex.
messages: Cytoplasm
messages: Extended rod-like protein with coiled-coil domains.
messages: Golgi apparatus membrane
messages: Homodimer (PubMed:14718928). Interacts with RAB6A (PubMed:10209123). Interacts with GTP-bound ARL1 and ARL3 (PubMed:11303027, PubMed:14580338, PubMed:14718928). Interacts with MACF1 (PubMed:15265687). Directly interacts with TBC1D23 (PubMed:29084197). Interacts with FAM91A1; this interaction may be mediated by TBC1D23 (PubMed:29084197).
messages: Involved in vesicular trafficking at the Golgi apparatus level. May play a role in delivery of transport vesicles containing GPI-linked proteins from the trans-Golgi network through its interaction with MACF1. Involved in endosome-to-Golgi trafficking (PubMed:29084197).
messages: trans-Golgi network membrane

9606:OR4F16
gene id: 9606:OR4F16
uniprot id: A0A126GV92
uniprot id: Q6IEY1
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Membrane
messages: Odorant receptor.

9606:MRPL47
gene id: 9606:MRPL47
uniprot id: Q9HD33
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the universal ribosomal protein uL29 family.
messages: Chimeric cDNA. Seems to include a portion of the orthologous murine sequence.
messages: Component of the mitochondrial large ribosomal subunit (mt-LSU) (PubMed:28892042, PubMed:25838379, PubMed:25278503). Mature mammalian 55S mitochondrial ribosomes consist of a small (28S) and a large (39S) subunit. The 28S small subunit contains a 12S ribosomal RNA (12S mt-rRNA) and 30 different proteins. The 39S large subunit contains a 16S rRNA (16S mt-rRNA), a copy of mitochondrial valine transfer RNA (mt-tRNA(Val)), which plays an integral structural role, and 52 different proteins.
messages: Mitochondrion

9606:OSBPL10
gene id: 9606:OSBPL10
uniprot id: Q9BXB5
uniprot id: Q9NX98
names: Domain
names: Function
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the OSBP family.
messages: Interacts with OSBPL9 (PubMed:22906437). Interacts with DIAPH1 (PubMed:23325789).
messages: Polymorphisms are associated with dyslipidemia. Variant Asn-254 is associated with LDL-cholesterol levels in Japanese population (PubMed:20224571). Association with peripheral arterial disease has also been observed (PubMed:20610895).
messages: Probable lipid transporter involved in lipid countertransport between the endoplasmic reticulum and the plasma membrane. Its ability to bind phosphatidylserine, suggests that it specifically exchanges phosphatidylserine with phosphatidylinositol 4-phosphate (PI4P), delivering phosphatidylserine to the plasma membrane in exchange for PI4P (PubMed:23934110) (Probable). Plays a role in negative regulation of lipid biosynthesis (PubMed:19554302). Negatively regulates APOB secretion from hepatocytes (PubMed:19554302, PubMed:22906437). Binds cholesterol and acidic phospholipids (PubMed:22906437). Also binds 25-hydroxycholesterol (PubMed:17428193). Binds phosphatidylserine (PubMed:23934110).
messages: The C-terminal region binds cholesterol, 25-hydroxysterol and acidic phospholipids and is required for localization to microtubules.
messages: The PH domain selectively interacts with phosphatidylinositol-4-phosphate.
messages: cytoskeleton

9606:SWT1
gene id: 9606:SWT1
uniprot id: Q5T5J6
names: Similarity
names: Tissue Specificity
messages: Belongs to the SWT1 family.
messages: Expressed weakly in testis.

9606:KLHL1
gene id: 9606:KLHL1
uniprot id: Q9NR64
names: Function
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Highly expressed in brain.
messages: May play a role in organizing the actin cytoskeleton of the brain cells.
messages: cytoskeleton

9606:FBLN7
gene id: 9606:FBLN7
uniprot id: Q53RD9
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: An adhesion molecule that interacts with extracellular matrix molecules in developing teeth and may play important roles in differentiation and maintenance of odontoblasts as well as in dentin formation.
messages: Belongs to the fibulin family.
messages: Interacts with heparin, FBLN1, FN1 and DSPP. Preferentially binds dental mesenchyme cells and odontoblasts but not dental epithelial cells or nondental cells. Binding requires a heparan sulfate-containing receptor on the cell surface as well as an integrin (By similarity).
messages: N-glycosylated.
messages: extracellular matrix

9606:PATE4
gene id: 9606:PATE4
uniprot id: P0C8F1
names: Caution
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the PATE family.
messages: It is uncertain whether Met-1 or Met-4 is the initiator.
messages: May modulate the function of nicotinic acetylcholine receptors. May enhance sperm motility.
messages: Secreted
messages: Specifically expressed in prostate, testis and spinal cord. Present in the acrosomal region of sperm cells. Present in apical epithelial cells of prostatic duct.
messages: acrosome

9606:DNAJC8
gene id: 9606:DNAJC8
uniprot id: O75937
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Interacts with SRPK1 (PubMed:19240134). Interacts with HSP70 (HSPA1A or HSPA1B) (PubMed:27133716).
messages: Nucleus
messages: Suppresses polyglutamine (polyQ) aggregation of ATXN3 in neuronal cells (PubMed:27133716).
messages: Ubiquitous.

9606:IFI27
gene id: 9606:IFI27
uniprot id: P40305
names: Function
names: Induction
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the IFI6/IFI27 family.
messages: Endoplasmic reticulum membrane
messages: Homodimer (PubMed:27673746). Interacts with hepatitis C virus/HCV non-structural protein NS5A; promotes the ubiquitin-mediated proteasomal degradation of NS5A (PubMed:27194766). Interacts with SKP2; promotes the ubiquitin-mediated proteasomal degradation of NS5A (PubMed:27194766). Interacts with NR4A1 (PubMed:22427340). May interact with BCL2 (PubMed:27673746).
messages: Major isoform in blood and cervix.
messages: Mitochondrion membrane
messages: Nucleus inner membrane
messages: Probable adapter protein involved in different biological processes (PubMed:22427340, PubMed:27194766). Part of the signaling pathways that lead to apoptosis (PubMed:18330707, PubMed:27673746, PubMed:24970806). Involved in type-I interferon-induced apoptosis characterized by a rapid and robust release of cytochrome C from the mitochondria and activation of BAX and caspases 2, 3, 6, 8 and 9 (PubMed:18330707, PubMed:27673746). Also functions in TNFSF10-induced apoptosis (PubMed:24970806). May also have a function in the nucleus, where it may be involved in the interferon-induced negative regulation of the transcriptional activity of NR4A1, NR4A2 and NR4A3 through the enhancement of XPO1-mediated nuclear export of these nuclear receptors (PubMed:22427340). May thereby play a role in the vascular response to injury (By similarity). In the innate immune response, has an antiviral activity towards hepatitis C virus/HCV (PubMed:27194766, PubMed:27777077). May prevent the replication of the virus by recruiting both the hepatitis C virus non-structural protein 5A/NS5A and the ubiquitination machinery via SKP2, promoting the ubiquitin-mediated proteasomal degradation of NS5A (PubMed:27194766, PubMed:27777077). Promotes also virus-induced pyroptosis by activating CASP3 in the mitochondria after 'Lys-6'-linked ubiquitination by TRIM21 (PubMed:36426955).
messages: Ubiquitinated by TRIM21 via 'Lys-6'-linked ubiquitin chains leading to IFI27 mitochondrial migration.
messages: Up-regulated by type-I and type-II interferons.

9606:COL25A1
gene id: 9606:COL25A1
uniprot id: Q9BXS0
names: Caution
names: Disease Annotation
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Expressed predominantly in brain. Deposited preferentially in primitive or neuritic amyloid plaques which are typical of Alzheimer disease.
messages: Forms homodimers and homotrimers. Binds to the fibrillized forms of amyloid-beta protein 40 (beta-APP40) and amyloid-beta protein 42 (beta-APP42). Found associated with beta-APP42 more frequently than with beta-APP40.
messages: Glycosylated.
messages: Hydroxylated on 11% of proline residues and 49% of lysine residues.
messages: Inhibits fibrillization of amyloid-beta peptide during the elongation phase. Has also been shown to assemble amyloid fibrils into protease-resistant aggregates. Binds heparin.
messages: Membrane
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The pyrrolidone carboxylic acid reported in PubMed:11927537 probably formed artifactually from Glu-113 during the extraction procedure in 70% formic acid. In PubMed:15522881, the protein was found to have unblocked Glu at the N-terminus.
messages: Undergoes proteolytic cleavage by furin protease to yield the soluble collagen-like Alzheimer amyloid plaque component.

9606:SEC16A
gene id: 9606:SEC16A
uniprot id: A0A8I5KPG1
uniprot id: F1T0I1
uniprot id: O15027
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acts as a molecular scaffold that plays a key role in the organization of the endoplasmic reticulum exit sites (ERES), also known as transitional endoplasmic reticulum (tER). SAR1A-GTP-dependent assembly of SEC16A on the ER membrane forms an organized scaffold defining an ERES. Required for secretory cargo traffic from the endoplasmic reticulum to the Golgi apparatus (PubMed:17192411, PubMed:17005010, PubMed:17428803, PubMed:21768384, PubMed:22355596). Mediates the recruitment of MIA3/TANGO to ERES (PubMed:28442536). Regulates both conventional (ER/Golgi-dependent) and GORASP2-mediated unconventional (ER/Golgi-independent) trafficking of CFTR to cell membrane (PubMed:28067262). Positively regulates the protein stability of E3 ubiquitin-protein ligases RNF152 and RNF183 and the ER localization of RNF183 (PubMed:29300766). Acts as a RAB10 effector in the regulation of insulin-induced SLC2A4/GLUT4 glucose transporter-enriched vesicles delivery to the cell membrane in adipocytes (By similarity).
messages: Belongs to the SEC16 family.
messages: Endoplasmic reticulum membrane
messages: Golgi apparatus membrane
messages: Microsome membrane
messages: Plays a role in the organization of the endoplasmic reticulum exit sites (ERES), also known as transitional endoplasmic reticulum (tER). Required for secretory cargo traffic from the endoplasmic reticulum to the Golgi apparatus.
messages: SEC16A and SEC16B are each present in multiple copies in a heteromeric complex (PubMed:17192411, PubMed:22355596). Interacts with SEC23A (PubMed:17192411, PubMed:17428803). Interacts with RNF183 and RNF152 (PubMed:29300766). Interacts with LRRK2 (via ROC domain) (PubMed:25201882). Interacts with SEC13 (PubMed:25201882, PubMed:19638414, PubMed:17428803). Interacts with RAB10 (By similarity). Interacts with MIA3 (PubMed:28442536). Interacts with GORASP2 in response to ER stress (PubMed:28067262).
messages: SEC16A and SEC16B are each present in multiple copies in a heteromeric complex.
messages: Ubiquitous. Expressed at higher levels in the pancreas.
messages: cytosol
messages: perinuclear region

9606:CXCL2
gene id: 9606:CXCL2
uniprot id: P19875
names: Function
names: PTM
names: Pharmaceutical
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the intercrine alpha (chemokine CxC) family.
messages: GRO-beta(5-73) is available under the name Garnocestim as immunomodulator. It is used prior to hematopoietic transplantation for peripheral blood stem cell mobilization and reduction of incidence, duration, and/or severity of chemotherapy induced cytopenias.
messages: Produced by activated monocytes and neutrophils and expressed at sites of inflammation. Hematoregulatory chemokine, which, in vitro, suppresses hematopoietic progenitor cell proliferation. GRO-beta(5-73) shows a highly enhanced hematopoietic activity.
messages: Secreted
messages: The N-terminal processed form GRO-beta(5-73) is produced by proteolytic cleavage after secretion from bone marrow stromal cells.

9606:GRM8
gene id: 9606:GRM8
uniprot id: O00222
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the G-protein coupled receptor 3 family.
messages: Cell membrane
messages: G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity.
messages: Interacts with PICK1.

9606:TAGLN3
gene id: 9606:TAGLN3
uniprot id: Q9UI15
names: Similarity
names: Tissue Specificity
messages: Belongs to the calponin family.
messages: Widely expressed in the brain. Expression is increased in the superior frontal cortex of alcoholics, but not in the motor cortex or cerebellum.

9606:SLC35E2B
gene id: 9606:SLC35E2B
uniprot id: P0CK96
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the TPT transporter family. SLC35E subfamily.
messages: Membrane
messages: Putative transporter.

9606:SYNPR
gene id: 9606:SYNPR
uniprot id: Q8TBG9
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the synaptophysin/synaptobrevin family.
messages: Intrinsic membrane protein of small synaptic vesicles. Probable vesicular channel protein (By similarity).
messages: synaptic vesicle membrane
messages: synaptosome

9606:TM4SF1
gene id: 9606:TM4SF1
uniprot id: P30408
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the L6 tetraspanin family.
messages: Highly expressed in lung, breast, colon and ovarian carcinomas. It is also present on some normal cells, endothelial cells in particular.
messages: Membrane
messages: Present in high molecular weight complexes in tumor cells. Interacts with SDCBP2 (PubMed:11102519).

9606:GPRC5A
gene id: 9606:GPRC5A
uniprot id: Q8NFJ5
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor 3 family.
messages: By all-trans retinoic acid (ATRA).
messages: Cell membrane
messages: Cytoplasmic vesicle membrane
messages: Expressed at high level in fetal and adult lung tissues but repressed in most human lung cancers (PubMed:9857033, PubMed:18000218). Constitutively expressed in fetal kidney and adult placenta, kidney, prostate, testis, ovary, small intestine, colon, stomach, and spinal cord at low to moderate levels. Not detectable in fetal heart, brain, and liver and adult heart, brain, liver, skeletal muscle, pancreas, spleen, thymus, and peripheral leukocytes. According to PubMed:10783259, expressed at low but detectable level in pancreas and heart.
messages: Interacts (via its transmembrane domain) with EGFR.
messages: Orphan receptor. Could be involved in modulating differentiation and maintaining homeostasis of epithelial cells. This retinoic acid-inducible GPCR provide evidence for a possible interaction between retinoid and G-protein signaling pathways. Functions as a negative modulator of EGFR signaling (By similarity). May act as a lung tumor suppressor (PubMed:18000218).
messages: Phosphorylated in two conserved double-tyrosine motifs, Tyr-317/Tyr-320 and Tyr-347/Tyr-350, by EGFR; leading to inactivation of the tumor suppressive function of GPRC5A in lung cancer cells. Tyr-317 and Tyr-320 are the preferred residues responsible for EGFR-mediated GPRC5A phosphorylation.

9606:RIBC1
gene id: 9606:RIBC1
uniprot id: Q8N443
names: Similarity
messages: Belongs to the RIB43A family.

9606:TRPA1
gene id: 9606:TRPA1
uniprot id: O75762
names: Activity Regulation
names: Developmental Stage
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: A cytosolic factor (probably pyrophosphate, polytriphosphate, polyP4, polyP25, polyP45, and/or polyP65) is necessary for TRPA1 activation by irritants (PubMed:17567811). Such factor acts by keeping TRPA1 in a agonist-sensitive state (PubMed:17567811). Inhibited by the potent blocker of TRPV channels ruthenium red, A-967079, AP-18, HC-030031, and aryl sulfonamide derivative (S)-N-(4-chlorobenzyl)-1-((4-fluorophenyl)sulfonyl)pyrrolidine-2-carboxamide (ASD) (PubMed:17567811, PubMed:21873995, PubMed:21402443, PubMed:30878828, PubMed:20547126). Non-covalently activated by the scorpion wasabi receptor toxin (PubMed:31447178). Activated by benzyl isothiocyanate (BITC), iodoacetamide, sulfhydryl reactive agent MTSEA, N-methyl maleimide (NMM), N-ethylmaleimide (NEM), and 2-aminoethyldiphenylborinate (2-APB) (PubMed:17164327, PubMed:17567811, PubMed:21873995, PubMed:27241698). Also activated by hyperoxia (PubMed:21873995).
messages: Belongs to the transient receptor (TC 1.A.4) family.
messages: C-terminal helices from the four subunits associate to form atypical coiled coil structure; this region is probably involved in binding the inositol polyphosphates that are required for optimal channel activity (in vitro).
messages: Cell membrane
messages: Expressed at very low levels in fibroblasts.
messages: Expressed in embryos at 12 weeks of age.
messages: Homotetramer (PubMed:25389312, PubMed:25855297). Interacts with TMEM100 (By similarity). Interacts with EGLN1 (By similarity). Interacts with the scorpion wasabi receptor toxin at the same site that electrophiles but in a non-covalent manner (PubMed:31447178).
messages: Hydroxylation is required for TRPA1 activity inhibition in normoxia. In hypoxia, the decrease in oxygen concentration diminishes the activity of the hydroxylase EGLN1, thus relieving TRPA1 from inhibition and ultimately leading to channel activation.
messages: Oxidation of Cys-633 and Cys-856 in hyperoxia may override the hydroxylase EGLN1-mediated inhibition, causing TRPA1 activation.
messages: Receptor-activated non-selective cation channel involved in pain detection and possibly also in cold perception, oxygen concentration perception, cough, itch, and inner ear function (PubMed:21873995, PubMed:23199233, PubMed:25389312, PubMed:25855297). Shows 8-fold preference for divalent over monovalent cations (PubMed:31447178). Has a central role in the pain response to endogenous inflammatory mediators and to a diverse array of irritants, such as allylthiocyanate (AITC) from mustard oil or wasabi, cinnamaldehyde, diallyl disulfide (DADS) from garlic, and acrolein, an irritant from tears gas and vehicle exhaust fumes (PubMed:25389312, PubMed:27241698, PubMed:30878828, PubMed:20547126). Acts also as an ionotropic cannabinoid receptor by being activated by delta(9)-tetrahydrocannabinol (THC), the psychoactive component of marijuana (PubMed:25389312). Is activated by a large variety of structurally unrelated electrophilic and non-electrophilic chemical compounds. Electrophilic ligands activate TRPA1 by interacting with critical N-terminal Cys residues in a covalent manner, whereas mechanisms of non-electrophilic ligands are not well determined. May be a component for the mechanosensitive transduction channel of hair cells in inner ear, thereby participating in the perception of sounds. Probably operated by a phosphatidylinositol second messenger system (By similarity).
messages: TRPA1 activation by electrophiles occurs though covalent modification of specific cysteine residues in the N-terminal cytoplasmic domain (PubMed:25389312).
messages: The ANK repeat domain consists of a convex stem structure formed by five ANK repeats and 11 additional ANK repeats that form a crescent-shaped structure that surrounds the protein core.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:NXPE3
gene id: 9606:NXPE3
uniprot id: Q969Y0
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the NXPE family.
messages: Secreted

9606:SLC4A2
gene id: 9606:SLC4A2
uniprot id: P04920
uniprot id: Q59GF1
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Apical cell membrane
messages: Basolateral cell membrane
messages: Belongs to the anion exchanger (TC 2.A.31) family.
messages: Cell membrane
messages: Expressed in the liver and kidney.
messages: Expressed in the liver, stomach, kidney, prostate, thyroid and rectum.
messages: Membrane
messages: Sodium-independent anion exchanger which mediates the electroneutral exchange of chloride for bicarbonate ions across the cell membrane (PubMed:15184086, PubMed:34668226). Plays an important role in osteoclast differentiation and function (PubMed:34668226). Regulates bone resorption and calpain-dependent actin cytoskeleton organization in osteoclasts via anion exchange-dependent control of pH (By similarity). Essential for intracellular pH regulation in CD8(+) T-cells upon CD3 stimulation, modulating CD8(+) T-cell responses (By similarity).

9606:PBK
gene id: 9606:PBK
uniprot id: Q96KB5
names: Activity Regulation
names: Function
names: PTM
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Activated by phosphorylation.
messages: Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily.
messages: Expressed in the testis and placenta. In the testis, restrictedly expressed in outer cell layer of seminiferous tubules.
messages: Interacts with DLG1 and TP53.
messages: Phosphorylated; in a cell-cycle dependent manner at mitosis.
messages: Phosphorylates MAP kinase p38. Seems to be active only in mitosis. May also play a role in the activation of lymphoid cells. When phosphorylated, forms a complex with TP53, leading to TP53 destabilization and attenuation of G2/M checkpoint during doxorubicin-induced DNA damage.

9606:SOHLH1
gene id: 9606:SOHLH1
uniprot id: Q5JUK2
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Cytoplasm
messages: Forms both hetero- and homodimers with SOHLH2.
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Transcription regulator of both male and female germline differentiation. Suppresses genes involved in spermatogonial stem cells maintenance, and induces genes important for spermatogonial differentiation. Coordinates oocyte differentiation without affecting meiosis I (By similarity).

9606:ELF1
gene id: 9606:ELF1
uniprot id: P32519
uniprot id: Q6MZZ4
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the ETS family.
messages: Binds to the underphosphorylated form of RB. May interact with other transcription factors in order to regulate specific genes. Interacts with RUNX1.
messages: In fetal tissues, it is highly expressed in heart, lung liver and kidney, and weakly expressed in brain. In adult, it is highly expressed in pancreas, spleen, thymus and peripheral blood leukocytes, expressed at moderate levels in heart, placenta, lung, liver, skeletal muscle, kidney, prostate, ovary, small intestine and colon, and weakly expressed in brain and testis.
messages: Nucleus
messages: Transcription factor that activates the LYN and BLK promoters. Appears to be required for the T-cell-receptor-mediated trans activation of HIV-2 gene expression. Binds specifically to two purine-rich motifs in the HIV-2 enhancer.

9606:FAM153A
gene id: 9606:FAM153A
uniprot id: Q9UHL3
names: Similarity
messages: Belongs to the FAM153 family.

9606:LAMB3
gene id: 9606:LAMB3
uniprot id: A0A0S2Z3R6
uniprot id: Q13751
names: Caution
names: Disease Annotation
names: Domain
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components.
messages: Domain VI is globular.
messages: Found in the basement membranes (major component).
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: Laminin is a complex glycoprotein, consisting of three different polypeptide chains (alpha, beta, gamma), which are bound to each other by disulfide bonds into a cross-shaped molecule comprising one long and three short arms with globules at each end. Beta-3 is a subunit of laminin-5 (laminin-332 or epiligrin/kalinin/nicein). Interacts with ECM1.
messages: The alpha-helical domains I and II are thought to interact with other laminin chains to form a coiled coil structure.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: basement membrane

9606:ZNF837
gene id: 9606:ZNF837
uniprot id: Q96EG3
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:OR2G6
gene id: 9606:OR2G6
uniprot id: A0A126GW53
uniprot id: Q5TZ20
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Membrane
messages: Odorant receptor.

9606:TMED4
gene id: 9606:TMED4
uniprot id: F8W7F7
uniprot id: Q7Z7H5
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the EMP24/GP25L family.
messages: Endoplasmic reticulum membrane
messages: Involved in vesicular protein trafficking, mainly in the early secretory pathway. targeting. Involved in the maintenance of the Golgi apparatus. Appears to play a role in the biosynthesis of secreted cargo including processing. Involved in endoplasmic reticulum stress response. May play a role in the regulation of heat-shock response and apoptosis (By similarity).
messages: Membrane

9606:CLDN12
gene id: 9606:CLDN12
uniprot id: B2R687
uniprot id: P56749
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the claudin family.
messages: Cell membrane
messages: Interacts with OCLN (PubMed:20375010).
messages: Membrane
messages: Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity.
messages: tight junction

9606:ETFB
gene id: 9606:ETFB
uniprot id: P38117
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Abundant in liver, heart and skeletal muscle. A weak expression is seen in the brain, placenta, lung, kidney and pancreas.
messages: Belongs to the ETF beta-subunit/FixA family.
messages: Heterodimer composed of ETFA and ETFB (PubMed:25023281, PubMed:25416781, PubMed:8962055, PubMed:15159392, PubMed:15975918). Identified in a complex that contains ETFA, ETFB and ETFRF1 (PubMed:27499296). Interacts with ACADM (PubMed:15159392, PubMed:15975918).
messages: Heterodimeric electron transfer flavoprotein that accepts electrons from several mitochondrial dehydrogenases, including acyl-CoA dehydrogenases, glutaryl-CoA and sarcosine dehydrogenase (PubMed:25416781, PubMed:15159392, PubMed:15975918). It transfers the electrons to the main mitochondrial respiratory chain via ETF-ubiquinone oxidoreductase (Probable). Required for normal mitochondrial fatty acid oxidation and normal amino acid metabolism (PubMed:12815589, PubMed:7912128). ETFB binds an AMP molecule that probably has a purely structural role (PubMed:8962055, PubMed:15159392, PubMed:15975918).
messages: Methylated. Trimethylation at Lys-200 and Lys-203 may negatively regulate the activity in electron transfer from acyl-CoA dehydrogenases.
messages: Mitochondrion matrix
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The recognition loop recognizes a hydrophobic patch at the surface of interacting dehydrogenases and acts as a static anchor at the interface.

9606:SEC22B
gene id: 9606:SEC22B
uniprot id: O75396
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the synaptobrevin family.
messages: Endoplasmic reticulum membrane
messages: Endoplasmic reticulum-Golgi intermediate compartment membrane
messages: Interacts with STX17 (By similarity). Component of two distinct SNARE complexes consisting of STX5, GOSR2/BOS1, BET1 and SEC22B or STX18, USE1L, BNIP1/SEC20L and SEC22B. YKT6 can probably replace SEC22B in either complex. Interacts with the COPII Sec23/24 complex composed of SEC23A and SEC24A; recruits SEC22B into COPII-coated vesicles to allow its transport from the endoplasmic reticulum to the Golgi (PubMed:17499046, PubMed:18843296).
messages: Melanosome
messages: SNARE involved in targeting and fusion of ER-derived transport vesicles with the Golgi complex as well as Golgi-derived retrograde transport vesicles with the ER.
messages: cis-Golgi network membrane
messages: trans-Golgi network membrane

9606:DEPTOR
gene id: 9606:DEPTOR
uniprot id: Q8TB45
names: Activity Regulation
names: Function
names: Induction
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: Associated component of the mechanistic target of rapamycin complex 1 (mTORC1) which contains MTOR, MLST8 and RPTOR (PubMed:19446321, PubMed:25936805, PubMed:34519269, PubMed:34519268). Associated component of the mechanistic target of rapamycin complex 2 (mTORC2) which contains MTOR, MLST8, PROTOR1, RICTOR, MAPKAP1 and DEPTOR (PubMed:19446321, PubMed:34519268). Interacts (via PDZ domain) with MTOR; interacts with MTOR within both mTORC1 and mTORC2 (PubMed:19446321). Interacts (via PDZ domain) with MINAR1 (via N-terminus) (PubMed:30080879). Interacts with SIK3 (PubMed:30232230).
messages: Expression is negatively regulated by both mTORC1 and mTORC2 (at protein level).
messages: Inhibited upon phosphatidic acid-binding: phosphatidic acid produced upon mitogenic stimulation promotes DEPTOR dissociatiom from the mTORC1 and mTORC2 complexes, leading to their activation (PubMed:25936805, PubMed:33865870). Specifically binds unsaturated phosphatidic acid, such as 16:0-18:1, 18:0-18:1 and di-18:1 (PubMed:25936805). Inhibited when nutrients are present via a feedback loop: phosphorylation by MTOR promotes DEPTOR ubiquitination and degradation (PubMed:22017875, PubMed:22017876, PubMed:22017877).
messages: Lysosome membrane
messages: Negative regulator of the mTORC1 and mTORC2 complexes: inhibits the protein kinase activity of MTOR, thereby inactivating both complexes (PubMed:19446321, PubMed:22017875, PubMed:22017876, PubMed:22017877, PubMed:25936805, PubMed:29382726, PubMed:34519269, PubMed:34519268). DEPTOR inhibits mTORC1 and mTORC2 to induce autophagy (PubMed:22017875, PubMed:22017876, PubMed:22017877). In contrast to AKT1S1/PRAS40, only partially inhibits mTORC1 activity (PubMed:34519269, PubMed:34519268).
messages: Phosphorylation weakens interaction with MTOR within mTORC1 and mTORC2 (PubMed:19446321). Phosphorylated at Ser-286, Ser-287 and Ser-291 in response to mitogenic stimulation by MTOR: DEPTOR is either directly phosphorylated by MTOR or indirectly via proteins kinases that are activated by MTOR, such as CK1/CSNK1A1 (PubMed:22017875, PubMed:22017876, PubMed:22017877). Phosphorylation at Ser-286, Ser-287 and Ser-291 promotes ubiquitination by the SCF(BTRC) complex, followed by degradation (PubMed:22017875, PubMed:22017876, PubMed:22017877). Phosphorylation at Ser-235 by MAPK3/ERK1 promotes deubiquitination by USP7, enhancing its stability (PubMed:35216969). Phosphorylation at Tyr-289 by SYK impairs its interaction with MTOR, promoting mTORC1 and mTORC2 signaling (PubMed:34634301).
messages: Ubiquitinated; leading to proteasomal degradation (PubMed:22017875, PubMed:22017876, PubMed:22017877, PubMed:30080879, PubMed:33110214). Ubiquitination by the SCF(BTRC) and SCF(FBXW11) complexes following phosphorylation at Ser-286, Ser-287 and Ser-291 by MTOR, leads to its degradation by the proteasome (PubMed:22017875, PubMed:22017876, PubMed:22017877, PubMed:33110214). Deubiquitinated by OTUB1 in response to amino acid via a non-canonical mechanism, leading to DEPTOR stability (PubMed:29382726). Deubiquitinated by USP7 following phosphorylation at Ser-235, promoting its stability (PubMed:35216969).

9606:POM121L2
gene id: 9606:POM121L2
uniprot id: Q96KW2
names: Caution
names: Similarity
messages: Belongs to the POM121 family.
messages: This sequence lacks full-length transcript support.

9606:TMEM256
gene id: 9606:TMEM256
uniprot id: Q8N2U0
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the TMEM256 family.
messages: Membrane

9606:ZNF248
gene id: 9606:ZNF248
uniprot id: Q8NDW4
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:PIGB
gene id: 9606:PIGB
uniprot id: Q92521
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the glycosyltransferase 22 family. PIGB subfamily.
messages: Endoplasmic reticulum membrane
messages: Mannosyltransferase involved in glycosylphosphatidylinositol-anchor biosynthesis. Transfers the third alpha-1,2-mannose to Man2-GlcN-acyl-PI during GPI precursor assembly.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:NDUFB5
gene id: 9606:NDUFB5
uniprot id: A0A087WYD0
uniprot id: O43674
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone.
messages: Belongs to the complex I NDUFB5 subunit family.
messages: Complex I is composed of 45 different subunits.
messages: Mitochondrion inner membrane

9606:TRAPPC5
gene id: 9606:TRAPPC5
uniprot id: Q8IUR0
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the TRAPP small subunits family. BET3 subfamily.
messages: Component of the multisubunit TRAPP (transport protein particle) complex, which includes at least TRAPPC2, TRAPPC2L, TRAPPC3, TRAPPC3L, TRAPPC4, TRAPPC5, TRAPPC8, TRAPPC9, TRAPPC10, TRAPPC11 and TRAPPC12.
messages: Endoplasmic reticulum
messages: May play a role in vesicular transport from endoplasmic reticulum to Golgi.
messages: cis-Golgi network

9606:LDLR
gene id: 9606:LDLR
uniprot id: P01130
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Acts as a receptor for Vesicular stomatitis virus.
messages: (Microbial infection) Acts as a receptor for hepatitis C virus in hepatocytes, but not through a direct interaction with viral proteins.
messages: (Microbial infection) In case of HIV-1 infection, may function as a receptor for extracellular Tat in neurons, mediating its internalization in uninfected cells.
messages: (Microbial infection) Interacts with C.difficile toxin TcdA, suggesting that it may contribute to TcdA toxin entry into cells.
messages: (Microbial infection) Interacts with vesicular stomatitis virus glycoprotein.
messages: (Microbial infection) May interact with HIV-1 Tat.
messages: Belongs to the LDLR family.
messages: Binds LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits.
messages: Cell membrane
messages: Early endosome
messages: Golgi apparatus
messages: Interacts (via NPXY motif) with DAB2 (via PID domain); the interaction is impaired by tyrosine phosphorylation of the NPXY motif (By similarity). Interacts (via NPXY motif) with LDLRAP1 (via PID domain) (PubMed:12221107, PubMed:22509010). Interacts with ARRB1 (PubMed:12944399). Interacts with SNX17 (PubMed:14739284). Interacts with the full-length immature form of PCSK9 (via C-terminus) (PubMed:17461796, PubMed:21149300).
messages: Late endosome
messages: Lysosome
messages: N- and O-glycosylated.
messages: The NPXY motif mediates the interaction with the clathrin adapter DAB2 and with LDLRAP1 which are involved in receptor internalization. A few residues outside the motif also play a role in the interaction.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitinated by MYLIP leading to degradation.
messages: clathrin-coated pit

9606:HSD3B2
gene id: 9606:HSD3B2
uniprot id: P26439
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: 3-beta-HSD is a bifunctional enzyme, that catalyzes the oxidative conversion of Delta(5)-ene-3-beta-hydroxy steroid, and the oxidative conversion of ketosteroids. The 3-beta-HSD enzymatic system plays a crucial role in the biosynthesis of all classes of hormonal steroids.
messages: Belongs to the 3-beta-HSD family.
messages: Endoplasmic reticulum membrane
messages: Expressed in adrenal gland, testis and ovary.
messages: Mild HSD3B2 deficiency in hyperandrogenic females is associated with characteristic traits of polycystic ovary syndrome, such as insulin resistance and luteinizing hormone hypersecretion.
messages: Mitochondrion membrane
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:TFAP2B
gene id: 9606:TFAP2B
uniprot id: Q92481
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the AP-2 family.
messages: Binds DNA as a dimer. Can form homodimers or heterodimers with other AP-2 family members. Interacts with CITED4. Interacts with UBE2I. Interacts with KCTD1; this interaction represses transcription activation. Interacts with CITED2 (via C-terminus); the interaction stimulates TFAP2B-transcriptional activity.
messages: Nucleus
messages: Sequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to regulate transcription of selected genes. AP-2 factors bind to the consensus sequence 5'-GCCNNNGGC-3' and activate genes involved in a large spectrum of important biological functions including proper eye, face, body wall, limb and neural tube development. They also suppress a number of genes including MCAM/MUC18, C/EBP alpha and MYC. AP-2-beta appears to be required for normal face and limb development and for proper terminal differentiation and function of renal tubular epithelia.
messages: Sumoylated on Lys-21; which inhibits transcriptional activity.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:PTPN7
gene id: 9606:PTPN7
uniprot id: P35236
names: Activity Regulation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the protein-tyrosine phosphatase family. Non-receptor class subfamily.
messages: Cytoplasm
messages: Expressed exclusively in thymus and spleen.
messages: Inhibited in cells after FCER1A triggering.
messages: Monomer. Interacts with MAPK1, MAPK3 and several other MAP kinases.
messages: Oxidized at active site cysteine. Treatment with pervanadate (vanadate and H(2)O(2)) or with antigen enhanced oxidation of active site cysteine (By similarity).
messages: Phosphorylated on serine residues in resting T-cells. Phosphorylation increases upon exposure to stimuli that increase intracellular cAMP levels. Phosphorylation leads to dissociation of bound MAP kinases.
messages: Protein phosphatase that acts preferentially on tyrosine-phosphorylated MAPK1. Plays a role in the regulation of T and B-lymphocyte development and signal transduction.
messages: cytoskeleton

9606:PSTK
gene id: 9606:PSTK
uniprot id: Q8IV42
names: Function
names: Similarity
messages: Belongs to the L-seryl-tRNA(Sec) kinase family.
messages: Specifically phosphorylates seryl-tRNA(Sec) to O-phosphoseryl-tRNA(Sec), an activated intermediate for selenocysteine biosynthesis.

9606:C3orf38
gene id: 9606:C3orf38
uniprot id: Q5JPI3
names: Function
messages: May be involved in apoptosis regulation.

9606:TRMO
gene id: 9606:TRMO
uniprot id: Q5T114
uniprot id: Q9BU70
names: Function
names: Sequence Caution
names: Similarity
messages: Belongs to the tRNA methyltransferase O family.
messages: Contaminating sequence.
messages: S-adenosyl-L-methionine-dependent methyltransferase responsible for the addition of the methyl group in the formation of N6-methyl-N6-threonylcarbamoyladenosine at position 37 (m(6)t(6)A37) of the tRNA anticodon loop of tRNA(Ser)(GCU) (PubMed:25063302). The methyl group of m(6)t(6)A37 may improve the efficiency of the tRNA decoding ability (By similarity).

9606:PBLD
gene id: 9606:PBLD
uniprot id: P30039
names: Similarity
names: Subunit
messages: Belongs to the PhzF family.
messages: Interacts with UNRIP/MAWD.

9606:MMP17
gene id: 9606:MMP17
uniprot id: Q9ULZ9
names: Cofactor
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the peptidase M10A family.
messages: Binds 1 zinc ion per subunit.
messages: Cell membrane
messages: Endopeptidase that degrades various components of the extracellular matrix, such as fibrin. May be involved in the activation of membrane-bound precursors of growth factors or inflammatory mediators, such as tumor necrosis factor-alpha. May also be involved in tumoral process. Cleaves pro-TNF-alpha at the '74-Ala-|-Gln-75' site. Not obvious if able to proteolytically activate progelatinase A. Does not hydrolyze collagen types I, II, III, IV and V, gelatin, fibronectin, laminin, decorin nor alpha1-antitrypsin.
messages: Expressed in brain, leukocytes, colon, ovary testis and breast cancer. Expressed also in many transformed and non-transformed cell types.
messages: The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.
messages: The precursor is cleaved by a furin endopeptidase.
messages: extracellular matrix

9606:TUBB4A
gene id: 9606:TUBB4A
uniprot id: P04350
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the tubulin family.
messages: Dimer of alpha and beta chains. A typical microtubule is a hollow water-filled tube with an outer diameter of 25 nm and an inner diameter of 15 nM. Alpha-beta heterodimers associate head-to-tail to form protofilaments running lengthwise along the microtubule wall with the beta-tubulin subunit facing the microtubule plus end conferring a structural polarity. Microtubules usually have 13 protofilaments but different protofilament numbers can be found in some organisms and specialized cells.
messages: Major isotype in brain, where it represents 46% of all beta-tubulins. In the brain, highest expression levels in the cerebellum, followed by putamen and white matter. Moderate levels in testis. Very low levels, if any, in other tissues.
messages: Phosphorylated on Ser-172 by CDK1 during the cell cycle, from metaphase to telophase, but not in interphase. This phosphorylation inhibits tubulin incorporation into microtubules.
messages: Some glutamate residues at the C-terminus are monoglycylated but not polyglycylated due to the absence of functional TTLL10 in human. Monoglycylation is mainly limited to tubulin incorporated into cilia and flagella axonemes, which is required for their stability and maintenance. Flagella glycylation controls sperm motility. Both polyglutamylation and monoglycylation can coexist on the same protein on adjacent residues, and lowering glycylation levels increases polyglutamylation, and reciprocally.
messages: Some glutamate residues at the C-terminus are polyglutamylated, resulting in polyglutamate chains on the gamma-carboxyl group (PubMed:26875866). Polyglutamylation plays a key role in microtubule severing by spastin (SPAST). SPAST preferentially recognizes and acts on microtubules decorated with short polyglutamate tails: severing activity by SPAST increases as the number of glutamates per tubulin rises from one to eight, but decreases beyond this glutamylation threshold (PubMed:26875866). Glutamylation is also involved in cilia motility (By similarity).
messages: The MREI motif is common among all beta-tubulin isoforms and may be critical for tubulin autoregulation.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The highly acidic C-terminal region may bind cations such as calcium.
messages: Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin.
messages: cytoskeleton

9606:HRK
gene id: 9606:HRK
uniprot id: O00198
names: Domain
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Interacts with BCL2 and BCL2L1. Interacts with C1QBP.
messages: Membrane
messages: Mitochondrion
messages: Promotes apoptosis.
messages: The BH3 motif is required for the induction of cell death.

9606:LNX1
gene id: 9606:LNX1
uniprot id: Q8TBB1
names: Domain
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cytoplasm
messages: E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of NUMB. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Mediates ubiquitination of isoform p66 and isoform p72 of NUMB, but not that of isoform p71 or isoform p65.
messages: Expressed in heart, placenta, kidney, pancreas and brain.
messages: Interacts with the phosphotyrosine interaction domain of all isoforms of NUMB (By similarity). Interacts with MAGEB18 and MAGEF1. Interacts with the Coxsackievirus and adenovirus receptor CXADR. Interacts with endogenous retrovirus K protein Np9. IGSF5/JAM4 interacts with isoform 2 through the second PDZ domain, other isoforms may also interact with IGSF5/JAM4 (By similarity).
messages: Isoform 2 provides an endocytic scaffold for IGSF5/JAM4.
messages: The NPXY motif is required for the interaction with the PID domain of NUMB. It is however not sufficient.
messages: The PDZ 1 domain participates in the interaction with the PID domain of NUMB, and participates in the isoform-specific ubiquitination of NUMB. The PDZ 2 domain of isoform 2 participates in the interaction with IGSF5/JAM4, other isoforms containing this domain may also interact with IGSF5/JAM4 (By similarity).

9606:GFPT1
gene id: 9606:GFPT1
uniprot id: Q06210
names: Disease Annotation
names: Function
names: Subunit
names: Tissue Specificity
messages: Controls the flux of glucose into the hexosamine pathway. Most likely involved in regulating the availability of precursors for N- and O-linked glycosylation of proteins. Regulates the circadian expression of clock genes BMAL1 and CRY1 (By similarity). Has a role in fine tuning the metabolic fluctuations of cytosolic UDP-GlcNAc and its effects on hyaluronan synthesis that occur during tissue remodeling (PubMed:26887390).
messages: Homotetramer (Probable), may also exist as homodimers.
messages: Isoform 1 is predominantly expressed in skeletal muscle. Not expressed in brain. Seems to be selectively expressed in striated muscle.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:KIFAP3
gene id: 9606:KIFAP3
uniprot id: Q92845
names: Function
names: PTM
names: Subunit
messages: Heterotrimer of KIFAP3, KIF3A and KIF3B. Interacts with RAP1GDS1/SMG GDS. Interacts with SMC3 subunit of the cohesin complex.
messages: Involved in tethering the chromosomes to the spindle pole and in chromosome movement. Binds to the tail domain of the KIF3A/KIF3B heterodimer to form a heterotrimeric KIF3 complex and may regulate the membrane binding of this complex (By similarity).
messages: Phosphorylated on tyrosine residues by SRC in vitro; this reduces the binding affinity of the protein for RAP1GDS1.

9606:DRAM2
gene id: 9606:DRAM2
uniprot id: Q6UX65
names: Disease Annotation
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Apical cell membrane
messages: Belongs to the DRAM/TMEM150 family.
messages: Expression is down-regulated in ovarian tumors (at protein level). Widely expressed with highest levels in placenta and heart. Expressed in the retina. Not detected in brain or thymus.
messages: Lysosome membrane
messages: Not induced by p53/TP53 or TP73/p73.
messages: Photoreceptor inner segment
messages: Plays a role in the initiation of autophagy. In the retina, might be involved in the process of photoreceptor cells renewal and recycling to preserve visual function. Induces apoptotic cell death when coexpressed with DRAM1.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:PPME1
gene id: 9606:PPME1
uniprot id: A0A140VK39
uniprot id: Q9Y570
names: Function
names: PTM
names: Similarity
names: Subunit
messages: Belongs to the AB hydrolase superfamily.
messages: Binds PPP2CA and PPP2CB.
messages: Demethylates proteins that have been reversibly carboxymethylated. Demethylates PPP2CB (in vitro) and PPP2CA. Binding to PPP2CA displaces the manganese ion and inactivates the enzyme.
messages: Phosphorylated by SIK1 following increases in intracellular sodium, leading to dissociation from the protein phosphatase 2A (PP2A) complex and subsequent dephosphorylation of sodium/potassium-transporting ATPase ATP1A1.

9606:RHEX
gene id: 9606:RHEX
uniprot id: Q6ZWK4
names: Function
names: Induction
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acts as a signaling transduction factor of the EPO-EPOR signaling pathway promoting erythroid cell differentiation (PubMed:25092874).
messages: Cell membrane
messages: Expressed in the proerythroblasts (at protein level) (PubMed:25092874). Expressed strongly in the kidney (PubMed:25092874). Expressed weakly in the pancreas, liver and lung (PubMed:25092874). Expressed strongly in erythroid progenitor cells (EPCs) (PubMed:25092874). Expressed weakly in T-cells and neutrophils (PubMed:25092874).
messages: Interacts with EPOR; this interaction occurs in a erythropoietin (EPO)-dependent manner (PubMed:25092874). Interacts with JAK2; this interaction occurs in a erythropoietin (EPO)-dependent manner (PubMed:25092874). Interacts (via tyrosine-phosphorylated form) with GRB2 (PubMed:25092874).
messages: Phosphorylated. Phosphorylation on Tyr-132 and Tyr-141 occurs in a erythropoietin (EPO)-dependent manner (PubMed:25092874).
messages: Up-regulated during erythroid differentiation (PubMed:25092874).

9606:PSMC5
gene id: 9606:PSMC5
uniprot id: A0A140VJS3
uniprot id: P62195
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the AAA ATPase family.
messages: Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits, a base containing 6 ATPases including PSMC5 and few additional components (PubMed:27428775, PubMed:27342858). Component of a complex with USP49 and RUVBL1 (PubMed:23824326). Interacts with PRPF19. Interacts with TRIM5 (PubMed:22078707). Interacts with NDC80 (PubMed:9295362, PubMed:10409732). Interacts with PAAF1 (PubMed:15831487). Interacts, in vitro, with the thyroid hormone receptor (in a thyroid hormone T3-dependent manner) and with retinoid X receptor (RXR) (By similarity). Interacts with ERCC6 (PubMed:26030138).
messages: Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. PSMC5 belongs to the heterohexameric ring of AAA (ATPases associated with diverse cellular activities) proteins that unfolds ubiquitinated target proteins that are concurrently translocated into a proteolytic chamber and degraded into peptides.
messages: Cytoplasm
messages: Nucleus

9606:NAPEPLD
gene id: 9606:NAPEPLD
uniprot id: Q6IQ20
names: Activity Regulation
names: Cofactor
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Activated by divalent cations (PubMed:16527816). Activated by bile acids and their conjugates, except for lithocholic acid which is rather inhibitory. Binding of deoxycholic acid favors the selective release of anandamide and likely other unsatured long FAEs (PubMed:27571266, PubMed:25684574). Inhibited by phosphatidylethanolamines (PubMed:25684574).
messages: Belongs to the NAPE-PLD family.
messages: Binds 2 zinc divalent cations per subunit.
messages: D-type phospholipase that hydrolyzes N-acyl-phosphatidylethanolamines (NAPEs) to produce bioactive N-acylethanolamines/fatty acid ethanolamides (NAEs/FAEs) and phosphatidic acid (PubMed:14634025, PubMed:16527816, PubMed:27571266, PubMed:25684574). Cleaves the terminal phosphodiester bond of diacyl- and alkenylacyl-NAPEs, primarily playing a role in the generation of long-chain saturated and monounsaturated NAEs in the brain (By similarity). May control NAPE homeostasis in dopaminergic neuron membranes and regulate neuron survival, partly through RAC1 activation (By similarity). As a regulator of lipid metabolism in the adipose tissue, mediates the crosstalk between adipocytes, gut microbiota and immune cells to control body temperature and weight. In particular, regulates energy homeostasis by promoting cold-induced brown or beige adipocyte differentiation program to generate heat from fatty acids and glucose. Has limited D-type phospholipase activity toward N-acyl lyso-NAPEs (By similarity).
messages: Early endosome membrane
messages: Golgi apparatus membrane
messages: Homodimer. Bile acids promote the assembly of inactive monomers into an active dimer and enable catalysis.
messages: Nucleus envelope
messages: Widely expressed. Highest expression in brain, kidney and testis (at protein level). Expressed in adipose tissue (at protein level).
messages: nucleoplasm

9606:DDB1
gene id: 9606:DDB1
uniprot id: Q16531
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Interacts with Simian virus 5 protein V.
messages: (Microbial infection) Interacts with hepatitis B virus protein HBX; the viral protein contains a short helical motif that competes for the same binding site as the N-terminal helical motif found in endogenous DCAF proteins.
messages: (Microbial infection) Interacts with human cytomegalovirus protein UL145; this interaction promotes STAT2 degradation.
messages: Acetylated, promoting interaction with CUL4 (CUL4A or CUL4B) and subsequent formation of DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes (PubMed:28886238). Deacetylation by SIRT7 impairs the interaction with CUL4 (CUL4A or CUL4B) and formation of DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes (PubMed:28886238).
messages: Belongs to the DDB1 family.
messages: Component of the UV-DDB complex which includes DDB1 and DDB2; the heterodimer dimerizes to give rise to a heterotetramer when bound to damaged DNA (PubMed:9632823, PubMed:16223728, PubMed:16527807, PubMed:19109893, PubMed:22822215). The UV-DDB complex interacts with monoubiquitinated histone H2A and binds to XPC via the DDB2 subunit (PubMed:16473935). Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, CUL4A or CUL4B and RBX1 (PubMed:11673459, PubMed:12732143, PubMed:15882621, PubMed:16678110, PubMed:18593899, PubMed:28886238, PubMed:28437394, PubMed:28302793, PubMed:31693891, PubMed:31686031, PubMed:31819272, PubMed:31693911). DDB1 may recruit specific substrate targeting subunits to the DCX complex (PubMed:11673459, PubMed:12732143, PubMed:15882621, PubMed:18593899, PubMed:28886238). These substrate targeting subunits are generally known as DCAF (DDB1- and CUL4-associated factor) or CDW (CUL4-DDB1-associated WD40-repeat) proteins (PubMed:17079684, PubMed:16949367, PubMed:18606781, PubMed:19608861, PubMed:16964240, PubMed:19966799). Interacts with AMBRA1, ATG16L1, BTRC, CRBN, DCAF1, DCAF4, DCAF5, DCAF6, DCAF7, DCAF8, DCAF9, DCAF10, DCAF11, DCAF12, DCAF15, DCAF16, DCAF17, DDA1, DET1, DTL, ERCC8, FBXW5, FBXW8, GRWD1, KATNB1, NLE1, NUP43, PAFAH1B1, PHIP, PWP1, RBBP4, RBBP5, RBBP7, COP1, SNRNP40, DCAF1, WDR5, WDR5B, WDR12, WDR26, WDR39, WDR42, WDR53, WDR59, WDR61, WSB1, WSB2, LRWD1 and WDTC1 (PubMed:14739464, PubMed:17079684, PubMed:16949367, PubMed:17041588, PubMed:18606781, PubMed:22935713, PubMed:23478445, PubMed:22118460, PubMed:25043012, PubMed:25108355). DCX complexes may associate with the COP9 signalosome, and this inhibits the E3 ubiquitin-protein ligase activity of the complex (PubMed:15448697, PubMed:16260596). Interacts with NF2, TSC1 and TSC2 (PubMed:18332868, PubMed:18381890). Interacts with AGO1 and AGO2 (PubMed:17932509). Associates with the E3 ligase complex containing DYRK2, EDD/UBR5, DDB1…
messages: Cytoplasm
messages: Nucleus
messages: Phosphorylated by ABL1.
messages: Protein, which is both involved in DNA repair and protein ubiquitination, as part of the UV-DDB complex and DCX (DDB1-CUL4-X-box) complexes, respectively (PubMed:15448697, PubMed:14739464, PubMed:16260596, PubMed:16482215, PubMed:17079684, PubMed:16407242, PubMed:16407252, PubMed:16940174). Core component of the UV-DDB complex (UV-damaged DNA-binding protein complex), a complex that recognizes UV-induced DNA damage and recruit proteins of the nucleotide excision repair pathway (the NER pathway) to initiate DNA repair (PubMed:15448697, PubMed:16260596, PubMed:16407242, PubMed:16940174). The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches (PubMed:15448697, PubMed:16260596, PubMed:16407242, PubMed:16940174). Also functions as a component of numerous distinct DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:14739464, PubMed:16407252, PubMed:16482215, PubMed:17079684, PubMed:25043012, PubMed:25108355, PubMed:18332868, PubMed:18381890, PubMed:19966799, PubMed:22118460, PubMed:28886238). The functional specificity of the DCX E3 ubiquitin-protein ligase complex is determined by the variable substrate recognition component recruited by DDB1 (PubMed:14739464, PubMed:16407252, PubMed:16482215, PubMed:17079684, PubMed:25043012, PubMed:25108355, PubMed:18332868, PubMed:18381890, PubMed:19966799, PubMed:22118460). DCX(DDB2) (also known as DDB1-CUL4-ROC1, CUL4-DDB-ROC1 and CUL4-DDB-RBX1) may ubiquitinate histone H2A, histone H3 and histone H4 at sites of UV-induced DNA damage (PubMed:16678110, PubMed:17041588, PubMed:16473935, PubMed:18593899). The ubiquitination of histones may facilitate their removal from the nucleosome and promote subsequent DNA repair (PubMed:16678110, PubMed:17041588, PubMed:16473935, PubMed:18593899). DCX(DDB2) also ubiquitinates XPC, which may enhance DNA-bi…
messages: The core of the protein consists of three WD40 beta-propeller domains.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitinated by CUL4A. Subsequently degraded by ubiquitin-dependent proteolysis.

9606:MED18
gene id: 9606:MED18
uniprot id: Q9BUE0
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the Mediator complex subunit 18 family.
messages: Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors.
messages: Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP.
messages: Nucleus

9606:PCDHGA9
gene id: 9606:PCDHGA9
uniprot id: Q9Y5G4
names: Function
names: Subcellular Location Annotation
messages: Cell membrane
messages: Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain.

9606:SETD9
gene id: 9606:SETD9
uniprot id: Q8NE22
names: Similarity
messages: Belongs to the class V-like SAM-binding methyltransferase superfamily.

9606:CADM2
gene id: 9606:CADM2
uniprot id: G3XHN4
uniprot id: Q8N3J6
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Adhesion molecule that engages in homo- and heterophilic interactions with the other nectin-like family members, leading to cell aggregation. Important for synapse organization, providing regulated trans-synaptic adhesion. Preferentially binds to oligodendrocytes.
messages: Belongs to the nectin family.
messages: Cell membrane
messages: Synapse
messages: axon

9606:KLB
gene id: 9606:KLB
uniprot id: B4DYH5
uniprot id: Q86Z14
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the glycosyl hydrolase 1 family.
messages: Belongs to the glycosyl hydrolase 1 family. Klotho subfamily.
messages: Cell membrane
messages: Contains 2 glycosyl hydrolase 1 regions. However, the first region lacks the essential Glu active site residue at position 241, and the second one lacks the essential Glu active site residue at position 889. These domains are therefore predicted to be inactive.
messages: Contributes to the transcriptional repression of cholesterol 7-alpha-hydroxylase (CYP7A1), the rate-limiting enzyme in bile acid synthesis. Probably inactive as a glycosidase. Increases the ability of FGFR1 and FGFR4 to bind FGF21 (By similarity).
messages: Interacts with FGFR1 and FGFR4 (By similarity). Interacts with FGF19; this interaction is direct. Interacts (via C-terminus) with FGF21; this interaction is direct.

9606:ADCK2
gene id: 9606:ADCK2
uniprot id: A4D1T6
uniprot id: Q7Z695
names: Function
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
messages: Aberrant splicing.
messages: Belongs to the protein kinase superfamily. ADCK protein kinase family.
messages: Membrane
messages: The function of this protein is not yet clear. It is not known if it has protein kinase activity and what type of substrate it would phosphorylate (Ser, Thr or Tyr).

9606:SCMH1
gene id: 9606:SCMH1
uniprot id: B3KMZ7
uniprot id: Q96GD3
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Associates with Polycomb group (PcG) multiprotein complexes; the complex class is required to maintain the transcriptionally repressive state of some genes.
messages: Belongs to the SCM family.
messages: Interacts with the SAM domain of PHC1 via its SAM domain in vitro (By similarity). Associates with a PRC1-like complex.
messages: May be due to intron retention.
messages: Nucleus
messages: Strongly expressed in heart, muscle and pancreas. Weakly expressed in brain, placenta, lung, liver and kidney.

9606:ECEL1
gene id: 9606:ECEL1
uniprot id: O95672
names: Cofactor
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the peptidase M13 family.
messages: Binds 1 zinc ion.
messages: Highly expressed in the CNS, in particular in putamen, spinal cord, medulla and subthalamic nucleus. A strong signal was also detected in uterine subepithelial cells and around renal blood vessels. Detected at lower levels in amygdala, caudate, thalamus, pancreas and skeletal muscle. Detected at very low levels in substantia nigra, cerebellum, cortex, corpus callosum and hippocampus.
messages: May contribute to the degradation of peptide hormones and be involved in the inactivation of neuronal peptides.
messages: Membrane
messages: N-glycosylated.
messages: The disease is caused by variants affecting the gene represented in this entry. ECEL1 mutations have also been found in patients with arthrogryposis, significant ophthalmoplegia, and refractive errors (PubMed:23808592).

9606:PGA5
gene id: 9606:PGA5
uniprot id: P0DJD9
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the peptidase A1 family.
messages: Secreted
messages: Shows particularly broad specificity; although bonds involving phenylalanine and leucine are preferred, many others are also cleaved to some extent.

9606:SMCO1
gene id: 9606:SMCO1
uniprot id: Q147U7
names: Subcellular Location Annotation
messages: Membrane

9606:SEC14L1
gene id: 9606:SEC14L1
uniprot id: Q92503
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cytoplasm
messages: Golgi apparatus
messages: Interacts with RIGI (via tandem CARD domain); the interaction is direct (PubMed:23843640). Interacts (via GOLD domain) with SLC18A3; the interaction is direct (PubMed:17092608). Interacts with SLC5A7 (via GOLD domain); the interaction is direct (PubMed:17092608).
messages: May play a role in innate immunity by inhibiting the antiviral RIG-I signaling pathway. In this pathway, functions as a negative regulator of RIGI, the cytoplasmic sensor of viral nucleic acids. Prevents the interaction of RIGI with MAVS/IPS1, an important step in signal propagation (PubMed:23843640). May also regulate the SLC18A3 and SLC5A7 cholinergic transporters (PubMed:17092608).
messages: Ubiquitous.

9606:IFI44
gene id: 9606:IFI44
uniprot id: Q8TCB0
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the IFI44 family.
messages: By alpha and beta interferons, but not by gamma interferons.
messages: Cytoplasm
messages: This protein aggregates to form microtubular structures.

9606:RPUSD1
gene id: 9606:RPUSD1
uniprot id: Q9UJJ7
names: Similarity
messages: Belongs to the pseudouridine synthase RluA family.

9606:PEX1
gene id: 9606:PEX1
uniprot id: A0A0C4DG33
uniprot id: O43933
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the AAA ATPase family.
messages: Component of the PEX1-PEX6 AAA ATPase complex, a protein dislocase complex that mediates the ATP-dependent extraction of the PEX5 receptor from peroxisomal membranes, an essential step for PEX5 recycling (PubMed:11439091, PubMed:16314507, PubMed:16854980, PubMed:21362118, PubMed:29884772). Specifically recognizes PEX5 monoubiquitinated at 'Cys-11', and pulls it out of the peroxisome lumen through the PEX2-PEX10-PEX12 retrotranslocation channel (PubMed:29884772). Extraction by the PEX1-PEX6 AAA ATPase complex is accompanied by unfolding of the TPR repeats and release of bound cargo from PEX5 (PubMed:29884772).
messages: Homooligomer; homooligomerizes in the cytosol, interaction with PEX6 promotes dissociation of the homooligomer (PubMed:16854980). Interacts with PEX6; forming the PEX1-PEX6 AAA ATPase complex, which is composed of a heterohexamer formed by a trimer of PEX1-PEX6 dimers (PubMed:12717447, PubMed:16854980, PubMed:21362118). Interacts indirectly with PEX26, via its interaction with PEX6 (PubMed:12717447).
messages: Peroxisome membrane
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: cytosol

9606:INHBA
gene id: 9606:INHBA
uniprot id: A4D1W7
uniprot id: P08476
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the TGF-beta family.
messages: Dimeric, linked by one or more disulfide bonds. Inhibin A is a dimer of alpha and beta-A. Inhibin B is a dimer of alpha and beta-B. Activin A is a homodimer of beta-A. Activin B is a homodimer of beta-B. Activin AB is a dimer of beta-A and beta-B. Interacts with FST and FSTL3.
messages: Inhibins and activins inhibit and activate, respectively, the secretion of follitropin by the pituitary gland. Inhibins/activins are involved in regulating a number of diverse functions such as hypothalamic and pituitary hormone secretion, gonadal hormone secretion, germ cell development and maturation, erythroid differentiation, insulin secretion, nerve cell survival, embryonic axial development or bone growth, depending on their subunit composition. Inhibins appear to oppose the functions of activins.
messages: Secreted

9606:IFNA13
gene id: 9606:IFNA13
uniprot id: A0A087WWS6
uniprot id: P01562
names: Function
names: Miscellaneous
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the alpha/beta interferon family.
messages: Interferons alpha-1 and alpha-13 have identical protein sequences.
messages: Produced by macrophages, IFN-alpha have antiviral activities. Interferon stimulates the production of two enzymes: a protein kinase and an oligoadenylate synthetase.
messages: Secreted
messages: Two forms exist; alpha-1a (shown here) and alpha-1b (PubMed:11032395).

9606:EXOSC4
gene id: 9606:EXOSC4
uniprot id: Q9NPD3
names: Caution
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the RNase PH family.
messages: Component of the RNA exosome complex (PubMed:29906447). Specifically part of the catalytically inactive RNA exosome core (Exo-9) complex which is believed to associate with catalytic subunits EXOSC10, and DIS3 or DIS3L in cytoplasmic- and nuclear-specific RNA exosome complex forms. Exo-9 is formed by a hexameric ring of RNase PH domain-containing subunits specifically containing the heterodimers EXOSC4-EXOSC9, EXOSC5-EXOSC8 and EXOSC6-EXOSC7, and peripheral S1 domain-containing components EXOSC1, EXOSC2 and EXOSC3 located on the top of the ring structure. Interacts with DDX60.
messages: Cytoplasm
messages: Non-catalytic component of the RNA exosome complex which has 3'->5' exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events. In the nucleus, the RNA exosome complex is involved in proper maturation of stable RNA species such as rRNA, snRNA and snoRNA, in the elimination of RNA processing by-products and non-coding 'pervasive' transcripts, such as antisense RNA species and promoter-upstream transcripts (PROMPTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. The RNA exosome may be involved in Ig class switch recombination (CSR) and/or Ig variable region somatic hypermutation (SHM) by targeting AICDA deamination activity to transcribed dsDNA substrates. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and specifically degrades inherently unstable mRNAs containing AU-rich elements (AREs) within their 3' untranslated regions, and in RNA surveillance pathways, preventing translation of aberrant mRNAs. It seems to be involved in degradation of histone mRNA. The catalytic inactive RNA exosome core complex of 9 subunits (Exo-9) is proposed to play a pivotal role in the binding and presentation of RNA for ribonucleolysis, and to serve as a scaffold for the association with catalytic subunits and accessory proteins or complexes. EXOSC4 binds to ARE-containing RNAs.
messages: Nucleus
messages: The six exosome core subunits containing a RNase PH-domain are not phosphorolytically active.
messages: nucleolus

9606:LMAN2
gene id: 9606:LMAN2
uniprot id: Q12907
names: Cofactor
names: Function
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Binds 2 calcium ions per subunit.
messages: Endoplasmic reticulum membrane
messages: Endoplasmic reticulum-Golgi intermediate compartment membrane
messages: Golgi apparatus membrane
messages: Plays a role as an intracellular lectin in the early secretory pathway. Interacts with N-acetyl-D-galactosamine and high-mannose type glycans and may also bind to O-linked glycans. Involved in the transport and sorting of glycoproteins carrying high mannose-type glycans (By similarity).
messages: Ubiquitous.

9606:AGTRAP
gene id: 9606:AGTRAP
uniprot id: Q6RW13
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Appears to be a negative regulator of type-1 angiotensin II receptor-mediated signaling by regulating receptor internalization as well as mechanism of receptor desensitization such as phosphorylation. Induces also a decrease in cell proliferation and angiotensin II-stimulated transcriptional activity.
messages: Cytoplasmic vesicle membrane
messages: Endoplasmic reticulum membrane
messages: Golgi apparatus membrane
messages: Interacts with RACK1, and with the C-terminal region of AGTR1.
messages: Ubiquitous but more abundant in kidney, heart, pancreas and thyroid.

9606:POU3F3
gene id: 9606:POU3F3
uniprot id: P20264
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the POU transcription factor family. Class-3 subfamily.
messages: Brain.
messages: Homodimer.
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Transcription factor that acts synergistically with SOX11 and SOX4. Plays a role in neuronal development (PubMed:31303265). Is implicated in an enhancer activity at the embryonic met-mesencephalic junction; the enhancer element contains the octamer motif (5'-ATTTGCAT-3') (By similarity).

9606:GPR20
gene id: 9606:GPR20
uniprot id: Q59GP3
uniprot id: Q99678
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Orphan receptor with constitutive G(i) signaling activity that activate cyclic AMP.
messages: Ubiquitous with highest levels in intestinal tissues. In the brain detected in thalamus, putamen, and caudate, but not in frontal cortex, pons and hypothalamus.

9606:GPSM3
gene id: 9606:GPSM3
uniprot id: Q9Y4H4
names: Domain
names: Function
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Cytoplasm
messages: Expressed in heart, placenta, lung and liver.
messages: Interacts with subunit of G(i) alpha proteins and regulates the activation of G(i) alpha proteins.
messages: The GoLoco 1 and/or GoLoco 3 domains exhibit GDI activity towards GDP-bound G(i) alpha protein, but not the GoLoco 2 domain.

9606:PHLDA3
gene id: 9606:PHLDA3
uniprot id: Q9Y5J5
names: Domain
names: Function
names: Induction
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the PHLDA3 family.
messages: By p53/TP53; expression is directly activated by TP53. TP53 phosphorylation on 'Ser-15' is required to activate the PHLDA3 promoter.
messages: Cytoplasm
messages: Membrane
messages: PHLDA3 genomic locus is frequently observed in primary lung cancers, suggesting a role in tumor suppression.
messages: The PH domain binds phosphoinositides with a broad specificity. It competes with the PH domain of AKT1 and directly interferes with AKT1 binding to phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol 3,4,5-trisphosphate (PIP3), preventing AKT1 association to membrane lipids and subsequent activation of AKT1 signaling.
messages: Widely expressed with lowest expression in liver and spleen.
messages: p53/TP53-regulated repressor of Akt/AKT1 signaling. Represses AKT1 by preventing AKT1-binding to membrane lipids, thereby inhibiting AKT1 translocation to the cellular membrane and activation. Contributes to p53/TP53-dependent apoptosis by repressing AKT1 activity. Its direct transcription regulation by p53/TP53 may explain how p53/TP53 can negatively regulate AKT1. May act as a tumor suppressor.

9606:WDR3
gene id: 9606:WDR3
uniprot id: Q9UNX4
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the WD repeat WDR3/UTP12 family.
messages: Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3.
messages: Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome.
messages: Ubiquitous.
messages: nucleolus

9606:B3GALT4
gene id: 9606:B3GALT4
uniprot id: B3KQP5
uniprot id: O96024
uniprot id: Q5STJ7
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the glycosyltransferase 31 family.
messages: Golgi apparatus membrane
messages: Highly expressed in heart, skeletal muscle and pancreas and, to a lesser extent, in brain, placenta, kidney, liver and lung.
messages: Involved in GM1/GD1B/GA1 ganglioside biosynthesis.
messages: Membrane

9606:H2AB2
gene id: 9606:H2AB2
uniprot id: P0C5Z0
names: Domain
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Atypical histone H2A which can replace conventional H2A in some nucleosomes and is associated with active transcription and mRNA processing. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. Nucleosomes containing this histone are less rigid and organize less DNA than canonical nucleosomes in vivo. They are enriched in actively transcribed genes and associate with the elongating form of RNA polymerase. They associate with spliceosome components and are required for mRNA splicing. May participate in spermatogenesis.
messages: Belongs to the histone H2A family.
messages: Chromosome
messages: In contrast to other H2A histones, it does not contain the conserved residues that are the target of post-translational modifications.
messages: Nucleus
messages: Present in mature sperm.
messages: The docking domain is responsible for the weaker heterodimerization with H2B.
messages: The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. May be incorporated into a proportion of nucleosomes, replacing one or more H2A molecules.

9606:ZMIZ1
gene id: 9606:ZMIZ1
uniprot id: Q9ULJ6
names: Disease Annotation
names: Domain
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acts as transcriptional coactivator. Increases ligand-dependent transcriptional activity of AR and promotes AR sumoylation. The stimulation of AR activity is dependent upon sumoylation (PubMed:14609956, PubMed:26522984). Also functions as a transcriptional coactivator in the TGF-beta signaling pathway by increasing the activity of the SMAD3/SMAD4 transcriptional complex (PubMed:16777850). Involved in transcriptional activation of a subset of NOTCH1 target genes including MYC. Involved in thymocyte and T cell development (By similarity). Involved in the regulation of postmitotic positioning of pyramidal neurons in the developing cerebral cortex (PubMed:30639322).
messages: Cytoplasm
messages: Expressed most abundantly in ovary and, at lower levels, in prostate, spleen and testis. Weak expression, if any, in thymus, small intestine, colon and peripheral blood leukocytes.
messages: Interacts with AR, but not with ESR1, NR3C1, PGR, THRB nor VDR. Interacts with NOTCH1 and RBPJ (PubMed:14609956, PubMed:26522984). Interacts with SMARCA4 (By similarity). Interacts (via SP-RING-type domain) with SMAD3 and SMAD4 (via MH2 domain) (PubMed:16777850).
messages: Nucleus
messages: The C-terminal proline-rich domain possesses a significant intrinsic transcriptional activity. This activity is inhibited by the N-terminus in the full-length protein.
messages: The SP-RING-type domain mediates interaction with SMAD3 and SMAD4.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: nucleoplasm

9606:COX16
gene id: 9606:COX16
uniprot id: Q9P0S2
names: Disease Annotation
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Associates with the MITRAC complex (PubMed:29381136). Interacts with MT-CO2/COX; specifically interacts with newly synthesized MT-CO2/COX (PubMed:29355485, PubMed:29381136). Interacts with SCO1, SCO2 and COA6 (PubMed:29381136).
messages: Belongs to the COX16 family.
messages: Mitochondrion inner membrane
messages: No COX16 mutations have been detected in patients with cytochrome c oxidase (COX) deficiency.
messages: Required for the assembly of the mitochondrial respiratory chain complex IV (CIV), also known as cytochrome c oxidase (PubMed:29355485, PubMed:29381136, PubMed:33169484). Promotes the insertion of copper into the active site of cytochrome c oxidase subunit II (MT-CO2/COX2) (PubMed:29355485, PubMed:29381136). Interacts specifically with newly synthesized MT-CO2/COX and its copper center-forming metallochaperones SCO1, SCO2 and COA6 (PubMed:29381136). Probably facilitates MT-CO2/COX2 association with the MITRAC assembly intermediate containing MT-CO1/COX1, thereby participating in merging the MT-CO1/COX1 and MT-CO2/COX2 assembly lines (PubMed:29381136).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Widely expressed. Expressed at higher level in skeletal muscle, heart and liver.

9606:PLA2G2A
gene id: 9606:PLA2G2A
uniprot id: P14555
names: Cofactor
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the phospholipase A2 family.
messages: Binds 1 Ca(2+) ion per subunit.
messages: Cell membrane
messages: Expressed in various tissues including heart, kidney, liver, lung, pancreas, placenta, skeletal muscle, prostate, ovary, colon and small intestine. Not detected in lymphoid organs and brain (PubMed:10455175, PubMed:10681567). Expressed in platelets (at protein level) (PubMed:25082876).
messages: Group II phospholipase A2 is found in many cells and also extracellularly. The membrane-bound and secreted forms are identical and are encoded by a single gene.
messages: Interaction with integrin ITGA4:ITGB3 is inhibited by a number of synthetic peptides including R-Ala-Trp-Asp-Ile and R-Gly-Arg-Gly-Asp-Asp-Asp which bind to PLA2G2A and disrupt its integrin-binding activity.
messages: Mitochondrion outer membrane
messages: Secreted
messages: Secretory calcium-dependent phospholipase A2 that primarily targets extracellular phospholipids with implications in host antimicrobial defense, inflammatory response and tissue regeneration (PubMed:10455175, PubMed:10681567, PubMed:2925633). Hydrolyzes the ester bond of the fatty acyl group attached at sn-2 position of phospholipids (phospholipase A2 activity) with preference for phosphatidylethanolamines and phosphatidylglycerols over phosphatidylcholines (PubMed:10455175, PubMed:10681567). Contributes to lipid remodeling of cellular membranes and generation of lipid mediators involved in pathogen clearance. Displays bactericidal activity against Gram-positive bacteria by directly hydrolyzing phospholipids of the bacterial membrane (PubMed:11694541, PubMed:10358193). Upon sterile inflammation, targets membrane phospholipids of extracellular mitochondria released from activated platelets, generating free unsaturated fatty acids such as arachidonate that is used by neighboring leukocytes to synthesize inflammatory eicosanoids such as leukotrienes. Simultaneously, by compromising mitochondrial membrane integrity, promotes the release in circulation of potent damage-associated molecular pattern molecules that activate the innate immune response (PubMed:25082876). Plays a stem cell regulator role in the intestinal crypt. Within intracellular compartment mediates Paneth cell differentiation and its stem cell supporting functions by inhibiting Wnt signaling pathway in intestinal stem cell (ICS). Secreted in the intestinal lumen upon inflammation, acts in an autocrine way and promotes prostaglandin E2 synthesis that stimulates Wnt signaling pathway in ICS cells and tissue regeneration (By similarity). May play a role in the biosynthesis of N-acyl ethanolamines that regulate energy metabolism and inflammation. Hydrolyzes N-acyl phosphatidylethanolamines to N-acyl lysophosphatidylethanolamines, which are further cleaved by a lysophospholipase D to release N-acyl ethanolamin…

9606:FAM50A
gene id: 9606:FAM50A
uniprot id: Q14320
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the FAM50 family.
messages: Interacts with EFTUD2, a component of the spliceosome U5 complex (PubMed:32703943). Interacts with DDX41, a component of the spliceosome C complex (PubMed:32703943).
messages: Nucleus
messages: Probably involved in the regulation of pre-mRNA splicing.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Widely expressed in fetal and adult tissues. Mostly abundant in fetal brain, liver and kidney; in the adult, high levels were also observed in heart, skeletal muscle, spleen, thymus, prostate and small intestine. Expressed in fetal cerebellum and hypothalamus. Low expression is observed in fetal temporal lobe (PubMed:32703943).

9606:PRAMEF1
gene id: 9606:PRAMEF1
uniprot id: B7ZM17
uniprot id: O95521
names: Similarity
messages: Belongs to the PRAME family.

9606:PIK3CG
gene id: 9606:PIK3CG
uniprot id: A8K9G9
uniprot id: P48736
names: Activity Regulation
names: Disease Annotation
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Activated by both the alpha and the beta-gamma G proteins following stimulation of G protein-coupled receptors (GPCRs). Activation by GPCRs is assisted by the regulatory subunits (PIK3R5 or PIK3R6) leading to the translocation from the cytosol to the plasma membrane and to kinase activation. Inhibited by AS-604850 and AS-605240.
messages: Autophosphorylation at Ser-1101 has no effect on the phosphatidylinositol-4,5-bisphosphate 3-kinase activity.
messages: Belongs to the PI3/PI4-kinase family.
messages: Belongs to the PI3/PI4-kinase family. Type III PI4K subfamily.
messages: Candidate target in therapy for inflammatory diseases. Selective inhibitors and protein ablation are anti-inflammatory in multiple disease models such as asthma, rheumatoid arthritis, allergy, systemic lupus erythematosus, airway inflammation, lung injury and pancreatitis (PubMed:18278175).
messages: Cell membrane
messages: Cytoplasm
messages: Heterodimer of a catalytic subunit PIK3CG and a PIK3R5 or PIK3R6 regulatory subunit. Interacts with GRK2 through the PIK helical domain. Interaction with GRK2 is required for targeting to agonist-occupied receptor. Interacts with PDE3B; regulates PDE3B activity and thereby cAMP levels in cells (By similarity). Interacts with TPM2. Interacts with EPHA8; regulates integrin-mediated cell adhesion to substrate. Interacts with HRAS; the interaction is required for membrane recruitment and beta-gamma G protein dimer-dependent activation of the PI3K gamma complex PIK3CG:PIK3R6 (By similarity).
messages: Pancreas, skeletal muscle, liver and heart.
messages: Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Links G-protein coupled receptor activation to PIP3 production. Involved in immune, inflammatory and allergic responses. Modulates leukocyte chemotaxis to inflammatory sites and in response to chemoattractant agents. May control leukocyte polarization and migration by regulating the spatial accumulation of PIP3 and by regulating the organization of F-actin formation and integrin-based adhesion at the leading edge. Controls motility of dendritic cells. Together with PIK3CD is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in T-lymphocyte migration. Regulates T-lymphocyte proliferation, activation, and cytokine production. Together with PIK3CD participates in T-lymphocyte development. Required for B-lymphocyte development and signaling. Together with PIK3CD participates in neutrophil respiratory burst. Together with PIK3CD is involved in neutrophil chemotaxis and extravasation. Together with PIK3CB promotes platelet aggregation and thrombosis. Regulates alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) adhesive function in platelets downstream of P2Y12 through a lipid kinase activity-independent mechanism. May have also a lipid kinase activity-dependent function in platelet aggregation. Involved in endothelial progenitor cell migration. Negative regulator of cardiac contractility. Modulates cardiac contractility by anchoring protein kinase A (PKA) and PDE3B activation, reducing cAMP levels. Regulates cardiac contractility also by promoting beta-adrenergic receptor internalization by binding to GRK2 and by non-muscle tropomyosin phosphory…
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:PTTG1
gene id: 9606:PTTG1
uniprot id: O95997
uniprot id: Q6IAL9
names: Developmental Stage
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the securin family.
messages: Cytoplasm
messages: Expressed at low level in most tissues, except in adult testis, where it is highly expressed. Overexpressed in many patients suffering from pituitary adenomas, primary epithelial neoplasias, and esophageal cancer.
messages: Interacts with RPS10 and DNAJA1 (By similarity). Interacts with the caspase-like ESPL1, and prevents its protease activity probably by covering its active site. Interacts with TP53 and blocks its activity probably by blocking its binding to DNA. Interacts with the Ku 70 kDa subunit of ds-DNA kinase. Interacts with PTTG1IP.
messages: Low level during G1 and S phases. Peaks at M phase. During anaphase, it is degraded.
messages: Nucleus
messages: Phosphorylated at Ser-165 by CDK1 during mitosis.
messages: Phosphorylated in vitro by ds-DNA kinase.
messages: Regulatory protein, which plays a central role in chromosome stability, in the p53/TP53 pathway, and DNA repair. Probably acts by blocking the action of key proteins. During the mitosis, it blocks Separase/ESPL1 function, preventing the proteolysis of the cohesin complex and the subsequent segregation of the chromosomes. At the onset of anaphase, it is ubiquitinated, conducting to its destruction and to the liberation of ESPL1. Its function is however not limited to a blocking activity, since it is required to activate ESPL1. Negatively regulates the transcriptional activity and related apoptosis activity of TP53. The negative regulation of TP53 may explain the strong transforming capability of the protein when it is overexpressed. May also play a role in DNA repair via its interaction with Ku, possibly by connecting DNA damage-response pathways with sister chromatid separation.
messages: The N-terminal destruction box (D-box) acts as a recognition signal for degradation via the ubiquitin-proteasome pathway.
messages: The TEK-boxes are required for 'Lys-11'-linked ubiquitination and facilitate the transfer of the first ubiquitin and ubiquitin chain nucleation. TEK-boxes may direct a catalytically competent orientation of the UBE2C/UBCH10-ubiquitin thioester with the acceptor lysine residue.
messages: Ubiquitinated through 'Lys-11' linkage of ubiquitin moieties by the anaphase promoting complex (APC) at the onset of anaphase, conducting to its degradation. 'Lys-11'-linked ubiquitination is mediated by the E2 ligase UBE2C/UBCH10.

9606:SRPX2
gene id: 9606:SRPX2
uniprot id: O60687
names: Disease Annotation
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acts as a ligand for the urokinase plasminogen activator surface receptor. Plays a role in angiogenesis by inducing endothelial cell migration and the formation of vascular network (cords). Involved in cellular migration and adhesion. Increases the phosphorylation levels of FAK. Interacts with and increases the mitogenic activity of HGF. Promotes synapse formation. May have a role in the perisylvian region, critical for language and cognitive development.
messages: Cell surface
messages: Contains chondroitin sulfate chains.
messages: Cytoplasm
messages: Expressed in neurons of the rolandic area of the brain (at protein level). Highly expressed in the brain, placenta, lung, trachea, uterus, adrenal gland, heart, ovary and placenta. Weakly expressed in the peripheral blood, brain and bone marrow. Expressed in numerous cancer cell lines and in gastrointestinal cancer cells. Higher levels found in colorectal cancers than in normal colonic mucosa.
messages: Forms homooligomers (By similarity). Interacts with PLAUR (via the UPAR/Ly6 domains), ADAMTS4 and CTSB. Interacts with HGF; the interaction increases the mitogenic activity of HGF.
messages: Secreted
messages: Synapse
messages: The disease may be caused by variants affecting the gene represented in this entry.

9606:MORC4
gene id: 9606:MORC4
uniprot id: Q8TE76
names: Domain
names: Function
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Expressed at low levels in normal tissues, with highest expression levels in placenta and testis. Expression is significantly increased in subset of diffuse large B-cell lymphomas.
messages: Histone methylation reader which binds to non-methylated (H3K4me0), monomethylated (H3K4me1), dimethylated (H3K4me2) and trimethylated (H3K4me3) 'Lys-4' on histone H3 (PubMed:26933034). The order of binding preference is H3K4me3 > H3K4me2 > H3K4me1 > H3K4me0 (PubMed:26933034).
messages: Nucleus
messages: The CW-TYPE zinc finger mediates its binding to trimethylated histone H3K4me3.

9606:FXYD6-FXYD2
gene id: 9606:FXYD6-FXYD2
uniprot id: A0A087WZ82
uniprot id: A0A0A6YYL5
names: Caution
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the FXYD family.
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: May be involved in forming the receptor site for cardiac glycoside binding or may modulate the transport function of the sodium ATPase.
messages: Membrane
messages: Regulatory subunit of the sodium/potassium-transporting ATPase which is composed of a catalytic alpha subunit, an auxiliary non-catalytic beta subunit and an additional regulatory subunit.

9606:FBXO15
gene id: 9606:FBXO15
uniprot id: Q8NCQ5
names: Function
names: Subunit
messages: Directly interacts with SKP1 and CUL1.
messages: Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex.

9606:XPOT
gene id: 9606:XPOT
uniprot id: O43592
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the exportin family.
messages: Cytoplasm
messages: Found in a complex with XPOT, Ran and tRNA. Probably found in a complex with nucleoporins. Interacts with Ran and tRNA in a GTP-dependent manner.
messages: Mediates the nuclear export of aminoacylated tRNAs. In the nucleus binds to tRNA and to the GTPase Ran in its active GTP-bound form. Docking of this trimeric complex to the nuclear pore complex (NPC) is mediated through binding to nucleoporins. Upon transit of a nuclear export complex into the cytoplasm, disassembling of the complex and hydrolysis of Ran-GTP to Ran-GDP (induced by RANBP1 and RANGAP1, respectively) cause release of the tRNA from the export receptor. XPOT then return to the nuclear compartment and mediate another round of transport. The directionality of nuclear export is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus.
messages: Nucleus

9606:KNL1
gene id: 9606:KNL1
uniprot id: Q8NG31
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: A chromosomal aberration involving KNL1 is associated with acute myeloblastic leukemia (AML). Translocation t(11;15)(q23;q14) with KMT2A. May give rise to a KMT2A-KNL1 fusion protein.
messages: Highly expressed in testis, where it is localized in germ cells, in particular in spermatocytes and in the pre-acrosome of round spermatids. Detected in the acrosome of ejaculated spermatozoa. Detected in adult thymus, bone marrow, colon, small intestine, appendix and placenta, and in fetal liver and thymus.
messages: Interacts with DSN1, MIS12, BUB1, BUB1B, NSL1 and ZWINT.
messages: Nucleus
messages: Performs two crucial functions during mitosis: it is essential for spindle-assembly checkpoint signaling and for correct chromosome alignment. Required for attachment of the kinetochores to the spindle microtubules. Directly links BUB1 and BUB1B to kinetochores. Part of the MIS12 complex, which may be fundamental for kinetochore formation and proper chromosome segregation during mitosis. Acts in coordination with CENPK to recruit the NDC80 complex to the outer kinetochore.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: kinetochore

9606:CYP2C19
gene id: 9606:CYP2C19
uniprot id: P33261
names: Caution
names: Function
names: Induction
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
messages: A cytochrome P450 monooxygenase involved in the metabolism of polyunsaturated fatty acids (PUFA) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates PUFA specifically at the omega-1 position (PubMed:18577768). Catalyzes the epoxidation of double bonds of PUFA (PubMed:20972997, PubMed:19965576). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine. Hydroxylates fenbendazole at the 4' position (PubMed:23959307).
messages: Belongs to the cytochrome P450 family.
messages: Endoplasmic reticulum membrane
messages: Genetic variation in CYP2C19 is responsible for poor drug metabolism [MIM:609535]. Individuals can be characterized as either extensive metabolizers (EM) or poor metabolizers (PM). The PM phenotype is inherited in an autosomal recessive manner, with the EM phenotype comprising both homozygous dominant and heterozygote genotypes. There are marked interracial differences in the frequency of this polymorphism. Poor metabolizers represent 2-5% of Caucasians, 13-23% of Asian populations, and as many as 38-79% of individuals of some of the islands of Polynesia and Micronesia. At least 38 different alleles are known including CYP2C19*1A, CYP2C19*1B, CYP2C19*1C, CYP2C19*2A (CYP2C19m1 or CYP2C19m1A), CYP2C19*2B (CYP2C19m1B), CYP2C19*2C (CYP2C19*21), CYP2C19*3A (CYP2C19m2), CYP2C19*3B (CYP2C19*20), CYP2C19*4 (CYP2C19m3), CYP2C19*5A (CYP2C19m4), CYP2C19*5B, CYP2C19*6, CYP2C19*7, CYP2C19*8, CYP2C19*9, CYP2C19*10, CYP2C19*11 CYP2C19*12, CYP2C19*13, CYP2C19*14 CYP2C19*15, CYP2C19*16, CYP2C19*18 and CYP2C19*19. Defective CYP2C19*2 and CYP2C19*3 alleles are characterized by a splice mutation and a stop codon, respectively, and account for most of the PM alleles. The sequence shown is that of allele CYP2C19*1A.
messages: Microsome membrane
messages: P450 can be induced to high levels in liver and other tissues by various foreign compounds, including drugs, pesticides, and carcinogens.
messages: P450-254C was originally listed as a separate gene (CYP2C17). Resequencing demonstrated that it is not a separate gene, but a chimera. The 5'-portion corresponds to a partial 2C18 clone, and the 3'-portion corresponds to a partial 2C19 clone.

9606:NCL
gene id: 9606:NCL
uniprot id: B3KM80
uniprot id: P19338
names: Function
names: PTM
names: Sequence Caution
names: Subcellular Location Annotation
names: Subunit
messages: Cytoplasm
messages: Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs (PubMed:17289661). Component of the SWAP complex that consists of NPM1, NCL/nucleolin, PARP1 and SWAP70 (By similarity). Component of a complex which is at least composed of HTATSF1/Tat-SF1, the P-TEFb complex components CDK9 and CCNT1, RNA polymerase II, SUPT5H, and NCL/nucleolin (PubMed:10393184). Interacts with AICDA (By similarity). Interacts with APTX (PubMed:15044383). Interacts with C1QBP (PubMed:21536856). Interacts with ERBB4 (PubMed:20858735). Interacts (via C-terminus) with FMR1 isoform 6 (via N-terminus) (PubMed:24658146). Interacts with GZF1; this interaction is important for nucleolar localization of GZF1 (PubMed:17674968). Interacts with NSUN2 (PubMed:17215513). Interacts with NVL (PubMed:21474449). Interacts (via N-terminus domain) with SETX (PubMed:21700224). Interacts (via RRM1 and C-terminal RRM4/Arg/Gly-rich domains) with TERT; the interaction is important for nucleolar localization of TERT (PubMed:15371412). Interacts with WDR46 (PubMed:23848194). Interacts with ZFP36 (PubMed:20221403). Interacts with LRRC34 (By similarity). Interacts with RRP1B (PubMed:19710015). Interacts with HNRNPU; this interaction occurs during mitosis (PubMed:21242313). Interacts with RIOK1; RIOK1 recruits NCL to PRMT5 for symmetrically methylation (PubMed:21081503). Interacts with ZBTB7B (By similarity). Interacts with MDK; this interaction promotes NCL clustering and lateral movements of this complex into lipid rafts leading to MDK internalization (PubMed:12147681). Interacts with HDGF (isoform 1) (PubMed:26845719). Interacts with ALKBH2.
messages: Nucleolin is the major nucleolar protein of growing eukaryotic cells. It is found associated with intranucleolar chromatin and pre-ribosomal particles. It induces chromatin decondensation by binding to histone H1. It is thought to play a role in pre-rRNA transcription and ribosome assembly. May play a role in the process of transcriptional elongation. Binds RNA oligonucleotides with 5'-UUAGGG-3' repeats more tightly than the telomeric single-stranded DNA 5'-TTAGGG-3' repeats.
messages: Some glutamate residues are glycylated by TTLL8. This modification occurs exclusively on glutamate residues and results in a glycine chain on the gamma-carboxyl group (By similarity).
messages: Symmetrically methylated by PRMT5.
messages: Unlikely isoform. Aberrant splice sites.
messages: nucleolus

9606:USP29
gene id: 9606:USP29
uniprot id: Q9HBJ7
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the peptidase C19 family.
messages: Deubiquitinase involved in innate antiviral immunity by mediating 'Lys-48'-linked deubiquitination of CGAS, thereby promoting its stabilization.
messages: perinuclear region

9606:SCAMP2
gene id: 9606:SCAMP2
uniprot id: A0A140VK92
uniprot id: A8K769
uniprot id: O15127
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the SCAMP family.
messages: Functions in post-Golgi recycling pathways. Acts as a recycling carrier to the cell surface.
messages: Interacts with SLC6A4 and SLC9A7 (PubMed:15840657, PubMed:16870614). Interacts with SLC9A5; this interaction regulates SLC9A5 cell-surface targeting and SLC9A5 activity (PubMed:19276089).
messages: Membrane
messages: Recycling endosome membrane
messages: Widely expressed.
messages: trans-Golgi network membrane

9606:FBP1
gene id: 9606:FBP1
uniprot id: P09467
uniprot id: Q2TU34
names: Activity Regulation
names: Cofactor
names: Disease Annotation
names: Function
names: Induction
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Belongs to the FBPase class 1 family.
messages: Binds 3 Mg(2+) ions per subunit.
messages: Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in the presence of divalent cations, acting as a rate-limiting enzyme in gluconeogenesis. Plays a role in regulating glucose sensing and insulin secretion of pancreatic beta-cells. Appears to modulate glycerol gluconeogenesis in liver. Important regulator of appetite and adiposity; increased expression of the protein in liver after nutrient excess increases circulating satiety hormones and reduces appetite-stimulating neuropeptides and thus seems to provide a feedback mechanism to limit weight gain.
messages: Expressed in pancreatic islets.
messages: Homotetramer.
messages: Subject to complex allosteric regulation. The enzyme can assume an active R-state, or an inactive T-state. Intermediate conformations may exist. AMP acts as allosteric inhibitor. AMP binding affects the turnover of bound substrate and not the affinity for substrate. Fructose 2,6-bisphosphate acts as competitive inhibitor. Fructose 2,6-bisphosphate and AMP have synergistic effects.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Up-regulated in pancreatic islets of individuals with type 2 diabetes.

9606:LAP3
gene id: 9606:LAP3
uniprot id: P28838
names: Cofactor
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the peptidase M17 family.
messages: Binds two metal ions per subunit. Two metal binding sites with different affinities are located in the enzyme active site and can be occupied in vitro by different metals: site 1 is occupied by Zn(2+), Mn(2+), Mg(2+) or Co(2+), while the tight binding site 2 can be occupied by only Zn(2+) or Co(2+). One Zn(2+) ion is tightly bound to site 2 and essential for enzyme activity in vivo, while site 1 can be occupied by different metals to give different enzymatic activities. Mn(2+) is required for Cys-Gly hydrolysis activity. A third metal binding site may serve a structural role, possibly stabilizing part of the interface between the N-terminal and the catalytic domain.
messages: Cytoplasm
messages: Cytosolic metallopeptidase that catalyzes the removal of unsubstituted N-terminal hydrophobic amino acids from various peptides. The presence of Zn(2+) ions is essential for the peptidase activity, and the association with other cofactors can modulate the substrate spectificity of the enzyme. For instance, in the presence of Mn(2+), it displays a specific Cys-Gly hydrolyzing activity of Cys-Gly-S-conjugates. Involved in the metabolism of glutathione and in the degradation of glutathione S-conjugates, which may play a role in the control of the cell redox status.
messages: Homohexamer.

9606:S100A16
gene id: 9606:S100A16
uniprot id: Q96FQ6
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the S-100 family.
messages: Calcium-binding protein. Binds one calcium ion per monomer (PubMed:17030513). Can promote differentiation of adipocytes (in vitro) (By similarity). Overexpression in preadipocytes increases their proliferation, enhances adipogenesis and reduces insulin-stimulated glucose uptake (By similarity).
messages: Cytoplasm
messages: Homodimer (PubMed:17030513, PubMed:21046186). Interacts with TP53 (By similarity).
messages: S100A16 proteins, but not other S100 proteins, have only one functional Ca(2+) binding site per monomer. Upon Ca(2+) binding, undergoes conformational changes leading to the exposure of hydrophobic patches which could be implicated in the Ca(2+) -dependent nuclear export. Binds Zn(2+). Ca(2+) and Zn(2+) do not bind to the same site. Does not bind Cu(2+).
messages: Ubiquitous (PubMed:14684152). Highly expressed in esophagus, adipose tissues and colon. Expressed at lower level in lung, brain, pancreas and skeletal muscle. Expression is up-regulated in tumors of bladder, lung, thyroid gland, pancreas and ovary (PubMed:14684152). Expressed in astrocytes (PubMed:17030513).
messages: nucleolus

9606:PRR12
gene id: 9606:PRR12
uniprot id: Q9ULL5
names: Disease Annotation
names: Sequence Caution
names: Subcellular Location Annotation
messages: Aberrant splicing.
messages: Nucleus
messages: Postsynaptic density
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: synaptosome

9606:PRPF6
gene id: 9606:PRPF6
uniprot id: O94906
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Identified in the spliceosome B complex (PubMed:28781166). Identified in the spliceosome C complex (PubMed:11991638). Associates with the U5 snRNP particle (PubMed:10788320). Component of the U4/U6-U5 tri-snRNP complex composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39, LSm proteins LSm2-8 and Sm proteins (PubMed:16723661, PubMed:26912367, PubMed:28781166). Interacts with ARAF (PubMed:10848612). Interacts with AR and NR3C1, but not ESR1, independently of the presence of hormones (PubMed:12039962). Interacts with USH1G (PubMed:34023904).
messages: Involved in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex, one of the building blocks of the spliceosome (PubMed:28781166, PubMed:21549338). Enhances dihydrotestosterone-induced transactivation activity of AR, as well as dexamethasone-induced transactivation activity of NR3C1, but does not affect estrogen-induced transactivation.
messages: Nucleus speckle
messages: The disease may be caused by variants affecting the gene represented in this entry. Cells from RP60 patients show intron retention for pre-mRNA bearing specific splicing signals.
messages: Widely expressed.
messages: nucleoplasm

9606:GPR137C
gene id: 9606:GPR137C
uniprot id: B3KW22
uniprot id: Q6AWC7
uniprot id: Q8N3F9
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the GPR137 family.
messages: Lysosomal integral membrane protein that may regulate MTORC1 complex translocation to lysosomes.
messages: Lysosome membrane
messages: Membrane

9606:HPS3
gene id: 9606:HPS3
uniprot id: G5E9V4
uniprot id: Q969F9
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Component of the biogenesis of lysosome-related organelles complex-2 (or BLOC2) composed of HPS3, HPS5 and HPS6.
messages: Component of the biogenesis of lysosome-related organelles complex-2 (or BLOC2) composed of HPS3, HPS5 and HPS6. Interacts with HPS5 (PubMed:15030569). Interacts with HPS6 (PubMed:15030569, PubMed:25189619).
messages: Cytoplasm
messages: Involved in early stages of melanosome biogenesis and maturation.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Widely expressed. Higher levels of expression are observed in kidney, liver and placenta.
messages: cytosol

9606:FAM111B
gene id: 9606:FAM111B
uniprot id: Q6SJ93
names: Disease Annotation
names: Function
names: Sequence Caution
names: Similarity
names: Tissue Specificity
messages: Belongs to the FAM111 family.
messages: Contaminating sequence. Potential poly-A sequence.
messages: Serine protease.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Widely expressed.

9606:BABAM1
gene id: 9606:BABAM1
uniprot id: J3KQS6
uniprot id: Q9NWV8
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the BABAM1 family.
messages: Component of the ARISC complex, at least composed of UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1 (PubMed:24075985). Component of the BRCA1-A complex, at least composed of BRCA1, BARD1, UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1 (PubMed:19261746, PubMed:19261749, PubMed:19261748, PubMed:21282113). In the BRCA1-A complex, interacts directly with ABRAXAS1 and BABAM2 (PubMed:19261749, PubMed:19261748). Component of the BRISC complex, at least composed of ABRAXAS2, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1 (PubMed:19214193, PubMed:21282113, PubMed:24075985, PubMed:25283148). Identified in a complex with SHMT2 and the other subunits of the BRISC complex (PubMed:24075985).
messages: Component of the BRCA1-A complex, a complex that specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). The BRCA1-A complex also possesses deubiquitinase activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX. In the BRCA1-A complex, it is required for the complex integrity and its localization at DSBs. Component of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys-63'-linked ubiquitin in various substrates (PubMed:24075985, PubMed:26195665). In these 2 complexes, it is probably required to maintain the stability of BABAM2 and help the 'Lys-63'-linked deubiquitinase activity mediated by BRCC3/BRCC36 component. The BRISC complex is required for normal mitotic spindle assembly and microtubule attachment to kinetochores via its role in deubiquitinating NUMA1 (PubMed:26195665). Plays a role in interferon signaling via its role in the deubiquitination of the interferon receptor IFNAR1; deubiquitination increases IFNAR1 activity by enhancing its stability and cell surface expression (PubMed:24075985). Down-regulates the response to bacterial lipopolysaccharide (LPS) via its role in IFNAR1 deubiquitination (PubMed:24075985).
messages: Cytoplasm
messages: Nucleus
messages: The VWFA-like region is similar to the VWFA domain. Its presence reveals similarities between the structure of the 19S proteasome and the BRCA1-A complexes.

9606:R3HCC1L
gene id: 9606:R3HCC1L
uniprot id: Q7Z5L2
names: Subunit
names: Tissue Specificity
messages: Expressed in placenta.
messages: May interact with the exon junction complex (EJC) composed at least of CASC3, EIF4A3, MAGOH and RBM8A.

9606:DDX5
gene id: 9606:DDX5
uniprot id: J3KTA4
uniprot id: P17844
names: Caution
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Arg-502 is dimethylated, probably to asymmetric dimethylarginine.
messages: Belongs to the DEAD box helicase family. DDX5/DBP2 subfamily.
messages: Cytoplasm
messages: DDX5 was reported to be a transcriptional coactivator of ESR1. However, this study has been retracted due to concerns of image manipulation.
messages: Identified in the spliceosome C complex (PubMed:11991638). Component of a ribonucleoprotein complex containing mRNAs and RNA-binding proteins including DDX5, HNRNPH2 and SRSF1 as well as splicing regulator ARVCF (PubMed:24644279). Interacts with RBM4; the interaction occurs in an RNA-independent manner. Interacts with AGO1 and AGO2. Interacts with ESR1, AR, EP300, CREBBP, POLR2A, TP53, RUNX2 and HDAC1. Self-associates. Interacts with DDX17. Interacts with BRDT. The large PER complex involved in the repression of transcriptional termination is composed of at least PER2, CDK9, DDX5, DHX9, NCBP1 and POLR2A (active). Interacts with DHX36; this interaction occurs in a RNA-dependent manner (PubMed:18279852). Interacts with NUPR1 (By similarity). Interacts with ERCC6 (PubMed:26030138). Interacts with DDX3X in the cytoplasm; this interaction may be more efficient when both proteins are unphosphorylated (PubMed:22034099).
messages: Involved in the alternative regulation of pre-mRNA splicing; its RNA helicase activity is necessary for increasing tau exon 10 inclusion and occurs in a RBM4-dependent manner. Binds to the tau pre-mRNA in the stem-loop region downstream of exon 10. The rate of ATP hydrolysis is highly stimulated by single-stranded RNA. Involved in transcriptional regulation; the function is independent of the RNA helicase activity. Transcriptional coactivator for androgen receptor AR but probably not ESR1. Synergizes with DDX17 and SRA1 RNA to activate MYOD1 transcriptional activity and involved in skeletal muscle differentiation. Transcriptional coactivator for p53/TP53 and involved in p53/TP53 transcriptional response to DNA damage and p53/TP53-dependent apoptosis. Transcriptional coactivator for RUNX2 and involved in regulation of osteoblast differentiation. Acts as transcriptional repressor in a promoter-specific manner; the function probably involves association with histone deacetylases, such as HDAC1. As component of a large PER complex is involved in the inhibition of 3' transcriptional termination of circadian target genes such as PER1 and NR1D1 and the control of the circadian rhythms.
messages: Nucleus
messages: Nucleus speckle
messages: Polyubiquitinated, leading to proteasomal degradation.
messages: Sumoylated; sumoylation, promoted by PIAS1, promotes interaction with HDAC1 and transcriptional repression activity. Sumoylation also significantly increases stability, and reduces polyubiquitination.
messages: Weakly phosphorylated in the G1/S phase of the cell cycle and much more at G2/M, especially at Thr and Tyr residues.
messages: nucleolus

9606:PRRG1
gene id: 9606:PRRG1
uniprot id: O14668
names: PTM
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Gla residues are produced after subsequent post-translational modifications of glutamate by a vitamin K-dependent gamma-carboxylase.
messages: Highly expressed in the spinal cord.
messages: Membrane

9606:CACUL1
gene id: 9606:CACUL1
uniprot id: Q86Y37
names: Function
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Belongs to the cullin family.
messages: Cell cycle associated protein capable of promoting cell proliferation through the activation of CDK2 at the G1/S phase transition.
messages: Interacts with CDK2.
messages: Ubiquitously expressed with highest expression in the mammary gland and large intestine. Highly expressed in cancer tissues and cancer cell lines. During cell cycle progression expression is high in G1/S, low in the middle of S phase, and increases again in S/G2 phase.

9606:BLZF1
gene id: 9606:BLZF1
uniprot id: Q9H2G9
names: Caution
names: Domain
names: Function
names: Induction
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: ADP-ribosylated by tankyrase TNKS and TNKS2. Poly-ADP-ribosylated protein is recognized by RNF146, followed by ubiquitination.
messages: Cytoplasm
messages: Detected in adrenal gland (PubMed:9129147).
messages: Golgi apparatus membrane
messages: Interacts with GORASP2. Interacts with the GTP-bound form of RAB2, but not with other Golgi Rab proteins (PubMed:11739401). Identified in a complex with RAB2 and GORASP2 (PubMed:11739401).
messages: Nucleus
messages: Required for normal Golgi structure and for protein transport from the endoplasmic reticulum (ER) through the Golgi apparatus to the cell surface.
messages: The tankyrase-binding motif (also named TBD) is required for interaction with tankyrase TNKS and TNKS2.
messages: Ubiquitinated by RNF146 when poly-ADP-ribosylated, leading to its degradation.
messages: Up-regulated by retinoids.
messages: Was originally identified as a potential transcription factor, because of the presence of a potential basic motif and leucine-zipper domain, and because isoform 1 is detected in the nucleus upon heterologous expression. However, homology at several typical position for basic or hydrophobic residues is missing. Besides, another publication showed it is important for normal Golgi apparatus structure and function.

9606:CTSA
gene id: 9606:CTSA
uniprot id: B4E324
uniprot id: P10619
uniprot id: X6R5C5
uniprot id: X6R8A1
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the peptidase S10 family.
messages: Heterodimer of a 32 kDa chain and a 20 kDa chain; disulfide-linked.
messages: Lysosome
messages: Protective protein appears to be essential for both the activity of beta-galactosidase and neuraminidase, it associates with these enzymes and exerts a protective function necessary for their stability and activity. This protein is also a carboxypeptidase and can deamidate tachykinins.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:TBCB
gene id: 9606:TBCB
uniprot id: Q99426
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Glycosylated residues by S.typhimurium protein Ssek1: arginine GlcNAcylation promotes microtubule stability.
messages: Belongs to the TBCB family.
messages: Binds to alpha-tubulin folding intermediates after their interaction with cytosolic chaperonin in the pathway leading from newly synthesized tubulin to properly folded heterodimer (PubMed:9265649). Involved in regulation of tubulin heterodimer dissociation. May function as a negative regulator of axonal growth (By similarity).
messages: Cytoplasm
messages: Found in most tissues.
messages: Phosphorylation by PAK1 is required for normal function.
messages: Supercomplex made of cofactors A to E. Cofactors A and D function by capturing and stabilizing tubulin in a quasi-native conformation. Cofactor E binds to the cofactor D-tubulin complex; interaction with cofactor C then causes the release of tubulin polypeptides that are committed to the native state (PubMed:9265649). Cofactors B and E can form a heterodimer which binds to alpha-tubulin and enhances their ability to dissociate tubulin heterodimers (By similarity). Interacts with GAN (PubMed:16303566). Interacts with DCTN1 (PubMed:22777741).
messages: Ubiquitinated in the presence of GAN which targets it for degradation by the proteasome.
messages: cytoskeleton

9606:TAS2R14
gene id: 9606:TAS2R14
uniprot id: Q9NYV8
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor T2R family.
messages: Expressed in subsets of taste receptor cells of the tongue and palate epithelium and exclusively in gustducin-positive cells. Expressed in testis (PubMed:16720576).
messages: Membrane
messages: Most taste cells may be activated by a limited number of bitter compounds; individual taste cells can discriminate among bitter stimuli.
messages: Receptor that may play a role in the perception of bitterness and is gustducin-linked. May play a role in sensing the chemical composition of the gastrointestinal content. The activity of this receptor may stimulate alpha gustducin, mediate PLC-beta-2 activation and lead to the gating of TRPM5 (By similarity).

9606:CMC2
gene id: 9606:CMC2
uniprot id: Q9NRP2
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the CMC family.
messages: May be involved in cytochrome c oxidase biogenesis.
messages: Mitochondrion

9606:ERLEC1
gene id: 9606:ERLEC1
uniprot id: Q96DZ1
uniprot id: V9HWD3
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the OS-9 family.
messages: Endoplasmic reticulum lumen
messages: Isoform 1 and isoform 2 are N-glycosylated.
messages: Lectin involved in the quality control of the secretory pathway. As a member of the endoplasmic reticulum-associated degradation lumenal (ERAD-L) surveillance system, targets misfolded endoplasmic reticulum lumenal glycoproteins for degradation.
messages: May form a complex with OS9, HSPA5, SYVN1, and SEL1L with which it interacts directly. Interacts (via PRKCSH 2 domain) with KREMEN2 (when glycosylated). Interacts with HSPA5.
messages: Probable lectin that binds selectively to improperly folded lumenal proteins. May function in endoplasmic reticulum quality control and endoplasmic reticulum-associated degradation (ERAD) of both non-glycosylated proteins and glycoproteins.

9606:ZNF780B
gene id: 9606:ZNF780B
uniprot id: Q9Y6R6
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:RGL3
gene id: 9606:RGL3
uniprot id: Q3MIN7
names: Domain
names: Function
names: Subunit
messages: Guanine nucleotide exchange factor (GEF) for Ral-A. Potential effector of GTPase HRas and Ras-related protein M-Ras. Negatively regulates Elk-1-dependent gene induction downstream of HRas and MEKK1 (By similarity).
messages: Interacts with GTP-bound forms of RIT1, HRAS and MRAS.
messages: The Ras-associating domain plays a central role in the activation of Ral-A GDP/GTP exchange activity.

9606:PRAME
gene id: 9606:PRAME
uniprot id: B7Z7K8
uniprot id: B7Z986
uniprot id: B7ZAT0
uniprot id: P78395
names: Function
names: Induction
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the PRAME family.
messages: Cell membrane
messages: Chromosome
messages: Component of a CRL2 E3 ubiquitin-protein ligase complex, also named ECS (Elongin BC-CUL2/5-SOCS-box protein) complex, composed of CUL2, Elongin BC (ELOB and ELOC), RBX1 and substrate-specific adapter PRAME (PubMed:21822215, PubMed:23460923, PubMed:26138980). Interacts with RARA (via the ligand-binding domain); the interaction is direct and ligand (retinoic acid)-dependent (PubMed:16179254). Interacts with EZH2; required to repress RAR signaling (PubMed:16179254).
messages: Cytoplasm
messages: Expressed in testis. Detected in samples of kidney, brain and skin.
messages: Golgi apparatus
messages: Nucleus
messages: Substrate-recognition component of a Cul2-RING (CRL2) E3 ubiquitin-protein ligase complex, which mediates ubiquitination of target proteins, leading to their degradation (PubMed:21822215, PubMed:26138980). The CRL2(PRAME) complex mediates ubiquitination and degradation of truncated MSRB1/SEPX1 selenoproteins produced by failed UGA/Sec decoding (PubMed:26138980). In the nucleus, the CRL2(PRAME) complex is recruited to epigenetically and transcriptionally active promoter regions bound by nuclear transcription factor Y (NFY) and probably plays a role in chromstin regulation (PubMed:21822215). Functions as a transcriptional repressor, inhibiting the signaling of retinoic acid through the retinoic acid receptors RARA, RARB and RARG: prevents retinoic acid-induced cell proliferation arrest, differentiation and apoptosis (PubMed:16179254).
messages: Tumor antigen recognized by cytolytic T lymphocytes.
messages: Up-regulated in response to interferon gamma (IFNG) treatment and exposure to bacterial PAMPs (pathogen associated molecular patterns).

9606:SHH
gene id: 9606:SHH
uniprot id: Q15465
names: Caution
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the hedgehog family.
messages: Binds calcium and zinc ions; this stabilizes the protein fold and is essential for protein-protein interactions mediated by this domain.
messages: Cell membrane
messages: Endoplasmic reticulum membrane
messages: Golgi apparatus membrane
messages: Interacts with HHATL/GUP1 which negatively regulates HHAT-mediated palmitoylation of the SHH N-terminus (By similarity). Interacts with BOC and CDON (By similarity). Interacts with HHIP (PubMed:19561609). Interacts with DISP1 via its cholesterol anchor (PubMed:22902404, PubMed:22677548). Interacts with SCUBE2 (PubMed:24522195, PubMed:22677548). Interacts with glypican GPC3 (By similarity).
messages: Multimer.
messages: N-palmitoylation by HHAT of ShhN is required for sonic hedgehog protein N-product multimerization and full activity (By similarity). It is a prerequisite for the membrane-proximal positioning and the subsequent shedding of this N-terminal peptide (PubMed:24522195).
messages: Secreted
messages: The C-terminal domain displays an autoproteolysis activity and a cholesterol transferase activity (By similarity). Both activities result in the cleavage of the full-length protein and covalent attachment of a cholesterol moiety to the C-terminal of the newly generated N-terminal fragment (ShhN) (By similarity). Cholesterylation is required for the sonic hedgehog protein N-product targeting to lipid rafts and multimerization (PubMed:24522195, PubMed:26875496). ShhN is the active species in both local and long-range signaling, whereas the C-product (ShhC) is degraded in the reticulum endoplasmic (By similarity).
messages: The C-terminal part of the sonic hedgehog protein precursor displays an autoproteolysis and a cholesterol transferase activity (By similarity). Both activities result in the cleavage of the full-length protein into two parts (ShhN and ShhC) followed by the covalent attachment of a cholesterol moiety to the C-terminal of the newly generated ShhN (By similarity). Both activities occur in the reticulum endoplasmic (By similarity). Once cleaved, ShhC is degraded in the endoplasmic reticulum (By similarity).
messages: The Cardin-Weintraub (CW) motif is required for heparan sulfate binding of the solubilized ShhNp (PubMed:23118222). The N-terminal palmitoylated peptide is cleaved at the heparan sulfate-binding Cardin-Weintraub (CW) motif site (PubMed:24522195). The cleavage reduced the interactions with heparan sulfate. The cleavage is enhanced by SCUBE2 (PubMed:24522195).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The dually lipidated sonic hedgehog protein N-product (ShhNp) is a morphogen which is essential for a variety of patterning events during development. Induces ventral cell fate in the neural tube and somites (PubMed:24863049). Involved in the patterning of the anterior-posterior axis of the developing limb bud (By similarity). Essential for axon guidance (By similarity). Binds to the patched (PTCH1) receptor, which functions in association with smoothened (SMO), to activate the transcription of target genes (PubMed:10753901). In the absence of SHH, PTCH1 represses the constitutive signaling activity of SMO (PubMed:10753901).
messages: The gene represented in this entry is involved in disease pathogenesis. Abnormal SHH limb expression with pathological consequences is caused by duplications (16-75 kb) involving the ZPA regulatory sequence (ZRS), a SHH long-range cis-regulatory element, located in LMBR1 intron 5 (PubMed:24456159).
messages: The gene represented in this entry is involved in disease pathogenesis. Mutations located in intron 5 of LMBR1 disrupt a long-range, cis-regulatory element of SHH and result in abnormal, ectopic SHH expression with pathological consequences (PubMed:12837695).
messages: The gene represented in this entry is involved in disease pathogenesis. Mutations located in intron 5 of LMBR1 disrupt a long-range, cis-regulatory element of SHH and result in abnormal, ectopic SHH expression with pathological consequences.
messages: The gene represented in this entry is involved in disease pathogenesis. SHH expression is altered due to disease-causing variants located in intron 5 of LMBR1 disrupt a long-range, cis-regulatory element of SHH.
messages: The lipidated N- and C-terminal peptides of ShhNp can be cleaved (shedding)(PubMed:24522195). The N-terminal palmitoylated peptide is cleaved at the Cardin-Weintraub (CW) motif site (PubMed:24522195). The cleavage reduced the interactions with heparan sulfate. The cleavage is enhanced by SCUBE2 (PubMed:24522195, PubMed:23118222).
messages: The several steps and mechanisms that permit controlled Shh dispersion and gradient formation remain controversial. The ShhNC C-terminal domain displays an autoproteolysis activity and a cholesterol transferase activity resulting in the cleavage and covalent attachment of a cholesterol moiety to the C-terminal of the newly generated N-terminal fragment (ShhN). The protein is further modified by covalent addition of palmitate at the N-terminal of ShhN, resulting to the dual-lipidated Shh (ShhNp). ShhNp is firmly tethered to the cell membrane where it forms multimers. Further solubilization and release from the cell surface seem to be achieved through different mechanisms, including the interaction with DISP1 and SCUBE2, movement by lipoprotein particles, transport by cellular extensions called cytonemes or by proteolytic removal of both terminal lipidated peptides (PubMed:26875496). Once released, the fully processed Shh can signal within embryonic tissues both at short and long-range.

9606:MICAL2
gene id: 9606:MICAL2
uniprot id: O94851
names: Activity Regulation
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the Mical family.
messages: Cytoplasm
messages: Interacts with PLXNA4 (By similarity). Interacts with RAB1B (PubMed:15694364, PubMed:27552051). Interacts with MAPK1/ERK2 (By similarity). Interacts with RAB35, RAB8A, RAB10, RAB13 and RAB15 (in their GTP-bound forms); binding to RAB35 is of low affinity compared to other Rab proteins; at least in case of RAB8A may bind 2 molecules of RAB8A simultaneously through a high and a low affinity binding site, respectively (PubMed:27552051). May interact with MAPK1/ERK2 (By similarity). Interacts with CORO1C; this interaction recruits MICAL2 to the actin filaments (PubMed:34106209).
messages: Methionine monooxygenase that promotes depolymerization of F-actin by mediating oxidation of residues 'Met-44' and 'Met-47' on actin to form methionine-sulfoxide, resulting in actin filament disassembly and preventing repolymerization (PubMed:24440334, PubMed:29343822). Regulates the disassembly of branched actin networks also by oxidizing ARP3B-containing ARP2/3 complexes leading to ARP3B dissociation from the network (PubMed:34106209). Acts as a key regulator of the SRF signaling pathway elicited by nerve growth factor and serum: mediates oxidation and subsequent depolymerization of nuclear actin, leading to increase MKL1/MRTF-A presence in the nucleus and promote SRF:MKL1/MRTF-A-dependent gene transcription. Does not activate SRF:MKL1/MRTF-A through RhoA (PubMed:24440334).
messages: Nucleus
messages: Specifically inhibited by CCG-1423, a small molecule inhibitor of SRF:MKL1/MRTF-A-dependent transcription.
messages: The C-terminal RAB-binding domain (RBD) (1796-1945), also described as bivalent Mical/EHBP Rab binding (bMERB) domain, mediates binding to predominantly RAB8A, RAB10, RAB13 and RAB15 (in their GTP-bound forms).

9606:CYP4F2
gene id: 9606:CYP4F2
uniprot id: P78329
names: Activity Regulation
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids, eicosanoids and vitamins (PubMed:18577768, PubMed:10833273, PubMed:10660572, PubMed:11997390, PubMed:17341693, PubMed:18574070). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase). Catalyzes predominantly the oxidation of the terminal carbon (omega-oxidation) of long- and very long-chain fatty acids. Displays high omega-hydroxylase activity toward polyunsaturated fatty acids (PUFAs) (PubMed:18577768). Participates in the conversion of arachidonic acid to omega-hydroxyeicosatetraenoic acid (20-HETE), a signaling molecule acting both as vasoconstrictive and natriuretic with overall effect on arterial blood pressure (PubMed:10660572, PubMed:17341693, PubMed:18574070). Plays a role in the oxidative inactivation of eicosanoids, including both pro-inflammatory and anti-inflammatory mediators such as leukotriene B4 (LTB4), lipoxin A4 (LXA4), and several HETEs (PubMed:8026587, PubMed:9799565, PubMed:10833273, PubMed:10660572, PubMed:17341693, PubMed:18574070, PubMed:18577768). Catalyzes omega-hydroxylation of 3-hydroxy fatty acids (PubMed:18065749). Converts monoepoxides of linoleic acid leukotoxin and isoleukotoxin to omega-hydroxylated metabolites (PubMed:15145985). Contributes to the degradation of very long-chain fatty acids (VLCFAs) by catalyzing successive omega-oxidations and chain shortening (PubMed:16547005, PubMed:18182499). Plays an important role in vitamin metabolism by chain shortening. Catalyzes omega-hydroxylation of the phytyl chain of tocopherols (forms of vitamin E), with preference for gamma-tocopherols over alpha-tocopherols, thus promoting retention of alpha-tocopherols in tissues (PubMed:11997390). Omega-hydroxylates and inactivates phylloquinone (vitamin…
messages: Belongs to the cytochrome P450 family.
messages: Disease susceptibility may be associated with variants affecting the gene represented in this entry. The variant Met-433 is associated with coumarin (the brand name of warfarin) resistance by increasing coumarin maintenance dose in patients on this anti-coagulant therapy. This is probably due to decreased activity of the phylloquinone omega-hydroxylase activity, leading to an increase in hepatic vitamin K levels that warfarin must antagonize (PubMed:24138531).
messages: Endoplasmic reticulum membrane
messages: Inhibited by dietary sesamin.
messages: Liver. Also present in kidney: specifically expressed in the S2 and S3 segments of proximal tubules in cortex and outer medulla (PubMed:10660572).
messages: Microsome membrane

9606:SDK1
gene id: 9606:SDK1
uniprot id: Q7Z5N4
names: Domain
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Adhesion molecule that promotes lamina-specific synaptic connections in the retina. Expressed in specific subsets of interneurons and retinal ganglion cells (RGCs) and promotes synaptic connectivity via homophilic interactions.
messages: Belongs to the sidekick family.
messages: Cell membrane
messages: Dysregulation of this protein may play an important role in podocyte dysfunction in HIV-associated nephropathy.
messages: Homodimer; mediates homophilic interactions to promote cell adhesion.
messages: Ig-like C2-type domains 1 and 2 mediate homophilic interactions.
messages: Synapse
messages: Up-regulated in glomeruli in HIV-associated nephropathy. In diseased glomeruli, significantly overexpressed and the expression is no longer restricted to mesangial cells but includes podocytes and parietal epithelial cells (PubMed:15213259).

9606:FZD8
gene id: 9606:FZD8
uniprot id: Q9H461
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor Fz/Smo family.
messages: Cell membrane
messages: Component of a Wnt-signaling complex that contains a WNT protein, a FZD protein and LRP5 or LRP6. Interacts directly with LRP5 or LRP6; the interaction is promoted by Wnt-binding and signaling and inhibited by DKK1. Interacts with GPOC, RSPO1 and RSPO3 (By similarity). Interacts with glypican GPC3 (PubMed:24496449).
messages: Golgi apparatus
messages: Lys-Thr-X-X-X-Trp motif interacts with the PDZ domain of Dvl (Disheveled) family members and is involved in the activation of the Wnt/beta-catenin signaling pathway.
messages: Membrane
messages: Most abundant in fetal kidney, followed by brain and lung. In adult tissues, expressed in kidney, heart, pancreas and skeletal muscle.
messages: Receptor for Wnt proteins. Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers beta-catenin signaling through inducing aggregation of receptor-ligand complexes into ribosome-sized signalosomes. The beta-catenin canonical signaling pathway leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes. A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to involve interactions with G-proteins. May be involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues. Coreceptor along with RYK of Wnt proteins, such as WNT1.
messages: The FZ domain is involved in binding with Wnt ligands.
messages: The PDZ-binding motif mediates interaction with GOPC.
messages: Ubiquitinated by ZNRF3, leading to its degradation by the proteasome.

9606:TSHZ2
gene id: 9606:TSHZ2
uniprot id: Q9NRE2
names: Function
names: PTM
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the teashirt C2H2-type zinc-finger protein family.
messages: Expressed in brain; strongly reduced in post-mortem elderly subjects with Alzheimer disease.
messages: Interacts (via homeobox domain) with APBB1 (via PID domain 1).
messages: Nucleus
messages: Probable transcriptional regulator involved in developmental processes. May act as a transcriptional repressor (Potential).
messages: Sumoylated.
messages: The sequence differs from that shown due translation of a 3'-UTR region.

9606:CD19
gene id: 9606:CD19
uniprot id: P15391
names: Disease Annotation
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cell membrane
messages: Detected on marginal zone and germinal center B cells in lymph nodes (PubMed:2463100). Detected on blood B cells (at protein level) (PubMed:2463100, PubMed:16672701).
messages: Functions as coreceptor for the B-cell antigen receptor complex (BCR) on B-lymphocytes. Decreases the threshold for activation of downstream signaling pathways and for triggering B-cell responses to antigens (PubMed:2463100, PubMed:1373518, PubMed:16672701). Activates signaling pathways that lead to the activation of phosphatidylinositol 3-kinase and the mobilization of intracellular Ca(2+) stores (PubMed:9382888, PubMed:9317126, PubMed:12387743, PubMed:16672701). Is not required for early steps during B cell differentiation in the blood marrow (PubMed:9317126). Required for normal differentiation of B-1 cells (By similarity). Required for normal B cell differentiation and proliferation in response to antigen challenges (PubMed:2463100, PubMed:1373518). Required for normal levels of serum immunoglobulins, and for production of high-affinity antibodies in response to antigen challenge (PubMed:9317126, PubMed:12387743, PubMed:16672701).
messages: Interacts with CR2/CD21 (PubMed:1702139). Part of a complex composed of CD19, CR2/CD21, CD81 and IFITM1/CD225 in the membrane of mature B-cells (PubMed:1383329). Interacts directly with CD81 (via the second extracellular domain); this interaction is initiated early during biosynthesis in the ER/pre-Golgi compartments and is essential for trafficking and compartmentalization of CD19 receptor on the cell surface of activated B cells (PubMed:16449649). Interacts with VAV (PubMed:10706702). Interacts with GRB2 and SOS when phosphorylated on Tyr-348 and/or Tyr-378. Interacts with PLCG2 when phosphorylated on Tyr-409 (PubMed:10706702). Interacts with LYN (PubMed:7687428). Interacts (when tyrosine phosphorylated) with the regulatory p85 subunit of phosphatidylinositol 3-kinase (PIK3R1 or PIK3R2) (PubMed:7684160).
messages: Membrane raft
messages: Phosphorylated on tyrosine following B-cell activation (PubMed:7684160, PubMed:7687539, PubMed:10706702, PubMed:12387743). Phosphorylated on tyrosine residues by LYN (PubMed:7687428). Tyrosine residues are phosphorylated sequentially after activation of the B cell receptor. Phosphorylation of Tyr-531 is extremely rapid, followed by phosphorylation at Tyr-409. In contrast, phosphorylation of Tyr-500 appears more slowly and is more transient, returning rapidly to basal levels (By similarity).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:RAD51AP2
gene id: 9606:RAD51AP2
uniprot id: Q09MP3
names: Subunit
names: Tissue Specificity
messages: Interacts with RAD51.
messages: Specifically expressed in meiotic tissues. Highly expressed in testis.

9606:WNT8A
gene id: 9606:WNT8A
uniprot id: D6RF47
uniprot id: Q9H1J5
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the Wnt family.
messages: Forms a soluble 1:1 complex with AFM; this prevents oligomerization and is required for prolonged biological activity (PubMed:26902720). The complex with AFM may represent the physiological form in body fluids (PubMed:26902720).
messages: Ligand for members of the frizzled family of seven transmembrane receptors.
messages: Ligand for members of the frizzled family of seven transmembrane receptors. Plays a role in embryonic patterning.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Palmitoleoylation is required for efficient binding to frizzled receptors (By similarity). Depalmitoleoylation leads to Wnt signaling pathway inhibition (By similarity).
messages: Proteolytic processing by TIKI1 and TIKI2 promotes oxidation and formation of large disulfide-bond oligomers, leading to inactivation of WNT8A.
messages: Secreted
messages: extracellular matrix

9606:MICB
gene id: 9606:MICB
uniprot id: Q29980
names: Disease Annotation
names: Function
names: Induction
names: Miscellaneous
names: PTM
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts with human cytomegalovirus/HHV-5 glycoprotein UL16; this interaction causes sequestration of MICB in the endoplasmic reticulum and increases resistance to KLRK1-mediated cytotoxicity.
messages: A GC to AG nucleotide substitution in intron 1 generates a splice junction which gives rise to an additional exon between exons 1 and 2. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Belongs to the MHC class I family. MIC subfamily.
messages: By heat shock, oxidative stress, retinoic acid, IFN-alpha and the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine. Induction by IFN-alpha is impaired in patients with chronic hepatitis C virus infection. Down-regulated by human cytomegalovirus UL112 microRNA during viral infection which leads to decreased binding of KLRK1/NKG2D and reduced killing by natural killer cells.
messages: Cell membrane
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry. The MICB*004 allele is associated with rheumatoid arthritis.
messages: Genetic variation in MICB is associated with cytomegalovirus and herpes simplex virus I seropositivity and this may be associated with schizophrenia risk.
messages: Proteolytically cleaved and released from the cell surface of tumor cells.
messages: Seems to have no role in antigen presentation. Acts as a stress-induced self-antigen that is recognized by gamma delta T cells. Ligand for the KLRK1/NKG2D receptor. Binding to KLRK1 leads to cell lysis.
messages: The following alleles of MICB are known: MICB*001, MICB*002, MICB*003, MICB*004, MICB*005, MICB*006, MICB*007, MICB*008, MICB*009N, MICB*010, MICB*011, MICB*012, MICB*013, MICB*014, MICB*015, MICB*016, MICB*018, MICB*019, MICB*020, MICB*021N and MICB*022. MICB*009N and MICB*021N are null alleles which are not expressed. The three most common MICB alleles in the human population could be MICB*005, MICB*004, and MICB*002. The sequence shown is that of MICB*004.
messages: Unlike classical MHC class I molecules, does not form a heterodimer with beta-2-microglobulin. Binds as a monomer to a KLRK1/NKG2D homodimer. KLRK1 forms a complex with HCST/DAP10 in which KLRK1 binds MICB while HCST acts as an adapter molecule which enables signal transduction. Receptor-ligand interaction induces clustering of both proteins in ordered structures called immune synapses and also leads to their intercellular transfer. This is associated with a reduction in the cytotoxicity of KLRK1-expressing cells.
messages: Widely expressed with the exception of the central nervous system where it is absent. Expressed in many, but not all, epithelial tumors of lung, breast, kidney, ovary, prostate and colon. In hepatocellular carcinomas, expressed in tumor cells but not in surrounding non-cancerous tissue.

9606:DDT
gene id: 9606:DDT
uniprot id: P30046
uniprot id: Q53Y51
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the MIF family.
messages: Cytoplasm
messages: Highly expressed in the liver and at lower levels in the heart, lung and pancreas.
messages: Homotrimer.
messages: Tautomerization of D-dopachrome with decarboxylation to give 5,6-dihydroxyindole (DHI).

9606:GSTO2
gene id: 9606:GSTO2
uniprot id: Q9H4Y5
names: Function
names: Similarity
names: Tissue Specificity
messages: Belongs to the GST superfamily. Omega family.
messages: Exhibits glutathione-dependent thiol transferase activity. Has high dehydroascorbate reductase activity and may contribute to the recycling of ascorbic acid. Participates in the biotransformation of inorganic arsenic and reduces monomethylarsonic acid (MMA).
messages: Expressed in a range of tissues, including the liver, kidney, skeletal muscle and prostate. Strongest expression in the testis.

9606:RAMAC
gene id: 9606:RAMAC
uniprot id: Q9BTL3
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the RAM family.
messages: Interacts with RNMT; this interaction enhances mRNA binding and cap methyltransferase activity.
messages: Nucleus
messages: Regulatory subunit of the mRNA-capping methyltransferase RNMT:RAMAC complex that methylates the N7 position of the added guanosine to the 5'-cap structure of mRNAs (PubMed:22099306, PubMed:27422871). Promotes the recruitment of the methyl donor, S-adenosyl-L-methionine, to RNMT (PubMed:27422871). Regulates RNMT expression by a post-transcriptional stabilizing mechanism (PubMed:22099306). Binds RNA (PubMed:22099306).

9606:ZNF146
gene id: 9606:ZNF146
uniprot id: Q15072
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: Binds DNA. Interacts with SUMO conjugating enzyme UBC9/UBE2I. Interacts with the telomeric protein TERF2IP.
messages: Liver, skeletal and heart muscle, mammary cells. Very low levels in brain, lung, placenta and kidney. Strongly overexpressed in many pancreas and colorectal cancers. Increased gene copy numbers are detected in 3 of 12 tumor cell lines and 2 of 12 primary pancreatic carcinomas. Overexpressed in 80% of colorectal cancers.
messages: Nucleus
messages: Sumoylated.

9606:TMEM17
gene id: 9606:TMEM17
uniprot id: Q86X19
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the TMEM17 family.
messages: Part of the tectonic-like complex (also named B9 complex).
messages: Transmembrane component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes. Required for ciliogenesis and sonic hedgehog/SHH signaling (By similarity).
messages: cilium membrane

9606:POU5F1B
gene id: 9606:POU5F1B
uniprot id: Q06416
names: Caution
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the POU transcription factor family. Class-5 subfamily.
messages: Could be the product of a pseudogene. Several pseudogenes of POU5F1 have been described on chromosomes 1, 3, 8, 10 and 12. Two of them, localized on chromosomes 8 and 10 have been shown to be preferentially transcribed in cancer tissues and may be involved in the regulation of POU5F1 gene activity in carcinogenesis.
messages: Detected at the mRNA level in several cancer tissues (breast, uterine cervix, lung, thyroid gland, esophagus, colon, urinary bladder, and glioma), but absent in normal tissues.
messages: Nucleus
messages: Shows weak transcriptional activator activity.

9606:NFASC
gene id: 9606:NFASC
uniprot id: O94856
names: Disease Annotation
names: Domain
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the immunoglobulin superfamily. L1/neurofascin/NgCAM family.
messages: Cell adhesion, ankyrin-binding protein which may be involved in neurite extension, axonal guidance, synaptogenesis, myelination and neuron-glial cell interactions.
messages: Cell membrane
messages: Homophilic adhesion is primarily mediated by the interaction of the second Ig-like domains.
messages: Horseshoe-shaped homodimer. Probable constituent of a NFASC/NRCAM/ankyrin-G complex. Associates with the sodium channel beta-1 (SCN1B) and beta-3 (SCN3B) subunits. Interacts with GLDN/gliomedin (By similarity). Interacts with MYOC.
messages: May be due to intron retention.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: paranodal septate junction

9606:ASCL2
gene id: 9606:ASCL2
uniprot id: Q99929
names: Developmental Stage
names: Function
names: Miscellaneous
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Efficient DNA binding requires dimerization with another basic helix-loop-helix (bHLH) protein. Forms heterodimers with bHLH transcription factor TCF3. May not heterodimerise with bHLH protein HAND1.
messages: Expressed in the ectoderm but not in the mesoderm or endoderm of the fetus at the second trimester (PubMed:12099555). At the second trimester, expressed in photoreceptor, bipolar, and ganglion cells of the retina, and in developing skin cells (PubMed:12099555). Expressed in developing neuronal cells of the brain and the spinal cord, but not in the peripheral nerves (PubMed:12099555).
messages: Expressed in the placenta at a stage between the first and second trimesters and when it matures, at about 32-36 weeks (PubMed:12099555). Expressed in the extravillous trophoblasts, the intermediate trophoblasts, and at lower levels in the cytotrophoblasts and stroma of chorionic villi of the developing placenta (PubMed:9175731, PubMed:12099555). Expressed in follicular T-helper (Tfh) cells (PubMed:24463518).
messages: In contrast to the mouse ortholog, the ASCL2 locus is not imprinted in human placenta.
messages: Nucleus
messages: Transcription factor. Binds to E-box motifs 5'-CANNTG-3' in the regulatory elements of target genes, probably as a heterodimer with another basic helix-loop-helix (bHLH) protein such as the transcription factor TCF3. May bind both open and closed chromatin, acting as a pioneer transcription factor to allow other factors to bind and activate lineage-specific genes. Required during post-implantation development for the generation of some differentiated trophoblast cell types. Transcriptional activity of ASCL2 may be antagonised in a subset of trophoblast cells by bHLH transcription factor HAND1, perhaps by competing for dimerization with other bHLH proteins. Involved in differentiation and function of follicular T-helper (Tfh) cells, thereby playing a role in germinal center responses; probably modulates expression of genes involved in Tfh cell function, such as BCL6. May also act as a suppressor of Th1-, Th2- and Th17-cell differentiation. Induces the formation of stem cells in intestinal crypts in vitro, synergistically activating transcription of target genes, such as SOX9, together with TCF4/beta-catenin. May form a bistable transcriptional switch, controlling expression of its own gene together with Wnt/R-spondin signaling, and thereby maintaining stem cell characteristics (By similarity). Modulates expression of target genes, including perhaps down-regulating EGR1/Krox24 and chemokine CXCL10/Mob-1 and up-regulating CXCR4 and CDKN1C/p57kip2, in Schwann cells. May play a role in reducing proliferation of Schwann cells, perhaps acting via modulation of expression of CDKN1C (By similarity). May be dispensable for blastocyst formation and later embryonic function (By similarity). May be involved in the determination of neuronal precursors (By similarity).

9606:NELL1
gene id: 9606:NELL1
uniprot id: B3KXR2
uniprot id: F5H6I3
uniprot id: J3KNC5
uniprot id: K9UUD5
uniprot id: Q92832
names: Caution
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Cytoplasm
messages: Homotrimer. Binds to PKC beta-1 (By similarity). Interacts with ATRAID; the interaction promotes osteoblast cell differentiation and mineralization.
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: Nucleus envelope
messages: Plays a role in the control of cell growth and differentiation. Promotes osteoblast cell differentiation and terminal mineralization.
messages: Secreted

9606:FREM2
gene id: 9606:FREM2
uniprot id: Q5SZK8
names: Disease Annotation
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the FRAS1 family.
messages: Cell membrane
messages: Extracellular matrix protein required for maintenance of the integrity of the skin epithelium and for maintenance of renal epithelia (PubMed:15838507). Required for epidermal adhesion (PubMed:15838507). Involved in the development of eyelids and the anterior segment of the eyeballs (PubMed:29688405, PubMed:30802441).
messages: Interacts with FREM1.
messages: The Calx-beta domains bind calcium with high affinity and undergo a major conformational shift upon binding.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:ATF4
gene id: 9606:ATF4
uniprot id: P18848
names: Domain
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Binds to a Tax-responsive enhancer element in the long terminal repeat of HTLV-I.
messages: Belongs to the bZIP family.
messages: Binds DNA as a homodimer and as a heterodimer (PubMed:11018027). Heterodimer; heterodimerizes with CEBPB (PubMed:11018027). Heterodimer; heterodimerizes with DDIT3/CHOP (PubMed:18940792). Interacts with CEP290 (via an N-terminal region) (PubMed:16682973). Interacts with NEK6, DAPK2 (isoform 2) and ZIPK/DAPK3 (PubMed:20873783, PubMed:21408167). Interacts (via its leucine zipper domain) with GABBR1 and GABBR2 (via their C-termini) (By similarity). Forms a heterodimer with TXLNG in osteoblasts (PubMed:15911876). Interacts (via its DNA binding domain) with FOXO1 (C-terminal half); the interaction occurs in osteoblasts and regulates glucose homeostasis through suppression of beta-cell proliferation and a decrease in insulin production (By similarity). Interacts with SATB2; the interaction results in enhanced DNA binding and transactivation by these transcription factors (By similarity). Interacts with ABRAXAS2 (PubMed:22974638). Interacts with TRIB3, inhibiting the transactivation activity of ATF4 (By similarity). Interacts with DISC1; which inhibits ATF4 transcription factor activity by disrupting ATF4 dimerization and DNA-binding (By similarity). Interacts with EP300/p300; EP300/p300 stabilizes ATF4 and increases its transcriptional activity independently of its catalytic activity by preventing its ubiquitination (PubMed:16219772).
messages: Cell membrane
messages: Cytoplasm
messages: Hydroxylated by PHD3, leading to decreased protein stability.
messages: Nucleus
messages: Nucleus speckle
messages: Phosphorylation at Ser-245 by RPS6KA3/RSK2 in osteoblasts enhances transactivation activity and promotes osteoblast differentiation (PubMed:15109498). Phosphorylated on the betaTrCP degron motif at Ser-219, followed by phosphorylation at Thr-213, Ser-224, Ser-231, Ser-235 and Ser-248, promoting interaction with BTRC and ubiquitination (By similarity). Phosphorylation is promoted by mTORC1 (By similarity). Phosphorylation at Ser-215 by CK2 decreases its stability (PubMed:23123191). Phosphorylated by NEK6 (PubMed:20873783).
messages: Regulated at the translational level in response to various stress such as endoplasmic reticulum stress, amino acid starvation or oxidative stress (PubMed:27629041, PubMed:33384352). In the absence of stress, ribosomes re-initiate translation at an inhibitory open reading frame (uORF) upstream of the ATF4 transcript, which precludes AFT4 translation. In response to stress and subsequent EIF2S1/eIF-2-alpha phosphorylation, ribosomes bypass the inhibitory uORF and re-initiate translation at the AFT4 coding sequence (PubMed:27629041).
messages: The BetaTrCP degron motif promotes binding to BTRC when phosphorylated.
messages: Transcription factor that binds the cAMP response element (CRE) (consensus: 5'-GTGACGT[AC][AG]-3') and displays two biological functions, as regulator of metabolic and redox processes under normal cellular conditions, and as master transcription factor during integrated stress response (ISR) (PubMed:17684156, PubMed:16682973, PubMed:31444471, PubMed:32132707). Binds to asymmetric CRE's as a heterodimer and to palindromic CRE's as a homodimer (By similarity). Core effector of the ISR, which is required for adaptation to various stress such as endoplasmic reticulum (ER) stress, amino acid starvation, mitochondrial stress or oxidative stress (PubMed:32132707). During ISR, ATF4 translation is induced via an alternative ribosome translation re-initiation mechanism in response to EIF2S1/eIF-2-alpha phosphorylation, and stress-induced ATF4 acts as a master transcription factor of stress-responsive genes in order to promote cell recovery (PubMed:32132706, PubMed:32132707). Promotes the transcription of genes linked to amino acid sufficiency and resistance to oxidative stress to protect cells against metabolic consequences of ER oxidation (By similarity). Activates the transcription of NLRP1, possibly in concert with other factors in response to ER stress (PubMed:26086088). Activates the transcription of asparagine synthetase (ASNS) in response to amino acid deprivation or ER stress (PubMed:11960987). However, when associated with DDIT3/CHOP, the transcriptional activation of the ASNS gene is inhibited in response to amino acid deprivation (PubMed:18940792). Together with DDIT3/CHOP, mediates programmed cell death by promoting the expression of genes involved in cellular amino acid metabolic processes, mRNA translation and the terminal unfolded protein response (terminal UPR), a cellular response that elicits programmed cell death when ER stress is prolonged and unresolved (By similarity). Together with DDIT3/CHOP, activates the transcription of the IRS-regulator TRIB3 and p…
messages: Ubiquitinated by SCF(BTRC) in response to mTORC1 signal, followed by proteasomal degradation and leading to down-regulate expression of SIRT4 (PubMed:11238952). Interaction with EP300/p300 inhibits ubiquitination by SCF(BTRC) (PubMed:16219772).
messages: centrosome

9606:FBXO28
gene id: 9606:FBXO28
uniprot id: Q9NVF7
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Part of a SCF (SKP1-cullin-F-box) protein ligase complex.
messages: Probably recognizes and binds to some phosphorylated proteins and promotes their ubiquitination and degradation.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: kinetochore

9606:STEAP1B
gene id: 9606:STEAP1B
uniprot id: Q6NZ63
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the STEAP family.
messages: Membrane

9606:GLDN
gene id: 9606:GLDN
uniprot id: Q14DE1
uniprot id: Q6ZMI3
names: Caution
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cell membrane
messages: Homotrimer (via collagen-like domains). Interacts with NRCAM and NFASC/neurofascin (PubMed:27616481). Interaction with glial NRCAM enhances interaction with axonal NFASC. Interacts with MYOC.
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: Ligand for NRCAM and NFASC/neurofascin that plays a role in the formation and maintenance of the nodes of Ranvier on myelinated axons. Mediates interaction between Schwann cell microvilli and axons via its interactions with NRCAM and NFASC. Nodes of Ranvier contain clustered sodium channels that are crucial for the saltatory propagation of action potentials along myelinated axons. During development, nodes of Ranvier are formed by the fusion of two heminodes. Required for normal clustering of sodium channels at heminodes; not required for the formation of mature nodes with normal sodium channel clusters. Required, together with NRCAM, for maintaining NFASC and sodium channel clusters at mature nodes of Ranvier.
messages: N-glycosylated.
messages: Proteolytic proccessing by a furin-like protease causes shedding of the ectodomain. Further cleavage by BMP1 releases the olfactomedin-like domain.
messages: Secreted
messages: Specifically expressed in spinal cord, brain, placenta and sciatic nerve. More abundant in peripheral than central nervous system.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The olfactomedin-like domain mediates NFASC/neurofascin and NRCAM binding.
messages: axon
messages: extracellular matrix

9606:DCTN3
gene id: 9606:DCTN3
uniprot id: O75935
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the dynactin subunit 3 family.
messages: Cleavage furrow
messages: Cytoplasm
messages: Midbody
messages: Part of the dynactin complex that activates the molecular motor dynein for ultra-processive transport along microtubules (By similarity). Together with dynein may be involved in spindle assembly and cytokinesis (PubMed:9722614).
messages: Subunit of dynactin, a multiprotein complex part of a tripartite complex with dynein and a adapter, such as BICDL1, BICD2 or HOOK3. The dynactin complex is built around ACTR1A/ACTB filament and consists of an actin-related filament composed of a shoulder domain, a pointed end and a barbed end. Its length is defined by its flexible shoulder domain. The soulder is composed of 2 DCTN1 subunits, 4 DCTN2 and 2 DCTN3. The 4 DCNT2 (via N-terminus) bind the ACTR1A filament and act as molecular rulers to determine the length. The pointed end is important for binding dynein-dynactin cargo adapters. Consists of 4 subunits: ACTR10, DCNT4, DCTN5 and DCTN6. The barbed end is composed of a CAPZA1:CAPZB heterodimers, which binds ACTR1A/ACTB filament and dynactin and stabilizes dynactin.
messages: Ubiquitously expressed. Highly expressed in muscle and pancreas and detected at lower levels in brain.
messages: centrosome
messages: kinetochore
messages: spindle

9606:WNT1
gene id: 9606:WNT1
uniprot id: P04628
names: Caution
names: Disease Annotation
names: Function
names: PTM
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: A palmitoylation site was proposed at Cys-93, but it was later shown that this cysteine is engaged in a disulfide bond.
messages: Belongs to the Wnt family.
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry.
messages: Forms a soluble 1:1 complex with AFM; this prevents oligomerization and is required for prolonged biological activity (PubMed:26902720). The complex with AFM may represent the physiological form in body fluids (PubMed:26902720). Interacts with PORCN. Interacts with RSPO1, RSPO2 and RSPO3 (By similarity). Interacts with WLS (By similarity).
messages: Genetic variations in WNT1 define the bone mineral density quantitative trait locus 16 (BMND16) [MIM:615221]. Variance in bone mineral density influences bone mass, contributes to size determination in the general population, and is a susceptibility factor for osteoporotic fractures.
messages: Ligand for members of the frizzled family of seven transmembrane receptors (Probable). Acts in the canonical Wnt signaling pathway by promoting beta-catenin-dependent transcriptional activation (PubMed:23499309, PubMed:26902720, PubMed:28528193, PubMed:23656646). In some developmental processes, is also a ligand for the coreceptor RYK, thus triggering Wnt signaling (By similarity). Plays an essential role in the development of the embryonic brain and central nervous system (CNS) (By similarity). Has a role in osteoblast function, bone development and bone homeostasis (PubMed:23499309, PubMed:23656646).
messages: Palmitoleoylation is required for efficient binding to frizzled receptors. Palmitoleoylation is necessary for proper trafficking to cell surface (Probable). Depalmitoleoylated by NOTUM, leading to inhibit Wnt signaling pathway (By similarity).
messages: Secreted
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: extracellular matrix

9606:AGBL2
gene id: 9606:AGBL2
uniprot id: A0A140VKH9
uniprot id: Q5U5Z8
names: Activity Regulation
names: Caution
names: Cofactor
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the peptidase M14 family.
messages: Binds 1 zinc ion per subunit.
messages: Inhibited by RARRES1.
messages: Interacts with RARRES1, KIF11 AND MAPRE1.
messages: Metallocarboxypeptidase that mediates deglutamylation of tubulin and non-tubulin target proteins. Catalyzes the removal of polyglutamate side chains present on the gamma-carboxyl group of glutamate residues within the C-terminal tail of tubulin protein. Specifically cleaves tubulin long-side-chains, while it is not able to remove the branching point glutamate. Also catalyzes the removal of polyglutamate residues from the carboxy-terminus of non-tubulin proteins such as MYLK.
messages: Was initially shown to catalyze the removal of carboxy-terminus tyrosine from alpha-tubulin (PubMed:21303978). However, later studies did not identified any detyrosinase or deglycylase activities from the carboxy-terminus of tubulin (By similarity).
messages: Was originally thought to have detyrosinating activity from C-terminal positions on tubulin.
messages: centriole
messages: cilium basal body
messages: cytosol

9606:MIS18A
gene id: 9606:MIS18A
uniprot id: Q9NYP9
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the mis18 family.
messages: Chromosome
messages: Detected in testis.
messages: Homodimer, and heterodimer with OIP5/MIS18B (PubMed:17199038, PubMed:26921242). Identified in a complex containing MIS18A, OIP5/MIS18B, MIS18BP1, RBBP7 and RBBP4 (PubMed:17199038).
messages: Nucleus
messages: Required for recruitment of CENPA to centromeres and normal chromosome segregation during mitosis.
messages: centromere

9606:DYNLL1
gene id: 9606:DYNLL1
uniprot id: P63167
uniprot id: Q6FGH9
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts with ebolavirus protein VP35; this interaction stabilizes VP35 N-terminal oligomerization domain and enhances viral RNA synthesis.
messages: (Microbial infection) Interacts with human spumaretrovirus Gag protein; this interaction is critical for intracellular microtubule-dependent viral genome transport toward the centrosome.
messages: Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. May play a role in changing or maintaining the spatial distribution of cytoskeletal structures.
messages: Belongs to the dynein light chain family.
messages: Binds and inhibits the catalytic activity of neuronal nitric oxide synthase/NOS1.
messages: Homodimer. Monomer; the monomeric form is incapable of binding to target proteins. The cytoplasmic dynein 1 complex consists of two catalytic heavy chains (HCs) and a number of non-catalytic subunits presented by intermediate chains (ICs), light intermediate chains (LICs) and light chains (LCs); the composition seems to vary in respect to the IC, LIC and LC composition. The heavy chain homodimer serves as a scaffold for the probable homodimeric assembly of the respective non-catalytic subunits. The ICs and LICs bind directly to the HC dimer and the LCs assemble on the IC dimer. Interacts with TXNDC17. Interacts with WWC1 and ESR1. The WWC1-DYNLL1 interaction is mandatory for the recruitment and transactivation functions of ESR1 or DYNLL1 to the target chromatin. Interacts with BCL2L11 isoform 1 and isoform 2. Interacts with BCL2; the interaction is greatly enhanced in the nucleus and in mitochondria upon induction of apoptosis. Interacts with PAK1; the interaction requires dimeric DYNLL1. Interacts with MYZAP. Part of an astrin (SPAG5)-kinastrin (SKAP) complex containing KNSTRN, SPAG5, PLK1, DYNLL1 and SGO2. Interacts with ATMIN; this interaction inhibits ATMIN transcriptional activity and hence may play a role in a feedback loop whereby DYNLL1 inhibits transactivation of its own promoter by ATMIN. Interacts with NEK9 (not phosphorylated at 'Ser-944'). Interacts with BICD2 (By similarity). Interacts with BCAS1 (By similarity). Interacts with Basson/BSN. Interacts with HDAC6 (PubMed:31505170). Interacts with TPPP (PubMed:31505170). Interacts with AMBRA1 (via TQT motifs); tethering AMBRA1 to the cytoskeleton (PubMed:20921139). Interacts with FAM83D/CHICA (via C-terminus) (PubMed:22965910). Interacts with HMMR, SPAG5/Astrin and KNSTRN/Kinastrin (PubMed:22965910). Interacts with TLK2 (PubMed:29955062, PubMed:33323470). Interacts with NOS1 (By similarity).
messages: Mitochondrion
messages: Nucleus
messages: Phosphorylation at Ser-88 appears to control the dimer-monomer transition. According to PubMed:15193260, it is phosphorylated at Ser-88 by PAK1, however, according to PubMed:18650427, the DYNLL1 dimer is not accessible for PAK1 and the phosphorylation could not be demonstrated in vitro.
messages: Promotes transactivation functions of ESR1 and plays a role in the nuclear localization of ESR1.
messages: Regulates apoptotic activities of BCL2L11 by sequestering it to microtubules. Upon apoptotic stimuli the BCL2L11-DYNLL1 complex dissociates from cytoplasmic dynein and translocates to mitochondria and sequesters BCL2 thus neutralizing its antiapoptotic activity.
messages: Ubiquitous (PubMed:8628263). Expressed in testis (PubMed:22965910).
messages: Up-regulated by ATMIN, PAK1 and estrogen.
messages: centrosome
messages: cytoskeleton

9606:OR6C70
gene id: 9606:OR6C70
uniprot id: A6NIJ9
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Odorant receptor.

9606:SLFN11
gene id: 9606:SLFN11
uniprot id: Q7Z7L1
names: Function
names: Induction
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the Schlafen family. Subgroup III subfamily.
messages: Chromosome
messages: Dominant determinant of sensitivity to DNA-damaging anticancer drugs: acts by mediating cell death in response to DNA damage induced by anticancer drugs (PubMed:29395061). Down-regulated in a number of chemoresistant tumors (PubMed:26625211, PubMed:28196596, PubMed:27440269, PubMed:28212573).
messages: Down-regulated in small cell lung cancer (SCLC) cells resistant to PARP inhibitor drugs (PubMed:26625211, PubMed:28196596, PubMed:27440269, PubMed:28212573). Up-regulated by type I interferons, poly-IC and poly-dAdT (PubMed:20956525, PubMed:23000900).
messages: Exhibits a wider expression range in ovarian and colon adenocarcinoma than in their corresponding healthy tissues.
messages: Inhibitor of DNA replication that promotes cell death in response to DNA damage (PubMed:22927417, PubMed:26658330, PubMed:29395061). Acts as a guardian of the genome by killing cells with defective replication (PubMed:29395061). Persistently blocks stressed replication forks by opening chromatin across replication initiation sites at stressed replication forks, possibly leading to unwind DNA ahead of the MCM helicase and block fork progression, ultimately leading to cell death (PubMed:29395061). Acts independently of ATR (PubMed:29395061). Also acts as an interferon (IFN)-induced antiviral protein which acts as an inhibitor of retrovirus protein synthesis (PubMed:23000900). Specifically abrogates the production of retroviruses such as human immunodeficiency virus 1 (HIV-1) by acting as a specific inhibitor of the synthesis of retroviruses encoded proteins in a codon-usage-dependent manner (PubMed:23000900). Binds to tRNAs and exploits the unique viral codon bias towards A/T nucleotides (PubMed:23000900). The exact inhibition mechanism is unclear: may either sequester tRNAs, prevent their maturation via post-transcriptional processing or may accelerate their deacylation (PubMed:23000900). Does not inhibit reverse transcription, integration or production and nuclear export of viral RNA (PubMed:23000900).
messages: Interacts with MCM3 (PubMed:29395061). Interacts with DHX9 (PubMed:26625211, PubMed:29395061). Interacts with RPA1 (PubMed:26658330, PubMed:29395061).
messages: Nucleus

9606:POTEI
gene id: 9606:POTEI
uniprot id: P0CG38
names: Similarity
messages: In the C-terminal section; belongs to the actin family.
messages: In the N-terminal section; belongs to the POTE family.

9606:C1S
gene id: 9606:C1S
uniprot id: F8WCZ6
uniprot id: P09871
names: Activity Regulation
names: Caution
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subunit
messages: Belongs to the peptidase S1 family.
messages: C1 is a calcium-dependent trimolecular complex of C1q, C1r and C1s in the molar ration of 1:2:2. Activated C1s is an disulfide-linked heterodimer of a heavy chain and a light chain.
messages: C1s B chain is a serine protease that combines with C1q and C1r to form C1, the first component of the classical pathway of the complement system. C1r activates C1s so that it can, in turn, activate C2 and C4.
messages: Inhibited by SERPING1.
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains.

9606:LACRT
gene id: 9606:LACRT
uniprot id: Q9GZZ8
names: Function
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Expressed in secretory granules of many acinar cells in lacrimal gland and in scattered acinar cells of salivary glands.
messages: Modulates secretion by lacrimal acinar cells.
messages: Secreted

9606:COLEC11
gene id: 9606:COLEC11
uniprot id: Q9BWP8
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the COLEC10/COLEC11 family.
messages: Homotrimer; disulfide-linked (PubMed:20956340, PubMed:25912189). Interacts with MASP1; probably triggers the lectin pathway of complement (PubMed:20956340).
messages: Lectin that plays a role in innate immunity, apoptosis and embryogenesis (PubMed:23954398, PubMed:25912189, PubMed:21258343). Calcium-dependent lectin that binds self and non-self glycoproteins presenting high mannose oligosaccharides with at least one terminal alpha-1,2-linked mannose epitope (PubMed:25912189). Primarily recognizes the terminal disaccharide of the glycan (PubMed:25912189). Also recognizes a subset of fucosylated glycans and lipopolysaccharides (PubMed:17179669, PubMed:25912189). Plays a role in innate immunity through its ability to bind non-self sugars presented by microorganisms and to activate the complement through the recruitment of MAPS1 (PubMed:20956340, PubMed:25912189). Also plays a role in apoptosis through its ability to bind in a calcium-independent manner the DNA present at the surface of apoptotic cells and to activate the complement in response to this binding (Probable). Finally, plays a role in development, probably serving as a guidance cue during the migration of neural crest cells and other cell types during embryogenesis (PubMed:21258343, PubMed:28301481).
messages: Secreted
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitous (PubMed:17179669). Detected in adrenal gland, kidney, liver, ovaries and testis (at protein level) (PubMed:20956340).

9606:SCOC
gene id: 9606:SCOC
uniprot id: Q9UIL1
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the SCOC family.
messages: Golgi apparatus membrane
messages: Homodimer (PubMed:24098481). Interacts with ARL1, ARL2 and ARL3 (PubMed:11303027). Directly interacts with FEZ1 and UVRAG (PubMed:22354037, PubMed:24098481). The interaction with UVRAG is reduced by amino acid starvation, but the complex is stabilized in the presence of FEZ1. Interacts with NRBF2 (PubMed:22354037).
messages: Positive regulator of amino acid starvation-induced autophagy.
messages: Widely expressed with highest levels in brain, heart and skeletal muscle.
messages: cytosol
messages: trans-Golgi network

9606:MAU2
gene id: 9606:MAU2
uniprot id: Q9Y6X3
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the SCC4/mau-2 family.
messages: Chromosome
messages: Heterodimerizes with MAU2/SCC2 to form the cohesin loading complex (PubMed:16682347, PubMed:16802858, PubMed:21934712, PubMed:28167679, PubMed:22628566). The NIPBL-MAU2 heterodimer interacts with the SMC1A-SMC3 heterodimer and with the cohesin complex composed of SMC1A, SMC3, RAD21 and STAG1 (PubMed:22628566).
messages: Nucleus
messages: Plays an important role in the loading of the cohesin complex on to DNA. Forms a heterodimeric complex (also known as cohesin loading complex) with NIPBL/SCC2 which mediates the loading of the cohesin complex onto chromatin (PubMed:28167679, PubMed:22628566). Plays a role in sister chromatid cohesion and normal progression through prometaphase (PubMed:16802858, PubMed:16682347).
messages: nucleoplasm

9606:GORASP1
gene id: 9606:GORASP1
uniprot id: B4E1H8
uniprot id: Q9BQQ3
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the GORASP family.
messages: Endoplasmic reticulum-Golgi intermediate compartment membrane
messages: Homodimer. Forms higher-order oligomers under interphase but not mitotic conditions. Dimers of the protein on one membrane might be able to interact with dimers on another and so stack cisternae (PubMed:26363069). Interacts with the C-terminus of GOLGA2/GM130 under both mitotic and non-mitotic conditions (PubMed:16489344, PubMed:26363069). The interaction is critical for the correct targeting of both proteins to the cis-Golgi. Interacts with TMED2 and TMED3 (By similarity).
messages: Key structural protein of the Golgi apparatus (PubMed:33301566). The membrane cisternae of the Golgi apparatus adhere to each other to form stacks, which are aligned side by side to form the Golgi ribbon (PubMed:33301566). Acting in concert with GORASP2/GRASP55, is required for the formation and maintenance of the Golgi ribbon, and may be dispensable for the formation of stacks (PubMed:33301566). However, other studies suggest that GORASP1 plays an important role in assembly and membrane stacking of the cisternae, and in the reassembly of Golgi stacks after breakdown during mitosis (By similarity). Caspase-mediated cleavage of GORASP1 is required for fragmentation of the Golgi during apoptosis (By similarity). Also mediates, via its interaction with GOLGA2/GM130, the docking of transport vesicles with the Golgi membranes (PubMed:16489344). Mediates ER stress-induced unconventional (ER/Golgi-independent) trafficking of core-glycosylated CFTR to cell membrane (PubMed:21884936).
messages: Myristoylated.
messages: Phosphorylated by CDC2/B1 and PLK kinases during mitosis. Phosphorylation cycle correlates with the cisternal stacking cycle. Phosphorylation of the homodimer prevents the association of dimers into higher-order oligomers, leading to cisternal unstacking.
messages: Target for caspase-3 cleavage during apoptosis. The cleavage contributes to Golgi fragmentation and occurs very early in the execution phase of apoptosis.
messages: cis-Golgi network membrane

9606:HECW1
gene id: 9606:HECW1
uniprot id: Q76N89
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cytoplasm
messages: E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent degradation of DVL1. Also targets the mutant SOD1 protein involved in familial amyotrophic lateral sclerosis (FALS). Forms cytotoxic aggregates with DVL1, SSR3 and mutant SOD1 that lead to motor neuron death in FALS.
messages: Interacts with DVL1 and SSR3. Also interacts with mutant SOD1.
messages: Predominantly expressed in neurons of adult and fetal brain. Weakly expressed in the kidney.

9606:CLEC2A
gene id: 9606:CLEC2A
uniprot id: Q6UVW9
names: Function
names: Induction
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: By phytohemagglutinin (PHA) in peripheral CD8(+) T cells.
messages: Cell membrane
messages: Homodimer; non-disulfide-linked. Interacts with KLRB1. Interacts with KLRF2.
messages: Mainly expressed in skin. Also expressed in keratinocytes, spleen, thymus, small intestine, peripheral blood monocytes, bone marrow, ovary, testis and skin. High expression in CD8(+), B-lymphocytes and naive CD4(+) T-cells. Restricted mostly to proliferating lymphocytes. Not detected in myeloid leukocytes or natural killer (NK) cells.
messages: N-glycosylated.
messages: Plays a role in modulating the extent of T-cell expansion. Enhances the expansion of TCR-stimulated T-cells by increasing their survival through enhanced expression of anti-apoptotic proteins. May modulate the capacity of T-cells to home to lymph nodes through SELL. Facilitates dedicated immune recognition of keratinocytes via interaction with its receptor KLRF2 by stimulating natural killer cell mediated cytotoxicity.

9606:SLCO4C1
gene id: 9606:SLCO4C1
uniprot id: Q6ZQN7
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Basolateral cell membrane
messages: Belongs to the organo anion transporter (TC 2.A.60) family.
messages: Mediates the transport of organic anions such as steroids (estrone 3-sulfate, chenodeoxycholate, glycocholate) and thyroid hormones (3,3',5-triiodo-L-thyronine (T3), L-thyroxine (T4)), in the kidney (PubMed:14993604, PubMed:19129463, PubMed:20610891). Capable of transporting cAMP and pharmacological substances such as digoxin, ouabain and methotrexate (PubMed:14993604). Transport is independent of sodium, chloride ion, and ATP (PubMed:14993604). Transport activity is stimulated by an acidic extracellular environment due to increased substrate affinity to the transporter (PubMed:19129463). The driving force for this transport activity is currently not known (By similarity). The role of hydrogencarbonate (HCO3(-), bicarbonate) as the probable counteranion that exchanges for organic anions is still not well defined (PubMed:19129463). Functions as an uptake transporter at the apical membrane, suggesting a role in renal reabsorption (By similarity). Involved in the renal secretion of the uremic toxin ADMA (N(omega),N(omega)-dimethyl-L-arginine or asymmetrical dimethylarginine), which is associated to cardiovascular events and mortality, and the structurally related amino acids L-arginine and L-homoarginine (a cardioprotective biomarker) (PubMed:30865704). Can act bidirectionally, suggesting a dual protective role of this transport protein; exporting L-homoarginine after being synthesized in proximal tubule cells, and mediating uptake of ADMA from the blood into proximal tubule cells where it is degraded by the enzyme dimethylarginine dimethylaminohydrolase 1 (DDAH1) (PubMed:30865704, PubMed:32642843). May be involved in sperm maturation by enabling directed movement of organic anions and compounds within or between cells (By similarity). This ion-transporting process is important to maintain the strict epididymal homeostasis necessary for sperm maturation (By similarity). May have a role in secretory functions since seminal vesicle epithelial cells are assumed to secrete…
messages: Predominantly expressed in kidney but also weakly expressed in both fetal liver and kidney.
messages: SLCO4C1-mediated digoxin uptake is inhibited by digoxin itself and related compounds such as ouabain, digitoxin and digoxigenin.

9606:LDHA
gene id: 9606:LDHA
uniprot id: P00338
uniprot id: V9HWB9
names: Activity Regulation
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the LDH/MDH superfamily. LDH family.
messages: Cytoplasm
messages: Fermentation of pyruvate to lactate is inhibited when bound to folliculin FLCN, perhaps partly by FLCN preventing binding of cofactor NADH (PubMed:34381247).
messages: Homotetramer (PubMed:11276087). Interacts with PTEN upstream reading frame protein MP31 (PubMed:33406399). Interacts with folliculin FLCN; the interaction is direct and inhibits enzymatic activity (PubMed:34381247).
messages: ISGylated.
messages: Interconverts simultaneously and stereospecifically pyruvate and lactate with concomitant interconversion of NADH and NAD(+).
messages: Predominantly expressed in anaerobic tissues such as skeletal muscle and liver.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:FABP12
gene id: 9606:FABP12
uniprot id: A6NFH5
names: Developmental Stage
names: Function
names: Similarity
names: Tissue Specificity
messages: Belongs to the calycin superfamily. Fatty-acid binding protein (FABP) family.
messages: Expressed in a number of retinoblastoma cell lines.
messages: May play a role in lipid transport.
messages: Not detected in fetal tissues.

9606:STK10
gene id: 9606:STK10
uniprot id: O94804
names: Activity Regulation
names: Disease Annotation
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Autophosphorylates following homodimerization, leading to activation of the protein.
messages: Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.
messages: Cell membrane
messages: Highly expressed in rapidly proliferating tissues (spleen, placenta, and peripheral blood leukocytes). Also expressed in brain, heart, skeletal muscle, colon, thymus, kidney, liver, small intestine and lung.
messages: Homodimer; homodimerization is required for activation segment autophosphorylation.
messages: Inhibited by the pyrrole-indolinone inhibitor SU11274 (K00593): intercalates between the ATP-binding Lys-65 and alpha-C glutamate (Glu-81), resulting in a partial disordering of the lysine side chain. Also specifically inhibited by erlotinib. Slightly inhibited by gefitinib.
messages: Inhibition by erlotinib, an orally administered EGFR tyrosine kinase inhibitor used for treatment, enhances STK10-dependent lymphocytic responses, possibly leading to the aggravation of skin inflammation observed upon treatment by erlotinib.
messages: Serine/threonine-protein kinase involved in regulation of lymphocyte migration. Phosphorylates MSN, and possibly PLK1. Involved in regulation of lymphocyte migration by mediating phosphorylation of ERM proteins such as MSN. Acts as a negative regulator of MAP3K1/MEKK1. May also act as a cell cycle regulator by acting as a polo kinase kinase: mediates phosphorylation of PLK1 in vitro; however such data require additional evidences in vivo.
messages: The disease may be caused by variants affecting the gene represented in this entry.

9606:H2AB1
gene id: 9606:H2AB1
uniprot id: P0C5Y9
names: Caution
names: Domain
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Although related to histone H2AB1 in mouse (AC Q9CQ70), it is unclear whether human and mouse H2AB1 proteins are involved in similar processes. In mouse, histone H2AB1 is specifically required to direct the transformation of dissociating nucleosomes to protamine in male germ cells during spermatogenesis. It is however unclear whether human protein, which participates in mRNA processing and is associated with active transcription, is also involved in nucleosomes to protamine replacement (PubMed:22795134).
messages: Atypical histone H2A which can replace conventional H2A in some nucleosomes and is associated with active transcription and mRNA processing (PubMed:22795134). Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability (PubMed:15257289, PubMed:16287874, PubMed:16957777, PubMed:17591702, PubMed:17726088, PubMed:18329190, PubMed:22795134). Nucleosomes containing this histone are less rigid and organize less DNA than canonical nucleosomes in vivo (PubMed:15257289, PubMed:16957777, PubMed:17591702, PubMed:24336483). They are enriched in actively transcribed genes and associate with the elongating form of RNA polymerase (PubMed:17591702, PubMed:24753410). They associate with spliceosome components and are required for mRNA splicing (PubMed:22795134).
messages: Belongs to the histone H2A family.
messages: Chromosome
messages: In contrast to other H2A histones, it does not contain the conserved residues that are the target of post-translational modifications.
messages: Nucleus
messages: Present in mature sperm.
messages: The docking domain is responsible for the weaker heterodimerization with H2B.
messages: The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. May be incorporated into a proportion of nucleosomes, replacing one or more H2A molecules.

9606:ATP8
gene id: 9606:ATP8
uniprot id: P03928
uniprot id: U5YV54
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the ATPase protein 8 family.
messages: F-type ATPases have 2 components, CF(1) - the catalytic core - and CF(0) - the membrane proton channel. Component of an ATP synthase complex composed of ATP5PB, ATP5MC1, ATP5F1E, ATP5PD, ATP5ME, ATP5PF, ATP5MF, MT-ATP6, MT-ATP8, ATP5F1A, ATP5F1B, ATP5F1D, ATP5F1C, ATP5PO, ATP5MG, ATP5MK and ATP5MJ (By similarity). Interacts with PRICKLE3 (PubMed:32516135).
messages: Membrane
messages: Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Part of the complex F(0) domain. Minor subunit located with subunit a in the membrane (By similarity).
messages: Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Part of the complex F(0) domain. Minor subunit located with subunit a in the membrane.
messages: Mitochondrion membrane
messages: The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:HTR7
gene id: 9606:HTR7
uniprot id: P34969
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Isoform A is the predominant isoform in spleen, caudate and hippocampus. Isoform B is expressed at lower levels. Isoform D is a minor isoform in terms of expression.
messages: This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that stimulate adenylate cyclase.

9606:ITGB1BP2
gene id: 9606:ITGB1BP2
uniprot id: Q9UKP3
names: Domain
names: Function
names: Subunit
names: Tissue Specificity
messages: Expressed in skeletal and cardiac muscles but not in other tissues.
messages: Interacts with beta-1 integrin subunit. This interaction is regulated by divalent cations, and it occurs only in absence of calcium.
messages: May play a role during maturation and/or organization of muscles cells.
messages: The tail domain binds to the cytoplasmic domain of both integrin beta-1a and beta-1d isoforms. The presence of Ca(2+) ions does not prevent binding of a fragment consisting of the second cysteine rich repeat and the tail domain but prevents the binding of the full-length protein.

9606:RNF149
gene id: 9606:RNF149
uniprot id: Q8NC42
names: Domain
names: Function
names: Subcellular Location Annotation
messages: E3 ubiquitin-protein ligase. Ubiquitinates BRAF, inducing its proteasomal degradation.
messages: Membrane
messages: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme.

9606:KRT3
gene id: 9606:KRT3
uniprot id: P12035
names: Disease Annotation
names: Miscellaneous
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Belongs to the intermediate filament family.
messages: Cornea specific.
messages: Heterotetramer of two type I and two type II keratins. Keratin-3 associates with keratin-12.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: There are two types of cytoskeletal and microfibrillar keratin: I (acidic; 40-55 kDa) and II (neutral to basic; 56-70 kDa).

9606:ZSCAN5A
gene id: 9606:ZSCAN5A
uniprot id: A0A0C4DGQ1
uniprot id: Q9BUG6
names: Function
names: Subcellular Location Annotation
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:PARP11
gene id: 9606:PARP11
uniprot id: Q9NR21
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
messages: Auto-mono-ADP-ribosylated.
messages: Belongs to the ARTD/PARP family.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Mono-ADP-ribosyltransferase that mediates mono-ADP-ribosylation of target proteins (PubMed:25043379, PubMed:25673562). Plays a role in nuclear envelope stability and nuclear remodeling during spermiogenesis (By similarity).
messages: nuclear pore complex

9606:DCTN4
gene id: 9606:DCTN4
uniprot id: A0A0S2Z5D4
uniprot id: Q9NSJ5
uniprot id: Q9UJW0
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the dynactin subunit 4 family.
messages: Part of the dynactin complex that activates the molecular motor dynein for ultra-processive transport along microtubules.
messages: Subunit of dynactin, a multiprotein complex part of a tripartite complex with dynein and a adapter, such as BICDL1, BICD2 or HOOK3. The dynactin complex is built around ACTR1A/ACTB filament and consists of an actin-related filament composed of a shoulder domain, a pointed end and a barbed end. Its length is defined by its flexible shoulder domain. The soulder is composed of 2 DCTN1 subunits, 4 DCTN2 and 2 DCTN3. The 4 DCNT2 (via N-terminus) bind the ACTR1A filament and act as molecular rulers to determine the length. The pointed end is important for binding dynein-dynactin cargo adapters. Consists of 4 subunits: ACTR10, DCNT4, DCTN5 and DCTN6. The barbed end is composed of a CAPZA1:CAPZB heterodimers, which binds ACTR1A/ACTB filament and dynactin and stabilizes dynactin (By similarity). Interacts with ATP7B, but not ATP7A, in a copper-dependent manner (PubMed:16554302). Interacts with ANK2; this interaction is required for localization at costameres (By similarity).
messages: cell cortex
messages: centrosome
messages: cytoskeleton
messages: sarcomere
messages: stress fiber

9606:EIF4E2
gene id: 9606:EIF4E2
uniprot id: A0A8I5KSA5
uniprot id: B8ZZ50
uniprot id: B8ZZL3
uniprot id: B9A023
uniprot id: O60573
uniprot id: Q53RG0
uniprot id: Q59FE1
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Upon SARS coronavirus-2/SARS-CoV-2 infection, the interaction with non-structural protein 2 (nsp2) with GIGYF2 enhances GIGYF2 binding to EIF4E2 and increases repression of translation initiation of genes involved in antiviral innate immune response such as IFNB1.
messages: Belongs to the eukaryotic initiation factor 4E family.
messages: Component of the 4EHP-GYF2 complex, a multiprotein complex that acts as a repressor of translation initiation (PubMed:22751931, PubMed:35878012). In association with GIGYF2, assists ribosome-associated quality control (RQC) by sequestering the mRNA cap, blocking ribosome initiation and decreasing the translational load on problematic messages. Part of a pathway that works in parallel to RQC-mediated degradation of the stalled nascent polypeptide. GIGYF2 and EIF4E2 work downstream and independently of ZNF598, which seems to work as a scaffold that can recruit them to faulty mRNA even if alternative recruitment mechanisms may exist (PubMed:32726578).
messages: Cytoplasm
messages: ISGylation enhances its cap structure-binding activity and translation-inhibition activity.
messages: Interacts with EIF4EBP1, EIF4EBP2 and EIF4EBP3 (PubMed:15153109, PubMed:17368478). Does not interact with eIF4G (EIF4G1, EIF4G2 or EIF4G3) (By similarity). Component of the 4EHP-GYF2 complex, at least composed of EIF4E2, GIGYF2 and ZNF598 (PubMed:22751931, PubMed:32726578). Interacts with GIGYF2 (via the 4EHP-binding motif); the interaction is direct (PubMed:22751931, PubMed:32726578, PubMed:33581076). Interacts with EIF4ENIF1/4E-T (via YXXXXLphi motif); increasing affinity for the 7-methylguanosine-containing mRNA cap (PubMed:23991149, PubMed:28487484).
messages: P-body
messages: Recognizes and binds the 7-methylguanosine-containing mRNA cap during an early step in the initiation. Acts as a repressor of translation initiation (PubMed:17368478, PubMed:22751931, PubMed:25624349, PubMed:33581076, PubMed:9582349). In contrast to EIF4E, it is unable to bind eIF4G (EIF4G1, EIF4G2 or EIF4G3), suggesting that it acts by competing with EIF4E and block assembly of eIF4F at the cap (By similarity). In P-bodies, component of a complex that promotes miRNA-mediated translational repression (PubMed:28487484). Involved in virus-induced host response by mediating miRNA MIR34A-induced translational silencing which controls IFNB1 production by a negative feedback mechanism (PubMed:28487484, PubMed:33581076).
messages: Ubiquitinated by ARIH1 (PubMed:14623119, PubMed:25624349). The consequences of ubiquitination are however unclear: according to a report, EIF4E2 ubiquitination leads to promote EIF4E2 cap-binding and protein translation arrest (PubMed:25624349). According to another report ubiquitination leads to its subsequent degradation (PubMed:14623119).

9606:AMIGO1
gene id: 9606:AMIGO1
uniprot id: Q86WK6
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the immunoglobulin superfamily. AMIGO family.
messages: Cell membrane
messages: Homodimer, and heterodimer with AMIGO2 and AMIGO3. Interacts with KCNB1.
messages: Perikaryon
messages: Promotes growth and fasciculation of neurites from cultured hippocampal neurons. May be involved in fasciculation as well as myelination of developing neural axons. May have a role in regeneration as well as neural plasticity in the adult nervous system. May mediate homophilic as well as heterophilic cell-cell interaction and contribute to signal transduction through its intracellular domain. Assembled with KCNB1 modulates the gating characteristics of the delayed rectifier voltage-dependent potassium channel KCNB1.
messages: The LRR repeat region mediates homodimerization.
messages: axon
messages: dendrite

9606:PSMB9
gene id: 9606:PSMB9
uniprot id: A0A1U9X8D7
uniprot id: P28065
names: Developmental Stage
names: Disease Annotation
names: Function
names: Induction
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Interacts with HIV-1 TAT protein.
messages: A model for self-activation in which residue Thr-21 serves as nucleophile and Lys-53 as proton donor/acceptor has been proposed. Subunit processing of mammalian beta-subunits proceeds via a novel ordered two-step mechanism involving autocatalysis.
messages: Autocleaved. The resulting N-terminal Thr residue of the mature subunit is responsible for the nucleophile proteolytic activity.
messages: Belongs to the peptidase T1B family.
messages: Component of the proteasome complex.
messages: Component of the proteasome, a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity.
messages: Cytoplasm
messages: Encoded in the MHC class II region.
messages: Highly expressed in immature dendritic cells (at protein level).
messages: Nucleus
messages: The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is composed of 28 subunits that are arranged in four stacked rings, resulting in a barrel-shaped structure. The two end rings are each formed by seven alpha subunits, and the two central rings are each formed by seven beta subunits. The catalytic chamber with the active sites is on the inside of the barrel. Component of the immunoproteasome, where it displaces the equivalent housekeeping subunit PSMB6. Component of the spermatoproteasome, a form of the proteasome specifically found in testis.
messages: The disease may be caused by variants affecting distinct genetic loci, including the gene represented in this entry.
messages: The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. This subunit is involved in antigen processing to generate class I binding peptides. Replacement of PSMB6 by PSMB9 increases the capacity of the immunoproteasome to cleave model peptides after hydrophobic and basic residues.
messages: Up-regulated by interferon gamma (at protein level). Up-regulated by IRF1. Up-regulated by tumor necrosis factor-alpha (at protein level). Up-regulated by tetrodotoxin (TTX) in glial cells. Up-regulated in Crohn's bowel disease (CD). Up-regulated by heat shock treatment. Up-regulated by CD40L via the NFKB1 pathway in cancer cells.

9606:KGD4
gene id: 9606:KGD4
uniprot id: P82909
names: Caution
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: May be necessary to recruit DLD/E3 to the mitochondrial 2-oxoglutarate dehydrogenase complex (OGDC) core composed of OGDH/E1-DLST/E2, hence stabilizes the complex.
messages: Mitochondrion
messages: Probable component of the 2-oxoglutarate dehydrogenase complex (OGDC), composed of OGDH (2-oxoglutarate dehydrogenase; also called E1 subunit), DLST (dihydrolipoamide succinyltransferase; also called E2 subunit) and DLD (dihydrolipoamide dehydrogenase; also called E3 subunit). Within OGDC, may interact (via N-terminus) with E3 subunit and (via C-terminus) with the complex core formed by E1 and E2 subunits.
messages: Was originally identified in the small subunit (28S) of mitochondrial ribosomes that were purified on sucrose gradients (By similarity). This observation has been challenged by experiments showing MRPS36 copurification with the oxoglutarate dehydrogenase complex (OGDC), also called alpha-ketoglutarate dehydrogenase complex (KGDH). Both mitochondrial ribosome 28S subunit and OGDC have a similar size and OGDC is highly abundant, therefore OGDC has been found to contaminate ribosomal preparations performed by sequential centrifugation steps (By similarity). In addition, MRPS36 could not be located in the structure of the human mitochondrial ribosome, supporting the hypothesis that it is not a mitoribosomal protein (PubMed:25838379).

9606:PDE6C
gene id: 9606:PDE6C
uniprot id: P51160
names: Cofactor
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: As cone-specific cGMP phosphodiesterase, it plays an essential role in light detection and cone phototransduction by rapidly decreasing intracellular levels of cGMP.
messages: Belongs to the cyclic nucleotide phosphodiesterase family.
messages: Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions.
messages: Cell membrane
messages: Composed of two alpha' subunits that are associated with 3 smaller proteins of 11, 13, and 15 kDa.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:SNU13
gene id: 9606:SNU13
uniprot id: P55769
uniprot id: Q6FHM6
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the eukaryotic ribosomal protein eL8 family.
messages: Common component of the spliceosome and rRNA processing machinery.
messages: Identified in the spliceosome B complex (PubMed:28781166). Component of the U4/U6-U5 tri-snRNP complex composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, WDR57, SNRNP40, DDX23, CD2BP2, PPIH, NHP2L1, EFTUD2, SART1 and USP39 (PubMed:16723661, PubMed:26912367). Interacts with RAD17 and PRPF31 (PubMed:10593953, PubMed:17412961, PubMed:21784869). The complex formed by SNU13 and PRPF31 binds U4 snRNA (PubMed:17412961). The complex formed by SNU13 and PRPF31 binds also U4atac snRNA, a characteristic component of specific, less abundant spliceosomal complexes (PubMed:21784869). Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3 (PubMed:34516797).
messages: Nucleus
messages: Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797). Involved in pre-mRNA splicing as component of the spliceosome (PubMed:28781166). Binds to the 5'-stem-loop of U4 snRNA and thereby contributes to spliceosome assembly (PubMed:10545122, PubMed:17412961). The protein undergoes a conformational change upon RNA-binding (PubMed:17412961, PubMed:10545122, PubMed:28781166).
messages: Ubiquitous.
messages: nucleolus

9606:PHC1
gene id: 9606:PHC1
uniprot id: P78364
uniprot id: Q6GMQ3
uniprot id: Q6N083
names: Disease Annotation
names: Function
names: Miscellaneous
names: Subcellular Location Annotation
names: Subunit
messages: Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility. Required for proper control of cellular levels of GMNN expression.
messages: Homodimer. Component of a PRC1-like complex (PubMed:12167701, PubMed:19636380, PubMed:21282530). Interacts with RNF2 and CBX7 (By similarity). Interacts with PHC2, PHC2 and BMI1 (By similarity).
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The hPRC-H complex purification reported by PubMed:12167701 probably presents a mixture of different PRC1-like complexes.

9606:APOM
gene id: 9606:APOM
uniprot id: A0A1U9X793
uniprot id: O95445
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the calycin superfamily. Lipocalin family. Highly divergent.
messages: Interacts with LRP2; LRP2 mediates APOM renal uptake and subsequent lysosomal degradation.
messages: Plasma protein. Expressed in liver and kidney.
messages: Probably involved in lipid transport. Can bind sphingosine-1-phosphate, myristic acid, palmitic acid and stearic acid, retinol, all-trans-retinoic acid and 9-cis-retinoic acid.
messages: Secreted

9606:SNTG2
gene id: 9606:SNTG2
uniprot id: Q9NY99
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Adapter protein that binds to and probably organizes the subcellular localization of a variety of proteins. May link various receptors to the actin cytoskeleton and the dystrophin glycoprotein complex (By similarity).
messages: Belongs to the syntrophin family.
messages: Interacts with the dystrophin protein DMD and related proteins DTNA and DTNB.
messages: The association with dystrophin or related proteins probably leaves the PDZ domain available to recruit proteins to the membrane.
messages: Widely expressed. Strong expression in brain and testis. In CNS, it is expressed in the perikaryon and proximal portion of the neuronal processes. Strong expression in the hippocampus, neuron-rich dendate granule cells, and pyramidal cell layers. Highly expressed in neurons of the cerebral cortex. Also expressed in the cerebellar cortex, deep cerebellar nuclei, thalamus, and basal ganglia.
messages: cytoskeleton
messages: sarcolemma

9606:DYNC1LI2
gene id: 9606:DYNC1LI2
uniprot id: O43237
uniprot id: Q63HJ8
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. May play a role in binding dynein to membranous organelles or chromosomes.
messages: Belongs to the dynein light intermediate chain family.
messages: Homodimer. The cytoplasmic dynein 1 complex consists of two catalytic heavy chains (HCs) and a number of non-catalytic subunits presented by intermediate chains (ICs), light intermediate chains (LICs) and light chains (LCs); the composition seems to vary in respect to the IC, LIC and LC composition. The heavy chain homodimer serves as a scaffold for the probable homodimeric assembly of the respective non-catalytic subunits. The ICs and LICs bind directly to the HC dimer and the LCs assemble on the IC dimer. Interacts with DYNC1H1; DYNC1LI1 and DYNC1LI2 bind mutually exclusive to DYNC1H.
messages: Homodimer. The cytoplasmic dynein 1 complex consists of two catalytic heavy chains (HCs) and a number of non-catalytic subunits presented by intermediate chains (ICs).
messages: cytoskeleton

9606:OR2A25
gene id: 9606:OR2A25
uniprot id: A0A126GVV5
uniprot id: A4D2G3
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Membrane
messages: Odorant receptor.

9606:PLIN3
gene id: 9606:PLIN3
uniprot id: A0A140VJN8
uniprot id: O60664
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the perilipin family.
messages: Cytoplasm
messages: Endosome membrane
messages: Homooligomer (PubMed:9590177). Interacts with M6PR (via the cytoplasmic domain) (PubMed:9590177). Interacts with IGF2R (via the cytoplasmic domain) (PubMed:9590177).
messages: Lipid droplet
messages: May exist as a homodimer.
messages: Phosphorylation at Tyr-251 by isoform 1 of CHKA (CHKalpha2) promotes dissociation from lipid droplets: dissociation is followed by recruitment of autophagosome machinery to lipid droplets and subsequent lipid droplet lipolysis.
messages: Structural component of lipid droplets, which is required for the formation and maintenance of lipid storage droplets (PubMed:34077757). Required for the transport of mannose 6-phosphate receptors (MPR) from endosomes to the trans-Golgi network (PubMed:9590177).

9606:CHRNA4
gene id: 9606:CHRNA4
uniprot id: P43681
uniprot id: Q4VAQ3
uniprot id: Q59FV0
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane permeable to sodium ions.
messages: Belongs to the ligand-gated ion channel (TC 1.A.9) family.
messages: Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Alpha-4/CHRNA4 sub-subfamily.
messages: Cell membrane
messages: Membrane
messages: Neuronal AChR is composed of two different types of subunits: alpha and beta. Alpha-4 subunit can be combined to beta-2 or beta-4 to give rise to functional receptors, complexes with beta-2 may be heteropentamers (PubMed:22361591). Interacts with RIC3; which is required for proper folding and assembly (PubMed:16120769). Interacts with LYPD6 (PubMed:27344019). The heteropentamer alpha-4-beta-2 interacts with alpha-conotoxins PnIA, GID and MII (By similarity).
messages: Postsynaptic cell membrane
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:HSD17B13
gene id: 9606:HSD17B13
uniprot id: Q7Z5P4
names: Function
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the short-chain dehydrogenases/reductases (SDR) family.
messages: Cytoplasm
messages: Does not have retinol/retinal dehydrogenase activity in vitro.
messages: Endoplasmic reticulum
messages: Has retinol/retinal dehydrogenase activity in vitro.
messages: Highly expressed in the liver (PubMed:29562163). Also detected in ovary, bone marrow, kidney, brain, lung, skeletal muscle, bladder and testis.
messages: Lipid droplet
messages: Plays a pivotal role in hepatic lipid metabolism (PubMed:29562163). In vitro, it catalyzes the oxidation of a variety of lipid substrates, including 17beta-estradiol, retinol, retinal, and leukotriene B4 (PubMed:29562163, PubMed:30415504, PubMed:32973038).
messages: The insertion of an adenine adjacent to the donor splice site of exon 6 (dbSNP:rs72613567) is associated with reduced risk of non-alcoholic fatty liver disease and protection from chronic liver disease [MIM:620116]. It is also associated with reduced risk of hepatocellular carcinoma (PubMed:29562163, PubMed:34930143). Variant rs72613567 alters mRNA splicing and results in the synthesis of a truncated, unstable protein. Liver samples from variant carriers contain reduced levels of isoform 1 and isoform 2 transcripts (PubMed:29562163).

9606:ARNT
gene id: 9606:ARNT
uniprot id: P27540
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Monomer. Homodimer only upon binding to a DNA (By similarity). Efficient DNA binding requires dimerization with another bHLH protein. Interacts with TACC3 (By similarity). Interacts with HIF1A, EPAS1, NPAS1 and NPAS3; forms a heterodimer that binds core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters (PubMed:20699359, PubMed:16181639) (By similarity). Forms a heterodimer with AHRR, as well as with other bHLH proteins (Probable). Interacts with NOCA7 (PubMed:10395741). Interacts with TACC3 (By similarity). Interacts with AHR; the heterodimer ARNT:AHR binds to core DNA sequence 5'-TGCGTG-3' within the dioxin response element (DRE) of target gene promoters and activates their transcription (PubMed:28396409, PubMed:34521881). Interacts with SIM1 and NPAS4 (By similarity).
messages: Nucleus
messages: Required for activity of the AHR. Upon ligand binding, AHR translocates into the nucleus, where it heterodimerizes with ARNT and induces transcription by binding to xenobiotic response elements (XRE). Not required for the ligand-binding subunit to translocate from the cytosol to the nucleus after ligand binding (PubMed:34521881). The complex initiates transcription of genes involved in the regulation of a variety of biological processes, including angiogenesis, hematopoiesis, drug and lipid metabolism, cell motility and immune modulation (Probable). The heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters and functions as a transcriptional regulator of the adaptive response to hypoxia (By similarity). The heterodimer ARNT:AHR binds to core DNA sequence 5'-TGCGTG-3' within the dioxin response element (DRE) of target gene promoters and activates their transcription (PubMed:28396409).

9606:MARCHF5
gene id: 9606:MARCHF5
uniprot id: Q9NX47
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Autoubiquitinated leading to degradation (short half-life).
messages: By binding to and ubiquitinating two ALS1 variants of SOD1 (mSOD1 variants Arg-86 and Ala-94) it attenuates their cytotoxicity.
messages: Endoplasmic reticulum membrane
messages: Expressed in brain, heart, liver, lung, spleen, stomach, testis, skeletal and muscle.
messages: Mitochondrial E3 ubiquitin-protein ligase that plays a crucial role in the control of mitochondrial morphology by acting as a positive regulator of mitochondrial fission. May play a role in the prevention of cell senescence acting as a regulator of mitochondrial quality control. Promotes ubiquitination of FIS1, DNM1L and MFN1.
messages: Mitochondrion outer membrane
messages: Monomer and homodimer. Interacts with MFN1, MFN2, DNM1L and FIS1.
messages: The RING-CH-type zinc finger domain is required for E3 ligase activity.

9606:VCL
gene id: 9606:VCL
uniprot id: B3KXA2
uniprot id: P18206
uniprot id: V9HWK2
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts via its globular head domain with the central portion of S.flexneri IcsA (also called VirG).
messages: Acetylated; mainly by myristic acid but also by a small amount of palmitic acid.
messages: Actin filament (F-actin)-binding protein involved in cell-matrix adhesion and cell-cell adhesion. Regulates cell-surface E-cadherin expression and potentiates mechanosensing by the E-cadherin complex. May also play important roles in cell morphology and locomotion.
messages: Belongs to the vinculin/alpha-catenin family.
messages: Cell membrane
messages: Exhibits self-association properties. Part of a complex composed of THSD1, PTK2/FAK1, TLN1 and VCL (PubMed:29069646). Interacts with APBB1IP and NRAP (By similarity). Interacts with TLN1. Interacts with CTNNB1 and this interaction is necessary for its localization to the cell-cell junctions and for its function in regulating cell surface expression of E-cadherin (By similarity). Interacts with SYNM. Interacts with SORBS1 (By similarity). Interacts with CTNNA1 (PubMed:26691986). Binds to ACTN4; this interaction triggers conformational changes (PubMed:15988023).
messages: Exists in at least two conformations. When in the closed, 'inactive' conformation, extensive interactions between the head and tail domains prevent detectable binding to most of its ligands. It takes on an 'active' conformation after cooperative and simultaneous binding of two different ligands. This activation involves displacement of the head-tail interactions and leads to a significant accumulation of ternary complexes. The active form then binds a number of proteins that have both signaling and structural roles that are essential for cell adhesion.
messages: Membrane
messages: Metavinculin is muscle-specific.
messages: Phosphorylated; on serines, threonines and tyrosines. Phosphorylation on Tyr-1133 in activated platelets affects head-tail interactions and cell spreading but has no effect on actin binding nor on localization to focal adhesion plaques (By similarity).
messages: The N-terminal globular head (Vh) comprises of subdomains D1-D4. The C-terminal tail (Vt) binds F-actin and cross-links actin filaments into bundles. In isoform 2 (metavinculin) a 68 residue insertion in the tail domain promotes actin severing instead of bundling. An intramolecular interaction between Vh and Vt masks the F-actin-binding domain located in Vt. The binding of talin and alpha-actinin to the D1 subdomain of vinculin induces a helical bundle conversion of this subdomain, leading to the disruption of the intramolecular interaction and the exposure of the cryptic F-actin-binding domain of Vt. Vt inhibits actin filament barbed end elongation without affecting the critical concentration of actin assembly.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: adherens junction
messages: cytoskeleton
messages: focal adhesion
messages: podosome
messages: sarcolemma

9606:ACD
gene id: 9606:ACD
uniprot id: Q96AP0
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Component of the shelterin complex (telosome) composed of TERF1, TERF2, TINF2, TERF2IP ACD and POT1. Forms heterodimers with POT1. Identified in a complex with POT1 and single-stranded telomeric DNA. Interacts with STN1 and TINF2.
messages: Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection. Shelterin associates with arrays of double-stranded TTAGGG repeats added by telomerase and protects chromosome ends. Without its protective activity, telomeres are no longer hidden from the DNA damage surveillance and chromosome ends are inappropriately processed by DNA repair pathways. Promotes binding of POT1 to single-stranded telomeric DNA. Modulates the inhibitory effects of POT1 on telomere elongation. The ACD-POT1 heterodimer enhances telomere elongation by recruiting telomerase to telomeres and increasing its processivity. May play a role in organogenesis.
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: telomere

9606:NRDC
gene id: 9606:NRDC
uniprot id: G3V1R5
uniprot id: O43847
uniprot id: Q6UUU9
names: Cofactor
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the peptidase M16 family.
messages: Binds 1 zinc ion per subunit.
messages: Cleaves peptide substrates on the N-terminus of arginine residues in dibasic pairs. Is a critical activator of BACE1- and ADAM17-mediated pro-neuregulin ectodomain shedding, involved in the positive regulation of axonal maturation and myelination. Required for proper functioning of 2-oxoglutarate dehydrogenase (OGDH) (By similarity).
messages: Interacts with BACE1 and NRG1.
messages: Mitochondrion
messages: Primarily in adult heart, skeletal muscle, and testis and at much lower levels in other tissues.
messages: dendrite

9606:OR52E6
gene id: 9606:OR52E6
uniprot id: A0A126GVK5
uniprot id: Q96RD3
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Membrane
messages: Odorant receptor.

9606:ZNF316
gene id: 9606:ZNF316
uniprot id: A6NFI3
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:HDGFL2
gene id: 9606:HDGFL2
uniprot id: Q7Z4V5
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acts as an epigenetic regulator of myogenesis in cooperation with DPF3a (isoform 2 of DPF3/BAF45C) (PubMed:32459350). Associates with the BAF complex via its interaction with DPF3a and HDGFL2-DPF3a activate myogenic genes by increasing chromatin accessibility through recruitment of SMARCA4/BRG1/BAF190A (ATPase subunit of the BAF complex) to myogenic gene promoters (PubMed:32459350). Promotes the repair of DNA double-strand breaks (DSBs) through the homologous recombination pathway by facilitating the recruitment of the DNA endonuclease RBBP8 to the DSBs (PubMed:26721387). Preferentially binds to chromatin regions marked by H3K9me3, H3K27me3 and H3K36me2 (PubMed:26721387, PubMed:32459350). Involved in cellular growth control, through the regulation of cyclin D1 expression (PubMed:25689719).
messages: Belongs to the HDGF family.
messages: Cytoplasm
messages: Interacts with HDGF (By similarity). Interacts with trimethylated 'Lys-36' of histone H3 (H3K36me3). Interacts with trimethylated 'Lys-79' of histone H3 (H3K79me3), but has higher affinity for H3K36me3. Interacts with IWS1 (PubMed:25689719). Interacts with H2AX, POGZ, RBBP8 and CBX1 (PubMed:26721387). Interacts with histones H3K9me3, H3K27me3 and H3K36me2 (PubMed:26721387, PubMed:32459350). Interacts with DPF3a (isoform 2 of DPF3/BAF45C) (PubMed:32459350). Interacts with SMARCA4/BRG1/BAF190A, SMARCC1/BAF155 and SMARCD1/BAF60A in a DPF3a-dependent manner (PubMed:32459350).
messages: Nucleus
messages: Widely expressed. High expression is found in heart, skeletal muscle, ovary and testis. Overexpression is frequently observed in hepatocellular carcinoma samples.

9606:P3H1
gene id: 9606:P3H1
uniprot id: Q32P28
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
messages: Basement membrane-associated chondroitin sulfate proteoglycan (CSPG). Has prolyl 3-hydroxylase activity catalyzing the post-translational formation of 3-hydroxyproline in -Xaa-Pro-Gly- sequences in collagens, especially types IV and V. May be involved in the secretory pathway of cells. Has growth suppressive activity in fibroblasts.
messages: Belongs to the leprecan family.
messages: Endoplasmic reticulum
messages: O-glycosylated; chondroitin sulfate.
messages: The disease is caused by variants affecting the gene represented in this entry. A splice site mutation leading to the absence of isoform 1 has been reported in 2 OI8 patients. Isoform 1 is the only form predicted to be located in the endoplasmic reticulum, which the appropriate location for the catalysis of collagen hydroxylation. These patients show indeed severely reduced COL1A1 hydroxylation (PubMed:19088120).
messages: extracellular matrix

9606:KRT25
gene id: 9606:KRT25
uniprot id: Q7Z3Z0
names: Disease Annotation
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the intermediate filament family.
messages: Cytoplasm
messages: Essential for the proper assembly of type I and type II keratin protein complexes and formation of keratin intermediate filaments in the inner root sheath (irs) (By similarity). Plays a role in the cytoskeleton organization (PubMed:26902920).
messages: Heterodimer of a type I and a type II keratin (PubMed:26902920). Heterodimer with type II keratin KRT5 leading to the formation of keratin intermediate filament (KIF) network (PubMed:28899683). Interacts with KRT6A to form filaments (By similarity).
messages: Strongly expressed in skin and scalp, and weak expression observed in thymus and tongue. In the hair follicle, expressed in Henle layer, Huxley layer and in the inner root sheath cuticle of the hair follicle. Expression extends from the bulb region up to the point of differentiation into the three layers. Also present in the medulla of beard hair (at protein level).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: There are two types of cytoskeletal and microfibrillar keratin: I (acidic; 40-55 kDa) and II (neutral to basic; 56-70 kDa).

9606:NUP153
gene id: 9606:NUP153
uniprot id: P49790
names: Cofactor
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Binds HIV-2 protein vpx and thereby promotes the nuclear translocation of the lentiviral genome (in vitro).
messages: (Microbial infection) FG repeats mediates interaction with HIV-1 capsid protein p24 (CA).
messages: (Microbial infection) Interacts (via C-terminus) with HIV-1 capsid protein p24 (CA) (via N-terminus).
messages: (Microbial infection) Interacts with Epstein-barr virus BGLF4; this interaction allows BGLF4 nuclear entry.
messages: (Microbial infection) Interacts with HIV-1 caspid protein P24 and thereby promotes the integration of the virus in the nucleus of non-dividing cells (in vitro).
messages: (Microbial infection) Interacts with HIV-1 integrase; this interaction might play a role in nuclear import of HIV pre-integration complex.
messages: (Microbial infection) Interacts with HIV-2 virus protein vpx; this interaction might promote vpx nuclear entry.
messages: (Microbial infection) Interacts with hepatitis B virus capsid protein; this interaction probably plays a role in nuclear import of HBV genome.
messages: Belongs to the NUP153 family.
messages: Binds at least 4 zinc ions per subunit.
messages: Component of the nuclear pore complex (NPC), a complex required for the trafficking across the nuclear envelope. Functions as a scaffolding element in the nuclear phase of the NPC essential for normal nucleocytoplasmic transport of proteins and mRNAs. Involved in the quality control and retention of unspliced mRNAs in the nucleus; in association with TPR, regulates the nuclear export of unspliced mRNA species bearing constitutive transport element (CTE) in a NXF1- and KHDRBS1-independent manner. Mediates TPR anchoring to the nuclear membrane at NPC. The repeat-containing domain may be involved in anchoring other components of the NPC to the pore membrane. Possible DNA-binding subunit of the nuclear pore complex (NPC).
messages: Contains FG repeats. FG repeats are interaction sites for karyopherins (importins, exportins) and form probably an affinity gradient, guiding the transport proteins unidirectionally with their cargo through the NPC. FG repeat regions are highly flexible and lack ordered secondary structure. The overall conservation of FG repeats regarding exact sequence, spacing, and repeat unit length is limited.
messages: Interacts with RAN; the interaction occurs in a GTP- and GDP-independent manner (By similarity). Part of the nuclear pore complex (NPC). Interacts with TPR (via coiled coil region); the interaction is direct and provides a link between the core structure and the TPR-containing nuclear basket of the nuclear pore complex (NPC). Interacts with HIKESHI, SENP2 and XPO5. Interacts with MCM3AP isoform GANP; this interaction is required for GANP localization at the nuclear pore complex (PubMed:20005110, PubMed:23652018).
messages: Nucleus
messages: Nucleus membrane
messages: O-glycosylated during cytokinesis at sites identical or close to phosphorylation sites, this interferes with the phosphorylation status.
messages: Phosphorylated in interphase, hyperphosphorylated during mitosis. May play a role in the reversible disassembly of the nuclear pore complex during mitosis (By similarity).
messages: Proteolytically degraded after poliovirus (PV) infection; degradation is partial and NCP- and TPR-binding domains withstand degradation.
messages: nuclear pore complex

9606:CLPS
gene id: 9606:CLPS
uniprot id: A0A087WZW1
uniprot id: P04118
names: Function
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the colipase family.
messages: Colipase is a cofactor of pancreatic lipase. It allows the lipase to anchor itself to the lipid-water interface. Without colipase the enzyme is washed off by bile salts, which have an inhibitory effect on the lipase.
messages: Enterostatin has a biological activity as a satiety signal.
messages: Expressed by the pancreas.
messages: Forms a 1:1 stoichiometric complex with pancreatic lipase.
messages: Secreted
messages: Variant Cys-109 is statistically significantly associated with an increased risk of type 2 diabetes.

9606:HSD3B7
gene id: 9606:HSD3B7
uniprot id: Q9H2F3
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the 3-beta-HSD family.
messages: Endoplasmic reticulum membrane
messages: The 3-beta-HSD enzymatic system plays a crucial role in the biosynthesis of all classes of hormonal steroids. HSD VII is active against four 7-alpha-hydroxylated sterols. Does not metabolize several different C(19/21) steroids as substrates. Involved in bile acid synthesis (PubMed:11067870). Plays a key role in cell positioning and movement in lymphoid tissues by mediating degradation of 7-alpha,25-dihydroxycholesterol (7-alpha,25-OHC): 7-alpha,25-OHC acts as a ligand for the G protein-coupled receptor GPR183/EBI2, a chemotactic receptor for a number of lymphoid cells.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:DLG2
gene id: 9606:DLG2
uniprot id: Q15700
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: An N-terminally truncated L27 domain is predicted in isoform 2 at positions 1 through 27.
messages: Belongs to the MAGUK family.
messages: Cell membrane
messages: Interacts through its PDZ domains with NETO1 (By similarity). Interacts with NOS1/nNOS through second PDZ domain (By similarity). Interacts with KCNJ2/Kir2.1 (via C-terminus) through one of its PDZ domains (PubMed:15304517). Interacts with KCNJ4 (By similarity), Interacts with FRMPD4 (via C-terminus) (PubMed:19118189). Interacts with LRFN1, LRFN2 and LRFN4 (PubMed:16630835). Interacts with FASLG (PubMed:19807924). Interacts with KCNJ4 (By similarity). Interacts with ADAM22 (By similarity). Interacts with DGKI (via PDZ-binding motif) (By similarity).
messages: Membrane
messages: Palmitoylation of isoform 1 is not required for targeting to postsynaptic density.
messages: Perikaryon
messages: Postsynaptic density
messages: Required for perception of chronic pain through NMDA receptor signaling. Regulates surface expression of NMDA receptors in dorsal horn neurons of the spinal cord. Interacts with the cytoplasmic tail of NMDA receptor subunits as well as inward rectifying potassium channels. Involved in regulation of synaptic stability at cholinergic synapses. Part of the postsynaptic protein scaffold of excitatory synapses (By similarity).
messages: Synapse
messages: axon

9606:WASL
gene id: 9606:WASL
uniprot id: O00401
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Interacts with E.coli effector protein EspF(U) (PubMed:19366662, PubMed:22921828). Identified in a complex containing at least WASL, BAIAP2L1 and E.coli EspF(U) (PubMed:22921828).
messages: (Microbial infection) Interacts with Shigella flexneri protein IcsA (PubMed:9582270, PubMed:10491394). The interaction with IcsA enhances the affinity of WASL for Arp2/3, thus assembling a tight complex which has maximal activity in actin assembly (PubMed:9582270, PubMed:10491394).
messages: Binds actin and the Arp2/3 complex (PubMed:22847007). Interacts with CDC42 (PubMed:9422512). Interacts with FCHSD1 (By similarity). Interacts with FCHSD2 (PubMed:29887380). Binds to SH3 domains of GRB2. Interacts with the C-terminal SH3 domain of DNMBP (PubMed:19767742, PubMed:24332715, PubMed:17015620). Interacts with SNX9 (By similarity). Interacts with the WW domains of PRPF40A/FBP11 (By similarity). Interacts with PTK2/FAK1 (By similarity). Interacts with PACSIN1, PACSIN2 and PACSIN3 (By similarity). Interacts with NOSTRIN (PubMed:16234328). Binds to TNK2 (PubMed:16257963). Interacts with SNX33 (PubMed:19487689). Interacts with NONO (via second RRM domain); the interaction is direct (PubMed:16767080). Component of a multiprotein complex with NONO and SFPQ; associates with the complex via direct interaction with NONO (PubMed:16767080).
messages: Cytoplasm
messages: Nucleus
messages: Phosphorylation at Ser-242, Tyr-256, Ser-484 and Ser-485 enhances actin polymerization activity.
messages: Regulates actin polymerization by stimulating the actin-nucleating activity of the Arp2/3 complex (PubMed:9422512, PubMed:16767080, PubMed:19366662, PubMed:19487689, PubMed:22847007, PubMed:22921828). Involved in various processes, such as mitosis and cytokinesis, via its role in the regulation of actin polymerization (PubMed:9422512, PubMed:19366662, PubMed:19487689, PubMed:22847007, PubMed:22921828). Together with CDC42, involved in the extension and maintenance of the formation of thin, actin-rich surface projections called filopodia (PubMed:9422512). In addition to its role in the cytoplasm, also plays a role in the nucleus by regulating gene transcription, probably by promoting nuclear actin polymerization (PubMed:16767080). Binds to HSF1/HSTF1 and forms a complex on heat shock promoter elements (HSE) that negatively regulates HSP90 expression (By similarity). Plays a role in dendrite spine morphogenesis (By similarity). Decreasing levels of DNMBP (using antisense RNA) alters apical junction morphology in cultured enterocytes, junctions curve instead of being nearly linear (PubMed:19767742).
messages: cytoskeleton

9606:RPS10-NUDT3
gene id: 9606:RPS10-NUDT3
uniprot id: A0A1W2PQS6
names: Similarity
messages: Belongs to the Nudix hydrolase family. DIPP subfamily.
messages: Belongs to the eukaryotic ribosomal protein eS10 family.

9606:PTH2
gene id: 9606:PTH2
uniprot id: Q96A98
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the parathyroid hormone family.
messages: Highly expressed in fetal and adult brain, cerebellum and trachea. Weakly expressed in spinal cord, fetal liver, kidney and heart.
messages: Ligand of high affinity for the PTH2 receptor (PTH2R).
messages: Plays a role as a potent and selective agonist of PTH2R resulting in adenyl cyclase activation and intracellular calcium levels elevation. Induces protein kinase C beta activation, recruitment of beta-arrestin and PTH2R internalization. May inhibit cell proliferation via its action on PTH2R activation. Neuropeptide which may also have a role in spermatogenesis. May activate nociceptors and nociceptive circuits.
messages: Secreted

9606:CLN3
gene id: 9606:CLN3
uniprot id: B4DFF3
uniprot id: B4DMY6
uniprot id: Q13286
uniprot id: Q2TA70
names: Caution
names: Disease Annotation
names: Domain
names: Function
names: Induction
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the battenin family.
messages: Cell membrane
messages: Early endosome membrane
messages: Expressed in the cortical brain, pancreas, spleen, and testis with weaker expression in the peripheral nerve (at protein level). Highly expressed in gray matter (at protein level).
messages: Farnesylation is important for trafficking to lysosomes.
messages: Golgi apparatus
messages: Golgi apparatus membrane
messages: Golgi stack
messages: Highly glycosylated.
messages: Homooligomer (By similarity). Interacts with DCTN1, KIF3A, RAB7A and RILP (PubMed:22261744). Interacts with CLN5 (PubMed:19941651, PubMed:14699076). May interact with HOOK1 (PubMed:15471887). Interacts with KCNIP3; this interaction is disrupted by intracellular increase of calcium level (PubMed:17189291). Interacts with TPP1, CLN6 and CLN8 (PubMed:17237713). Interacts with MYH10; this interaction may play a role in regulation of cytoskeleton organization (PubMed:20850431). Interacts with SBDS (PubMed:20015955). Interacts with sodium/potassium-transporting ATPase complex (via ATP1A1) and fodrin heteromer (via SPTAN1); this interaction regulates their localization at the plasma membrane (Probable). Interacts with HSPA5 (Probable). Interacts (via dileucine motif) with AP3D1 and AP1G1; this interaction facilitates lysosomal targeting (PubMed:15598649). Interacts (via dileucine motif) with AP2A2 (PubMed:15598649).
messages: Increased by osmotic stress.
messages: Late endosome
messages: Late endosome membrane
messages: Lysosome
messages: Lysosome membrane
messages: Mao et al suggest that CLN3 has five transmembranes with a long lumenal N-terminus because their antibody does not immunoprecipitate the N-terminus in the presence of microsomes.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Mediates microtubule-dependent, anterograde transport connecting the Golgi network, endosomes, autophagosomes, lysosomes and plasma membrane, and participates in several cellular processes such as regulation of lysosomal pH, lysosome protein degradation, receptor-mediated endocytosis, autophagy, transport of proteins and lipids from the TGN, apoptosis and synaptic transmission (PubMed:10924275, PubMed:18817525, PubMed:18317235, PubMed:22261744, PubMed:15471887, PubMed:20850431). Facilitates the proteins transport from trans-Golgi network (TGN)-to other membrane compartments such as transport of microdomain-associated proteins to the plasma membrane, IGF2R transport to the lysosome where it regulates the CTSD release leading to regulation of CTSD maturation and thereby APP intracellular processing (PubMed:10924275, PubMed:18817525). Moreover regulates CTSD activity in response to osmotic stress (PubMed:23840424, PubMed:28390177). Also binds galactosylceramide and transports it from the trans Golgi to the rafts, which may have immediate and downstream effects on cell survival by modulating ceramide synthesis (PubMed:18317235). At the plasma membrane, regulates actin-dependent events including filopodia formation, cell migration, and pinocytosis through ARF1-CDC42 pathway and also the cytoskeleton organization through interaction with MYH10 and fodrin leading to the regulation of the plasma membrane association of Na+, K+ ATPase complex (PubMed:20850431). Regulates synaptic transmission in the amygdala, hippocampus, and cerebellum through regulation of synaptic vesicles density and their proximity to active zones leading to modulation of short-term plasticity and age-dependent anxious behavior, learning and memory (By similarity). Regulates autophagic vacuoles (AVs) maturation by modulating the trafficking between endocytic and autophagolysosomal/lysosomal compartments, which involves vesicle fusion leading to regulation of degradation process (By similarity). Particip…
messages: Membrane
messages: Membrane raft
messages: Phosphorylated on both serine and threonine residues by PKA, PKG and CK2.
messages: Recycling endosome
messages: The C-terminal (153-438) mediates KCNIP3 interaction and the cytoprotective activity (PubMed:17189291). the dileucine motif mediates AP1G1 and AP3D1 interaction (PubMed:15598649).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: autophagosome
messages: caveola
messages: synaptosome
messages: trans-Golgi network

9606:ZSCAN4
gene id: 9606:ZSCAN4
uniprot id: Q8NAM6
names: Function
names: Subcellular Location Annotation
messages: Embryonic stem (ES) cell-specific transcription factor required to regulate ES cell pluripotency. Binds telomeres and plays a key role in genomic stability in ES cells by regulating telomere elongation. Acts as an activator of spontaneous telomere sister chromatid exchange (T-SCE) and telomere elongation in undifferentiated ES cells (By similarity).
messages: Nucleus
messages: telomere

9606:MNS1
gene id: 9606:MNS1
uniprot id: B3KQ70
uniprot id: Q8NEH6
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Able to form oligomers (By similarity). Interacts with ODAD1 (PubMed:30148830).
messages: Belongs to the MNS1 family.
messages: Expressed in nasal respiratory epithelium and in the sperm.
messages: Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating (PubMed:36191189). May play a role in the control of meiotic division and germ cell differentiation through regulation of pairing and recombination during meiosis. Required for sperm flagella assembly (By similarity). May play a role in the assembly and function of the outer dynein arm-docking complex (ODA-DC). ODA-DC mediates outer dynein arms (ODA) binding onto the axonemal doublet microtubules (PubMed:30148830).
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: cilium axoneme
messages: flagellum axoneme

9606:MSH3
gene id: 9606:MSH3
uniprot id: P20585
names: Disease Annotation
names: Function
names: Sequence Caution
names: Similarity
names: Subunit
messages: Belongs to the DNA mismatch repair MutS family. MSH3 subfamily.
messages: Component of the DNA mismatch repair (MMR) complex composed at least of MSH2, MSH3, MSH6, PMS1 and MLH1 (PubMed:26300262). Heterodimer consisting of MSH2-MSH3 (MutS beta) (PubMed:8942985). Forms a ternary complex with MutL alpha (MLH1-PMS1). Interacts with EXO1 (PubMed:11427529). Interacts with MCM9 (PubMed:26300262).
messages: Component of the post-replicative DNA mismatch repair system (MMR). Heterodimerizes with MSH2 to form MutS beta which binds to DNA mismatches thereby initiating DNA repair. When bound, the MutS beta heterodimer bends the DNA helix and shields approximately 20 base pairs. MutS beta recognizes large insertion-deletion loops (IDL) up to 13 nucleotides long. After mismatch binding, forms a ternary complex with the MutL alpha heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis.
messages: Contaminating sequence. Potential poly-A sequence.
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:SHC1
gene id: 9606:SHC1
uniprot id: P29353
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts with herpes simplex virus 1 UL46.
messages: Cytoplasm
messages: In response to a variety of growth factors, isoform p46Shc and isoform p52Shc bind to phosphorylated Trk receptors through their phosphotyrosine binding (PID) and/or SH2 domains. The PID and SH2 domains bind to specific phosphorylated tyrosine residues in the Asn-Pro-Xaa-Tyr(P) motif of the Trk receptors. Isoform p46Shc and isoform p52Shc are in turn phosphorylated on three tyrosine residues within the extended proline-rich domain. These phosphotyrosines act as docking site for GRB2 and thereby are involved in Ras activation (By similarity).
messages: Interacts with CPNE3; this interaction may mediate the binding of CPNE3 with ERBB2 (PubMed:20010870). Interacts with the NPXY motif of tyrosine-phosphorylated IGF1R and INSR in vitro via the PID domain. Once activated, binds to GRB2. Interacts with tyrosine-phosphorylated CD3T and DDR2. Interacts with the N-terminal region of SH2B2. Interacts with phosphorylated LRP1 and IRS4. Interacts with INPP5D/SHIP1 and INPPL1/SHIP2. Interacts with TRIM31. Interacts with PTPN6/SHP (tyrosine phosphorylated). Identified in a complex containing FGFR4, NCAM1, CDH2, PLCG1, FRS2, SRC, SHC1, GAP43 and CTT (By similarity). Interacts with ALK, GAB2, GRB7 and KIT. Interacts with FLT4 (tyrosine-phosphorylated). Interacts with EPHB1 and GRB2; activates the MAPK/ERK cascade to regulate cell migration. Interacts with PDGFRB (tyrosine-phosphorylated). Interacts with ERBB4. Interacts with TEK/TIE2 (tyrosine-phosphorylated). Interacts with the Trk receptors NTRK1, NTRK2 and NTRK3; in a phosphotyrosine-dependent manner. Interacts with PTK2/FAK1. Interacts with CEACAM1; this interaction is CEACAM1-phosphorylation-dependent and mediates interaction with EGFR or INSR resulting in decrease coupling of SHC1 to the MAPK3/ERK1-MAPK1/ERK2 pathway (By similarity). Interacts (via PID domain) with PEAK1 (when phosphorylated at 'Tyr-1188') (PubMed:23846654, PubMed:35687021). Found in a complex with PPP1CA, PPP1CC, SHC1 and PEAK1 (PubMed:23846654).
messages: Mitochondrion
messages: Mitochondrion matrix
messages: Phosphorylated by activated epidermal growth factor receptor. Phosphorylated in response to FLT4 and KIT signaling. Isoform p46Shc and isoform p52Shc are phosphorylated on tyrosine residues of the Pro-rich domain. Isoform p66Shc is phosphorylated on Ser-36 by PRKCB upon treatment with insulin, hydrogen peroxide or irradiation with ultraviolet light (By similarity). Tyrosine phosphorylated in response to FLT3 signaling (By similarity). Tyrosine phosphorylated by activated PTK2B/PYK2 (By similarity). Tyrosine phosphorylated by ligand-activated ALK. Tyrosine phosphorylated by ligand-activated PDGFRB. Tyrosine phosphorylated by TEK/TIE2. May be tyrosine phosphorylated by activated PTK2/FAK1; tyrosine phosphorylation was seen in an astrocytoma biopsy, where PTK2/FAK1 kinase activity is high, but not in normal brain tissue. Isoform p52Shc dephosphorylation by PTPN2 may regulate interaction with GRB2.
messages: Produced by alternative splicing.
messages: Regulated by epigenetic modifications of its promoter region.
messages: Signaling adapter that couples activated growth factor receptors to signaling pathways. Participates in a signaling cascade initiated by activated KIT and KITLG/SCF. Isoform p46Shc and isoform p52Shc, once phosphorylated, couple activated receptor tyrosine kinases to Ras via the recruitment of the GRB2/SOS complex and are implicated in the cytoplasmic propagation of mitogenic signals. Isoform p46Shc and isoform p52Shc may thus function as initiators of the Ras signaling cascade in various non-neuronal systems. Isoform p66Shc does not mediate Ras activation, but is involved in signal transduction pathways that regulate the cellular response to oxidative stress and life span. Isoform p66Shc acts as a downstream target of the tumor suppressor p53 and is indispensable for the ability of stress-activated p53 to induce elevation of intracellular oxidants, cytochrome c release and apoptosis. The expression of isoform p66Shc has been correlated with life span (By similarity). Participates in signaling downstream of the angiopoietin receptor TEK/TIE2, and plays a role in the regulation of endothelial cell migration and sprouting angiogenesis.
messages: Widely expressed. Expressed in neural stem cells but absent in mature neurons.
messages: focal adhesion

9606:GALK2
gene id: 9606:GALK2
uniprot id: B4DW43
uniprot id: B7ZAX5
uniprot id: Q01415
names: Function
names: Similarity
names: Subunit
messages: Acts on GalNAc. Also acts as a galactokinase when galactose is present at high concentrations. May be involved in a salvage pathway for the reutilization of free GalNAc derived from the degradation of complex carbohydrates.
messages: Belongs to the GHMP kinase family. GalK subfamily.
messages: Monomer.

9606:SLC16A9
gene id: 9606:SLC16A9
uniprot id: Q7RTY1
names: Activity Regulation
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: 4-guanidinobutyrate and guanidinoethyl sulfonate inhibit the transport activity.
messages: Belongs to the major facilitator superfamily. Monocarboxylate porter (TC 2.A.1.13) family.
messages: Cell membrane
messages: Extracellular pH-and Na(+)-sensitive low-affinity creatine transporter (PubMed:31784090). Functions also as a pH-independent carnitine efflux transporter (PubMed:21886157).

9606:BCR
gene id: 9606:BCR
uniprot id: P11274
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: A chromosomal aberration involving BCR has been found in patients with chronic myeloid leukemia. Translocation t(9;22)(q34;q11) with ABL1. The translocation produces a BCR-ABL found also in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL).
messages: Autophosphorylated. Phosphorylated by FES/FPS on tyrosine residues, leading to down-regulation of the BCR kinase activity. Phosphorylation at Tyr-177 by HCK is important for interaction with GRB2.
messages: Homotetramer. Interacts with PDZK1 (PubMed:15494376). May interact with CCPG1 (By similarity). Interacts with FES/FPS, ABL1, PIK3R1 and GRB2 (PubMed:15302586, PubMed:1712671, PubMed:9407116). Interacts with HCK (PubMed:9407116). Interacts with SH2D5 (PubMed:25331951). Interacts with DLG4 (PubMed:20962234).
messages: Postsynaptic density
messages: Protein with a unique structure having two opposing regulatory activities toward small GTP-binding proteins. The C-terminus is a GTPase-activating protein (GAP) domain which stimulates GTP hydrolysis by RAC1, RAC2 and CDC42. Accelerates the intrinsic rate of GTP hydrolysis of RAC1 or CDC42, leading to down-regulation of the active GTP-bound form (PubMed:7479768, PubMed:1903516, PubMed:17116687). The central Dbl homology (DH) domain functions as guanine nucleotide exchange factor (GEF) that modulates the GTPases CDC42, RHOA and RAC1. Promotes the conversion of CDC42, RHOA and RAC1 from the GDP-bound to the GTP-bound form (PubMed:7479768, PubMed:23940119). The amino terminus contains an intrinsic kinase activity (PubMed:1657398). Functions as an important negative regulator of neuronal RAC1 activity (By similarity). Regulates macrophage functions such as CSF1-directed motility and phagocytosis through the modulation of RAC1 activity (PubMed:17116687). Plays a major role as a RHOA GEF in keratinocytes being involved in focal adhesion formation and keratinocyte differentiation (PubMed:23940119).
messages: Synapse
messages: The DH domain is involved in interaction with CCPG1.
messages: The amino terminus contains an intrinsic kinase activity. The central Dbl homology (DH) domain functions as guanine nucleotide exchange factor (GEF) that modulates the GTPases CDC42, RHOA and RAC1. Promotes the conversion of CDC42, RHOA and RAC1 from the GDP-bound to the GTP-bound form. The C-terminus is a Rho-GAP domain which stimulates GTP hydrolysis by RAC1, RAC2 and CDC42. The protein has a unique structure having two opposing regulatory activities toward small GTP-binding proteins.
messages: The gene represented in this entry is involved in disease pathogenesis.
messages: The region involved in binding to ABL1 SH2-domain is rich in serine residues and needs to be Ser/Thr phosphorylated prior to SH2 binding. This region is essential for the activation of the ABL1 tyrosine kinase and transforming potential of the chimeric BCR-ABL oncogene.
messages: axon
messages: dendritic spine

9606:BAMBI
gene id: 9606:BAMBI
uniprot id: Q13145
names: Developmental Stage
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the BAMBI family.
messages: Expression in poorly metastatic human melanoma cell lines; no expression in highly metastatic human melanoma cell lines.
messages: High expression in kidney medulla, placenta and spleen; low in kidney cortex, liver, prostate and gut. Not expressed in normal skin, expression is high in melanocytes and in 3 out of 11 melanoma metastases tested.
messages: Membrane
messages: Negatively regulates TGF-beta signaling.

9606:MESP1
gene id: 9606:MESP1
uniprot id: Q9BRJ9
names: Function
names: Miscellaneous
names: Subcellular Location Annotation
messages: Nucleus
messages: The N- and C-terminal domains are separated by a 2-repeat G-Q region.
messages: Transcription factor. Plays a role in the epithelialization of somitic mesoderm and in the development of cardiac mesoderm. Defines the rostrocaudal patterning of the somites by participating in distinct Notch pathways (By similarity).

9606:NR4A2
gene id: 9606:NR4A2
uniprot id: F1D8N6
uniprot id: P43354
uniprot id: Q53EL4
names: Developmental Stage
names: Disease Annotation
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the nuclear hormone receptor family.
messages: Belongs to the nuclear hormone receptor family. NR4 subfamily.
messages: Cytoplasm
messages: Expressed in a number of cell lines of T-cell, B-cell and fibroblast origin. Strong expression in brain tissue.
messages: Interacts with SFPQ, NCOR2, SIN3A and HADC1. The interaction with NCOR2 increases in the absence of PITX3. Interacts with PER2 (By similarity).
messages: Interacts with SFPQ, NCOR2, SIN3A and HADC1. The interaction with NCOR2 increases in the absence of PITX3. Interacts with PER2.
messages: Nucleus
messages: Rapidly and only very transiently expressed after cell activation, during the G0-G1 transition of the cell cycle.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Transcriptional regulator which is important for the differentiation and maintenance of meso-diencephalic dopaminergic (mdDA) neurons during development (PubMed:17184956, PubMed:15716272). It is crucial for expression of a set of genes such as SLC6A3, SLC18A2, TH and DRD2 which are essential for development of mdDA neurons (By similarity).
messages: the ligand-binding domain (LBD) contains no cavity as a result of the tight packing of side chains from several bulky hydrophobic residues in the region normally occupied by ligands. NR4A2 lacks a 'classical' binding site for coactivators (PubMed:12774125).

9606:SSTR2
gene id: 9606:SSTR2
uniprot id: P30874
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Cytoplasm
messages: Expressed in both pancreatic alpha- and beta-cells (at protein level). Expressed at higher levels in the pancreas than other somatostatin receptors. Also expressed in the cerebrum and kidney and, in lesser amounts, in the jejunum, colon and liver. In the developing nervous system, expressed in the cortex where it is located in the preplate at early stages and is enriched in the outer part of the germinal zone at later stages. In the cerebellum, expressed in the deep part of the external granular layer at gestational week 19. This pattern persists until birth but disappears at adulthood.
messages: Homodimer and heterodimer with SSTR3 and SSTR5. Heterodimerization with SSTR3 inactivates SSTR3 receptor function. Heterodimerization with SSTR5 is enhanced by agonist stimulation of SSTR2 and increases SSTR2 cell growth inhibition activity. Following agonist stimulation, homodimers dissociate into monomers which is required for receptor internalization. Interacts with beta-arrestin; this interaction is necessary for receptor internalization and is destabilized by heterodimerization with SSTR5 which results in increased recycling of SSTR2 to the cell surface. Interacts (via C-terminus) with SHANK1 (via PDZ domain).
messages: Phosphorylated on serine and threonine residues in response to agonist stimulation, leading to receptor desensitization and rapid internalization. Phosphorylated to a greater extent on serine than threonine residues. Threonine phosphorylation is required for arrestin binding and receptor endocytosis but is not necessary for desensitization (By similarity).
messages: Receptor for somatostatin-14 and -28. This receptor is coupled via pertussis toxin sensitive G proteins to inhibition of adenylyl cyclase. In addition it stimulates phosphotyrosine phosphatase and PLC via pertussis toxin insensitive as well as sensitive G proteins. Inhibits calcium entry by suppressing voltage-dependent calcium channels. Acts as the functionally dominant somatostatin receptor in pancreatic alpha- and beta-cells where it mediates the inhibitory effect of somatostatin-14 on hormone secretion. Inhibits cell growth through enhancement of MAPK1 and MAPK2 phosphorylation and subsequent up-regulation of CDKN1B. Stimulates neuronal migration and axon outgrowth and may participate in neuron development and maturation during brain development. Mediates negative regulation of insulin receptor signaling through PTPN6. Inactivates SSTR3 receptor function following heterodimerization.

9606:SERPINB9
gene id: 9606:SERPINB9
uniprot id: A0A024QZT4
uniprot id: P50453
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the serpin family. Ov-serpin subfamily.
messages: Cytoplasm
messages: Granzyme B inhibitor.

9606:ALX3
gene id: 9606:ALX3
uniprot id: O95076
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the paired homeobox family.
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Transcriptional regulator with a possible role in patterning of mesoderm during development.

9606:CUTC
gene id: 9606:CUTC
uniprot id: Q9NTM9
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the CutC family.
messages: Cytoplasm
messages: Homotetramer.
messages: May play a role in copper homeostasis. Can bind one Cu(1+) per subunit.
messages: Nucleus
messages: Ubiquitous.

9606:SEPTIN11
gene id: 9606:SEPTIN11
uniprot id: A0A384P5S0
uniprot id: Q9NVA2
names: Disease Annotation
names: Function
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: A chromosomal aberration involving SEPTIN11 may be a cause of chronic neutrophilic leukemia. Translocation t(4;11)(q21;q23) with KMT2A/MLL1.
messages: Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. Septin GTPase family.
messages: Contaminating sequence. Potential poly-A sequence.
messages: Filament-forming cytoskeletal GTPase.
messages: Filament-forming cytoskeletal GTPase. May play a role in cytokinesis (Potential). May play a role in the cytoarchitecture of neurons, including dendritic arborization and dendritic spines, and in GABAergic synaptic connectivity (By similarity). During Listeria monocytogenes infection, not required for the bacterial entry process, but restricts its efficacy.
messages: Septins polymerize into heterooligomeric protein complexes that form filaments, and can associate with cellular membranes, actin filaments and microtubules. Forms homooligomers. GTPase activity is required for filament formation. Interacts with SEPTIN7, SEPTIN9 and SEPTIN12.
messages: Septins polymerize into heterooligomeric protein complexes that form filaments.
messages: Synapse
messages: Widely expressed, except in leukocytes.
messages: axon
messages: cytoskeleton
messages: dendritic spine

9606:FOXA3
gene id: 9606:FOXA3
uniprot id: P55318
names: Developmental Stage
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Detected in prenatal liver nuclear extracts (12.4-27 weeks estimated gestational age). Not detected in postnatal liver samples.
messages: Expressed in erythroleukemia and hepatoma cell lines and in liver and pancreas. Not expressed in any other cell lines or tissues examined.
messages: Interacts with FOXA2.
messages: Nucleus
messages: Transcription factor that is thought to act as a 'pioneer' factor opening the compacted chromatin for other proteins through interactions with nucleosomal core histones and thereby replacing linker histones at target enhancer and/or promoter sites (By similarity). Originally described as a transcription activator for a number of liver genes such as AFP, albumin, tyrosine aminotransferase, PEPCK, etc. Interacts with the cis-acting regulatory regions of these genes. Involved in glucose homeostasis; binds to and activates transcription from the G6PC1 promoter. Binds to the CYP3A4 promoter and activates its transcription in cooperation with CEBPA. Binds to the CYP3A7 promoter together with members of the CTF/NF-I family. Involved in regulation of neuronal-specific transcription. May be involved in regulation of spermatogenesis.

9606:WHRN
gene id: 9606:WHRN
uniprot id: Q9P202
names: Disease Annotation
names: Function
names: Miscellaneous
names: Subcellular Location Annotation
names: Subunit
messages: Cytoplasm
messages: Forms homooligomers (By similarity). Interacts (via C-terminal PDZ domain) with MYO15A; this interaction is necessary for localization of WHRN to stereocilia tips (By similarity). Interacts (via C-terminal PDZ domain) with MPP1/p55 (PubMed:17584769). Interacts with LRRC4C/NGL1. Interacts with MYO7A. Interacts with RPGR. Interacts with EPS8 (By similarity). Interacts with CASK (By similarity). Interacts with CIB2 (PubMed:23023331). Component of USH2 complex, composed of ADGRV1, PDZD7, USH2A and WHRN. Interacts (via PDZ domains) with PDZD7; the interaction is direct. Interacts (via N-terminal PDZ domain) with USH2A (via cytoplasmic region) (PubMed:16434480). Interacts with ADGRV1/MASS1 (via cytoplasmic region) (PubMed:16434480).
messages: Involved in hearing and vision as member of the USH2 complex. Necessary for elongation and maintenance of inner and outer hair cell stereocilia in the organ of Corti in the inner ear. Involved in the maintenance of the hair bundle ankle region, which connects stereocilia in cochlear hair cells of the inner ear. In retina photoreceptors, required for the maintenance of periciliary membrane complex that seems to play a role in regulating intracellular protein transport.
messages: May be due to an intron retention.
messages: Photoreceptor inner segment
messages: Synapse
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: growth cone
messages: stereocilium

9606:RAPSN
gene id: 9606:RAPSN
uniprot id: A0A0S2Z4A2
uniprot id: A0A0S2Z4A6
uniprot id: A0A0S2Z4F8
uniprot id: A0A0S2Z4M9
uniprot id: Q13702
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
messages: A cysteine-rich region homologous to part of the regulatory domain of protein kinase C may be important in interactions of this protein with the lipid bilayer.
messages: Belongs to the RAPsyn family.
messages: Cell membrane
messages: Postsynaptic cell membrane
messages: Postsynaptic protein required for clustering of nicotinic acetylcholine receptors (nAChRs) at the neuromuscular junction. It may link the receptor to the underlying postsynaptic cytoskeleton, possibly by direct association with actin or spectrin.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitinated by the BCR(KLHL8) complex, leading to its degradation.
messages: cytoskeleton

9606:LAGE3
gene id: 9606:LAGE3
uniprot id: Q14657
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the CTAG/PCC1 family.
messages: Component of the EKC/KEOPS complex composed of at least GON7, TP53RK, TPRKB, OSGEP and LAGE3; the whole complex dimerizes.
messages: Component of the EKC/KEOPS complex that is required for the formation of a threonylcarbamoyl group on adenosine at position 37 (t(6)A37) in tRNAs that read codons beginning with adenine (PubMed:22912744, PubMed:27903914). The complex is probably involved in the transfer of the threonylcarbamoyl moiety of threonylcarbamoyl-AMP (TC-AMP) to the N6 group of A37 (PubMed:22912744, PubMed:27903914). LAGE3 functions as a dimerization module for the complex (PubMed:22912744, PubMed:27903914).
messages: Cytoplasm
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitous.

9606:FAM187B
gene id: 9606:FAM187B
uniprot id: Q17R55
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the FAM187 family.
messages: Membrane

9606:RRP7A
gene id: 9606:RRP7A
uniprot id: Q9Y3A4
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the RRP7 family.
messages: Expressed in the apical radial glial cells in the developing brain.
messages: Nucleolar protein that is involved in ribosomal RNA (rRNA) processing (PubMed:33199730). Also plays a role in primary cilia resorption, and cell cycle progression in neurogenesis and neocortex development (PubMed:33199730). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797).
messages: Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3 (PubMed:34516797). Interacts with NOL6; required for NOL6 localization to nucleolus.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: centrosome
messages: cilium
messages: nucleolus

9606:LY6G5C
gene id: 9606:LY6G5C
uniprot id: A0A1U9X7Y6
uniprot id: Q5SRR4
names: Caution
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Detected in T-cell lines and fetal and adult lung.
messages: Forms oligomers.
messages: It is uncertain whether Met-1 or Met-4 is the initiator.
messages: May have a role in hematopoietic cell differentiation.
messages: N-glycosylated.
messages: Secreted

9606:PRICKLE4
gene id: 9606:PRICKLE4
uniprot id: Q2TBC4
names: Similarity
names: Tissue Specificity
messages: Belongs to the prickle / espinas / testin family.
messages: Expressed in a broad range of normal tissues as well as in hepatocellular carcinoma, breast cancer and prostate cancer tissues.

9606:H2AJ
gene id: 9606:H2AJ
uniprot id: Q9BTM1
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the histone H2A family.
messages: Chromosome
messages: Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
messages: Glutamine methylation at Gln-105 (H2AQ104me) by FBL is specifically dedicated to polymerase I. It is present at 35S ribosomal DNA locus and impairs binding of the FACT complex (By similarity).
messages: Monoubiquitination of Lys-120 (H2AXK119ub) gives a specific tag for epigenetic transcriptional repression. Following DNA double-strand breaks (DSBs), it is ubiquitinated through 'Lys-63' linkage of ubiquitin moieties (By similarity).
messages: Nucleus
messages: Phosphorylation on Ser-2 (H2AS1ph) is enhanced during mitosis. Phosphorylation on Ser-2 by RPS6KA5/MSK1 directly represses transcription. Acetylation of H3 inhibits Ser-2 phosphorylation by RPS6KA5/MSK1. Phosphorylation at Thr-121 (H2AT120ph) by DCAF1 is present in the regulatory region of many tumor suppresor genes and down-regulates their transcription (By similarity).
messages: The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.

9606:CMTR2
gene id: 9606:CMTR2
uniprot id: Q8IYT2
names: Function
names: Subcellular Location Annotation
messages: Cytoplasm
messages: Nucleus
messages: S-adenosyl-L-methionine-dependent methyltransferase that mediates mRNA cap2 2'-O-ribose methylation to the 5'-cap structure of mRNAs. Methylates the ribose of the second nucleotide of a m(7)GpppG-capped mRNA and small nuclear RNA (snRNA) (cap0) to produce m(7)GpppRmpNm (cap2). Recognizes a guanosine cap on RNA independently of its N(7) methylation status. Display cap2 methylation on both cap0 and cap1. Displays a preference for cap1 RNAs.

9606:PPP2R5B
gene id: 9606:PPP2R5B
uniprot id: Q15173
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: As the regulatory component of the serine/threonine-protein phosphatase 2A (PP2A) holoenzyme, modulates substrate specificity, subcellular localization, and responsiveness to phosphorylation. The phosphorylated form mediates the interaction between PP2A and AKT1, leading to AKT1 dephosphorylation.
messages: Belongs to the phosphatase 2A regulatory subunit B56 family.
messages: By retinoic acid; in neuroblastoma cell lines.
messages: Component of the serine/threonine-protein phosphatase 2A complex (PP2A). This complex consists of a common heterodimeric core enzyme, composed of a 36 kDa catalytic subunit (subunit C) and a 65 kDa constant scaffold subunit (PR65 or subunit A), that associates with a variety of regulatory subunits. Proteins that associate with the core dimer include three families of regulatory subunits B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56 families), the 48 kDa variable regulatory subunit, viral proteins, and cell signaling molecules (PubMed:23135275). Interacts with SGO1 (PubMed:16541025). Interacts with AKT1 (PubMed:21329884). Interacts with CUL3 and KLHL15; this interaction leads to proteasomal degradation (PubMed:23135275).
messages: Cytoplasm
messages: Highest expression in brain.
messages: Ubiquitinated by E3 CUL3-KLHL15 complex; this modification leads to proteasomal degradation.

9606:GABRR1
gene id: 9606:GABRR1
uniprot id: P24046
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRR1 sub-subfamily.
messages: Cell membrane
messages: GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel. Rho-1 GABA receptor could play a role in retinal neurotransmission.
messages: Generally pentameric. There are five types of GABA(A) receptor chains: alpha, beta, gamma, delta, and rho. Interacts with SQSTM1 (By similarity).
messages: Highly expressed in the retina and in a lesser extent in brain, lung and thymus.
messages: Postsynaptic cell membrane

9606:ATP10B
gene id: 9606:ATP10B
uniprot id: O94823
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Autophosphorylated at the conserved aspartate of the P-type ATPase signature sequence.
messages: Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IV subfamily.
messages: Catalytic component of a P4-ATPase flippase complex, which catalyzes the hydrolysis of ATP coupled to the transport of glucosylceramide (GlcCer) from the outer to the inner leaflet of lysosome membranes. Plays an important role in the maintenance of lysosome membrane integrity and function in cortical neurons.
messages: Component of a P4-ATPase flippase complex which consists of a catalytic alpha subunit ATP10B and an accessory beta subunit TMEM30A.
messages: Endoplasmic reticulum membrane
messages: Expressed in predominantly in brain structures including medulla oblongata, substantia nigra and basal ganglia. Expressed in the gastrointestinal system with highest levels in the small intestine and colon. Also expressed at low levels in testis and thymus.
messages: Late endosome membrane
messages: Lysosome membrane

9606:CAPSL
gene id: 9606:CAPSL
uniprot id: Q8WWF8
names: Subcellular Location Annotation
messages: Cytoplasm

9606:RGS20
gene id: 9606:RGS20
uniprot id: O76081
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cytoplasm
messages: Fatty acylated. Heavily palmitoylated in the cysteine string motif (By similarity).
messages: Forms a complex with G(alpha)z/i2 subunits and mu-opioid receptors; the formation of this complex results in mu-opioid receptor desensitization. Interacts with OPRM1 (By similarity).
messages: Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form. Binds selectively to G(z)-alpha and G(alpha)-i2 subunits, accelerates their GTPase activity and regulates their signaling activities. The G(z)-alpha activity is inhibited by the phosphorylation and palmitoylation of the G-protein. Negatively regulates mu-opioid receptor-mediated activation of the G-proteins (By similarity).
messages: Isoform 5 is expressed in brain at high levels in the caudate nucleus and temporal lobe.
messages: Membrane
messages: N- and O-glycosylated in synapsomal membranes.
messages: Nucleus
messages: Serine phosphorylated in synapsomal membranes.
messages: Sumoylated with SUMO1 and SUMO2 in synaptosomes. The sumoylated forms act as a scaffold for sequestering mu-opioid receptor-activated G(alpha) subunits (By similarity).

9606:NCOA7
gene id: 9606:NCOA7
uniprot id: B3KXK4
uniprot id: Q8N3C8
uniprot id: Q8NI08
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the OXR1 family.
messages: Enhances the transcriptional activities of several nuclear receptors. Involved in the coactivation of different nuclear receptors, such as ESR1, THRB, PPARG and RARA.
messages: Highly expressed in brain. Weakly expressed in mammary gland, ovary, uterus, prostate, stomach, bladder, spinal cord and pancreas. Expressed in cancer cell line.
messages: Interacts with ESR1, ESR2A, ESR2B, THRB, PPARG and RARA in a ligand-inducible manner. Interacts with the heterodimer AHR-ARNT.
messages: Nucleus

9606:NMRK1
gene id: 9606:NMRK1
uniprot id: Q9NWW6
names: Function
names: Similarity
names: Subunit
messages: Belongs to the uridine kinase family. NRK subfamily.
messages: Catalyzes the phosphorylation of nicotinamide riboside (NR) and nicotinic acid riboside (NaR) to form nicotinamide mononucleotide (NMN) and nicotinic acid mononucleotide (NaMN). The enzyme also phosphorylates the antitumor drugs tiazofurin and 3-deazaguanosine.
messages: Monomer.

9606:GNG8
gene id: 9606:GNG8
uniprot id: Q9UK08
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the G protein gamma family.
messages: Cell membrane
messages: G proteins are composed of 3 units, alpha, beta and gamma.
messages: Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction.

9606:CHST6
gene id: 9606:CHST6
uniprot id: Q9GZX3
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the sulfotransferase 1 family. Gal/GlcNAc/GalNAc subfamily.
messages: Expressed in cornea. Mainly expressed in brain. Also expressed in spinal cord and trachea.
messages: Golgi apparatus membrane
messages: Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the transfer of sulfate to position 6 of non-reducing N-acetylglucosamine (GlcNAc) residues of keratan (PubMed:11352640, PubMed:11278593, PubMed:12218059, PubMed:17690104). Cooperates with B4GALT4 galactosyltransferase and B3GNT7 N-acetylglucosaminyltransferase to construct and elongate the sulfated disaccharide unit [->3Galbeta1->4(6-sulfoGlcNAcbeta)1->] within keratan sulfate polymer. Involved in biosynthesis of keratan sulfate in cornea, with an impact on proteoglycan fibril organization and corneal transparency (PubMed:17690104, PubMed:11278593, PubMed:12218059). Involved in sulfation of endothelial mucins such as GLYCAM1 (PubMed:11352640).
messages: The disease is caused by variants affecting the gene represented in this entry. CHST6 homozygous missense mutations have been observed in patients with macular corneal dystrophy type I, while type II patients show a large deletion and replacement in the upstream region of CHST6. The only missense mutation for type II is Cys-50, which is heterozygous with a replacement in the upstream region on the other allele of CHST6.

9606:SLC25A48
gene id: 9606:SLC25A48
uniprot id: Q6ZT89
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the mitochondrial carrier (TC 2.A.29) family.
messages: Mitochondrion inner membrane

9606:CACNA1E
gene id: 9606:CACNA1E
uniprot id: Q15878
uniprot id: Q59FG1
names: Disease Annotation
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family.
messages: Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family. CACNA1E subfamily.
messages: Each of the four internal repeats contains five hydrophobic transmembrane segments (S1, S2, S3, S5, S6) and one positively charged transmembrane segment (S4). S4 segments probably represent the voltage-sensor and are characterized by a series of positively charged amino acids at every third position.
messages: Expressed in neuronal tissues and in kidney.
messages: Interacts with EFHC1. Voltage-dependent calcium channels are multisubunit complexes, consisting of alpha-1, alpha-2, beta and delta subunits in a 1:1:1:1 ratio. The channel activity is directed by the pore-forming and voltage-sensitive alpha-1 subunit. In many cases, this subunit is sufficient to generate voltage-sensitive calcium channel activity. The auxiliary subunits beta and alpha-2/delta linked by a disulfide bridge regulate the channel activity.
messages: Membrane
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells (PubMed:30343943). They are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1E gives rise to R-type calcium currents. R-type calcium channels belong to the 'high-voltage activated' (HVA) group and are blocked by nickel. They are however insensitive to dihydropyridines (DHP). Calcium channels containing alpha-1E subunit could be involved in the modulation of firing patterns of neurons which is important for information processing.
messages: Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1E gives rise to R-type calcium currents.

9606:TAS1R1
gene id: 9606:TAS1R1
uniprot id: A8K7J9
uniprot id: Q7RTX1
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the G-protein coupled receptor 3 family. TAS1R subfamily.
messages: Cell membrane
messages: Forms heterodimers with TAS1R3.
messages: Incomplete sequence.
messages: Membrane
messages: Putative taste receptor. TAS1R1/TAS1R3 responds to the umami taste stimulus (the taste of monosodium glutamate). Sequence differences within and between species can significantly influence the selectivity and specificity of taste responses.

9606:KLF4
gene id: 9606:KLF4
uniprot id: O43474
names: Biotechnology
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: Cytoplasm
messages: Interacts with POU5F1/OCT4 and SOX2 (By similarity). Interacts with MUC1 (via the C-terminal domain) (PubMed:17308127). Interacts with MEIS2 isoform 4 and PBX1 isoform PBX1a (PubMed:21746878). Interacts with ZNF296 (By similarity). Interacts with GLIS1 (PubMed:21654807). Interacts with BTRC; this interaction leads to KLF4 ubiquitination and subsequent degradation (By similarity). Interacts with IPO7; the interaction facilitates nuclear translocation of KLF4 in dental papilla cells (By similarity).
messages: Nucleus
messages: POU5F1/OCT4, SOX2, MYC/c-Myc and KLF4 are the four Yamanaka factors. When combined, these factors are sufficient to reprogram differentiated cells to an embryonic-like state designated iPS (induced pluripotent stem) cells. iPS cells exhibit the morphology and growth properties of ES cells and express ES cell marker genes.
messages: Polyglutamylated by TTLL1 and TTLL4 at Glu-411, which inhibits KLF4 binding with E3 ligase component BTRC, thereby impeding ubiquitination. Deglutamylated by CCP1 and CCP6; deglutamylation promotes KLF4 ubiquitination. KLF4 glutamylation state plays a critical role in the regulation of its function in cell reprogramming, pluripotency maintenance and embryogenesis.
messages: Transcription factor; can act both as activator and as repressor. Binds the 5'-CACCC-3' core sequence. Binds to the promoter region of its own gene and can activate its own transcription. Regulates the expression of key transcription factors during embryonic development. Plays an important role in maintaining embryonic stem cells, and in preventing their differentiation. Required for establishing the barrier function of the skin and for postnatal maturation and maintenance of the ocular surface. Involved in the differentiation of epithelial cells and may also function in skeletal and kidney development. Contributes to the down-regulation of p53/TP53 transcription.
messages: Ubiquitinated. 'Lys-48'-linked ubiquitinated and targeted for proteasomal degradation by the SCF(BTRC) E3 ubiquitin-protein ligase complex, thereby negatively regulating cell pluripotency maintenance and embryogenesis.
messages: the 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.

9606:NUS1
gene id: 9606:NUS1
uniprot id: Q96E22
names: Activity Regulation
names: Disease Annotation
names: Domain
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Activated by phospholipids including cardiolipin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol and phosphatidylserine.
messages: Belongs to the UPP synthase family.
messages: Contains the RXG motif, which is important for substrate binding and prenyltransferase activity. The catalytic site at NUS1-DHDDS interface accomodates both the allylic and the homoallylic IPP substrates to the S1 and S2 pockets respectively. The beta-phosphate groups of IPP substrates form hydrogen bonds with the RXG motif of NUS1 and four conserved residues of DHDDS (Arg-85, Arg-205, Arg-211 and Ser-213), while the allylic isopentenyl group is pointed toward the hydrophobic tunnel of the S1 pocket where the product elongation occurs.
messages: Endoplasmic reticulum membrane
messages: Forms an active dehydrodolichyl diphosphate synthase complex with DHDDS (NUS1-DHDDS) (PubMed:28842490, PubMed:19723497, PubMed:25066056, PubMed:32817466). Interacts with NPC2 (PubMed:21572394).
messages: NUS1 seems to exist in two topological orientations, a minor glycosylated species with its C-terminus oriented towards the lumen regulating NPC2 stability, and a major fraction oriented with its C-terminus directed towards the cytosol where it regulates cis-IPTase activity.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: With DHDDS, forms the dehydrodolichyl diphosphate synthase (DDS) complex, an essential component of the dolichol monophosphate (Dol-P) biosynthetic machinery. Both subunits contribute to enzymatic activity, i.e. condensation of multiple copies of isopentenyl pyrophosphate (IPP) to farnesyl pyrophosphate (FPP) to produce dehydrodolichyl diphosphate (Dedol-PP), a precursor of dolichol phosphate which is utilized as a sugar carrier in protein glycosylation in the endoplasmic reticulum (ER) (PubMed:21572394, PubMed:25066056, PubMed:28842490, PubMed:32817466). Synthesizes long-chain polyprenols, mostly of C95 and C100 chain length (PubMed:32817466). Regulates the glycosylation and stability of nascent NPC2, thereby promoting trafficking of LDL-derived cholesterol. Acts as a specific receptor for the N-terminus of Nogo-B, a neural and cardiovascular regulator (PubMed:16835300).

9606:EPHX4
gene id: 9606:EPHX4
uniprot id: Q8IUS5
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the AB hydrolase superfamily. Epoxide hydrolase family.
messages: Membrane

9606:FGFR1
gene id: 9606:FGFR1
uniprot id: A0A0S2Z3Q6
uniprot id: A0A3B3ISD1
uniprot id: P11362
names: Activity Regulation
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Autophosphorylated. Binding of FGF family members together with heparan sulfate proteoglycan or heparin promotes receptor dimerization and autophosphorylation on tyrosine residues. Autophosphorylation occurs in trans between the two FGFR molecules present in the dimer and proceeds in a highly ordered manner. Initial autophosphorylation at Tyr-653 increases the kinase activity by a factor of 50 to 100. After this, Tyr-583 becomes phosphorylated, followed by phosphorylation of Tyr-463, Tyr-766, Tyr-583 and Tyr-585. In a third stage, Tyr-654 is autophosphorylated, resulting in a further tenfold increase of kinase activity. Phosphotyrosine residues provide docking sites for interacting proteins and so are crucial for FGFR1 function and its regulation.
messages: Belongs to the protein kinase superfamily. Tyr protein kinase family. Fibroblast growth factor receptor subfamily.
messages: Cell membrane
messages: Chromosomal aberrations involving FGFR1 are a cause of chromosome 8p11 myeloproliferative syndrome. Translocation t(8;13)(p11;q12) with ZMYM2. Translocation t(6;8)(q27;p11) with CEP43. Insertion ins(12;8)(p11;p11p22) with FGFR1OP2. Translocation t(8;9)(p12;q33) with CNTRL. Translocation t(2;8)(q12;p11) with RANBP2. Chromosome 8p11 myeloproliferative syndrome is characterized by myeloid hyperplasia, eosinophilia and T-cell or B-cell lymphoblastic lymphoma. In general it progresses to acute myeloid leukemia. The fusion proteins FGFR1OP2-FGFR1, CEP43-FGFR1 or FGFR1-CEP43 may exhibit constitutive kinase activity and be responsible for the transforming activity. The fusion protein CNTRL-FGFR1 is found in the cytoplasm, exhibits constitutive kinase activity and may be responsible for the transforming activity.
messages: Cytoplasmic vesicle
messages: Detected in astrocytoma, neuroblastoma and adrenal cortex cell lines. Some isoforms are detected in foreskin fibroblast cell lines, however isoform 17, isoform 18 and isoform 19 are not detected in these cells.
messages: Membrane
messages: Monomer. Homodimer after ligand binding. Interacts predominantly with FGF1 and FGF2, but can also interact with FGF3, FGF4, FGF5, FGF6, FGF8, FGF10, FGF19, FGF21, FGF22 and FGF23 (in vitro) (PubMed:1697263, PubMed:1722683, PubMed:8663044, PubMed:9655399, PubMed:12181353, PubMed:16597617, PubMed:17623664). Ligand specificity is determined by tissue-specific expression of isoforms, and differences in the third Ig-like domain are crucial for ligand specificity. Affinity for fibroblast growth factors (FGFs) is increased by heparan sulfate glycosaminoglycans that function as coreceptors. Likewise, KLB increases the affinity for FGF19, FGF21 and FGF23 (PubMed:19966287). Interacts (phosphorylated on Tyr-766) with PLCG1 (via SH2 domains) (PubMed:1656221, PubMed:1379697, PubMed:21765395). Interacts with FRS2 (PubMed:21765395). Interacts with RPS6KA1 (PubMed:15117958). Interacts (via C-terminus) with NEDD4 (via WW3 domain) (PubMed:21765395). Interacts with KL (By similarity). Interacts with SHB (via SH2 domain) (PubMed:12181353). Interacts with GRB10 (PubMed:10454568). Interacts with ANOS1; this interaction does not interfere with FGF2-binding to FGFR1, but prevents binding of heparin-bound FGF2 (PubMed:19696444). Interacts with SOX2 and SOX3. Interacts with FLRT1, FLRT2 and FLRT3 (By similarity). Found in a ternary complex with FGF1 and ITGAV:ITGB3 (PubMed:20422052, PubMed:18441324).
messages: N-glycosylated in the endoplasmic reticulum. The N-glycan chains undergo further maturation to an Endo H-resistant form in the Golgi apparatus.
messages: Nucleus
messages: Present in an inactive conformation in the absence of bound ligand. Ligand binding leads to dimerization and activation by sequential autophosphorylation on tyrosine residues. Inhibited by ARQ 069; this compound maintains the kinase in an inactive conformation and inhibits autophosphorylation. Inhibited by PD173074.
messages: The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry. Some patients carrying mutations in FGFR1 also have a mutation other HH-associated genes including DUSP6, FGF8, FGF17, FLRT3, GNRH1, GNRHR, HS6ST1, IL17RD, ANOS1, KISS1R, NSMF, PROKR2, SPRY4 and TACR3 (PubMed:23643382).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The second and third Ig-like domains directly interact with fibroblast growth factors (FGF) and heparan sulfate proteoglycans. Isoforms lacking the first Ig-like domain have higher affinity for fibroblast growth factors (FGF) and heparan sulfate proteoglycans than isoforms with all three Ig-like domains.
messages: Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration. Required for normal mesoderm patterning and correct axial organization during embryonic development, normal skeletogenesis and normal development of the gonadotropin-releasing hormone (GnRH) neuronal system. Phosphorylates PLCG1, FRS2, GAB1 and SHB. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Promotes phosphorylation of SHC1, STAT1 and PTPN11/SHP2. In the nucleus, enhances RPS6KA1 and CREB1 activity and contributes to the regulation of transcription. FGFR1 signaling is down-regulated by IL17RD/SEF, and by FGFR1 ubiquitination, internalization and degradation.
messages: Ubiquitinated. FGFR1 is rapidly ubiquitinated by NEDD4 after autophosphorylation, leading to internalization and lysosomal degradation. CBL is recruited to activated FGFR1 via FRS2 and GRB2, and mediates ubiquitination and subsequent degradation of FGFR1.
messages: Vesicle
messages: cytosol

9606:POSTN
gene id: 9606:POSTN
uniprot id: B1ALD9
uniprot id: Q15063
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Gamma-carboxylation is controversial. Gamma-carboxyglutamated; gamma-carboxyglutamate residues are formed by vitamin K dependent carboxylation; this may be required for calcium binding (PubMed:18450759). According to a more recent report, does not contain vitamin K-dependent gamma-carboxyglutamate residues (PubMed:26273833).
messages: Golgi apparatus
messages: Homodimer (PubMed:29754429). Interacts with BMP1 and fibronectin.
messages: Induces cell attachment and spreading and plays a role in cell adhesion (PubMed:12235007). Enhances incorporation of BMP1 in the fibronectin matrix of connective tissues, and subsequent proteolytic activation of lysyl oxidase LOX (By similarity).
messages: Secreted
messages: Widely expressed with highest levels in aorta, stomach, lower gastrointestinal tract, placenta, uterus, thyroid tissue and breast. Up-regulated in epithelial ovarian tumors. Not expressed in normal ovaries. Also highly expressed at the tumor periphery of lung carcinoma tissue but not within the tumor. Overexpressed in breast cancers.
messages: extracellular matrix

9606:OR6A2
gene id: 9606:OR6A2
uniprot id: A0A126GW91
uniprot id: O95222
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Membrane
messages: Odorant receptor.

9606:TULP3
gene id: 9606:TULP3
uniprot id: B7Z1E7
uniprot id: O75386
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Associates with the IFT complex A (IFT-A) (PubMed:20889716, PubMed:27932497). Interacts with SIRT1 (PubMed:35397207).
messages: Belongs to the TUB family.
messages: Cell membrane
messages: Cytoplasm
messages: Expressed at high levels in testis, ovaries, thyroid, and spinal chord.
messages: Negative regulator of the Shh signaling transduction pathway: recruited to primary cilia via association with the IFT complex A (IFT-A) and is required for recruitment of G protein-coupled receptor GPR161 to cilia, a promoter of PKA-dependent basal repression machinery in Shh signaling. Binds to phosphorylated inositide (phosphoinositide) lipids. Both IFT-A- and phosphoinositide-binding properties are required to regulate ciliary G protein-coupled receptor trafficking. During adipogenesis, regulates ciliary trafficking of FFAR4 in preadipocytes.
messages: Nucleus
messages: Secreted
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: cilium

9606:SNRPB2
gene id: 9606:SNRPB2
uniprot id: P08579
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the RRM U1 A/B'' family.
messages: Identified in the spliceosome B complex (PubMed:28781166). Identified in the spliceosome C complex (PubMed:11991638, PubMed:28502770, PubMed:28076346). Present in a spliceosome complex assembled in vitro, and composed of SNRPB2, HPRP8BP and CRNKL1 (PubMed:12084575). Contributes to the binding of stem loop IV of U2 snRNA with SNRPP1 (PubMed:9716128).
messages: Involved in pre-mRNA splicing as component of the spliceosome (PubMed:11991638, PubMed:28502770, PubMed:28781166, PubMed:28076346). Associated with sn-RNP U2, where it contributes to the binding of stem loop IV of U2 snRNA (PubMed:9716128).
messages: Nucleus
messages: Patients with systemic lupus erythematosus produce antibodies which interact with snRNP proteins.

9606:TTC8
gene id: 9606:TTC8
uniprot id: Q8TAM2
names: Disease Annotation
names: Function
names: Miscellaneous
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cytoplasm
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Part of BBSome complex, that contains BBS1, BBS2, BBS4, BBS5, BBS7, BBS8/TTC8, BBS9 and BBIP10. Interacts with PCM1. Interacts with CCDC28B. Interacts with PKD1 (PubMed:24939912).
messages: The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia. The BBSome complex is required for ciliogenesis but is dispensable for centriolar satellite function. This ciliogenic function is mediated in part by the Rab8 GDP/GTP exchange factor, which localizes to the basal body and contacts the BBSome. Rab8(GTP) enters the primary cilium and promotes extension of the ciliary membrane. Firstly the BBSome associates with the ciliary membrane and binds to RAB3IP/Rabin8, the guanosyl exchange factor (GEF) for Rab8 and then the Rab8-GTP localizes to the cilium and promotes docking and fusion of carrier vesicles to the base of the ciliary membrane. The BBSome complex, together with the LTZL1, controls SMO ciliary trafficking and contributes to the sonic hedgehog (SHH) pathway regulation. Required for proper BBSome complex assembly and its ciliary localization.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Widely expressed.
messages: centriolar satellite
messages: centrosome
messages: cilium
messages: cilium membrane

9606:STK32A
gene id: 9606:STK32A
uniprot id: B7Z9H7
uniprot id: Q8WU08
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the protein kinase superfamily.
messages: Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.
messages: Cell membrane

9606:LRRC38
gene id: 9606:LRRC38
uniprot id: Q5VT99
names: Domain
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Auxiliary protein of the large-conductance, voltage and calcium-activated potassium channel (BK alpha). Modulates gating properties by producing a marked shift in the BK channel's voltage dependence of activation in the hyperpolarizing direction, and in the absence of calcium.
messages: Cell membrane
messages: Interacts with KCNMA1.
messages: Mainly expressed in adrenal gland, thymus and skeletal muscle.
messages: The transmembrane domain is necessary for interaction with KCNMA1.

9606:OR4F21
gene id: 9606:OR4F21
uniprot id: O95013
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Odorant receptor.

9606:HMGCL
gene id: 9606:HMGCL
uniprot id: P35914
names: Activity Regulation
names: Disease Annotation
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the HMG-CoA lyase family.
messages: Highest expression in liver. Expressed in pancreas, kidney, intestine, testis, fibroblasts and lymphoblasts. Very low expression in brain and skeletal muscle. The relative expression of isoform 2 (at mRNA level) is highest in heart (30%), skeletal muscle (22%), and brain (14%).
messages: Homodimer; disulfide-linked. Can also form homotetramers.
messages: Mitochondrial 3-hydroxymethyl-3-methylglutaryl-CoA lyase that catalyzes a cation-dependent cleavage of (S)-3-hydroxy-3-methylglutaryl-CoA into acetyl-CoA and acetoacetate, a key step in ketogenesis. Terminal step in leucine catabolism. Ketone bodies (beta-hydroxybutyrate, acetoacetate and acetone) are essential as an alternative source of energy to glucose, as lipid precursors and as regulators of metabolism.
messages: Mitochondrion matrix
messages: Peroxisome
messages: Stimulated by reducing agents such as dithiothreitol (DTT).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The transcript is not translated, but would result in a catalytically impaired product if it was.
messages: Very low expression. The transcript is not translated, but would result in a catalytically inactive product if it was.

9606:ITCH
gene id: 9606:ITCH
uniprot id: Q96J02
names: Activity Regulation
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts with Epstein-Barr virus LMP2A.
messages: (Microbial infection) Interacts with Human cytomegalovirus (HCMV) protein UL42; this interaction induces ubiquitination and degradation of ITCH.
messages: (Microbial infection) Interacts with ebola virus protein VP40; this interaction is required for efficient viral egress from the infected cell.
messages: (Microbial infection) Interacts with herpesvirus 1 (HHV-1) UL56 protein; this interaction induces ubiquitination and probably degradation of ITCH.
messages: (Microbial infection) Interacts with herpesvirus 2 (HHV-2) UL56 protein.
messages: (Microbial infection) Interacts with herpesvirus 6A (HHV-6A) U24 protein.
messages: (Microbial infection) Interacts with influenza A virus matrix protein 1.
messages: (Microbial infection) Interacts with varicella-zoster virus (VZV) Orf0 protein.
messages: Activated by NDFIP1- and NDFIP2-binding (PubMed:25631046). Activated by PI4K2A-binding (PubMed:23146885). Inhibited by DTX3L-binding (PubMed:24790097). Inhibited by N4BP1 binding (By similarity).
messages: Acts as an E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates (PubMed:14602072, PubMed:17028573, PubMed:16387660, PubMed:18718448, PubMed:18718449, PubMed:11046148, PubMed:19592251, PubMed:19116316, PubMed:19881509, PubMed:20491914, PubMed:20392206, PubMed:20068034, PubMed:23146885, PubMed:24790097, PubMed:25631046, PubMed:15051726). Catalyzes 'Lys-29'-, 'Lys-48'- and 'Lys-63'-linked ubiquitin conjugation (PubMed:17028573, PubMed:18718448, PubMed:19131965, PubMed:19881509). Involved in the control of inflammatory signaling pathways (PubMed:19131965). Essential component of a ubiquitin-editing protein complex, comprising also TNFAIP3, TAX1BP1 and RNF11, that ensures the transient nature of inflammatory signaling pathways (PubMed:19131965). Promotes the association of the complex after TNF stimulation (PubMed:19131965). Once the complex is formed, TNFAIP3 deubiquitinates 'Lys-63' polyubiquitin chains on RIPK1 and catalyzes the formation of 'Lys-48'-polyubiquitin chains (PubMed:19131965). This leads to RIPK1 proteasomal degradation and consequently termination of the TNF- or LPS-mediated activation of NFKB1 (PubMed:19131965). Ubiquitinates RIPK2 by 'Lys-63'-linked conjugation and influences NOD2-dependent signal transduction pathways (PubMed:19592251). Regulates the transcriptional activity of several transcription factors, and probably plays an important role in the regulation of immune response (PubMed:18718448, PubMed:20491914). Ubiquitinates NFE2 by 'Lys-63' linkages and is implicated in the control of the development of hematopoietic lineages (PubMed:18718448). Mediates JUN ubiquitination and degradation (By similarity). Mediates JUNB ubiquitination and degradation (PubMed:16387660). Critical regulator of type 2 helper T (Th2) cell cytokine production by inducing JUNB ubiquitination and degradation (By similarity). Involved in the ne…
messages: Cell membrane
messages: Cytoplasm
messages: Early endosome membrane
messages: Endosome membrane
messages: Monomer. Part of a ternary complex composed of SMAD3, ITCH/AIP4 and NEDD9/HEF1; within the complex NEDD9/HEF1 interacts (via N-terminus) with ITCH/AIP4 (via WW domains); the complex mediates ubiquitination and proteasomal degradation of NEDD9/HEF1 (PubMed:15051726). Interacts (via WW domains) with OCNL (By similarity). Interacts (via WW domains) with NOTCH1 (By similarity). Interacts (via WW domains) with JUN (By similarity). Interacts with JUNB; the interaction promotes ITCH-mediated ubiquitination and degradation of JUNB (PubMed:16387660). Interacts with FYN; the interaction phosphorylates ITCH on Tyr-420 decreasing binding of JUNB (PubMed:16387660). Interacts (via WW domain 2) with N4BP1; the interaction inhibits the E3 ubiquitin-protein ligase activity (By similarity). Interacts with NDFIP1 and NDFIP2; this interaction activates the E3 ubiquitin-protein ligase and may induce its recruitment to exosomes (By similarity). Interacts with ARHGEF7 (PubMed:17652093). Interacts with RNF11 (PubMed:14559117, PubMed:19131965). Interacts (via the WW 1 domain) with NFE2 (via the PXY motif 1); the interaction promotes 'Lys-63'-linked ubiquitination of NFE2, retains it in the cytoplasm and prevents its transactivation activity (PubMed:11318614, PubMed:18718448). Interacts (via WW domains) with CXCR4 (via C-terminus); the interaction depends on CXCR4 phosphorylation (PubMed:19116316). Found in a complex with E3 ligase DTX3L and ESCRT-0 components HGS and STAM (PubMed:24790097). Interacts with DTX3L (via C-terminus); the interaction is increased upon CXCL12 stimulation and inhibits ITCH catalytic activity (the interaction is direct) (PubMed:24790097). Interacts with HGS (PubMed:14602072). Interacts (via WW domains) with PCBP2 within a complex containing ITCH, MAVS and PCBP2 (PubMed:19881509). Interacts (via WW domains) with TXNIP (via C-terminus) (PubMed:20068034). Interacts with p15 BID (PubMed:20392206). Interacts with ERBB4 (PubMed:20858735). Interacts with DTX1 (PubMed:17028…
messages: Monoubiquitinated (PubMed:19116316). Autopolyubiquitinated with 'Lys-63' linkages which does not lead to protein degradation (PubMed:18718449, PubMed:23146885, PubMed:24790097).
messages: Nucleus
messages: On T-cell activation, phosphorylation by the JNK cascade on serine and threonine residues surrounding the PRR domain accelerates the ubiquitination and degradation of JUN and JUNB. The increased ITCH catalytic activity due to phosphorylation by JNK1 may occur due to a conformational change disrupting the interaction between the PRR/WW motifs domain and the HECT domain and, thus exposing the HECT domain (By similarity). Phosphorylation by FYN reduces interaction with JUNB and negatively controls JUN ubiquitination and degradation.
messages: The WW domain 4 mediates interaction with ENTREP1.
messages: The WW domains mediate interaction with PPxY motif-containing proteins.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Widely expressed.

9606:DYSF
gene id: 9606:DYSF
uniprot id: O75923
names: Developmental Stage
names: Disease Annotation
names: Domain
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: All seven C2 domains associate with lipid membranes in a calcium-dependent manner. Domains C2 1 and 3 have the highest affinity for calcium, the C2 domain 1 seems to be largely unstructured in the absence of bound ligands. The C2 domain 1 from isoform 14 does not bind calcium in the absence of bound phospholipid (PubMed:24239457, PubMed:24461013).
messages: Belongs to the ferlin family.
messages: Cell membrane
messages: Cytoplasmic vesicle membrane
messages: Expressed in skeletal muscle, myoblast, myotube and in the syncytiotrophoblast (STB) of the placenta (at protein level). Ubiquitous. Highly expressed in skeletal muscle. Also found in heart, brain, spleen, intestine, placenta and at lower levels in liver, lung, kidney and pancreas.
messages: Expression in limb tissue from 5-6 weeks embryos; persists throughout development.
messages: Interacts with CACNA1S. Interacts with ANXA1; the interaction is Ca(2+)- and injury state-dependent. Interacts with ANXA2; the interaction is Ca(2+)- and injury state-dependent. Interacts with CACNA1S and PARVB. Interacts with TRIM72/MG53; interaction is required for transport to sites of cell injury during repair patch formation (By similarity). Interacts with RIPOR2; this interaction occurs during early myogenic differentiation (PubMed:24687993). Interacts with CAV3 and PARVB. Interacts with AHNAK; the interaction is direct and Ca(2+)-independent. Interacts with AHNAK2; the interaction is direct and Ca(2+)-independent.
messages: Key calcium ion sensor involved in the Ca(2+)-triggered synaptic vesicle-plasma membrane fusion. Plays a role in the sarcolemma repair mechanism of both skeletal muscle and cardiomyocytes that permits rapid resealing of membranes disrupted by mechanical stress (By similarity).
messages: Produced by alternative promoter usage.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: sarcolemma

9606:AEBP2
gene id: 9606:AEBP2
uniprot id: Q6ZN18
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Acts as an accessory subunit for the core Polycomb repressive complex 2 (PRC2), which mediates histone H3K27 (H3K27me3) trimethylation on chromatin leading to transcriptional repression of the affected target gene (PubMed:15225548, PubMed:31959557, PubMed:29499137). Plays a role in nucleosome localization of the PRC2 complex (PubMed:29499137).
messages: Belongs to the AEBP2/jing C2H2-type zinc-finger family.
messages: Nucleus
messages: Self-associates (PubMed:15225548). Associates with the PRC2 complex, which consists of the core components EED, EZH1 or EZH2, SUZ12, and RBBP4, and various combinations of accessory subunits including AEBP2, JARID2, PHF19, MTF2 and EPOP (PubMed:12351676, PubMed:15225548, PubMed:31959557, PubMed:29499137). Found in a monomeric PRC2.2 (class 2) complex consisting of at least SUZ12, RBBP4, AEBP2 and JARID2 (PubMed:29499137). Within the PRC2 complex, interacts directly with SUZ12; competes with PHF19 for SUZ12 binding (PubMed:12351676, PubMed:29499137). Interacts with EED, EZH2, and RBBP4 (PubMed:12351676, PubMed:15225548). May also interact with RBBP7 (PubMed:12351676).

9606:DERL1
gene id: 9606:DERL1
uniprot id: E5RGY0
uniprot id: Q9BUN8
names: Caution
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) In case of infection by cytomegaloviruses, it plays a central role in the export from the ER and subsequent degradation of MHC class I heavy chains via its interaction with US11 viral protein, which recognizes and associates with MHC class I heavy chains. Also participates in the degradation process of misfolded cytomegalovirus US2 protein.
messages: (Microbial infection) Interacts with the cytomegalovirus US11 protein.
messages: Belongs to the derlin family.
messages: Endoplasmic reticulum membrane
messages: Functional component of endoplasmic reticulum-associated degradation (ERAD) for misfolded lumenal proteins (PubMed:15215856, PubMed:33658201). Forms homotetramers which encircle a large channel traversing the endoplasmic reticulum (ER) membrane (PubMed:33658201). This allows the retrotranslocation of misfolded proteins from the ER into the cytosol where they are ubiquitinated and degraded by the proteasome (PubMed:33658201). The channel has a lateral gate within the membrane which provides direct access to membrane proteins with no need to reenter the ER lumen first (PubMed:33658201). May mediate the interaction between VCP and the misfolded protein (PubMed:15215856). Also involved in endoplasmic reticulum stress-induced pre-emptive quality control, a mechanism that selectively attenuates the translocation of newly synthesized proteins into the endoplasmic reticulum and reroutes them to the cytosol for proteasomal degradation (PubMed:26565908). By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway (PubMed:26692333).
messages: Functional component of endoplasmic reticulum-associated degradation (ERAD) for misfolded lumenal proteins. May act by forming a channel that allows the retrotranslocation of misfolded proteins into the cytosol where they are ubiquitinated and degraded by the proteasome.
messages: Homotetramer (PubMed:33658201). The four subunits of the tetramer are arranged in a twofold symmetry (PubMed:33658201). Forms heterooligomers with DERL2 and DERL3; binding to DERL3 is poorer than that between DERL2 and DERL3. Interacts (via SHP-box motif) with VCP (PubMed:16289116, PubMed:16186510, PubMed:16186509, PubMed:16449189, PubMed:27714797). Interacts with AMFR, SELENOS, SEL1L, SELENOK and SYVN1, as well as with SEL1L-SYVN1 and VCP-SELENOS protein complexes; this interaction is weaker than that observed between DERL2 and these complexes. Interacts with NGLY1 and YOD1. Does not bind to EDEM1. Interacts with DNAJB9. Interacts with RNF103 (PubMed:15215856, PubMed:16055502, PubMed:16186509, PubMed:16186510, PubMed:16289116, PubMed:16449189, PubMed:18675248, PubMed:19818707, PubMed:22016385). Interacts with HM13 (PubMed:25239945). Interacts with XBP1 isoform 1 (via luminal/ectodomain domain); the interaction obviates the need for ectodomain shedding prior HM13/SPP-mediated XBP1 isoform 1 cleavage (PubMed:25239945). Interacts with the signal recognition particle/SRP and the SRP receptor; in the process of endoplasmic reticulum stress-induced pre-emptive quality control (PubMed:26565908). May interact with UBXN6 (PubMed:19275885). Interacts with ZFAND2B; probably through VCP (PubMed:24160817). Interacts with CCDC47 (By similarity). Interacts with C18orf32 (PubMed:29275994). May interact with TRAM1 (PubMed:19121997).
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: Membrane
messages: Ubiquitous.

9606:MTUS1
gene id: 9606:MTUS1
uniprot id: Q9ULD2
names: Disease Annotation
names: Function
names: Induction
names: Miscellaneous
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the MTUS1 family.
messages: Cell membrane
messages: Contaminating sequence. Potential poly-A sequence.
messages: Cooperates with AGTR2 to inhibit ERK2 activation and cell proliferation. May be required for AGTR2 cell surface expression. Together with PTPN6, induces UBE2V2 expression upon angiotensin-II stimulation. Isoform 1 inhibits breast cancer cell proliferation, delays the progression of mitosis by prolonging metaphase and reduces tumor growth.
messages: Down-regulated in invasive breast carcinomas (at protein level).
messages: Expressed at very low levels in most tissues.
messages: Golgi apparatus
messages: Homodimer. Interacts with AGTR2. Interacts with PTPN6 (By similarity). Isoform 1 associates with microtubules.
messages: Mitochondrion
messages: Nucleus
messages: The gene represented in this entry may be involved in disease pathogenesis.
messages: Ubiquitously expressed (at protein level). Highly expressed in brain. Down-regulated in ovarian carcinoma, pancreas carcinoma, colon carcinoma and head and neck squamous cell carcinoma (HNSCC). Isoform 1 is the major isoform in most peripheral tissues. Isoform 2 is abundant in most peripheral tissues. Isoform 3 is the major isoform in brain, female reproductive tissues, thyroid and heart. Within brain it is highly expressed in corpus callosum and pons. Isoform 6 is brain-specific, it is the major isoform in cerebellum and fetal brain.
messages: centrosome
messages: spindle

9606:ASL
gene id: 9606:ASL
uniprot id: A0A024RDL8
uniprot id: A0A0S2Z316
uniprot id: P04424
names: Activity Regulation
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subunit
messages: Acetylation modifies enzyme activity in response to alterations of extracellular nutrient availability. Acetylation increased with trichostin A (TSA) or with nicotinamide (NAM). Glucose increases acetylation by about a factor of 3 with decreasing enzyme activity. Acetylation on Lys-288 is decreased on the addition of extra amino acids resulting in activation of enzyme activity.
messages: Belongs to the lyase 1 family. Argininosuccinate lyase subfamily.
messages: Catalyzes the reversible cleavage of L-argininosuccinate to fumarate and L-arginine, an intermediate step reaction in the urea cycle mostly providing for hepatic nitrogen detoxification into excretable urea as well as de novo L-arginine synthesis in nonhepatic tissues (PubMed:11747433, PubMed:11747432, PubMed:9045711, PubMed:22081021, PubMed:2263616). Essential regulator of intracellular and extracellular L-arginine pools. As part of citrulline-nitric oxide cycle, forms tissue-specific multiprotein complexes with argininosuccinate synthase ASS1, transport protein SLC7A1 and nitric oxide synthase NOS1, NOS2 or NOS3, allowing for cell-autonomous L-arginine synthesis while channeling extracellular L-arginine to nitric oxide synthesis pathway (PubMed:22081021).
messages: Enzyme activity is regulated by acetylation.
messages: Homotetramer (PubMed:11747433). Forms tissue-specific complexes with ASS1, SLC7A1, HSP90AA1 and nitric oxide synthase NOS1, NOS2 or NOS3; the complex maintenance is independent of ASL catalytic function (By similarity).
messages: The disease is caused by variants affecting the gene represented in this entry. The phenotype heterogeneity among patients is associated with interallelic complementation resulting in either complete loss of activity or partial regeneration of functional active sites in the heterotetrameric mutant protein.

9606:PRRX2
gene id: 9606:PRRX2
uniprot id: A0A140VJS2
uniprot id: Q99811
names: Developmental Stage
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the paired homeobox family.
messages: Higher expression in fetus than in adult.
messages: In fetal skin, highest expression found in cells of mesodermal origin within the dermal papilla of the developing hair shaft. Not detected in epidermis or dermis. In adult skin, weakly expressed within the basal layers of the epidermis. Not expressed in dermis.
messages: May play a role in the scarless healing of cutaneous wounds during the first two trimesters of development.
messages: Nucleus

9606:CTRC
gene id: 9606:CTRC
uniprot id: Q99895
names: Disease Annotation
names: Function
names: Similarity
names: Tissue Specificity
messages: Belongs to the peptidase S1 family. Elastase subfamily.
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry. Loss-of-function CTRC variants predispose to pancreatitis by diminishing its protective trypsin-degrading activity (PubMed:18059268). They cause loss of function by one or more of three mechanisms: reduced secretion, catalytic defect and increased degradation by trypsin (PubMed:22942235).
messages: Pancreas.
messages: Regulates activation and degradation of trypsinogens and procarboxypeptidases by targeting specific cleavage sites within their zymogen precursors. Has chymotrypsin-type protease activity and hypocalcemic activity.

9606:RFPL2
gene id: 9606:RFPL2
uniprot id: O75678
names: Miscellaneous
names: Tissue Specificity
messages: May be due to intron retention.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Seems to be expressed in prostate and less abundantly in adult brain, fetal liver, and fetal kidney.

9606:SLITRK4
gene id: 9606:SLITRK4
uniprot id: Q8IW52
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the SLITRK family.
messages: Cell membrane
messages: Expressed in the cerebral cortex of the brain and at higher levels in some astrocytic brain tumors such as astrocytomas, glioblastomas and primitive neuroectodermal tumors.
messages: Interacts (via LRR 1 and 2 repeats) with PTPRD (via extracellular domain).
messages: It is involved in synaptogenesis and promotes synapse differentiation (PubMed:27812321). Suppresses neurite outgrowth (By similarity).
messages: Membrane

9606:GSR
gene id: 9606:GSR
uniprot id: P00390
uniprot id: V9HW90
names: Cofactor
names: Disease Annotation
names: Domain
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the class-I pyridine nucleotide-disulfide oxidoreductase family.
messages: Binds 1 FAD per subunit.
messages: Cytoplasm
messages: Each subunit can be divided into 4 domains that are consecutive along the polypeptide chain. Domains 1 and 2 bind FAD and NADPH, respectively. Domain 4 forms the interface.
messages: Expressed at very high levels in peripheral blood.
messages: Homodimer; disulfide-linked.
messages: Maintains high levels of reduced glutathione in the cytosol.
messages: Mitochondrion
messages: Produced by alternative initiation of isoform Mitochondrial.
messages: The active site is a redox-active disulfide bond.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:UBR5
gene id: 9606:UBR5
uniprot id: O95071
names: Function
names: Miscellaneous
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts with human T-cell leukemia virus 1/HTLV-1 protein HBZ; this interaction modulates HBZ stability.
messages: A cysteine residue is required for ubiquitin-thioester formation.
messages: Binds TOPBP1. Associates with CDK9 and TFIIS/TCEA1 and forms a transcription regulatory complex made of CDK9, RNAP II, UBR5 and TFIIS/TCEA1 that can stimulate target gene transcription (e.g. gamma fibrinogen/FGG) by recruiting their promoters. Associates with the E3 ligase complex containing DYRK2, EDD/UBR5, DDB1 and DCAF1 proteins (EDVP complex). Interacts directly with DYRK2. Interacts with PIH1D1 (PubMed:24656813).
messages: E3 ubiquitin-protein ligase which is a component of the N-end rule pathway. Recognizes and binds to proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation (By similarity). Involved in maturation and/or transcriptional regulation of mRNA by activating CDK9 by polyubiquitination. May play a role in control of cell cycle progression. May have tumor suppressor function. Regulates DNA topoisomerase II binding protein (TopBP1) in the DNA damage response. Plays an essential role in extraembryonic development. Ubiquitinates acetylated PCK1. Also acts as a regulator of DNA damage response by acting as a suppressor of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites, thereby acting as a guard against excessive spreading of ubiquitinated chromatin at damaged chromosomes.
messages: Nucleus
messages: Widely expressed. Most abundant in testis and expressed at high levels in brain, pituitary and kidney.

9606:TRAPPC14
gene id: 9606:TRAPPC14
uniprot id: Q8WVR3
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Broadly expressed. High levels in brain, cerebellum, testis and whole blood.
messages: Component of the multisubunit TRAPP II complex, which includes at least TRAPPC1, TRAPPC2, TRAPPC2L, TRAPPC3, TRAPPC4, TRAPPC5, TRAPPC6A/B, TRAPPC9, TRAPPC10 and TRAPPC14. TRAPPC9, TRAPPC10 and TRAPPC14 are specific subunits of the TRAPP II complex (PubMed:31467083). Interacts with alpha-tubulin during mitosis (PubMed:30715179). Interacts with RAB3IP (via the N-terminal region); this interaction mediates RAB3IP association with the TRAPP II complex (PubMed:31467083). Interacts with TRAPPC10 (PubMed:31467083). Interacts with FBF1 (PubMed:31467083).
messages: Cytoplasm
messages: Midbody
messages: Specific subunit of the TRAPP (transport protein particle) II complex, a highly conserved vesicle tethering complex that functions in late Golgi trafficking as a membrane tether (PubMed:31467083, PubMed:30715179). TRAPP II complex has also GEF activity toward RAB1A (By similarity). TRAPPC14 is dispensable for TRAPPII complex integrity but mediates RAB3IP preciliary vesicle trafficking to the mother centriole during ciliogenesis (PubMed:31467083). Modulates YAP1 activity as transcriptional regulator (PubMed:30447097).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Vesicle
messages: spindle

9606:DYNC1LI1
gene id: 9606:DYNC1LI1
uniprot id: E9PHI6
uniprot id: Q9Y6G9
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Interacts with human adenovirus 5 hexon protein; this interaction probably allows virus intracellular transport.
messages: Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. May play a role in binding dynein to membranous organelles or chromosomes.
messages: Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. May play a role in binding dynein to membranous organelles or chromosomes. Probably involved in the microtubule-dependent transport of pericentrin. Is required for progress through the spindle assembly checkpoint. The phosphorylated form appears to be involved in the selective removal of MAD1L1 and MAD1L2 but not BUB1B from kinetochores. Forms a functional Rab11/RAB11FIP3/dynein complex onto endosomal membrane that regulates the movement of peripheral sorting endosomes (SE) along microtubule tracks toward the microtubule organizing center/centrosome, generating the endosomal recycling compartment (ERC) (PubMed:20026645).
messages: Belongs to the dynein light intermediate chain family.
messages: Cytoplasm
messages: Homodimer (By similarity). The cytoplasmic dynein 1 complex consists of two catalytic heavy chains (HCs) and a number of non-catalytic subunits presented by intermediate chains (ICs), light intermediate chains (LICs) and light chains (LCs); the composition seems to vary in respect to the IC, LIC and LC composition. The heavy chain homodimer serves as a scaffold for the probable homodimeric assembly of the respective non-catalytic subunits. The ICs and LICs bind directly to the HC dimer and the LCs assemble on the IC dimer. Self-associates. Interacts with DYNC1H1; DYNC1LI1 and DYNC1LI2 bind mutually exclusive to DYNC1H1. Interacts with PCNT (By similarity). Forms a complex with RAB11FIP3 and RAB11A1; the interaction between DYNC1LI1 and RAB11FIP3 is direct and induces DYNC1LI1 localization onto endosomal membrane; the complex regulates endocytic trafficking (PubMed:20026645).
messages: Homodimer. The cytoplasmic dynein 1 complex consists of two catalytic heavy chains (HCs) and a number of non-catalytic subunits presented by intermediate chains (ICs).
messages: Phosphorylated during mitosis but not in interphase.
messages: Recycling endosome membrane
messages: cytoskeleton
messages: kinetochore
messages: spindle pole

9606:USP17L7
gene id: 9606:USP17L7
uniprot id: P0C7H9
names: Caution
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the peptidase C19 family. USP17 subfamily.
messages: Endoplasmic reticulum
messages: Nucleus
messages: Phe-89 is present instead of the conserved Cys which is expected to be an active site residue suggesting that this protein has lost its catalytic activity.
messages: The RS447 megasatellite DNA is a highly polymorphic conserved tandem repetitive sequence which contains a copy of the USP17 gene. It is present with an interindividual variation in copy number, ranging from 20 to 103, and can be found in the genome both on chromosome 4 and chromosome 8. The high similarity between the UPS17-like genes makes impossible to clearly assign data to one of the genes of the family. Oligonucleotides designed in RNAi experiments are for instance not specific of a given UPS17-like gene.

9606:CARS2
gene id: 9606:CARS2
uniprot id: Q9HA77
names: Cofactor
names: Disease Annotation
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the class-I aminoacyl-tRNA synthetase family.
messages: Binds 1 zinc ion per subunit.
messages: Mitochondrion matrix
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:RBM38
gene id: 9606:RBM38
uniprot id: Q9H0Z9
names: Caution
names: Function
names: Induction
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
messages: (Microbial infection) Essential factor for the splicing of the pre-mRNAs of human parvovirus B19 (B19V) and for the expression of B19V 11-kDa protein, which enhances viral replication.
messages: Belongs to the RBM38 family.
messages: By p53/TP53 family. Directly induced by p53/TP53, TP63/p63 and TP73/p73.
messages: Chimeric cDNA.
messages: It is uncertain whether Met-1 or Met-24 is the initiator.
messages: Nucleus
messages: RNA-binding protein that specifically bind the 3'-UTR of CDKN1A transcripts, leading to maintain the stability of CDKN1A transcripts, thereby acting as a mediator of the p53/TP53 family to regulate CDKN1A. CDKN1A is a cyclin-dependent kinase inhibitor transcriptionally regulated by the p53/TP53 family to induce cell cycle arrest. Isoform 1, but not isoform 2, has the ability to induce cell cycle arrest in G1 and maintain the stability of CDKN1A transcripts induced by p53/TP53. Also acts as a mRNA splicing factor. Specifically regulates the expression of FGFR2-IIIb, an epithelial cell-specific isoform of FGFR2. Plays a role in myogenic differentiation.
messages: cytosol

9606:ING3
gene id: 9606:ING3
uniprot id: Q9NXR8
names: Disease Annotation
names: Domain
names: Function
names: Miscellaneous
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the ING family.
messages: Component of the NuA4 histone acetyltransferase (HAT) complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair. NuA4 may also play a direct role in DNA repair when directly recruited to sites of DNA damage. Component of a SWR1-like complex that specifically mediates the removal of histone H2A.Z/H2AZ1 from the nucleosome.
messages: Expressed in brain, heart, kidney, liver, lung, ovaries, placenta, prostate, skeletal muscle, small intestine, spleen, testis and thymus.
messages: Interacts with H3K4me3 and to a lesser extent with H3K4me2. Component of the NuA4 histone acetyltransferase complex which contains the catalytic subunit KAT5/TIP60 and the subunits EP400, TRRAP/PAF400, BRD8/SMAP, EPC1, DMAP1/DNMAP1, RUVBL1/TIP49, RUVBL2, ING3, actin, ACTL6A/BAF53A, MORF4L1/MRG15, MORF4L2/MRGX, MRGBP, YEATS4/GAS41, VPS72/YL1 and MEAF6. The NuA4 complex interacts with MYC and the adenovirus E1A protein. HTATTIP/TIP60, EPC1, and ING3 together constitute a minimal HAT complex termed Piccolo NuA4. Component of a SWR1-like complex.
messages: Intron retention.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Nucleus
messages: The PHD-type zinc finger mediates the binding to H3K4me3.
messages: The disease may be caused by variants affecting the gene represented in this entry.

9606:CTRB2
gene id: 9606:CTRB2
uniprot id: Q6GPI1
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the peptidase S1 family.
messages: extracellular space

9606:RNF103
gene id: 9606:RNF103
uniprot id: O00237
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acts as an E2-dependent E3 ubiquitin-protein ligase, probably involved in the ER-associated protein degradation pathway.
messages: Endoplasmic reticulum membrane
messages: Highly expressed in the normal cerebellum but not in the cerebral cortex.
messages: Interacts with DERL1 and VCP.

9606:SYF2
gene id: 9606:SYF2
uniprot id: O95926
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Abundantly expressed in the heart, skeletal muscle and kidney. Expressed at lower level other tissues.
messages: Belongs to the SYF2 family.
messages: Identified in the spliceosome C complex (PubMed:11991638, PubMed:28502770, PubMed:28076346). Interacts with CCNDBP1 (PubMed:11118353).
messages: Involved in pre-mRNA splicing as component of the spliceosome (PubMed:11991638, PubMed:28502770, PubMed:28076346).
messages: Nucleus

9606:TMEM72
gene id: 9606:TMEM72
uniprot id: A0PK05
names: Subcellular Location Annotation
messages: Membrane

9606:WDR43
gene id: 9606:WDR43
uniprot id: Q15061
names: Developmental Stage
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the UTP5 family.
messages: Expressed during embryonic development, expression decreases at blastocyst stage.
messages: N-terminal domain is required for nucleoplasm location and C-terminal domain for nucleolus location.
messages: Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3 (PubMed:34516797). May be a component of the proposed t-UTP subcomplex of the ribosomal small subunit (SSU) processome containing at least UTP4, WDR43, HEATR1, UTP15, WDR75 (PubMed:17699751, PubMed:22916032). Binds to RNA; binding is required for its chromatin association. Interacts with CDK9, DDX21 and SUPT6H. Interacts with RNA polymerase II (By similarity). Interacts directly with UTP4 and UTP15 (PubMed:24219289).
messages: Ribosome biogenesis factor that coordinates hyperactive transcription and ribogenesis (PubMed:17699751). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome. Involved in nucleolar processing of pre-18S ribosomal RNA. Required for optimal pre-ribosomal RNA transcription by RNA polymerase I (PubMed:17699751, PubMed:34516797). Essential for stem cell pluripotency and embryonic development. In the nucleoplasm, recruited by promoter-associated/nascent transcripts and transcription to active promoters where it facilitates releases of elongation factor P-TEFb and paused RNA polymerase II to allow transcription elongation and maintain high-level expression of its targets genes (By similarity).
messages: nucleolus
messages: nucleolus fibrillar center
messages: nucleoplasm

9606:EPOP
gene id: 9606:EPOP
uniprot id: A6NHQ4
names: Domain
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Associates with the PRC2 complex, which consists of the core components EED, EZH1 or EZH2, SUZ12, and RBBP4, and various combinations of accessory subunits including AEBP2, JARID2, PHF19, MTF2 and EPOP (PubMed:24550272, PubMed:29499137). Within the complex, interacts with SUZ12 (via C2H2 zinc finger domain); competes with JARID2 for SUZ12 binding (PubMed:29499137). Associates with the elongin BC complex (By similarity). Interacts with USP7 (By similarity).
messages: Chromosome
messages: Nucleus
messages: Scaffold protein that serves as a bridging partner between the PRC2/EZH2 complex and the elongin BC complex: required to fine-tune the transcriptional status of Polycomb group (PcG) target genes in embryonic stem cells (ESCs). Plays a key role in genomic regions that display both active and repressive chromatin properties in pluripotent stem cells by sustaining low level expression at PcG target genes: acts by recruiting the elongin BC complex, thereby restricting excessive activity of the PRC2/EZH2 complex. Interaction with USP7 promotes deubiquitination of H2B at promoter sites. Acts as a regulator of neuronal differentiation.
messages: The BC-box, which mediates binding to the elongin BC complex.

9606:TMEM238
gene id: 9606:TMEM238
uniprot id: C9JI98
names: Subcellular Location Annotation
messages: Membrane

9606:KBTBD8
gene id: 9606:KBTBD8
uniprot id: Q8NFY9
names: Developmental Stage
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the KBTBD8 family.
messages: Component of the BCR(KBTBD8) E3 ubiquitin ligase complex, at least composed of CUL3, KBTBD8 and RBX1 (PubMed:26399832).
messages: Down-regulated in differentiating embryonic stem cells (ESCs) (at protein level).
messages: Golgi apparatus
messages: Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a regulator of neural crest specification (PubMed:26399832). The BCR(KBTBD8) complex acts by mediating monoubiquitination of NOLC1 and TCOF1: monoubiquitination promotes the formation of a NOLC1-TCOF1 complex that acts as a platform to connect RNA polymerase I with enzymes responsible for ribosomal processing and modification, leading to remodel the translational program of differentiating cells in favor of neural crest specification (PubMed:26399832).
messages: spindle

9606:GINS2
gene id: 9606:GINS2
uniprot id: Q9Y248
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the GINS2/PSF2 family.
messages: Chromosome
messages: Component of the GINS complex which is a heterotetramer of GINS1, GINS2, GINS3 and GINS4 (PubMed:17417653, PubMed:17545466, PubMed:17557111, PubMed:17652513, PubMed:32453425). Forms a stable subcomplex with GINS3. GINS complex interacts with DNA primase in vitro (PubMed:17417653, PubMed:17545466, PubMed:17557111, PubMed:17652513). Component of the CMG helicase complex, a hexameric ring of related MCM2-7 subunits stabilized by CDC45 and the tetrameric GINS complex (PubMed:34700328, PubMed:34694004, PubMed:32453425).
messages: Nucleus
messages: Required for correct functioning of the GINS complex, a complex that plays an essential role in the initiation of DNA replication, and progression of DNA replication forks (PubMed:17417653). GINS complex is a core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built (PubMed:32453425, PubMed:34694004, PubMed:34700328, PubMed:35585232).

9606:XPR1
gene id: 9606:XPR1
uniprot id: Q9UBH6
names: Caution
names: Developmental Stage
names: Disease Annotation
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the SYG1 (TC 2.A.94) family.
messages: Cell membrane
messages: Confers susceptibility to xenotropic murine leukemia retrovirus (X-MLV) infection in vitro, but it is unclear whether its ability to act as a receptor for xenotropic and polytropic murine leukemia retroviruses is relevant in vivo and whether such viruses can infect human.
messages: Expressed in fetal liver.
messages: Inorganic ion transporter that mediates phosphate ion export across plasma membrane. Plays a major role in phosphate homeostasis, preventing intracellular phosphate accumulation and possible calcium phosphate precipitation, ultimately preserving calcium signaling. The molecular mechanism of phosphate transport, whether electrogenic, electroneutral or coupled to other ions, remains to be elucidated (PubMed:23791524, PubMed:25938945, PubMed:31043717) (By similarity). Binds inositol hexakisphosphate (Ins6P) and similar inositol polyphosphates, such as 5-diphospho-inositol pentakisphosphate (5-InsP7), important intracellular signaling molecules involved in regulation of phosphate flux (PubMed:27080106).
messages: The SPX domain has high affinity for inositol polyphosphates, such as myo-inositol hexakisphosphate and 5-diphospho-myo-inositol pentakisphosphate (5-InsP7). Its affinity for inorganic phosphate is tow to three orders of magnitude lower.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Widely expressed. Detected in spleen, lymph node, thymus, leukocytes, bone marrow, heart, kidney, pancreas and skeletal muscle.

9606:KIR2DL3
gene id: 9606:KIR2DL3
uniprot id: P43628
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the immunoglobulin superfamily.
messages: Cell membrane
messages: Interacts with ARRB2.
messages: Receptor on natural killer (NK) cells for HLA-C alleles (HLA-Cw1, HLA-Cw3 and HLA-Cw7). Inhibits the activity of NK cells thus preventing cell lysis.

9606:PABPN1L
gene id: 9606:PABPN1L
uniprot id: A6NDY0
names: Function
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Binds the poly(A) tail of mRNA.
messages: Cytoplasm
messages: Expressed in various adult tissues.

9606:CCDC90B
gene id: 9606:CCDC90B
uniprot id: Q9GZT6
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the CCDC90 family.
messages: Interacts with MCU (PubMed:27184846).
messages: Mitochondrion membrane

9606:FADS6
gene id: 9606:FADS6
uniprot id: A0A087WYB9
uniprot id: Q8N9I5
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the fatty acid desaturase type 1 family.
messages: Membrane
messages: The N-terminus contains a duplication of the repeated 'MEPTEP' sequence. It is unclear whether such duplication is due to a sequencing error or a polymorphism.

9606:TCL1B
gene id: 9606:TCL1B
uniprot id: O95988
names: Function
names: Miscellaneous
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Activated in chronic T-cell leukemias (T-CLL) carrying rearrangements of the 14q32.1 region.
messages: Belongs to the TCL1 family.
messages: Enhances the phosphorylation and activation of AKT1 and AKT2.
messages: Expressed in a variety of tissues including placenta and testis.
messages: Interacts with AKT1 and AKT2 (via PH domain). Does not interact with AKT3.

9606:DCAF7
gene id: 9606:DCAF7
uniprot id: P61962
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the WD repeat DCAF7 family.
messages: Cytoplasm
messages: Interacts with DYRK1A, DYRK1B and DIAPH1. Interacts with DDB1. Interacts with ZNF703. Interacts with human adenovirus 5 E1A protein (PubMed:23864635).
messages: Involved in craniofacial development. Acts upstream of the EDN1 pathway and is required for formation of the upper jaw equivalent, the palatoquadrate. The activity required for EDN1 pathway function differs between the first and second arches (By similarity). Associates with DIAPH1 and controls GLI1 transcriptional activity. Could be involved in normal and disease skin development. May function as a substrate receptor for CUL4-DDB1 E3 ubiquitin-protein ligase complex.
messages: Nucleus

9606:INA
gene id: 9606:INA
uniprot id: Q16352
names: Developmental Stage
names: Function
names: PTM
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Belongs to the intermediate filament family.
messages: Class-IV neuronal intermediate filament that is able to self-assemble. It is involved in the morphogenesis of neurons. It may form an independent structural network without the involvement of other neurofilaments or it may cooperate with NEFL to form the filamentous backbone to which NEFM and NEFH attach to form the cross-bridges. May also cooperate with the neuronal intermediate filament protein PRPH to form filamentous networks (By similarity).
messages: Expressed in brain as early as the 16th week of gestation, and increased rapidly and reached a steady state level by the 18th week of gestation.
messages: Forms homodimers (in vitro) (By similarity). Forms heterodimers with NEFL, NEFM or NEFH (in vitro) (By similarity).
messages: Found predominantly in adult CNS.
messages: O-glycosylated.

9606:SLC39A7
gene id: 9606:SLC39A7
uniprot id: A0A024RCX7
uniprot id: B4DZZ8
uniprot id: Q92504
names: Activity Regulation
names: Disease Annotation
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the ZIP transporter (TC 2.A.5) family. KE4/Catsup subfamily.
messages: Down-regulated by Zn(+2).
messages: Endoplasmic reticulum membrane
messages: Homodimer.
messages: Membrane
messages: Methylation at some His residue by METTL9 leads to reduced zinc-binding.
messages: Phosphorylation activates zinc transport activity.
messages: Rapidly phosphorylated by CK2 following Zn(2+) treatment. This phosphorylation is required for efficient cytosolic Zn(2+) release.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Transports Zn(2+) from the endoplasmic reticulum (ER)/Golgi apparatus to the cytosol, playing an essential role in the regulation of cytosolic zinc levels (PubMed:14525538, PubMed:15705588, PubMed:29980658, PubMed:28205653). Acts as gatekeeper of zinc release from intracellular stores, requiring post-translational activation by phosphorylation, resulting in activation of multiple downstream pathways leading to cell growth and proliferation (PubMed:29980658, PubMed:22317921, PubMed:28205653). Has an essential role in B cell development and is required for proper B cell receptor signaling (PubMed:30718914). Plays an important role in maintaining intestinal epithelial homeostasis and skin dermis development by regulating ER function (By similarity). Controls cell signaling pathways involved in glucose metabolism in skeletal muscle (By similarity). Has a protective role against ER stress in different biological contexts (PubMed:29980658, PubMed:30237509). Mediates Zn(2+)-induced ferroptosis (PubMed:33608508).
messages: Widely expressed.
messages: cis-Golgi network membrane

9606:MUTYH
gene id: 9606:MUTYH
uniprot id: E5KP25
uniprot id: E5KP26
uniprot id: E5KP27
uniprot id: E5KP28
uniprot id: E9PM53
uniprot id: Q9UIF7
names: Cofactor
names: Disease Annotation
names: Function
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
messages: Adenine glycosylase active on G-A mispairs.
messages: Belongs to the Nth/MutY family.
messages: Binds 1 [4Fe-4S] cluster.
messages: Binds 1 [4Fe-4S] cluster. The cluster does not appear to play a role in catalysis, but is probably involved in the proper positioning of the enzyme along the DNA strand.
messages: Involved in oxidative DNA damage repair. Initiates repair of A*oxoG to C*G by removing the inappropriately paired adenine base from the DNA backbone. Possesses both adenine and 2-OH-A DNA glycosylase activities.
messages: Mitochondrion
messages: Nucleus
messages: Probable cloning artifact.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The gene represented in this entry may be involved in disease pathogenesis. Somatic mutations contribute to the development of a sub-set of sporadic gastric cancers in carriers of Helicobacter pylori (PubMed:15273732).

9606:TYMS
gene id: 9606:TYMS
uniprot id: P04818
uniprot id: Q53Y97
names: Disease Annotation
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the thymidylate synthase family.
messages: Catalyzes the reductive methylation of 2'-deoxyuridine 5'-monophosphate (dUMP) to thymidine 5'-monophosphate (dTMP), using the cosubstrate, 5,10- methylenetetrahydrofolate (CH2H4folate) as a 1-carbon donor and reductant and contributes to the de novo mitochondrial thymidylate biosynthesis pathway.
messages: Cytoplasm
messages: Expressed both in normal and cancerous tissues.
messages: Expressed only in cancerous tissues.
messages: Homodimer.
messages: Mitochondrion
messages: Mitochondrion inner membrane
messages: Mitochondrion matrix
messages: Nucleus
messages: The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry. TYMS germline variants in the presence of a common ENOSF1 haplotype (defined by rs699517, rs2790 and rs1512643) result in severe thymidylate synthase deficiency and disease. The pathogenic mechanism involves increased expression of ENOSF1 relative to TYMS, and post-transcriptional inhibition of TYMS translation through ENOSF1-TYMS RNA-RNA interactions.

9606:SHCBP1
gene id: 9606:SHCBP1
uniprot id: Q8NEM2
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Interacts directly with isoform p52shc of SHC1 via its SH2 domain (By similarity). Interacts with TRIM71; leading to enhanced SHCBP1 protein stability (By similarity). Interacts with both members of the centralspindlin complex, KIF23 and RACGAP1 (PubMed:21187330).
messages: May play a role in signaling pathways governing cellular proliferation, cell growth and differentiation. May be a component of a novel signaling pathway downstream of Shc. Acts as a positive regulator of FGF signaling in neural progenitor cells.
messages: Midbody
messages: spindle

9606:FCRL1
gene id: 9606:FCRL1
uniprot id: Q96LA6
names: Function
names: Induction
names: PTM
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Cell membrane
messages: Down-regulated in activated B-cells.
messages: May function as an activating coreceptor in B-cells. May function in B-cells activation and differentiation.
messages: Phosphorylated on tyrosines upon activation.
messages: Primarily expressed in secondary lymphoid tissues by mature subsets of B-cells. Detected in spleen, lymph node, heart, skeletal muscle, kidney, liver and placenta. Specifically expressed by mature B lineage cells with higher expression in naive versus memory B-cells (at protein level).

9606:PRPF18
gene id: 9606:PRPF18
uniprot id: Q99633
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the PRP18 family.
messages: Heterodimer with PPIH. Interacts with PRPF4 and with the spliceosome. Part of a complex containing U4/U6 snRNPs.
messages: Nucleus speckle
messages: Participates in the second step of pre-mRNA splicing.

9606:MRPL36
gene id: 9606:MRPL36
uniprot id: Q9P0J6
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the bacterial ribosomal protein bL36 family.
messages: Component of the mitochondrial large ribosomal subunit (mt-LSU). Mature mammalian 55S mitochondrial ribosomes consist of a small (28S) and a large (39S) subunit. The 28S small subunit contains a 12S ribosomal RNA (12S mt-rRNA) and 30 different proteins. The 39S large subunit contains a 16S rRNA (16S mt-rRNA), a copy of mitochondrial valine transfer RNA (mt-tRNA(Val)), which plays an integral structural role, and 52 different proteins. bL36m has a zinc binding site.
messages: Mitochondrion

9606:EMC2
gene id: 9606:EMC2
uniprot id: Q15006
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the EMC2 family.
messages: Component of the ER membrane protein complex (EMC) (PubMed:22119785, PubMed:29242231, PubMed:32439656, PubMed:32459176, PubMed:33964204). Interacts with WNK1 (via amphipathic alpha-helix region); promoting the ER membrane protein complex assembly by preventing EMC2 ubiquitination (PubMed:33964204).
messages: Endoplasmic reticulum membrane
messages: Part of the endoplasmic reticulum membrane protein complex (EMC) that enables the energy-independent insertion into endoplasmic reticulum membranes of newly synthesized membrane proteins (PubMed:30415835, PubMed:29809151, PubMed:29242231, PubMed:32459176, PubMed:32439656, PubMed:33964204). Preferentially accommodates proteins with transmembrane domains that are weakly hydrophobic or contain destabilizing features such as charged and aromatic residues (PubMed:30415835, PubMed:29809151, PubMed:29242231). Involved in the cotranslational insertion of multi-pass membrane proteins in which stop-transfer membrane-anchor sequences become ER membrane spanning helices (PubMed:30415835, PubMed:29809151). It is also required for the post-translational insertion of tail-anchored/TA proteins in endoplasmic reticulum membranes (PubMed:29809151, PubMed:29242231). By mediating the proper cotranslational insertion of N-terminal transmembrane domains in an N-exo topology, with translocated N-terminus in the lumen of the ER, controls the topology of multi-pass membrane proteins like the G protein-coupled receptors (PubMed:30415835). By regulating the insertion of various proteins in membranes, it is indirectly involved in many cellular processes (Probable).
messages: Ubiquitinated when soluble in the cytoplasm, leading to its degradation by the proteasome (PubMed:33964204). Interaction with EMC2 prevents its ubiquitination and degradation (PubMed:33964204).

9606:RFNG
gene id: 9606:RFNG
uniprot id: F5H3H7
uniprot id: Q8N9R1
uniprot id: Q9Y644
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the glycosyltransferase 31 family.
messages: Glycosyltransferase that initiates the elongation of O-linked fucose residues attached to EGF-like repeats in the extracellular domain of Notch molecules. Modulates NOTCH1 activity by modifying O-fucose residues at specific EGF-like domains resulting in enhancement of NOTCH1 activation by DLL1 and JAG1. May be involved in limb formation and in neurogenesis.
messages: Golgi apparatus membrane
messages: Membrane

9606:WDR47
gene id: 9606:WDR47
uniprot id: O94967
names: Subcellular Location Annotation
names: Subunit
messages: Interacts with MAP1S (via WD repeats).
messages: cytoskeleton

9606:TMEM108
gene id: 9606:TMEM108
uniprot id: Q6UXF1
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: Early endosome
messages: Endosome membrane
messages: Glycosylated.
messages: Interacts with DST (isoform 1). Interacts with SH3GL2. Interacts (via N-terminus) with CYFIP1 and CYFIP2; the interactions associate TMEM108 with the WAVE1 complex.
messages: Membrane
messages: Postsynaptic density
messages: Transmembrane protein required for proper cognitive functions. Involved in the development of dentate gyrus (DG) neuron circuitry, is necessary for AMPA receptors surface expression and proper excitatory postsynaptic currents of DG granule neurons. Regulates the organization and stability of the microtubule network of sensory neurons to allow axonal transport. Through the interaction with DST, mediates the docking of the dynein/dynactin motor complex to vesicle cargos for retrograde axonal transport. In hippocampal neurons, required for BDNF-dependent dendrite outgrowth. Cooperates with SH3GL2 and recruits the WAVE1 complex to facilitate actin-dependent BDNF:NTRK2 early endocytic trafficking and mediate signaling from early endosomes.
messages: axon
messages: dendrite

9606:KDM8
gene id: 9606:KDM8
uniprot id: Q8N371
names: Caution
names: Cofactor
names: Function
names: Induction
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Bifunctional enzyme that acts both as an endopeptidase and 2-oxoglutarate-dependent monooxygenase (PubMed:28847961, PubMed:29459673, PubMed:28982940, PubMed:29563586). Endopeptidase that cleaves histones N-terminal tails at the carboxyl side of methylated arginine or lysine residues, to generate 'tailless nucleosomes', which may trigger transcription elongation (PubMed:28847961, PubMed:29459673, PubMed:28982940). Preferentially recognizes and cleaves monomethylated and dimethylated arginine residues of histones H2, H3 and H4. After initial cleavage, continues to digest histones tails via its aminopeptidase activity (PubMed:28847961, PubMed:29459673). Upon DNA damage, cleaves the N-terminal tail of histone H3 at monomethylated lysine residues, preferably at monomethylated 'Lys-9' (H3K9me1). The histone variant H3F3A is the major target for cleavage (PubMed:28982940). Additionnally, acts as Fe(2+) and 2-oxoglutarate-dependent monooxygenase, catalyzing (R)-stereospecific hydroxylation at C-3 of 'Arg-137' of RPS6 and 'Arg-141' of RCCD1, but the biological significance of this activity remains to be established (PubMed:29563586). Regulates mitosis through different mechanisms: Plays a role in transcriptional repression of satellite repeats, possibly by regulating H3K36 methylation levels in centromeric regions together with RCCD1. Possibly together with RCCD1, is involved in proper mitotic spindle organization and chromosome segregation (PubMed:24981860). Negatively regulates cell cycle repressor CDKN1A/p21, which controls G1/S phase transition (PubMed:24740926). Required for G2/M phase cell cycle progression. Regulates expression of CCNA1/cyclin-A1, leading to cancer cell proliferation (PubMed:20457893). Also, plays a role in regulating alpha-tubulin acetylation and cytoskeletal microtubule stability involved in epithelial to mesenchymal transition (PubMed:28455245). Regulates the circadian gene expression in the liver (By similarity). Represses the transcriptional acti…
messages: Binds 1 Fe(2+) ion per subunit.
messages: Can form homodimers (via JmjC domain) (PubMed:24100311, PubMed:28982940). Found in a complex with RCCD1 (PubMed:24981860). Interacts (via N-terminus) with RCCD1 (via N-terminus); this interaction stimulates H3K36me3 and H3K36me2 demethylation (PubMed:28455245, PubMed:24981860). Interacts (via JmjC domain) with H3C1 (PubMed:28982940). Interacts with FBXL3 and PSMD2 (By similarity). Interacts with CRY1 in a FBXL3-dependent manner (By similarity).
messages: Chromosome
messages: Nucleus
messages: The demethylase activity of JMJD5 is controversial. Demethylase activity toward H3K36me2 was observed in vivo and in vitro (PubMed:20457893). In addition, demethylase activity toward H3K36me3 when in a complex with RCCD1 has been observed (PubMed:24981860). In contrast, in other studies, JMJD5 was shown not to display any demethylase activity toward methylated H3K36 nor toward other methyllysines in the N-terminal tails of H3 and H4 in vitro (PubMed:28982940, PubMed:22851697, PubMed:24100311).
messages: Up-regulated upon starvation, DNA replication stress, UV treatment and by camptothecin and etoposide treatment.
messages: Weakly expressed in most cells. Highly expressed in breast cancer cells (PubMed:20457893). Expressed in embryonic stem cells (PubMed:24740926).

9606:DNAJA1
gene id: 9606:DNAJA1
uniprot id: B7Z5C0
uniprot id: P31689
names: Function
names: Induction
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Co-chaperone for HSPA8/Hsc70 (PubMed:10816573). Stimulates ATP hydrolysis, but not the folding of unfolded proteins mediated by HSPA1A (in vitro) (PubMed:24318877). Plays a role in protein transport into mitochondria via its role as co-chaperone. Functions as co-chaperone for HSPA1B and negatively regulates the translocation of BAX from the cytosol to mitochondria in response to cellular stress, thereby protecting cells against apoptosis (PubMed:14752510). Promotes apoptosis in response to cellular stress mediated by exposure to anisomycin or UV (PubMed:24512202).
messages: Cytoplasm
messages: Identified in a complex with HSPA1B and BAX (PubMed:14752510). Interacts with RNF207 (PubMed:25281747).
messages: Membrane
messages: Microsome
messages: Mitochondrion
messages: Nucleus
messages: Ubiquitous. Isoform 2 is highly expressed in testis and lung, but detected at low levels in thymus, prostate, colon and liver.
messages: Up-regulated by heat shock.
messages: perinuclear region

9606:CFHR3
gene id: 9606:CFHR3
uniprot id: Q02985
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry. A deletion encompassing CFHR1 and CFHR3 is associated with an increased risk of atypical hemolytic uremic syndrome, likely due to a defective regulation of complement activation (PubMed:17367211). Some patients carrying the deletion have serum anti-CFH autoantibodies (PubMed:18006700).
messages: Expressed by the liver and secreted in plasma.
messages: Might be involved in complement regulation.
messages: Secreted

9606:LPL
gene id: 9606:LPL
uniprot id: A0A1B1RVA9
uniprot id: P06858
names: Activity Regulation
names: Caution
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the AB hydrolase superfamily. Lipase family.
messages: Cell membrane
messages: Detected in blood plasma (PubMed:2340307, PubMed:11893776, PubMed:12641539). Detected in milk (at protein level) (PubMed:2340307).
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry.
messages: Homodimer (PubMed:16179346, PubMed:26725083, PubMed:11893776) (Probable). Interacts with GPIHBP1 with 1:1 stoichiometry (PubMed:17997385, PubMed:27929370, PubMed:26725083, PubMed:27811232, PubMed:29899144, PubMed:30559189). Interacts with APOC2; the interaction activates LPL activity in the presence of lipids (By similarity). Interaction with heparan sulfate proteoglycans is required to protect LPL against loss of activity (PubMed:11342582). Associates with lipoprotein particles in blood plasma (PubMed:11342582, PubMed:11893776). Interacts with LMF1 and SEL1L; interaction with SEL1L is required to prevent aggregation of newly synthesized LPL in the endoplasmic reticulum (ER), and for normal export of LPL from the ER to the extracellular space (PubMed:25066055). Interacts with SORL1; SORL1 acts as a sorting receptor, promoting LPL localization to endosomes and later to lysosomes, leading to degradation of newly synthesized LPL (PubMed:21385844).
messages: Homodimer. Interacts with APOC2; the interaction activates LPL activity in the presence of lipids.
messages: Key enzyme in triglyceride metabolism. Catalyzes the hydrolysis of triglycerides from circulating chylomicrons and very low density lipoproteins (VLDL), and thereby plays an important role in lipid clearance from the blood stream, lipid utilization and storage (PubMed:8675619, PubMed:11342582, PubMed:27578112). Although it has both phospholipase and triglyceride lipase activities it is primarily a triglyceride lipase with low but detectable phospholipase activity (PubMed:7592706, PubMed:12032167). Mediates margination of triglyceride-rich lipoprotein particles in capillaries (PubMed:24726386). Recruited to its site of action on the luminal surface of vascular endothelium by binding to GPIHBP1 and cell surface heparan sulfate proteoglycans (PubMed:11342582, PubMed:27811232).
messages: Key enzyme in triglyceride metabolism. Catalyzes the hydrolysis of triglycerides from circulating chylomicrons and very low density lipoproteins (VLDL), and thereby plays an important role in lipid clearance from the blood stream, lipid utilization and storage. Mediates margination of triglyceride-rich lipoprotein particles in capillaries. Recruited to its site of action on the luminal surface of vascular endothelium by binding to GPIHBP1 and cell surface heparan sulfate proteoglycans.
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: Secreted
messages: The apolipoprotein APOC2 acts as a coactivator of LPL activity (PubMed:12032167). Ca(2+) binding promotes protein stability and formation of the active homodimer (PubMed:16179346). Interaction with GPIHBP1 protects LPL against inactivation by ANGPTL4 (PubMed:27929370, PubMed:29899144). Inhibited by NaCl (PubMed:12032167).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Tyrosine nitration after lipopolysaccharide (LPS) challenge down-regulates the lipase activity.
messages: extracellular matrix

9606:GCC1
gene id: 9606:GCC1
uniprot id: Q96CN9
names: Domain
names: Function
names: Subcellular Location Annotation
messages: Cytoplasm
messages: Extended rod-like protein with coiled-coil domains.
messages: Golgi apparatus membrane
messages: Probably involved in maintaining Golgi structure.

9606:AFMID
gene id: 9606:AFMID
uniprot id: Q63HM1
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the kynurenine formamidase family.
messages: Catalyzes the hydrolysis of N-formyl-L-kynurenine to L-kynurenine, the second step in the kynurenine pathway of tryptophan degradation. Kynurenine may be further oxidized to nicotinic acid, NAD(H) and NADP(H). Required for elimination of toxic metabolites.
messages: Homodimer.
messages: Nucleus
messages: The main chain amide nitrogen atoms of the second glycine and its adjacent residue in the HGGXW motif define the oxyanion hole, and stabilize the oxyanion that forms during the nucleophilic attack by the catalytic serine during substrate cleavage.
messages: cytosol

9606:S100B
gene id: 9606:S100B
uniprot id: A0A0S2Z4C5
uniprot id: P04271
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Although predominant among the water-soluble brain proteins, S100 is also found in a variety of other tissues.
messages: Belongs to the S-100 family.
messages: Cytoplasm
messages: Dimer of either two alpha chains, or two beta chains, or one alpha and one beta chain (PubMed:12480931, PubMed:20950652). The S100B dimer binds two molecules of STK38 (By similarity). Interacts with CACYBP in a calcium-dependent manner (By similarity). Interacts with ATAD3A; this interaction probably occurs in the cytosol prior to ATAD3A mitochondrial targeting (PubMed:20351179). Interacts with S100A6 (PubMed:9925766). The S100B dimer interacts with two molecules of CAPZA1 (PubMed:12480931). Interacts with AGER (PubMed:20943659). Interacts with PPP5C (via TPR repeats); the interaction is calcium-dependent and modulates PPP5C activity (PubMed:22399290). Interacts with TPPP; this interaction inhibits TPPP dimerization (PubMed:33831707). Interacts with isoform CLSTN3beta of CLSTN3; interaction promotes secretion (By similarity).
messages: Nucleus
messages: Secreted
messages: Small zinc- and- and calcium-binding protein that is highly expressed in astrocytes and constitutes one of the most abundant soluble proteins in brain (PubMed:6487634, PubMed:20950652). Weakly binds calcium but binds zinc very tightly-distinct binding sites with different affinities exist for both ions on each monomer (PubMed:6487634, PubMed:20950652). Physiological concentrations of potassium ion antagonize the binding of both divalent cations, especially affecting high-affinity calcium-binding sites (By similarity). Acts as a neurotrophic factor that promotes astrocytosis and axonal proliferation (By similarity). Involved in innervation of thermogenic adipose tissue by acting as an adipocyte-derived neurotrophic factor that promotes sympathetic innervation of adipose tissue (By similarity). Binds to and initiates the activation of STK38 by releasing autoinhibitory intramolecular interactions within the kinase (By similarity). Interaction with AGER after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53/TP53 signaling (By similarity). Could assist ATAD3A cytoplasmic processing, preventing aggregation and favoring mitochondrial localization (PubMed:20351179). May mediate calcium-dependent regulation on many physiological processes by interacting with other proteins, such as TPR-containing proteins, and modulating their activity (PubMed:22399290).

9606:GKN1
gene id: 9606:GKN1
uniprot id: Q9NS71
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the gastrokine family.
messages: Cytoplasmic granule
messages: Expressed in stomach (at protein level). No expression is detected in cancer tissue or gastric cancer cell lines.
messages: Golgi apparatus
messages: Has mitogenic activity and may be involved in maintaining the integrity of the gastric mucosal epithelium.
messages: Secreted

9606:SNED1
gene id: 9606:SNED1
uniprot id: Q8TER0
names: PTM
names: Sequence Caution
names: Subcellular Location Annotation
messages: Intron retention. The N-terminal region arises from intron retention.
messages: N-glycosylated.
messages: Phosphorylated on serine and threonine residues.
messages: extracellular matrix

9606:WASHC4
gene id: 9606:WASHC4
uniprot id: Q2M389
names: Caution
names: Disease Annotation
names: Function
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Acts as a component of the WASH core complex that functions as a nucleation-promoting factor (NPF) at the surface of endosomes, where it recruits and activates the Arp2/3 complex to induce actin polymerization, playing a key role in the fission of tubules that serve as transport intermediates during endosome sorting.
messages: Belongs to the SWIP family.
messages: Component of the WASH core complex also described as WASH regulatory complex (SHRC) composed of WASH (WASHC1, WASH2P or WASH3P), WASHC2 (WASHC2A or WASHC2C), WASHC3, WASHC4 and WASHC5. The WASH core complex associates via WASHC2 with the F-actin-capping protein dimer (formed by CAPZA1, CAPZA2 or CAPZA3 and CAPZB) in a transient or substoichiometric manner which was initially described as WASH complex.
messages: Contaminating sequence. Potential poly-A sequence.
messages: Early endosome
messages: One study reported a nucleation-promoting factor (NPF) activity towards the Arp2/3 complex using partially purified samples of the WASH complex (PubMed:19922875). In another study, the in vitro reconstituted and purified recombinant WASH core complex, consisting of WASHC3, WASHC4, WASHC5, WASHC1 and the N-terminal residues 1-356 of WASHC2, did not show activity toward Arp2/3 complex (PubMed:20498093).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:AP3D1
gene id: 9606:AP3D1
uniprot id: O14617
names: Disease Annotation
names: Function
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: AP-3 associates with the BLOC-1 complex (By similarity). Adaptor protein complex 3 (AP-3) is a heterotetramer composed of two large adaptins (delta-type subunit AP3D1 and beta-type subunit AP3B1 or AP3B2), a medium adaptin (mu-type subunit AP3M1 or AP3M2) and a small adaptin (sigma-type subunit APS1 or AP3S2) (By similarity). Interacts with SLC30A2 (PubMed:25808614). Interacts with CLN3 (via dileucine motif); this interaction facilitates lysosomal targeting (PubMed:15598649).
messages: Belongs to the adaptor complexes large subunit family.
messages: Contaminating sequence. Presence of an unrelated sequence found on chromosome 7.
messages: Cytoplasm
messages: Golgi apparatus membrane
messages: Lack of 8 exons and truncation of 2 other exons in the C- terminus. Alternative splicing seems doubtful, since exon-intron junctions are not the consensus ones.
messages: Part of the AP-3 complex, an adaptor-related complex which is not clathrin-associated. The complex is associated with the Golgi region as well as more peripheral structures. It facilitates the budding of vesicles from the Golgi membrane and may be directly involved in trafficking to lysosomes. Involved in process of CD8+ T-cell and NK cell degranulation (PubMed:26744459). In concert with the BLOC-1 complex, AP-3 is required to target cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals (By similarity).
messages: Present in all adult tissues examined with the highest levels in skeletal muscle, heart, pancreas and testis.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:WDR45
gene id: 9606:WDR45
uniprot id: Q9Y484
names: Activity Regulation
names: Disease Annotation
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Activated upon amino-acid starvation.
messages: Belongs to the WD repeat PROPPIN family.
messages: Component of the autophagy machinery that controls the major intracellular degradation process by which cytoplasmic materials are packaged into autophagosomes and delivered to lysosomes for degradation (PubMed:23435086, PubMed:28561066). Binds phosphatidylinositol 3-phosphate (PtdIns3P) (PubMed:28561066). Activated by the STK11/AMPK signaling pathway upon starvation, WDR45 is involved in autophagosome assembly downstream of WIPI2, regulating the size of forming autophagosomes (PubMed:28561066). Together with WIPI1, promotes ATG2 (ATG2A or ATG2B)-mediated lipid transfer by enhancing ATG2-association with phosphatidylinositol 3-monophosphate (PI3P)-containing membranes (PubMed:31271352). Probably recruited to membranes through its PtdIns3P activity (PubMed:28561066).
messages: Cytoplasm
messages: Interacts with WIPI1 (PubMed:28561066). Interacts with WIPI2 (PubMed:28561066). Interacts with ATG2A and ATG2B (PubMed:28820312, PubMed:28561066, PubMed:32483132). Interacts with ULK1 (PubMed:28561066). May interact with the PRKAA1, PRKAA2, PRKAB1 and PRKAG1 subunits of the AMPK kinase (PubMed:28561066). May interact with NUDC (PubMed:28561066).
messages: Preautophagosomal structure
messages: The L/FRRG motif is required for recruitment to PtdIns3P.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitously expressed, with high expression in skeletal muscle and heart. Weakly expressed in liver and placenta. Expression is down-regulated in pancreatic and in kidney tumors.

9606:CPLX1
gene id: 9606:CPLX1
uniprot id: O14810
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the complexin/synaphin family.
messages: Binds to the SNARE core complex containing SNAP25, VAMP2 and STX1A.
messages: Nervous system. In hippocampus and cerebellum, expressed mainly by inhibitory neurons. Overexpressed in substantia nigra from patients with Parkinson disease.
messages: Perikaryon
messages: Positively regulates a late step in exocytosis of various cytoplasmic vesicles, such as synaptic vesicles and other secretory vesicles (PubMed:21785414). Organizes the SNAREs into a cross-linked zigzag topology that, when interposed between the vesicle and plasma membranes, is incompatible with fusion, thereby preventing SNAREs from releasing neurotransmitters until an action potential arrives at the synapse (PubMed:21785414). Also involved in glucose-induced secretion of insulin by pancreatic beta-cells. Essential for motor behavior.
messages: Presynapse
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: cytosol

9606:RBM23
gene id: 9606:RBM23
uniprot id: Q86U06
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Aryl sulfonamide anticancer drugs, such as indisulam (E7070) or E7820, promote ubiquitination and subsequent degradation by the DCX(DCAF15) complex (PubMed:31693891, PubMed:31686031, PubMed:31819272). Aryl sulfonamide anticancer drugs change the substrate specificity of DCAF15 by acting as a molecular glue that promotes binding between DCAF15 and weak affinity interactor RBM23 (PubMed:31686031, PubMed:31819272).
messages: Belongs to the splicing factor SR family.
messages: Highly expressed in placenta, liver, skeletal muscle, heart and kidney (PubMed:15694343). Expressed at lower levels in the colon, thymus, spleen, small intestine and lung (PubMed:15694343).
messages: Nucleus
messages: RNA-binding protein that acts both as a transcription coactivator and pre-mRNA splicing factor (PubMed:15694343). Regulates steroid hormone receptor-mediated transcription, independently of the pre-mRNA splicing factor activity (PubMed:15694343).

9606:CRADD
gene id: 9606:CRADD
uniprot id: P78560
names: Disease Annotation
names: Domain
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Adapter protein that associates with PIDD1 and the caspase CASP2 to form the PIDDosome, a complex that activates CASP2 and triggers apoptosis (PubMed:9044836, PubMed:15073321, PubMed:16652156, PubMed:17159900, PubMed:17289572). Also recruits CASP2 to the TNFR-1 signaling complex through its interaction with RIPK1 and TRADD and may play a role in the tumor necrosis factor-mediated signaling pathway (PubMed:8985253).
messages: Constitutively expressed in most tissues, with particularly high expression in adult heart, testis, liver, skeletal muscle, fetal liver and kidney.
messages: Cytoplasm
messages: Forms a complex named the PIDDosome with PIDD1 and CASP2 (PubMed:9044836, PubMed:8985253, PubMed:15073321, PubMed:16652156, PubMed:17159900, PubMed:17289572). Interacts (via Death domain) with RIPK1 (via Death domain); the interaction is direct (PubMed:9044836). Interacts with TRADD (PubMed:8985253). Interacts with TNFRSF1A (PubMed:8985253).
messages: Nucleus
messages: The CARD domain mediates a direct interaction with CASP2.
messages: The Death domain mediates the interaction with PIDD1 and the formation of a complex composed of 5 PIDD1 and 7 CRADD proteins which in turn probably recruit 7 CASP2 to form the PIDDosome (PubMed:17289572). The Death domain mediates a direct interaction with the Death domain of RIPK1 (PubMed:9044836).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:OR4E2
gene id: 9606:OR4E2
uniprot id: A0A126GVR8
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Membrane

9606:GRAMD1A
gene id: 9606:GRAMD1A
uniprot id: B3KUH3
uniprot id: M0QZ12
uniprot id: Q96CP6
names: Domain
names: Function
names: Induction
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Cell membrane
messages: Cholesterol transporter that mediates non-vesicular transport of cholesterol from the plasma membrane (PM) to the endoplasmic reticulum (ER) (By similarity). Contains unique domains for binding cholesterol and the PM, thereby serving as a molecular bridge for the transfer of cholesterol from the PM to the ER (By similarity). Plays a crucial role in cholesterol homeostasis and has the unique ability to localize to the PM based on the level of membrane cholesterol (By similarity). In lipid-poor conditions localizes to the ER membrane and in response to excess cholesterol in the PM is recruited to the endoplasmic reticulum-plasma membrane contact sites (EPCS) which is mediated by the GRAM domain (By similarity). At the EPCS, the sterol-binding VASt/ASTER domain binds to the cholesterol in the PM and facilitates its transfer from the PM to ER (By similarity). May play a role in tumor progression (By similarity). Plays a role in autophagy regulation and is required for biogenesis of the autophagosome (PubMed:31222192). This function in autophagy requires its cholesterol-transfer activity (PubMed:31222192).
messages: Endoplasmic reticulum membrane
messages: Expressed in liver.
messages: GRAM domain binds phosphatidylserine in the PM and mediates protein recruitment to endoplasmic reticulum-plasma membrane contact sites (EPCS) in response to excess cholesterol in the PM.
messages: Membrane
messages: Up-regulated in hepatocellular carcinoma tissues.
messages: VASt (VAD1 Analog of StAR-related lipid transfer) domain, also known as ASTER (Greek for star) domain is a sterol-binding domain.
messages: autophagosome

9606:NOP56
gene id: 9606:NOP56
uniprot id: O00567
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the NOP5/NOP56 family.
messages: Cytoplasm
messages: Involved in the early to middle stages of 60S ribosomal subunit biogenesis. Core component of box C/D small nucleolar ribonucleoprotein (snoRNP) particles. Required for the biogenesis of box C/D snoRNAs such U3, U8 and U14 snoRNAs (PubMed:12777385, PubMed:15574333). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797).
messages: Part of a large pre-ribosomal ribonucleoprotein (RNP) complex, that consists of at least 62 ribosomal proteins, 45 nonribosomal proteins and both pre-rRNA and mature rRNA species. Within this complex directly interacts with TCOF1 in an RNA-independent manner. Core component of box C/D small nucleolar ribonucleoprotein (snoRNP) particles; the core proteins SNU13, NOP56, NOP58 and FBL assemble stepwise onto the snoRNA. Interacts with NOP1 and NOP58. Interacts with NUFIP1, RUVBL1 and RUVBL2; RUVBL1:RUVBL2 seem to bridge the association of NOP56 with NUFIP1. Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3 (PubMed:34516797).
messages: The disease is caused by variants affecting the gene represented in this entry. Caused by large hexanucleotide CGCCTG repeat expansions within intron 1. These expansions induce RNA foci and sequester the RNA-binding protein SRSF2. In addition, the transcription of MIR1292, a microRNA gene located just 19 bp 3' of the GGCCTG repeat, is significantly decreased.
messages: nucleolus
messages: nucleoplasm

9606:GMPR2
gene id: 9606:GMPR2
uniprot id: H0YNJ6
uniprot id: Q6PKC0
uniprot id: Q9P2T1
names: Caution
names: Function
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Belongs to the IMPDH/GMPR family. GuaC type 1 subfamily.
messages: Catalyzes the irreversible NADPH-dependent deamination of GMP to IMP. It functions in the conversion of nucleobase, nucleoside and nucleotide derivatives of G to A nucleotides, and in maintaining the intracellular balance of A and G nucleotides (PubMed:12009299, PubMed:12669231, PubMed:16359702, PubMed:22037469). Plays a role in modulating cellular differentiation (PubMed:12669231).
messages: Catalyzes the irreversible NADPH-dependent deamination of GMP to IMP. It functions in the conversion of nucleobase, nucleoside and nucleotide derivatives of G to A nucleotides, and in maintaining the intracellular balance of A and G nucleotides.
messages: Highly expressed in heart, skeletal muscle, kidney, brain, liver, prostate, spleen, placenta, testis and ovary. Low expression in colon, thymus and peripheral blood leukocytes.
messages: Homotetramer.
messages: Lacks conserved residue(s) required for the propagation of feature annotation.

9606:MYEF2
gene id: 9606:MYEF2
uniprot id: Q9P2K5
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Monomer.
messages: Nucleus
messages: Transcriptional repressor of the myelin basic protein gene (MBP). Binds to the proximal MB1 element 5'-TTGTCC-3' of the MBP promoter. Its binding to MB1 and function are inhibited by PURA (By similarity).

9606:UGT3A1
gene id: 9606:UGT3A1
uniprot id: A8K444
uniprot id: B7Z3N0
uniprot id: Q6NUS8
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the UDP-glycosyltransferase family.
messages: Membrane
messages: UDP-glucuronosyltransferases catalyze phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase water solubility and enhance excretion. They are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds (By similarity).

9606:PGRMC1
gene id: 9606:PGRMC1
uniprot id: O00264
names: Caution
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the cytochrome b5 family. MAPR subfamily.
messages: Component of a progesterone-binding protein complex (PubMed:28396637). Binds progesterone (PubMed:25675345). Has many reported cellular functions (heme homeostasis, interaction with CYPs). Required for the maintenance of uterine histoarchitecture and normal female reproductive lifespan (By similarity). Intracellular heme chaperone. Regulates heme synthesis via interactions with FECH and acts as a heme donor for at least some hemoproteins (PubMed:27599036).
messages: Detected in urine (at protein level) (PubMed:36213313). Expressed by endometrial glands and stroma (at protein level) (PubMed:23793472). Widely expressed, with highest expression in liver and kidney.
messages: Homodimer. Forms stable homodimer through hydrophobic heme-heme stacking interactions (PubMed:26988023, PubMed:28396637). Interacts with FECH; the interaction results in decreased FECH activity (PubMed:27599036). Interacts with EGFR, CYP1A1 and CYP3A4; the interactions require PGRMC1 homodimerization (PubMed:28396637).
messages: Microsome membrane
messages: Mitochondrion outer membrane
messages: Non-classical progesterone receptors involved in extranuclear signaling are classified in 2 groups: the class II progestin and adipoQ receptor (PAQR) family (also called mPRs) (PAQR5, PAQR6, PAQR7, PAQR8 and PAQR9) and the b5-like heme/steroid-binding protein family (also called MAPRs) (PGRMC1, PGRMC2, NENF and CYB5D2).
messages: O-glycosylated; contains chondroitin sulfate attached to Ser-54. Ser-54 is in the cytoplasmic domain but the glycosylated form was detected in urine, suggesting that the membrane-bound form is cleaved, allowing for production of a secreted form which is glycosylated.
messages: Secreted
messages: Smooth endoplasmic reticulum membrane
messages: The cytochrome b5 heme-binding domain lacks the conserved iron-binding His residues at positions 107 and 131.
messages: Was initially identified as sigma-2 receptor, which is thought to play important role in regulating cell survival, morphology and differentiation (PubMed:21730960, PubMed:22292588, PubMed:28007569). However, it was later shown that it is not the case (PubMed:28007569). The sigma-2 receptor has been identified as TMEM97 (AC Q5BJF2) (PubMed:28559337).

9606:MYH7B
gene id: 9606:MYH7B
uniprot id: A7E2Y1
names: Caution
names: Developmental Stage
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.
messages: Expressed in heart, skeletal muscle, testis, and all specific brain regions examined. Slightly lower expression was detected in ovary and kidney, and intermediate expression was detected in lung, pancreas, spleen and liver.
messages: Expression does not vary in normal patients compared to patients with acute monocytic leukemia.
messages: Found in fetal liver and brain.
messages: Involved in muscle contraction.
messages: Membrane
messages: Muscle myosin is a hexameric protein that consists of 2 heavy chain subunits (MHC), 2 alkali light chain subunits (MLC) and 2 regulatory light chain subunits (MLC-2).
messages: Represents a conventional myosin. This protein should not be confused with the unconventional myosin-7 (MYO7).
messages: The cardiac alpha isoform is a 'fast' ATPase myosin, while the beta isoform is a 'slow' ATPase.
messages: This protein sequence has been named 'Slow A' MYH14, but it also appears also as 'Slow B' MYH15 within the reference.

9606:SPATA31F3
gene id: 9606:SPATA31F3
uniprot id: A0A0U1RRK5
uniprot id: A6NFA0
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the SPATA31 family.
messages: Membrane

9606:JAG2
gene id: 9606:JAG2
uniprot id: Q9Y219
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Expressed in heart, placenta and skeletal muscle and to a lesser extent in pancreas. Very low expression in brain, lung, liver and kidney.
messages: Membrane
messages: Putative Notch ligand involved in the mediation of Notch signaling. Involved in limb development (By similarity).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:MACROH2A1
gene id: 9606:MACROH2A1
uniprot id: A0A994J4J7
uniprot id: O75367
names: Caution
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the histone H2A family.
messages: Chromosome
messages: In contrast to isoform 1, does not bind poly-ADP-ribose (PubMed:15902274). Represses SOD3 gene expression (PubMed:23022728).
messages: In contrast to other Macro-domain containing proteins, lacks ADP-ribose glycohydrolase activity.
messages: Interacts with PARP1.
messages: Isoform that specifically binds poly-ADP-ribose and O-acetyl-ADP-ribose and plays a key role in NAD(+) metabolism (PubMed:15902274). Able to bind to the ends of poly-ADP-ribose chains created by PARP1 and cap them (By similarity). This prevents PARP1 from further addition of ADP-ribose and thus limits the consumption of nuclear NAD(+), allowing the cell to maintain proper NAD(+) levels in both the nucleus and the mitochondria to promote proper mitochondrial respiration (By similarity). Increases the expression of genes involved in redox metabolism, including SOD3 (PubMed:23022728).
messages: Monoubiquitinated at either Lys-116 or Lys-117. May also be polyubiquitinated. Ubiquitination is mediated by the CUL3/SPOP E3 complex and does not promote proteasomal degradation. Instead, it is required for enrichment in inactive X chromosome chromatin.
messages: Nucleus
messages: Preferentially expressed over isoform 2 in the absence of DDX5/DDX17.
messages: The macro domain specifically binds poly-ADP-ribose.
messages: The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. Interacts with HDAC1 and HDAC2 (PubMed:16107708). Interacts with SPOP (PubMed:15897469, PubMed:19818708). Part of a complex consisting of MACROH2A1, CUL3 and SPOP (PubMed:15897469, PubMed:19818708).
messages: The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.
messages: The preferential expression of isoform 2 over that of isoform 1 requires the presence of DDX5/DDX17.
messages: Variant histone H2A which replaces conventional H2A in a subset of nucleosomes where it represses transcription (PubMed:12718888, PubMed:15621527, PubMed:16428466). Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template (PubMed:15897469). Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability (PubMed:15897469). DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. Involved in stable X chromosome inactivation (PubMed:15897469). Inhibits the binding of transcription factors, including NF-kappa-B, and interferes with the activity of remodeling SWI/SNF complexes (PubMed:12718888, PubMed:16428466). Inhibits histone acetylation by EP300 and recruits class I HDACs, which induces a hypoacetylated state of chromatin (PubMed:16428466, PubMed:16107708).
messages: Widely expressed.

9606:VANGL2
gene id: 9606:VANGL2
uniprot id: A8K4L6
uniprot id: Q9ULK5
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the Vang family.
messages: Cell membrane
messages: Homodimer and heterodimer with VANGL1. Interacts through its C-terminal region with the N-terminal half of DVL1, DVL2 and DVL3. The PDZ domain of DVL1, DVL2 and DVL3 is required for the interaction. Also interacts with the PDZ domains of MAGI3, SCRIB/SCRB1 and FZD3 (By similarity). Interacts with PRICKLE3 (By similarity).
messages: Involved in the control of early morphogenesis and patterning of both axial midline structures and the development of neural plate. Plays a role in the regulation of planar cell polarity, particularly in the orientation of stereociliary bundles in the cochlea. Required for polarization and movement of myocardializing cells in the outflow tract and seems to act via RHOA signaling to regulate this process. Required for cell surface localization of FZD3 and FZD6 in the inner ear (By similarity).
messages: Membrane
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:SPTSSA
gene id: 9606:SPTSSA
uniprot id: Q969W0
names: Caution
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the SPTSS family. SPTSSA subfamily.
messages: Component of the serine palmitoyltransferase (SPT) complex, which is composed of SPTLC1, SPTLC2 or SPTLC3 and SPTSSA or SPTSSB (PubMed:19416851, PubMed:33558761, PubMed:33558762, PubMed:37308477). The heterodimer consisting of SPTLC1 and SPTLC2/SPTLC3 forms the catalytic core of the enzyme, while SPTSSA or SPTSSB subunits determine substrate specificity (PubMed:33558762, PubMed:37308477). SPT also interacts with ORMDL proteins, especially ORMDL3, which negatively regulate SPT activity in the presence of ceramides (PubMed:33558762, PubMed:37308477). Interacts with MBOAT7; the interaction plays a role in MBOAT7 localization to mitochondria-associated membranes (PubMed:23510452).
messages: Component of the serine palmitoyltransferase multisubunit enzyme (SPT) that catalyzes the initial and rate-limiting step in sphingolipid biosynthesis by condensing L-serine and activated acyl-CoA (most commonly palmitoyl-CoA) to form long-chain bases (PubMed:19416851). The SPT complex is composed of SPTLC1, SPTLC2 or SPTLC3 and SPTSSA or SPTSSB. Within this complex, the heterodimer consisting of SPTLC1 and SPTLC2/SPTLC3 forms the catalytic core (PubMed:19416851). Within the SPT complex, SPTSSA stimulates the catalytic activity and plays a role in substrate specificity, which depends upon the overall complex composition (PubMed:19416851, PubMed:33558761). The SPTLC1-SPTLC2-SPTSSA complex shows a strong preference for C16-CoA substrate, while the SPTLC1-SPTLC3-SPTSSA isozyme uses both C14-CoA and C16-CoA as substrates, with a slight preference for C14-CoA (PubMed:19416851). Independently of its action as a SPT component, may be involved in MBOAT7 localization to mitochondria-associated membranes, a membrane bridge between the endoplasmic reticulum and mitochondria, may hence affect MBOAT7-catalyzed incorporation of arachidonic acid into phosphatidylinositol (PubMed:23510452).
messages: Endoplasmic reticulum membrane
messages: It is uncertain whether Met-1 or Met-4 is the initiator.

9606:COMMD5
gene id: 9606:COMMD5
uniprot id: Q9GZQ3
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cytoplasm
messages: Highly expressed in heart, stomach, jejunum, kidney, liver, and adrenal gland. Expression was generally higher in adult organs than in fetal tissues, particularly in heart, kidney, and liver.
messages: Interacts (via COMM domain) with COMMD1 (via COMM domain). Interacts with RELA, RELB, NFKB1/p105. Interacts with CCDC22, CCDC93, SCNN1B, CUL2, CUL3, CUL4A, CUL4B, CUL7.
messages: May modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes (PubMed:21778237). Negatively regulates cell proliferation. Negatively regulates cell cycle G2/M phase transition probably by transactivating p21/CDKN1A through the p53/TP53-independent signaling pathway. Involved in kidney proximal tubule morphogenesis (By similarity). Down-regulates activation of NF-kappa-B (PubMed:15799966).
messages: Nucleus

9606:MTA1
gene id: 9606:MTA1
uniprot id: Q13330
names: Developmental Stage
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acetylation is essential for its transcriptional coactivator activity.
messages: Binds to ESR1 and sequesters it in the cytoplasm and enhances its non-genomic responses.
messages: Component of the nucleosome remodeling and deacetylase (NuRD) repressor complex, composed of core proteins MTA1, MTA2, MTA3, RBBP4, RBBP7, HDAC1, HDAC2, MBD2, MBD3, and peripherally associated proteins CDK2AP1, CDK2AP2, GATAD2A, GATAD2B, CHD3, CHD4 and CHD5 (PubMed:33283408, PubMed:9885572, PubMed:28977666, PubMed:16428440). The exact stoichiometry of the NuRD complex is unknown, and some subunits such as MBD2 and MBD3, GATAD2A and GATAD2B, and CHD3, CHD4 and CHD5 define mutually exclusive NuRD complexes (PubMed:33283408, PubMed:16428440, PubMed:28977666). Interacts with RBBP4; the interaction is direct (PubMed:24920672). Interacts with BMAL1 (By similarity). Interacts with CLOCK (By similarity). Interacts with COP1 (PubMed:19805145). Interacts with CSNK1G2 in the cytoplasm (PubMed:15077195). Interacts with EP300 (PubMed:16617102). Interacts with HDAC2 (PubMed:17671180, PubMed:19805145, PubMed:21965678, PubMed:24970816). Interacts with IFI16 (PubMed:24413532). Interacts with ITGB3BP/CENPR (PubMed:15254226). Interacts with MBD3L2 (PubMed:15701600). Interacts with MDM2 (PubMed:19837670). Interacts with NACC2 (PubMed:22926524). Interacts with p53/TP53 (PubMed:19837670). Interacts with PIAS1 (PubMed:21965678). Interacts with PIAS3 (PubMed:21965678). Interacts with PIAS4 (PubMed:21965678). Interacts with PWWP2A (PubMed:30327463). Interacts with PWWP2B (By similarity). Interacts with SENP1 (PubMed:21965678). Interacts with SENP2 (PubMed:21965678). Interacts with SIX3; facilitates the binding of SIX3 to the core DNA motif of SIX3 promoter (PubMed:20682799). Interacts with SUMO1 (PubMed:21965678). Interacts with SUMO2 (PubMed:21965678). Interacts with TFCP2L1; which is indispensable for TFCP2L1-mediated self-renewal-promoting effect and endoderm-inhibiting action (By similarity). Interacts with TFAP2C (PubMed:24413532). Interacts with TPR (PubMed:24970816). Interacts with UBE2I/UBC9 (PubMed:21965678).
messages: Cytoplasm
messages: Highly expressed in metastatic cells.
messages: Involved in the epigenetic regulation of ESR1 expression in breast cancer in a TFAP2C, IFI16 and HDAC4/5/6-dependent manner.
messages: Isoform Short contains a Leu-Arg-Ile-Leu-Leu motif (ER binding motif).
messages: Nucleus
messages: Nucleus envelope
messages: Phosphorylation by CSNK1G2/CK1 triggered by estrogen enhances corepression of estrogen receptor (ER).
messages: Sumoylation positively regulates its transcriptional corepressor activity but does not affect the protein stability. Sumoylated preferentially by SUMO2 or SUMO3 than SUMO1. Sumoylation is enhanced by PIAS1/3/4 and preferentially sumoylated by SUMO2 in the presence of PIAS1/3/4. Desumoylated by SENP1.
messages: Transcriptional coregulator which can act as both a transcriptional corepressor and coactivator (PubMed:16617102, PubMed:17671180, PubMed:17922032, PubMed:21965678, PubMed:24413532). Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin (PubMed:16428440, PubMed:28977666). In the NuRD complex, regulates transcription of its targets by modifying the acetylation status of the target chromatin and cofactor accessibility to the target DNA (PubMed:17671180). In conjunction with other components of NuRD, acts as a transcriptional corepressor of BRCA1, ESR1, TFF1 and CDKN1A (PubMed:17922032, PubMed:24413532). Acts as a transcriptional coactivator of BCAS3, and SUMO2, independent of the NuRD complex (PubMed:21965678, PubMed:17671180, PubMed:16617102). Stimulates the expression of WNT1 by inhibiting the expression of its transcriptional corepressor SIX3 (By similarity). Regulates p53-dependent and -independent DNA repair processes following genotoxic stress (PubMed:19837670). Regulates the stability and function of p53/TP53 by inhibiting its ubiquitination by COP1 and MDM2 thereby regulating the p53-dependent DNA repair (PubMed:19837670). Plays a role in the regulation of the circadian clock and is essential for the generation and maintenance of circadian rhythms under constant light and for normal entrainment of behavior to light-dark (LD) cycles (By similarity). Positively regulates the CLOCK-BMAL1 heterodimer mediated transcriptional activation of its own transcription and the transcription of CRY1 (By similarity). Regulates deacetylation of BMAL1 by regulating SIRT1 expression, resulting in derepressing CRY1-mediated transcription repression (By similarity). With TFCP2L1, promotes establishment and maintenance of pluripotency in embryonic stem cells (ESCs) and inhibits endoderm differentiation (By similarity).
messages: Ubiquitinated by COP1, which leads to proteasomal degradation.
messages: Widely expressed. High expression in brain, liver, kidney, and cardiac muscle, ovaries, adrenal glands and virgin mammary glands. Higher in tumors than in adjacent normal tissue from the same individual. Up-regulated in a wide variety of cancers including breast, liver, ovarian, and colorectal cancer and its expression levels are closely correlated with tumor aggressiveness and metastasis.
messages: cytoskeleton

9606:DAZ3
gene id: 9606:DAZ3
uniprot id: Q9NR90
names: Disease Annotation
names: Domain
names: Function
names: Miscellaneous
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the RRM DAZ family.
messages: Cytoplasm
messages: Forms a heterodimer with BOLL and DAZL. Interacts with PUM2, DAZAP1, DAZAP2, DZIP1 and DZIP3.
messages: Nucleus
messages: RNA-binding protein that plays an essential role in spermatogenesis. May act by binding to the 3'-UTR of mRNAs and regulating their translation.
messages: Testis specific.
messages: The DAZ domains are essential and mediate the interaction with DAZAP1 and DAZAP2.
messages: The DAZ proteins (DAZ, DAZ2, DAZ4 and DAZ4) are all encoded by a strongly repeated region of the Y chromosome, in two clusters each comprising an inverted pair of DAZ genes. They are very similar, which gives their indidual characterization difficult. Thus, most experiments do not discriminate between the different members. One can therefore suppose that reported interactions with a DAZ protein involve all the 4 proteins.
messages: The disease may be caused by variants affecting the gene represented in this entry. AZFc deletions in the Yq11.23 region including the DAZ genes are the most common known genetic cause of human male infertility.
messages: The number as well as the precise structure of the DAZ proteins probably differs within the population.

9606:DZIP1L
gene id: 9606:DZIP1L
uniprot id: Q8IYY4
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the DZIP C2H2-type zinc-finger protein family.
messages: Interacts with SEPTIN2 (PubMed:28530676).
messages: Involved in primary cilium formation (PubMed:19852954, PubMed:28530676). Probably acts as a transition zone protein required for localization of PKD1/PC1 and PKD2/PC2 to the ciliary membrane (PubMed:28530676).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: centriole
messages: cilium basal body

9606:DMAP1
gene id: 9606:DMAP1
uniprot id: Q9NPF5
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Component of the NuA4 histone acetyltransferase complex which contains the catalytic subunit KAT5/TIP60 and the subunits EP400, TRRAP/PAF400, BRD8/SMAP, EPC1, DMAP1/DNMAP1, RUVBL1/TIP49, RUVBL2, ING3, actin, ACTL6A/BAF53A, MORF4L1/MRG15, MORF4L2/MRGX, MRGBP, YEATS4/GAS41, VPS72/YL1 and MEAF6. Component of a NuA4-related complex which contains EP400, TRRAP/PAF400, SRCAP, BRD8/SMAP, EPC1, DMAP1/DNMAP1, RUVBL1/TIP49, RUVBL2, actin, ACTL6A/BAF53A, VPS72 and YEATS4/GAS41. DMAP1 also forms a complex with DNMT1 and HDAC2. Throughout S phase it interacts directly with the N-terminus of DNMT1, which serves to recruit DMAP1 to replication foci. DMAP1 interacts with ING1, a component of the mSin3A transcription repressor complex, although this interaction is not required for recruitment of ING1 to heterochromatin. Interacts directly with the transcriptional corepressor TSG101. Interacts with the pro-apoptotic protein DAXX. Interacts with URI1.
messages: Cytoplasm
messages: Involved in transcription repression and activation. Its interaction with HDAC2 may provide a mechanism for histone deacetylation in heterochromatin following replication of DNA at late firing origins. Can also repress transcription independently of histone deacetylase activity. May specifically potentiate DAXX-mediated repression of glucocorticoid receptor-dependent transcription. Component of the NuA4 histone acetyltransferase (HAT) complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair. NuA4 may also play a direct role in DNA repair when recruited to sites of DNA damage. Participates in the nuclear localization of URI1 and increases its transcriptional corepressor activity.
messages: Nucleus

9606:C12orf4
gene id: 9606:C12orf4
uniprot id: Q9NQ89
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
messages: Cytoplasm
messages: Plays a role in mast cell degranulation.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:ZNF621
gene id: 9606:ZNF621
uniprot id: Q6ZSS3
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:MEGF8
gene id: 9606:MEGF8
uniprot id: Q7Z7M0
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
messages: Acts as a negative regulator of hedgehog signaling.
messages: Membrane
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:CHAC2
gene id: 9606:CHAC2
uniprot id: Q8WUX2
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the gamma-glutamylcyclotransferase family. ChaC subfamily.
messages: Catalyzes the cleavage of glutathione into 5-oxo-L-proline and a Cys-Gly dipeptide. Acts specifically on glutathione, but not on other gamma-glutamyl peptides.
messages: Monomer.
messages: cytosol

9606:PRSS54
gene id: 9606:PRSS54
uniprot id: Q6PEW0
names: Caution
names: Similarity
names: Subcellular Location Annotation
messages: Although related to peptidase S1 family, lacks the essential His, Asp, and Ser residues of the catalytic triad at positions 83, 129 and 221 and is therefore predicted to have lost protease activity.
messages: Belongs to the peptidase S1 family. Plasma kallikrein subfamily.
messages: Secreted

9606:OR2A2
gene id: 9606:OR2A2
uniprot id: A0A126GW45
uniprot id: Q6IF42
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Membrane
messages: Odorant receptor.

9606:POU4F2
gene id: 9606:POU4F2
uniprot id: Q12837
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the POU transcription factor family. Class-4 subfamily.
messages: Cytoplasm
messages: Expressed in the brain (PubMed:7691107). Expressed in the ganglion cell layer of the retina (PubMed:7691107).
messages: Interacts with POU4F1; this interaction inhibits both POU4F1 DNA-binding and transcriptional activities. Interacts (C-terminus) with ESR1 (via DNA-binding domain); this interaction increases the estrogen receptor ESR1 transcriptional activity in a DNA- and ligand 17-beta-estradiol-independent manner. Interacts (via C-terminus) with TP53 (via N-terminus). Interacts with DLX1 (via homeobox DNA-binding domain); this interaction suppresses DLX1-mediated transcriptional activity in postnatal retina enhancing retinal ganglion cell (RGC) differentiation. Interacts with DLX2 (via homeobox DNA-binding domain); this interaction enhances RGC differentiation. Interacts (via C-terminus) with ISL1 (via C-terminus). Interacts with ISL2. Interacts with LHX2.
messages: Nucleus
messages: Nucleus speckle
messages: The N-terminal transcriptional activation region is sufficient to induce transcriptional activity.
messages: The POU-specific domain and POU homeodomain regions are necessary for DNA-binding activity and transcriptional repression.
messages: The polyhistidine motif acts as a targeting signal to nuclear speckles.
messages: Tissue-specific DNA-binding transcription factor involved in the development and differentiation of target cells (PubMed:19266028, PubMed:23805044). Functions either as activator or repressor modulating the rate of target gene transcription through RNA polymerase II enzyme in a promoter-dependent manner (PubMed:19266028, PubMed:23805044). Binds to the consensus octamer motif 5'-AT[A/T]A[T/A]T[A/T]A-3' of promoter of target genes. Plays a fundamental role in the gene regulatory network essential for retinal ganglion cell (RGC) differentiation. Binds to an octamer site to form a ternary complex with ISL1; cooperates positively with ISL1 and ISL2 to potentiate transcriptional activation of RGC target genes being involved in RGC fate commitment in the developing retina and RGC axon formation and pathfinding. Inhibits DLX1 and DLX2 transcriptional activities preventing DLX1- and DLX2-mediated ability to promote amacrine cell fate specification. In cooperation with TP53 potentiates transcriptional activation of BAX promoter activity increasing neuronal cell apoptosis. Negatively regulates BAX promoter activity in the absence of TP53. Acts as a transcriptional coactivator via its interaction with the transcription factor ESR1 by enhancing its effect on estrogen response element (ERE)-containing promoter. Antagonizes the transcriptional stimulatory activity of POU4F1 by preventing its binding to an octamer motif. Involved in TNFSF11-mediated terminal osteoclast differentiation (By similarity).

9606:RPL22
gene id: 9606:RPL22
uniprot id: P35268
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the eukaryotic ribosomal protein eL22 family.
messages: Binds to Epstein-Barr virus small RNAs and to heparin.
messages: Component of the large ribosomal subunit (PubMed:23636399, PubMed:32669547). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399, PubMed:32669547).
messages: Component of the large ribosomal subunit.
messages: Cytoplasm

9606:TBL2
gene id: 9606:TBL2
uniprot id: Q9Y4P3
names: Disease Annotation
messages: TBL2 is located in the Williams-Beuren syndrome (WBS) critical region. WBS results from a hemizygous deletion of several genes on chromosome 7q11.23, thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region. Haploinsufficiency of TBL2 may be the cause of certain cardiovascular and musculo-skeletal abnormalities observed in the disease.

9606:UBA1
gene id: 9606:UBA1
uniprot id: A0A024R1A3
uniprot id: P22314
names: Disease Annotation
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the ubiquitin-activating E1 family.
messages: Catalyzes the first step in ubiquitin conjugation to mark cellular proteins for degradation through the ubiquitin-proteasome system (PubMed:1606621, PubMed:1447181, PubMed:33108101). Activates ubiquitin by first adenylating its C-terminal glycine residue with ATP, and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding a ubiquitin-E1 thioester and free AMP (PubMed:1447181). Essential for the formation of radiation-induced foci, timely DNA repair and for response to replication stress. Promotes the recruitment of TP53BP1 and BRCA1 at DNA damage sites (PubMed:22456334).
messages: Cytoplasm
messages: Detected in erythrocytes (at protein level). Ubiquitous.
messages: ISGylated.
messages: Mitochondrion
messages: Monomer (By similarity). Interacts with GAN (via BTB domain).
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The disease is caused by variants affecting the gene represented in this entry. Somatic variants affecting the initiator methionine of isoform 2 are recurrently found in VEXAS patients. These variants cause loss of isoform 2 and production of a shorter isoform with strongly reduced enzymatic activity from a downstream methionine (Met-67).
messages: The first 11 amino acids are essential for phosphorylation and exclusive nuclear localization.
messages: There are two active sites within the E1 molecule, allowing it to accommodate two ubiquitin moieties at a time, with a new ubiquitin forming an adenylate intermediate as the previous one is transferred to the thiol site.

9606:SYNPO
gene id: 9606:SYNPO
uniprot id: Q8N3V7
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Actin-associated protein that may play a role in modulating actin-based shape and motility of dendritic spines and renal podocyte foot processes. Seems to be essential for the formation of spine apparatuses in spines of telencephalic neurons, which is involved in synaptic plasticity (By similarity).
messages: Belongs to the synaptopodin family.
messages: Expressed in cerebral cortex.
messages: Interacts with BAIAP1. Interacts with actin (By similarity). Interacts (via PPxY motifs) with WWC1 (via WW domains).
messages: O-glycosylated.
messages: Perikaryon
messages: Postsynaptic density
messages: Synapse
messages: cytoskeleton
messages: cytosol
messages: dendritic spine
messages: tight junction

9606:ARMC10
gene id: 9606:ARMC10
uniprot id: Q8N2F6
names: Function
names: Miscellaneous
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Depletion of isoform 2 results in cell apoptosis while its overexpression in cells leads to accelerated growth rate and tumorogenicity.
messages: Endoplasmic reticulum membrane
messages: Expressed in all tissues tested with higher expression in placenta, liver, kidney, heart and brain.
messages: Interacts with the DNA-binding domain of p53/TP53.
messages: May play a role in cell survival and cell growth. May suppress the transcriptional activity of p53/TP53.
messages: Mitochondrion outer membrane

9606:PNPLA8
gene id: 9606:PNPLA8
uniprot id: Q9NP80
names: Activity Regulation
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Calcium-independent and membrane-bound phospholipase, that catalyzes the esterolytic cleavage of fatty acids from glycerophospholipids to yield free fatty acids and lysophospholipids, hence regulating membrane physical properties and the release of lipid second messengers and growth factors (PubMed:10833412, PubMed:10744668, PubMed:15695510, PubMed:15908428, PubMed:17213206, PubMed:18171998, PubMed:28442572). Hydrolyzes phosphatidylethanolamine, phosphatidylcholine and probably phosphatidylinositol with a possible preference for the former (PubMed:15695510). Has also a broad substrate specificity in terms of fatty acid moieties, hydrolyzing saturated and mono-unsaturated fatty acids at nearly equal rates from either the sn-1 or sn-2 position in diacyl phosphatidylcholine (PubMed:10833412, PubMed:10744668, PubMed:15695510, PubMed:15908428). However, has a weak activity toward polyunsaturated fatty acids at the sn-2 position, and thereby favors the production of 2-arachidonoyl lysophosphatidylcholine, a key branch point metabolite in eicosanoid signaling (PubMed:15908428). On the other hand, can produce arachidonic acid from the sn-1 position of diacyl phospholipid and from the sn-2 position of arachidonate-containing plasmalogen substrates (PubMed:15908428). Therefore, plays an important role in the mobilization of arachidonic acid in response to cellular stimuli and the generation of lipid second messengers (PubMed:15695510, PubMed:15908428). Can also hydrolyze lysophosphatidylcholine (PubMed:15695510). In the mitochondrial compartment, catalyzes the hydrolysis and release of oxidized aliphatic chains from cardiolipin and integrates mitochondrial bioenergetics and signaling. It is essential for maintaining efficient bioenergetic mitochondrial function through tailoring mitochondrial membrane lipid metabolism and composition (PubMed:28442572).
messages: Calcium-independent phospholipase (PubMed:10833412, PubMed:10744668). Inhibited by (E)-6-bromomethylene-3-1-naphthalenyl-2H-tetrahydropyran-2-one (BEL) (PubMed:10744668, PubMed:15908428, PubMed:18171998). The activity toward 1-hexadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine is stimulated by cardiolipin (PubMed:28442572).
messages: Endoplasmic reticulum membrane
messages: Expressed in parenchymal tissues including heart, skeletal muscle, placenta, brain, liver and pancreas. Also expressed in bronchial epithelial cells and kidney. Highest expression is observed in skeletal muscle and heart.
messages: Mitochondrion membrane
messages: Peroxisome membrane
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:BBLN
gene id: 9606:BBLN
uniprot id: Q9BUW7
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the UPF0184 (EST00098) family.
messages: Cell junction
messages: Essential for intermediate filament organization in intestinal cells, interacts with intermediate filament and regulates intestinal lumen morphology.
messages: cytoskeleton

9606:ERICH6
gene id: 9606:ERICH6
uniprot id: Q7L0X2
names: Similarity
messages: Belongs to the ERICH6 family.

9606:BACH2
gene id: 9606:BACH2
uniprot id: Q9BYV9
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: B-cell specific.
messages: Belongs to the bZIP family. CNC subfamily.
messages: Cytoplasm
messages: Homodimer; disulfide-linked (PubMed:22194330). Heterodimer of BACH2 and Maf-related transcription factors (By similarity).
messages: Nucleus
messages: Phosphorylation at Ser-521 downstream of the PI-3K pathway promotes nuclear export.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The reversible disulfide bond may provide a mechanism to regulate the activity in oxidative stress responses.
messages: Transcriptional regulator that acts as repressor or activator (By similarity). Binds to Maf recognition elements (MARE) (By similarity). Plays an important role in coordinating transcription activation and repression by MAFK (By similarity). Induces apoptosis in response to oxidative stress through repression of the antiapoptotic factor HMOX1 (PubMed:17018862). Positively regulates the nuclear import of actin (By similarity). Is a key regulator of adaptive immunity, crucial for the maintenance of regulatory T-cell function and B-cell maturation (PubMed:28530713).

9606:RYBP
gene id: 9606:RYBP
uniprot id: Q8N488
names: Domain
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1-like complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility (PubMed:25519132). Component of a PRC1-like complex that mediates monoubiquitination of histone H2A 'Lys-119' on the X chromosome and is required for normal silencing of one copy of the X chromosome in XX females. May stimulate ubiquitination of histone H2A 'Lys-119' by recruiting the complex to target sites (By similarity). Inhibits ubiquitination and subsequent degradation of TP53, and thereby plays a role in regulating transcription of TP53 target genes (PubMed:19098711). May also regulate the ubiquitin-mediated proteasomal degradation of other proteins like FANK1 to regulate apoptosis (PubMed:14765135, PubMed:27060496). May be implicated in the regulation of the transcription as a repressor of the transcriptional activity of E4TF1 (PubMed:11953439). May bind to DNA (By similarity). May play a role in the repression of tumor growth and metastasis in breast cancer by down-regulating SRRM3 (PubMed:27748911).
messages: Cytoplasm
messages: Down-regulated in breast cancer tissues and in several breast cancer cell lines (at protein level) (PubMed:27748911). Widely expressed with highest levels in lymphoid tissues and placenta.
messages: Intrinsically unstructured in the absence of binding partners. Folds upon binding to DNA or RNF2 (By similarity).
messages: Monomer. Component of repressive BCOR complex containing Polycomb group subcomplex at least composed of BCOR, PCGF1, RING1 and RNF2/RING2 (PubMed:16943429). Component of PCR1-like complexes (PubMed:26687479, PubMed:20696397). Interacts with PCGF1 (PubMed:26687479). Part of a PCR1-like complex that contains AUTS2, PCGF5, RNF2, CSNK2B and RYBP (PubMed:25519132). Interacts with RNF2; the interaction is direct (PubMed:20696397). Interacts with CBX2, YAF2, RING1 and RNF2 (By similarity). Interacts with ubiquitin and ubiquitinated proteins (By similarity). Interacts with ubiquitinated histone H2A (By similarity). Interacts with apoptin, DEDD, FADD, CASP8, CASP10, YY1 and GABPB1 (PubMed:11395500, PubMed:11953439, PubMed:14765135). Together with GABPB1 and YY1, it forms a ternary complex, probably being the bridge factor between these two transcription factors (PubMed:11953439). Interacts with MDM2, and thereby inhibits ubiquitination of TP53 (PubMed:19098711). Identified in a ternary complex containing MDM2, TP53 and RYBP (PubMed:19098711). Interacts with FANK1; may prevent the ubiquitin-mediated proteasomal degradation of FANK1 (PubMed:27060496). Interacts with IFT57 (By similarity).
messages: Monoubiquitinated.
messages: Nucleus
messages: nucleoplasm

9606:CLXN
gene id: 9606:CLXN
uniprot id: Q9HAE3
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Component of the outer dynein arm-docking complex (ODA-DC) that mediates outer dynein arms (ODA) binding onto the doublet microtubule. Seems to regulate the assembly of both ODAs and their axonemal docking complex onto ciliary microtubules (By similarity). Regulates ciliary and flagellar motility and is required for cilia-driven determination of body laterality (By similarity).
messages: Component of the outer dynein arm-docking complex along with ODAD1, ODAD2, ODAD3 and ODAD4.
messages: cilium axoneme

9606:OR56A4
gene id: 9606:OR56A4
uniprot id: A0A126GWQ5
uniprot id: A0A2C9F2M6
uniprot id: Q8NGH8
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Membrane
messages: Odorant receptor.

9606:ZNF813
gene id: 9606:ZNF813
uniprot id: Q6ZN06
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:PIGC
gene id: 9606:PIGC
uniprot id: Q92535
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the PIGC family.
messages: Component of the glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex composed at least by PIGA, PIGC, PIGH, PIGP, PIGQ, PIGY and DPM2 (PubMed:16162815, PubMed:9463366). Interacts with PIGQ (PubMed:9463366). Interacts with the heterodimer PIGA:PIGH (PubMed:9463366).
messages: Endoplasmic reticulum membrane
messages: Part of the glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex that catalyzes the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to phosphatidylinositol and participates in the first step of GPI biosynthesis.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:SHISA3
gene id: 9606:SHISA3
uniprot id: A0PJX4
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the shisa family.
messages: Endoplasmic reticulum membrane
messages: Plays an essential role in the maturation of presomitic mesoderm cells by individual attenuation of both FGF and WNT signaling.

9606:KCNK4
gene id: 9606:KCNK4
uniprot id: Q2YDA1
uniprot id: Q9NYG8
names: Activity Regulation
names: Disease Annotation
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Activated by arachidonic acid.
messages: Belongs to the two pore domain potassium channel (TC 1.A.1.8) family.
messages: Cell membrane
messages: Channel opening is brought about by a conformation change that involves buckling of the second transmembrane helix and affects the position and orientation of the fourth transmembrane helix.
messages: Homodimer; disulfide-linked.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Membrane
messages: N-glycosylated.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Voltage-insensitive potassium channel (PubMed:22282805). Channel opening is triggered by mechanical forces that deform the membrane (PubMed:22282805, PubMed:25471887, PubMed:25500157, PubMed:30290154). Channel opening is triggered by raising the intracellular pH to basic levels (By similarity). The channel is inactive at 24 degrees Celsius (in vitro); raising the temperature to 37 degrees Celsius increases the frequency of channel opening, with a further increase in channel activity when the temperature is raised to 42 degrees Celsius (By similarity). Plays a role in the perception of pain caused by heat (By similarity). Plays a role in the sensory perception of pain caused by pressure (By similarity).

9606:LCE6A
gene id: 9606:LCE6A
uniprot id: A0A183
names: Function
names: Miscellaneous
names: Similarity
messages: Belongs to the LCE cluster present on 1q21.
messages: Belongs to the LCE family.
messages: Precursors of the cornified envelope of the stratum corneum.

9606:COX5B
gene id: 9606:COX5B
uniprot id: P10606
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the cytochrome c oxidase subunit 5B family.
messages: Component of the cytochrome c oxidase (complex IV, CIV), a multisubunit enzyme composed of 14 subunits. The complex is composed of a catalytic core of 3 subunits MT-CO1, MT-CO2 and MT-CO3, encoded in the mitochondrial DNA, and 11 supernumerary subunits COX4I1 (or COX4I2), COX5A, COX5B, COX6A1 (or COX6A2), COX6B1 (or COX6B2), COX6C, COX7A2 (or COX7A1), COX7B, COX7C, COX8A and NDUFA4, which are encoded in the nuclear genome (PubMed:30030519). The complex exists as a monomer or a dimer and forms supercomplexes (SCs) in the inner mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), resulting in different assemblies (supercomplex SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)) (PubMed:28844695).
messages: Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix.
messages: Mitochondrion inner membrane

9606:KRTAP4-11
gene id: 9606:KRTAP4-11
uniprot id: Q9BYQ6
names: Function
names: Polymorphism
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Belongs to the KRTAP type 4 family.
messages: Expressed in the hair follicles.
messages: In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.
messages: Interacts with hair keratins.
messages: Numerous size polymorphism are present in KRTAP4 gene family, which are mainly due to variations in the sequence encoding cysteine-rich repeat segments (PubMed:15955084).

9606:TMEM117
gene id: 9606:TMEM117
uniprot id: Q9H0C3
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the TMEM117 family.
messages: Cell membrane
messages: Involved in endoplasmic reticulum (ER) stress-induced cell death pathway.

9606:CCNL2
gene id: 9606:CCNL2
uniprot id: Q96S94
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the cyclin family. Cyclin L subfamily.
messages: Contains a RS region (arginine-serine dipeptide repeat) within the C-terminal domain which is the hallmark of the SR family of splicing factors. This region probably plays a role in protein-protein interactions (By similarity).
messages: Interacts with CDK11A, CDK11B, CDK12, CDK13 and POLR2A, the hyperphosphorylated C-terminal domain (CTD) of RNA polymerase II (PubMed:14684736, PubMed:18216018). May form a ternary complex with CDK11B and casein kinase II (CKII) (PubMed:18216018). Interacts with pre-mRNA-splicing factors, including at least SRSF1, SRSF2 AND SRSF7/SLU7 (PubMed:14684736, PubMed:18216018).
messages: Involved in pre-mRNA splicing. May induce cell death, possibly by acting on the transcription and RNA processing of apoptosis-related factors.
messages: Nucleus speckle
messages: Widely expressed.
messages: nucleoplasm

9606:SPAG7
gene id: 9606:SPAG7
uniprot id: O75391
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Detected in fetal brain.
messages: Nucleus

9606:PI4K2B
gene id: 9606:PI4K2B
uniprot id: G5E9Z4
uniprot id: Q8TCG2
names: Activity Regulation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the PI3/PI4-kinase family. Type II PI4K subfamily.
messages: Cell membrane
messages: Early endosome membrane
messages: Endoplasmic reticulum membrane
messages: Golgi apparatus membrane
messages: Inhibited by phenylarsine oxide and adenosine (PubMed:11923287). Activation through membrane association is stimulated by active RAC1 (PubMed:12324459).
messages: Membrane
messages: Together with PI4K2A and the type III PI4Ks (PIK4CA and PIK4CB) it contributes to the overall PI4-kinase activity of the cell (PubMed:11923287, PubMed:12324459). This contribution may be especially significant in plasma membrane, endosomal and Golgi compartments (PubMed:11923287, PubMed:12324459). The phosphorylation of phosphatidylinositol (PI) to PI4P is the first committed step in the generation of phosphatidylinositol 4,5-bisphosphate (PIP2), a precursor of the second messenger inositol 1,4,5-trisphosphate (InsP3) (PubMed:11923287, PubMed:12324459). Contributes to the production of InsP3 in stimulated cells and is likely to be involved in the regulation of vesicular trafficking.
messages: Widely expressed.
messages: cytosol

9606:B4GALNT1
gene id: 9606:B4GALNT1
uniprot id: Q00973
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the glycosyltransferase 2 family.
messages: Golgi apparatus membrane
messages: Homodimer; disulfide-linked.
messages: Involved in the biosynthesis of gangliosides GM2, GD2, GT2 and GA2 from GM3, GD3, GT3 and GA3, respectively.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:VSTM1
gene id: 9606:VSTM1
uniprot id: Q6UX27
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Behaves as a cytokine, promoting IL17A secretion by CD4+ T-cells, and differentiation and activation of IL17 producing helper T-cells (TH17).
messages: Contains 2 copies of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases. Both motives are required for full inhibition of FCER1A-mediated degranulation.
messages: Expressed on myeloid (neutrophils, eosinophils and monocytes) but not on lymphoid cells.
messages: Inhibitory immune receptor involved in the regulation of phagocytes.
messages: Isoform 2 is N-glycosylated.
messages: Mainly detected in immune tissues and cells.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Membrane
messages: Secreted

9606:LENG1
gene id: 9606:LENG1
uniprot id: Q96BZ8
names: Miscellaneous
messages: Belongs to the leukocyte receptor cluster (LRC) present on 19q13.4.

9606:FIRRM
gene id: 9606:FIRRM
uniprot id: Q9NSG2
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: Interacts (via its N-terminal region) with PLK1; controls PLK1 kinase activity (PubMed:34260926). Interacts (via the KVVXF motif) with PPP1CC; controls PLK1 kinase activity (PubMed:34260926). Interacts with FIGNL1; may regulate homologous recombination (PubMed:29608566).
messages: Midbody
messages: Nucleus
messages: Phosphorylation at Ser-43 by PLK1 strengthens FIRRM-PLK1 interaction (PubMed:34260926). Phosphorylation at Ser-744 by PLK1 negatively regulates its interaction with PPP1CC (PubMed:34260926).
messages: Regulates PLK1 kinase activity at kinetochores and promotes faithful chromosome segregation in prometaphase by bridging kinase and phosphatase activities (PubMed:34260926). Phosphorylation of FIRRM by PLK1 negatively regulates its interaction with the phosphatase, PPP1CC, thus creating a negative feedback loop for maintaining proper PLK1 kinase activity during mitosis (PubMed:34260926). In complex with FIGL1 may regulate homologous recombination (PubMed:29608566).
messages: centromere
messages: kinetochore
messages: spindle

9606:PCDHA2
gene id: 9606:PCDHA2
uniprot id: Q9Y5H9
names: Function
names: Subcellular Location Annotation
messages: Cell membrane
messages: Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain.

9606:METTL21A
gene id: 9606:METTL21A
uniprot id: Q8WXB1
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the methyltransferase superfamily. METTL21 family.
messages: Cytoplasm
messages: Interacts with heat shock protein 70 family members; at least some of these proteins are methylation substrates (PubMed:23349634, PubMed:23921388).
messages: Protein-lysine methyltransferase that selectively trimethylates residues in heat shock protein 70 (HSP70) family members. Contributes to the in vivo trimethylation of Lys residues in HSPA1 and HSPA8. In vitro methylates 'Lys-561' in HSPA1, 'Lys-564' in HSPA2, 'Lys-585' in HSPA5, 'Lys-563' in HSPA6 and 'Lys-561' in HSPA8.

9606:ZGLP1
gene id: 9606:ZGLP1
uniprot id: P0C6A0
names: Function
names: Subcellular Location Annotation
messages: Nucleus
messages: Transcriptional regulator that plays a key role in germ cell development. Determines the oogenic fate by activating key genes for the oogenic program and meiotic prophase entry. Acts downstream of bone morphogenetic protein (BMP) by regulating expression of genes required for the oogenic programs, which are repressed by Polycomb activities in sexually uncommitted germ cells. Regulates expression of STRA8, a central downstream effector for the meiotic program. Acts independently of retinoic acid (RA). In males, not required for germ-cell sex determination, but required to allow the spermatogonia to efficiently accomplish the meiotic prophase.

9606:ARHGEF15
gene id: 9606:ARHGEF15
uniprot id: O94989
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Expressed in the vascular smooth muscle of coronary artery.
messages: Interacts with EPHB2 (By similarity). Interacts with EPHA4.
messages: Phosphorylated on tyrosine residues upon EFNA1 stimulation. EPHB2-dependent phosphorylation at Tyr-353 triggers UBE3A-mediated ubiquitination (By similarity).
messages: Specific GEF for RhoA activation. Does not activate RAC1 or CDC42. Regulates vascular smooth muscle contractility. Negatively regulates excitatory synapse development by suppressing the synapse-promoting activity of EPHB2.
messages: Ubiquitinated; UBE3A-mediated ubiquitination and degradation by the proteasome promotes EFNB1-dependent synapse formation.
messages: dendrite

9606:PHACTR2
gene id: 9606:PHACTR2
uniprot id: O75167
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the phosphatase and actin regulator family.
messages: Binds PPP1CA and actin.
messages: Membrane

9606:CHRNA1
gene id: 9606:CHRNA1
uniprot id: P02708
uniprot id: Q53SH4
names: Disease Annotation
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acetylcholine receptors incorporating that alpha subunit do not bind alpha-bungarotoxin.
messages: Belongs to the ligand-gated ion channel (TC 1.A.9) family.
messages: Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Alpha-1/CHRNA1 sub-subfamily.
messages: Cell membrane
messages: Is able to interact with other subunits of the acetylcholine receptor but is not assembled into functional acetylcholine-gated cation-selective channels.
messages: Isoform 1 is only expressed in skeletal muscle. Isoform 2 is constitutively expressed in skeletal muscle, brain, heart, kidney, liver, lung and thymus.
messages: Membrane
messages: Non functional acetylcholine receptor alpha subunit which is not integrated into functional acetylcholine-gated cation-selective channels.
messages: One of the alpha chains that assemble within the acetylcholine receptor, a pentamer of two alpha chains, a beta, a delta, and a gamma (in immature muscle) or epsilon (in mature muscle) chains. The muscle heteropentamer composed of alpha-1, beta-1, delta, epsilon subunits interacts with the alpha-conotoxin ImII (PubMed:15609996).
messages: Postsynaptic cell membrane
messages: Synaptic cell membrane
messages: The alpha subunit is the main focus for antibody binding in myasthenia gravis. Myasthenia gravis is characterized by sporadic muscular fatigability and weakness, occurring chiefly in muscles innervated by cranial nerves, and characteristically improved by cholinesterase-inhibiting drugs.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Upon acetylcholine binding, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.

9606:APOA5
gene id: 9606:APOA5
uniprot id: A0A0B4RUS7
uniprot id: Q6Q788
names: Caution
names: Disease Annotation
names: Function
names: Induction
names: Miscellaneous
names: PTM
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the apolipoprotein A1/A4/E family.
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry.
messages: Early endosome
messages: Induced in early phase of liver regeneration.
messages: Interacts with GPIHBP1 (PubMed:17997385). Interacts with SORL1; this interaction leads to APOA5 internalization and sorting either to lysosomes and degradation, or to the trans-Golgi network (PubMed:17326667, PubMed:18603531).
messages: It is uncertain whether Met-1 or Met-4 is the initiator.
messages: Late endosome
messages: Liver and plasma.
messages: Minor apolipoprotein mainly associated with HDL and to a lesser extent with VLDL. May also be associated with chylomicrons. Important determinant of plasma triglyceride (TG) levels by both being a potent stimulator of apo-CII lipoprotein lipase (LPL) TG hydrolysis and an inhibitor of the hepatic VLDL-TG production rate (without affecting the VLDL-apoB production rate) (By similarity). Activates poorly lecithin:cholesterol acyltransferase (LCAT) and does not enhance efflux of cholesterol from macrophages. Binds heparin (PubMed:17326667).
messages: Phosphorylated by FAM20C in the extracellular medium.
messages: Secreted
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Three common alleles are known: allele APOA5*1, APOA5*2 and APOA5*3. The APOA5*2 haplotype, which consists of 3 non-coding SNPs, is present in approximately 16% of Caucasians and is associated with increased plasma triglyceride concentrations. APOA5*3 haplotype is defined by the rare Ser-19-Trp substitution. Together, the APOA5*2 and APOA5*3 haplotypes are found in 25 to 50% of African Americans, Hispanics, and Caucasians.
messages: Up-regulated by PPARA agonists, which are used clinically to lower serum TG (such as fibrates).
messages: trans-Golgi network

9606:CATSPERD
gene id: 9606:CATSPERD
uniprot id: Q86XM0
names: Caution
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Auxiliary component of the CatSper complex, a complex involved in sperm cell hyperactivation. Sperm cell hyperactivation is needed for sperm motility which is essential late in the preparation of sperm for fertilization. Required for CATSPER1 stability before intraflagellar transport and/or incorporation of the CatSper complex channel into the flagellar membrane.
messages: Belongs to the CATSPERD family.
messages: Component of the CatSper complex or CatSpermasome composed of the core pore-forming members CATSPER1, CATSPER2, CATSPER3 and CATSPER4 as well as auxiliary members CATSPERB, CATSPERG, CATSPERD, CATSPERE, CATSPERZ, C2CD6/CATSPERT, TMEM249, TMEM262 and EFCAB9 (By similarity). HSPA1 may be an additional auxiliary complex member (By similarity). The core complex members CATSPER1, CATSPER2, CATSPER3 and CATSPER4 form a heterotetrameric channel. The auxiliary CATSPERB, CATSPERG, CATSPERD and CATSPERE subunits form a pavilion-like structure over the pore which stabilizes the complex through interactions with CATSPER4, CATSPER3, CATSPER1 and CATSPER2 respectively. TMEM262/CATSPERH interacts with CATSPERB, further stabilizing the complex. C2CD6/CATSPERT interacts at least with CATSPERD and is required for targeting the CatSper complex in the flagellar membrane (By similarity).
messages: In mouse, Slco6c1 is an additional auxiliary subunit of the CatSper complex. It is unclear if the related SLCO6A1 protein performs the same role in non-rodent species.
messages: It is uncertain whether Met-1 or Met-5 is the initiator.
messages: flagellum membrane

9606:RBM42
gene id: 9606:RBM42
uniprot id: Q9BTD8
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the RRM RBM42 family.
messages: Binds (via the RRM domain) to the 3'-untranslated region (UTR) of CDKN1A mRNA.
messages: Cytoplasm
messages: Interacts with HNRNPK.
messages: Nucleus

9606:HPGD
gene id: 9606:HPGD
uniprot id: P15428
names: Disease Annotation
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the short-chain dehydrogenases/reductases (SDR) family.
messages: Catalyzes the NAD-dependent dehydrogenation (oxidation) of a broad array of hydroxylated polyunsaturated fatty acids (mainly eicosanoids and docosanoids, including prostaglandins, lipoxins and resolvins), yielding their corresponding keto (oxo) metabolites (PubMed:8086429, PubMed:10837478, PubMed:16828555, PubMed:16757471, PubMed:21916491, PubMed:25586183). Decreases the levels of the pro-proliferative prostaglandins such as prostaglandin E2 (whose activity is increased in cancer because of an increase in the expression of cyclooxygenase 2) and generates oxo-fatty acid products that can profoundly influence cell function by abrogating pro-inflammatory cytokine expression (PubMed:25586183, PubMed:15574495). Converts resolvins E1, D1 and D2 to their oxo products, which represents a mode of resolvin inactivation. Resolvin E1 plays important roles during the resolution phase of acute inflammation, while resolvins D1 and D2 have a unique role in obesity-induced adipose inflammation (PubMed:16757471, PubMed:22844113).
messages: Cytoplasm
messages: Detected in colon epithelium (at protein level).
messages: Down-regulated by cortisol, dexamethasone and betamethasone. Down-regulated in colon cancer. Up-regulated by TGFB1.
messages: Homodimer.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:RCBTB1
gene id: 9606:RCBTB1
uniprot id: Q8NDN9
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Tissue Specificity
messages: May be involved in cell cycle regulation by chromatin remodeling.
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitously expressed (PubMed:11306461, PubMed:27486781). In the retina, present in the nerve fiber layer and to a lesser extent in the inner and outer plexiform layers (at protein level) (PubMed:27486781).

9606:RSAD1
gene id: 9606:RSAD1
uniprot id: Q9HA92
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the anaerobic coproporphyrinogen-III oxidase family. HemW subfamily.
messages: May be a heme chaperone, appears to bind heme. Homologous bacterial proteins do not have oxygen-independent coproporphyrinogen-III oxidase activity (Probable). Binds 1 [4Fe-4S] cluster. The cluster is coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine (By similarity).
messages: Might carry two S-adenosyl-L-methionine binding sites with only one binding to the iron-sulfur cluster.
messages: Mitochondrion

9606:KCNJ14
gene id: 9606:KCNJ14
uniprot id: Q9UNX9
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ14 subfamily.
messages: Expressed preferentially in retina.
messages: Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. KCNJ14 gives rise to low-conductance channels with a low affinity to the channel blockers Barium and Cesium (By similarity).
messages: Membrane

9606:DDX6
gene id: 9606:DDX6
uniprot id: B2R858
uniprot id: P26196
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: A chromosomal aberration involving DDX6 may be a cause of hematopoietic tumors such as B-cell lymphomas. Translocation t(11;14)(q23;q32).
messages: Abundantly expressed in most tissues.
messages: Belongs to the DEAD box helicase family.
messages: Belongs to the DEAD box helicase family. DDX6/DHH1 subfamily.
messages: Cytoplasm
messages: Essential for the formation of P-bodies, cytosolic membrane-less ribonucleoprotein granules involved in RNA metabolism through the coordinated storage of mRNAs encoding regulatory functions (PubMed:25995375, PubMed:27342281, PubMed:31422817). Plays a role in P-bodies to coordinate the storage of translationally inactive mRNAs in the cytoplasm and prevent their degradation (PubMed:27342281). In the process of mRNA degradation, plays a role in mRNA decapping (PubMed:16364915). Blocks autophagy in nutrient-rich conditions by repressing the expression of ATG-related genes through degradation of their transcripts (PubMed:26098573).
messages: Interacts with LSM14A, LSM14B, EIF4ENIF1/4E-T, PATL1, EDC3 and EDC4 (PubMed:26027925, PubMed:31422817, PubMed:27342281, PubMed:28216671, PubMed:32354837, PubMed:26489469, PubMed:29510985, PubMed:31439631). Forms a complex with DCP1A, DCP2, EDC3 and EDC4/HEDLS (PubMed:16364915, PubMed:19285948). Interacts with LIMD1, WTIP and AJUBA (PubMed:20616046). Interacts with APOBEC3G in an RNA-dependent manner (PubMed:16699599). Interacts with RC3H1 (By similarity). Interacts with ATXN2L (PubMed:23209657). Interacts with MCRIP1 (PubMed:26184334). Interacts with MCRIP2 (PubMed:26184334). Interacts with NUFIP2 (PubMed:26184334). Interacts with TRIM71 (via NHL repeats) in an RNA-dependent manner (PubMed:23125361). Interacts with GIGYF1 and GIGYF2 (PubMed:31439631).
messages: Nucleus
messages: P-body
messages: Sumoylated (PubMed:26184334).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:ZNF77
gene id: 9606:ZNF77
uniprot id: Q15935
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:PTGIS
gene id: 9606:PTGIS
uniprot id: Q16647
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the cytochrome P450 family.
messages: Catalyzes the biosynthesis and metabolism of eicosanoids. Catalyzes the isomerization of prostaglandin H2 to prostacyclin (= prostaglandin I2), a potent mediator of vasodilation and inhibitor of platelet aggregation (PubMed:18032380, PubMed:25623425, PubMed:12372404, PubMed:15115769). Additionally, displays dehydratase activity, toward hydroperoxyeicosatetraenoates (HPETEs), especially toward (15S)-hydroperoxy-(5Z,8Z,11Z,13E)-eicosatetraenoate (15(S)-HPETE) (PubMed:17459323).
messages: Endoplasmic reticulum membrane
messages: The disease may be caused by variants affecting the gene represented in this entry.
messages: Widely expressed; particularly abundant in ovary, heart, skeletal muscle, lung and prostate.

9606:RND2
gene id: 9606:RND2
uniprot id: P52198
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the small GTPase superfamily. Rho family.
messages: Highly expressed in testis.
messages: Interacts with the Rho-GAP domain of RACGAP1 (PubMed:12590651). Interacts with UBXD5 (PubMed:11940653). Interacts with PRAG1 (By similarity).
messages: May be specifically involved in neuronal and hepatic functions. Is a C3 toxin-insensitive member of the Rho subfamily (By similarity).
messages: acrosome membrane

9606:TMEM231
gene id: 9606:TMEM231
uniprot id: Q9H6L2
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the TMEM231 family.
messages: Part of the tectonic-like complex (also named B9 complex). Interacts with TMEM107.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Transmembrane component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes. Required for ciliogenesis and sonic hedgehog/SHH signaling (By similarity).
messages: cilium membrane

9606:ST7L
gene id: 9606:ST7L
uniprot id: Q8TDW4
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the ST7 family.
messages: Membrane

9606:CATSPERZ
gene id: 9606:CATSPERZ
uniprot id: Q9NTU4
names: Caution
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: A report observed N-glycosylation at Asn-58 (PubMed:19139490). However, as the protein is not predicted to localize in an extracellular compartment of the cell, additional evidence is required to confirm this result.
messages: Auxiliary component of the CatSper complex, a complex involved in sperm cell hyperactivation. Sperm cell hyperactivation is needed for sperm motility which is essential late in the preparation of sperm for fertilization. Required for a distribution of the CatSper complex in linear quadrilateral nanodomains along the flagellum, maximizing fertilization inside the mammalian female reproductive tract. Together with EFCAB9, associates with the CatSper channel pore and is required for the two-row structure of each single CatSper channel.
messages: Component of the CatSper complex or CatSpermasome composed of the core pore-forming members CATSPER1, CATSPER2, CATSPER3 and CATSPER4 as well as auxiliary members CATSPERB, CATSPERG, CATSPERD, CATSPERE, CATSPERZ, C2CD6/CATSPERT, TMEM249, TMEM262 and EFCAB9 (By similarity). HSPA1 may be an additional auxiliary complex member (By similarity). The core complex members CATSPER1, CATSPER2, CATSPER3 and CATSPER4 form a heterotetrameric channel (By similarity). The auxiliary CATSPERB, CATSPERG, CATSPERD and CATSPERE subunits form a pavilion-like structure over the pore which stabilizes the complex through interactions with CATSPER4, CATSPER3, CATSPER1 and CATSPER2 respectively (By similarity). TMEM262/CATSPERH interacts with CATSPERB, further stabilizing the complex. C2CD6/CATSPERT interacts at least with CATSPERD and is required for targeting the CatSper complex in the flagellar membrane (By similarity). Interacts with EFCAB9; the interaction is direct, Ca(2+)-dependent and connects EFCAB9 with the CatSper complex (By similarity). Dissociates from EFCAB9 at elevated pH (By similarity).
messages: In mouse, Slco6c1 is an additional auxiliary subunit of the CatSper complex. It is unclear if the related SLCO6A1 protein performs the same role in non-rodent species.
messages: flagellum membrane

9606:PTCH2
gene id: 9606:PTCH2
uniprot id: Q9Y6C5
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the patched family.
messages: Membrane
messages: Plays a role in the control of cellular growth (PubMed:18285427). May have a role in epidermal development. May act as a receptor for Sonic hedgehog (SHH).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:SCGB1C1
gene id: 9606:SCGB1C1
uniprot id: Q8TD33
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the secretoglobin family.
messages: Secreted

9606:NAPA
gene id: 9606:NAPA
uniprot id: P54920
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the SNAP family.
messages: Cell membrane
messages: Interacts with PRKCABP, and disrupts the interaction between GRIA2 and PRKCABP, leading to the internalization of GRIA2 (By similarity). Found in a complex with VAMP8 (By similarity). Component of a SNARE-like complex that contains at least ZW10, USE1L, RINT1, STX18 and NAPA/SNAP-alpha (PubMed:15029241). Interacts with VTI1A (By similarity). Interacts with STX12 (By similarity). Interacts with GNA12 (via N-terminus); the interaction promotes CDH5 localization to plasma membrane (PubMed:15980433).
messages: Required for vesicular transport between the endoplasmic reticulum and the Golgi apparatus (Probable). Together with GNA12 promotes CDH5 localization to plasma membrane (PubMed:15980433).

9606:TET2
gene id: 9606:TET2
uniprot id: A0A158SIU0
uniprot id: Q6N021
names: Caution
names: Cofactor
names: Disease Annotation
names: Function
names: Miscellaneous
names: PTM
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the TET family.
messages: Binds 1 Fe(2+) ion per subunit.
messages: Binds 3 zinc ions per subunit. The zinc ions have a structural role (PubMed:24315485).
messages: Broadly expressed. Highly expressed in hematopoietic cells; highest expression observed in granulocytes. Expression is reduced in granulocytes from peripheral blood of patients affected by myelodysplastic syndromes.
messages: Chromosome
messages: Contaminating sequence. Potential poly-A sequence.
messages: Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) and plays a key role in active DNA demethylation. Has a preference for 5-hydroxymethylcytosine in CpG motifs. Also mediates subsequent conversion of 5hmC into 5-formylcytosine (5fC), and conversion of 5fC to 5-carboxylcytosine (5caC). Conversion of 5mC into 5hmC, 5fC and 5caC probably constitutes the first step in cytosine demethylation. Methylation at the C5 position of cytosine bases is an epigenetic modification of the mammalian genome which plays an important role in transcriptional regulation. In addition to its role in DNA demethylation, also involved in the recruitment of the O-GlcNAc transferase OGT to CpG-rich transcription start sites of active genes, thereby promoting histone H2B GlcNAcylation by OGT.
messages: Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) and plays a key role in epigenetic chromatin reprogramming during embryonic development.
messages: Interacts with HCFC1 (PubMed:23353889). Interacts with OGT (PubMed:23353889, PubMed:23222540). Interacts with PROSER1; this interaction mediates TET2 O-GlcNAcylation and stability by promoting the interaction between OGT and TET2 (PubMed:34667079). Directly interacts (via C-terminus) with the DCAF1 component of the CRL4(VprBP) E3 ubiquitin-protein ligase complex (PubMed:24357321, PubMed:25557551).
messages: May be glycosylated. It is unclear whether interaction with OGT leads to GlcNAcylation. According to a report, it is not GlcNAcylated by OGT (PubMed:23353889). In contrast, another group reports GlcNAcylation by OGT in mouse ortholog.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Monoubiquitinated at Lys-1299 by the DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex called CRL4(VprBP) or CUL4A-RBX1-DDB1-DCAF1/VPRBP complex; this modification promotes binding to DNA.
messages: Nucleus
messages: Subsequent steps in cytosine demethylation are subject to discussion. According to a first model cytosine demethylation occurs through deamination of 5hmC into 5-hydroxymethyluracil (5hmU) and subsequent replacement by unmethylated cytosine by the base excision repair system. According to another model, cytosine demethylation is rather mediated via conversion of 5hmC into 5fC and 5caC, followed by excision by TDG (PubMed:21817016).
messages: TET2 is frequently mutated in myeloproliferative disorders (MPD). These constitute a heterogeneous group of disorders, also known as myeloproliferative diseases or myeloproliferative neoplasms (MPN), characterized by cellular proliferation of one or more hematologic cell lines in the peripheral blood, distinct from acute leukemia. Included diseases are: essential thrombocythemia, polycythemia vera, primary myelofibrosis (chronic idiopathic myelofibrosis). Bone marrow samples from patients display uniformly low levels of hmC in genomic DNA compared to bone marrow samples from healthy controls as well as hypomethylation relative to controls at the majority of differentially methylated CpG sites.
messages: TET2 is frequently mutated in systemic mastocytosis; also known as systemic mast cell disease. A condition with features in common with myeloproliferative diseases. It is a clonal disorder of the mast cell and its precursor cells. The clinical symptoms and signs of systemic mastocytosis are due to accumulation of clonally derived mast cells in different tissues, including bone marrow, skin, the gastrointestinal tract, the liver, and the spleen.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The disease is caused by variants affecting the gene represented in this entry. Bone marrow samples from patients display uniformly low levels of hmC in genomic DNA compared to bone marrow samples from healthy controls as well as hypomethylation relative to controls at the majority of differentially methylated CpG sites.
messages: The zinc ions have a structural role.

9606:PML
gene id: 9606:PML
uniprot id: P29590
names: Disease Annotation
names: Domain
names: Function
names: Induction
names: Miscellaneous
names: PTM
names: Sequence Caution
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Cleaved at two different sites by enterovirus 71 protease 3C, leading to impaired PML-Nuclear bodies formation.
messages: (Microbial infection) Immediate early protein IE1 of human cytomegalovirus (HHV-5) interferes with the sumoylation of PML (PubMed:15163746, PubMed:10233977, PubMed:27903803). Immediate early protein IE1 inhibits PML de novo sumoylation (PubMed:27903803).
messages: (Microbial infection) Interacts with Lassa virus Z protein and rabies virus phosphoprotein.
messages: (Microbial infection) Interacts with human cytomegalovirus (HHV-5) immediate early protein IE1; this interaction mediates PML desumoylation and PML-mediated sumoylation of IE1.
messages: (Microbial infection) Isoform PML-1 interacts with herpes simplex virus-1/HHV-1 ICP0.
messages: (Microbial infection) Isoform PML-2 interacts with human adenovirus 2 E1A and this interaction stimulates E1A-dependent transcriptional activation.
messages: (Microbial infection) Isoform PML-3 interacts (via RING-type zinc finger) with human foamy virus bel1/tas and bet.
messages: (Microbial infection) Isoform PML-4 and isoform PML-5 interact with human adenovirus 5 E1B-55K protein; these interactions promote efficient subnuclear targeting of E1B-55K to PML nuclear bodies.
messages: (Microbial infection) Isoform PML-4 interacts with VZV capsid protein VP26/ORF23 capsid protein.
messages: (Microbial infection) Isoform PML-6 interacts with moloney murine leukemia virus (MoMLV) integrase (IN) and reverse transcriptase (RT).
messages: (Microbial infection) The RING-type zinc finger is necessary for the sumoylation of human cytomegalovirus (HHV-5) immediate early protein IE1.
messages: (Microbial infection) The sumoylated isoform PML-4 interacts with encephalomyocarditis virus (EMCV) RNA-directed RNA polymerase 3D-POL (P3D-POL).
messages: (Microbial infection) Upon infection with Epstein-Barr virus, phosphorylated by CK2. Viral EBNA1 increases the association of CK2 with PML proteins, which increases PML phosphorylation by CK2, triggering the USP7-dependent polyubiquitylation and degradation of PML.
messages: A chromosomal aberration involving PML may be a cause of acute promyelocytic leukemia (APL). Translocation t(15;17)(q21;q21) with RARA. The PML breakpoints (type A and type B) lie on either side of an alternatively spliced exon.
messages: Acetylation at Lys-487 is essential for its nuclear localization. Deacetylated at Lys-487 by SIRT1 and this deacetylation promotes PML control of PER2 nuclear localization.
messages: Binds arsenic via the RING-type zinc finger.
messages: By interferons alpha, beta and gamma. Up-regulated by IRF3 and p53/TP53.
messages: Chimeric cDNA.
messages: Cytoplasm
messages: Early endosome membrane
messages: Endoplasmic reticulum membrane
messages: Exhibits antiviral activity against both DNA and RNA viruses. The antiviral activity can involve one or several isoform(s) and can be enhanced by the permanent PML-NB-associated protein DAXX or by the recruitment of p53/TP53 within these structures. Isoform PML-4 restricts varicella zoster virus (VZV) via sequestration of virion capsids in PML-NBs thereby preventing their nuclear egress and inhibiting formation of infectious virus particles. The sumoylated isoform PML-4 restricts rabies virus by inhibiting viral mRNA and protein synthesis. The cytoplasmic isoform PML-14 can restrict herpes simplex virus-1 (HHV-1) replication by sequestering the viral E3 ubiquitin-protein ligase ICP0 in the cytoplasm. Isoform PML-6 shows restriction activity towards human cytomegalovirus (HHV-5) and influenza A virus strains PR8(H1N1) and ST364(H3N2). Sumoylated isoform PML-4 and isoform PML-12 show antiviral activity against encephalomyocarditis virus (EMCV) by promoting nuclear sequestration of viral polymerase (P3D-POL) within PML NBs. Isoform PML-3 exhibits antiviral activity against poliovirus by inducing apoptosis in infected cells through the recruitment and the activation of p53/TP53 in the PML-NBs. Isoform PML-3 represses human foamy virus (HFV) transcription by complexing the HFV transactivator, bel1/tas, preventing its binding to viral DNA. PML may positively regulate infectious hepatitis C viral (HCV) production and isoform PML-2 may enhance adenovirus transcription. Functions as an E3 SUMO-protein ligase that sumoylates (HHV-5) immediate early protein IE1, thereby participating in the antiviral response (PubMed:20972456, PubMed:28250117). Isoforms PML-3 and PML-6 display the highest levels of sumoylation activity (PubMed:20972456, PubMed:28250117).
messages: Functions via its association with PML-nuclear bodies (PML-NBs) in a wide range of important cellular processes, including tumor suppression, transcriptional regulation, apoptosis, senescence, DNA damage response, and viral defense mechanisms. Acts as the scaffold of PML-NBs allowing other proteins to shuttle in and out, a process which is regulated by SUMO-mediated modifications and interactions. Inhibits EIF4E-mediated mRNA nuclear export by reducing EIF4E affinity for the 5' 7-methylguanosine (m7G) cap of target mRNAs (PubMed:11500381, PubMed:11575918, PubMed:18391071). Isoform PML-4 has a multifaceted role in the regulation of apoptosis and growth suppression: activates RB1 and inhibits AKT1 via interactions with PP1 and PP2A phosphatases respectively, negatively affects the PI3K pathway by inhibiting MTOR and activating PTEN, and positively regulates p53/TP53 by acting at different levels (by promoting its acetylation and phosphorylation and by inhibiting its MDM2-dependent degradation). Isoform PML-4 also: acts as a transcriptional repressor of TBX2 during cellular senescence and the repression is dependent on a functional RBL2/E2F4 repressor complex, regulates double-strand break repair in gamma-irradiation-induced DNA damage responses via its interaction with WRN, acts as a negative regulator of telomerase by interacting with TERT, and regulates PER2 nuclear localization and circadian function. Isoform PML-6 inhibits specifically the activity of the tetrameric form of PKM. The nuclear isoforms (isoform PML-1, isoform PML-2, isoform PML-3, isoform PML-4 and isoform PML-5) in concert with SATB1 are involved in local chromatin-loop remodeling and gene expression regulation at the MHC-I locus. Isoform PML-2 is required for efficient IFN-gamma induced MHC II gene transcription via regulation of CIITA. Cytoplasmic PML is involved in the regulation of the TGF-beta signaling pathway. PML also regulates transcription activity of ELF4 and can act as an important media…
messages: Key component of PML bodies. PML bodies are formed by the interaction of PML homodimers (via SUMO-binding motif) with sumoylated PML, leading to the assembly of higher oligomers. Several types of PML bodies have been observed. PML bodies can form hollow spheres that can sequester target proteins inside. Interacts (via SUMO-binding motif) with sumoylated proteins. Interacts (via C-terminus) with p53/TP53. Recruits p53/TP53 and CHEK2 into PML bodies, which promotes p53/TP53 phosphorylation at 'Ser-20' and prevents its proteasomal degradation. Interacts with MDM2, and sequesters MDM2 in the nucleolus, thereby preventing ubiquitination of p53/TP53. Interaction with PML-RARA oncoprotein and certain viral proteins causes disassembly of PML bodies and abolishes the normal PML function. Interacts with HIPK2, TERT, SIRT1, TOPBP1, TRIM27 and TRIM69. Interacts with ELF4 (via C-terminus). Interacts with ITPR3. Interacts (in the cytoplasm) with TGFBR1, TGFBR2 and PKM. Interacts (via the coiled-coil domain and when sumoylated) with SATB1. Interacts with UBE2I; the interaction is enhanced by arsenic binding. Interacts (PML-RARA oncoprotein, via the coiled-coil domain) with UBE2I; the interaction is enhanced by arsenic binding and is required for PML-RARA oncoprotein sumoylation and inhibition of RARA transactivational activity. Interacts with RB1, PPP1A, SMAD2, SMAD3, DAXX, RPL11 and MTOR. Interacts with PPARGC1A and KAT2A. Interacts with CSNK2A1 and CSNK2A3. Interacts with ANKRD2; the interaction is direct. Interacts (via SUMO-interacting motif) with sumoylated MORC3 (PubMed:20501696). Isoform PML-1, isoform PML-2, isoform PML-3, isoform PML-4, isoform PML-5 and isoform PML-6 interact with RNF4. Isoform PML-1 interacts with NLRP3. Isoform PML-1, isoform PML-2, isoform PML-3, isoform PML-4 and isoform PML-5 interact with MAGEA2, RBL2, PER2 and E2F4. Isoform PML-2 interacts with CIITA. Isoform PML-2, isoform PML-3 and isoform PML-4 interact with TBX2. Isoform PML-4 interacts with R…
messages: Non-canonical splice sites. Might alternatively represent a polymorphic variation.
messages: Nucleus
messages: PML body
messages: Phosphorylation is a major regulatory mechanism that controls PML protein abundance and the number and size of PML nuclear bodies (PML-NBs). Phosphorylated in response to DNA damage, probably by ATR (PubMed:15195100). HIPK2-mediated phosphorylation at Ser-8, Ser-36 and Ser-38 leads to increased accumulation of PML protein and its sumoylation and is required for the maximal pro-apoptotic activity of PML after DNA damage (PubMed:19015637). CHEK2-mediated phosphorylation at Ser-117 is important for PML-mediated apoptosis following DNA damage (PubMed:12402044). MAPK1-mediated phosphorylations at Ser-403, Ser-505, Ser-527 and Ser-530 and CDK1/2-mediated phosphorylation at Ser-518 promote PIN1-dependent PML degradation (PubMed:22033920, PubMed:21840486). CK2-mediated phosphorylation at Ser-565 primes PML ubiquitination via an unidentified ubiquitin ligase (PubMed:22406621, PubMed:20719947).
messages: Sumoylation regulates PML's: stability in response to extracellular or intracellular stimuli, transcription directly and indirectly, through sequestration of or dissociation of the transcription factors from PML-NBs, ability to regulate apoptosis and its anti-viral activities. It is also essential for: maintaining proper PML nuclear bodies (PML-NBs) structure and normal function, recruitment of components of PML-NBs, the turnover and retention of PML in PML-NBs and the integrity of PML-NBs. Undergoes 'Lys-11'-linked sumoylation. Sumoylation on all three sites (Lys-65, Lys-160 and Lys-490) is required for nuclear body formation. Sumoylation on Lys-160 is a prerequisite for sumoylation on Lys-65. Lys-65 and Lys-160 are sumoylated by PISA1 and PIAS2. PIAS1-mediated sumoylation of PML promotes its interaction with CSNK2A1/CK2 and phosphorylation at Ser-565 which in turn triggers its ubiquitin-mediated degradation. PIAS1-mediated sumoylation of PML-RARA promotes its ubiquitin-mediated degradation. The PML-RARA fusion protein requires the coiled-coil domain for sumoylation. Sumoylation at Lys-490 by RANBP2 is essential for the proper assembly of PML-NBs. SUMO1P1/SUMO5 conjugated PML at Lys-160, Lys-380, Lys-400, Lys-490 and Lys-497, but Lys-380, Lys-400 and Lys-497 are not key acceptor lysines. SUMO1P1/SUMO5 forms polymeric chain on Lys-160 of PML by successive conjugation at 'Lys-18'; facilitating recruitment of PML-NB components, which enlarges PML. SUMO1P1/SUMO5 conjugation of PML increases SUMO2/3 conjugation, which leads to the recruitment of RNF4 and ubiquitin-dependent disintegration of PML-NBs. SUMO1P1/SUMO5 monoconjugated Lys-490 (PubMed:27211601). DNA damage triggers its sumoylation while some but not all viral infections can abolish sumoylation. Desumoylated by SENP1, SENP2, SENP3, SENP5 and SENP6 (PubMed:27211601, PubMed:12419228, PubMed:21148299). Arsenic induces PML and PML-RARA polysumoylation and their subsequent RNF4-dependent ubiquitination and proteasom…
messages: The B box-type zinc binding domain and the coiled-coil domain mediate its interaction with PIAS1.
messages: The Sumo interaction motif (SIM) is required for efficient ubiquitination, recruitment of proteasome components within PML-NBs and PML degradation in response to arsenic trioxide.
messages: The coiled-coil domain mediates a strong homo/multidimerization activity essential for core assembly of PML-NBs. Interacts with PKM via its coiled-coil domain (PubMed:18298799).
messages: The unique C-terminal domains of isoform PML-2 and isoform PML-5 play an important role in regulating the localization, assembly dynamics, and functions of PML-NBs.
messages: Ubiquitinated; mediated by RNF4, RNF111, UHRF1, UBE3A/E6AP, BCR(KLHL20) E3 ubiquitin ligase complex E3 ligase complex, SIAH1 or SIAH2 and leading to subsequent proteasomal degradation (PubMed:18408734, PubMed:21840486, PubMed:22033920). Ubiquitination by BCR(KLHL20) E3 ubiquitin ligase complex E3 ligase complex requires CDK1/2-mediated phosphorylation at Ser-518 which in turn is recognized by prolyl-isopeptidase PIN1 and PIN1-catalyzed isomerization further potentiates PML interaction with KLHL20 (PubMed:21840486, PubMed:22033920). 'Lys-6'-, 'Lys-11'-, 'Lys-48'- and 'Lys-63'-linked polyubiquitination by RNF4 is polysumoylation-dependent (PubMed:18408734). Ubiquitination by RNF111 is polysumoylation-dependent (By similarity).
messages: nucleolus
messages: nucleoplasm

9606:UBE2A
gene id: 9606:UBE2A
uniprot id: A0A0D9SG71
uniprot id: P49459
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subunit
messages: Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In association with the E3 enzyme BRE1 (RNF20 and/or RNF40), it plays a role in transcription regulation by catalyzing the monoubiquitination of histone H2B at 'Lys-120' to form H2BK120ub1. H2BK120ub1 gives a specific tag for epigenetic transcriptional activation, elongation by RNA polymerase II, telomeric silencing, and is also a prerequisite for H3K4me and H3K79me formation. In vitro catalyzes 'Lys-11', as well as 'Lys-48'-linked polyubiquitination. Required for postreplication repair of UV-damaged DNA.
messages: Belongs to the ubiquitin-conjugating enzyme family.
messages: Interacts with RAD18 and WAC (PubMed:21329877). Interacts with RFPL4A and CCNB1 (By similarity).
messages: Phosphorylation at Ser-120 by CDK9 increases activity towards histone H2B.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:PRG3
gene id: 9606:PRG3
uniprot id: Q9Y2Y8
names: Function
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Cytoplasmic granule
messages: Expressed in bone marrow. Not detected in placenta.
messages: Possesses similar cytotoxic and cytostimulatory activities to PRG2/MBP. In vitro, stimulates neutrophil superoxide production and IL8 release, and histamine and leukotriene C4 release from basophils.

9606:TMEM187
gene id: 9606:TMEM187
uniprot id: Q14656
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Membrane
messages: Ubiquitous.

9606:OTOL1
gene id: 9606:OTOL1
uniprot id: A6NHN0
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the OTOL1 family.
messages: Collagen-like protein specifically expressed in the inner ear, which provides an organic scaffold for otoconia, a calcium carbonate structure in the saccule and utricle of the ear. Acts as a scaffold for biomineralization: sequesters calcium and forms interconnecting fibrils between otoconia that are incorporated into the calcium crystal structure. Together with OC90, modulates calcite crystal morphology and growth kinetics.
messages: Homooligomer; disulfide-linked; probably forms homotrimers. Interacts with OC90. Interacts with CBLN1.
messages: The C1q domain mediates calcium-binding.
messages: extracellular matrix

9606:MRPL37
gene id: 9606:MRPL37
uniprot id: Q9BZE1
uniprot id: S4R369
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the mitochondrion-specific ribosomal protein mL37 family.
messages: Component of the mitochondrial large ribosomal subunit (mt-LSU) (PubMed:28892042, PubMed:25838379, PubMed:25278503). Mature mammalian 55S mitochondrial ribosomes consist of a small (28S) and a large (39S) subunit. The 28S small subunit contains a 12S ribosomal RNA (12S mt-rRNA) and 30 different proteins. The 39S large subunit contains a 16S rRNA (16S mt-rRNA), a copy of mitochondrial valine transfer RNA (mt-tRNA(Val)), which plays an integral structural role, and 52 different proteins. mL37 forms a heterodimer with mL65.
messages: Mitochondrion

9606:GPRIN2
gene id: 9606:GPRIN2
uniprot id: O60269
names: Function
names: Subunit
names: Tissue Specificity
messages: Expressed specifically in the cerebellum.
messages: Interacts with activated forms of GNAO1 and GNAZ.
messages: May be involved in neurite outgrowth.

9606:MTG2
gene id: 9606:MTG2
uniprot id: Q9H4K7
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Associates with the mitochondrial ribosome large subunit; the association occurs in a GTP-dependent manner.
messages: Belongs to the TRAFAC class OBG-HflX-like GTPase superfamily. OBG GTPase family.
messages: Mitochondrion
messages: Mitochondrion inner membrane
messages: Plays a role in the regulation of the mitochondrial ribosome assembly and of translational activity. Displays GTPase activity. Involved in the ribosome maturation process.

9606:POLR3F
gene id: 9606:POLR3F
uniprot id: Q05DB8
uniprot id: Q9H1D9
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the eukaryotic RPC34/RPC39 RNA polymerase subunit family.
messages: Component of the RNA polymerase III (Pol III) complex consisting of 17 subunits. RPC3/POLR3C, RPC6/POLR3F and RPC7/POLR3G form a Pol III subcomplex (By similarity). Directly interacts with POLR3C (PubMed:21358628). Interacts with TBP and TFIIIB90 and GTF3C4 (By similarity) (PubMed:10523658). Interacts with MAF1 (PubMed:18377933). As part of the RNA polymerase III (Pol III) complex, interacts with PKP2 (PubMed:11416169).
messages: DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Specific peripheric component of RNA polymerase III which synthesizes small RNAs, such as 5S rRNA and tRNAs.
messages: DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Specific peripheric component of RNA polymerase III which synthesizes small RNAs, such as 5S rRNA and tRNAs. May direct RNA Pol III binding to the TFIIIB-DNA complex. Plays a key role in sensing and limiting infection by intracellular bacteria and DNA viruses, including varicella zoster virus (PubMed:30211253). Acts as nuclear and cytosolic DNA sensor detecting AT-rich DNA, involved in innate immune response. Can sense non-self dsDNA that serves as template for transcription into dsRNA. The non-self RNA polymerase III transcripts, such as Epstein-Barr virus-encoded RNAs (EBERs) induce type I interferon and NF- Kappa-B through the RIG-I pathway. Preferentially binds double-stranded DNA (dsDNA) (PubMed:21358628).
messages: Nucleus
messages: The disease may be caused by variants affecting the gene represented in this entry.

9606:ACADSB
gene id: 9606:ACADSB
uniprot id: A0A0S2Z3P9
uniprot id: P45954
names: Activity Regulation
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the acyl-CoA dehydrogenase family.
messages: Competitively inhibited by valproyl-CoA.
messages: Homotetramer.
messages: Mitochondrion matrix
messages: Short and branched chain specific acyl-CoA dehydrogenase that catalyzes the removal of one hydrogen from C-2 and C-3 of the fatty acyl-CoA thioester, resulting in the formation of trans-2-enoyl-CoA (PubMed:7698750, PubMed:11013134, PubMed:21430231, PubMed:10832746). Among the different mitochondrial acyl-CoA dehydrogenases, acts specifically on short and branched chain acyl-CoA derivatives such as (S)-2-methylbutyryl-CoA as well as short straight chain acyl-CoAs such as butyryl-CoA (PubMed:7698750, PubMed:11013134, PubMed:21430231, PubMed:10832746). Plays an important role in the metabolism of L-isoleucine by catalyzing the dehydrogenation of 2-methylbutyryl-CoA, one of the steps of the L-isoleucine catabolic pathway (PubMed:11013134, PubMed:10832746). Can also act on valproyl-CoA, a metabolite of valproic acid, an antiepileptic drug (PubMed:8660691).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitously expressed.

9606:SPSB2
gene id: 9606:SPSB2
uniprot id: Q99619
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Interacts (via C-terminus) with HCV envelope glycoprotein E1. Interacts (via C-terminus) with HCV non-structural protein 5A; this interaction targets NS5A for ubiquitination and degradation.
messages: Belongs to the SPSB family.
messages: Component of the probable ECS(SPSB2) E3 ubiquitin-protein ligase complex which contains CUL5, RNF7/RBX2, Elongin BC complex and SPSB2 (PubMed:15601820). Interacts with CUL5, RNF7, ELOB and ELOC (PubMed:15601820). Interacts with MET (PubMed:15713673). Interacts (via B30.2/SPRY domain) with PAWR; this interaction occurs in association with the Elongin BC complex (PubMed:16498413, PubMed:20561531). Interacts with NOS2 (PubMed:21199876).
messages: Cytoplasm
messages: Substrate recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:15601820, PubMed:21199876). Negatively regulates nitric oxide (NO) production and limits cellular toxicity in activated macrophages by mediating the ubiquitination and proteasomal degradation of NOS2 (PubMed:21199876). Acts as a bridge which links NOS2 with the ECS E3 ubiquitin ligase complex components ELOC and CUL5 (PubMed:21199876).
messages: The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes (By similarity). Essential for its ability to link NOS2 and the ECS E3 ubiquitin ligase complex components ELOC and CUL5.
messages: cytosol

9606:TNFRSF25
gene id: 9606:TNFRSF25
uniprot id: Q93038
names: Function
names: Miscellaneous
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Glycosylated at Arg-352 by enteropathogenic E.coli protein NleB1.
messages: Abundantly expressed in thymocytes and lymphocytes. Detected in lymphocyte-rich tissues such as thymus, colon, intestine, and spleen. Also found in the prostate.
messages: Cell membrane
messages: Glycosylated.
messages: Homodimer. Interacts strongly via the death domains with TNFRSF1 and TRADD to activate at least two distinct signaling cascades, apoptosis and NF-kappa-B signaling. Interacts with BAG4.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Receptor for TNFSF12/APO3L/TWEAK. Interacts directly with the adapter TRADD. Mediates activation of NF-kappa-B and induces apoptosis. May play a role in regulating lymphocyte homeostasis.
messages: Secreted

9606:PDC
gene id: 9606:PDC
uniprot id: P20941
uniprot id: Q52LP8
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the phosducin family.
messages: Forms a complex with the beta and gamma subunits of the GTP-binding protein, transducin. Interacts with CRX.
messages: Light-induced changes in cyclic nucleotide levels modulate the phosphorylation of this protein by cAMP kinase.
messages: May participate in the regulation of visual phototransduction or in the integration of photoreceptor metabolism. Inhibits the transcriptional activation activity of the cone-rod homeobox CRX.
messages: Nucleus
messages: Photoreceptor inner segment
messages: cytosol
messages: photoreceptor outer segment

9606:RPS6KB1
gene id: 9606:RPS6KB1
uniprot id: P23443
names: Activity Regulation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Activation requires multiple phosphorylation events on serine/threonine residues. Activation appears to be first mediated by phosphorylation of multiple sites in the autoinhibitory domain, which facilitates phosphorylation at Thr-412, disrupting the autoinhibitory mechanism and allowing phosphorylation of Thr-252 by PDPK1. The active conformation of the kinase is believed to be stabilized by a mechanism involving three conserved phosphorylation sites located in the kinase domain activation loop (Thr-252) and in the AGC-kinase C-terminal domain (Ser-394 in the middle of the tail/linker region and Thr-412 within a hydrophobic motif at its end). Activated by mTORC1; isoform Alpha I and isoform Alpha II are sensitive to rapamycin, which inhibits activating phosphorylation at Thr-412. Activated by PDPK1.
messages: Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. S6 kinase subfamily.
messages: Cytoplasm
messages: Interacts with PPP1R9A/neurabin-1 (By similarity). Interacts with RPTOR (PubMed:12150926). Interacts with IRS1 (PubMed:18952604). Interacts with EIF3B and EIF3C (PubMed:16286006). Interacts with TRAF4 (PubMed:12801526). Interacts with POLDIP3 (PubMed:15341740). Interacts (via N-terminus) with IER5 (PubMed:26496226).
messages: Mitochondrion
messages: Mitochondrion outer membrane
messages: Nucleus
messages: Phosphorylation at Thr-412 is regulated by mTORC1. The phosphorylation at this site is maintained by an agonist-dependent autophosphorylation mechanism (PubMed:29236692, PubMed:18925875, PubMed:19085255, PubMed:22017876, PubMed:23429703). Activated by phosphorylation at Thr-252 by PDPK1 (PubMed:9445476, PubMed:19864428). Dephosphorylation by PPP1CC at Thr-412 in mitochondrion (PubMed:17936702).
messages: Serine/threonine-protein kinase that acts downstream of mTOR signaling in response to growth factors and nutrients to promote cell proliferation, cell growth and cell cycle progression (PubMed:11500364, PubMed:12801526, PubMed:14673156, PubMed:15071500, PubMed:15341740, PubMed:16286006, PubMed:17052453, PubMed:17053147, PubMed:17936702, PubMed:18952604, PubMed:19085255, PubMed:19720745, PubMed:19935711, PubMed:19995915, PubMed:23429703, PubMed:28178239, PubMed:22017876). Regulates protein synthesis through phosphorylation of EIF4B, RPS6 and EEF2K, and contributes to cell survival by repressing the pro-apoptotic function of BAD (PubMed:11500364, PubMed:12801526, PubMed:14673156, PubMed:15071500, PubMed:15341740, PubMed:16286006, PubMed:17052453, PubMed:17053147, PubMed:17936702, PubMed:18952604, PubMed:19085255, PubMed:19720745, PubMed:19935711, PubMed:19995915, PubMed:23429703, PubMed:28178239, PubMed:22017876). Under conditions of nutrient depletion, the inactive form associates with the EIF3 translation initiation complex (PubMed:16286006). Upon mitogenic stimulation, phosphorylation by the mechanistic target of rapamycin complex 1 (mTORC1) leads to dissociation from the EIF3 complex and activation (PubMed:16286006). The active form then phosphorylates and activates several substrates in the pre-initiation complex, including the EIF2B complex and the cap-binding complex component EIF4B (PubMed:16286006). Also controls translation initiation by phosphorylating a negative regulator of EIF4A, PDCD4, targeting it for ubiquitination and subsequent proteolysis (PubMed:17053147). Promotes initiation of the pioneer round of protein synthesis by phosphorylating POLDIP3/SKAR (PubMed:15341740). In response to IGF1, activates translation elongation by phosphorylating EEF2 kinase (EEF2K), which leads to its inhibition and thus activation of EEF2 (PubMed:11500364). Also plays a role in feedback regulation of mTORC2 by mTORC1 by phosphorylating RICTOR, resulting in the inhibitio…
messages: The TOS (TOR signaling) motif is essential for activation by mTORC1.
messages: The autoinhibitory domain is believed to block phosphorylation within the AGC-kinase C-terminal domain and the activation loop.
messages: Widely expressed.
messages: synaptosome

9606:HMSD
gene id: 9606:HMSD
uniprot id: A8MTL9
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the serpin family.
messages: Highly expressed in dendritic cells and primary leukemia cells, especially those of myeloid lineage.
messages: Putative serine protease inhibitor.
messages: Secreted

9606:KLK2
gene id: 9606:KLK2
uniprot id: P20151
names: Function
names: Miscellaneous
names: Similarity
messages: Belongs to the peptidase S1 family. Kallikrein subfamily.
messages: Glandular kallikreins cleave Met-Lys and Arg-Ser bonds in kininogen to release Lys-bradykinin.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

9606:CMTM4
gene id: 9606:CMTM4
uniprot id: Q8IZR5
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acts as a backup for CMTM6 to regulate plasma membrane expression of PD-L1/CD274, an immune inhibitory ligand critical for immune tolerance to self and antitumor immunity. May protect PD-L1/CD274 from being polyubiquitinated and targeted for degradation.
messages: Belongs to the chemokine-like factor family.
messages: Highly expressed in testis and prostate.
messages: Interacts with PD-L1/CD274 and CMTM6.
messages: Membrane

9606:ACAD8
gene id: 9606:ACAD8
uniprot id: Q9UKU7
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the acyl-CoA dehydrogenase family.
messages: Detected at comparable levels in heart, lung, brain, skeletal muscle, pancreas and placenta. Weakly expressed in liver and kidney.
messages: Homotetramer, formed by a dimer of dimers (PubMed:11013134, PubMed:14752098). May be part of the large multiprotein complex ARC/DRIP (PubMed:10235267).
messages: Isobutyryl-CoA dehydrogenase which catalyzes the conversion of 2-methylpropanoyl-CoA to (2E)-2-methylpropenoyl-CoA in the valine catabolic pathway (PubMed:11013134, PubMed:12359132, PubMed:16857760). To a lesser extent, also able to catalyze the oxidation of (2S)-2-methylbutanoyl-CoA (PubMed:11013134, PubMed:12359132).
messages: Mitochondrion
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:HCRT
gene id: 9606:HCRT
uniprot id: O43612
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Abundantly expressed in subthalamic nucleus but undetectable in other brain regions tested (hypothalamus was not tested) and in heart, placenta, lung, liver, skeletal muscle, kidney and pancreas.
messages: Belongs to the orexin family.
messages: Binds to orexin receptor HCRTR2/OX2R only (By similarity). Stimulates food intake (By similarity). Modulates pituitary luteinizing hormone secretion in an ovarian steroid-dependent manner (By similarity).
messages: Binds to orexin receptors HCRTR1/OX1R and HCRTR2/OX2R with a high affinity (By similarity). Stimulates food intake (By similarity). Modulates pituitary luteinizing hormone secretion in an ovarian steroid-dependent manner (By similarity).
messages: Cytoplasmic vesicle
messages: Neuropeptides that play a significant role in the regulation of food intake and sleep-wakefulness, possibly by coordinating the complex behavioral and physiologic responses of these complementary homeostatic functions. A broader role in the homeostatic regulation of energy metabolism, autonomic function, hormonal balance and the regulation of body fluids, is also suggested.
messages: Rough endoplasmic reticulum
messages: Specific enzymatic cleavages at paired basic residues yield the different active peptides.
messages: Synapse
messages: The disease is caused by variants affecting the gene represented in this entry. Human narcolepsy is associated with a deficient orexin system. Orexins are absent and/or greatly diminished in the brain and cerebrospinal fluid (CSF) of most narcoleptic patients.

9606:MAGEA2
gene id: 9606:MAGEA2
uniprot id: P43356
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Expressed in many tumors of several types, such as melanoma, head and neck squamous cell carcinoma, lung carcinoma and breast carcinoma, but not in normal tissues except for testes.
messages: Interacts with TRIM28 and UBE2H. Interacts with HDAC3. Interacts with PML (isoform PML-1, isoform PML-2, isoform PML-3, isoform PML-4 and isoform PML-5).
messages: Nucleus
messages: PML body
messages: Reduces p53/TP53 transactivation function through recruitment of HDAC3 to p53/TP53 transcription sites. Also represses p73/TP73 activity. Proposed to enhance ubiquitin ligase activity of RING-type zinc finger-containing E3 ubiquitin-protein ligases. In vitro enhances ubiquitin ligase activity of TRIM28 and stimulates p53/TP53 ubiquitination by TRIM28 potentially in presence of Ubl-conjugating enzyme UBE2H. Proposed to act through recruitment and/or stabilization of the Ubl-conjugating enzyme (E2) at the E3:substrate complex. May play a role in embryonal development and tumor transformation or aspects of tumor progression. In vitro promotes cell viability in melanoma cell lines. Antigen recognized on a melanoma by autologous cytolytic T-lymphocytes. Negatively regulates acetylation and sumoylation of PML and represses PML-induced p53/TP53 acetylation and activation.

9606:PNPLA5
gene id: 9606:PNPLA5
uniprot id: Q7Z6Z6
names: Developmental Stage
names: Function
names: Tissue Specificity
messages: Expressed in brain and pituitary gland.
messages: Has abundant triacylglycerol lipase activity.
messages: No differential expression during adipocyte differentiation.

9606:NACAD
gene id: 9606:NACAD
uniprot id: O15069
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the NAC-alpha family.
messages: Cytoplasm
messages: May prevent inappropriate targeting of non-secretory polypeptides to the endoplasmic reticulum (ER). May bind to nascent polypeptide chains as they emerge from the ribosome and block their interaction with the signal recognition particle (SRP), which normally targets nascent secretory peptides to the ER. May also reduce the inherent affinity of ribosomes for protein translocation sites in the ER membrane (M sites) (By similarity).
messages: Nucleus

9606:PCDHA11
gene id: 9606:PCDHA11
uniprot id: Q9Y5I1
names: Function
names: Subcellular Location Annotation
messages: Cell membrane
messages: Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain.

9606:EFR3A
gene id: 9606:EFR3A
uniprot id: Q14156
names: Disease Annotation
names: Function
names: PTM
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the EFR3 family.
messages: Cell membrane
messages: Component of a complex required to localize phosphatidylinositol 4-kinase (PI4K) to the plasma membrane (PubMed:23229899, PubMed:25608530, PubMed:26571211). The complex acts as a regulator of phosphatidylinositol 4-phosphate (PtdIns(4)P) synthesis (Probable). In the complex, EFR3A probably acts as the membrane-anchoring component (PubMed:23229899). Also involved in responsiveness to G-protein-coupled receptors; it is however unclear whether this role is direct or indirect (PubMed:25380825).
messages: Component of a phosphatidylinositol 4-kinase (PI4K) complex, composed of PI4KA, EFR3 (EFR3A or EFR3B), TTC7 (TTC7A or TTC7B) and HYCC (HYCC1 or HYCC2) (PubMed:26571211).
messages: Contaminating sequence. Potential poly-A sequence.
messages: Genetic variations in EFR3A may be associated with susceptibility to autism.
messages: Palmitoylated at its N-terminus, anchoring the protein to the plasma membrane.
messages: cytosol

9606:GALR3
gene id: 9606:GALR3
uniprot id: O60755
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Receptor for the hormone galanin (PubMed:25691535). Receptor for the hormone spexin-1 (PubMed:24517231).

9606:RNASEH1
gene id: 9606:RNASEH1
uniprot id: E5KN15
uniprot id: O60930
names: Activity Regulation
names: Cofactor
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the RNase H family.
messages: Binds 1 Mg(2+) ion per subunit. May bind a second metal ion at a regulatory site, or after substrate binding.
messages: Cytoplasm
messages: Endonuclease that specifically degrades the RNA of RNA-DNA hybrids (PubMed:10497183). Plays a role in RNA polymerase II (RNAp II) transcription termination by degrading R-loop RNA-DNA hybrid formation at G-rich pause sites located downstream of the poly(A) site and behind the elongating RNAp II (PubMed:21700224).
messages: Endonuclease that specifically degrades the RNA of RNA-DNA hybrids.
messages: In the presence of magnesium, manganese is inhibitory.
messages: Monomer.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitous.

9606:PLAC1
gene id: 9606:PLAC1
uniprot id: Q9HBJ0
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the PLAC1 family.
messages: Expressed in placenta. Localizes primarily to differentiated syncytiotrophoblast throughout gestation as well as to a small population of villous cytotrophoblasts. Also detected in maternal blood and rapidly disappears following delivery, but is not detected in other adult or fetal tissues examined.
messages: May play a role in placental development.
messages: Secreted
messages: Up-regulated during trophoblast differentiation and by FGF7 in trophoblast cells.

9606:ZNF154
gene id: 9606:ZNF154
uniprot id: Q13106
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:GSTM2
gene id: 9606:GSTM2
uniprot id: A0A384P5E9
uniprot id: P28161
uniprot id: Q0D2I8
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the GST superfamily. Mu family.
messages: Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Participates in the formation of novel hepoxilin regioisomers (PubMed:21046276).
messages: Cytoplasm
messages: Homodimer.
messages: Muscle.

9606:RALYL
gene id: 9606:RALYL
uniprot id: B3KT61
uniprot id: Q86SE5
names: Similarity
names: Tissue Specificity
messages: Belongs to the RRM HNRPC family. RALY subfamily.
messages: Widely expressed, with highest levels in brain.

9606:LMCD1
gene id: 9606:LMCD1
uniprot id: Q9NZU5
names: Domain
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cytoplasm
messages: Expressed in the heart (at protein level). Expressed in many tissues with highest abundance in skeletal muscle.
messages: Interacts with GATA1 and GATA4 (By similarity). Interacts with beta-dystroglycan. Interacts with GATA6.
messages: Nucleus
messages: The LIM zinc-binding domains and the Cys-rich region mediate interaction with GATA6.
messages: Transcriptional cofactor that restricts GATA6 function by inhibiting DNA-binding, resulting in repression of GATA6 transcriptional activation of downstream target genes. Represses GATA6-mediated trans activation of lung- and cardiac tissue-specific promoters. Inhibits DNA-binding by GATA4 and GATA1 to the cTNC promoter (By similarity). Plays a critical role in the development of cardiac hypertrophy via activation of calcineurin/nuclear factor of activated T-cells signaling pathway.

9606:BATF
gene id: 9606:BATF
uniprot id: Q16520
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: AP-1 family transcription factor that controls the differentiation of lineage-specific cells in the immune system: specifically mediates the differentiation of T-helper 17 cells (Th17), follicular T-helper cells (TfH), CD8(+) dendritic cells and class-switch recombination (CSR) in B-cells. Acts via the formation of a heterodimer with JUNB that recognizes and binds DNA sequence 5'-TGA[CG]TCA-3'. The BATF-JUNB heterodimer also forms a complex with IRF4 (or IRF8) in immune cells, leading to recognition of AICE sequence (5'-TGAnTCA/GAAA-3'), an immune-specific regulatory element, followed by cooperative binding of BATF and IRF4 (or IRF8) and activation of genes. Controls differentiation of T-helper cells producing interleukin-17 (Th17 cells) by binding to Th17-associated gene promoters: regulates expression of the transcription factor RORC itself and RORC target genes such as IL17 (IL17A or IL17B). Also involved in differentiation of follicular T-helper cells (TfH) by directing expression of BCL6 and MAF. In B-cells, involved in class-switch recombination (CSR) by controlling the expression of both AICDA and of germline transcripts of the intervening heavy-chain region and constant heavy-chain region (I(H)-C(H)). Following infection, can participate in CD8(+) dendritic cell differentiation via interaction with IRF4 and IRF8 to mediate cooperative gene activation. Regulates effector CD8(+) T-cell differentiation by regulating expression of SIRT1. Following DNA damage, part of a differentiation checkpoint that limits self-renewal of hematopoietic stem cells (HSCs): up-regulated by STAT3, leading to differentiation of HSCs, thereby restricting self-renewal of HSCs (By similarity).
messages: Belongs to the bZIP family.
messages: Cytoplasm
messages: Expressed at highest levels in lung, and at lower levels in placenta, liver, kidney, spleen, and peripheral blood. Detected in SW480 colorectal cancer cell line and several hematopoietic tumor cell lines, including Raji Burkitt's lymphoma. Strongly expressed in mature B- and T-lymphocytes. Also expressed in moderate levels in lymph node and appendix and at low levels in thymus and bone marrow (PubMed:10777209).
messages: Heterodimer; mainly heterodimerizes with JUNB. The BATF-JUNB heterodimer interacts with IRF4 and IRF8. Interacts (via bZIP domain) with IRF4 and IRF8; the interaction is direct (By similarity). Also forms heterodimers with JUN and JUND. Also interacts with IFI35.
messages: Nucleus
messages: Phosphorylated on serine and threonine residues and at least one tyrosine residue. Phosphorylation at Ser-43 inhibit DNA binding activity and transforms it as a negative regulator of AP-1 mediated transcription (By similarity).
messages: Phosphorylated.
messages: Up-regulated by PDCD1 following infection by HIV-1 virus, leading to inhibit T-cell functions and exhaust T-cells. Up-regulated by Epstein-Barr virus (EBV) protein EBNA2 following infection by EBV.

9606:AMELY
gene id: 9606:AMELY
uniprot id: Q99218
names: Developmental Stage
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the amelogenin family.
messages: Plays a role in biomineralization. Seems to regulate the formation of crystallites during the secretory stage of tooth enamel development. Thought to play a major role in the structural organization and mineralization of developing enamel.
messages: Transiently but abundantly expressed by ameloblasts during tooth development. Amelogenin is the predominant protein in developing dental enamel.
messages: extracellular matrix

9606:DIPK2A
gene id: 9606:DIPK2A
uniprot id: B3KTD4
uniprot id: Q8NDZ4
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the DIPK family.
messages: COPI-coated vesicle
messages: Genetic variations in C3orf58 may be associated with susceptibility to autism (PubMed:18621663).
messages: Golgi apparatus
messages: May play a role in cardiomyocyte proliferation through paracrine signaling and activation of the PPI3K-AKT-CDK7 signaling cascade.
messages: Secreted

9606:PRCD
gene id: 9606:PRCD
uniprot id: Q00LT1
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the PRCD family.
messages: Endoplasmic reticulum
messages: Golgi apparatus
messages: Interacts with RHO/rhodopsin; the interaction promotes PRCD stability.
messages: Involved in vision.
messages: Membrane
messages: Palmitoylated at Cys-2 (PubMed:27613864). Palmitoylation is essential for protein stability and trafficking to the photoreceptor outer segment, but does not appear to be essential for membrane localization (PubMed:27613864). Probably palmitoylated by ZDHHC3 (PubMed:27613864).
messages: Phosphorylated.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: photoreceptor outer segment

9606:ABCC5
gene id: 9606:ABCC5
uniprot id: O15440
names: Activity Regulation
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds, and xenobiotics from cells. Mediates ATP-dependent transport of endogenous metabolites such as cAMP and cGMP, folic acid and N-lactoyl-amino acids (in vitro) (PubMed:10893247, PubMed:15899835, PubMed:25964343, PubMed:17229149, PubMed:12695538, PubMed:12637526). Acts also as a general glutamate conjugate and analog transporter that can limit the brain levels of endogenous metabolites, drugs, and toxins (PubMed:26515061). Confers resistance to the antiviral agent PMEA (PubMed:12695538). Able to transport several anticancer drugs including methotrexate, and nucleotide analogs in vitro, however it does with low affinity, thus the exact role of ABCC5 in mediating resistance still needs to be elucidated (PubMed:10840050, PubMed:15899835, PubMed:12435799, PubMed:12695538). Acts as a heme transporter required for the translocation of cytosolic heme to the secretory pathway (PubMed:24836561). May play a role in energy metabolism by regulating the glucagon-like peptide 1 (GLP-1) secretion from enteroendocrine cells (By similarity).
messages: Although other labs have confirmed the ability of ABCC5 to transport cGMP in an ATP-dependent manner, they obtained a much lower affinity for this substrate (PubMed:12637526, PubMed:12695538). The authors conclude that ABCC5 is a low-affinity cyclic nucleotide transporter a major function in cGMP excretion is unlikely (PubMed:12637526, PubMed:12695538).
messages: Apical cell membrane
messages: Basolateral cell membrane
messages: Belongs to the ABC transporter superfamily. ABCC family. Conjugate transporter (TC 3.A.1.208) subfamily.
messages: Cytoplasmic granule
messages: Endosome membrane
messages: Golgi apparatus lumen
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Predominant isoform in retinal pigment epithelium, bladder, and stomach.
messages: Ubiquitously expressed, but levels in brain and muscle are especially high (PubMed:9827529, PubMed:10438534, PubMed:15501592). All isoforms are equally expressed in retina (PubMed:17521428).
messages: cGMP transport is highly sensitive to inhibitors of cGMP phosphodiesterase, such as zaprinast, trequinsin and sildenafil.

9606:NEK8
gene id: 9606:NEK8
uniprot id: Q86SG6
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the protein kinase superfamily. NEK Ser/Thr protein kinase family. NIMA subfamily.
messages: Cytoplasm
messages: Highest expression in thyroid, adrenal gland and skin. Low levels in spleen, colon and uterus. Overexpressed in breast tumors, with highest expression in infiltrating ductal carcinomas and moderate levels in mucinous adenocarcinoma.
messages: Interacts with PKD2; may regulate PKD2 targeting to the cilium (By similarity). Component of a complex containing at least ANKS6, INVS, NEK8 and NPHP3 (PubMed:23418306, PubMed:23793029). ANKS6 may organize complex assembly by linking INVS and NPHP3 to NEK8 and INVS may target the complex to the proximal ciliary axoneme (PubMed:23418306, PubMed:23793029). Interacts with ANKS3 (PubMed:26188091).
messages: Required for renal tubular integrity. May regulate local cytoskeletal structure in kidney tubule epithelial cells. May regulate ciliary biogenesis through targeting of proteins to the cilia (By similarity). Plays a role in organogenesis and is involved in the regulation of the Hippo signaling pathway.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: centrosome
messages: cilium
messages: cytoskeleton

9606:CAPS2
gene id: 9606:CAPS2
uniprot id: Q9BXY5
names: Tissue Specificity
messages: Abundantly expressed in many tissues. Expressed in brain, colon, heart, kidney, liver, lung, liver, pancreas, placenta, skeletal muscle, testis and thymus. Highest expression in colon, testis, lung, placenta and brain.

9606:AXL
gene id: 9606:AXL
uniprot id: M0R0W6
uniprot id: P30530
names: Activity Regulation
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Acts as a receptor for Ebolavirus, possibly through GAS6 binding to phosphatidyl-serine at the surface of virion envelope.
messages: (Microbial infection) Acts as a receptor for lassa virus and lymphocytic choriomeningitis virus, possibly through GAS6 binding to phosphatidyl-serine at the surface of virion envelope.
messages: (Microbial infection) Promotes Zika virus entry in glial cells, Sertoli cells and astrocytes (PubMed:28076778, PubMed:29379210, PubMed:31311882). Additionally, Zika virus potentiates AXL kinase activity to antagonize type I interferon signaling and thereby promotes infection (PubMed:28076778). Interferon signaling inhibition occurs via an SOCS1-dependent mechanism (PubMed:29379210).
messages: AXL and its ligand GAS6 are highly expressed in thyroid carcinoma tissues, and might thus be involved in thyroid tumorigenesis. Overexpression of AXL and its ligand was also detected in many other cancers such as myeloproliferative disorders, prostatic carcinoma cells, or breast cancer.
messages: Activated by GAS6-binding and subsequent autophosphorylation.
messages: Belongs to the protein kinase superfamily. Tyr protein kinase family. AXL/UFO subfamily.
messages: Cell membrane
messages: Heterodimer and heterotetramer with ligand GAS6. Interacts with CBL, GRB2, LCK, NCK2, PIK3R1, PIK3R2, PIK3R3, PLCG1, SOCS1 and TNS2. Part of a complex including AXL, TNK2 and GRB2, in which GRB2 promotes AXL recruitment by TNK2.
messages: Highly expressed in metastatic colon tumors. Expressed in primary colon tumors. Weakly expressed in normal colon tissue.
messages: Membrane
messages: Monoubiquitinated upon GAS6-binding. A very small proportion of the receptor could be subjected to polyubiquitination in a very transient fashion.
messages: Phosphorylated at tyrosine residues by autocatalysis, which activates kinase activity.
messages: Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding growth factor GAS6 and which is thus regulating many physiological processes including cell survival, cell proliferation, migration and differentiation. Ligand binding at the cell surface induces dimerization and autophosphorylation of AXL. Following activation by ligand, AXL binds and induces tyrosine phosphorylation of PI3-kinase subunits PIK3R1, PIK3R2 and PIK3R3; but also GRB2, PLCG1, LCK and PTPN11. Other downstream substrate candidates for AXL are CBL, NCK2, SOCS1 and TNS2. Recruitment of GRB2 and phosphatidylinositol 3 kinase regulatory subunits by AXL leads to the downstream activation of the AKT kinase. GAS6/AXL signaling plays a role in various processes such as endothelial cell survival during acidification by preventing apoptosis, optimal cytokine signaling during human natural killer cell development, hepatic regeneration, gonadotropin-releasing hormone neuron survival and migration, platelet activation, or regulation of thrombotic responses. Also plays an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response.

9606:OTUD6B
gene id: 9606:OTUD6B
uniprot id: Q8N6M0
names: Caution
names: Disease Annotation
names: Function
names: Subunit
messages: Deubiquitinating enzyme that may play a role in the ubiquitin-dependent regulation of protein synthesis, downstream of mTORC1 (PubMed:21267069, PubMed:27864334). May associate with the protein synthesis initiation complex and modify its ubiquitination to repress translation (PubMed:27864334). May also repress DNA synthesis and modify different cellular targets thereby regulating cell growth and proliferation (PubMed:27864334). May also play a role in proteasome assembly and function (PubMed:28343629).
messages: Initially, no deubiquitinase activity could be detected when tested (PubMed:23827681). Other studies, show an obvious deubiquitinase activity (PubMed:21267069, PubMed:28343629, PubMed:27864334).
messages: Interacts with the eukaryotic translation initiation factor 4F complex.
messages: Stimulates protein synthesis. Influences the expression of CCND1/cyclin D1 by promoting its translation and regulates MYC/c-Myc protein stability.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:RFX8
gene id: 9606:RFX8
uniprot id: Q6ZV50
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the RFX family.
messages: May be a transcription factor.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Nucleus

9606:MEFV
gene id: 9606:MEFV
uniprot id: O15553
names: Developmental Stage
names: Disease Annotation
names: Domain
names: Function
names: Induction
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cleaved by CASP1 (Probable). The N-terminal cleavage product localizes to the nucleus as a filamentous network and to the cytoplasm, interacts more strongly with RELA and NFKBIA than the full-length protein, enhances the nuclear localization of RELA and induces NFKBIA proteolysis. The C-terminal cleavage product localizes to the cytoplasm (Probable).
messages: Cytoplasm
messages: Degraded along with the delivery of its substrates to autolysosomal compartments (at protein level).
messages: Expressed in peripheral blood leukocytes, particularly in mature granulocytes and to a lesser extent in monocytes but not in lymphocytes. Detected in spleen, lung and muscle, probably as a result of leukocyte infiltration in these tissues. Not expressed in thymus, prostate, testis, ovary, small intestine, colon, heart, brain, placenta, liver, kidney, pancreas. Expression detected in several myeloid leukemic, colon cancer, and prostate cancer cell lines.
messages: First detected in bone marrow promyelocytes. Expression increases throughout myelocyte differentiation and peaks in the mature myelomonocytic cells.
messages: Homotrimer. Interacts (via the B box-type zinc finger) with PSTPIP1 (PubMed:14595024, PubMed:17964261, PubMed:19109554, PubMed:28835462). Interacts (via the B30.2/SPRY domain) with several components of the inflammasome complex, including CASP1 p20 and p10 subunits, CASP5, PYCARD, NLRP1, NLRP2 and NLRP3, as well as with unprocessed IL1B; this interaction may lead to autophagic degradation of these proteins (PubMed:11498534, PubMed:16785446, PubMed:17431422, PubMed:17964261, PubMed:26347139). Component of the AIM2 PANoptosome complex, a multiprotein complex that drives inflammatory cell death (PANoptosis) (By similarity). Interacts with NFKBIA and RELA (PubMed:18577712). Interacts weakly with VASP and ACTR3 (PubMed:19109554). Interacts with active ULK1 (phosphorylated on 'Ser-317') and BECN1 simultaneously. Also interacts with ATG16L1 (via WD repeats), and with ATG8 family members, including GABARAP, GABARAPL1 and, to a lesser extent, GABARAPL2, MAP1LC3A/LC3A and MAP1LC3C/LC3C. Interacts with TRIM21 (PubMed:26347139, PubMed:28835462). Interacts with YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ and YWHAZ; the interaction is required for the down-regulation of pyrin pro-inflammatory activity (PubMed:27030597, PubMed:28835462).
messages: In monocytes, up-regulated by treatment with colchicine and IFN-alpha, by the pro-inflammatory cytokines IFNG/IFN-gamma and TNF, by bacterial lipopolysaccharides (LPS) and by retroviral infection. Repressed in monocytes by the anti-inflammatory cytokines IL10/interleukin-10, TGFB1 and IL4/interleukin-4. In neutrophils and macrophages, up-regulated by IFNG/IFN-gamma with a peak after 8 hours of treatment.
messages: Involved in the regulation of innate immunity and the inflammatory response in response to IFNG/IFN-gamma (PubMed:10807793, PubMed:11468188, PubMed:17964261, PubMed:18577712, PubMed:19109554, PubMed:19584923, PubMed:16037825, PubMed:27030597, PubMed:28835462, PubMed:16785446, PubMed:17431422, PubMed:26347139). Organizes autophagic machinery by serving as a platform for the assembly of ULK1, Beclin 1/BECN1, ATG16L1, and ATG8 family members and recognizes specific autophagy targets, thus coordinating target recognition with assembly of the autophagic apparatus and initiation of autophagy (PubMed:16785446, PubMed:17431422, PubMed:26347139). Acts as an autophagy receptor for the degradation of several inflammasome components, including CASP1, NLRP1 and NLRP3, hence preventing excessive IL1B- and IL18-mediated inflammation (PubMed:16785446, PubMed:17431422, PubMed:26347139). However, it can also have a positive effect in the inflammatory pathway, acting as an innate immune sensor that triggers PYCARD/ASC specks formation, caspase-1 activation, and IL1B and IL18 production (PubMed:16037825, PubMed:27030597, PubMed:28835462). Together with AIM2, also acts as a mediator of pyroptosis, necroptosis and apoptosis (PANoptosis), an integral part of host defense against pathogens, in response to bacterial infection (By similarity). It is required for PSTPIP1-induced PYCARD/ASC oligomerization and inflammasome formation (PubMed:10807793, PubMed:11468188, PubMed:17964261, PubMed:18577712, PubMed:19109554, PubMed:19584923). Recruits PSTPIP1 to inflammasomes, and is required for PSTPIP1 oligomerization (PubMed:10807793, PubMed:11468188, PubMed:17964261, PubMed:18577712, PubMed:19109554, PubMed:19584923).
messages: Nucleus
messages: Phosphorylation at Ser-242 is required for the interaction with 14-3-3 proteins and down-regulation of pyrin pro-inflammatory activity.
messages: The B box-type zinc finger interacts, possibly intramolecularly, with the pyrin domain; this may be an autoinhibitory mechanism released by PSTPIP1 binding.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The disease is caused by variants affecting the gene represented in this entry. The disease-associated mutations in the B30.2/SPRY domain perturb ULK1 recruitment and autophagic degradation of inflammasome components, including NLRP3, and hence may contribute to the inflammatory phenotype associated with ARFMF.
messages: autophagosome
messages: cytoskeleton
messages: lamellipodium
messages: ruffle

9606:CCDC103
gene id: 9606:CCDC103
uniprot id: Q8IW40
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the CCDC103/PR46b family.
messages: Cytoplasm
messages: Dynein-attachment factor required for cilia motility.
messages: Homodimer.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: flagellum

9606:TRIM43
gene id: 9606:TRIM43
uniprot id: Q96BQ3
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the TRIM/RBCC family.
messages: By DUX4 during herpesvirus infection.
messages: E3 ligase that regulates nuclear lamina integrity and the association of viral chromatin with transcriptionally-active host chromatin. Acts thereby as a herpesvirus-specific antiviral factor and mediates the ubiquitination-dependent proteasomal degradation of PCNT.
messages: centrosome

9606:ARHGAP10
gene id: 9606:ARHGAP10
uniprot id: A1A4S6
names: Domain
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cell membrane
messages: Cytoplasm
messages: Endosome membrane
messages: GTPase-activating protein that catalyzes the conversion of active GTP-bound Rho GTPases to their inactive GDP-bound form, thus suppressing various Rho GTPase-mediated cellular processes (PubMed:11432776). Also converts Cdc42 to an inactive GDP-bound state (PubMed:11432776). Essential for PTKB2 regulation of cytoskeletal organization via Rho family GTPases. Inhibits PAK2 proteolytic fragment PAK-2p34 kinase activity and changes its localization from the nucleus to the perinuclear region. Stabilizes PAK-2p34 thereby increasing stimulation of cell death (By similarity). Associates with MICAL1 on the endosomal membrane to promote Rab8-Rab10-dependent tubule extension. After dissociation with MICAL1, recruits WDR44 which connects the endoplasmic reticulum (ER) with the endosomal tubule, thereby participating in the export of a subset of neosynthesized proteins (PubMed:32344433).
messages: High levels of expression in heart and skeletal muscle.
messages: Interacts with PKN3 (PubMed:11432776). Interacts with caspase-activated PAK2 proteolytic fragment PAK-2p34; the interaction does not affect GRAF2/ARHGAP10 GTPase activation activity towards RHOA and CDC42 (By similarity). Interacts via its SH3 domain with PTK2/FAK1 (By similarity). Interacts with PTK2B/PYK2; the interaction negatively regulates GRAF2/ARHGAP10 GTPase-activating activity (By similarity). Interacts with MICAL1 and WDR44; complex formation might transit from GRAF2/ARHGAP10-MICAL1 to GRAF2/ARHGAP10-WDR44 complexes (PubMed:32344433).
messages: Phosphorylated. Phosphorylated in vitro by constitutive active PKN3.
messages: The BAR domain is important to associate RAB8A (or RAB8B) and RAB10 to endosomal membrane to promote tubule extension. The BAR domain is also important to recruit WDR44 to endosomal tubules.
messages: perinuclear region

9606:ARPC4
gene id: 9606:ARPC4
uniprot id: P59998
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Actin-binding component of the Arp2/3 complex, a multiprotein complex that mediates actin polymerization upon stimulation by nucleation-promoting factor (NPF) (PubMed:9230079). The Arp2/3 complex mediates the formation of branched actin networks in the cytoplasm, providing the force for cell motility (PubMed:9230079). In addition to its role in the cytoplasmic cytoskeleton, the Arp2/3 complex also promotes actin polymerization in the nucleus, thereby regulating gene transcription and repair of damaged DNA (PubMed:29925947). The Arp2/3 complex promotes homologous recombination (HR) repair in response to DNA damage by promoting nuclear actin polymerization, leading to drive motility of double-strand breaks (DSBs) (PubMed:29925947).
messages: Belongs to the ARPC4 family.
messages: Cell projection
messages: Component of the Arp2/3 complex composed of ACTR2/ARP2, ACTR3/ARP3, ARPC1B/p41-ARC, ARPC2/p34-ARC, ARPC3/p21-ARC, ARPC4/p20-ARC and ARPC5/p16-ARC.
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: cytoskeleton

9606:TSPY8
gene id: 9606:TSPY8
uniprot id: A6NGL4
uniprot id: P0CW00
names: Function
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the nucleosome assembly protein (NAP) family.
messages: Cytoplasm
messages: Maps to a tandemly repeated region on chromosome Yp11; additionally at least one copy is reported originating from Yq. The gene is thought to be present with an inter-individual variation in copy number and between 20 and 60 copies per Y chromosome are expected. 35 tandemly repeated gene copies on Yp11 originating from one individual have been reported (PubMed:12815422).
messages: May be involved in sperm differentiation and proliferation.
messages: Nucleus

9606:IQCA1
gene id: 9606:IQCA1
uniprot id: Q86XH1
names: Function
names: Miscellaneous
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the AAA ATPase family. DRC11 subfamily.
messages: Chimeric cDNA.
messages: Component of the nexin-dynein regulatory complex (N-DRC), a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes.
messages: Component of the nexin-dynein regulatory complex (N-DRC).
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Unlikely isoform. Aberrant splice sites.
messages: flagellum axoneme

9606:NAA60
gene id: 9606:NAA60
uniprot id: A0A384NYU5
uniprot id: Q9H7X0
names: Caution
names: Function
names: Induction
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: According to a report, displays histone acetyltransferase activity while localized in the Golgi apparatus (PubMed:21981917). May mediate acetylation of free histone H4 and promote nucleosome assembly (PubMed:21981917). Such results are however unclear in vivo and recent reports strongly suggest that it acts as a N-alpha-acetyltransferase that specifically targets N-terminal residues of transmembrane proteins (PubMed:21750686, PubMed:25732826).
messages: Acetylated: autoacetylation is required for optimal acetyltransferase activity.
messages: Belongs to the acetyltransferase family. NAA60 subfamily.
messages: Golgi apparatus membrane
messages: In placenta and leukocytes, expressed from the maternal allele, due to imprinting of the paternal allele.
messages: Isoform 2: Imprinted (PubMed:21593219). Promoter methylation of the paternal allele may restrict expression to the maternal allele in placenta and leukocytes (PubMed:21593219). Isoform 1: Biallelically expressed (PubMed:21593219).
messages: Monomer and homodimer; monomer in presence of substrate and homodimer in its absence (PubMed:27320834).
messages: N-alpha-acetyltransferase that specifically mediates the acetylation of N-terminal residues of the transmembrane proteins, with a strong preference for N-termini facing the cytosol (PubMed:25732826). Displays N-terminal acetyltransferase activity towards a range of N-terminal sequences including those starting with Met-Lys, Met-Val, Met-Ala and Met-Met (PubMed:21750686, PubMed:25732826, PubMed:27550639, PubMed:27320834). Required for normal chromosomal segregation during anaphase (PubMed:21750686). May also show histone acetyltransferase activity; such results are however unclear in vivo and would require additional experimental evidences (PubMed:21981917).
messages: Produced by alternative splicing.

9606:ACKR1
gene id: 9606:ACKR1
uniprot id: Q16570
uniprot id: Q5Y7A1
uniprot id: Q5Y7A2
names: Function
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Atypical chemokine receptor that controls chemokine levels and localization via high-affinity chemokine binding that is uncoupled from classic ligand-driven signal transduction cascades, resulting instead in chemokine sequestration, degradation, or transcytosis. Also known as interceptor (internalizing receptor) or chemokine-scavenging receptor or chemokine decoy receptor. Has a promiscuous chemokine-binding profile, interacting with inflammatory chemokines of both the CXC and the CC subfamilies but not with homeostatic chemokines. Acts as a receptor for chemokines including CCL2, CCL5, CCL7, CCL11, CCL13, CCL14, CCL17, CXCL5, CXCL6, IL8/CXCL8, CXCL11, GRO, RANTES, MCP-1 and TARC. May regulate chemokine bioavailability and, consequently, leukocyte recruitment through two distinct mechanisms: when expressed in endothelial cells, it sustains the abluminal to luminal transcytosis of tissue-derived chemokines and their subsequent presentation to circulating leukocytes; when expressed in erythrocytes, serves as blood reservoir of cognate chemokines but also as a chemokine sink, buffering potential surges in plasma chemokine levels.
messages: Atypical chemokine receptor that controls chemokine levels and localization via high-affinity chemokine binding that is uncoupled from classic ligand-driven signal transduction cascades, resulting instead in chemokine sequestration, degradation, or transcytosis. Also known as interceptor (internalizing receptor) or chemokine-scavenging receptor or chemokine decoy receptor. Has a promiscuous chemokine-binding profile, interacting with inflammatory chemokines of both the CXC and the CC subfamilies but not with homeostatic chemokines. Acts as a receptor for chemokines including CCL2, CCL5, CCL7, CCL11, CCL13, CCL14, CCL17, CXCL5, CXCL6, IL8/CXCL8, CXCL11, GRO, RANTES, MCP-1, TARC and also for the malaria parasites P.vivax and P.knowlesi. May regulate chemokine bioavailability and, consequently, leukocyte recruitment through two distinct mechanisms: when expressed in endothelial cells, it sustains the abluminal to luminal transcytosis of tissue-derived chemokines and their subsequent presentation to circulating leukocytes; when expressed in erythrocytes, serves as blood reservoir of cognate chemokines but also as a chemokine sink, buffering potential surges in plasma chemokine levels.
messages: Belongs to the G-protein coupled receptor 1 family. Atypical chemokine receptor subfamily.
messages: DARC is responsible for the Duffy blood group system (FY) [MIM:110700]. The molecular basis of the Fy(A)=Fy1/Fy(B)=Fy2 blood group antigens is a single variation in position 42; Gly-42 corresponds to Fy(A) and Asp-42 to Fy(B). Individuals that do not produce the Duffy antigen (FY(A-B-)) are more resistant to infection by the malarial parasite Plasmodium vivax. This allele is found predominantly in population of African origin [MIM:611162].
messages: Early endosome
messages: Found in adult kidney, adult spleen, bone marrow and fetal liver. In particular, it is expressed along postcapillary venules throughout the body, except in the adult liver. Erythroid cells and postcapillary venule endothelium are the principle tissues expressing duffy. Fy(-A-B) individuals do not express duffy in the bone marrow, however they do, in postcapillary venule endothelium.
messages: Genetic variations in DARC define the white blood cell count quantitative trait locus 1 (WBCQ1) [MIM:611862]. Peripheral white blood cell count (WBC) is a common clinical measurement, used to determine evidence of acute inflammation or infection. Peripheral WBC is the sum of several cell types including neutrophils and lymphocytes, which are the most common types of WBC, as well as less common cell types such as eosinophils, basophils, and monocytes. Elevated WBC has been associated with risk of coronary heart disease, cancer, and all-cause mortality. White blood cell levels have widespread clinical applications including assessment of patients undergoing chemotherapy and evaluation of infection.
messages: Membrane
messages: Recycling endosome

9606:PLLP
gene id: 9606:PLLP
uniprot id: Q9Y342
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Appears to be involved in myelination. Could also participate in ion transport events as addition of plasmolipin to lipid bilayers induces the formation of ion channels, which are voltage-dependent and K(+)-selective (By similarity).
messages: Belongs to the MAL family.
messages: Hexamer arranged as a trimer of two plasmolipin subunits.
messages: Membrane

9606:NUDT18
gene id: 9606:NUDT18
uniprot id: Q6ZVK8
names: Function
names: Similarity
messages: Belongs to the Nudix hydrolase family.
messages: Mediates the hydrolysis of oxidized nucleoside diphosphate derivatives. Hydrolyzes 8-oxo-7,8-dihydroguanine (8-oxo-Gua)-containing deoxyribo- and ribonucleoside diphosphates to the monophosphates. Hydrolyzes 8-oxo-dGDP and 8-oxo-GDP with the same efficiencies. Hydrolyzes also 8-OH-dADP and 2-OH-dADP. Exhibited no or minimal hydrolysis activity against 8-oxo-dGTP, 8-oxo-GTP, dGTP, GTP, dGDP and GDP. Probably removes oxidized guanine nucleotides from both the DNA and RNA precursor pools.

9606:SRARP
gene id: 9606:SRARP
uniprot id: Q8NEQ6
names: Function
names: Induction
names: Subunit
names: Tissue Specificity
messages: Expressed in breast tumors with a higher expression level in estrogen receptor-positive cancers (PubMed:22341523, PubMed:28915724).
messages: Interacts with 14-3-3 proteins (PubMed:28915724).
messages: May regulate the transcriptional function of androgen and estrogen receptors.
messages: Up-regulated in breast cancers (PubMed:22341523).

9606:ATP13A5
gene id: 9606:ATP13A5
uniprot id: Q4VNC0
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type V subfamily.
messages: Membrane
messages: Unlikely isoform. Cloning artifact.

9606:PARP2
gene id: 9606:PARP2
uniprot id: Q9UGN5
names: Activity Regulation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: ADP-ribosyltransferase activity is regulated via an allosteric activation mechanism (PubMed:34108479). In absence of activation signal, PARP2 is autoinhibited by the PARP alpha-helical domain (also named HD region), which prevents effective NAD(+)-binding (PubMed:34108479). Activity is highly stimulated by signals, which unfold the PARP alpha-helical domain, relieving autoinhibition (PubMed:34108479). Poly-ADP-ribosyltransferase activity is tightly regulated and PARP2 is removed from damaged chromatin following initial poly-ADP-ribosylation of chromatin to avoid prolonged residence (trapping) that has cytotoxic consequences (PubMed:33275888). CHD1L promotes PARP2 removal from chromatin (PubMed:33275888). ADP-ribosyltransferase activity is inhibited by a number of PARP inhibitors (PARPi) compounds, that are used the treatment of breast or ovarian cancers that have defects in DNA repair by homologous recombination (PubMed:35349716). PARPi molecules (niraparib, talazoparib, and, to a lesser extent, olaparib) also trap PARP2 at DNA damage sites (PubMed:33275888, PubMed:35349716).
messages: Acetylation reduces DNA binding and enzymatic activity.
messages: Auto poly-ADP-ribosylated on serine residues, leading to dissociation of the PARP2-HPF1 complex from chromatin (PubMed:32939087, PubMed:34108479). Poly-ADP-ribosylated by PARP1 (By similarity).
messages: Belongs to the ARTD/PARP family.
messages: Chromosome
messages: Component of a base excision repair (BER) complex, containing at least XRCC1, PARP1, POLB and LRIG3 (By similarity). Homo- and heterodimer with PARP1 (PubMed:20092359). Interacts (via the PARP catalytic domain) with HPF1 (PubMed:27067600, PubMed:28190768, PubMed:32028527, PubMed:32939087, PubMed:33141820, PubMed:34108479). Interacts with core nucleosomes (PubMed:32939087, PubMed:33141820).
messages: Nucleus
messages: Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair (PubMed:10364231, PubMed:25043379, PubMed:27471034, PubMed:30104678, PubMed:32028527, PubMed:32939087, PubMed:34486521, PubMed:34874266, PubMed:34108479). Mediates glutamate, aspartate or serine ADP-ribosylation of proteins: the ADP-D-ribosyl group of NAD(+) is transferred to the acceptor carboxyl group of target residues and further ADP-ribosyl groups are transferred to the 2'-position of the terminal adenosine moiety, building up a polymer with an average chain length of 20-30 units (PubMed:25043379, PubMed:30104678, PubMed:30321391). Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage (PubMed:32939087). Mediates glutamate and aspartate ADP-ribosylation of target proteins in absence of HPF1 (PubMed:25043379). Following interaction with HPF1, catalyzes serine ADP-ribosylation of target proteins; HPF1 conferring serine specificity by completing the PARP2 active site (PubMed:28190768, PubMed:32028527, PubMed:34486521, PubMed:34874266, PubMed:34108479). PARP2 initiates the repair of double-strand DNA breaks: recognizes and binds DNA breaks within chromatin and recruits HPF1, licensing serine ADP-ribosylation of target proteins, such as histones, thereby promoting decompaction of chromatin and the recruitment of repair factors leading to the reparation of DNA strand breaks (PubMed:10364231, PubMed:32939087, PubMed:34108479). HPF1 initiates serine ADP-ribosylation but restricts the polymerase activity of PARP2 in order to limit the length of poly-ADP-ribose chains (PubMed:34732825, PubMed:34795260). Specifically mediates formation of branched poly-ADP-ribosylation (PubMed:30104678). Branched poly-ADP-ribose chains are specifically recognized by some factors, such as APLF (PubMed:30104678). In addition to proteins, also able to ADP-ribosylate DNA: preferentially acts on 5'-terminal phosphates…
messages: Proteolytically cleaved by caspase-8 (CASP8) in response to apoptosis, leading to its inactivation.
messages: The N-terminal disordered region does not act as a key DNA-binding domain (PubMed:26704974). The WGR and PARP catalytic domains function together to recruit PARP2 to sites of DNA breaks. The N-terminal disordered region is only required for activation on specific types of DNA damage (PubMed:26704974).
messages: The N-terminal region (NTR) recognizes and binds poly-ADP-ribose chains produced by PARP1, leading to its recruitment to DNA damage sites.
messages: The PARP alpha-helical domain (also named HD region) prevents effective NAD(+)-binding in absence of activation signal (PubMed:34108479). Binding to damaged DNA unfolds the PARP alpha-helical domain, relieving autoinhibition (PubMed:34108479).
messages: The WGR domain bridges two nucleosomes, with the broken DNA aligned in a position suitable for ligation (PubMed:30321391, PubMed:32939087, PubMed:33141820). The bridging induces structural changes in PARP2 that signal the recognition of a DNA break to the catalytic domain of PARP2, promoting HPF1 recruitment and subsequent activation of PARP2, licensing serine ADP-ribosylation of target proteins (PubMed:32939087).
messages: Widely expressed, mainly in actively dividing tissues (PubMed:10364231). The highest levels are in the brain, heart, pancreas, skeletal muscle and testis; also detected in kidney, liver, lung, placenta, ovary and spleen; levels are low in leukocytes, colon, small intestine, prostate and thymus (PubMed:10364231).

9606:SLC5A4
gene id: 9606:SLC5A4
uniprot id: Q9NY91
names: Activity Regulation
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Although it belongs to the sodium:solute symporter (SSF) (TC 2.A.21) family, lacks Na(+)/glucose symporter activity.
messages: Belongs to the sodium:solute symporter (SSF) (TC 2.A.21) family.
messages: Cell membrane
messages: Does not function as sodium/D-glucose symporter (PubMed:13130073, PubMed:20421923, PubMed:22766068). However, may function as a D-glucose sensor by generating a D-glucose-induced depolarization which is pH-independent, Na(+)-dependent at neutral pH and probably H(+)-dependent at acidic pH (PubMed:13130073, PubMed:22766068, PubMed:17110502, PubMed:20421923).
messages: Expressed in skeletal muscle, where it may localize to the neuromuscular junction (at protein level) (PubMed:13130073). Expressed in small intestine where it may localize to cholinergic neurons of the submucosal plexus and myenteric plexus (at protein level) (PubMed:13130073). Detected in kidney (at protein level) (PubMed:22766068).
messages: Inhibited by phlorizin.

9606:PTH2R
gene id: 9606:PTH2R
uniprot id: B4DFN8
uniprot id: P49190
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor 2 family.
messages: Binds to TIPF39/TIP39.
messages: Cell membrane
messages: Expressed abundantly in brain and pancreas. Also expressed in the testis.
messages: Membrane
messages: This is a specific receptor for parathyroid hormone. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase. PTH2R may be responsible for PTH effects in a number of physiological systems. It may play a significant role in pancreatic function. PTH2R presence in neurons indicates that it may function as a neurotransmitter receptor (By similarity).

9606:GPATCH2
gene id: 9606:GPATCH2
uniprot id: Q9NW75
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Enhances the ATPase activity of DHX15 in vitro.
messages: Interacts with DHX15.
messages: Nucleus speckle
messages: Testis.
messages: nucleolus

9606:EPOR
gene id: 9606:EPOR
uniprot id: P19235
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the type I cytokine receptor family. Type 1 subfamily.
messages: Cell membrane
messages: Contains 1 copy of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases.
messages: Erythroid cells and erythroid progenitor cells. Isoform EPOR-F is the most abundant form in EPO-dependent erythroleukemia cells and in late-stage erythroid progenitors. Isoform EPOR-S and isoform EPOR-T are the predominant forms in bone marrow. Isoform EPOR-T is the most abundant from in early-stage erythroid progenitor cells.
messages: Forms homodimers on EPO stimulation. The tyrosine-phosphorylated form interacts with several SH2 domain-containing proteins including LYN (By similarity), the adapter protein SH2B2, PTPN6 (By similarity), PTPN11, JAK2, PI3 kinases, STAT5A/B, SOCS3, CRKL (By similarity). Interacts with INPP5D/SHIP1 (By similarity). The N-terminal SH2 domain of PTPN6 binds Tyr-454 and inhibits signaling through dephosphorylation of JAK2 (By similarity). SH2B2 binding also inhibits the JAK-STAT signaling. Binding to PTPN11, preferentially through the N-terminal SH2 domain, promotes mitogenesis and phosphorylation of PTPN11 (By similarity). Binding of JAK2 (through its N-terminal) promotes cell-surface expression (By similarity). Interacts with RHEX; this interaction occurs in a erythropoietin (EPO)-dependent manner (PubMed:25092874). Interaction with the ubiquitin ligase NOSIP mediates EPO-induced cell proliferation. Interacts with ATXN2L.
messages: Isoform EPOR-T acts as a dominant-negative receptor of EPOR-mediated signaling.
messages: On EPO stimulation, phosphorylated on C-terminal tyrosine residues by JAK2. The phosphotyrosine motifs are also recruitment sites for several SH2-containing proteins and adapter proteins which mediate cell proliferation. Phosphorylation on Tyr-454 is required for PTPN6 interaction, Tyr-426 for PTPN11. Tyr-426 is also required for SOCS3 binding, but Tyr-454/Tyr-456 motif is the preferred binding site.
messages: Receptor for erythropoietin. Mediates erythropoietin-induced erythroblast proliferation and differentiation. Upon EPO stimulation, EPOR dimerizes triggering the JAK2/STAT5 signaling cascade. In some cell types, can also activate STAT1 and STAT3. May also activate the LYN tyrosine kinase.
messages: Secreted
messages: The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.
messages: The box 1 motif is required for JAK interaction and/or activation.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitination at Lys-281 mediates receptor internalization, whereas ubiquitination at Lys-453 promotes trafficking of activated receptors to the lysosomes for degradation (By similarity). Ubiquitinated by NOSIP; appears to be either multi-monoubiquitinated or polyubiquitinated. Ubiquitination mediates proliferation and survival of EPO-dependent cells.

9606:CARD19
gene id: 9606:CARD19
uniprot id: Q96LW7
names: Function
names: Miscellaneous
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Appears to be the dominant isoform in peripheral blood cell fractions. Contains a transmembrane helix.
messages: Associates with BCL10 by CARD-CARD interaction (PubMed:15637807).
messages: Endoplasmic reticulum membrane
messages: Expressed in ovary, testis, placenta, skeletal muscle, kidney, lung, heart and liver (at protein level). Expressed in thymus and brain.
messages: Mitochondrion membrane
messages: Nucleus
messages: Plays a role in inhibiting the effects of BCL10-induced activation of NF-kappa-B. May inhibit the phosphorylation of BCL10 in a CARD-dependent manner.

9606:CDKN1A
gene id: 9606:CDKN1A
uniprot id: P38936
names: Domain
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acetylation leads to protein stability. Acetylated in vitro on Lys-141, Lys-154, Lys-161 and Lys-163. Deacetylation by HDAC1 is prevented by competitive binding of C10orf90/FATS to HDAC1 (By similarity).
messages: Activated by p53/TP53, mezerein (antileukemic compound) and IFNB1. Repressed by HDAC1.
messages: Belongs to the CDI family.
messages: Cytoplasm
messages: Expressed in all adult tissues, with 5-fold lower levels observed in the brain.
messages: Interacts with HDAC1; the interaction is prevented by competitive binding of C10orf90/FATS to HDAC1 facilitating acetylation and protein stabilization of CDKN1A/p21 (By similarity). Interacts with MKRN1 (PubMed:19536131). Interacts with PSMA3 (PubMed:11350925). Interacts with PCNA (PubMed:11595739, PubMed:18794347, PubMed:18703516, PubMed:8861913). Component of the ternary complex, cyclin D-CDK4-CDKN1A. Interacts (via its N-terminal domain) with CDK4; the interaction promotes the assembly of the cyclin D-CDK4 complex, its nuclear translocation and promotes the cyclin D-dependent enzyme activity of CDK4 (PubMed:9106657). Binding to CDK2 leads to CDK2/cyclin E inactivation at the G1-S phase DNA damage checkpoint, thereby arresting cells at the G1-S transition during DNA repair (PubMed:19445729). Interacts with PIM1 (PubMed:12431783). Interacts with STK11 and NUAK1 (PubMed:25329316). Interacts wih DTL (PubMed:23213251). Interacts with isoform 1 and isoform 2 of TRIM39 (PubMed:23213251).
messages: Nucleus
messages: Phosphorylation of Thr-145 by Akt or of Ser-146 by PKC impairs binding to PCNA. Phosphorylation at Ser-114 by GSK3-beta enhances ubiquitination by the DCX(DTL) complex. Phosphorylation of Thr-145 by PIM2 enhances CDKN1A stability and inhibits cell proliferation. Phosphorylation of Thr-145 by PIM1 results in the relocation of CDKN1A to the cytoplasm and enhanced CDKN1A protein stability. UV radiation-induced phosphorylation at Thr-80 by LKB1 and at Ser-146 by NUAK1 leads to its degradation.
messages: Plays an important role in controlling cell cycle progression and DNA damage-induced G2 arrest (PubMed:9106657). Involved in p53/TP53 mediated inhibition of cellular proliferation in response to DNA damage. Also involved in p53-independent DNA damage-induced G2 arrest mediated by CREB3L1 in astrocytes and osteoblasts (By similarity). Binds to and inhibits cyclin-dependent kinase activity, preventing phosphorylation of critical cyclin-dependent kinase substrates and blocking cell cycle progression. Functions in the nuclear localization and assembly of cyclin D-CDK4 complex and promotes its kinase activity towards RB1. At higher stoichiometric ratios, inhibits the kinase activity of the cyclin D-CDK4 complex. Inhibits DNA synthesis by DNA polymerase delta by competing with POLD3 for PCNA binding (PubMed:11595739).
messages: The C-terminal is required for nuclear localization of the cyclin D-CDK4 complex.
messages: The PIP-box K+4 motif mediates both the interaction with PCNA and the recruitment of the DCX(DTL) complex: while the PIP-box interacts with PCNA, the presence of the K+4 submotif, recruits the DCX(DTL) complex, leading to its ubiquitination.
messages: Ubiquitinated by MKRN1; leading to polyubiquitination and 26S proteasome-dependent degradation. Ubiquitinated by the DCX(DTL) complex, also named CRL4(CDT2) complex, leading to its degradation during S phase or following UV irradiation. Ubiquitination by the DCX(DTL) complex is essential to control replication licensing and is PCNA-dependent: interacts with PCNA via its PIP-box, while the presence of the containing the 'K+4' motif in the PIP box, recruit the DCX(DTL) complex, leading to its degradation. Ubiquitination at Ser-2 leads to degradation by the proteasome pathway. Ubiquitinated by RNF114; leading to proteasomal degradation.

9606:TM2D1
gene id: 9606:TM2D1
uniprot id: Q9BX74
names: Caution
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the TM2 family.
messages: Interacts with APP beta-APP42 (amyloid-beta protein 42).
messages: May participate in amyloid-beta-induced apoptosis via its interaction with beta-APP42.
messages: Membrane
messages: N-glycosylated.
messages: Was originally (PubMed:11278849) thought to modulate amyloid-beta toxicity by coupling to G protein. However, PubMed:12836168 showed that this effect is not direct.
messages: Widely expressed.

9606:SYT6
gene id: 9606:SYT6
uniprot id: Q5T7P8
names: Cofactor
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the synaptotagmin family.
messages: Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2 domains.
messages: Cell membrane
messages: Isoform 1: Homodimer; disulfide-linked via the cysteine motif. Isoform 1: Can also form heterodimers with SYT3, SYT7, SYT9 and SYT10. Isoform 1: Interacts with STX1A, STX1B and STX2; the interaction is Ca(2+)-dependent. Isoform 2: Is not able to form homodimer and heterodimers.
messages: May be involved in Ca(2+)-dependent exocytosis of secretory vesicles through Ca(2+) and phospholipid binding to the C2 domain or may serve as Ca(2+) sensors in the process of vesicular trafficking and exocytosis. May mediate Ca(2+)-regulation of exocytosis in acrosomal reaction in sperm (By similarity).
messages: Membrane
messages: The cysteine motif mediates homo- or heterodimer formation via formation of disulfide bonds.
messages: cytosol
messages: synaptic vesicle membrane

9606:PSMA1
gene id: 9606:PSMA1
uniprot id: B4E0X6
uniprot id: P25786
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the peptidase T1A family.
messages: Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex).
messages: Cytoplasm
messages: Induced in breast cancer tissue (at protein level). Up-regulated in liver tumor tissues.
messages: Nucleus
messages: The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits (PubMed:25599644, PubMed:26133119, PubMed:27342858, PubMed:27428775, PubMed:27493187, PubMed:34711951). The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings (PubMed:25599644, PubMed:26133119, PubMed:27342858, PubMed:27428775, PubMed:27493187). The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits (PubMed:25599644, PubMed:26133119, PubMed:27342858, PubMed:27428775, PubMed:27493187). The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7 (PubMed:25599644, PubMed:26133119, PubMed:27342858, PubMed:27428775, PubMed:27493187). Interacts with NOTCH3 (PubMed:17292860). Interacts with ZFAND1 (PubMed:29804830).
messages: The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits.

9606:IRF5
gene id: 9606:IRF5
uniprot id: A0A0G2USB5
uniprot id: Q13568
names: Activity Regulation
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: 'Lys-63'-linked polyubiquitination by TRAF6 is required for activation.
messages: (Microbial infection) Activated upon coronavirus SARS-CoV-2 infection.
messages: Belongs to the IRF family.
messages: Cytoplasm
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry.
messages: Homodimer, when phosphorylated (PubMed:25326418, PubMed:18836453). Interacts with TASL (via pLxIS motif); interaction takes place downstream of TLR7, TLR8 or TLR9, leading to its activation (PubMed:32433612). Interacts with MYD88 and TRAF6 (By similarity).
messages: Maintained as a monomer in an autoinhibited state (PubMed:25326418, PubMed:18836453, PubMed:22412986). Phosphorylation and activation follow the following steps: innate adapter protein TASL recruits IRF5, thereby licensing IRF5 for phosphorylation by IKBKB (PubMed:32433612). Phosphorylated IRF5 dissociates from the adapter proteins, dimerizes, and then enters the nucleus to induce IFNs (PubMed:25326418, PubMed:32433612).
messages: Nucleus
messages: Phosphorylation of serine and threonine residues by IKBKB in a C-terminal autoinhibitory region, stimulates dimerization, transport into the nucleus, assembly with the coactivator CBP/EP300 and initiation of transcription.
messages: Transcription factor that plays a critical role in innate immunity by activating expression of type I interferon (IFN) IFNA and INFB and inflammatory cytokines downstream of endolysosomal toll-like receptors TLR7, TLR8 and TLR9 (PubMed:11303025, PubMed:15695821, PubMed:22412986, PubMed:25326418, PubMed:32433612). Regulates the transcription of type I IFN genes (IFN-alpha and IFN-beta) and IFN-stimulated genes (ISG) by binding to an interferon-stimulated response element (ISRE) in their promoters (By similarity). Can efficiently activate both the IFN-beta (IFNB) and the IFN-alpha (IFNA) genes and mediate their induction downstream of the TLR-activated, MyD88-dependent pathway (By similarity). Key transcription factor regulating the IFN response during SARS-CoV-2 infection (PubMed:33440148).

9606:RAB14
gene id: 9606:RAB14
uniprot id: P61106
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the small GTPase superfamily. Rab family.
messages: Early endosome membrane
messages: Golgi apparatus membrane
messages: Interacts with KIF16B (By similarity). Interacts with ZFYVE20.
messages: Involved in membrane trafficking between the Golgi complex and endosomes during early embryonic development. Regulates the Golgi to endosome transport of FGFR-containing vesicles during early development, a key process for developing basement membrane and epiblast and primitive endoderm lineages during early postimplantation development. May act by modulating the kinesin KIF16B-cargo association to endosomes (By similarity). Regulates, together with its guanine nucleotide exchange factor DENND6A, the specific endocytic transport of ADAM10, N-cadherin/CDH2 shedding and cell-cell adhesion.
messages: Recycling endosome
messages: phagosome
messages: trans-Golgi network membrane

9606:BEST2
gene id: 9606:BEST2
uniprot id: Q8NFU1
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the anion channel-forming bestrophin (TC 1.A.46) family. Calcium-sensitive chloride channel subfamily.
messages: Cell membrane
messages: Forms calcium-sensitive chloride channels. Permeable to bicarbonate.
messages: Mainly confined to the retinal pigment epithelium and colon.

9606:RBBP9
gene id: 9606:RBBP9
uniprot id: O75884
names: Activity Regulation
names: Function
names: Miscellaneous
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Belongs to the RBBP9 family.
messages: Expressed at higher levels in tumor tissues such as carcinoma.
messages: Inhibited by the natural product emetine produced by the ipecac root.
messages: Interacts with RB1; the interaction disrupts RB1 binding to E2F1 (PubMed:21689726). Interacts with RBL1 and RBL2 (By similarity).
messages: Plays a role in maintaining pluripotency in human stem cells in vitro.
messages: Serine hydrolase whose substrates have not been identified yet (PubMed:19329999, PubMed:20080647). May negatively regulate basal or autocrine TGF-beta signaling by suppressing SMAD2-SMAD3 phosphorylation (PubMed:20080647). May play a role in the transformation process due to its capacity to confer resistance to the growth-inhibitory effects of TGF-beta through interaction with RB1 and the subsequent displacement of E2F1 (PubMed:9697699).

9606:SFRP4
gene id: 9606:SFRP4
uniprot id: Q6FHJ7
names: Disease Annotation
names: Domain
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the secreted frizzled-related protein (sFRP) family.
messages: Expressed in mesenchymal cells. Highly expressed in the stroma of proliferative endometrium. Expressed in cardiomyocytes. Shows moderate to strong expression in ovarian tumors with expression increasing as the tumor stage increases. In ovarian tumors, expression levels are inversely correlated with expression of CTNNB1 (at protein level).
messages: Increased levels in failing myocardium. Up-regulated in several tumor types including ostomalacia-associated tumors and endometrial and breast carcinomas.
messages: Secreted
messages: Soluble frizzled-related proteins (sFRPS) function as modulators of Wnt signaling through direct interaction with Wnts. They have a role in regulating cell growth and differentiation in specific cell types (By similarity). SFRP4 plays a role in bone morphogenesis. May also act as a regulator of adult uterine morphology and function. May also increase apoptosis during ovulation possibly through modulation of FZ1/FZ4/WNT4 signaling (By similarity). Has phosphaturic effects by specifically inhibiting sodium-dependent phosphate uptake (PubMed:12952927).
messages: The FZ domain is involved in binding with Wnt ligands.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:GPHA2
gene id: 9606:GPHA2
uniprot id: A0A024R579
uniprot id: Q96T91
names: Caution
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the glycoprotein hormones subunit alpha family.
messages: Found in a variety of tissues.
messages: Functions as a heterodimeric glycoprotein hormone with GPHB5 able to bind and activate the thyroid-stimulating hormone receptor (TSHR), leading to increased cAMP production (PubMed:12045258). Plays a central role in controlling thyroid cell metabolism (PubMed:12045258).
messages: Glycosylated.
messages: Heterodimer with GPHB5; this heterodimer interacts with thyroid-stimulating hormone receptor (TSHR), and hence stimulates cAMP production.
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: Secreted

9606:CDK12
gene id: 9606:CDK12
uniprot id: Q9NYV4
names: Activity Regulation
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts with human herpes virus 1 (HHV-1) transcriptional regulator ICP22.
messages: Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.
messages: Chromosomal aberrations involving CDK12 may be a cause gastric cancer. Deletions within 17q12 region producing fusion transcripts with ERBB2, leading to CDK12-ERBB2 fusion leading to trunctated CDK12 protein not in-frame with ERBB2.
messages: Cyclin-dependent kinase that phosphorylates the C-terminal domain (CTD) of the large subunit of RNA polymerase II (POLR2A), thereby acting as a key regulator of transcription elongation. Regulates the expression of genes involved in DNA repair and is required for the maintenance of genomic stability. Preferentially phosphorylates 'Ser-5' in CTD repeats that are already phosphorylated at 'Ser-7', but can also phosphorylate 'Ser-2'. Required for RNA splicing, possibly by phosphorylating SRSF1/SF2. Involved in regulation of MAP kinase activity, possibly leading to affect the response to estrogen inhibitors.
messages: Inhibited by the ATP analog flavopiridol, purvalanol A, purvalanol B, staurosporine and CR8.
messages: Interacts with CCNL1 and CCNL2 (By similarity). Interacts with CCNK.
messages: Nucleus
messages: Nucleus speckle
messages: Phosphorylation at Thr-893 increases kinase activity.
messages: Widely expressed.

9606:IL1B
gene id: 9606:IL1B
uniprot id: P01584
names: Activity Regulation
names: Function
names: Induction
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Cleavage by S.pyogenes cysteine protease SpeB promotes its activation independently of CASP1 (PubMed:28331908, PubMed:32719155). SpeB-mediated maturation of IL1B plays a dual role depending on infection site: while IL1B inflammatory response prevents bacterial growth during invasive skin infections, it promotes streptococcal infection of the nasopharynx by disrupting colonization resistance mediated by the microbiota (PubMed:28331908, PubMed:32719155).
messages: (Microbial infection) Cleavage by S.pyogenes cysteine protease SpeB promotes its activation independently of CASP1.
messages: Activation of the IL1B precursor involves a CASP1-catalyzed proteolytic cleavage. Processing and secretion are temporarily associated.
messages: Belongs to the IL-1 family.
messages: By LPS (PubMed:15192144). Transcription and translation induced by M.tuberculosis and a number of different M.tuberculosis components in macrophages; EsxA is the most potent activator tested (at protein level) (PubMed:20148899). In pancreatic islets, release is increased by high glucose treatment. In pancreatic islets and macrophages, release is also increased by endocannabinoid anandamide/AEA (PubMed:23955712).
messages: Expressed in activated monocytes/macrophages (at protein level).
messages: Lysosome
messages: Monomer. In its precursor form, weakly interacts with full-length MEFV; the mature cytokine does not interact at all (PubMed:17431422). Interacts with integrins ITGAV:ITGBV and ITGA5:ITGB1; integrin-binding is required for IL1B signaling (PubMed:29030430). Interacts with cargo receptor TMED10; the interaction is direct and is required for the secretion of IL1B mature form (PubMed:32272059). Interacts with HSP90AB1; the interaction facilitates cargo translocation into the ERGIC (PubMed:32272059). Interacts with HSP90B1; the interaction facilitates cargo translocation into the ERGIC (PubMed:32272059).
messages: Potent pro-inflammatory cytokine (PubMed:3920526, PubMed:10653850, PubMed:12794819, PubMed:28331908). Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil influx and activation, T-cell activation and cytokine production, B-cell activation and antibody production, and fibroblast proliferation and collagen production (PubMed:3920526). Promotes Th17 differentiation of T-cells. Synergizes with IL12/interleukin-12 to induce IFNG synthesis from T-helper 1 (Th1) cells (PubMed:10653850). Plays a role in angiogenesis by inducing VEGF production synergistically with TNF and IL6 (PubMed:12794819). Involved in transduction of inflammation downstream of pyroptosis: its mature form is specifically released in the extracellular milieu by passing through the gasdermin-D (GSDMD) pore (PubMed:33377178, PubMed:33883744). Acts as a sensor of S.pyogenes infection in skin: cleaved and activated by pyogenes SpeB protease, leading to an inflammatory response that prevents bacterial growth during invasive skin infection (PubMed:28331908).
messages: Secreted
messages: The IL1B production occurs in 2 steps, each being controlled by different stimuli. First, inflammatory signals, such as LPS, stimulate the synthesis and promote the accumulation of cytosolic stores of pro-IL1B (priming). Then additional signals are required for inflammasome assembly, leading to CASP1 activation, pro-IL1B processing and eventually secretion of the active cytokine. IL1B processing and secretion are temporarily associated.
messages: cytosol
messages: extracellular exosome

9606:RABEP2
gene id: 9606:RABEP2
uniprot id: Q9H5N1
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the rabaptin family.
messages: Cytoplasm
messages: Early endosome
messages: Heterodimer with RABGEF1. The dimer binds RAB5A that has been activated by GTP-binding. Interacts with SDCCAG8; this interaction is important for ciliogenesis regulation (PubMed:27224062). Interacts with RAB4A; this interaction may mediate VEGFR2 cell surface expression (PubMed:29425100).
messages: Plays a role in membrane trafficking and in homotypic early endosome fusion (PubMed:9524116). Participates in arteriogenesis by regulating vascular endothelial growth factor receptor 2/VEGFR2 cell surface expression and endosomal trafficking (PubMed:29425100). By interacting with SDCCAG8, localizes to centrosomes and plays a critical role in ciliogenesis (PubMed:27224062).
messages: centrosome
messages: cilium basal body

9606:H2AC20
gene id: 9606:H2AC20
uniprot id: Q16777
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the histone H2A family.
messages: Chromosome
messages: Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
messages: Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.
messages: Deiminated on Arg-4 in granulocytes upon calcium entry.
messages: Glutamine methylation at Gln-105 (H2AQ104me) by FBL is specifically dedicated to polymerase I. It is present at 35S ribosomal DNA locus and impairs binding of the FACT complex (PubMed:24352239).
messages: Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.
messages: Monoubiquitination of Lys-120 (H2AK119Ub) by RING1, TRIM37 and RNF2/RING2 complex gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. It is involved in the initiation of both imprinted and random X inactivation. Ubiquitinated H2A is enriched in inactive X chromosome chromatin. Ubiquitination of H2A functions downstream of methylation of 'Lys-27' of histone H3 (H3K27me). H2AK119Ub by RNF2/RING2 can also be induced by ultraviolet and may be involved in DNA repair. Monoubiquitination of Lys-120 (H2AK119Ub) by TRIM37 may promote transformation of cells in a number of breast cancers (PubMed:25470042). Following DNA double-strand breaks (DSBs), it is ubiquitinated through 'Lys-63' linkage of ubiquitin moieties by the E2 ligase UBE2N and the E3 ligases RNF8 and RNF168, leading to the recruitment of repair proteins to sites of DNA damage. Ubiquitination at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) in response to DNA damage is initiated by RNF168 that mediates monoubiquitination at these 2 sites, and 'Lys-63'-linked ubiquitin are then conjugated to monoubiquitin; RNF8 is able to extend 'Lys-63'-linked ubiquitin chains in vitro. Deubiquitinated by USP51 at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) after damaged DNA is repaired (PubMed:27083998). H2AK119Ub and ionizing radiation-induced 'Lys-63'-linked ubiquitination (H2AK13Ub and H2AK15Ub) are distinct events.
messages: Nucleus
messages: Phosphorylation on Ser-2 (H2AS1ph) is enhanced during mitosis. Phosphorylation on Ser-2 by RPS6KA5/MSK1 directly represses transcription. Acetylation of H3 inhibits Ser-2 phosphorylation by RPS6KA5/MSK1. Phosphorylation at Thr-121 (H2AT120ph) by DCAF1 is present in the regulatory region of many tumor suppresor genes and down-regulates their transcription.
messages: Symmetric dimethylation on Arg-4 by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage.
messages: The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.

9606:LNX2
gene id: 9606:LNX2
uniprot id: Q8N448
names: Domain
names: Subunit
messages: Interacts with the phosphotyrosine interaction domain of NUMB.
messages: The NPXY motif is required for the interaction with the PID domain of NUMB. It is however not sufficient.

9606:SRGN
gene id: 9606:SRGN
uniprot id: P10124
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the serglycin family.
messages: Binds to activated CD44 and to GZMB.
messages: By Epstein-Barr virus (EBV).
messages: Cytolytic granule
messages: Cytoplasmic granule
messages: Golgi apparatus
messages: O-glycosylated; contains chondroitin sulfate and heparan sulfate.
messages: Plays a role in formation of mast cell secretory granules and mediates storage of various compounds in secretory vesicles. Required for storage of some proteases in both connective tissue and mucosal mast cells and for storage of granzyme B in T-lymphocytes. Plays a role in localizing neutrophil elastase in azurophil granules of neutrophils. Mediates processing of MMP2. Plays a role in cytotoxic cell granule-mediated apoptosis by forming a complex with granzyme B which is delivered to cells by perforin to induce apoptosis. Regulates the secretion of TNF-alpha and may also regulate protease secretion. Inhibits bone mineralization.
messages: extracellular space

9606:BLNK
gene id: 9606:BLNK
uniprot id: Q8WV28
names: Disease Annotation
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Associates with PLCG1, VAV1 and NCK1 in a B-cell antigen receptor-dependent fashion. Interacts with VAV3, PLCG2 and GRB2. Interacts through its SH2 domain with CD79A. Interacts (via SH2 domain) with SYK; phosphorylated and activated by SYK. Interacts (via SH2 domain) with SCIMP; this interaction is dependent on phosphorylation of SCIMP 'Tyr-131' (PubMed:21930792).
messages: Cell membrane
messages: Cytoplasm
messages: Expressed in B-cell lineage and fibroblast cell lines (at protein level). Highest levels of expression in the spleen, with lower levels in the liver, kidney, pancreas, small intestines and colon.
messages: Following BCR activation, phosphorylated on tyrosine residues by SYK and LYN. When phosphorylated, serves as a scaffold to assemble downstream targets of antigen activation, including PLCG1, VAV1, GRB2 and NCK1. Phosphorylation of Tyr-84, Tyr-178 and Tyr-189 facilitates PLCG1 binding. Phosphorylation of Tyr-96 facilitates BTK binding. Phosphorylation of Tyr-72 facilitates VAV1 and NCK1 binding. Phosphorylation is required for both Ca(2+) and MAPK signaling pathways.
messages: Functions as a central linker protein, downstream of the B-cell receptor (BCR), bridging the SYK kinase to a multitude of signaling pathways and regulating biological outcomes of B-cell function and development. Plays a role in the activation of ERK/EPHB2, MAP kinase p38 and JNK. Modulates AP1 activation. Important for the activation of NF-kappa-B and NFAT. Plays an important role in BCR-mediated PLCG1 and PLCG2 activation and Ca(2+) mobilization and is required for trafficking of the BCR to late endosomes. However, does not seem to be required for pre-BCR-mediated activation of MAP kinase and phosphatidyl-inositol 3 (PI3) kinase signaling. May be required for the RAC1-JNK pathway. Plays a critical role in orchestrating the pro-B cell to pre-B cell transition. May play an important role in BCR-induced B-cell apoptosis.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:LRRC75A
gene id: 9606:LRRC75A
uniprot id: Q8NAA5
names: Similarity
messages: Belongs to the LRRC75 family.

9606:DEFA4
gene id: 9606:DEFA4
uniprot id: P12838
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the alpha-defensin family.
messages: Expressed in neutrophils (at protein level) (PubMed:2843187, PubMed:2500436, PubMed:2501794). Expressed in bone marrow (PubMed:8469233).
messages: Homodimer; homodimerization seems to be required for killing S.aureus, but not E.coli (PubMed:17088326, PubMed:30658057). Interacts with CD4 (PubMed:15620707). Interacts with HIV-1 surface protein gp120; homodimerization is required for the interaction (PubMed:15620707, PubMed:30658057). Interacts with Bacillus anthracis lef; homodimerization is required for the interaction (PubMed:30658057).
messages: Host-defense peptide that has antimicrobial activity against Gram-negative bacteria, and to a lesser extent also against Gram-positive bacteria and fungi (PubMed:2500436, PubMed:2501794, PubMed:15317502, PubMed:15616305, PubMed:30658057). Exhibits antimicrobial activity against Gram-negative E.coli and E.aerogenes and Gram-positive S.faecalis, S.aureus and B.cereus and the yeast C.albicans (in vitro) (PubMed:2500436, PubMed:2501794, PubMed:15317502, PubMed:15616305, PubMed:17088326, PubMed:30658057). Interacts with pathogenic surface proteins and toxins, such as HIV-1 surface protein gp120 and B.anthracis anthrax lethal factor lef (PubMed:15620707, PubMed:30658057). Protects blood cells against infection with HIV-1 (in vitro) (PubMed:15620707). Inhibits enzymatic activity of B.anthracis lef/anthrax lethal factor (in vitro) (PubMed:30658057). Inhibits corticotropin (ACTH)-stimulated corticosterone production (in vitro) (PubMed:2843187).
messages: Secreted
messages: The three-dimensional structure formed by the three intramolecular disulfide bridges is indispensable for effective bacterial killing.
messages: secretory vesicle

9606:ARID5A
gene id: 9606:ARID5A
uniprot id: Q03989
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: Binds to AT-rich stretches in the modulator region upstream of the human cytomegalovirus major intermediate early gene enhancer. May act as repressor and down-regulate enhancer-dependent gene expressison (PubMed:8649988). May positively regulate chondrocyte-specific transcription such as of COL2A1 in collaboration with SOX9 and positively regulate histone H3 acetylation at chondrocyte-specific genes. May stimulate early-stage chondrocyte differentiation and inhibit later stage differention (By similarity). Can repress ESR1-mediated transcriptional activation; proposed to act as corepressor for selective nuclear hormone receptors (PubMed:15941852). As RNA-binding protein involved in the regulation of inflammatory response by stabilizing selective inflammation-related mRNAs, such as IL6, STAT3 and TBX21. Binds to stem loop structures located in the 3'UTRs of IL6, STAT3 and TBX21 mRNAs; at least for STAT3 prevents binding of ZC3H12A to the mRNA stem loop structure thus inhibiting its degradation activity. Contributes to elevated IL6 levels possibly implicated in autoimmunity processes. IL6-dependent stabilization of STAT3 mRNA may promote differentiation of naive CD4+ T-cells into T-helper Th17 cells. In CD4+ T-cells may also inhibit RORC-induced Th17 cell differentiation independently of IL6 signaling. Stabilization of TBX21 mRNA contributes to elevated interferon-gamma secretion in Th1 cells possibly implicated in the establishment of septic shock (By similarity). Stabilizes TNFRSF4/OX40 mRNA by binding to the conserved stem loop structure in its 3'UTR; thereby competing with the mRNA-destabilizing functions of RC3H1 and endoribonuclease ZC3H12A (By similarity).
messages: Interacts with SOX9 (By similarity). Interacts with ESR1 (PubMed:15941852). Interacts with RORC (By similarity).
messages: Nucleus
messages: Phosphorylated by MAPK14 on serine residues involving a TLR4 signaling pathway upon lipopolysaccharide (LPS) stimulation leading to its ubiquitination and proteasomal degradation.
messages: Ubiquitinated leading to proteasomal degradation; involving WWP1 linked to MAPK14-mediated phosphorylation upon LPS stimulation.

9606:ERLIN1
gene id: 9606:ERLIN1
uniprot id: O75477
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Required early in hepatitis C virus (HCV) infection to initiate RNA replication, and later in the infection to support infectious virus production.
messages: Belongs to the band 7/mec-2 family.
messages: Component of the ERLIN1/ERLIN2 complex which mediates the endoplasmic reticulum-associated degradation (ERAD) of inositol 1,4,5-trisphosphate receptors (IP3Rs). Involved in regulation of cellular cholesterol homeostasis by regulation the SREBP signaling pathway. Binds cholesterol and may promote ER retention of the SCAP-SREBF complex (PubMed:24217618).
messages: Endoplasmic reticulum membrane
messages: Expressed in heart, placenta, liver, kidney, pancreas, prostate, testis, ovary and small intestine.
messages: Forms a heteromeric complex with ERLIN2 (PubMed:19240031). In complex with ERLIN2, interacts with RNF170 (PubMed:21610068). Interacts with AMFR and SYVN1 (PubMed:21343306).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:ELN
gene id: 9606:ELN
uniprot id: B3KRT8
uniprot id: B4E3S4
uniprot id: E7EN65
uniprot id: E7ENM0
uniprot id: G3V0G6
uniprot id: G5E950
uniprot id: P15502
uniprot id: Q6ZUN2
uniprot id: Q8NBI4
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the elastin family.
messages: ELN is located in the Williams-Beuren syndrome (WBS) critical region. WBS results from a hemizygous deletion of several genes on chromosome 7q11.23, thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region. Haploinsufficiency of ELN may be the cause of certain cardiovascular and musculo-skeletal abnormalities observed in the disease (PubMed:8812460).
messages: Elastin is formed through the cross-linking of its soluble precursor tropoelastin. Cross-linking is initiated through the action of lysyl oxidase on exposed lysines to form allysine. Subsequent spontaneous condensation reactions with other allysine or unmodified lysine residues result in various bi-, tri-, and tetrafunctional cross-links. The most abundant cross-links in mature elastin fibers are lysinonorleucine, allysine aldol, desmosine, and isodesmosine.
messages: Expressed within the outer myometrial smooth muscle and throughout the arteriolar tree of uterus (at protein level). Also expressed in the large arteries, lung and skin.
messages: Hydroxylation on proline residues within the sequence motif, GXPG, is most likely 4-hydroxy as this fits the requirement for 4-hydroxylation in vertebrates.
messages: Major structural protein of tissues such as aorta and nuchal ligament, which must expand rapidly and recover completely. Molecular determinant of the late arterial morphogenesis, stabilizing arterial structure by regulating proliferation and organization of vascular smooth muscle (By similarity).
messages: Major structural protein of tissues such as aorta and nuchal ligament, which must expand rapidly and recover completely. Molecular determinant of the late arterial morphogenesis, stabilizing arterial structure by regulating proliferation and organization of vascular smooth muscle.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The polymeric elastin chains are cross-linked together into an extensible 3D network. Forms a ternary complex with BGN and MFAP2. Interacts with MFAP2 via divalent cations (calcium > magnesium > manganese) in a dose-dependent and saturating manner. Interacts with FBLN5 (PubMed:15790312, PubMed:17035250). Interacts with FBN1 (PubMed:15790312). Forms a ternary complex with FBN1 and FBLN2 or FBLN5 (PubMed:17255108). Interacts with MFAP4 in a Ca (2+)-dependent manner; this interaction promotes ELN self-assembly (By similarity) (PubMed:15790312, PubMed:17035250, PubMed:17255108). Interacts with EFEMP2 with moderate affinity (PubMed:16478991).
messages: extracellular matrix

9606:YJEFN3
gene id: 9606:YJEFN3
uniprot id: A6XGL0
names: Function
names: Subunit
names: Tissue Specificity
messages: Expressed in theca cells in ovary and in Leydig cells in testis (at protein level). Also expressed in brain and mammary gland.
messages: Interacts with APOA1 (PubMed:23719382). Binds to HDL (PubMed:17533573).
messages: May accelerate cholesterol efflux from endothelial cells to high-density lipoprotein (HDL) and thereby regulates angiogenesis. May orchestrate hematopoietic stem and progenitor cell emergence from the hemogenic endothelium, a type of specialized endothelium manifesting hematopoietic potential. YJEFN3-mediated cholesterol efflux activates endothelial SREBF2, the master transcription factor for cholesterol biosynthesis, which in turn transactivates NOTCH and promotes hematopoietic stem and progenitor cell emergence (By similarity). May play a role in spermiogenesis and oogenesis (PubMed:17533573).

9606:KLF2
gene id: 9606:KLF2
uniprot id: Q9Y5W3
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: Interacts with WWP1.
messages: Nucleus
messages: The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.
messages: Transcription factor that binds to the CACCC box in the promoter of target genes such as HBB/beta globin or NOV and activates their transcription (PubMed:21063504). Might be involved in transcriptional regulation by modulating the binding of the RARA nuclear receptor to RARE DNA elements (PubMed:28167758).
messages: Ubiquitinated. Polyubiquitination involves WWP1 and leads to proteasomal degradation of this protein (By similarity).

9606:MRPS5
gene id: 9606:MRPS5
uniprot id: A0A8Q3SIP9
uniprot id: P82675
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the universal ribosomal protein uS5 family.
messages: Component of the mitochondrial small ribosomal subunit (mt-SSU). Mature mammalian 55S mitochondrial ribosomes consist of a small (28S) and a large (39S) subunit. The 28S small subunit contains a 12S ribosomal RNA (12S mt-rRNA) and 30 different proteins. The 39S large subunit contains a 16S rRNA (16S mt-rRNA), a copy of mitochondrial valine transfer RNA (mt-tRNA(Val)), which plays an integral structural role, and 52 different proteins.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Mitochondrion

9606:CENPA
gene id: 9606:CENPA
uniprot id: P49450
names: Developmental Stage
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Interacts directly with herpes virus HHV-1 protein ICP0.
messages: Antibodies against CENPA are present in sera from patients with autoimmune diseases that developed autoantibodies against centrosomal proteins.
messages: Belongs to the histone H3 family.
messages: Component of centromeric nucleosomes, where DNA is wrapped around a histone octamer core (PubMed:23818633, PubMed:26878239, PubMed:20739937, PubMed:21743476). The octamer contains two molecules each of H2A, H2B, CENPA and H4 assembled in one CENPA-H4 heterotetramer and two H2A-H2B heterodimers (PubMed:23818633, PubMed:26878239, PubMed:20739937, PubMed:21743476). CENPA modulates the DNA-binding characteristics of nucleosomes so that protruding DNA ends have higher flexibility than in nucleosomes containing conventional histone H3 (PubMed:27499292, PubMed:21743476). Inhibits binding of histone H1 to nucleosomes, since histone H1 binds preferentially to rigid DNA linkers that protrude from nucleosomes (PubMed:27499292). Nucleosomes containing CENPA also contain histone H2A variants such as MACROH2A and H2A.Z/H2AZ1 (Probable). The CENPA-H4 heterotetramer is more compact and structurally more rigid than corresponding H3-H4 heterotetramers (PubMed:15282608, PubMed:20739937). Can assemble into nucleosomes that contain both CENPA and histone H3.3; these nucleosomes interact with a single CENPC chain (PubMed:25408271). Heterotrimer composed of HJURP, CENPA and histone H4, where HJURP interacts with the dimer formed by CENPA and histone H4 and prevents tetramerization of CENPA and H4 (PubMed:21478274). Component of the CENPA-NAC complex, at least composed of CENPA, CENPC, CENPH, CENPM, CENPN, CENPT and CENPU (PubMed:16622419). Interacts (via CATD domain) with HJURP; the interaction is direct and is required for its localization to centromeres (PubMed:15282608, PubMed:19410544, PubMed:19410545, PubMed:23818633, PubMed:25556658). Interacts with CENPC, CENPN and CENPT; interaction is direct. Part of a centromere complex consisting of CENPA, CENPT and CENPW (PubMed:19533040). Identified in centromere complexes containing histones H2A, H2B and H4, and at least CENPA, CENPB, CENPC, CENPT, CENPN, HJURP, SUPT16H, SSRP1 and RSF1 (PubMed:27499292). Can self-associate (PubMed:9024683). …
messages: Expression varies across the cell cycle, with high levels in G2 phase (at the mRNA level).
messages: Histone H3-like nucleosomal protein that is specifically found in centromeric nucleosomes (PubMed:7962047, PubMed:9024683, PubMed:11756469, PubMed:14667408, PubMed:15702419, PubMed:15475964, PubMed:15282608, PubMed:17651496, PubMed:19114591, PubMed:27499292, PubMed:20739937). Replaces conventional H3 in the nucleosome core of centromeric chromatin that serves as an assembly site for the inner kinetochore (PubMed:18072184). The presence of CENPA subtly modifies the nucleosome structure and the way DNA is wrapped around the nucleosome and gives rise to protruding DNA ends that are less well-ordered and rigid compared to nucleosomes containing histone H3 (PubMed:27499292, PubMed:26878239). May serve as an epigenetic mark that propagates centromere identity through replication and cell division (PubMed:15475964, PubMed:15282608, PubMed:26878239, PubMed:20739937, PubMed:21478274). Required for recruitment and assembly of kinetochore proteins, and as a consequence required for progress through mitosis, chromosome segregation and cytokinesis (PubMed:11756469, PubMed:14667408, PubMed:18072184, PubMed:23818633, PubMed:25556658, PubMed:27499292).
messages: Nucleus
messages: Phosphorylated by CDK1 at Ser-68 during early mitosis; this abolishes association with chromatin and centromeres, prevents interaction with HJURP and thereby prevents premature assembly of CENPA into centromeres (PubMed:25556658). Dephosphorylated at Ser-68 by PPP1CA during late mitosis (PubMed:25556658). Phosphorylation of Ser-7 by AURKA and AURKB during prophase is required for localization of AURKA and AURKB at inner centromere and is essential for normal cytokinesis (PubMed:11756469, PubMed:14667408, PubMed:18239465). Initial phosphorylation during prophase is mediated by AURKA and is maintained by AURKB.
messages: Poly-ADP-ribosylated by PARP1.
messages: The CATD (CENPA targeting domain) region is responsible for the more compact structure of nucleosomes containing CENPA (PubMed:15282608). It is necessary and sufficient to mediate the localization into centromeres (PubMed:7962047, PubMed:15282608).
messages: Trimethylated by NTMT1 at the N-terminal glycine after cleavage of Met-1. Methylation is low before incorporation into nucleosomes and increases with cell cycle progression, with the highest levels in mitotic nucleosomes.
messages: Ubiquitinated (Probable). Interaction with herpes virus HSV-1 ICP0 protein, leads to its degradation by the proteasome pathway.
messages: centromere

9606:PGPEP1
gene id: 9606:PGPEP1
uniprot id: Q9NXJ5
uniprot id: S4R2Y9
uniprot id: U3KQ24
names: Activity Regulation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the peptidase C15 family.
messages: Cytoplasm
messages: Inhibited by transition metal ions including Ni(2+), Zn(2+), and Cu(2+) and by sulfhydryl-blocking agents.
messages: Monomer.
messages: Removes 5-oxoproline from various penultimate amino acid residues except L-proline.

9606:MFSD14A
gene id: 9606:MFSD14A
uniprot id: Q96MC6
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the major facilitator superfamily.
messages: Membrane

9606:ATP6V0C
gene id: 9606:ATP6V0C
uniprot id: P27449
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Interacts with HTLV-1 accessory protein p12I.
messages: Belongs to the V-ATPase proteolipid subunit family.
messages: Proton-conducting pore forming subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons (PubMed:33065002). V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment (By similarity).
messages: Ubiquitinated by RNF182, leading to its degradation via the ubiquitin-proteasome pathway.
messages: V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex (PubMed:33065002). The V1 complex consists of three catalytic AB heterodimers that form a heterohexamer, three peripheral stalks each consisting of EG heterodimers, one central rotor including subunits D and F, and the regulatory subunits C and H (PubMed:33065002). The proton translocation complex V0 consists of the proton transport subunit a, a ring of proteolipid subunits c9c'', rotary subunit d, subunits e and f, and the accessory subunits ATP6AP1/Ac45 and ATP6AP2/PRR (PubMed:33065002). Interacts with the V0 complex V-ATPase subunit a4 ATP6V0A4 (By similarity). Interacts with LASS2 (PubMed:11543633). Interacts with RNF182; this interaction leads to ubiquitination and degradation via the proteasome pathway (PubMed:18298843).
messages: clathrin-coated vesicle membrane
messages: synaptic vesicle membrane

9606:NDUFB9
gene id: 9606:NDUFB9
uniprot id: E9PH64
uniprot id: Q9Y6M9
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed to be not involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone.
messages: Belongs to the complex I LYR family.
messages: Mammalian complex I is composed of 45 different subunits.
messages: Mitochondrion inner membrane
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:OR2T12
gene id: 9606:OR2T12
uniprot id: Q8NG77
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Odorant receptor.

9606:CPNE4
gene id: 9606:CPNE4
uniprot id: B7Z370
uniprot id: Q96A23
names: Function
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Belongs to the copine family.
messages: Interacts (via VWFA domain) with ACTB, BCOR, BICD2, CCDC22, CDC42BPB, CEP162, MYCBP2, NONO, PDCD6, PITPNM2, RDX, SKIL, SKT, SPTBN1, UBE2O and WTAP (PubMed:12522145).
messages: Probable calcium-dependent phospholipid-binding protein that may play a role in calcium-mediated intracellular processes.
messages: Widely expressed (PubMed:12670487, PubMed:12949241). Expressed strongly in the brain, heart and prostate (PubMed:12670487, PubMed:12949241). Expressed strongly in peripheral blood leukocytes (PubMed:12949241).

9606:IL23A
gene id: 9606:IL23A
uniprot id: Q9NPF7
names: Developmental Stage
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Associates with IL12B to form the pro-inflammatory cytokine IL-23 that plays different roles in innate and adaptive immunity (PubMed:11114383). Released by antigen-presenting cells such as dendritic cells or macrophages, binds to a heterodimeric receptor complex composed of IL12RB1 and IL23R to activate JAK2 and TYK2 which then phosphorylate the receptor to form a docking site leading to the phosphorylation of STAT3 and STAT4 (PubMed:32474165, PubMed:29287995, PubMed:33606986). This process leads to activation of several pathways including p38 MAPK or NF-kappa-B and promotes the production of pro-inflammatory cytokines such as interleukin-17A/IL17A (PubMed:12023369). In turn, participates in the early and effective intracellular bacterial clearance (PubMed:32474165). Promotes the expansion and survival of T-helper 17 cells, a CD4-positive helper T-cell subset that produces IL-17, as well as other IL-17-producing cells (PubMed:17676044).
messages: Belongs to the IL-6 superfamily.
messages: Expressed by newborns dendritic cells.
messages: Heterodimer with IL12B; disulfide-linked (PubMed:11114383, PubMed:18680750). The heterodimer is known as interleukin IL-23 (PubMed:11114383, PubMed:18680750). Interacts with IL23R; this interaction enables recruitment of IL12RB1 (PubMed:29287995, PubMed:33606986).
messages: Secreted
messages: Secreted by activated dendritic and phagocytic cells and keratinocytes. Also expressed by dermal Langerhans cells (at protein level).
messages: Up-regulated by a wide array of pathogens and pathogen-products together with self-signals for danger or injury. Up-regulated in psoriatic dermal tissues, in dendritic cells of multiple sclerosis patients and in tumors.

9606:CLSTN3
gene id: 9606:CLSTN3
uniprot id: Q9BQT9
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: According to PubMed:12498782, expressed predominantly in the brain and in kidney (PubMed:12498782). Low levels in heart, skeletal muscle, liver, placenta, pancreas and lung (PubMed:12498782). According to PubMed:12972431, predominant expression in brain, and only marginal in kidney (PubMed:12972431). In brain, present throughout all cortical layers, highest levels in GABAergic neurons (based on morphology and distribution pattern) (PubMed:12972431).
messages: Adipose-specific isoform that plays a key role in adaptive thermogenesis. Facilitates the efficient use of stored triglyceride by promoting multilocular morphology of thermogenic adipocytes: acts by inhibiting the activity of CIDEA and CIDEC on lipid droplets, thereby preventing lipid droplet fusion and facilitating lipid utilization. May also participate in adaptive thermogenesis by promoting sympathetic innervation of thermogenic adipose tissue: acts by driving secretion of neurotrophic factor S100B from brown adipocytes, stimulating neurite outgrowth from sympathetic neurons.
messages: Belongs to the calsyntenin family.
messages: Endoplasmic reticulum membrane
messages: Expression is restricted to adipose tissue, with high expression in multilocular thermogenic adipocytes (brown adipose tissue).
messages: Golgi apparatus membrane
messages: Interacts (via cadherin domains) with both alpha and beta isoforms of neurexins (NRXN1, NRXN2 and NRXN3) (By similarity). Directly interacts with APBA2 (PubMed:12972431). Forms a tripartite complex with APBA2 and APP (PubMed:12972431). Interacts with low affinity with KLC1 (By similarity). Interacts with SLC23A2/SVCT2 (PubMed:34673103).
messages: Interacts with CIDEA; inhibiting the lipid transferase activity of CIDEA (By similarity). Interacts with CIDEC; inhibiting the lipid transferase activity of CIDEC (By similarity).
messages: Lipid droplet
messages: Postsynaptic adhesion molecule that binds to presynaptic neurexins to mediate both excitatory and inhibitory synapse formation (PubMed:25352602). Promotes synapse development by acting as a cell adhesion molecule at the postsynaptic membrane, which associates with both neurexin-alpha and neurexin-beta proteins at the presynaptic membrane (PubMed:25352602). Regulates the balance between excitatory and inhibitory synapses by inhibiting formation of excitatory parallel-fiber synapses and promoting formation of inhibitory synapses in the same neuron (By similarity). May also be involved in ascorbate (vitamin C) uptake via its interaction with SLC23A2/SVCT2 (PubMed:34673103). Complex formation with APBA2 and APP, stabilizes APP metabolism and enhances APBA2-mediated suppression of beta-APP40 secretion, due to the retardation of intracellular APP maturation (PubMed:12972431) (Probable).
messages: Postsynaptic cell membrane
messages: Proteolytically processed under normal cellular conditions (PubMed:15037614). A primary zeta-cleavage generates a large extracellular (soluble) N-terminal domain (sAlc) and a short C-terminal transmembrane fragment (CTF1) (PubMed:15037614). A secondary cleavage catalyzed by gamma-secretase within the transmembrane domain releases the beta-Alc-beta chain in the extracellular milieu and produces an intracellular fragment (AlcICD) (PubMed:15037614). This processing is strongly suppressed in the tripartite complex formed with APBA2 and APP, which seems to prevent the association with gamma-secretase (PubMed:15037614).
messages: The cytoplasmic domain binds synaptic Ca(2+).
messages: Ubiquitinated: endoplasmic reticulum-localized protein is ubiquitinated and degraded by the endoplasmic reticulum-associated degradation (ERAD) pathway.
messages: dendrite

9606:WWC1
gene id: 9606:WWC1
uniprot id: Q8IX03
names: Domain
names: Function
names: Induction
names: PTM
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the WWC family. KIBRA subfamily.
messages: Cytoplasm
messages: Expressed in mammary epithelial cells and breast cancer cell lines. Found in the luminal epithelium surrounding the ducts in the normal breast. In the brain, expressed in somatodendritic compartment of neurons in the cortex and hippocampus and in the cerebellum it is found in the Purkinje cells and some granule cells (at protein level). Detected in brain, heart, colon and kidney. In the kidney, expressed in glomerular podocytes, in some tubules and in the collecting duct.
messages: Genetic variations in WWC1 define the memory quantitative trait locus (MEMRYQTL) [MIM:615602].
messages: Homodimer. Interacts with DDN. Interacts with DYNLL1 and histone H3. The interaction with DYNLL1 is mandatory for the recruitment and transactivation functions of ESR1 or DYNLL1 to the target chromatin and the interaction with histone H3 ensures proper regulatory interaction of WWC1-DYNLL1-ESR1 complexes with target chromatin. Interacts (via WW domains) with DDR1 (via PPxY motif) in a collagen-regulated manner. Interacts with PRKCZ (via the protein kinase domain). Forms a tripartite complex with DDR1 and PRKCZ, but predominantly in the absence of collagen. Interacts (via the ADDV motif) with PATJ (via PDZ domain 8). Interacts (via WW domains) with SYNPO (via PPxY motifs). Interacts with NF2 and SNX4.
messages: Nucleus
messages: Phosphorylation at Ser-542 and Ser-931 by CDK1 in response to spindle damage stress regulates mitotic exit, these two sites are dephosphorylated by CDC14B.
messages: Probable regulator of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway, a signaling pathway that plays a pivotal role in tumor suppression by restricting proliferation and promoting apoptosis. Along with NF2 can synergistically induce the phosphorylation of LATS1 and LATS2 and can probably function in the regulation of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway. Acts as a transcriptional coactivator of ESR1 which plays an essential role in DYNLL1-mediated ESR1 transactivation. Regulates collagen-stimulated activation of the ERK/MAPK cascade. Modulates directional migration of podocytes. Acts as a substrate for PRKCZ. Plays a role in cognition and memory performance (PubMed:15081397, PubMed:16684779, PubMed:18190796, PubMed:18596123, PubMed:18672031, PubMed:20159598, PubMed:23778582). Plays an important role in regulating AMPA-selective glutamate receptors (AMPARs) trafficking underlying synaptic plasticity and learning (By similarity).
messages: Strongly up-regulated by progestin treatment.
messages: The C2-domain mediates homodimerization. It is a calcium-sensitive lipid-binding domain with preference for PI(3)P.
messages: perinuclear region
messages: ruffle membrane

9606:CTR9
gene id: 9606:CTR9
uniprot id: Q6PD62
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) The PAF1 complex interacts with Dengue virus DENV2 16681 non-structural protein 5/NS5 (PubMed:30550790). The PAF1 complex interacts with Dengue virus DENV4 Dominica/814669/1981 non-structural protein 5/NS5 (PubMed:30550790). The interaction with viral NS5 proteins may reduce the antiviral immune response by inhibiting the recruitment of the PAF1 complex to interferon-stimulated genes, thus preventing their transcription (PubMed:30550790).
messages: (Microbial infection) The PAF1 complex interacts with Zika virus French Polynesia 10087PF/2013 non-structural protein 5/NS5 (PubMed:30550790). The interaction with viral NS5 proteins may reduce the antiviral immune response by inhibiting the recruitment of the PAF1 complex to interferon-stimulated genes, thus preventing their transcription (PubMed:30550790).
messages: Component of the PAF1 complex (PAF1C) which has multiple functions during transcription by RNA polymerase II and is implicated in regulation of development and maintenance of embryonic stem cell pluripotency. PAF1C associates with RNA polymerase II through interaction with POLR2A CTD non-phosphorylated and 'Ser-2'- and 'Ser-5'-phosphorylated forms and is involved in transcriptional elongation, acting both independently and synergistically with TCEA1 and in cooperation with the DSIF complex and HTATSF1. PAF1C is required for transcription of Hox and Wnt target genes. PAF1C is involved in hematopoiesis and stimulates transcriptional activity of KMT2A/MLL1; it promotes leukemogenesis through association with KMT2A/MLL1-rearranged oncoproteins, such as KMT2A/MLL1-MLLT3/AF9 and KMT2A/MLL1-MLLT1/ENL. PAF1C is involved in histone modifications such as ubiquitination of histone H2B and methylation on histone H3 'Lys-4' (H3K4me3). PAF1C recruits the RNF20/40 E3 ubiquitin-protein ligase complex and the E2 enzyme UBE2A or UBE2B to chromatin which mediate monoubiquitination of 'Lys-120' of histone H2B (H2BK120ub1); UB2A/B-mediated H2B ubiquitination is proposed to be coupled to transcription. PAF1C is involved in mRNA 3' end formation probably through association with cleavage and poly(A) factors. In case of infection by influenza A strain H3N2, PAF1C associates with viral NS1 protein, thereby regulating gene transcription. Required for mono- and trimethylation on histone H3 'Lys-4' (H3K4me3) and dimethylation on histone H3 'Lys-79' (H3K4me3). Required for Hox gene transcription. Required for the trimethylation of histone H3 'Lys-4' (H3K4me3) on genes involved in stem cell pluripotency; this function is synergistic with CXXC1 indicative for an involvement of the SET1 complex. Involved in transcriptional regulation of IL6-responsive genes and in JAK-STAT pathway; may regulate DNA-association of STAT3 (By similarity).
messages: Component of the PAF1 complex, which consists of CDC73, PAF1, LEO1, CTR9, RTF1 and SKIC8 (PubMed:16024656, PubMed:19952111, PubMed:20178742). The PAF1 complex interacts with PHF5A (By similarity). Interacts with KMT2A/MLL1 (PubMed:20541477). Interacts with STAT3 (By similarity). Interacts with SETD5 (By similarity). Interacts with ERCC6 (PubMed:26030138).
messages: Nucleus speckle
messages: Widely expressed.

9606:WNT10A
gene id: 9606:WNT10A
uniprot id: A0A2K8FR47
uniprot id: Q9GZT5
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the Wnt family.
messages: Forms a soluble 1:1 complex with AFM; this prevents oligomerization and is required for prolonged biological activity (PubMed:26902720). The complex with AFM may represent the physiological form in body fluids (PubMed:26902720).
messages: Ligand for members of the frizzled family of seven transmembrane receptors (Probable). Functions in the canonical Wnt/beta-catenin signaling pathway (By similarity). Plays a role in normal ectoderm development (PubMed:17847007, PubMed:28589954). Required for normal tooth development (PubMed:17847007, PubMed:29178643, PubMed:28589954). Required for normal postnatal development and maintenance of tongue papillae and sweat ducts (PubMed:28589954). Required for normal proliferation of basal cells in tongue filiform papillae, plantar epithelium and sweat ducts. Required for normal expression of keratins in tongue papillae (By similarity). Required for normal expression of KRT9 in foot plant epithelium (PubMed:28589954). Required for normal hair follicle function (PubMed:28589954).
messages: Ligand for members of the frizzled family of seven transmembrane receptors.
messages: Palmitoleoylation is required for efficient binding to frizzled receptors. Depalmitoleoylation leads to Wnt signaling pathway inhibition.
messages: Secreted
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: extracellular matrix

9606:GAB2
gene id: 9606:GAB2
uniprot id: Q9UQC2
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Adapter protein which acts downstream of several membrane receptors including cytokine, antigen, hormone, cell matrix and growth factor receptors to regulate multiple signaling pathways. Regulates osteoclast differentiation mediating the TNFRSF11A/RANK signaling. In allergic response, it plays a role in mast cells activation and degranulation through PI-3-kinase regulation. Also involved in the regulation of cell proliferation and hematopoiesis.
messages: Belongs to the GAB family.
messages: Cell membrane
messages: Cytoplasm
messages: Dephosphorylated by PTPN11.
messages: Membrane raft
messages: Part of a complex composed of EEIG1, TNFRSF11A/RANK, PLCG2, GAB2, TEC and BTK; complex formation increases in the presence of TNFSF11/RANKL (PubMed:23478294). Interacts with SHC1; may mediate interaction with receptors (By similarity). Interacts with SYK (By similarity). Interacts with PI-3 kinase. Interacts with GRB2 (via SH3 2 domain). Interacts (phosphorylated) with PTPN11. Interacts with TNFRSF11A (via cytoplasmic domain). Interacts (phosphorylated) with 14-3-3 family proteins SFN, YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ and YWHAZ; prevents interaction with GRB2 and attenuates GAB2 signaling. Interacts with HCK.
messages: Phosphorylated on tyrosine residue(s) by the thrombopoietin receptor (TPOR), stem cell factor receptor (SCFR), and T-cell and B-cell antigen receptors, gp130, IL-2R and IL-3R (By similarity). Phosphorylated upon stimulation of TNFRSF11A/RANK by TNFSF11/RANKL (By similarity). Phosphorylated upon EGF stimulation. Phosphorylated on tyrosine residues by HCK upon IL6 signaling.
messages: The PH domain mediates phosphatidylinositol 3,4,5-trisphosphate and phosphatidylinositol 3,4-bisphosphate binding.
messages: The SH3-binding motifs mediate interaction with SHC1 and GRB2.

9606:SFMBT1
gene id: 9606:SFMBT1
uniprot id: Q9UHJ3
names: Domain
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Expressed in all cell lines and normal tissues tested, including the thymus.
messages: Histone-binding protein, which is part of various corepressor complexes. Mediates the recruitment of corepressor complexes to target genes, followed by chromatin compaction and repression of transcription. Plays a role during myogenesis: required for the maintenance of undifferentiated states of myogenic progenitor cells via interaction with MYOD1. Interaction with MYOD1 leads to the recruitment of associated corepressors and silencing of MYOD1 target genes. Part of the SLC complex in germ cells, where it may play a role during spermatogenesis.
messages: Interacts with MYOD1 (By similarity). Component of the SLC (SFMBT1-LSD1-CoREST) corepressor complex, which also contains KDM1A/LSD1 and RCOR1/CoREST. Interacts with KDM1A/LSD1 and RCOR1/CoREST. Interacts with L3MBTL3 (By similarity).
messages: Nucleus
messages: The MBT repeats mediate binding to histones tails; however, in contrast to other MBT repeats, does not bind specific histone lysine modifications. The MBT repeats lack the conserved Asp and aromatic cage at conserved positions (PubMed:23592795).

9606:SMG5
gene id: 9606:SMG5
uniprot id: Q9UPR3
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cytoplasm
messages: Interacts with TERT, PPP2CA and SMG1. Part of a complex that contains SMG1, SMG5, SMG7, PPP2CA, a short isoform of UPF3A (isoform UPF3AS, but not isoform UPF3AL) and phosphorylated UPF1. Not detected in complexes that contain unphosphorylated UPF1.
messages: Nucleus
messages: Plays a role in nonsense-mediated mRNA decay. Does not have RNase activity by itself. Promotes dephosphorylation of UPF1. Together with SMG7 is thought to provide a link to the mRNA degradation machinery involving exonucleolytic pathways, and to serve as an adapter for UPF1 to protein phosphatase 2A (PP2A), thereby triggering UPF1 dephosphorylation. Necessary for TERT activity.
messages: Ubiquitous.

9606:ADAT3
gene id: 9606:ADAT3
uniprot id: Q96EY9
names: Caution
names: Disease Annotation
names: Similarity
messages: Belongs to the cytidine and deoxycytidylate deaminase family. ADAT3 subfamily.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Val-225 is present instead of the conserved Glu which is an active site in the cytidine and deoxycytidylate deaminase family of enzymes. It is suggested that this protein may act as a regulatory subunit.

9606:CMSS1
gene id: 9606:CMSS1
uniprot id: Q9BQ75
names: Similarity
messages: Belongs to the CMS1 family.

9606:CCDC17
gene id: 9606:CCDC17
uniprot id: Q96LX7
names: Miscellaneous
names: Sequence Caution
messages: Incompletely spliced mRNA.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

9606:BECN2
gene id: 9606:BECN2
uniprot id: A8MW95
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the beclin family.
messages: Cytoplasm
messages: Homodimer (via coiled-coil domain) (PubMed:28218432). Interacts (via coiled-coil domain) with ATG14 (via coiled-coil domain); this interaction is tighter than BECN2 self-association (PubMed:23954414, PubMed:28218432). Interacts with AMBRA1, UVRAG and PIK3C3/VPS34; these interactions are not disrupted by starvation (PubMed:23954414). Does not interact with RUBCN (PubMed:23954414). Interacts (via N-terminus) with GPRASP1/GASP1; the interaction is direct (PubMed:23954414).
messages: Involved in 2 distinct lysosomal degradation pathways: acts as a regulator of autophagy and as a regulator of G-protein coupled receptors turnover. Regulates degradation in lysosomes of a variety of G-protein coupled receptors via its interaction with GPRASP1/GASP1.
messages: Present in fetal and adult brain (at protein level).

9606:MUC19
gene id: 9606:MUC19
uniprot id: Q7Z5P9
names: Caution
names: Function
names: Induction
names: Subcellular Location Annotation
names: Tissue Specificity
messages: According to the Genome Reference Consortium, the reference genome GRCh38/hg38 is in conflict with the sequence shown here.
messages: Down-regulated in Sjoegren syndrome patients (at protein level).
messages: Expressed corneal epithelial cells, conjunctival goblet and epithelial cells and lacrimal gland cells (at protein level). Expressed by mucous cells of the submandibular gland and submucosal gland of the trachea. Expressed by middle ear epithelial cells.
messages: May function in ocular mucus homeostasis.
messages: Secreted

9606:PADI4
gene id: 9606:PADI4
uniprot id: Q9UM07
names: Activity Regulation
names: Cofactor
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Autocitrullination at Arg-372 and Arg-374 inactivates the enzyme.
messages: Belongs to the protein arginine deiminase family.
messages: Binds 5 Ca(2+) ions per subunit.
messages: Catalyzes the citrullination/deimination of arginine residues of proteins such as histones, thereby playing a key role in histone code and regulation of stem cell maintenance (PubMed:15339660, PubMed:15345777, PubMed:16567635, PubMed:21245532). Citrullinates histone H1 at 'Arg-54' (to form H1R54ci), histone H3 at 'Arg-2', 'Arg-8', 'Arg-17' and/or 'Arg-26' (to form H3R2ci, H3R8ci, H3R17ci, H3R26ci, respectively) and histone H4 at 'Arg-3' (to form H4R3ci) (PubMed:15339660, PubMed:15345777, PubMed:16567635, PubMed:21245532). Acts as a key regulator of stem cell maintenance by mediating citrullination of histone H1: citrullination of 'Arg-54' of histone H1 (H1R54ci) results in H1 displacement from chromatin and global chromatin decondensation, thereby promoting pluripotency and stem cell maintenance (PubMed:15339660, PubMed:15345777, PubMed:16567635, PubMed:21245532). Promotes profound chromatin decondensation during the innate immune response to infection in neutrophils by mediating formation of H1R54ci (PubMed:18209087). Required for the formation of neutrophil extracellular traps (NETs); NETs are mainly composed of DNA fibers and are released by neutrophils to bind pathogens during inflammation (By similarity). Citrullination of histone H3 prevents their methylation by CARM1 and HRMT1L2/PRMT1 and represses transcription (PubMed:15345777). Citrullinates EP300/P300 at 'Arg-2142', which favors its interaction with NCOA2/GRIP1 (PubMed:15731352).
messages: Cytoplasm
messages: Cytoplasmic granule
messages: Expressed in eosinophils and neutrophils, not expressed in peripheral monocytes or lymphocytes.
messages: Nucleus
messages: Strongly Inhibited by F-amidine and N-alpha-benzoyl-N5-(2-chloro-1-iminoethyl)-L-ornithine amide (Cl-amidine). These inhibitors are however not specific to PADI4 and also inhibit other members of the family (PubMed:17002273). Incorporation of a carboxylate ortho to the backbone amide of Cl-amidine results in inhibitors with increased specificity for PADI4: N-alpha-(2-carboxyl)benzoyl-N(5)-(2-fluoro-1-iminoethyl)-L-ornithine amide (o-F-amidine) and N-alpha-(2-carboxyl)benzoyl-N(5)-(2-chloro-1-iminoethyl)-L-ornithine amide (o-Cl-amidine) (PubMed:21882827). Strongly and specifically inhibited by Thr-Asp-F-amidine (TDFA); other members of the family are not inhibited (PubMed:22004374).
messages: The gene represented in this entry may be involved in disease pathogenesis. The association to rheumatoid arthritis was initially thought to result from increased citrullination of target proteins (PubMed:12833157). However, variants that have been associated to rheumatoid arthritis (Ser-55, Ala-82 and Ala-112) do not affect the catalytic activity or the citrullination activity of PADI4, suggesting that these variants may affect the mRNA stability rather than the protein (PubMed:21245532).

9606:EIF4G3
gene id: 9606:EIF4G3
uniprot id: A0A0A0MSA7
uniprot id: O43432
uniprot id: Q59GJ0
names: Function
names: PTM
names: Similarity
names: Subunit
messages: Belongs to the eukaryotic initiation factor 4G family.
messages: Component of the protein complex eIF4F, which is involved in the recognition of the mRNA cap, ATP-dependent unwinding of 5'-terminal secondary structure and recruitment of mRNA to the ribosome (PubMed:9418880). Functional homolog of EIF4G1 (PubMed:9418880).
messages: Following infection by certain enteroviruses, rhinoviruses and aphthoviruses, EIF4G1 is cleaved by the viral protease 2A, or the leader protease in the case of aphthoviruses. This shuts down the capped cellular mRNA transcription.
messages: Interacts with EIF4A, EIF4E, eIF3 and PABPC1 (PubMed:9418880). Part of a complex with EIF4E (By similarity). eIF4F is a multi-subunit complex, the composition of which varies with external and internal environmental conditions (By similarity). It is composed of at least EIF4A, EIF4E and EIF4G1/EIF4G3. EIF4G1/EIF4G3 interacts through its C-terminus with the serine/threonine kinases MKNK1, and with MKNK2. Appears to act as a scaffold protein, holding these enzymes in place to phosphorylate eIF4E. Non-phosphorylated EIF4EBP1 competes with EIF4G1/EIFG3 to interact with EIF4E; insulin stimulated MAP-kinase (MAPK1 and MAPK3) phosphorylation of EIF4EBP1 causes dissociation of the complex allowing EIF4G1/EIF4G3 to bind and consequent initiation of translation. EIF4G1/EIF4G3 interacts with PABPC1 to bring about circularization of the mRNA (By similarity). Interacts with FXR1; promoting translation of FXR1 target mRNAs (By similarity).

9606:ADAMTS13
gene id: 9606:ADAMTS13
uniprot id: Q76LX8
names: Activity Regulation
names: Cofactor
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Polymorphism
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Binds 1 zinc ion per subunit.
messages: Binds 4 Ca(2+) ions.
messages: Cleaves the vWF multimers in plasma into smaller forms thereby controlling vWF-mediated platelet thrombus formation.
messages: Genetic variations in ADAMTS13 coding region influence plasmatic ADAMTS13 activity levels. Dependent on the sequence context, the same polymorphisms might be either positive or negative modifiers of gene expression, thereby altering the phenotype of ADAMTS13 deficiency.
messages: Glycosylated. O-fucosylated by POFUT2 on a serine or a threonine residue found within the consensus sequence C1-X(2)-(S/T)-C2-G of the TSP type-1 repeat domains where C1 and C2 are the first and second cysteine residue of the repeat, respectively. Fucosylated repeats can then be further glycosylated by the addition of a beta-1,3-glucose residue by the glucosyltransferase, B3GALTL. Fucosylation mediates the efficient secretion of ADAMTS13. May also be C-glycosylated on tryptophan residues within the consensus sequence W-X-X-W of the TPRs, and also N-glycosylated. These other glycosylations can also facilitate secretion.
messages: Plasma. Expressed primarily in liver.
messages: Secreted
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The globular cysteineless spacer domain adopts a jelly-roll topology, and is necessary to recognize and cleave vWF. The C-terminal TSP type-1 and CUB domains may modulate this interaction.
messages: The precursor is processed by a furin endopeptidase which cleaves off the pro-domain.
messages: The pro-domain is not required for folding or secretion and does not perform the common function of maintening enzyme latency.
messages: Zinc and calcium ions cooperatively modulate enzyme activity. The cleavage of the pro-domain is not required for protease activity. Dependence on calcium for proteolytic activity is mediated by the high affinity site.

9606:WDR74
gene id: 9606:WDR74
uniprot id: Q6RFH5
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Isoform 1 interacts (through WDR repeats) with NVL; the interaction is independent of RNA or pre-60S ribosome particles. Isoform 2 does not interact with NVL (PubMed:28416111). Interacts with MTREX; the interaction dissociation in a late stage of rRNA synthesis is required for appropriate maturation of pre-60S particles and depends on the ATPase activity of NVL (PubMed:26456651, PubMed:29107693).
messages: Nucleus
messages: Regulatory protein of the MTREX-exosome complex involved in the synthesis of the 60S ribosomal subunit (PubMed:26456651). Participates in an early cleavage of the pre-rRNA processing pathway in cooperation with NVL (PubMed:29107693). Required for blastocyst formation, is necessary for RNA transcription, processing and/or stability during preimplantation development (By similarity).
messages: nucleolus

9606:NSUN6
gene id: 9606:NSUN6
uniprot id: Q8TEA1
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the class I-like SAM-binding methyltransferase superfamily. RsmB/NOP family.
messages: Cytoplasm
messages: S-adenosyl-L-methionine-dependent methyltransferase that specifically methylates the C5 position of cytosine 72 in tRNA(Thr)(TGT) and tRNA(Cys)(GCA) (PubMed:26160102, PubMed:27703015, PubMed:28531330). In vitro also methylates tRNA(Thr)(AGT) (PubMed:27703015, PubMed:26160102). Methylation requires, in the acceptor stem region, the presence of the 3'-CCA terminus, the target site C72, the discriminator base U73, and the second and third base pairs (2:71 and 3:70) in the tRNA substrates (PubMed:26160102, PubMed:27703015).
messages: The PUA domain plays a role in tRNA recognition through precisely recognizing the CCA end and the D-stem region of tRNA.

9606:NAA16
gene id: 9606:NAA16
uniprot id: Q6N069
names: Function
names: Subunit
messages: Auxillary subunit of the N-terminal acetyltransferase A (NatA) complex which displays alpha (N-terminal) acetyltransferase activity.
messages: Component of the N-terminal acetyltransferase A (NatA) complex composed of NAA10 and NAA16.

9606:SYNJ1
gene id: 9606:SYNJ1
uniprot id: A0A0D9SGJ6
uniprot id: B9EGN3
uniprot id: C9JFZ1
uniprot id: J3KQV8
uniprot id: O43426
uniprot id: Q05CZ1
names: Disease Annotation
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the synaptojanin family.
messages: Binds to EPS15 (a clathrin coat-associated protein) via a C-terminal domain containing three Asn-Pro-Phe (NPF) repeats.
messages: Concentrated at clathrin-coated endocytic intermediates in nerve terminals. Isoform 1 is more enriched than isoform 2 in developing brain as well as non-neuronal cells. Isoform 2 is very abundant in nerve terminals.
messages: In the central section; belongs to the inositol 1,4,5-trisphosphate 5-phosphatase family.
messages: Interacts with ASH/GRB2. Interacts with PACSIN1, PACSIN2 and PACSIN3 (By similarity). Binds AMPH, SH3GL1, SH3GL2 and SH3GL3 (PubMed:10542231). Interacts with MYO1E (via SH3 domain) (PubMed:17257598). Interacts with BIN1 and DNM1 (By similarity).
messages: Phosphatase that acts on various phosphoinositides, including phosphatidylinositol 4-phosphate, phosphatidylinositol (4,5)-bisphosphate and phosphatidylinositol (3,4,5)-trisphosphate (PubMed:27435091). Has a role in clathrin-mediated endocytosis (By similarity). Hydrolyzes PIP2 bound to actin regulatory proteins resulting in the rearrangement of actin filaments downstream of tyrosine kinase and ASH/GRB2 (By similarity).
messages: The C-terminal proline-rich region mediates binding to a variety of SH3 domain-containing proteins including AMPH, SH3GL1, SH3GL2, SH3GL3 and GRB2.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: perinuclear region

9606:BTD
gene id: 9606:BTD
uniprot id: P43251
names: Caution
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the carbon-nitrogen hydrolase superfamily. BTD/VNN family.
messages: Catalytic release of biotin from biocytin, the product of biotin-dependent carboxylases degradation.
messages: It is uncertain whether Met-1 or Met-21 is the initiator.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: extracellular space

9606:THUMPD1
gene id: 9606:THUMPD1
uniprot id: Q9NXG2
names: Disease Annotation
names: Function
names: Similarity
names: Subunit
messages: Belongs to the THUMPD1 family.
messages: Functions as a tRNA-binding adapter to mediate NAT10-dependent tRNA acetylation modifying cytidine to N4-acetylcytidine (ac4C) (PubMed:25653167, PubMed:35196516).
messages: Interacts with NAT10 (PubMed:25653167). Binds tRNA (PubMed:35196516).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:SMG7
gene id: 9606:SMG7
uniprot id: A0A8I5KSL3
uniprot id: E9PD50
uniprot id: Q92540
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Cytoplasm
messages: Nucleus
messages: Part of a complex that contains SMG5, SMG7, PPP2CA, a short isoform of UPF3A (isoform UPF3AS, but not isoform UPF3AL) and phosphorylated UPF1 (PubMed:14636577). Interacts with DHX34; the interaction is RNA-independent (PubMed:25220460).
messages: Plays a role in nonsense-mediated mRNA decay.
messages: Plays a role in nonsense-mediated mRNA decay. Recruits UPF1 to cytoplasmic mRNA decay bodies. Together with SMG5 is thought to provide a link to the mRNA degradation machinery involving exonucleolytic pathways, and to serve as an adapter for UPF1 to protein phosphatase 2A (PP2A), thereby triggering UPF1 dephosphorylation.

9606:THBS1
gene id: 9606:THBS1
uniprot id: P07996
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions (PubMed:2430973, PubMed:6489349, PubMed:15014436, PubMed:18285447). Multifunctional, involved in inflammation, angiogenesis, wound healing, reactive oxygen species (ROS) signaling, nitrous oxide (NO) signaling, apoptosis, senescence, aging, cellular self-renewal, stemness, and cardiovascular and metabolic homeostasis (PubMed:14568985, PubMed:1371676, PubMed:10613822, PubMed:11134179, PubMed:24511121, PubMed:29042481, PubMed:32679764). Negatively modulates dendritic cell activation and cytokine release, as part of an autocrine feedback loop, contributing to the resolution of inflammation and immune homeostasis (PubMed:14568985). Ligand for receptor CD47 (PubMed:8550562, PubMed:19004835). Modulates nitrous oxide (NO) signaling via CD47, hence playing a role as a pressor agent, supporting blood pressure (By similarity). Plays a role in endothelial cell senescence, acting via CD47, by increasing the abundance and activation of NADPH oxidase NOX1, and so generating excess ROS (PubMed:29042481). Inhibits stem cell self-renewal, acting via CD47 signaling, probably by regulation of the stem cell transcription factors POU5F1/OCT4, SOX2, MYC/c-Myc and KLF4 (By similarity). Negatively modulates wound healing, acting via CD47 (By similarity). Ligand for receptor CD36 (PubMed:1371676, PubMed:10613822, PubMed:11134179). Involved in inducing apoptosis in podocytes in response to elevated free fatty acids, acting via CD36 (By similarity). Plays a role in suppressing angiogenesis, acting, depending on context, via CD36 or CD47 (PubMed:1371676, PubMed:10613822, PubMed:32679764, PubMed:11134179). Promotes cellular senescence in a TP53-CDKN1A-RB1 signaling-dependent manner (PubMed:29042481). Ligand for immunoglobulin-like cell surface receptor SIRPA (PubMed:24511121). Involved in ROS signaling in non-phagocytic cells, stimulating NADPH oxidase-derived ROS production, acting via interaction with SIRPA (PubM…
messages: Belongs to the thrombospondin family.
messages: Cell surface
messages: Endoplasmic reticulum
messages: Expressed by platelets (at protein level) (PubMed:101549). Expressed by monocyte-derived immature and mature dendritic cells (at protein level) (PubMed:14568985).
messages: Expression is induced by PGE2, S.aureus and lipopolysaccharide (PubMed:14568985). Induced in arteries and lung parenchyma following injury or stress (PubMed:27742621). Expression in vasculature, including arteries, increases in normal aging (PubMed:32679764, PubMed:29042481).
messages: Homotrimer; disulfide-linked (PubMed:101549, PubMed:18285447). Can bind to fibrinogen, fibronectin, laminin, type V collagen and integrins alpha-V/beta-1, alpha-V/beta-3 and alpha-IIb/beta-3 (PubMed:6489349, PubMed:6693501, PubMed:2478219). Binds heparin (PubMed:101549, PubMed:16407063, PubMed:18065761). Interacts (via the C-terminal domain) with CD47 (PubMed:8550562, PubMed:19004835). Interacts (via the TSP type I repeats) with CD36; the interaction conveys an antiangiogenic effect (PubMed:1371676, PubMed:10613822). Interacts (via the TSP type I repeats) with HRG; the interaction blocks the antiangiogenic effect of THBS1 with CD36 (PubMed:11134179). Interacts with ATF6 (via lumenal domain) (By similarity). Interacts with FN1; this interaction is enhanced by TNFAIP6, which may act as a bridging molecule between FN1 and THBS1 (PubMed:18042364). Interacts with SIRPA; the interaction stimulates phosphorylation of SIRPA (PubMed:24511121).
messages: Sarcoplasmic reticulum
messages: Secreted
messages: extracellular matrix

9606:BMAL2
gene id: 9606:BMAL2
uniprot id: Q8WYA1
names: Function
names: Induction
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Component of the circadian core oscillator, which includes the CRY proteins, CLOCK, or NPAS2, BMAL1 or BMAL2, CSNK1D and/or CSNK1E, TIMELESS and the PER proteins. Interacts directly with CLOCK to form the BMAL2-CLOCK transactivator. Can form heterodimers or homodimers which interact directly with CLOCK to form the transcription activator. Interacts with NPAS2 and HIF1A. Interacts with PER2 (By similarity).
messages: Constitutively expressed. Has no circadian rhythm expression pattern.
messages: Expressed in fetal brain. Highly expressed in brain and placenta. Lower levels in heart, liver, thymus, kidney and lung. Located to endothelial cells and neuronal cells of the suprachiasmatic nucleus (SCN). Also detected in endothelial cells of the heart, lung and kidney. In the brain, specifically expressed in the thalamus, hippocampus and amygdala.
messages: Nucleus
messages: Transcriptional activator which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots 'circa' (about) and 'diem' (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN. The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle. Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day. Transcription and translation of core clock components (CLOCK, NPAS2, BMAL1, BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle). A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a …

9606:OVGP1
gene id: 9606:OVGP1
uniprot id: Q12889
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the glycosyl hydrolase 18 family.
messages: Binds to oocyte zona pellucida in vivo. May play a role in the fertilization process and/or early embryonic development.
messages: Oviduct.
messages: secretory vesicle

9606:NOX1
gene id: 9606:NOX1
uniprot id: A6NGA6
uniprot id: Q1ZYL4
uniprot id: Q9Y5S8
names: Activity Regulation
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cell membrane
messages: Defects in NOX1 may play a role in the pathogenesis of very early onset inflammatory bowel disease (VEOIBD), a chronic, relapsing inflammation of the gastrointestinal tract with a complex etiology diagnosed before 6 years of age. VEOIBD is subdivided into Crohn disease and ulcerative colitis phenotypes. Crohn disease may affect any part of the gastrointestinal tract from the mouth to the anus, but the phenotype of children with onset of Crohn disease occurring younger than the age of 10 is predominantly colonic, with a lower risk of ileal disease. Bowel inflammation is transmural and discontinuous; it may contain granulomas or be associated with intestinal or perianal fistulas. In contrast, in ulcerative colitis, the inflammation is continuous and limited to rectal and colonic mucosal layers; fistulas and granulomas are not observed. Both diseases include extraintestinal inflammation of the skin, eyes, or joints.
messages: Membrane
messages: NOH-1L is detected in colon, uterus, prostate, and colon carcinoma, but not in peripheral blood leukocytes. NOH-1S is detected only in colon and colon carcinoma cells.
messages: NOH-1S is a voltage-gated proton channel that mediates the H(+) currents of resting phagocytes and other tissues. It participates in the regulation of cellular pH and is blocked by zinc. NOH-1L is a pyridine nucleotide-dependent oxidoreductase that generates superoxide and might conduct H(+) ions as part of its electron transport mechanism, whereas NOH-1S does not contain an electron transport chain.
messages: NOX1, NOXA1, NOXO1, RAC1 and CYBA forms a functional multimeric complex supporting reactive oxygen species (ROS) production. Interacts with NOXA1 and NOXO1.
messages: The oxidase activity is potentiated by NOXA1 and NOXO1.
messages: invadopodium membrane

9606:PILRB
gene id: 9606:PILRB
uniprot id: Q9UKJ0
names: Function
names: Subcellular Location Annotation
messages: Membrane
messages: Paired receptors consist of highly related activating and inhibitory receptors and are widely involved in the regulation of the immune system. PILRB is thought to act as a cellular signaling activating receptor that associates with ITAM-bearing adapter molecules on the cell surface.

9606:PRRT1
gene id: 9606:PRRT1
uniprot id: A0A1U9X8D6
uniprot id: Q99946
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the CD225/Dispanin family.
messages: Cell membrane
messages: Component of the outer core of AMPAR complex. AMPAR complex consists of an inner core made of 4 pore-forming GluA/GRIA proteins (GRIA1, GRIA2, GRIA3 and GRIA4) and 4 major auxiliary subunits arranged in a twofold symmetry. One of the two pairs of distinct binding sites is occupied either by CNIH2, CNIH3 or CACNG2, CACNG3. The other harbors CACNG2, CACNG3, CACNG4, CACNG8 or GSG1L. This inner core of AMPAR complex is complemented by outer core constituents binding directly to the GluA/GRIA proteins at sites distinct from the interaction sites of the inner core constituents. Outer core constituents include at least PRRT1, PRRT2, CKAMP44/SHISA9, FRRS1L and NRN1. The proteins of the inner and outer core serve as a platform for other, more peripherally associated AMPAR constituents. Alone or in combination, these auxiliary subunits control the gating and pharmacology of the AMPAR complex and profoundly impact their biogenesis and protein processing (By similarity).
messages: Required to maintain a pool of extrasynaptic AMPA-regulated glutamate receptors (AMPAR) which is necessary for synapse development and function. Regulates basal AMPAR function and synaptic transmission during development but is dispensable at mature hippocampal synapses. Plays a role in regulating basal phosphorylation levels of glutamate receptor GRIA1 and promotes GRIA1 and GRIA2 cell surface expression.
messages: Synapse

9606:WRAP53
gene id: 9606:WRAP53
uniprot id: Q9BUR4
names: Disease Annotation
names: Function
names: Induction
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Over-expressed following infection by Epstein-Barr virus.
messages: Belongs to the TCAB1 family.
messages: Cajal body
messages: Chromosome
messages: Component of the telomerase holoenzyme complex composed of one molecule of TERT, one molecule of WRAP53/TCAB1, two molecules of H/ACA ribonucleoprotein complex subunits DKC1, NOP10, NHP2 and GAR1, and a telomerase RNA template component (TERC) (PubMed:19179534, PubMed:20351177, PubMed:26170453, PubMed:29695869). The telomerase holoenzyme complex is associated with TEP1, SMG6/EST1A and POT1 (PubMed:19179534). Interacts with the chaperonin-containing T-complex (TRiC) complex; which mediates the folding of WRAP53/TCAB1 (PubMed:25467444). Interacts with COIL (PubMed:21072240). Interacts with SMN1 (PubMed:21072240). Interacts with RNF8 (PubMed:25512560). Interacts with histone H2AX (PubMed:26734725, PubMed:27715493).
messages: Expressed in all tissues and cell lines examined.
messages: Phosphorylated at Ser-64 by ATM in response to DNA damage, promoting its interaction with histone H2AX and localization to sites of DNA double-strand breaks.
messages: RNA chaperone that plays a key role in telomere maintenance and RNA localization to Cajal bodies (PubMed:29804836, PubMed:29695869). Specifically recognizes and binds the Cajal body box (CAB box) present in both small Cajal body RNAs (scaRNAs) and telomerase RNA template component (TERC) (PubMed:19285445, PubMed:20351177, PubMed:29804836, PubMed:29695869). Essential component of the telomerase holoenzyme complex, a ribonucleoprotein complex essential for the replication of chromosome termini that elongates telomeres in most eukaryotes (PubMed:19179534, PubMed:20351177, PubMed:26170453, PubMed:29695869). In the telomerase holoenzyme complex, required to stimulate the catalytic activity of the complex (PubMed:27525486, PubMed:29804836). Acts by specifically binding the CAB box of the TERC RNA and controlling the folding of the CR4/CR5 region of the TERC RNA, a critical step for telomerase activity (PubMed:29804836). In addition, also controls telomerase holoenzyme complex localization to Cajal body (PubMed:22547674). During S phase, required for delivery of TERC to telomeres during S phase and for telomerase activity (PubMed:29804836). In addition to its role in telomere maintenance, also required for Cajal body formation, probably by mediating localization of scaRNAs to Cajal bodies (PubMed:19285445, PubMed:21072240). Also plays a role in DNA repair: phosphorylated by ATM in response to DNA damage and relocalizes to sites of DNA double-strand breaks to promote the repair of DNA double-strand breaks (PubMed:25512560, PubMed:27715493). Acts by recruiting the ubiquitin ligase RNF8 to DNA breaks and promote both homologous recombination (HR) and non-homologous end joining (NHEJ) (PubMed:25512560, PubMed:27715493).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The mRNA encoding this protein plays a critical role in the regulation of p53/TP53 expression at the post-transcriptional level; it is involved both in maintaining basal p53/TP53 mRNA levels and in p53/TP53 induction upon DNA damage.
messages: telomere

9606:TATDN1
gene id: 9606:TATDN1
uniprot id: A0A0D9SGD3
uniprot id: Q6P1N9
names: Cofactor
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the metallo-dependent hydrolases superfamily. TatD-type hydrolase family.
messages: Binds 2 divalent metal cations per subunit.
messages: Deoxyribonuclease which catalyzes (in vitro) the decatenation of kinetoplast DNA, which are circular DNA catenated to each other, producing linear DNA molecules (By similarity). Plays an important role in chromosomal segregation and cell cycle progression during eye development probably via its DNA decatenation activity (By similarity).
messages: Nucleus

9606:ACYP2
gene id: 9606:ACYP2
uniprot id: A0A140VJD7
uniprot id: E9PF46
uniprot id: F8WA34
uniprot id: P14621
uniprot id: U3KQL2
names: Function
names: Similarity
messages: Belongs to the acylphosphatase family.
messages: Its physiological role is not yet clear.

9606:PCSK5
gene id: 9606:PCSK5
uniprot id: Q92824
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: AC 1 and AC 2 (clusters of acidic amino acids) contain sorting information. AC 1 directs TGN localization and interacts with the TGN sorting protein PACS-1 (By similarity).
messages: Belongs to the peptidase S8 family.
messages: Endomembrane system
messages: Expressed in T-lymphocytes.
messages: Secreted
messages: Serine endoprotease that processes various proproteins by cleavage at paired basic amino acids, recognizing the RXXX[KR]R consensus motif. Likely functions in the constitutive and regulated secretory pathways. Plays an essential role in pregnancy establishment by proteolytic activation of a number of important factors such as BMP2, CALD1 and alpha-integrins.
messages: The propeptide domain acts as an intramolecular chaperone assisting the folding of the zymogen within the endoplasmic reticulum.

9606:CTAGE8
gene id: 9606:CTAGE8
uniprot id: P0CG41
uniprot id: Q8IX94
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the cTAGE family.
messages: Expressed in testis, placenta and skin. Expressed at lower level in mammary gland and stomach.
messages: Membrane
messages: Tumor-associated antigen found in several cutaneous T-cell lymphoma (CTCL). Also found in colorectal and breast carcinomas, head and neck squamous cell carcinomas and melanoma.
messages: Tumor-associated antigen.

9606:RIOX2
gene id: 9606:RIOX2
uniprot id: A0A6M8YDW1
uniprot id: Q8IUF8
names: Cofactor
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the ROX family. MINA53 subfamily.
messages: Binds 1 Fe(2+) ion per subunit.
messages: Expressed in liver, skeletal muscle, heart, pancreas, and placenta. Not detected in brain, lung or kidney. Expressed in several lung cancer tissues, but is barely detected in the adjacent non-cancerous tissues. Also highly expressed in several esophageal squamous cell carcinoma (ESCC), and colon cancer tissues, and in various cancer cell lines.
messages: Nucleus
messages: Oxygenase that can act as both a histone lysine demethylase and a ribosomal histidine hydroxylase.
messages: Oxygenase that can act as both a histone lysine demethylase and a ribosomal histidine hydroxylase. Is involved in the demethylation of trimethylated 'Lys-9' on histone H3 (H3K9me3), leading to an increase in ribosomal RNA expression. Also catalyzes the hydroxylation of 60S ribosomal protein L27a on 'His-39'. May play an important role in cell growth and survival. May be involved in ribosome biogenesis, most likely during the assembly process of pre-ribosomal particles.
messages: Up-regulated in response to MYC, in alveolar macrophages from coal miners and in silica particle-treated A549 lung cancer cells.
messages: nucleolus

9606:SIRT7
gene id: 9606:SIRT7
uniprot id: Q9NRC8
names: Activity Regulation
names: Caution
names: Cofactor
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the sirtuin family. Class IV subfamily.
messages: Binds 1 zinc ion per subunit.
messages: Chromosome
messages: Cytoplasm
messages: Interacts with UBTF and the RNA polymerase I complex (PubMed:16618798, PubMed:19174463). Interacts with components of the B-WICH complex, such as MYBBP1A, SMARCA5/SNF2H and BAZ1B/WSTF (PubMed:22586326). Interacts with ELK4, leading to stabilization at target promoters for H3K18Ac deacetylation (PubMed:22722849). Interacts with histone H2A and/or histone H2B (PubMed:22722849). Interacts with DNMT1 (By similarity). Interacts with SIRT1 (By similarity).
messages: Methylation at Arg-388 by PRMT6 inhibits the H3K18Ac histone deacetylase activity, promoting mitochondria biogenesis and maintaining mitochondria respiration.
messages: NAD-dependent protein-lysine deacetylase and deacylase activities are activated by nucleic acids (PubMed:26907567, PubMed:27997115). Histone deacetylase activity is activated by DNA and nucleosomes (PubMed:27997115, PubMed:35939806). Protein-lysine deacylase activity is activated by RNA (PubMed:26907567). H3K18Ac histone deacetylase activity is inhibited by methylation at Arg-388 (PubMed:30420520). H3K18Ac histone deacetylase activity is inhibited by deubiquitination by USP7 (PubMed:28655758).
messages: NAD-dependent protein-lysine deacylase that can act both as a deacetylase or deacylase (desuccinylase, depropionylase, deglutarylase and dedecanoylase), depending on the context (PubMed:22722849, PubMed:26907567, PubMed:30653310, PubMed:31542297, PubMed:35939806). Specifically mediates deacetylation of histone H3 at 'Lys-18' (H3K18Ac) (PubMed:22722849, PubMed:30420520, PubMed:35939806). In contrast to other histone deacetylases, displays strong preference for a specific histone mark, H3K18Ac, directly linked to control of gene expression (PubMed:22722849, PubMed:30653310). H3K18Ac is mainly present around the transcription start site of genes and has been linked to activation of nuclear hormone receptors; SIRT7 thereby acts as a transcription repressor (PubMed:22722849). Moreover, H3K18 hypoacetylation has been reported as a marker of malignancy in various cancers and seems to maintain the transformed phenotype of cancer cells (PubMed:22722849). Also able to mediate deacetylation of histone H3 at 'Lys-36' (H3K36Ac) in the context of nucleosomes (PubMed:30653310). Also mediates deacetylation of non-histone proteins, such as ATM, CDK9, DDX21, DDB1, FBL, FKBP5/FKBP51, GABPB1, RAN, RRP9/U3-55K and POLR1E/PAF53 (PubMed:24207024, PubMed:26867678, PubMed:28147277, PubMed:28886238, PubMed:28426094, PubMed:30540930, PubMed:31075303, PubMed:30944854, PubMed:28790157). Enriched in nucleolus where it stimulates transcription activity of the RNA polymerase I complex (PubMed:16618798, PubMed:19174463, PubMed:24207024). Acts by mediating the deacetylation of the RNA polymerase I subunit POLR1E/PAF53, thereby promoting the association of RNA polymerase I with the rDNA promoter region and coding region (PubMed:16618798, PubMed:19174463, PubMed:24207024). In response to metabolic stress, SIRT7 is released from nucleoli leading to hyperacetylation of POLR1E/PAF53 and decreased RNA polymerase I transcription (PubMed:24207024). Required to restore the transcription of ribosomal RNA (rRN…
messages: Overexpressed in thyroid carcinoma cell lines and tissues, but not in adenomas.
messages: Phosphorylated during mitosis.
messages: Ubiquitinated via 'Lys-63'-linked ubiquitin chains (PubMed:28655758). Deubiquitinated by USP7, inhibiting the H3K18Ac histone deacetylase activity and regulating gluconeogenesis (PubMed:28655758). Ubiquitinated by E3 ubiquitin-protein ligase complex containing FBXO7; leading to proteasomal degradation.
messages: Was originally termed SIR-T8/SIRT8 (PubMed:11953824). This was later retracted (PubMed:12454780, PubMed:12454781).
messages: nucleolus
messages: nucleoplasm

9606:ANAPC10
gene id: 9606:ANAPC10
uniprot id: Q9UM13
names: Function
names: Similarity
names: Subunit
messages: Belongs to the APC10 family.
messages: Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains.
messages: The mammalian APC/C is composed at least of 14 distinct subunits ANAPC1, ANAPC2, CDC27/APC3, ANAPC4, ANAPC5, CDC16/APC6, ANAPC7, CDC23/APC8, ANAPC10, ANAPC11, CDC26/APC12, ANAPC13, ANAPC15 and ANAPC16 that assemble into a complex of at least 19 chains with a combined molecular mass of around 1.2 MDa; APC/C interacts with FZR1 and FBXO5 (PubMed:26083744, PubMed:25043029). The C-terminus of APC10 binds to CDC27/APC3 (PubMed:11524682). Interacts with PIWIL1; interaction only takes place when PIWIL1 binds piRNA (By similarity). Interacts with FBXO43; the interaction is direct.

9606:EML1
gene id: 9606:EML1
uniprot id: O00423
names: Disease Annotation
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the WD repeat EMAP family.
messages: Contains a tandem atypical propeller in EMLs (TAPE) domain. The N-terminal beta-propeller is formed by canonical WD repeats; in contrast, the second beta-propeller contains one blade that is formed by discontinuous parts of the polypeptide chain.
messages: Cytoplasm
messages: Homotrimer; self-association is mediated by the N-terminal coiled coil (By similarity). Does not interact with EML3 (PubMed:25740311). Binds repolymerizing microtubules (PubMed:24859200). Binds unpolymerized tubulins via its WD repeat region (PubMed:24706829). Interacts with TASOR (By similarity).
messages: Modulates the assembly and organization of the microtubule cytoskeleton, and probably plays a role in regulating the orientation of the mitotic spindle and the orientation of the plane of cell division. Required for normal proliferation of neuronal progenitor cells in the developing brain and for normal brain development. Does not affect neuron migration per se.
messages: The N-terminal coiled coil is required for association with microtubules.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitous; expressed in most tissues with the exception of thymus and peripheral blood lymphocytes.
messages: cytoskeleton
messages: perinuclear region

9606:GLI3
gene id: 9606:GLI3
uniprot id: A0A2R8YGX0
uniprot id: P10071
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the GLI C2H2-type zinc-finger protein family.
messages: Cytoplasm
messages: Has a dual function as a transcriptional activator and a repressor of the sonic hedgehog (Shh) pathway, and plays a role in limb development. The full-length GLI3 form (GLI3FL) after phosphorylation and nuclear translocation, acts as an activator (GLI3A) while GLI3R, its C-terminally truncated form, acts as a repressor. A proper balance between the GLI3 activator and the repressor GLI3R, rather than the repressor gradient itself or the activator/repressor ratio gradient, specifies limb digit number and identity. In concert with TRPS1, plays a role in regulating the size of the zone of distal chondrocytes, in restricting the zone of PTHLH expression in distal cells and in activating chondrocyte proliferation. Binds to the minimal GLI-consensus sequence 5'-GGGTGGTC-3'.
messages: Is expressed in a wide variety of normal adult tissues, including lung, colon, spleen, placenta, testis, and myometrium.
messages: Nucleus
messages: Phosphorylated on multiple sites by protein kinase A (PKA) and phosphorylation by PKA primes further phosphorylation by CK1 and GSK3. Phosphorylated by DYRK2 (in vitro). Phosphorylation is essential for its proteolytic processing.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The full-length GLI3 form (GLI3FL) interacts with SUFU and this interaction regulates the formation of either repressor or activator forms of GLI3. Its association with SUFU is regulated by Hh signaling and dissociation of the SUFU-GLI3 interaction requires the presence of the ciliary motor KIF3A (By similarity). Interacts with KIF7. The activator form of GLI3 (GLI3A) but not the repressor form (GLI3R) can interact with TRPS1. The phosphorylated form interacts with BTRC. Interacts with ZIC1. Interacts with ZIC3 (via C2H2-type domains 3, 4 and 5); the interaction enhances its transcriptional activity. Interacts with WRD11; the interaction associates EMX1 with GLI3 (PubMed:29263200). Interacts with DZIP1; retains GLI3 within the cytoplasm (PubMed:23955340).
messages: Transcriptional repressor GLI3R, a C-terminally truncated form, is generated from the full-length GLI3 protein (GLI3FL/GLI3-190) through proteolytic processing. This process requires PKA-primed phosphorylation of GLI3, ubiquitination of GLI3 and the presence of BTRC. GLI3FL is complexed with SUFU in the cytoplasm and is maintained in a neutral state. Without the Hh signal, the SUFU-GLI3 complex is recruited to cilia, leading to the efficient processing of GLI3FL into GLI3R. GLI3R formation leads to its dissociation from SUFU, allowing it to translocate into the nucleus, and repress Hh target genes. When Hh signaling is initiated, SUFU dissociates from GLI3FL and this has two consequences. First, GLI3R production is halted. Second, free GLI3FL translocates to the nucleus, where it is phosphorylated, destabilized, and converted to a transcriptional activator (GLI3A). Phosphorylated in vitro by ULK3.
messages: cilium

9606:AMN
gene id: 9606:AMN
uniprot id: B3KP64
uniprot id: Q9BXJ7
names: Disease Annotation
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: A soluble form arises by proteolytic removal of the membrane anchor.
messages: Apical cell membrane
messages: Cell membrane
messages: Detected in proximal tubules in the kidney cortex (at protein level) (PubMed:14576052, PubMed:29402915). Long isoforms are highly expressed in small intestine, colon and kidney (renal proximal tubule epithelial cells). Shorter isoforms are detected at lower levels in testis, thymus and peripheral blood leukocytes.
messages: Endosome membrane
messages: Interacts (via extracellular region) with CUBN/cubilin, giving rise to a huge complex containing one AMN chain and three CUBN chains.
messages: Membrane
messages: Membrane-bound component of the endocytic receptor formed by AMN and CUBN (PubMed:14576052, PubMed:30523278, PubMed:29402915). Required for normal CUBN glycosylation and trafficking to the cell surface (PubMed:14576052, PubMed:29402915). The complex formed by AMN and CUBN is required for efficient absorption of vitamin B12 (PubMed:12590260, PubMed:14576052, PubMed:26040326). Required for normal CUBN-mediated protein transport in the kidney (Probable).
messages: N-glycosylated.
messages: Secreted
messages: The complex formed by AMN and CUBN is composed of a 400 Angstrom long stem and a globular crown region. The stem region is probably formed by AMN and the CUBN N-terminal region, including the EGF-like domains. The crown is probably formed by the CUBN CUB domains.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The role of Amn in embryonic development seems to be species specific. In mice, null mutations lead to embryonic lethality. Human mutations give rise to much milder symptoms.
messages: coated pit

9606:GPX2
gene id: 9606:GPX2
uniprot id: P18283
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the glutathione peroxidase family.
messages: Could play a major role in protecting mammals from the toxicity of ingested organic hydroperoxides (PubMed:8428933). Tert-butyl hydroperoxide, cumene hydroperoxide and linoleic acid hydroperoxide but not phosphatidycholine hydroperoxide, can act as acceptors (PubMed:8428933).
messages: Homotetramer.
messages: Mostly in liver and gastrointestinal tract, not found in heart or kidney.
messages: cytosol

9606:FCER2
gene id: 9606:FCER2
uniprot id: P06734
names: Function
names: Miscellaneous
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: Cell membrane
messages: Homotrimer. Interacts (via C-type lectin domain) with IGHE (via CH3 region); this interaction regulates IgE homeostasis. Interacts (via the C-terminus) with CR2/CD21 (via Sushi domain 1 and 2).
messages: Low-affinity receptor for immunoglobulin E (IgE) and CR2/CD21. Has essential roles in the regulation of IgE production and in the differentiation of B cells. On B cells, initiates IgE-dependent antigen uptake and presentation to T cells (PubMed:2167225). On macrophages, upon IgE binding and antigen cross-linking induces intracellular killing of parasites through activation of L-Arginine-nitric oxide pathway (PubMed:7544003).
messages: N- and O-glycosylated.
messages: Secreted
messages: The secreted form sCD23 is produced by ADAM10-mediated ectodomain shedding.
messages: There are two kinds of Fc receptors for IgE, which differ in both structure and function: high affinity receptors on basophils and mast cells and low affinity receptors on lymphocytes and monocytes.

9606:TNFAIP1
gene id: 9606:TNFAIP1
uniprot id: Q13829
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the BACURD family.
messages: By TNF, IL1B/interleukin-1 beta and bacterial lipopolysaccharides (LPS).
messages: Component of the BCR(TNFAIP1) E3 ubiquitin ligase complex, at least composed of CUL3, TNFAIP1/BACURD2 and RBX1. Interacts with RHOA; with a preference for RhoA-GDP. Interacts with RHOB. Interacts with PCNA. Interacts with CSNK2B.
messages: Cytoplasm
messages: Endosome
messages: Nucleus
messages: Phosphorylation at Ser-280 by CK2 facilitates the nucleus localization and increases interaction with PCNA.
messages: Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex involved in regulation of cytoskeleton structure. The BCR(TNFAIP1) E3 ubiquitin ligase complex mediates the ubiquitination of RHOA, leading to its degradation by the proteasome, thereby regulating the actin cytoskeleton and cell migration. Its interaction with RHOB may regulate apoptosis. May enhance the PCNA-dependent DNA polymerase delta activity.

9606:CEP170B
gene id: 9606:CEP170B
uniprot id: Q9Y4F5
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the CEP170 family.
messages: Plays a role in microtubule organization.
messages: cytoskeleton

9606:KARS1
gene id: 9606:KARS1
uniprot id: Q15046
names: Activity Regulation
names: Disease Annotation
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Interacts directly with HIV-1 virus GAG protein (PubMed:12756246, PubMed:15220430).
messages: (Microbial infection) Interacts with HIV-1 virus GAG protein, facilitating the selective packaging of tRNA(3)(Lys), the primer for reverse transcription initiation.
messages: Belongs to the class-II aminoacyl-tRNA synthetase family.
messages: Catalyzes the specific attachment of an amino acid to its cognate tRNA in a 2 step reaction: the amino acid (AA) is first activated by ATP to form AA-AMP and then transferred to the acceptor end of the tRNA (PubMed:9278442, PubMed:18029264, PubMed:18272479). When secreted, acts as a signaling molecule that induces immune response through the activation of monocyte/macrophages (PubMed:15851690). Catalyzes the synthesis of the signaling molecule diadenosine tetraphosphate (Ap4A), and thereby mediates disruption of the complex between HINT1 and MITF and the concomitant activation of MITF transcriptional activity (PubMed:5338216, PubMed:14975237, PubMed:19524539, PubMed:23159739).
messages: Cell membrane
messages: Cytoplasm
messages: Homodimer and tetradimer (PubMed:18272479, PubMed:23159739, PubMed:26074468, PubMed:28887846). Part of the multisynthetase complex (MSC), a multisubunit complex that groups tRNA ligases for Arg (RARS), Asp (DARS), Gln (QARS), Ile (IARS), Leu (LARS), Lys (KARS), Met (MARS) the bifunctional ligase for Glu and Pro (EPRS) and the auxiliary subunits AIMP1/p43, AIMP2/p38 and EEF1E1/p18 (PubMed:19131329, PubMed:19289464, PubMed:24312579, PubMed:23159739). Interacts with AIMP2 (via N-terminus) and MITF (PubMed:9878398, PubMed:14975237, PubMed:15220430, PubMed:23159739, PubMed:26074468, PubMed:31116475). Interacts with TARSL2 (PubMed:24312579).
messages: Mitochondrial precursor. Contains a mitochondrial transit peptide at positions 1-16.
messages: Mitochondrion
messages: Nucleus
messages: Phosphorylated on a serine residue after mast cell stimulation with immunoglobulin E (IgE).
messages: Secreted
messages: Shares a bidirectional promoter with TERF2IP/RAP1.
messages: The N-terminal domain (1-65) of the cytoplasmic isoform is a functional tRNA-binding domain, is required for nuclear localization, is involved in the interaction with DARS, but has a repulsive role in the binding to EEF1A1. A central domain (208-259) is involved in homodimerization and is required for interaction with HIV-1 GAG and incorporation into virions. The C-terminal domain (452-597) is not required for interaction with AIMP2.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Up-regulated by DARS and EEF1A1, but not by AIMP2.
messages: cytosol

9606:ANKAR
gene id: 9606:ANKAR
uniprot id: Q7Z5J8
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Membrane
messages: Ubiquitously expressed with highest level in pancreas and lowest in skeletal muscle.

9606:TUT1
gene id: 9606:TUT1
uniprot id: A0A0A8K9B1
uniprot id: F5H0R1
uniprot id: Q9H6E5
names: Activity Regulation
names: Cofactor
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Adenylyltransferase activity is specifically phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2).
messages: Associates with the cleavage and polyadenylation specificity factor (CPSF) complex (PubMed:21102410). Interacts with CPSF1 and CPSF3; the interaction is direct (PubMed:21102410). Interacts with PIP5K1A (PubMed:18288197).
messages: Belongs to the DNA polymerase type-B-like family.
messages: Binds 1 divalent cation per subunit.
messages: Nucleus speckle
messages: Phosphorylated by CK1 in the proline-rich (Pro-rich) region.
messages: Poly(A) polymerase that creates the 3'-poly(A) tail of specific pre-mRNAs (PubMed:18288197, PubMed:21102410). Localizes to nuclear speckles together with PIP5K1A and mediates polyadenylation of a select set of mRNAs, such as HMOX1 (PubMed:18288197). In addition to polyadenylation, it is also required for the 3'-end cleavage of pre-mRNAs: binds to the 3'UTR of targeted pre-mRNAs and promotes the recruitment and assembly of the CPSF complex on the 3'UTR of pre-mRNAs (PubMed:21102410). In addition to adenylyltransferase activity, also has uridylyltransferase activity (PubMed:16790842, PubMed:18288197, PubMed:28589955). However, the ATP ratio is higher than UTP in cells, suggesting that it functions primarily as a poly(A) polymerase (PubMed:18288197). Acts as a specific terminal uridylyltransferase for U6 snRNA in vitro: responsible for a controlled elongation reaction that results in the restoration of the four 3'-terminal UMP-residues found in newly transcribed U6 snRNA (PubMed:16790842, PubMed:18288197, PubMed:28589955). Not involved in replication-dependent histone mRNA degradation.
messages: The RRM domain is required for terminal uridylyltransferase activity (PubMed:28589955). Together with the zinc-finger domain, binds the 5'-area of U6 snRNA (PubMed:28589955).
messages: The proline-rich region is dispensable for terminal uridylyltransferase activity.
messages: The zinc-finger domain is required for terminal uridylyltransferase activity (PubMed:28589955). Together with the RRM domain, binds the 5'-area of U6 snRNA (PubMed:28589955).
messages: Widely expressed.
messages: nucleolus

9606:OBSCN
gene id: 9606:OBSCN
uniprot id: A6NGQ3
uniprot id: Q5VST9
names: Caution
names: Disease Annotation
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: A chromosomal aberration involving OBSCN has been found in Wilms tumor. Translocation t(1;7)(q42;p15) with PTHB1.
messages: Autophosphorylated by protein kinase domains 1 and 2.
messages: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry.
messages: Initially the name obscurin was used to describe isoform 3 which lacks the kinase domains.
messages: Interacts (via protein kinase domain 2) with CDH2 and (via protein kinase domain 1) with ATP1B1 (By similarity). Isoform 3 interacts with TTN/titin and calmodulin (PubMed:11448995, PubMed:11717165). Isoform 3 interacts with ANK1 isoform Mu17/ank1.5 (PubMed:12527750).
messages: Lacks the kinase domain. Initially described as obscurin.
messages: M line
messages: Nucleus
messages: Structural component of striated muscles which plays a role in myofibrillogenesis. Probably involved in the assembly of myosin into sarcomeric A bands in striated muscle (PubMed:11448995, PubMed:16205939). Has serine/threonine protein kinase activity and phosphorylates N-cadherin CDH2 and sodium/potassium-transporting ATPase subunit ATP1B1 (By similarity). Binds (via the PH domain) strongly to phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2), and to a lesser extent to phosphatidylinositol 3-phosphate (PtdIns(3)P), phosphatidylinositol 4-phosphate (PtdIns(4)P), phosphatidylinositol 5-phosphate (PtdIns(5)P) and phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) (PubMed:28826662).
messages: Z line
messages: sarcolemma

9606:POPDC2
gene id: 9606:POPDC2
uniprot id: Q9HBU9
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the popeye family.
messages: Expressed predominantly in the heart and in the skeletal muscle.
messages: Important for the maintenance of cardiac function. Plays a regulatory function in heart rate dynamics mediated, at least in part, through cAMP-binding and, probably, by increasing cell surface expression of the potassium channel KCNK2 and enhancing current density.
messages: Membrane
messages: sarcolemma

9606:SH2D3A
gene id: 9606:SH2D3A
uniprot id: Q9BRG2
names: Function
names: PTM
names: Subunit
names: Tissue Specificity
messages: Interacts with BCAR1.
messages: May play a role in JNK activation.
messages: Phosphorylated on tyrosine.
messages: Weakly expressed in placenta, fetal kidney, fetal lung, adult pancreas, adult kidney and adult lung.

9606:OR8J3
gene id: 9606:OR8J3
uniprot id: A0A126GVE3
uniprot id: Q8NGG0
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Membrane
messages: Odorant receptor.

9606:RASGRP3
gene id: 9606:RASGRP3
uniprot id: Q8IV61
names: Function
names: Similarity
messages: Belongs to the RASGRP family.
messages: Guanine nucleotide exchange factor (GEF) for Ras and Rap1.

9606:GABRG3
gene id: 9606:GABRG3
uniprot id: Q99928
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRG3 sub-subfamily.
messages: Cell membrane
messages: GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
messages: Generally pentameric. There are five types of GABA(A) receptor chains: alpha, beta, gamma, delta, and rho.
messages: May be palmitoylated.
messages: Postsynaptic cell membrane
messages: This subunit carries the benzodiazepine binding site.

9606:NFKBID
gene id: 9606:NFKBID
uniprot id: Q8NI38
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the NF-kappa-B inhibitor family.
messages: Interacts with NFKB1, RELA and RELB; in the nucleus.
messages: Nucleus
messages: Regulates the expression of IL-2, IL-6, and other cytokines through regulation on NF-kappa-B activity. Functions in the regulation of inflammatory responses. Involved in the induction of T helper 17 cells (Th17) differentiation upon recognition of antigen by T cell antigen receptor (TCR). May also regulate TCR-induced negative selection of thymocytes.

9606:TMPRSS5
gene id: 9606:TMPRSS5
uniprot id: Q9H3S3
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the peptidase S1 family.
messages: Brain-specific. Predominantly expressed in neurons, in their axons, and at the synapses of motoneurons in the spinal cord.
messages: Cell membrane
messages: Defects in TMPRSS5 may be a cause of deafness.
messages: May play a role in hearing.

9606:EFCAB6
gene id: 9606:EFCAB6
uniprot id: Q5THR3
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Binds PARK7. Part of a ternary complex containing PARK7, EFCAB6/DJBP and AR.
messages: Negatively regulates the androgen receptor by recruiting histone deacetylase complex, and protein DJ-1 antagonizes this inhibition by abrogation of this complex (PubMed:12612053). Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating (Probable).
messages: Nucleus
messages: Specifically expressed in the testis.
messages: cilium axoneme

9606:PSG2
gene id: 9606:PSG2
uniprot id: P11465
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the immunoglobulin superfamily. CEA family.
messages: Secreted

9606:ZNF846
gene id: 9606:ZNF846
uniprot id: Q147U1
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:DISP1
gene id: 9606:DISP1
uniprot id: Q96F81
names: Function
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the dispatched family.
messages: Contaminating sequence. Potential poly-A sequence.
messages: Functions in hedgehog (Hh) signaling. Regulates the release and extracellular accumulation of cholesterol-modified hedgehog proteins and is hence required for effective production of the Hh signal (By similarity). Synergizes with SCUBE2 to cause an increase in SHH secretion (PubMed:22902404).
messages: Interacts with SHH via the cholesterol anchor of the dually lipid-modified SHH (ShhNp) (PubMed:22902404).
messages: Membrane

9606:TBL1Y
gene id: 9606:TBL1Y
uniprot id: Q9BQ87
names: Disease Annotation
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the WD repeat EBI family.
messages: F-box-like protein involved in the recruitment of the ubiquitin/19S proteasome complex to nuclear receptor-regulated transcription units. Plays an essential role in transcription activation mediated by nuclear receptors. Probably acts as integral component of corepressor complexes that mediates the recruitment of the 19S proteasome complex, leading to the subsequent proteasomal degradation of transcription repressor complexes, thereby allowing cofactor exchange (By similarity).
messages: Fetal brain and prostate. Expressed in the cochlear spiral ganglion neurons, and in outer and inner hair cells (PubMed:30341416).
messages: Nucleus
messages: Probable component of the N-Cor repressor complex and some E3 ubiquitin ligase complex. Interacts with NCOR2 (PubMed:30341416).
messages: The F-box-like domain is related to the F-box domain, and apparently displays the same function as component of ubiquitin E3 ligase complexes.
messages: The disease may be caused by variants affecting the gene represented in this entry.

9606:PTPRT
gene id: 9606:PTPRT
uniprot id: A0A075B6H0
uniprot id: O14522
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the protein-tyrosine phosphatase family. Receptor class 2B subfamily.
messages: Expressed in colon, lung, heart and testis, as well as in fetal and adult brain. Not detected in muscle and peripheral blood leukocytes.
messages: May be involved in both signal transduction and cellular adhesion in the CNS.
messages: Membrane

9606:COMMD1
gene id: 9606:COMMD1
uniprot id: Q8N668
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acetylated by EP300 ina stimuli-specific manner; protecting it from XIAP-mediated proteasomal degradation and required for interaction with RElA in response to stress.
messages: Cytoplasm
messages: Cytoplasmic vesicle
messages: Early endosome
messages: Endosome membrane
messages: Monomer, homodimer. Can form heterodimers with other COMM domain-containing proteins but only certain combinations may exist in vivo (PubMed:23563313). Interacts (via COMM domain) with COMMD2, COMMD3, COMMD4, COMMD5, COMMD6, COMMD7, COMMD8 and COMMD10 (via COMM domain). Identified in a complex with an E3 ubiquitin ligase complex composed of TCEB1/elongin C, CUL2, SOCS1 and RBX1; in the complex interacts directly with SOCS1 and CUL2. Interacts directly with ATP7B (via the N-terminal region). Interacts with CCS, CDKN2A, RELA, REL, RELB, NFKB1/p105, NFKB2/p100, NFKBIB, SCNN1D, SCNN1B, CFTR, CLU, SGK1, AKT1, CUL1, CUL2, CUL3, CUL4A, CUL4B, CUL5, CUL7, HIF1A. Identified in a complex with NF-kappa-B. Interacts directly with SLC12A2. Interacts with CCDC22 and CCDC93; proposed to be a component of the CCC (COMMD/CCDC22/CCDC93) complex which contains at least COMMD1 (and possibly other COMM domain-containing proteins), CCDC22, CCDC93 (PubMed:25355947, PubMed:28892079). Interacts with VPS35L; the interaction associates CCC complex with retriever complex (PubMed:28892079, PubMed:25355947). Interacts with ATP7A (PubMed:21667063). Interacts with FAM107A; this interaction stabilizes COMMD1 in the nucleus (PubMed:28604741).
messages: Nucleus
messages: Proposed scaffold protein that is implicated in diverse physiological processes and whose function may be in part linked to its ability to regulate ubiquitination of specific cellular proteins. Can modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes by displacing CAND1; in vitro promotes CRL E3 activity and dissociates CAND1 from CUL1 and CUL2 (PubMed:21778237). Promotes ubiquitination of NF-kappa-B subunit RELA and its subsequent proteasomal degradation. Down-regulates NF-kappa-B activity (PubMed:15799966, PubMed:17183367, PubMed:20048074). Involved in the regulation of membrane expression and ubiquitination of SLC12A2 (PubMed:23515529). Modulates Na(+) transport in epithelial cells by regulation of apical cell surface expression of amiloride-sensitive sodium channel (ENaC) subunits and by promoting their ubiquitination presumably involving NEDD4L. Promotes the localization of SCNN1D to recycling endosomes (PubMed:14645214, PubMed:20237237, PubMed:21741370). Promotes CFTR cell surface expression through regulation of its ubiquitination (PubMed:21483833). Down-regulates SOD1 activity by interfering with its homodimerization (PubMed:20595380). Plays a role in copper ion homeostasis. Involved in copper-dependent ATP7A trafficking between the trans-Golgi network and vesicles in the cell periphery; the function is proposed to depend on its association within the CCC complex and cooperation with the WASH complex on early endosomes (PubMed:25355947). Can bind one copper ion per monomer (PubMed:17309234). May function to facilitate biliary copper excretion within hepatocytes. Binds to phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) (PubMed:18940794). Involved in the regulation of HIF1A-mediated transcription; competes with ARNT/Hif-1-beta for binding to HIF1A resulting in decreased DNA binding and impaired transcriptional activation by HIF-1 (PubMed:20458141). Negatively regulates neuroblastoma G1/S phase cell cycle progression and cell proliferation…
messages: Recycling endosome
messages: Ubiquitinated; undergoes both 'Lys-63'- and 'Lys-48'-linked polyubiquitination. Ubiquitinated by XIAP, leading to its proteasomal degradation.
messages: Ubiquitous. Highest expression in the liver, with lower expression in brain, lung, placenta, pancreas, small intestine, heart, skeletal muscle, kidney and placenta. Down-regulated in cancer tissues.

9606:DCC
gene id: 9606:DCC
uniprot id: P43146
names: Disease Annotation
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the immunoglobulin superfamily. DCC family.
messages: Found in axons of the central and peripheral nervous system and in differentiated cell types of the intestine. Not expressed in colorectal tumor cells that lost their capacity to differentiate into mucus producing cells.
messages: Inactivation of DCC due to allelic deletion and/or point mutations is related to lymphatic and hematogenous metastatic tumor dissemination.
messages: Interacts with the cytoplasmic part of UNC5A, UNC5B, UNC5C and probably UNC5D (By similarity). Interacts with DSCAM (By similarity). Interacts with PTK2/FAK1 and MAPK1 (By similarity). Interacts with NTN1 (By similarity). Interacts with MYO10 (PubMed:21642953). Interacts with CBLN4; this interaction can be competed by NTN1 (By similarity). Interacts with SIAH1 and SIAH2 (PubMed:9334332).
messages: Membrane
messages: Receptor for netrin required for axon guidance. Mediates axon attraction of neuronal growth cones in the developing nervous system upon ligand binding. Its association with UNC5 proteins may trigger signaling for axon repulsion. It also acts as a dependence receptor required for apoptosis induction when not associated with netrin ligand. Implicated as a tumor suppressor gene.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitinated; mediated by SIAH1 or SIAH2 and leading to its subsequent proteasomal degradation.

9606:COL4A3
gene id: 9606:COL4A3
uniprot id: Q01955
names: Disease Annotation
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Alpha 3 and alpha 4 type IV collagens are colocalized and present in kidney, eye, basement membranes of lens capsule, cochlea, lung, skeletal muscle, aorta, synaptic fibers, fetal kidney and fetal lung. PubMed:8083201 reports similar levels of expression of alpha 3 and alpha 4 type IV collagens in kidney, but PubMed:7523402 reports that in kidney levels of alpha 3 type IV collagen are significantly lower than those of alpha 4 type IV collagen. According to PubMed:8083201, alpha 3 type IV collagen is not detected in heart, brain, placenta, liver, pancreas, extrasynaptic muscle fibers, endoneurial and perineurial nerves, fetal brain, fetal heart and fetal liver. According to PubMed:7523402, alpha 3 type IV collagen is strongly expressed in pancreas, neuroretina and calvaria and not expressed in adrenal, ileum and skin. Isoform 1 and isoform 3 are strongly expressed in kidney, lung, suprarenal capsule, muscle and spleen, in each of these tissues isoform 1 is more abundant than isoform 3. Isoform 1 and isoform 3 are expressed at low levels in artery, fat, pericardium and peripherical nerve, but not in placenta, mesangium, skin, pleura and cultured umbilical endothelial cells.
messages: Alpha chains of type IV collagen have a non-collagenous domain (NC1) at their C-terminus, frequent interruptions of the G-X-Y repeats in the long central triple-helical domain (which may cause flexibility in the triple helix), and a short N-terminal triple-helical 7S domain.
messages: Autoantibodies against the NC1 domain of alpha 3(IV) are found in Goodpasture syndrome, an autoimmune disease of lung and kidney.
messages: Belongs to the type IV collagen family.
messages: Isoform 2 contains an additional N-linked glycosylation site.
messages: Phosphorylated. Thought to be phosphorylated by CERT, but CERT does not have kinase activity.
messages: Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The epitopes recognized by the Goodpasture autoantibodies are sequestered within the NC1 hexamer of the type IV collagen network.
messages: The trimeric structure of the NC1 domains is stabilized by covalent bonds between Lys and Met residues.
messages: There are six type IV collagen isoforms, alpha 1(IV)-alpha 6(IV), each of which can form a triple helix structure with 2 other chains to generate type IV collagen network. The alpha 3(IV) chain forms a triple helical protomer with alpha 4(IV) and alpha 5(IV); this triple helical structure dimerizes through NC1-NC1 domain interactions such that the alpha 3(IV), alpha 4(IV) and alpha 5(IV) chains of one protomer connect with the alpha 5(IV), alpha 4(IV) and alpha 3(IV) chains of the opposite promoter, respectively (PubMed:12193605). Interacts with ITGB3 (PubMed:12682293). Associates with LAMB2 at the neuromuscular junction and in GBM (By similarity).
messages: Tumstatin, a cleavage fragment corresponding to the collagen alpha 3(IV) NC1 domain, possesses both anti-angiogenic and anti-tumor cell activity; these two anti-tumor properties may be regulated via RGD-independent ITGB3-mediated mechanisms.
messages: Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen.
messages: Type IV collagens contain numerous cysteine residues which are involved in inter- and intramolecular disulfide bonding. 12 of these, located in the NC1 domain, are conserved in all known type IV collagens.
messages: basement membrane

9606:UQCRH
gene id: 9606:UQCRH
uniprot id: P07919
uniprot id: Q567R0
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the UQCRH/QCR6 family.
messages: Component of the ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), a multisubunit enzyme composed of 11 subunits. The complex is composed of 3 respiratory subunits cytochrome b, cytochrome c1 and Rieske protein UQCRFS1, 2 core protein subunits UQCRC1/QCR1 and UQCRC2/QCR2, and 6 low-molecular weight protein subunits UQCRH/QCR6, UQCRB/QCR7, UQCRQ/QCR8, UQCR10/QCR9, UQCR11/QCR10 and subunit 9, the cleavage product of Rieske protein UQCRFS1 (By similarity). The complex exists as an obligatory dimer and forms supercomplexes (SCs) in the inner mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and cytochrome c oxidase (complex IV, CIV), resulting in different assemblies (supercomplex SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)) (PubMed:28844695).
messages: Component of the ubiquinol-cytochrome c oxidoreductase, a multisubunit transmembrane complex that is part of the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. The cytochrome b-c1 complex catalyzes electron transfer from ubiquinol to cytochrome c, linking this redox reaction to translocation of protons across the mitochondrial inner membrane, with protons being carried across the membrane as hydrogens on the quinol. In the process called Q cycle, 2 protons are consumed from the matrix, 4 protons are released into the intermembrane space and 2 electrons are passed to cytochrome c.
messages: Mitochondrion inner membrane
messages: The disease may be caused by variants affecting the gene represented in this entry.

9606:TAF13
gene id: 9606:TAF13
uniprot id: Q15543
names: Disease Annotation
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the TAF13 family.
messages: Component of the TFIID basal transcription factor complex, composed of TATA-box-binding protein TBP, and a number of TBP-associated factors (TAFs), including TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13 (PubMed:33795473). Interacts with TBP, and more strongly with TAF10 and TAF11 (PubMed:9695952).
messages: Nucleus
messages: The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription (PubMed:33795473, PubMed:9695952). TFIID recognizes and binds promoters via its subunit TBP, a TATA-box-binding protein, and promotes assembly of the pre-initiation complex (PIC) (PubMed:33795473). The TFIID complex consists of TBP and TBP-associated factors (TAFs), including TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13 (PubMed:33795473). TAF13, together with TAF11 and TBP, play key roles during promoter binding by the TFIID and TFIIA transcription factor complexes (PubMed:33795473).
messages: The binding of TAF10 and TAF11 requires distinct domains of TAF13.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:HOXD3
gene id: 9606:HOXD3
uniprot id: P31249
names: Caution
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the Antp homeobox family.
messages: It is uncertain whether Met-1 or Met-17 is the initiator.
messages: Nucleus
messages: Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis.

9606:GADD45B
gene id: 9606:GADD45B
uniprot id: O75293
names: Function
names: Similarity
names: Subunit
messages: Belongs to the GADD45 family.
messages: Interacts with GADD45GIP1.
messages: Involved in the regulation of growth and apoptosis. Mediates activation of stress-responsive MTK1/MEKK4 MAPKKK.

9606:UGT2B28
gene id: 9606:UGT2B28
uniprot id: Q9BY64
names: Function
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Aberrant splicing.
messages: Belongs to the UDP-glycosyltransferase family.
messages: Endoplasmic reticulum membrane
messages: Expressed in the liver, breast and kidney.
messages: Lack UDP-glucuronosyltransferase (UGT) activity.
messages: UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:11300766). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:11300766). Catalyzes the glucuronidation of endogenous steroid hormones such as androgens (androsterone, 3alpha-androstanediol) and estrogens (estradiol, estrone) (PubMed:11300766). Catalyzes the glucuronidation of bile acid substrates, which are natural detergents for dietary lipids absorption (PubMed:11300766). Displays glucuronidation activity toward the phenolic compounds eugenol (PubMed:11300766).
messages: perinuclear region

9606:IMPDH1
gene id: 9606:IMPDH1
uniprot id: B3KRZ3
uniprot id: P20839
uniprot id: Q6ZNB1
names: Activity Regulation
names: Caution
names: Disease Annotation
names: Function
names: Induction
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Because IMPDH activity is tightly linked with cell proliferation, it has been recognized as a target for cancer and viral chemotherapy and as a target for immunosuppressive drugs. The activities of the antitumor drug tiazofurin, the antiviral drug ribavirin, and the immunosuppressive drugs mizoribine and mycophenolic acid (MPA) are attributed to the inhibition of IMPDH. In addition, bacterial and parasitic IMPDH's differ significantly from mammalian enzymes, which makes it a suitable target for anti-infective drugs.
messages: Belongs to the IMPDH/GMPR family.
messages: Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth. Could also have a single-stranded nucleic acid-binding activity and could play a role in RNA and/or DNA metabolism. It may also have a role in the development of malignancy and the growth progression of some tumors.
messages: Constitutively expressed.
messages: Cytoplasm
messages: Homotetramer.
messages: IMP type I is the main species in normal leukocytes and type II predominates over type I in the tumor.
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: Mycophenolic acid (MPA) is a non-competitive inhibitor that prevents formation of the closed enzyme conformation by binding to the same site as the amobile flap. In contrast, mizoribine monophosphate (MZP) is a competitive inhibitor that induces the closed conformation. MPA is a potent inhibitor of mammalian IMPDHs but a poor inhibitor of the bacterial enzymes. MZP is a more potent inhibitor of bacterial IMPDH.
messages: Mycophenolic acid (MPA) is a non-competitive inhibitor that prevents formation of the closed enzyme conformation by binding to the same site as the amobile flap. In contrast, mizoribine monophosphate (MZP) is a competitive inhibitor that induces the closed conformation. MPA is a potent inhibitor of mammalian IMPDHs but a poor inhibitor of the bacterial enzymes. MZP is a more potent inhibitor of bacterial IMPDH. Subject to product inhibition by XMP and NADH. Also inhibited by ADP.
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:PNCK
gene id: 9606:PNCK
uniprot id: Q6P2M8
names: Activity Regulation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
messages: Activated by Ca(2+)/calmodulin.
messages: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily.
messages: Calcium/calmodulin-dependent protein kinase belonging to a proposed calcium-triggered signaling cascade. In vitro phosphorylates CREB1 and SYN1/synapsin I. Phosphorylates and activates CAMK1 (By similarity).
messages: Cytoplasm
messages: Nucleus
messages: Phosphorylated by CAMKK1.

9606:ENO2
gene id: 9606:ENO2
uniprot id: P09104
uniprot id: Q6FHV6
names: Cofactor
names: Developmental Stage
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Activated by human cytomegalovirus (HCMV) UL38 in order to provide the virus with glycosyl building blocks.
messages: Belongs to the enolase family.
messages: Cell membrane
messages: Cytoplasm
messages: During ontogenesis, there is a transition from the alpha/alpha homodimer to the alpha/beta heterodimer in striated muscle cells, and to the alpha/gamma heterodimer in nerve cells.
messages: Has neurotrophic and neuroprotective properties on a broad spectrum of central nervous system (CNS) neurons. Binds, in a calcium-dependent manner, to cultured neocortical neurons and promotes cell survival (By similarity).
messages: Levels of ENO2 increase dramatically in cardiovascular accidents, cerebral trauma, brain tumors and Creutzfeldt-Jakob disease.
messages: Mammalian enolase is composed of 3 isozyme subunits, alpha, beta and gamma, which can form homodimers or heterodimers which are cell-type and development-specific.
messages: Mg(2+) is required for catalysis and for stabilizing the dimer.
messages: The alpha/alpha homodimer is expressed in embryo and in most adult tissues. The alpha/beta heterodimer and the beta/beta homodimer are found in striated muscle, and the alpha/gamma heterodimer and the gamma/gamma homodimer in neurons.

9606:FABP2
gene id: 9606:FABP2
uniprot id: P12104
names: Domain
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the calycin superfamily. Fatty-acid binding protein (FABP) family.
messages: By EGF.
messages: Cytoplasm
messages: Expressed in the small intestine and at much lower levels in the large intestine. Highest expression levels in the jejunum.
messages: FABPs are thought to play a role in the intracellular transport of long-chain fatty acids and their acyl-CoA esters. FABP2 is probably involved in triglyceride-rich lipoprotein synthesis. Binds saturated long-chain fatty acids with a high affinity, but binds with a lower affinity to unsaturated long-chain fatty acids. FABP2 may also help maintain energy homeostasis by functioning as a lipid sensor.
messages: Forms a beta-barrel structure that accommodates the hydrophobic ligand in its interior.

9606:PSMD9
gene id: 9606:PSMD9
uniprot id: O00233
names: Caution
names: Function
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Acts as a chaperone during the assembly of the 26S proteasome, specifically of the base subcomplex of the PA700/19S regulatory complex (RC). During the base subcomplex assembly is part of an intermediate PSMD9:PSMC6:PSMC3 module, also known as modulator trimer complex; PSMD9 is released during the further base assembly process.
messages: Belongs to the proteasome subunit p27 family.
messages: Expressed in all tissues tested, highly expressed in liver and kidney.
messages: Interacts with PSMC3. Part of a transient complex (modulator) containing PSMD9, PSMC6 and PSMC3 formed during the assembly of the 26S proteasome.
messages: Was initially identified as a component of the 26S proteasome.

9606:EPB41L3
gene id: 9606:EPB41L3
uniprot id: Q9Y2J2
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cell junction
messages: Cell membrane
messages: Cytoplasm
messages: Expressed at high levels in brain, with lower levels in kidney, intestine, and testis. Detected in lung.
messages: Interacts (via FERM domain) with CADM1 (PubMed:12234973, PubMed:21131357). Interacts (via FERM domain) with PRMT3; the interaction is direct and inhibits the protein-arginine N-methyltransferase activity of PRMT3 (PubMed:15334060). Interacts with PRMT5 (PubMed:15334060, PubMed:15737618). Interacts with PRMT6 (PubMed:15334060).
messages: Tumor suppressor that inhibits cell proliferation and promotes apoptosis. Modulates the activity of protein arginine N-methyltransferases, including PRMT3 and PRMT5.
messages: cytoskeleton

9606:PABIR1
gene id: 9606:PABIR1
uniprot id: B3KX07
uniprot id: Q96E09
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Acts as an inhibitor of serine/threonine-protein phosphatase 2A (PP2A) activity (PubMed:27588481, PubMed:33108758). Potentiates ubiquitin-mediated proteasomal degradation of serine/threonine-protein phosphatase 2A catalytic subunit alpha (PPP2CA) (PubMed:27588481). Inhibits PP2A-mediated dephosphorylation of WEE1, promoting ubiquitin-mediated proteolysis of WEE1, thereby releasing G2/M checkpoint (PubMed:33108758).
messages: Belongs to the FAM122 family.
messages: CHEK1-mediated phosphorylation at Ser-37 negatively regulates its ability to inhibit serine/threonine-protein phosphatase 2A (PP2A) activity. Phosphorylation leads to its release from the PP2A complex and its sequestration by 14-3-3 proteins in the cytoplasm resulting in its inability to translocate to the nucleus, where it otherwise inhibits PP2A.
messages: Cytoplasm
messages: Interacts with PPP2CA and PPP2R1A (PubMed:27588481). Interacts with PPP2R2A (PubMed:27588481, PubMed:33108758). The CHEK1-mediated Ser-37 phosphorylated form interacts with 14-3-3 proteins (PubMed:33108758).
messages: Nucleus

9606:MRGPRE
gene id: 9606:MRGPRE
uniprot id: Q86SM8
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family. Mas subfamily.
messages: Cell membrane
messages: Orphan receptor. May regulate nociceptor function and/or development, including the sensation or modulation of pain.

9606:FZD6
gene id: 9606:FZD6
uniprot id: B4DL33
uniprot id: B4E236
uniprot id: O60353
names: Caution
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Apical cell membrane
messages: Belongs to the G-protein coupled receptor Fz/Smo family.
messages: Cell membrane
messages: Cell surface
messages: Cytoplasmic vesicle membrane
messages: Detected in adult heart, brain, placenta, lung, liver, skeletal muscle, kidney, pancreas, thymus, prostate, testis, ovary, small intestine and colon. In the fetus, expressed in brain, lung, liver and kidney.
messages: Endoplasmic reticulum membrane
messages: Interacts with LMBR1L.
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: Lys-Thr-X-X-X-Trp motif interacts with the PDZ domain of Dvl (Disheveled) family members and is involved in the activation of the Wnt/beta-catenin signaling pathway.
messages: Membrane
messages: Rare non-synonymous variants in FZD6 may contribute to neural tube defects, congenital malformations of the central nervous system and adjacent structures related to defective neural tube closure during the first trimester of pregnancy.
messages: Receptor for Wnt proteins. Most of frizzled receptors are coupled to the beta-catenin canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes. A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to involve interactions with G-proteins. May be involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues. Together with FZD3, is involved in the neural tube closure and plays a role in the regulation of the establishment of planar cell polarity (PCP), particularly in the orientation of asymmetric bundles of stereocilia on the apical faces of a subset of auditory and vestibular sensory cells located in the inner ear (By similarity).
messages: The FZ domain is involved in binding with Wnt ligands.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitinated by ZNRF3, leading to its degradation by the proteasome.

9606:VAMP1
gene id: 9606:VAMP1
uniprot id: F5GZV7
uniprot id: P23763
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Targeted and hydrolyzed by C.botulinum neurotoxin type B (BoNT/B, botB) which probably hydrolyzes the 78-Gln-|-Phe-79 bond and inhibits neurotransmitter release (PubMed:22289120).
messages: (Microbial infection) Targeted and hydrolyzed by C.botulinum neurotoxin type D (BoNT/D, botD) which probably hydrolyzes the 61-Arg-|-Leu-62 bond and inhibits neurotransmitter release (PubMed:22289120). BoNT/D has low catalytic activity on this protein due to its sequence (PubMed:22289120). Note that humans are not known to be infected by C.botulinum type D.
messages: (Microbial infection) Targeted and hydrolyzed by C.botulinum neurotoxin type F (BoNT/F, botF) which probably hydrolyzes the 60-Gln-|-Lys-61 bond and inhibits neurotransmitter release (PubMed:22289120).
messages: (Microbial infection) Targeted and hydrolyzed by C.botulinum neurotoxin type X (BoNT/X) which probably hydrolyzes the 68-Arg-|-Ala-69 bond and inhibits neurotransmitter release (PubMed:29540745). It remains unknown whether BoNT/X is ever produced, or what organisms it targets.
messages: Belongs to the synaptobrevin family.
messages: Cytoplasmic vesicle membrane
messages: Interacts with VAPA and VAPB.
messages: Involved in the targeting and/or fusion of transport vesicles to their target membrane.
messages: Membrane
messages: Mitochondrion outer membrane
messages: Nervous system, skeletal muscle and adipose tissue.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The disease is caused by variants affecting the gene represented in this entry. A mutation affecting a critical donor site for the splicing of VAMP1 isoforms leads to the loss of neuron-specific isoform 1 and subsequently results in haploinsufficiency (PubMed:22958904). Therefore, there would be less neurotransmitter exocytosis in specific regions of the brain, causing the symptoms of SPAX1.
messages: synaptic vesicle membrane
messages: synaptosome

9606:ALG13
gene id: 9606:ALG13
uniprot id: A0A087WX43
uniprot id: Q9NP73
names: Disease Annotation
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the glycosyltransferase 28 family.
messages: Contains 1 OTU domain with intact active sites. No deubiquitinase activity has been detected when tested (PubMed:23827681).
messages: Endoplasmic reticulum
messages: Isoform 2 may interact with ALG14.
messages: May be involved in protein N-glycosylation, second step of the dolichol-linked oligosaccharide pathway.
messages: Possible multifunctional enzyme with both glycosyltransferase and deubiquitinase activities.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:SIN3B
gene id: 9606:SIN3B
uniprot id: O75182
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: Acts as a transcriptional repressor. Interacts with MXI1 to repress MYC responsive genes and antagonize MYC oncogenic activities. Interacts with MAD-MAX heterodimers by binding to MAD. The heterodimer then represses transcription by tethering SIN3B to DNA. Also forms a complex with FOXK1 which represses transcription. With FOXK1, regulates cell cycle progression probably by repressing cell cycle inhibitor genes expression.
messages: Interacts with FOXK1/MNF, MXI, MAD, NCOR1 and SAP30. Interaction with SUDS3 enhances the interaction with HDAC1 to form a complex. Interacts with CRY1, HCFC1, MAD3, MAD4, MAEL, REST, RNF220 and SETDB1. Interacts with C6orf89 (PubMed:23460338). Interacts with MYT1L (By similarity).
messages: Nucleus
messages: Ubiquitinated by RNF220 that leads to proteasomal degradation.

9606:SGO2
gene id: 9606:SGO2
uniprot id: B7Z7S9
uniprot id: Q562F6
names: Function
names: Miscellaneous
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the shugoshin family.
messages: Contaminating sequence. Potential poly-A sequence.
messages: Cooperates with PPP2CA to protect centromeric cohesin from separase-mediated cleavage in oocytes specifically during meiosis I. Has a crucial role in protecting REC8 at centromeres from cleavage by separase. During meiosis, protects centromeric cohesion complexes until metaphase II/anaphase II transition, preventing premature release of meiosis-specific REC8 cohesin complexes from anaphase I centromeres. Is thus essential for an accurate gametogenesis. May act by targeting PPP2CA to centromeres, thus leading to cohesin dephosphorylation (By similarity). Essential for recruiting KIF2C to the inner centromere and for correcting defective kinetochore attachments. Involved in centromeric enrichment of AUKRB in prometaphase.
messages: Directly interacts with PPP2CA. Part of an astrin (SPAG5) -kinastrin (SKAP) complex containing KNSTRN, SPAG5, PLK1, DYNLL1 and SGO2. Interacts with CDCA8.
messages: Nucleus
messages: Shugoshin is Japanese for guardian spirit (as it is known to be a protector of centromeric cohesin).
messages: centromere
messages: kinetochore

9606:TRPC3
gene id: 9606:TRPC3
uniprot id: Q13507
names: Activity Regulation
names: Disease Annotation
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Activated by diacylglycerol (DAG) in a membrane-delimited fashion, independently of protein kinase C (PubMed:9930701). Activated by inositol 1,4,5-triphosphate receptors (ITPR) with bound IP3 (PubMed:10611319). May be activated by internal calcium store depletion. Inhibited by intracellular Ca(2+) (PubMed:35051376).
messages: Belongs to the transient receptor (TC 1.A.4) family. STrpC subfamily. TRPC3 sub-subfamily.
messages: Cell membrane
messages: Expressed predominantly in brain and at much lower levels in ovary, colon, small intestine, lung, prostate, placenta and testis.
messages: Forms a receptor-activated non-selective calcium permeant cation channel (PubMed:8646775, PubMed:9417057, PubMed:9930701, PubMed:20095964, PubMed:30139744, PubMed:29726814, PubMed:35051376). May be operated by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases or G-protein coupled receptors (PubMed:8646775).
messages: Homotetramer (PubMed:29700422, PubMed:30139744, PubMed:29726814, PubMed:35051376). Interacts with ITPR1 (PubMed:9853757). Interacts with ITPR3 (PubMed:10611319). Interacts with MX1 (PubMed:15757897). Interacts with RNF24 (PubMed:17850865). Interacts with JPH2; the interaction is involved in maintaining Ca(2+) homeostasis in skeletal muscle and is mediated by JPH2 'Ser-165' phosphorylation (PubMed:20095964).
messages: Interacts with isoform short of TRPC1.
messages: The cytoplasmic portion of the protein is required for channel assembly and gating.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:RNF10
gene id: 9606:RNF10
uniprot id: A0A024RBP0
uniprot id: Q8N5U6
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the RNF10 family.
messages: Cytoplasm
messages: E3 ubiquitin-protein ligase that catalyzes monoubiquitination of 40S ribosomal proteins RPS2/us5 and RPS3/us3 in response to ribosome stalling (PubMed:34348161, PubMed:34469731). Part of a ribosome quality control that takes place when ribosomes have stalled during translation initiation (iRQC): RNF10 acts by mediating monoubiquitination of RPS2/us5 and RPS3/us3, promoting their degradation by the proteasome (PubMed:34348161, PubMed:34469731). Also promotes ubiquitination of 40S ribosomal proteins in response to ribosome stalling during translation elongation (PubMed:34348161). The action of RNF10 in iRQC is counteracted by USP10 (PubMed:34469731). May also act as a transcriptional factor involved in the regulation of MAG (Myelin-associated glycoprotein) expression (By similarity). Acts as a regulator of Schwann cell differentiation and myelination (By similarity).
messages: Interacts with MEOX2.
messages: Nucleus

9606:FKBP9
gene id: 9606:FKBP9
uniprot id: O95302
names: Activity Regulation
names: Function
names: PTM
names: Subcellular Location Annotation
messages: Endoplasmic reticulum
messages: Inhibited by FK506.
messages: PPIases accelerate the folding of proteins during protein synthesis.
messages: Phosphorylated.

9606:YIPF5
gene id: 9606:YIPF5
uniprot id: Q969M3
names: Developmental Stage
names: Disease Annotation
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the YIP1 family.
messages: By TGFB1.
messages: COPII-coated vesicle
messages: Endoplasmic reticulum membrane
messages: Expressed in developing cortex at all stages examined but most strikingly at 12 gestational weeks. Expression is found in both progenitor (ventricular zone) and neuronal (intermediate zone and cortical plate) compartments. Also selectively expressed within the choroid plexus within the cerebral ventricles.
messages: Interacts with the COPII coat components Sec23 (SEC23A and/or SEC23B) and Sec24 (SEC24A and/or SEC24B) (PubMed:11489904). Interacts with YIF1A (PubMed:15990086). May interact with RAB1A (PubMed:15611160). Interacts with YIPF3 and YIPF4 (PubMed:27999994).
messages: Plays a role in transport between endoplasmic reticulum and Golgi. In pancreatic beta cells, required to transport proinsulin from endoplasmic reticulum into the Golgi (PubMed:33164986).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitously expressed with abundant expression in pancreatic tissue, islets, beta cells, and brain. Highly expressed in coronary smooth muscles.
messages: cis-Golgi network membrane

9606:ZNF792
gene id: 9606:ZNF792
uniprot id: Q3KQV3
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:DNAAF2
gene id: 9606:DNAAF2
uniprot id: Q9NVR5
names: Disease Annotation
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the PIH1 family. Kintoun subfamily.
messages: Cytoplasm
messages: Dynein axonemal particle
messages: Interacts with CFAP300 (PubMed:29727693). Interacts with DNAAF4 (PubMed:23872636). Interacts with DNAAF6/PIH1D3 (PubMed:28041644). Interacts with DNAI2 and HSPA1A (By similarity).
messages: May be due to exon skipping.
messages: Required for cytoplasmic pre-assembly of axonemal dyneins, thereby playing a central role in motility in cilia and flagella. Involved in pre-assembly of dynein arm complexes in the cytoplasm before intraflagellar transport loads them for the ciliary compartment.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:PFAS
gene id: 9606:PFAS
uniprot id: A8K9T9
uniprot id: O15067
uniprot id: Q6P4B4
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Cytoplasm
messages: In the N-terminal section; belongs to the FGAMS family.
messages: Phosphoribosylformylglycinamidine synthase involved in the purines biosynthetic pathway. Catalyzes the ATP-dependent conversion of formylglycinamide ribonucleotide (FGAR) and glutamine to yield formylglycinamidine ribonucleotide (FGAM) and glutamate.

9606:ICAM1
gene id: 9606:ICAM1
uniprot id: A0A384MEK5
uniprot id: P05362
names: Function
names: PTM
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Acts as a receptor for Coxsackievirus A21 capsid proteins.
messages: (Microbial infection) Acts as a receptor for major receptor group rhinovirus A-B capsid proteins.
messages: (Microbial infection) Interacts with Coxsackievirus A21 capsid proteins (PubMed:11160747, PubMed:16004874, PubMed:9539703).
messages: (Microbial infection) Interacts with major receptor group rhinovirus A-B capsid proteins (PubMed:1968231, PubMed:2538243).
messages: (Microbial infection) Upon Kaposi's sarcoma-associated herpesvirus/HHV-8 infection, is degraded by viral E3 ubiquitin ligase MIR2, presumably to prevent lysis of infected cells by cytotoxic T-lymphocytes and NK cell.
messages: Belongs to the immunoglobulin superfamily. ICAM family.
messages: Homodimer (Probable). Interacts with MUC1 and promotes cell aggregation in epithelial cells. Interacts with ARHGEF26/SGEF. Interacts (on T cell side) with CD81, CD247 and CD9 at immunological synapses between antigen-presenting cells and T cells.
messages: Homozygotes with ICAM1-Kalifi Met-56 seem to have an increased risk for cerebral malaria [MIM:611162].
messages: ICAM proteins are ligands for the leukocyte adhesion protein LFA-1 (integrin alpha-L/beta-2). During leukocyte trans-endothelial migration, ICAM1 engagement promotes the assembly of endothelial apical cups through ARHGEF26/SGEF and RHOG activation.
messages: Membrane
messages: Monoubiquitinated, which is promoted by MARCH9 and leads to endocytosis.

9606:OR4Q3
gene id: 9606:OR4Q3
uniprot id: A0A126GW32
uniprot id: Q8NH05
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Membrane
messages: Odorant receptor.

9606:DNM1
gene id: 9606:DNM1
uniprot id: B4DK06
uniprot id: B7ZAC0
uniprot id: Q05193
names: Disease Annotation
names: Function
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the TRAFAC class dynamin-like GTPase superfamily. Dynamin/Fzo/YdjA family.
messages: Cytoplasm
messages: Interacts with CAV1 and SH3GLB1. Binds SH3GL1, SH3GL2 and SH3GL3 (By similarity). Interacts with PHOCN. Interacts with PACSIN1, PACSIN2 and PACSIN3 (By similarity). Interacts with SNX9. Interacts with MYO1E (via SH3 domain). Interacts with SNX33 (via SH3 domain). Interacts with UNC119; leading to a decrease of DNM1 GTPase activity (By similarity). Interacts with DIAPH1 (PubMed:23325789). Interacts with AMPH, BIN1 and SYNJ1 (By similarity).
messages: Microtubule-associated force-producing protein involved in producing microtubule bundles and able to bind and hydrolyze GTP. Most probably involved in vesicular trafficking processes. Involved in receptor-mediated endocytosis.
messages: Probable cloning artifact.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: cytoskeleton

9606:FAM174A
gene id: 9606:FAM174A
uniprot id: Q8TBP5
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the FAM174 family.
messages: Membrane

9606:RHOH
gene id: 9606:RHOH
uniprot id: Q15669
names: Disease Annotation
names: Domain
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: A chromosomal aberration involving RHOH is found in a non-Hodgkin lymphoma cell line. Translocation t(3;4)(q27;p11) with BCL6.
messages: Belongs to the small GTPase superfamily. Rho family.
messages: By CSF2/GM-CSF. Down-regulated by phorbol myristate acetate (PMA).
messages: Cell membrane
messages: Cytoplasm
messages: Expressed only in hematopoietic cells. Present at very high levels in the thymus, less abundant in the spleen, and least abundant in the bone marrow. Expressed at a higher level in the TH1 subtype of T-helper cells than in the TH2 subpopulation. Expressed in neutrophils under inflammatory conditions, such as cystic fibrosis, ulcerative colitis and appendicitis.
messages: Interacts with ZAP70 (via SH2 domains) and the interaction is enhanced by its phosphorylation by LCK. Interacts with SYK and the interaction is enhanced by its phosphorylation by FYN (By similarity). Interacts with GDI1 and GDI2. Interacts with PAK5 (By similarity).
messages: Negative regulator of hematopoietic progenitor cell proliferation, survival and migration. Critical regulator of thymocyte development and T-cell antigen receptor (TCR) signaling by mediating recruitment and activation of ZAP70. Required for phosphorylation of CD3Z, membrane translocation of ZAP70 and subsequent activation of the ZAP70-mediated pathways. Essential for efficient beta-selection and positive selection by promoting the ZAP70-dependent phosphorylation of the LAT signalosome during pre-TCR and TCR signaling. Crucial for thymocyte maturation during DN3 to DN4 transition and during positive selection. Plays critical roles in mast cell function by facilitating phosphorylation of SYK in Fc epsilon RI-mediated signal transduction. Essential for the phosphorylation of LAT, LCP2, PLCG1 and PLCG2 and for Ca(2+) mobilization in mast cells (By similarity). Binds GTP but lacks intrinsic GTPase activity and is resistant to Rho-specific GTPase-activating proteins. Inhibits the activation of NF-kappa-B by TNF and IKKB and the activation of CRK/p38 by TNF. Inhibits activities of RAC1, RHOA and CDC42. Negatively regulates leukotriene production in neutrophils.
messages: Phosphorylated on tyrosine by LCK. Phosphorylated by FYN. Phosphorylation enhances the interactions with ZAP70 and SYK and is critical for its function in thymocyte development (By similarity).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The region involved in interaction with ZAP70 is a non-canonical immunoreceptor tyrosine-based activation motif (ITAM).

9606:PRSS56
gene id: 9606:PRSS56
uniprot id: P0CW18
names: Disease Annotation
names: Function
names: Similarity
names: Tissue Specificity
messages: Belongs to the peptidase S1 family.
messages: Expressed neural retina, cornea, sclera and optic nerve.
messages: Serine protease required during eye development.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:USH1G
gene id: 9606:USH1G
uniprot id: Q495M9
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cajal body
messages: Cell membrane
messages: Expressed in vestibule of the inner ear, eye and small intestine.
messages: Nucleus speckle
messages: Part of a complex composed of USH1C, USH1G and MYO7A (PubMed:21709241, PubMed:21311020). Interacts with USH1C (via the first PDZ domain) (PubMed:20142502, PubMed:12588794). Interacts with PDZD7 (PubMed:19028668). Interacts with CDH23 and PCDH15; these interactions may recruit USH1G to the plasma membrane (By similarity). Interacts with intraflagellar transport proteins IFT20, IFT52 and IFT57 (PubMed:31637240). Interacts with splicing factors SF3B1, PRPF6, PRPF31 and SON (PubMed:34023904). Interacts with the U4/U6.U5 tri-small nuclear ribonucleoprotein (tri-snRNP) complex in the presence of pre-mRNAs (PubMed:34023904). Interacts (via SAM domain) with MAGI2 (via PDZ 6 domain); the interaction is triggered by phosphorylation of USH1G by CK2 and negatively regulates MAGI2-mediated endocytosis (PubMed:24608321).
messages: Photoreceptor inner segment
messages: Plays a role in pre-mRNA splicing by regulating the release and transfer of U4/U6.U5 tri-small nuclear ribonucleoprotein (tri-snRNP) complexes from their assembly site in Cajal bodies to nuclear speckles, thereby contributing to the assembly of the pre-catalytic spliceosome on target pre-mRNAs (PubMed:34023904). May also participate in recycling of snRNPs back to Cajal bodies during splicing (PubMed:34023904). Plays a role in regulating MAGI2-mediated endocytosis (PubMed:24608321). Anchoring/scaffolding protein that is a part of the functional network formed by USH1C, USH1G, CDH23 and MYO7A that mediates mechanotransduction in cochlear hair cells. Required for normal development and maintenance of cochlear hair cell bundles. Required for normal hearing.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The first cases with non-syndromic sensorineural hearing loss based on mutations in USH1G. The hearing loss has an onset during early childhood, is progressive, and has a downsloping audiogram configuration. Ophthalmic and vestibular abnormalities are absent.
messages: centrosome
messages: cilium
messages: cytoskeleton
messages: cytosol

9606:MS4A13
gene id: 9606:MS4A13
uniprot id: Q5J8X5
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the MS4A family.
messages: May be involved in signal transduction as a component of a multimeric receptor complex.
messages: Membrane

9606:BCL6B
gene id: 9606:BCL6B
uniprot id: Q8N143
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acts as a sequence-specific transcriptional repressor in association with BCL6. May function in a narrow stage or be related to some events in the early B-cell development.
messages: Associates with BCL6 through the BTB domain.
messages: Nucleus
messages: Ubiquitously expressed with higher expression found in heart and placenta.

9606:PCDHB15
gene id: 9606:PCDHB15
uniprot id: Q9Y5E8
names: Function
names: Subcellular Location Annotation
messages: Cell membrane
messages: Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain.

9606:NNT
gene id: 9606:NNT
uniprot id: E9PCX7
uniprot id: Q13423
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Homodimer.
messages: In the C-terminal section; belongs to the PNT beta subunit family.
messages: In the N-terminal section; belongs to the AlaDH/PNT family.
messages: Mitochondrion inner membrane
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The transhydrogenation between NADH and NADP is coupled to respiration and ATP hydrolysis and functions as a proton pump across the membrane (By similarity). May play a role in reactive oxygen species (ROS) detoxification in the adrenal gland (PubMed:22634753).
messages: Widely expressed with expression most readily detectable in adrenal, heart, kidney, thyroid and adipose tissues.

9606:LMF2
gene id: 9606:LMF2
uniprot id: Q9BU23
names: Function
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the lipase maturation factor family.
messages: Chimeric cDNA.
messages: Endoplasmic reticulum membrane
messages: Involved in the maturation of specific proteins in the endoplasmic reticulum. May be required for maturation and transport of active lipoprotein lipase (LPL) through the secretory pathway (By similarity).

9606:ZNF883
gene id: 9606:ZNF883
uniprot id: P0CG24
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:SKIC3
gene id: 9606:SKIC3
uniprot id: Q6PGP7
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the SKI3 family.
messages: Component of the SKI complex which consists of SKIC2, SKIC3 and SKIC8 (PubMed:16024656, PubMed:32006463, PubMed:35120588). Interacts with PAF1 (PubMed:16024656).
messages: Component of the SKI complex, a multiprotein complex that assists the RNA-degrading exosome during the mRNA decay and quality-control pathways (PubMed:16024656, PubMed:32006463, PubMed:35120588). The SKI complex catalyzes mRNA extraction from 80S ribosomal complexes in the 3'-5' direction and channels mRNA to the cytosolic exosome for degradation (PubMed:32006463, PubMed:35120588). SKI-mediated extraction of mRNA from stalled ribosomes allow binding of the Pelota-HBS1L complex and subsequent ribosome disassembly by ABCE1 for ribosome recycling (PubMed:32006463). In the nucleus, the SKI complex associates with transcriptionally active genes in a manner dependent on PAF1 complex (PAF1C) (PubMed:16024656).
messages: Cytoplasm
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Widely expressed with the highest levels observed in vascular tissues, lymph node, pituitary, lung and intestine. Not expressed in the liver.

9606:NDUFA3
gene id: 9606:NDUFA3
uniprot id: O95167
uniprot id: Q6FGG4
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone.
messages: Belongs to the complex I NDUFA3 subunit family.
messages: Complex I is composed of 45 different subunits.
messages: Membrane
messages: Mitochondrion inner membrane

9606:BOK
gene id: 9606:BOK
uniprot id: A0A024R4A8
uniprot id: Q9UMX3
names: Developmental Stage
names: Domain
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Apoptosis regulator that functions through different apoptotic signaling pathways (PubMed:27076518, PubMed:15102863, PubMed:20673843). Plays a roles as pro-apoptotic protein that positively regulates intrinsic apoptotic process in a BAX- and BAK1-dependent manner or in a BAX- and BAK1-independent manner (PubMed:27076518, PubMed:15102863). In response to endoplasmic reticulum stress promotes mitochondrial apoptosis through downstream BAX/BAK1 activation and positive regulation of PERK-mediated unfolded protein response (By similarity). Activates apoptosis independently of heterodimerization with survival-promoting BCL2 and BCL2L1 through induction of mitochondrial outer membrane permeabilization, in a BAX- and BAK1-independent manner, in response to inhibition of ERAD-proteasome degradation system, resulting in cytochrome c release (PubMed:27076518). In response to DNA damage, mediates intrinsic apoptotic process in a TP53-dependent manner (PubMed:15102863). Plays a role in granulosa cell apoptosis by CASP3 activation (PubMed:20673843). Plays a roles as anti-apoptotic protein during neuronal apoptotic process, by negatively regulating poly ADP-ribose polymerase-dependent cell death through regulation of neuronal calcium homeostasis and mitochondrial bioenergetics in response to NMDA excitation (By similarity). In addition to its role in apoptosis, may regulate trophoblast cell proliferation during the early stages of placental development, by acting on G1/S transition through regulation of CCNE1 expression (PubMed:19942931). May also play a role as an inducer of autophagy by disrupting interaction between MCL1 and BECN1 (PubMed:24113155).
messages: BH4 domain mediates interaction with ITPR1.
messages: Belongs to the Bcl-2 family.
messages: Cytoplasm
messages: Early endosome membrane
messages: Endoplasmic reticulum
messages: Endoplasmic reticulum membrane
messages: Expressed mainly in oocytes; weak expression in granulosa cells of the developing follicles. In adult human ovaries, expressed in granulosa cells at all follicular stages, but expression in primordial/primary follicles granulosa cell is stronger than in secondary and antral follicles.
messages: Isoform 1: at 5-7 weeks of gestation, detected primarily in the cytotrophoblast layer. By 10-13 weeks, expression becomes restricted primarily to the apical border of the syncytiotrophoblast (PubMed:19942931). Isoform 2: expression significantly increased around 6-8 weeks (PubMed:15775999).
messages: Membrane
messages: Mitochondrion
messages: Mitochondrion inner membrane
messages: Mitochondrion membrane
messages: Mitochondrion outer membrane
messages: Monomer; positively regulates apoptotic process. Homodimer (By similarity). Heterodimer (By similarity). Oligomer; promoted by apoptotic stimuli and BH3-only proteins; mediates constitutive activation (PubMed:15868100). Interacts (via BH4 domain) with ITPR1; enhances BOK expression and stabilization; limits apoptosis and prevents ubiquitination and then degradation; protects ITPR1 from proteolysis by CASP3 during apoptosis (PubMed:23884412). Interacts with ITPR2 and ITPR3; binds most strongly to ITPR2, and barely to ITPR3; regulates their expression (By similarity). Interacts with XPO1; translocates to the cytoplasm (PubMed:16302269). Interacts with BNIP3; promotes oligomerization (PubMed:15868100).
messages: Nucleus
messages: Nucleus outer membrane
messages: Pro-apoptotic molecule exerting its function through the mitochondrial pathway.
messages: Recycling endosome membrane
messages: Ubiquitinated by AMFR/gp78 E3 ubiquitin ligase complex; mediates degradation by ubiquitin-proteasome pathway in a VCP/p97-dependent manner; prevents from pro-apoptotic activity; promotes degradation of newly synthesized proteins that are not ITPR1 associated.
messages: Up-regulated by DNA damage.
messages: cis-Golgi network membrane
messages: trans-Golgi network membrane

9606:SLC30A2
gene id: 9606:SLC30A2
uniprot id: Q9BRI3
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the cation diffusion facilitator (CDF) transporter (TC 2.A.4) family. SLC30A subfamily.
messages: Cell membrane
messages: Electroneutral proton-coupled antiporter concentrating zinc ions into a variety of intracellular organelles including endosomes, zymogen granules and mitochondria. Thereby, plays a crucial role in cellular zinc homeostasis to confer upon cells protection against its potential cytotoxicity (PubMed:21289295, PubMed:25808614, PubMed:25657003, PubMed:30893306, PubMed:17065149, PubMed:22733820). Regulates the zinc concentration of milk, through the transport of zinc ions into secretory vesicles of mammary cells (PubMed:19496757). By concentrating zinc ions into lysosomes participates to lysosomal-mediated cell death during early mammary gland involution (PubMed:25808614).
messages: Electroneutral proton-coupled antiporter mediating the efflux of zinc ions through the plasma membrane.
messages: Endosome membrane
messages: Homodimer (PubMed:22733820). Interacts (via lysosomal targeting motif) with AP3D1; in AP-3-mediated transport to lysosomes (PubMed:25808614). Interacts with TMEM163 (PubMed:36204728).
messages: Lysosome membrane
messages: Mitochondrion inner membrane
messages: Phosphorylated at Ser-296. Phosphorylation at Ser-296 prevents localization to lysosomes. Dephosphorylation of Ser-296 which triggers localization to lysosomes, accumulation of zinc into lysosomes and lysosomal-mediated cell death is induced by TNF-alpha.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Zymogen granule membrane
messages: secretory vesicle membrane

9606:ALDOC
gene id: 9606:ALDOC
uniprot id: A0A024QZ64
uniprot id: P09972
names: Miscellaneous
names: Similarity
names: Subunit
messages: Belongs to the class I fructose-bisphosphate aldolase family.
messages: Homotetramer. Interacts with ATP6V1E1. May interact with PLD2.
messages: In vertebrates, three forms of this ubiquitous glycolytic enzyme are found, aldolase A in muscle, aldolase B in liver and aldolase C in brain.

9606:IFNA6
gene id: 9606:IFNA6
uniprot id: A0A7R8C308
uniprot id: P05013
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the alpha/beta interferon family.
messages: Produced by macrophages, IFN-alpha have antiviral activities. Interferon stimulates the production of two enzymes: a protein kinase and an oligoadenylate synthetase.
messages: Secreted

9606:WNT8B
gene id: 9606:WNT8B
uniprot id: A0A384NKY7
uniprot id: Q93098
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the Wnt family.
messages: Expression is restricted to the brain, and more specifically to the forebrain.
messages: Ligand for members of the frizzled family of seven transmembrane receptors.
messages: Ligand for members of the frizzled family of seven transmembrane receptors. May play an important role in the development and differentiation of certain forebrain structures, notably the hippocampus.
messages: Palmitoleoylation is required for efficient binding to frizzled receptors (By similarity). Depalmitoleoylation leads to Wnt signaling pathway inhibition (By similarity).
messages: Proteolytic processing by TIKI1 and TIKI2 promotes oxidation and formation of large disulfide-bond oligomers, leading to inactivation of WNT8B.
messages: extracellular matrix

9606:CD5
gene id: 9606:CD5
uniprot id: P06127
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: Cell membrane
messages: Interacts with CD72/LYB-2. Interacts with PTPN6/SHP-1 (By similarity).
messages: May act as a receptor in regulating T-cell proliferation.
messages: Phosphorylated on tyrosine residues by LYN; this creates binding sites for PTPN6/SHP-1.

9606:EBLN1
gene id: 9606:EBLN1
uniprot id: P0CF75
names: Function
names: Miscellaneous
names: Tissue Specificity
messages: Bornavirus is a non-retroviral RNA virus that does not generate DNA forms during viral replication. Therefore, integration of EBLN-1 must have occur through a mechanism relying on an endogenous reverse transcriptase activity.
messages: Expression detected by RT-PCR in a few cell lines, including OL, HEK293T and MOLT-4. Not observed in HeLa cells (PubMed:20054395).
messages: May act as an RNA-binding protein. Highly homologous to the bornavirus nucleocapsid N protein that binds viral RNA and oligomerizes (By similarity).

9606:SPRTN
gene id: 9606:SPRTN
uniprot id: Q9H040
names: Activity Regulation
names: Developmental Stage
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Acetylated following deubiquitination by VCPIP1, leading to recruitment to chromatin and DNA damage sites.
messages: Autocatalytically cleaved in response to double-stranded DNA-binding: autocatalytic cleavage takes place in trans and leads to inactivation.
messages: Belongs to the Spartan family.
messages: Chromosome
messages: DNA-binding activates the protease activity: single-stranded DNA-binding specifically activates ability to cleave covalent DNA-protein cross-links (DPCs) (PubMed:27871366, PubMed:27871365, PubMed:30893605). In contrast, double-stranded DNA-binding specifically activates autocatalytic cleavage, and subsequent inactivation (PubMed:27852435, PubMed:27871365, PubMed:30893605).
messages: DNA-dependent metalloendopeptidase that mediates the proteolytic cleavage of covalent DNA-protein cross-links (DPCs) during DNA synthesis, thereby playing a key role in maintaining genomic integrity (PubMed:27852435, PubMed:27871366, PubMed:27871365, PubMed:32649882, PubMed:30893605). DPCs are highly toxic DNA lesions that interfere with essential chromatin transactions, such as replication and transcription, and which are induced by reactive agents, such as UV light or formaldehyde (PubMed:27852435, PubMed:27871366, PubMed:27871365, PubMed:32649882). Associates with the DNA replication machinery and specifically removes DPCs during DNA synthesis (PubMed:27852435, PubMed:27871366, PubMed:27871365, PubMed:32649882). Acts as a pleiotropic protease for DNA-binding proteins cross-linked with DNA, such as TOP1, TOP2A, histones H3 and H4 (PubMed:27871366). Mediates degradation of DPCs that are not ubiquitinated, while it is not able to degrade ubiquitinated DPCs (By similarity). SPRTN activation requires polymerase collision with DPCs followed by helicase bypass of DPCs (By similarity). Involved in recruitment of VCP/p97 to sites of DNA damage (PubMed:22902628, PubMed:23042605, PubMed:23042607, PubMed:32152270). Also acts as an activator of CHEK1 during normal DNA replication by mediating proteolytic cleavage of CHEK1, thereby promoting CHEK1 removal from chromatin and subsequent activation (PubMed:31316063). Does not activate CHEK1 in response to DNA damage (PubMed:31316063). May also act as a 'reader' of ubiquitinated PCNA: recruited to sites of UV damage and interacts with ubiquitinated PCNA and RAD18, the E3 ubiquitin ligase that monoubiquitinates PCNA (PubMed:22681887, PubMed:22894931, PubMed:22902628, PubMed:22987070). Facilitates chromatin association of RAD18 and is required for efficient PCNA monoubiquitination, promoting a feed-forward loop to enhance PCNA ubiquitination and translesion DNA synthesis (PubMed:22681887).
messages: Homodimer (PubMed:30893605). Interacts (VIA PIP-box) with PCNA (when ubiquitinated) (PubMed:22894931, PubMed:22902628, PubMed:22681887, PubMed:23042605, PubMed:23042607, PubMed:22987070, PubMed:27084448). Interacts (via its SHP-box) with VCP/p97 (PubMed:22902628, PubMed:23042605, PubMed:23042607). Interacts with RAD18 (PubMed:22681887). Interacts with KCTD13 and POLD3 (PubMed:22902628).
messages: Monoubiquitinated; monoubiquitination promotes exclusion from chromatin (PubMed:27871365, PubMed:32649882). Deubiquitinated by VCPIP1: deubiquitination is required for subsequent acetylation and recruitment to chromatin and DNA damage sites (PubMed:27871365, PubMed:32649882).
messages: Nucleus
messages: Phosphorylation by CHEK1 promotes recruitment to chromatin.
messages: Predominantly expressed during S- and G2-phases and early M-phase (PubMed:23042605). It then drops, and is probably degraded by the APC/C complex (PubMed:23042605).
messages: The PIP-box mediates the interaction with PCNA, while the UBZ4-type zinc finger mediates binding to 'Lys-48'- and 'Lys-63'-linked polyubiquitin.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:KIF1A
gene id: 9606:KIF1A
uniprot id: A0A3B3IT28
uniprot id: A0A3B3ITE5
uniprot id: A0A3B3IU40
uniprot id: Q12756
names: Disease Annotation
names: Function
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family.
messages: Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. Unc-104 subfamily.
messages: Expressed in neurons.
messages: KIF1A dysfunction is associated with a large spectrum of neurologic disorders, including HSN2C, SPG30 and NESCAVS. It has been proposed to collectively name them KIF1A-Associated Neurological Disorder (KAND). Some variants reported here are based on this broad classification.
messages: Monomer. Interacts with PPFIA1 and PPFIA4 (By similarity). Interacts with CALM1; the interaction is increased in presence of calcium and increases neuronal dense core vesicles motility (PubMed:30021165). Interacts with PPFIA2 and TANC2; both interactions allow the recruitment of neuronal dense core vesicles to dendritic spines and decrease in presence of calcium (PubMed:30021165). Interacts with SYT4 (unphosphorylated) and SYT11; both interactions increase in presence of calcium (By similarity). Interacts with MADD (By similarity).
messages: Motor for anterograde axonal transport of synaptic vesicle precursors (PubMed:33880452). Also required for neuronal dense core vesicles (DCVs) transport to the dendritic spines and axons. The interaction calcium-dependent with CALM1 increases vesicle motility and interaction with the scaffolding proteins PPFIA2 and TANC2 recruits DCVs to synaptic sites.
messages: Probable cloning artifact leading to C-terminal exon with non-canonical splice junction.
messages: Synapse
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: axon
messages: cytoskeleton
messages: neuron projection
messages: neuronal dense core vesicle membrane
messages: perinuclear region

9606:WDFY3
gene id: 9606:WDFY3
uniprot id: Q8IZQ1
names: Disease Annotation
names: Domain
names: Function
names: Sequence Caution
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Aberrant splicing.
messages: Directly interacts with ATG5 and associates with the ATG12-ATG5-ATG16L complex (PubMed:20417604). Interacts with p62/SQSTM1; this interaction is required to recruit WDFY3 to cytoplasmic bodies and to PML bodies (PubMed:20168092, PubMed:20971078). Directly interacts with GABARAP, GABARAPL1 and GABARAPL2; the interaction with GABARAP is required for WDFY3 recruitment to MAP1LC3B-positive p62/SQSTM1 bodies. Weakly interacts with MAP1LC3C; this interaction is direct. Does not interact with MAP1LC3A, nor MAP1LC3B (PubMed:24668264). Interacts with TRAF6 (By similarity).
messages: Expressed in osteoclast and their mononuclear precursors (at protein level).
messages: Membrane
messages: Nucleus membrane
messages: PML body
messages: Perikaryon
messages: Required for selective macroautophagy (aggrephagy). Acts as an adapter protein by linking specific proteins destined for degradation to the core autophagic machinery members, such as the ATG5-ATG12-ATG16L E3-like ligase, SQSTM1 and LC3 (PubMed:20417604). Along with p62/SQSTM1, involved in the formation and autophagic degradation of cytoplasmic ubiquitin-containing inclusions (p62 bodies, ALIS/aggresome-like induced structures). Along with SQSTM1, required to recruit ubiquitinated proteins to PML bodies in the nucleus (PubMed:20168092). Important for normal brain development. Essential for the formation of axonal tracts throughout the brain and spinal cord, including the formation of the major forebrain commissures. Involved in the ability of neural cells to respond to guidance cues. Required for cortical neurons to respond to the trophic effects of netrin-1/NTN1 (By similarity). Regulates Wnt signaling through the removal of DVL3 aggregates, likely in an autophagy-dependent manner. This process may be important for the determination of brain size during embryonic development (PubMed:27008544). May regulate osteoclastogenesis by acting on the TNFSF11/RANKL - TRAF6 pathway (By similarity). After cytokinetic abscission, involved in midbody remnant degradation (PubMed:24128730). In vitro strongly binds to phosphatidylinositol 3-phosphate (PtdIns3P) (PubMed:15292400).
messages: The FYVE domain mediates binding to phosphatidylinositol 3-phosphate (PtdIns3P).
messages: The LIR (LC3-interacting region) motif mediates the interaction with MAP1LC3C and other ATG8 family members.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: axon
messages: cytosol

9606:SAMD9L
gene id: 9606:SAMD9L
uniprot id: Q8IVG5
names: Disease Annotation
names: Function
names: Miscellaneous
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Dubious isoform produced through aberrant splice sites.
messages: Early endosome
messages: Interacts with EEA1.
messages: May be involved in endosome fusion. Mediates down-regulation of growth factor signaling via internalization of growth factor receptors.
messages: Mitochondrion
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The disease is caused by variants affecting the gene represented in this entry. Germline variants in SAMD9L with a suppressive effect on the cell cycle are associated with somatic loss of the chromosome 7 harboring the mutant allele. This results in the deletion of several genes and predisposes to the development of myelodysplastic syndrome and acute myelogenous leukemia.
messages: Widely expressed in adult and fetal tissues. Expressed in the cerebellum (PubMed:35310830). Variable expression in tumors. Down-regulated in breast cancer.

9606:SLC43A1
gene id: 9606:SLC43A1
uniprot id: O75387
names: Developmental Stage
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Apical cell membrane
messages: Belongs to the SLC43A transporter (TC 2.A.1.44) family.
messages: Cell membrane
messages: Endoplasmic reticulum membrane
messages: Highly expressed in the capillary loop stage and very faintly in the S-shaped body stage of glomerulus in fetal kidney of 16 weeks of gestation.
messages: Ubiquitously expressed in fetus and adult (PubMed:9722952). Highest expression in adult pancreas, liver, skeletal muscle (PubMed:9722952, PubMed:12930836). In fetus, highest expression in liver and lower levels in kidney, and lung (PubMed:12930836). Exclusively expressed in the glomeruli along the glomerular capillary walls (PubMed:19443642).
messages: Uniport that mediates the transport of neutral amino acids such as L-leucine, L-isoleucine, L-valine, and L-phenylalanine (PubMed:12930836). The transport activity is sodium ions-independent, electroneutral and mediated by a facilitated diffusion (PubMed:12930836).

9606:ARSD
gene id: 9606:ARSD
uniprot id: A0A140VK06
uniprot id: P51689
names: Cofactor
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the sulfatase family.
messages: Binds 1 Ca(2+) ion per subunit.
messages: Expressed in the pancreas, kidney, liver, lung, placenta, brain and heart.
messages: Lysosome
messages: The conversion to 3-oxoalanine (also known as C-formylglycine, FGly), of a serine or cysteine residue in prokaryotes and of a cysteine residue in eukaryotes, is critical for catalytic activity.

9606:OR7G1
gene id: 9606:OR7G1
uniprot id: A0A126GVS6
uniprot id: Q8NGA0
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Membrane
messages: Odorant receptor.

9606:NHERF4
gene id: 9606:NHERF4
uniprot id: Q86UT5
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acts as a regulatory protein that associates with GUCY2C and negatively modulates its heat-stable enterotoxin-mediated activation (PubMed:11950846). Stimulates SLC9A3 activity in the presence of elevated calcium ions (PubMed:19088451).
messages: Cell membrane
messages: Cytoplasm
messages: Expressed in kidney and the gastrointestinal tract. Not detected in brain, heart, skeletal muscle or cells of hematopoietic origin.
messages: Interacts with the C-terminal region of GUCY2C (PubMed:11950846). Interacts with the C-terminal region SLC9A3 and the interactions decrease in response to elevated calcium ion levels (PubMed:19088451). Interacts with the C-terminal region of SLC34A1 (By similarity). Interacts with USP2 isoform 4 (PubMed:26756164). Interacts (via the third PDZ domain) with SLC26A3 (via PDZ-binding motif); interaction leads to decreased expression of SLC26A3 on the cell membrane resulting in its reduced exchanger activity (PubMed:22627094).
messages: Phosphorylation at Ser-395 negatively regulates its interaction with SLC26A3.

9606:NEXMIF
gene id: 9606:NEXMIF
uniprot id: Q5QGS0
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Cytoplasm
messages: Highly expressed in fetal and adult brain, predominantly in the cerebral cortex and the cerebellum. Also expressed in other tissues but to a lesser extent.
messages: Involved in neurite outgrowth by regulating cell-cell adhesion via the N-cadherin signaling pathway. May act by regulating expression of protein-coding genes, such as N-cadherins and integrin beta-1 (ITGB1).
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry. A chromosomal aberration involving NEXMIF is found in patients with severe intellectual disability. Pericentric inversion inv(X)(p22.3;q13.2) with P2RY8 leading to inactivation of NEXMIF (PubMed:15466006). XLID98 transmission pattern is consistent with X-linked recessive inheritance (PubMed:23615299). In some cases, de novo heterozygous loss-of-function mutations have been found in affected females, while some female carriers are asymptomatic (PubMed:26576034, PubMed:27358180, PubMed:27568816). The female phenotype partially overlaps with the reported male phenotype but includes epilepsy as a relevant feature. The variability of disease manifestation in female carriers is probably due to skewed X inactivation with differential expression in the brain (PubMed:26576034, PubMed:27358180, PubMed:27568816).

9606:OCSTAMP
gene id: 9606:OCSTAMP
uniprot id: Q9BR26
names: Function
names: Subcellular Location Annotation
messages: Membrane
messages: Probable cell surface receptor that plays a role in cellular fusion and cell differentiation. Cooperates with DCSTAMP in modulating cell-cell fusion in both osteoclasts and foreign body giant cells (FBGCs). Involved in osteoclast bone resorption. Promotes osteoclast differentiation and may play a role in the multinucleated osteoclast maturation (By similarity).

9606:OPTC
gene id: 9606:OPTC
uniprot id: Q9UBM4
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the small leucine-rich proteoglycan (SLRP) family. SLRP class III subfamily.
messages: Expressed in cartilage and synovial membranes (at protein level) (PubMed:18164633, PubMed:23845380). Expressed in the retina, iris, ligament, skin and fetal liver (at protein level) (PubMed:12019215, PubMed:25136834). Expressed in the retinal pigment epithelium (at protein level) (PubMed:25136834). Expressed in synovial fibroblasts and subchondral bone osteoblasts (PubMed:18164633).
messages: Homodimer.
messages: Inhibits angiogenesis in the vitreous humor of the eye, and therefore represses neovascularization (By similarity). Binds collagen fibrils (By similarity). May be involved in collagen fiber organization via regulation of other members of the small leucine-rich repeat proteoglycan superfamily (By similarity).
messages: O-glycosylated.
messages: Proteolytically cleaved by MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, ADAMTS4, and ADAMTS5 (PubMed:23845380). Proteolytically cleaved by MMP13 (By similarity). The degradation of OPTC by proteases may contribute to osteoarthritis pathophysiology (PubMed:23845380).
messages: Sulfated on tyrosine residues.
messages: extracellular matrix

9606:FOXR1
gene id: 9606:FOXR1
uniprot id: Q6PIV2
names: Disease Annotation
names: Function
names: Induction
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Cytoplasm
messages: Defects in FOXR1 may be the cause of a severe neurological disorder characterized by postnatal microcephaly, progressive brain atrophy and global developmental delay.
messages: Expressed in testis (at protein level).
messages: Induced by cellular stress.
messages: Nucleus
messages: Transcription factor which acts as both an activator and a repressor (PubMed:34723967). Activates transcription of a number of genes including the heat shock chaperones HSPA1A and HSPA6 and the antioxidant NADPH-dependent reductase DHRS2 which are involved in protection against oxidative stress (PubMed:34723967). Required for normal brain development (By similarity).
messages: perinuclear region

9606:RASSF10
gene id: 9606:RASSF10
uniprot id: A6NK89
names: Function
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Expressed in brain. Tends to be down-regulated in astrocytic gliomas due to promoter methylation. Methylation occurs early in gliomagenesis and the extent of methylation parallels with higher glioma grades, so that methylation is observed in close to 70% WHO grade IV primary glioblastomas, but not in grade I astrocytomas.
messages: Plays an important role in regulating embryonic neurogenesis.
messages: centrosome
messages: cytosol
messages: spindle pole

9606:RHD
gene id: 9606:RHD
uniprot id: A0A1B1R0Y1
uniprot id: B4DLT8
uniprot id: E7EVW1
uniprot id: Q02161
uniprot id: Q1KT12
uniprot id: Q5XLS8
uniprot id: Q5XLT0
uniprot id: Q5XLT3
uniprot id: Q7RU08
uniprot id: Q9UPC8
names: Disease Annotation
names: Function
names: PTM
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the ammonium transporter (TC 2.A.49) family. Rh subfamily.
messages: Cell membrane
messages: May be part of an oligomeric complex which is likely to have a transport or channel function in the erythrocyte membrane.
messages: Membrane
messages: Palmitoylated.
messages: RHD and RHCE are responsible for the Rh blood group system. The molecular basis of the Tar=Rh40 blood group antigen is a variant in position 110. Homozygous deletion of the RHD gene results in Rh-negative (dd) individuals (PubMed:1824267, PubMed:10845894). Some polymorhisms lead to weak RHD expression. This phenotype called weak D, formerly known as D(u), is observed in about 0.2% to 1% of Caucasians (PubMed:9864185). Moderately decreased RHD expression results in a phenotype called DHMi (PubMed:9864185).
messages: Restricted to tissues or cell lines expressing erythroid characters.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:RFTN2
gene id: 9606:RFTN2
uniprot id: Q52LD8
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the raftlin family.
messages: Cell membrane
messages: Upon bacterial lipopolysaccharide stimulation, mediates clathrin-dependent internalization of TLR4 in dendritic cells, resulting in activation of TICAM1-mediated signaling and subsequent IFNB1 production. May regulate B-cell antigen receptor-mediated signaling.

9606:FAM76B
gene id: 9606:FAM76B
uniprot id: F5GX09
uniprot id: Q5HYJ3
names: Domain
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the FAM76 family.
messages: Nucleus speckle
messages: The polyhistidine repeat acts as a targeting signal to nuclear speckles.

9606:SLC7A14
gene id: 9606:SLC7A14
uniprot id: Q8TBB6
names: Caution
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the amino acid-polyamine-organocation (APC) superfamily. Cationic amino acid transporter (CAT) (TC 2.A.3.3) family.
messages: Expressed in skin fibroblasts.
messages: Imports 4-aminobutanoate (GABA) into lysosomes. May act as a GABA sensor that regulates mTORC2-dependent INS signaling and gluconeogenesis. The transport mechanism and substrate selectivity remain to be elucidated.
messages: Initially postulated to transport L-arginine based on studies with a chimeric protein, which was not confirmed by other groups using the wild-type protein. It was latter shown to rather function as a GABA importer.
messages: Lysosome membrane
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:USP10
gene id: 9606:USP10
uniprot id: A0A7G6J4N4
uniprot id: Q14694
names: Activity Regulation
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the peptidase C19 family. USP10 subfamily.
messages: Cytoplasm
messages: Deubiquitinating enzyme that removes conjugated ubiquitin from specific proteins to regulate different cellular processes.
messages: Early endosome
messages: Following DNA damage. Down-regulated in renal cell carcinomas.
messages: Found in a deubiquitination complex with TANK, USP10 and ZC3H12A; this complex inhibits genotoxic stress- or interleukin-1-beta (IL1B)-mediated NF-kappa-B activation by promoting IKBKG or TRAF6 deubiquitination (PubMed:25861989). Interacts with IKBKG; this interaction increases in response to DNA damage (PubMed:25861989). Interacts with TANK; this interaction increases in response to DNA damage (PubMed:25861989). Interacts with TRAF6; this interaction increases in response to DNA damage (PubMed:25861989). Interacts with ZC3H12A; this interaction increases in response to DNA damage (PubMed:25861989). Interacts with G3BP1 (via NTF2 domain) and G3BP2 (via NTF2 domain); inhibiting stress granule formation (PubMed:11439350, PubMed:23279204, PubMed:27022092, PubMed:32302570, PubMed:31981475, PubMed:36183834, PubMed:36279435).
messages: Hydrolase that can remove conjugated ubiquitin from target proteins such as p53/TP53, RPS2/us5, RPS3/us3, RPS10/eS10, BECN1, SNX3 and CFTR (PubMed:11439350, PubMed:18632802, PubMed:31981475). Acts as an essential regulator of p53/TP53 stability: in unstressed cells, specifically deubiquitinates p53/TP53 in the cytoplasm, leading to counteract MDM2 action and stabilize p53/TP53 (PubMed:20096447). Following DNA damage, translocates to the nucleus and deubiquitinates p53/TP53, leading to regulate the p53/TP53-dependent DNA damage response (PubMed:20096447). Component of a regulatory loop that controls autophagy and p53/TP53 levels: mediates deubiquitination of BECN1, a key regulator of autophagy, leading to stabilize the PIK3C3/VPS34-containing complexes (PubMed:21962518). In turn, PIK3C3/VPS34-containing complexes regulate USP10 stability, suggesting the existence of a regulatory system by which PIK3C3/VPS34-containing complexes regulate p53/TP53 protein levels via USP10 and USP13 (PubMed:21962518). Does not deubiquitinate MDM2 (PubMed:20096447). Plays a key role in 40S ribosome subunit recycling when a ribosome has stalled during translation: acts both by inhibiting formation of stress granules, which store stalled translation pre-initiation complexes, and mediating deubiquitination of 40S ribosome subunits (PubMed:27022092, PubMed:31981475, PubMed:34348161, PubMed:34469731). Acts as a negative regulator of stress granules formation by lowering G3BP1 and G3BP2 valence, thereby preventing G3BP1 and G3BP2 ability to undergo liquid-liquid phase separation (LLPS) and assembly of stress granules (PubMed:11439350, PubMed:27022092, PubMed:32302570). Promotes 40S ribosome subunit recycling following ribosome dissociation in response to ribosome stalling by mediating deubiquitination of 40S ribosomal proteins RPS2/us5, RPS3/us3 and RPS10/eS10, thereby preventing their degradation by the proteasome (PubMed:31981475, PubMed:34348161, PubMed:34469731). Part of a ribosome quality…
messages: Nucleus
messages: Phosphorylated by ATM following DNA damage, leading to stablization and translocation it to the nucleus.
messages: Specifically inhibited by spautin-1 (specific and potent autophagy inhibitor-1), a derivative of MBCQ that binds to USP10 and inhibits deubiquitinase activity. Regulated by PIK3C3/VPS34-containing complexes.
messages: Ubiquitinated. Deubiquitinated by USP13.
messages: Widely expressed.

9606:ZNF438
gene id: 9606:ZNF438
uniprot id: Q7Z4V0
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: Isoform 1 acts as a transcriptional repressor.
messages: Nucleus
messages: Ubiquitous.

9606:DPP10
gene id: 9606:DPP10
uniprot id: Q8N608
names: Caution
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the peptidase S9B family. DPPIV subfamily.
messages: Cell membrane
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry.
messages: Found in serum, T-cells and brain (at protein level). Expressed in brain, pancreas, spinal cord and adrenal glands.
messages: Gly-651 is present instead of the conserved Ser which is expected to be an active site residue suggesting that this protein has no peptidase activity.
messages: May form oligomers. Interacts with KCND1 (Probable). Interacts with KCND2.
messages: N-glycosylation is important for cell surface expression, specially at Asn-257, which is crucial.
messages: Promotes cell surface expression of the potassium channel KCND2 (PubMed:15454437). Modulates the activity and gating characteristics of the potassium channel KCND2 (PubMed:15454437). Has no dipeptidyl aminopeptidase activity (PubMed:12662155).

9606:TUFT1
gene id: 9606:TUFT1
uniprot id: Q9NNX1
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the tuftelin family.
messages: Interacts with TFIP11.
messages: Involved in the mineralization and structural organization of enamel.
messages: Present in the extracellular enamel and is mainly associated with the crystal component.
messages: Secreted

9606:HPN
gene id: 9606:HPN
uniprot id: B7Z1L4
uniprot id: P05981
names: Caution
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Apical cell membrane
messages: Belongs to the peptidase S1 family.
messages: Cell membrane
messages: Detected in liver and kidney.
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: Serine protease that cleaves extracellular substrates, and contributes to the proteolytic processing of growth factors, such as HGF and MST1/HGFL (PubMed:21875933, PubMed:15839837). Plays a role in cell growth and maintenance of cell morphology (PubMed:8346233, PubMed:21875933). Plays a role in the proteolytic processing of ACE2 (PubMed:24227843). Mediates the proteolytic cleavage of urinary UMOD that is required for UMOD polymerization (PubMed:26673890).

9606:USP17L21
gene id: 9606:USP17L21
uniprot id: D6R901
names: Caution
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the peptidase C19 family. USP17 subfamily.
messages: Deubiquitinating enzyme that removes conjugated ubiquitin from specific proteins to regulate different cellular processes that may include cell proliferation, progression through the cell cycle, apoptosis, cell migration, and the cellular response to viral infection.
messages: Endoplasmic reticulum
messages: Nucleus
messages: The RS447 megasatellite DNA is a highly polymorphic conserved tandem repetitive sequence which contains a copy of the USP17 gene. It is present with an interindividual variation in copy number, ranging from 20 to 103, and can be found in the genome on chromosome 4 and chromosome 8. The high similarity between the UPS17-like genes makes it impossible to specifically assign data to a particular gene of the family. Oligonucleotides designed in RNAi experiments are for instance not specific for a given UPS17-like gene.

9606:FLACC1
gene id: 9606:FLACC1
uniprot id: Q96Q35
names: Subcellular Location Annotation
messages: Cytoplasm
messages: Cytoplasmic granule
messages: flagellum

9606:CRYGB
gene id: 9606:CRYGB
uniprot id: P07316
names: Disease Annotation
names: Domain
names: Function
names: Similarity
names: Subunit
messages: Belongs to the beta/gamma-crystallin family.
messages: Crystallins are the dominant structural components of the vertebrate eye lens.
messages: Has a two-domain beta-structure, folded into four very similar Greek key motifs.
messages: Monomer.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:SCAF4
gene id: 9606:SCAF4
uniprot id: O95104
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Anti-terminator protein required to prevent early mRNA termination during transcription (PubMed:31104839). Together with SCAF8, acts by suppressing the use of early, alternative poly(A) sites, thereby preventing the accumulation of non-functional truncated proteins (PubMed:31104839). Mechanistically, associates with the phosphorylated C-terminal heptapeptide repeat domain (CTD) of the largest RNA polymerase II subunit (POLR2A), and subsequently binds nascent RNA upstream of early polyadenylation sites to prevent premature mRNA transcript cleavage and polyadenylation (PubMed:31104839). Independently of SCAF8, also acts as a suppressor of transcriptional readthrough (PubMed:31104839).
messages: Interacts with POLR2A; via C-terminal heptapeptide repeat domain (CTD) phosphorylated at 'Ser-2' and 'Ser-5'.
messages: Nucleus

9606:FNDC10
gene id: 9606:FNDC10
uniprot id: F2Z333
names: Subcellular Location Annotation
messages: Membrane

9606:SPANXN5
gene id: 9606:SPANXN5
uniprot id: Q5MJ07
names: Similarity
messages: Belongs to the SPAN-X family.

9606:ATP6V0D2
gene id: 9606:ATP6V0D2
uniprot id: Q8N8Y2
names: Function
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Belongs to the V-ATPase V0D/AC39 subunit family.
messages: Kidney, osteoclast and lung.
messages: Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons. V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment (By similarity). May play a role in coupling of proton transport and ATP hydrolysis (By similarity). Regulator of osteoclast fusion and bone formation (By similarity).
messages: V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex. The V1 complex consists of three catalytic AB heterodimers that form a heterohexamer, three peripheral stalks each consisting of EG heterodimers, one central rotor including subunits D and F, and the regulatory subunits C and H. The proton translocation complex V0 consists of the proton transport subunit a, a ring of proteolipid subunits c9c'', rotary subunit d, subunits e and f, and the accessory subunits ATP6AP1/Ac45 and ATP6AP2/PRR.

9606:KLF14
gene id: 9606:KLF14
uniprot id: Q8TD94
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the Sp1 C2H2-type zinc-finger protein family.
messages: Nucleus

9606:BNIPL
gene id: 9606:BNIPL
uniprot id: Q7Z465
names: Function
names: Subunit
names: Tissue Specificity
messages: Homodimer. Interacts with BCL2, ARHGAP1, MIF and GFER.
messages: Isoform 2 is expressed in placenta and lung.
messages: May be a bridge molecule between BCL2 and ARHGAP1/CDC42 in promoting cell death.

9606:TCTA
gene id: 9606:TCTA
uniprot id: P57738
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: A chromosomal aberration involving TCTA is associated with T-cell acute lymphoblastic leukemia (T-ALL). Translocation t(1;3)(p34;p21).
messages: Belongs to the TCTA family.
messages: May be required for cellular fusion during osteoclastogenesis.
messages: Membrane
messages: Ubiquitous. Highest level of expression in kidney. Present in monocytes, osteoclasts, macrophages, synoviocytes and synovial lining cells (at protein level).

9606:CHRNA3
gene id: 9606:CHRNA3
uniprot id: P32297
names: Disease Annotation
names: Function
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
messages: Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Alpha-3/CHRNA3 sub-subfamily.
messages: Cell membrane
messages: Genetic variations in CHRNA3 have been associated with susceptibility to smoking-related behavioral traits and lung cancer, contributing to the smoking quantitative trait locus 3 (SQTL3) [MIM:612052].
messages: Neuronal AChR is composed of two different types of subunits: alpha and beta. Alpha-3 subunit can be combined to beta-2 or beta-4 to give rise to functional receptors. Interacts with RIC3; which is required for proper folding and assembly (PubMed:16120769). Interacts with LYPD6 (PubMed:27344019). The heteropentamer alpha-3-beta-2 interacts with alpha-conotoxins ImI and ImII (PubMed:15609996). The heteropentamer alpha-3-beta-2 interacts with alpha-conotoxins ImI, ImII, PnIA, GID and MII (By similarity). The heteropentamer alpha-3-beta-4 interacts with the alpha-conotoxin ImI (PubMed:15609996).
messages: Postsynaptic cell membrane
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:YLPM1
gene id: 9606:YLPM1
uniprot id: P49750
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Expressed in neuronal, neuroblastoma and embryonic kidney cell lines (at protein level).
messages: Interacts with PPP1CA and NCOA5. Forms a complex with ILF2, ILF3, KHDRBS1, RBMX, NCOA5 and PPP1CA (By similarity).
messages: Nucleus
messages: Nucleus speckle
messages: Plays a role in the reduction of telomerase activity during differentiation of embryonic stem cells by binding to the core promoter of TERT and controlling its down-regulation.

9606:OR2T5
gene id: 9606:OR2T5
uniprot id: Q6IEZ7
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Odorant receptor.

9606:TMTC4
gene id: 9606:TMTC4
uniprot id: Q5T4D3
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the TMTC family.
messages: Endoplasmic reticulum
messages: Membrane
messages: Transfers mannosyl residues to the hydroxyl group of serine or threonine residues. The 4 members of the TMTC family are O-mannosyl-transferases dedicated primarily to the cadherin superfamily, each member seems to have a distinct role in decorating the cadherin domains with O-linked mannose glycans at specific regions. Also acts as O-mannosyl-transferase on other proteins such as PDIA3.

9606:IL3RA
gene id: 9606:IL3RA
uniprot id: P26951
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the type I cytokine receptor family. Type 5 subfamily.
messages: Cell surface receptor for IL3 expressed on hematopoietic progenitor cells, monocytes and B-lymphocytes that controls the production and differentiation of hematopoietic progenitor cells into lineage-restricted cells (PubMed:10527461). Ligand stimulation rapidly induces hetrodimerization with IL3RB, phosphorylation and enzyme activity of effector proteins such as JAK2 and PI3K that play a role in signaling cell proliferation and differentiation. Activation of JAK2 leads to STAT5-mediated transcriptional program (By similarity).
messages: Interacts with IL3 (PubMed:29374162). Heterodimer of an alpha and a beta subunit. The beta subunit is common to the IL3, IL5 and GM-CSF receptors.
messages: Membrane
messages: The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.
messages: The box 1 motif is required for JAK interaction and/or activation.
messages: The gene coding for this protein is located in the pseudoautosomal region 1 (PAR1) of X and Y chromosomes.
messages: Ubiquitinated by RNFT2 in response to IL3. Ubiquitination leads ligand-induced degradation by the proteasome.

9606:FBXW10
gene id: 9606:FBXW10
uniprot id: Q5XX13
names: Function
names: Induction
messages: By disease-causing laminin A mutants also inducing CBX5 and CBX1 proteasomal degradation.
messages: Probable substrate-recognition component of a SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Overexpression is leading to degradation of CBX5 and CBX1.

9606:UGT2B11
gene id: 9606:UGT2B11
uniprot id: O75310
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the UDP-glycosyltransferase family.
messages: Endoplasmic reticulum membrane
messages: Microsome membrane
messages: UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.
messages: Widely expressed.

9606:PER2
gene id: 9606:PER2
uniprot id: O15055
names: Disease Annotation
names: Function
names: Induction
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acetylated. Deacetylated by SIRT1, resulting in decreased protein stability. Deacetylated by SIRT6, preventing its degradation by the proteasome, resulting in increased protein stability.
messages: Cytoplasm
messages: Homodimer. Component of the circadian core oscillator, which includes the CRY proteins, CLOCK or NPAS2, BMAL1 or BMAL2, CSNK1D and/or CSNK1E, TIMELESS, and the PER proteins. Interacts with CLOCK-BMAL1 (off DNA).Interacts with BMAL2. Interacts directly with PER1 and PER3, and through a C-terminal domain, with CRY1 and CRY2. Interacts (via PAS 2 domain) with TIMELESS (PubMed:31138685). Interacts with NFIL3. Different large complexes have been identified with different repressive functions. The core of PER complexes is composed of at least PER1, PER2, PER3, CRY1, CRY2, CSNK1D and/or CSNK1E. The large PER complex involved in the repression of transcriptional termination is composed of at least PER2, CDK9, DDX5, DHX9, NCBP1 and POLR2A (active). The large PER complex involved in the histone deacetylation is composed of at least HDAC1, PER2, SFPQ and SIN3A. The large PER complex involved in the histone methylation is composed of at least PER2, CBX3, TRIM28, SUV39H1 and/or SUV39H2; CBX3 mediates the formation of the complex. Interacts with SETX; the interaction inhibits termination of circadian target genes. Interacts with the nuclear receptors HNF4A, NR1D1, NR4A2, RORA, PPARA, PPARG and THRA; the interaction with at least PPARG is ligand dependent. Interacts with PML. Interacts (phosphorylated) with BTRC and FBXW11; the interactions trigger proteasomal degradation. Interacts with NONO and SFPQ. Interacts with CAVIN3 (By similarity). Interacts with MAGEL2 (By similarity). Interacts with MAP1LC3B (By similarity). Interacts with HNF4A (PubMed:30530698).
messages: Nucleus
messages: Oscillates diurnally. Rhythmic levels are critical for the generation of circadian rhythms in central as well as peripheral clocks. Targeted degradation of PER and CRY proteins enables the reactivation of CLOCK-BMAL1, thus initiating a new circadian transcriptional cycle with an intrinsic period of 24 hours.
messages: Phosphorylated by CSNK1E and CSNK1D. Phosphorylation results in PER2 protein degradation. May be dephosphorylated by PP1.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Transcriptional repressor which forms a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots 'circa' (about) and 'diem' (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN. The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle. Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day. Transcription and translation of core clock components (CLOCK, NPAS2, BMAL1, BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle). A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a …
messages: Ubiquitinated, leading to its proteasomal degradation. Ubiquitination may be inhibited by CRY1.
messages: Widely expressed. Found in heart, brain, placenta, lung, liver, skeleatal muscle, kidney and pancreas. High levels in skeletal muscle and pancreas. Low levels in lung. Isoform 2 is expressed in keratinocytes (at protein level).
messages: nucleolus
messages: perinuclear region

9606:TF
gene id: 9606:TF
uniprot id: P02787
uniprot id: Q06AH7
names: Disease Annotation
names: Domain
names: Function
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Binds to Neisseria transferrin-binding protein A (tbpA or tbp1). Forms a large complex with TbpA and TbpB.
messages: (Microbial infection) Binds to Neisseria transferrin-binding protein B (tbpb or tbp2).
messages: (Microbial infection) Binds to Neisseria transferrin-binding proteins A and B via its C-terminal lobe only. The L3 helix finger of TbpA inserts into the C-terminal lobe of TF, altering its conformation and probably disturbing the coordination of iron 2. Electron microscopy suggests that in the TbpA-TbpB-TF complex, TF is captured directly above the loop domain of TbpA in a chamber of about 1000 Angstroms(3) formed by the 3 proteins, where interactions between the proteins serve to abstract iron 2 from TF (PubMed:22343719, PubMed:22327295). Binding to TbpB does not alter the conformation of the C-terminal lobe (PubMed:22343719).
messages: (Microbial infection) Serves as an iron source for Neisseria species, which capture the protein and extract its iron for their own use.
messages: (Microbial infection) Serves as an iron source for parasite T.brucei (strain 427), which capture TF via its own transferrin receptor ESAG6:ESAG7 and extract its iron for its own use.
messages: Belongs to the transferrin family.
messages: Different polymorphic variants of transferrin are known. The sequence shown is the predominant electrophoretic variant (C1 or TF*C1).
messages: Expressed by the liver and secreted in plasma.
messages: Has a bilobed structure, each lobe binds a single Fe(3+) ion. Does not always bind 2 Fe(3+) ions.
messages: Monomer.
messages: Secreted
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites of absorption and heme degradation to those of storage and utilization. Serum transferrin may also have a further role in stimulating cell proliferation.

9606:SEMG1
gene id: 9606:SEMG1
uniprot id: P04279
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Alpha-inhibin-92 and alpha-inhibin-31, derived from the proteolytic degradation of semenogelin, inhibit the secretion of pituitary follicle-stimulating hormone.
messages: Belongs to the semenogelin family.
messages: Occurs in disulfide-linked complexes which may also contain two less abundant 71- and 76-kDa semenogelin-related polypeptides. Interacts with EPPIN (via C-terminus); Cys-239 is a critical amino acid for both binding to EPPIN.
messages: Predominant protein in semen. It participates in the formation of a gel matrix entrapping the accessory gland secretions and ejaculated spermatozoa. Fragments of semenogelin and/or fragments of the related proteins may contribute to the activation of progressive sperm movements as the gel-forming proteins are fragmented by KLK3/PSA.
messages: Rapidly cleaved after ejaculation by KLK3/PSA, resulting in liquefaction of the semen coagulum and the progressive release of motile spermatozoa.
messages: Secreted
messages: Seminal vesicle.
messages: Transglutaminase substrate.

9606:SLC25A31
gene id: 9606:SLC25A31
uniprot id: Q9H0C2
names: Activity Regulation
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: ADP:ATP antiporter that mediates import of ADP into the mitochondrial matrix for ATP synthesis, and export of ATP out to fuel the cell (PubMed:15670820) (By similarity). Cycles between the cytoplasmic-open state (c-state) and the matrix-open state (m-state): operates by the alternating access mechanism with a single substrate-binding site intermittently exposed to either the cytosolic (c-state) or matrix (m-state) side of the inner mitochondrial membrane (By similarity). Specifically required during spermatogenesis, probably to mediate ADP:ATP exchange in spermatocytes (PubMed:17137571). Large ATP supplies from mitochondria may be critical for normal progression of spermatogenesis during early stages of meiotic prophase I, including DNA double-strand break repair and chromosomal synapsis (By similarity). In addition to its ADP:ATP antiporter activity, also involved in mitochondrial uncoupling and mitochondrial permeability transition pore (mPTP) activity (By similarity). Plays a role in mitochondrial uncoupling by acting as a proton transporter: proton transport uncouples the proton flows via the electron transport chain and ATP synthase to reduce the efficiency of ATP production and cause mitochondrial thermogenesis (By similarity). Proton transporter activity is inhibited by ADP:ATP antiporter activity, suggesting that SLC25A31/ANT4 acts as a master regulator of mitochondrial energy output by maintaining a delicate balance between ATP production (ADP:ATP antiporter activity) and thermogenesis (proton transporter activity) (By similarity). Proton transporter activity requires free fatty acids as cofactor, but does not transport it (By similarity). Among nucleotides, may also exchange ADP for dATP and dADP (PubMed:15670820). Also plays a key role in mPTP opening, a non-specific pore that enables free passage of the mitochondrial membranes to solutes of up to 1.5 kDa, and which contributes to cell death (By similarity). It is however unclear if SLC25A31/ANT4 constitu…
messages: Belongs to the mitochondrial carrier (TC 2.A.29) family.
messages: Expressed in brain, liver, sperm and testis (PubMed:15670820, PubMed:17137571). In testis, expressed at higher level in spermatocytes, while it is expressed at lower level in spermatogonial cells (PubMed:17681941). Expressed in erythrocytes (at protein level) (PubMed:27641616).
messages: Membrane
messages: Mitochondrion inner membrane
messages: Monomer.
messages: The matrix-open state (m-state) is inhibited by the membrane-permeable bongkrekic acid (BKA). The cytoplasmic-open state (c-state) is inhibited by the membrane-impermeable toxic inhibitor carboxyatractyloside (CATR) (By similarity). Proton transporter activity is inhibited by ADP:ATP antiporter activity (By similarity).
messages: The transmembrane helices are not perpendicular to the plane of the membrane, but cross the membrane at an angle. Odd-numbered transmembrane helices exhibit a sharp kink, due to the presence of a conserved proline residue.
messages: flagellum membrane

9606:CD58
gene id: 9606:CD58
uniprot id: P19256
names: Function
names: Miscellaneous
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Interacts with human cytomegalovirus protein UL148; this interaction retains immature CD58 intracellularly.
messages: Cell membrane
messages: Interacts with CD2 (PubMed:10380930, PubMed:3309127). Interacts with CMTM6 (PubMed:28813417).
messages: Ligand of the T-lymphocyte CD2 glycoprotein. This interaction is important in mediating thymocyte interactions with thymic epithelial cells, antigen-independent and -dependent interactions of T-lymphocytes with target cells and antigen-presenting cells and the T-lymphocyte rosetting with erythrocytes. In addition, the LFA-3/CD2 interaction may prime response by both the CD2+ and LFA-3+ cells.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

9606:KCNE1
gene id: 9606:KCNE1
uniprot id: A7LFK2
uniprot id: A7LFK4
uniprot id: C7S316
uniprot id: P15382
uniprot id: Q6FHJ6
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Ancillary protein that assembles as a beta subunit with a voltage-gated potassium channel complex of pore-forming alpha subunits. Modulates the gating kinetics and enhances stability of the channel complex. Assembled with KCNB1 modulates the gating characteristics of the delayed rectifier voltage-dependent potassium channel KCNB1 (PubMed:19219384). Assembled with KCNQ1/KVLQT1 is proposed to form the slowly activating delayed rectifier cardiac potassium (IKs) channel. The outward current reaches its steady state only after 50 seconds. Assembled with KCNH2/HERG may modulate the rapidly activating component of the delayed rectifying potassium current in heart (IKr).
messages: Apical cell membrane
messages: Belongs to the potassium channel KCNE family.
messages: Cell membrane
messages: Expressed in lung, kidney, testis, ovaries, small intestine, peripheral blood leukocytes. Expressed in the heart (PubMed:19219384). Not detected in pancreas, spleen, prostate and colon. Restrictively localized in the apical membrane portion of epithelial cells.
messages: Interacts with KCNB1. Interacts with KCNC2 (By similarity). Associates with KCNH2/HERG (PubMed:9230439). Interacts with KNCQ1; targets the complex KNCQ1-KCNE1 to the membrane raft (PubMed:20533308). The complex KNCQ1-KNCE1 interacts with the scolopendra toxin SSD609 (PubMed:26307551).
messages: Membrane
messages: Membrane raft
messages: N-glycosylation at Asn-26 occurs post-translationally, and requires prior cotranslational glycosylation at Asn-5.
messages: Phosphorylation inhibits the potassium current.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:TMEM268
gene id: 9606:TMEM268
uniprot id: Q5VZI3
names: Subcellular Location Annotation
messages: Membrane

9606:SLC44A4
gene id: 9606:SLC44A4
uniprot id: A0A140VJH4
uniprot id: A0A1U9X8K7
uniprot id: Q53GD3
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: An interstitial deletion causing the fusion of exon 10 of CTL4 with the 3'-UTR of NEU has been detected in two patients affected by sialidosis.
messages: Apical cell membrane
messages: Belongs to the CTL (choline transporter-like) family.
messages: Cell membrane
messages: Choline transporter that plays a role in the choline-acetylcholine system and is required to the efferent innervation of hair cells in the olivocochlear bundle for the maintenance of physiological function of outer hair cells and the protection of hair cells from acoustic injury (By similarity) (PubMed:23651124, PubMed:28013291). Also described as a thiamine pyrophosphate transporter in colon, may mediate the absorption of microbiota-generated thiamine pyrophosphate and contribute to host thiamine (vitamin B1) homeostasis (PubMed:24379411, PubMed:26741288).
messages: Choline transporter.
messages: Expressed in colon at low levels.
messages: Has also thiamine pyrophosphate transporter activity.
messages: Highly expressed in colon, also detected in prostate, trachea and lung (PubMed:24379411). Isoform 3 is also expressed in colon but a lower levels (PubMed:24379411).
messages: Membrane
messages: N-glycosylated; N-glycosylation of Asn-69, Asn-155 and Asn-393 is required for a proper thiamine pyrophosphate uptake.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:TWNK
gene id: 9606:TWNK
uniprot id: Q96RR1
names: Activity Regulation
names: Caution
names: Disease Annotation
names: Domain
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: High relative levels in skeletal muscle, testis and pancreas. Lower levels of expression in the heart, brain, placenta, lung, liver, kidney, spleen, thymus, prostate, ovary, small intestine, colon and leukocytes. Expression is coregulated with MRPL43.
messages: Homohexamer (via C-terminus) which assembled in a ring-like structure (PubMed:18039713, PubMed:17324440, PubMed:22383523, PubMed:25824949, PubMed:30496414, PubMed:18971204). Homoheptamer which assembled in a ring-like structure (PubMed:25824949, PubMed:30496414). Oligomerization is Mg(2+), nucleotide and DNA-independent, however, Mg(2+) and nucleotide stabilize the homohexameric form (PubMed:18039713). Interacts with POLG in vitro (PubMed:15167897).
messages: In vitro, can catalyze the hydrolysis of different nucleotide triphosphate (NTP) substrates with different efficiency.
messages: Interacts with LONP1.
messages: Lack DNA unwinding and ATP hydrolysis activities (PubMed:18039713). Does not bind single-stranded or double-stranded DNA (PubMed:18039713).
messages: Mitochondrial helicase involved in mtDNA replication and repair (PubMed:12975372, PubMed:15167897, PubMed:17324440, PubMed:18039713, PubMed:18971204, PubMed:25824949, PubMed:26887820, PubMed:27226550). Might have a role in mtDNA repair (PubMed:27226550). Has DNA strand separation activity needed to form a processive replication fork for leading strand synthesis which is catalyzed by the formation of a replisome complex with POLG and mtSDB (PubMed:12975372, PubMed:15167897, PubMed:18039713, PubMed:22383523, PubMed:26887820, PubMed:27226550). Preferentially unwinds DNA substrates with pre-existing 5'-and 3'- single-stranded tails but is also active on a 5'- flap substrate (PubMed:12975372, PubMed:15167897, PubMed:18039713, PubMed:22383523, PubMed:26887820, PubMed:27226550). Can dissociate the invading strand of immobile or mobile D-loop DNA structures irrespective of the single strand polarity of the third strand (PubMed:27226550). In addition to its DNA strand separation activity, also has DNA strand annealing, DNA strand-exchange and DNA branch migration activities (PubMed:22383523, PubMed:26887820, PubMed:27226550).
messages: Monomer (PubMed:18039713). Does not form oligomers (PubMed:18039713).
messages: N-terminus enhances protein stability and hexamer formation, which is important for DNA binding, and is required for DNA helicase activity and, ultimately, for mtDNA replisome processivity.
messages: Strand annealing activity is inhibited by 150 mM NaCl (in vitro).
messages: The N-terminus contains a putative primase-like domain; however the absence of the zinc binding domain and other motifs important for catalysis suggests that TWNK lacks primase activity.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: mitochondrion nucleoid

9606:BNC2
gene id: 9606:BNC2
uniprot id: Q6ZN30
names: Developmental Stage
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Highly expressed in testis, uterus and small intestine, and weakly expressed in colon and prostate. Also expressed in skin, primary keratinocytes, immortalized keratinocytes, and HeLa and HEK293 cells. Not detected in blood, thymus, spleen or Hep-G2 cells.
messages: In a 7-week embryo, expressed in the urogenital sinus, the precursor of the bladder, and its outflow tract. The most prominent expression is in the primitive urothelium, and there is weaker expression in the surrounding mesenchyme. Expression also detected in the urothelium of the adult male urethra.
messages: Nucleus
messages: Probable transcription factor specific for skin keratinocytes. May play a role in the differentiation of spermatozoa and oocytes (PubMed:14988505). May also play an important role in early urinary-tract development (PubMed:31051115).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:SNTB1
gene id: 9606:SNTB1
uniprot id: Q13884
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Adapter protein that binds to and probably organizes the subcellular localization of a variety of membrane proteins. May link various receptors to the actin cytoskeleton and the dystrophin glycoprotein complex.
messages: Belongs to the syntrophin family.
messages: Cell junction
messages: Monomer and homodimer (Probable). Interacts with the other members of the syntrophin family SNTA1 and SNTB2; with the sodium channel proteins SCN4A and SCN5A (By similarity). Interacts with the viral HTLV-1 TAX protein and with dystrophin protein DMD and related proteins DTNA and UTRN. Interacts with DTNB (By similarity).
messages: Phosphorylated by CaM-kinase II.
messages: The PDZ domain binds to the last three or four amino acids of ion channels and receptor proteins. The association with dystrophin or related proteins probably leaves the PDZ domain available to recruit proteins to the membrane (By similarity).
messages: The PH 1 domain mediates the oligomerization in a calcium dependent manner.
messages: The SU domain binds calmodulin in a calcium-dependent manner.
messages: Ubiquitous.
messages: cytoskeleton
messages: sarcolemma

9606:CYP2F1
gene id: 9606:CYP2F1
uniprot id: P24903
names: Function
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the cytochrome P450 family.
messages: Eight non disease-associated alleles are known: CYP2F1*1, CYP2F1*2A, CYP2F1*2B, CYP2F1*3, CYP2F1*4, CYP2F1*5A, CYP2F1*5B and CYP2F1*6. The sequence shown corresponds to allele CYP2F1*1.
messages: Endoplasmic reticulum membrane
messages: Expressed in lung. Rarely detected in liver and placenta.
messages: May be involved in the metabolism of various pneumotoxicants including naphthalene. Is able to dealkylate ethoxycoumarin, propoxycoumarin, and pentoxyresorufin but possesses no activity toward ethoxyresorufin and only trace dearylation activity toward benzyloxyresorufin. Bioactivates 3-methylindole (3MI) by dehydrogenation to the putative electrophile 3-methylene-indolenine.
messages: Microsome membrane

9606:SZRD1
gene id: 9606:SZRD1
uniprot id: Q7Z422
names: Similarity
messages: Belongs to the SZRD1 family.

9606:SLC18A2
gene id: 9606:SLC18A2
uniprot id: Q05940
names: Activity Regulation
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the major facilitator superfamily. Vesicular transporter family.
messages: Electrogenic antiporter that exchanges one cationic monoamine with two intravesicular protons across the membrane of secretory and synaptic vesicles. Uses the electrochemical proton gradient established by the V-type proton-pump ATPase to accumulate high concentrations of monoamines inside the vesicles prior to their release via exocytosis. Transports a variety of catecholamines such as dopamine, adrenaline and noradrenaline, histamine, and indolamines such as serotonin (PubMed:8643547, PubMed:23363473). Regulates the transvesicular monoaminergic gradient that determines the quantal size. Mediates somatodendritic dopamine release in hippocampal neurons, likely as part of a regulated secretory pathway that integrates retrograde synaptic signals (By similarity). Acts as a primary transporter for striatal dopamine loading ensuring impulse-dependent release of dopamine at the synaptic cleft (By similarity). Responsible for histamine and serotonin storage and subsequent corelease from mast cell granules (PubMed:8860238) (By similarity).
messages: Expressed in neuronal and neuroendocrine tissues. Detected in central and peripheral nervous system in particular in axonal and dendritic processes in dopaminergic cells of substantia nigra, histaminergic neuronal cell bodies of substantia nigra and tuberomammillary nucleus, in ganglion cells of sympathetic glia and in peripheral sympathetic nerve terminals in stomach and duodenum (at protein level). Highly expressed in chromaffin cells of the adrenal medulla and histamine-storing enterochromaffin-like cells of oxyntic mucosa (at protein level).
messages: Interacts with SLC6A3.
messages: Strongly inhibited by reserpine and tetrabenazine (PubMed:8643547, PubMed:8860238). Also inhibited to a lesser extent by ketanserin and fenfluramine. Inhibited by tetrabenazine.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: axon
messages: dendrite
messages: secretory vesicle membrane
messages: synaptic vesicle membrane

9606:PRLR
gene id: 9606:PRLR
uniprot id: P16471
names: Disease Annotation
names: Domain
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the type I cytokine receptor family. Type 1 subfamily.
messages: Does not transduce prolactin signaling.
messages: Expressed in breast, placenta, kidney, liver and pancreas.
messages: Homodimer upon hormone binding. Interacts with SMARCA1. Interacts with GH1. Interacts with CSH. Interacts with NEK3 and VAV2 and this interaction is prolactin-dependent.
messages: Includes exon 11. Does not transduce prolactin signaling.
messages: Membrane
messages: Produced by deletion of part of exon 10 and frameshift.
messages: SF1b with deletion of exon 4. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Secreted
messages: Soluble isoform that appears specific for the BT-474 breast cancer cell line.
messages: Splices from exon 7 to exon 11.
messages: The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.
messages: The box 1 motif is required for JAK interaction and/or activation.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: This is a receptor for the anterior pituitary hormone prolactin (PRL). Acts as a prosurvival factor for spermatozoa by inhibiting sperm capacitation through suppression of SRC kinase activation and stimulation of AKT. Isoform 4 is unable to transduce prolactin signaling. Isoform 6 is unable to transduce prolactin signaling.

9606:TDRD12
gene id: 9606:TDRD12
uniprot id: Q587J7
names: Function
names: Subunit
messages: Component of a mRNP complex containing PIWIL2, TDRD1 and piRNAs. Component of the PET complex, at least composed of EXD1, PIWIL2, TDRD12 and piRNAs.
messages: Probable ATP-binding RNA helicase required during spermatogenesis to repress transposable elements and preventing their mobilization, which is essential for the germline integrity. Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and governs the methylation and subsequent repression of transposons. Involved in the secondary piRNAs metabolic process. Acts via the PET complex, a multiprotein complex required during the secondary piRNAs metabolic process for the PIWIL2 slicing-triggered loading of PIWIL4 piRNAs.

9606:KHNYN
gene id: 9606:KHNYN
uniprot id: O15037
names: Similarity
messages: Belongs to the N4BP1 family.

9606:LRCH2
gene id: 9606:LRCH2
uniprot id: Q5VUJ6
names: Function
messages: May play a role in the organization of the cytoskeleton.

9606:CYB5D2
gene id: 9606:CYB5D2
uniprot id: Q8WUJ1
names: Domain
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the cytochrome b5 family. MAPR subfamily.
messages: Heme-binding protein which promotes neuronal but not astrocyte differentiation.
messages: Non-classical progesterone receptors involved in extranuclear signaling are classified in 2 groups: the class II progestin and adipoQ receptor (PAQR) family (also called mPRs) (PAQR5, PAQR6, PAQR7, PAQR8 and PAQR9) and the b5-like heme/steroid-binding protein family (also called MAPRs) (PGRMC1, PGRMC2, NENF and CYB5D2).
messages: Secreted
messages: The cytochrome b5 heme-binding domain was proven to bind heme, although it lacks the conserved iron-binding His residues at position 73 and 106.

9606:CHMP1A
gene id: 9606:CHMP1A
uniprot id: Q9HD42
names: Caution
names: Disease Annotation
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the SNF7 family.
messages: By muristerone.
messages: Cytoplasm
messages: Endosome membrane
messages: Expressed in placenta, cultured skin fibroblasts and in osteoblast cell line MG-63.
messages: Nucleus matrix
messages: Probable peripherally associated component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. The MVB pathway appears to require the sequential function of ESCRT-O, -I,-II and -III complexes. ESCRT-III proteins mostly dissociate from the invaginating membrane before the ILV is released. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis and the budding of enveloped viruses (HIV-1 and other lentiviruses). ESCRT-III proteins are believed to mediate the necessary vesicle extrusion and/or membrane fission activities, possibly in conjunction with the AAA ATPase VPS4. Involved in cytokinesis. Involved in recruiting VPS4A and/or VPS4B to the midbody of dividing cells. May also be involved in chromosome condensation. Targets the Polycomb group (PcG) protein BMI1/PCGF4 to regions of condensed chromatin. May play a role in stable cell cycle progression and in PcG gene silencing.
messages: Probable peripherally associated component of the endosomal sorting required for transport complex III (ESCRT-III). ESCRT-III components are thought to multimerize to form a flat lattice on the perimeter membrane of the endosome. Several assembly forms of ESCRT-III may exist that interact and act sequentially. Self-associates. Interacts with CHMP1B. Interacts with VPS4A. Interacts with VPS4B. Interacts with PHF1. Interacts with IST1. Interacts with MITD1.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Was originally (PubMed:8863740) thought to be a metalloprotease (PRSM1). This was based on a wrong translation of the ORF which gave rise to a putative protein of 318 AA containing a pattern reminiscent of zinc metalloproteases.

9606:ADPRH
gene id: 9606:ADPRH
uniprot id: A8K6X2
uniprot id: B4E341
uniprot id: P54922
names: Cofactor
names: Function
names: Similarity
names: Subunit
messages: Belongs to the ADP-ribosylglycohydrolase family.
messages: Binds 2 magnesium ions per subunit.
messages: Monomer.
messages: Specifically acts as an arginine mono-ADP-ribosylhydrolase by mediating the removal of mono-ADP-ribose attached to arginine residues on proteins.

9606:PEX5L
gene id: 9606:PEX5L
uniprot id: Q8IYB4
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Accessory subunit of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, regulating their cell-surface expression and cyclic nucleotide dependence.
messages: Belongs to the peroxisomal targeting signal receptor family.
messages: Cytoplasm
messages: Interacts with RAB8B. Forms an obligate 4:4 complex with HCN2 (By similarity). May interact with the C-terminal PTS1-type tripeptide peroxisomal targeting signal (SKL-type); the relevance of such interaction is however unclear (PubMed:11463335). Interacts with HCN3 (By similarity).
messages: Mainly expressed in brain. Also expressed in pancreas, testis and pituitary.
messages: Membrane

9606:PNMA8B
gene id: 9606:PNMA8B
uniprot id: Q9ULN7
names: Similarity
messages: Belongs to the PNMA family.

9606:TARS1
gene id: 9606:TARS1
uniprot id: P26639
names: Activity Regulation
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the class-II aminoacyl-tRNA synthetase family.
messages: Catalyzes the attachment of threonine to tRNA(Thr) in a two-step reaction: threonine is first activated by ATP to form Thr-AMP and then transferred to the acceptor end of tRNA(Thr) (PubMed:25824639, PubMed:31374204). Also edits incorrectly charged tRNA(Thr) via its editing domain, at the post-transfer stage (By similarity).
messages: Cytoplasm
messages: Homodimer.
messages: ISGylated.
messages: Inhibited by borrelidin (BN, IC 50 is 7 nM), which binds to 4 distinct subsites in the protein, preventing binding of all 3 substrates (PubMed:25824639).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:DDX3X
gene id: 9606:DDX3X
uniprot id: A0A2R8YFS5
uniprot id: O00571
names: Caution
names: Disease Annotation
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Directly interacts with hepatitis C virus (HCV) core protein in the cytoplasm.
messages: (Microbial infection) Facilitates Dengue virus (DENV) replication.
messages: (Microbial infection) Facilitates HIV-1 replication (PubMed:15507209, PubMed:18583960, PubMed:21589879, PubMed:22872150, PubMed:29899501). Acts as a cofactor for XPO1-mediated nuclear export of HIV-1 Rev RNAs (PubMed:15507209, PubMed:18583960, PubMed:29899501). This function is strongly stimulated in the presence of TBK1 and requires DDX3X ATPase activity (PubMed:18583960).
messages: (Microbial infection) Facilitates Venezuelan equine encephalitis virus (VEEV) replication.
messages: (Microbial infection) Facilitates Zika virus (ZIKV) replication.
messages: (Microbial infection) Facilitates hepatitis C virus (HCV) replication (PubMed:29899501). During infection, HCV core protein inhibits the interaction between MAVS and DDX3X and therefore impairs MAVS-dependent INFB induction and might recruit DDX3X to HCV replication complex (PubMed:21170385).
messages: (Microbial infection) Interacts with HIV-1 protein Rev.
messages: (Microbial infection) Interacts with Venezuelan equine encephalitis virus non-structural protein 3.
messages: (Microbial infection) Interacts with hepatitis B virus (HBV) polymerase in the cytoplasm; this interaction may inhibit DDX3X interaction with the IKBKE/TBK1 complex, and hence impair IKBKE/TBK1-mediated increase in IFNB production.
messages: (Microbial infection) Interacts with vaccinia virus (VACV) protein K7.
messages: Belongs to the DEAD box helicase family.
messages: Belongs to the DEAD box helicase family. DDX3/DED1 subfamily.
messages: Cell membrane
messages: Cytoplasm
messages: Encoded by an chromosome X-linked gene which may escape X chromosome inactivation in females. DDX3Y, its homolog on chromosome Y, is located on the Y non-recombinant portion.
messages: Homodimer; can bind RNA as a monomer and as a dimer/oligomer (PubMed:27546789, PubMed:31300642). Interacts with TDRD3 (PubMed:18632687). Interacts (when phosphorylated at Ser-102) with IRF3; the interaction facilitates the phosphorylation and activation of IRF3 by IKBKE (PubMed:23478265, PubMed:27980081). Directly interacts with XPO1/CRM1 (PubMed:15507209, PubMed:30131165, PubMed:31575075). The interaction with XPO1/CMR1 is dependent on the DDX3X nuclear export signal motif and XPO1 interaction with GTPase RAN in its active GTP-bound form (PubMed:31575075, PubMed:30131165). Weakly interacts with TBKBP1/SINTBAD (PubMed:27980081). Directly interacts with TRAF3; this interaction stimulates TRAF3 'Lys-63' ubiquitination (PubMed:27980081). Interacts with CSNK1E in a Wnt-dependent manner; this interaction greatly enhances CSNK1E affinity for ATP, stimulates its kinase activity and promotes CSNK1E-mediated DVL2 phosphorylation (PubMed:23413191, PubMed:29222110). In the presence of RNA, the interaction is decreased (PubMed:29222110). Also interacts with CSNK1D and stimulates its kinase activity (PubMed:23413191, PubMed:29222110). Interacts with TRPV4; this interaction is decreased when the TRPV4 channel is activated, leading to DDX3X relocalization to the nucleus (PubMed:29899501). Interacts with MAP3K14/NIK (PubMed:30341167). Directly interacts with CHUK/IKKA after physiological activation of the TLR7 and TLR8 pathways; this interaction enhances CHUK autophosphorylation (PubMed:30341167). May associate with EIF4F complex, composed of at least EIF4A, EIF4E and EIF4G1/EIF4G3 (Probable). Directly interacts with EIF4E in an RNA-independent manner; this interaction enhances EIF4E cap-binding ability (PubMed:17667941, PubMed:21883093, PubMed:28733330). Directly interacts with EIF4G1 in an RNA-independent manner (PubMed:22872150). DDX3X competes with EIF4G1 for interaction with EIF4E (PubMed:17667941, PubMed:21883093). Interacts with EIF4A1 and EIF2S1 in an RNA-independent manner…
messages: Inflammasome
messages: Multifunctional ATP-dependent RNA helicase (PubMed:17357160, PubMed:21589879, PubMed:31575075). The ATPase activity can be stimulated by various ribo-and deoxynucleic acids indicative for a relaxed substrate specificity (PubMed:29222110). In vitro can unwind partially double-stranded DNA with a preference for 5'-single-stranded DNA overhangs (PubMed:17357160, PubMed:21589879). Binds RNA G-quadruplex (rG4s) structures, including those located in the 5'-UTR of NRAS mRNA (PubMed:30256975). Involved in many cellular processes, which do not necessarily require its ATPase/helicase catalytic activities (Probable). Involved in transcription regulation (PubMed:16818630, PubMed:18264132). Positively regulates CDKN1A/WAF1/CIP1 transcription in an SP1-dependent manner, hence inhibits cell growth. This function requires its ATPase, but not helicase activity (PubMed:16818630, PubMed:18264132). CDKN1A up-regulation may be cell-type specific (PubMed:18264132). Binds CDH1/E-cadherin promoter and represses its transcription (PubMed:18264132). Potentiates HNF4A-mediated MTTP transcriptional activation; this function requires ATPase, but not helicase activity. Facilitates HNF4A acetylation, possibly catalyzed by CREBBP/EP300, thereby increasing the DNA-binding affinity of HNF4 to its response element. In addition, disrupts the interaction between HNF4 and SHP that forms inactive heterodimers and enhances the formation of active HNF4 homodimers. By promoting HNF4A-induced MTTP expression, may play a role in lipid homeostasis (PubMed:28128295). May positively regulate TP53 transcription (PubMed:28842590). Associates with mRNPs, predominantly with spliced mRNAs carrying an exon junction complex (EJC) (PubMed:17095540, PubMed:18596238). Involved in the regulation of translation initiation (PubMed:18628297, PubMed:17667941, PubMed:22872150). Not involved in the general process of translation, but promotes efficient translation of selected complex mRNAs, containing highly structured 5'-untra…
messages: Nucleus
messages: Phosphorylated by TBK1; the phosphorylation is required for the synergistic induction of IFNB mediated by TBK1 and DDX3X (PubMed:18583960). Phosphorylated by IKBKE at Ser-102 after ssRNA viral infection; enhances the induction of INFB promoter by IRF3 (PubMed:18583960, PubMed:23478265). The cytoplasmic form is highly phosphorylated in the G1/S phase of the cell cycle and much less at G2/M (PubMed:22034099). Phosphorylation by CSNK1E may inhibit RNA-stimulated ATPase activity (PubMed:29222110).
messages: Stress granule
messages: The C-terminus (residues 536-662) is dispensable for DDX3X trafficking.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The role of the nuclear export signal (NES) motif in XPO1-mediated DDX3X export is controversial (PubMed:30131165, PubMed:31575075, PubMed:15507209). In one study, NES has been found dispensable for DDX3X export while the helicase domain mediates the interaction with XPO1 (PubMed:15507209). However, in two other studies, DDX3X nuclear export is dependent on both NES and Ran in its GTP-bound form while the helicase domain is not required (PubMed:30131165, PubMed:31575075).
messages: Upon stimulation of death receptors, including TNFRSF10B, recruited to receptors and cleaved by caspases. Proteolytic fragments remain associated with the receptors. This cleavage presumably inactivates DDX3X anti-apoptotic function.
messages: Widely expressed (PubMed:15294876). In testis, expressed in spermatids (PubMed:15294876). Expressed in epidermis and liver (at protein level) (PubMed:16818630, PubMed:16301996).
messages: centrosome
messages: lamellipodium

9606:PEX3
gene id: 9606:PEX3
uniprot id: P56589
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the peroxin-3 family.
messages: Found in all examined tissues.
messages: Interacts with PEX19.
messages: Involved in peroxisome biosynthesis and integrity. Assembles membrane vesicles before the matrix proteins are translocated. As a docking factor for PEX19, is necessary for the import of peroxisomal membrane proteins in the peroxisomes.
messages: Peroxisome membrane
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:CPLX2
gene id: 9606:CPLX2
uniprot id: Q6PUV4
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the complexin/synaphin family.
messages: Binds to the SNARE core complex containing SNAP25, VAMP2 and STX1A.
messages: Negatively regulates the formation of synaptic vesicle clustering at active zone to the presynaptic membrane in postmitotic neurons. Positively regulates a late step in exocytosis of various cytoplasmic vesicles, such as synaptic vesicles and other secretory vesicles. Also involved in mast cell exocytosis (By similarity).
messages: Nervous system. In hippocampus and cerebellum, expressed mainly by excitatory neurons. Down-regulated in brain cortex from patients suffering from Huntington disease, bipolar disorder or major depression. Down-regulated in cerebellum from patients with schizophrenia.
messages: Nucleus
messages: Perikaryon
messages: Presynapse
messages: cytosol

9606:KCNA5
gene id: 9606:KCNA5
uniprot id: P22460
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the potassium channel family. A (Shaker) (TC 1.A.1.2) subfamily. Kv1.5/KCNA5 sub-subfamily.
messages: Cell membrane
messages: Homotetramer and heterotetramer of potassium channel proteins. Interacts with DLG1, which enhances channel currents. Forms a ternary complex with DLG1 and CAV3 (By similarity). Interacts with KCNAB1 (PubMed:12130714). Interacts with UBE2I (PubMed:17261810).
messages: Pancreatic islets and insulinoma.
messages: Sumoylated on Lys-221, and Lys-536, preferentially with SUMO3. Sumoylation regulates the voltage sensitivity of the channel.
messages: The amino terminus may be important in determining the rate of inactivation of the channel while the C-terminal PDZ-binding motif may play a role in modulation of channel activity and/or targeting of the channel to specific subcellular compartments.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The transmembrane segment S4 functions as voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Channel opening and closing is effected by a conformation change that affects the position and orientation of the voltage-sensor paddle formed by S3 and S4 within the membrane. A transmembrane electric field that is positive inside would push the positively charged S4 segment outwards, thereby opening the pore, while a field that is negative inside would pull the S4 segment inwards and close the pore. Changes in the position and orientation of S4 are then transmitted to the activation gate formed by the inner helix bundle via the S4-S5 linker region.
messages: Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane. Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:12130714). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation (PubMed:12130714). Homotetrameric channels display rapid activation and slow inactivation (PubMed:8505626, PubMed:12130714). May play a role in regulating the secretion of insulin in normal pancreatic islets. Isoform 2 exhibits a voltage-dependent recovery from inactivation and an excessive cumulative inactivation (PubMed:11524461).

9606:CORT
gene id: 9606:CORT
uniprot id: O00230
uniprot id: Q8IUV6
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the somatostatin family.
messages: Binds to all human somatostatin receptor (SSTR) subtypes. It also inhibits cAMP production induced by forskolin through SSTRs.
messages: Expressed in a subset of GABAergic cells in the cortex and hippocampus.
messages: Secreted

9606:GATAD1
gene id: 9606:GATAD1
uniprot id: Q8WUU5
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Component of a chromatin complex, at least composed of KDM5A, GATAD1 and EMSY.
messages: Component of some chromatin complex recruited to chromatin sites methylated 'Lys-4' of histone H3 (H3K4me), with a preference for trimethylated form (H3K4me3).
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitously expressed among various tissue types. Expressed in left ventricular myocytes.

9606:FUT7
gene id: 9606:FUT7
uniprot id: Q11130
names: Activity Regulation
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the glycosyltransferase 10 family.
messages: By T-cell activation (PubMed:8666674). Up-regulated by LIF (PubMed:19455659). Induced by IL1B (PubMed:29138114). Induced at higher levels by interleukin 12 in activated T cells (PubMed:9858509). Down-regulated by IL4 (PubMed:9858509).
messages: Catalyzes the transfer of L-fucose, from a guanosine diphosphate-beta-L-fucose, to the N-acetyl glucosamine (GlcNAc) of a distal alpha2,3 sialylated lactosamine unit of a glycoprotein or a glycolipid-linked sialopolylactosamines chain through an alpha-1,3 glycosidic linkage and participates in the final fucosylation step in the biosynthesis of the sialyl Lewis X (sLe(x)), a carbohydrate involved in cell and matrix adhesion during leukocyte trafficking and fertilization (PubMed:8207002, PubMed:8752218, PubMed:8666674, PubMed:9299472, PubMed:9405391, PubMed:9473504, PubMed:9499379, PubMed:9461592, PubMed:15632313, PubMed:15926890, PubMed:18553500, PubMed:18402946, PubMed:11404359, PubMed:29593094). In vitro, also synthesizes sialyl-dimeric-Lex structures, from VIM-2 structures and both di-fucosylated and trifucosylated structures from mono-fucosylated precursors (PubMed:9499379). However does not catalyze alpha 1-3 fucosylation when an internal alpha 1-3 fucosylation is present in polylactosamine chain and the fucosylation rate of the internal GlcNAc residues is reduced once fucose has been added to the distal GlcNAc (PubMed:9473504, PubMed:9499379). Also catalyzes the transfer of a fucose from GDP-beta-fucose to the 6-sulfated a(2,3)sialylated substrate to produce 6-sulfo sLex mediating significant L-selectin-dependent cell adhesion (PubMed:10200296, PubMed:8752218). Through sialyl-Lewis(x) biosynthesis, can control SELE- and SELP-mediated cell adhesion with leukocytes and allows leukocytes tethering and rolling along the endothelial tissue thereby enabling the leukocytes to accumulate at a site of inflammation (PubMed:10386892, PubMed:29138114, PubMed:8666674, PubMed:9473504, PubMed:9834120). May enhance embryo implantation through sialyl Lewis X (sLeX)-mediated adhesion of embryo cells to endometrium (PubMed:18402946, PubMed:18553500). May affect insulin signaling by up-regulating the phosphorylation and expression of some signaling molecules involved in the insuli…
messages: Golgi stack membrane
messages: Inhibited by NaCl (Probable). Inhibited by GDP in a concentration dependent manner, with an IC(50) value of 93 uM (PubMed:9405391, PubMed:15632313). Also inhibited by GMP and GTP (PubMed:9405391). Inhibited by N-ethylmaleimide (Probable). Activated by poly(ethylene glycol) by enhancing the thermal stability of FUT7 (PubMed:9405391). Activated by Mn2+, Ca2+, and Mg2+ (PubMed:9405391). Both panosialin A and B inhibit activity with IC(50) values of 4.8 and 5.3 ug/ml, respectively (PubMed:10386892). Inhibited by gallic acid (GA) and (-)-epigallocatechin gallate (EGCG) in a time-dependent and irreversible manner with IC(50) values of 60 and 700 nM, respectively (PubMed:15081893).
messages: Leukocytic/myeloid lineage cells.
messages: N-glycosylated.

9606:TAS2R46
gene id: 9606:TAS2R46
uniprot id: P59540
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor T2R family.
messages: Expressed in subsets of taste receptor cells of the tongue and exclusively in gustducin-positive cells. Expressed on ciliated airway epithelium.
messages: Membrane
messages: Most taste cells may be activated by a limited number of bitter compounds; individual taste cells can discriminate among bitter stimuli.
messages: Receptor that may play a role in the perception of bitterness and is gustducin-linked. May play a role in sensing the chemical composition of the gastrointestinal content. The activity of this receptor may stimulate alpha gustducin, mediate PLC-beta-2 activation and lead to the gating of TRPM5 (By similarity). In airway epithelial cells, binding of bitter compounds increases the intracellular calcium ion concentration and stimulates ciliary beat frequency (By similarity).
messages: cilium membrane

9606:SAMD4B
gene id: 9606:SAMD4B
uniprot id: M0QZ22
uniprot id: Q5PRF9
uniprot id: Q66K25
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the SMAUG family.
messages: Cytoplasm
messages: Has transcriptional repressor activity. Overexpression inhibits the transcriptional activities of AP-1, p53/TP53 and CDKN1A.
messages: Nucleus
messages: Widely expressed in embryonic and adult tissues.

9606:GPN2
gene id: 9606:GPN2
uniprot id: Q9H9Y4
names: Function
names: Similarity
names: Subunit
messages: Belongs to the GPN-loop GTPase family.
messages: Heterodimers with GPN1 or GPN3 (By similarity). Binds to RNA polymerase II (RNAPII) (PubMed:20864038).
messages: Small GTPase required for proper localization of RNA polymerase II and III (RNAPII and RNAPIII). May act at an RNAP assembly step prior to nuclear import.

9606:DAPK1
gene id: 9606:DAPK1
uniprot id: P53355
names: Activity Regulation
names: Domain
names: Function
names: Induction
names: PTM
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Activated by Ca(2+)/calmodulin. Regulated by a locking mechanism, involving autophosphorylation at Ser-308 and calmodulin binding. In the inactive state, Ser-308 is phosphorylated. Activation involves its dephosphorylation and a release-of-autoinhibition mechanism where binding of calmodulin induces a conformational change that relieves the steric block of the active site by the autoinhibitory domain. Activity is modulated by UNC5B and NTN1. UNC5B activates it by inhibiting the phosphorylation at Ser-308, whereas NTN1 inhibits UNC5B-mediated activation of DAPK1. Endoplasmic-stress activates by causing Ser-308 dephosphorylation.
messages: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. DAP kinase subfamily.
messages: Calcium/calmodulin-dependent serine/threonine kinase involved in multiple cellular signaling pathways that trigger cell survival, apoptosis, and autophagy. Regulates both type I apoptotic and type II autophagic cell deaths signal, depending on the cellular setting. The former is caspase-dependent, while the latter is caspase-independent and is characterized by the accumulation of autophagic vesicles. Phosphorylates PIN1 resulting in inhibition of its catalytic activity, nuclear localization, and cellular function. Phosphorylates TPM1, enhancing stress fiber formation in endothelial cells. Phosphorylates STX1A and significantly decreases its binding to STXBP1. Phosphorylates PRKD1 and regulates JNK signaling by binding and activating PRKD1 under oxidative stress. Phosphorylates BECN1, reducing its interaction with BCL2 and BCL2L1 and promoting the induction of autophagy. Phosphorylates TSC2, disrupting the TSC1-TSC2 complex and stimulating mTORC1 activity in a growth factor-dependent pathway. Phosphorylates RPS6, MYL9 and DAPK3. Acts as a signaling amplifier of NMDA receptors at extrasynaptic sites for mediating brain damage in stroke. Cerebral ischemia recruits DAPK1 into the NMDA receptor complex and it phosphorylates GRINB at Ser-1303 inducing injurious Ca(2+) influx through NMDA receptor channels, resulting in an irreversible neuronal death. Required together with DAPK3 for phosphorylation of RPL13A upon interferon-gamma activation which is causing RPL13A involvement in transcript-selective translation inhibition.
messages: Contaminating sequence. Sequence of unknown origin in the C-terminal part.
messages: Cytoplasm
messages: In response to mitogenic stimulation (PMA or EGF), phosphorylated at Ser-289; phosphorylation suppresses DAPK1 pro-apoptotic function. Autophosphorylation at Ser-308 inhibits its catalytic activity. Phosphorylation at Ser-734 by MAPK1 increases its catalytic activity and promotes cytoplasmic retention of MAPK1. Endoplasmic-stress can cause dephosphorylation at Ser-308.
messages: Interacts with KLHL20 (PubMed:20389280). Interacts (via death domain) with MAPK1 and MAPK3 (PubMed:15616583). Interacts with MAP1B (via N-terminus) (PubMed:18195017). Interacts with PRKD1 in an oxidative stress-regulated manner (PubMed:17703233). Interacts with PIN1, PDCD6, BECN1, TSC2 and STX1A (PubMed:12730201, PubMed:16132846, PubMed:18974095, PubMed:19180116, PubMed:21497122). Interacts (via kinase domain) with DAPK3 (via kinase domain) (PubMed:15367680). Interacts with GRINB (By similarity). Interacts (via death domain) with UNC5B (via death domain) (PubMed:15729359). Interacts with UNC5C (via death domain) (PubMed:27068745).
messages: Isoform 2 cannot induce apoptosis but can induce membrane blebbing.
messages: Isoform 2 is expressed in normal intestinal tissue as well as in colorectal carcinomas.
messages: Removal of the C-terminal tail of isoform 2 (corresponding to amino acids 296-337 of isoform 2) by proteolytic cleavage stimulates maximally its membrane-blebbing function.
messages: The autoinhibitory domain sterically blocks the substrate peptide-binding site by making both hydrophobic and electrostatic contacts with the kinase core.
messages: Ubiquitinated by the BCR(KLHL20) E3 ubiquitin ligase complex, leading to its degradation by the proteasome.
messages: Up-regulated following treatment with IFNG/IFN-gamma.
messages: cytoskeleton

9606:PPP1R2
gene id: 9606:PPP1R2
uniprot id: P41236
names: Function
names: PTM
names: Similarity
names: Subunit
messages: Belongs to the protein phosphatase inhibitor 2 family.
messages: Heterodimer with PP1.
messages: Inhibitor of protein-phosphatase 1.
messages: Phosphorylation on Thr-73 by GSK3 activates PP1 by dissociating the PP1-PPP1R2 complex (By similarity). Phosphorylation on Ser-44 by ATM activates PP1 by dissociating the PP1-PPP1R2 complex.

9606:GMIP
gene id: 9606:GMIP
uniprot id: Q9P107
names: Function
names: Subunit
messages: Interacts with GEM through its N-terminal.
messages: Stimulates, in vitro and in vivo, the GTPase activity of RhoA.

9606:ANKRD9
gene id: 9606:ANKRD9
uniprot id: Q96BM1
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Cytoplasmic vesicle
messages: Part of an E3 ubiquitin-protein ligase complex with Elongin BC (ELOB and ELOC), CUL5 and ANKRD9 (PubMed:30293565). Interacts with IMPDH2; leading to ubiquitination of IMPDH2 and its subsequent proteasomal degradation (PubMed:31337707).
messages: Substrate receptor subunit of a cullin-RING superfamily E3 ligase complex (CUL5-based E3 ubiquitin ligase complex) which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:30293565). Depending of the metabolic state of the cell, promotes the proteasomal degradation of IMPDH2, the rate-limiting enzyme in GTP biosynthesis or protects IMPDH2 by stabilizing IMPDH2 filaments assembly (PubMed:30293565, PubMed:31337707). Implicated in different cellular processes, like copper homeostasis and cell proliferation (PubMed:24522796, PubMed:30293565).
messages: cytosol

9606:PITX1
gene id: 9606:PITX1
uniprot id: P78337
uniprot id: X5D9A5
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the paired homeobox family. Bicoid subfamily.
messages: Interacts with POU1F1 (PubMed:26612202).
messages: Nucleus
messages: Sequence-specific transcription factor that binds gene promoters and activates their transcription. May play a role in the development of anterior structures, and in particular, the brain and facies and in specifying the identity or structure of hindlimb.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The gene represented in this entry is involved in disease pathogenesis. A chromosomal aberration involving the PITX1 locus results in LBNBG. Translocation t(5;18)(q31.1;q12.3). Additionally, two chromosome 5 deletions located 5'of PITX1 have been found in LBNBG patients. These structural variations cause altered expression of PITX1 in the forelimb via the activation of ectopic enhancers (PubMed:23022097).

9606:CIMAP1A
gene id: 9606:CIMAP1A
uniprot id: Q96PU9
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: 'Shippo' is a Japanese word for tail.
messages: Belongs to the CIMAP family.
messages: Cytoplasm
messages: Outer dense fibers are filamentous structures located on the outside of the axoneme in the midpiece and principal piece of the mammalian sperm tail. May help to maintain the passive elastic structures and elastic recoil of the sperm tail.
messages: Testis-specific.
messages: flagellum

9606:STAT1
gene id: 9606:STAT1
uniprot id: P42224
names: Caution
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Interacts with Epstein-Barr virus (EBV) tegument protein BGLF2; this interaction leads to STAT1 dephosphorylation and inhibition.
messages: (Microbial infection) Interacts with HCV core protein; the interaction results in STAT1 degradation.
messages: (Microbial infection) Interacts with Nipah virus P, V and W proteins preventing activation of ISRE and GAS promoter.
messages: (Microbial infection) Interacts with Rabies virus phosphoprotein preventing activation of ISRE and GAS promoter.
messages: (Microbial infection) Interacts with Sendai virus C', C, Y1 and Y2 proteins, preventing activation of ISRE and GAS promoter.
messages: (Microbial infection) Interacts with ebolavirus protein VP24.
messages: (Microbial infection) Ubiquitinated by Herpes simplex virus 2 E3 ubiquitin ligase ICP22.
messages: Belongs to the transcription factor STAT family.
messages: Cytoplasm
messages: Deubiquitinated by USP13; leading to STAT1 stabilization and positive regulation of type I and type II IFN signalings.
messages: Has been shown to be mono-ADP-ribosylated at Glu-657 and Glu-705 by PARP14 which prevents phosphorylation at Tyr-701 (PubMed:27796300). However, the role of ADP-ribosylation in the prevention of phosphorylation has been called into question (PubMed:29858569). It has been suggested that the lack of phosphorylation may be due to sumoylation of Lys-703 (PubMed:29858569).
messages: ISGylated.
messages: Isoform alpha homodimerizes upon IFN-gamma induced phosphorylation (PubMed:8605877, PubMed:28753426). Heterodimer with STAT2 upon IFN-alpha/beta induced phosphorylation (PubMed:8605877). The heterodimer STAT1:STAT2 forms the interferon-stimulated gene factor 3 complex (ISGF3) with IRF9 (By similarity). Interacts (phosphorylated at Ser-727) with PIAS1; the interaction results in release of STAT1 from its target gene (PubMed:9724754, PubMed:17897103). Interacts with IFNAR1; the interaction requires the phosphorylation of IFNAR1 at 'Tyr-466' (PubMed:9121453). Interacts with IFNAR2 (PubMed:9121453). Found in a complex with NMI and CREBBP/CBP (PubMed:9989503). Interacts with NMI which is required for CREBBP/CBP recruitment to the complex (PubMed:9989503). Interacts with PTK2/FAK1 (PubMed:11278462). Interacts with SRC (By similarity). Interacts with ERBB4 (phosphorylated) (PubMed:18721752). Interacts with PARP9 and DTX3L independently of IFN-beta or IFN-gamma-mediated STAT1 'Tyr-701' phosphorylation (PubMed:26479788). Interacts with histone acetyltransferase EP300/p300 in response to INF-gamma stimulation (PubMed:16257975, PubMed:26479788). Interacts with OTOP1 (By similarity). Interacts with IFNGR1 (PubMed:8156998). Interacts with STAT4 (PubMed:34508746).
messages: Mono-ADP-ribosylated at Glu-657 and Glu-705 by PARP14; ADP-ribosylation prevents phosphorylation at Tyr-701 (PubMed:27796300). However, the role of ADP-ribosylation in the prevention of phosphorylation has been called into question and the lack of phosphorylation may be due to sumoylation of Lys-703 (PubMed:29858569).
messages: Monomethylated at Lys-525 by SETD2; monomethylation is necessary for phosphorylation at Tyr-701, translocation into the nucleus and activation of the antiviral defense.
messages: Nucleus
messages: Phosphorylated on tyrosine and serine residues in response to a variety of cytokines/growth hormones including IFN-alpha, IFN-gamma, PDGF and EGF (PubMed:28753426, PubMed:26479788). Activated KIT promotes phosphorylation on tyrosine residues and subsequent translocation to the nucleus (PubMed:21135090). Upon EGF stimulation, phosphorylation on Tyr-701 (lacking in beta form) by JAK1, JAK2 or TYK2 promotes dimerization and subsequent translocation to the nucleus (PubMed:7657660, PubMed:28753426). Growth hormone (GH) activates STAT1 signaling only via JAK2 (PubMed:7657660). Tyrosine phosphorylated in response to constitutively activated FGFR1, FGFR2, FGFR3 and FGFR4 (PubMed:17561467, PubMed:19088846). Phosphorylation on Ser-727 by several kinases including MAPK14, ERK1/2, CAMK2/CAMKII and CK2 in response to IFN-gamma stimulation, is required for maximal transcriptional activity (PubMed:7543024, PubMed:15322115, PubMed:16799645, PubMed:17897103). Phosphorylated on Ser-727 by CAMK2/CAMKII in response to IFN-gamma stimulation and calcium mobilization, promoting activity (PubMed:11972023, PubMed:16257975). Phosphorylated by CAMK2/CAMKII in response to IFN-beta stimulation and calcium mobilization in epithelial cells, promoting activity (PubMed:35568036). Phosphorylation on Ser-727 promotes sumoylation though increasing interaction with PIAS (PubMed:17897103). Phosphorylation on Ser-727 by PRKCD induces apoptosis in response to DNA-damaging agents (PubMed:15322115). Phosphorylated on tyrosine residues when PTK2/FAK1 is activated; most likely this is catalyzed by a SRC family kinase (PubMed:11278462). Dephosphorylation on tyrosine residues by PTPN2 negatively regulates interferon-mediated signaling (PubMed:12138178). Upon viral infection or IFN induction, phosphorylation on Ser-708 occurs much later than phosphorylation on Tyr-701 and is required for the binding of ISGF3 on the ISREs of a subset of IFN-stimulated genes IKBKE-dependent (PubMed:22065572). Phosphorylation at Ty…
messages: Signal transducer and transcription activator that mediates cellular responses to interferons (IFNs), cytokine KITLG/SCF and other cytokines and other growth factors (PubMed:9724754, PubMed:12855578, PubMed:12764129, PubMed:15322115, PubMed:34508746, PubMed:35568036, PubMed:23940278). Following type I IFN (IFN-alpha and IFN-beta) binding to cell surface receptors, signaling via protein kinases leads to activation of Jak kinases (TYK2 and JAK1) and to tyrosine phosphorylation of STAT1 and STAT2. The phosphorylated STATs dimerize and associate with ISGF3G/IRF-9 to form a complex termed ISGF3 transcription factor, that enters the nucleus (PubMed:28753426, PubMed:35568036). ISGF3 binds to the IFN stimulated response element (ISRE) to activate the transcription of IFN-stimulated genes (ISG), which drive the cell in an antiviral state (PubMed:28753426, PubMed:35568036). In response to type II IFN (IFN-gamma), STAT1 is tyrosine- and serine-phosphorylated (PubMed:26479788). It then forms a homodimer termed IFN-gamma-activated factor (GAF), migrates into the nucleus and binds to the IFN gamma activated sequence (GAS) to drive the expression of the target genes, inducing a cellular antiviral state (PubMed:8156998). Becomes activated in response to KITLG/SCF and KIT signaling (PubMed:15526160). May mediate cellular responses to activated FGFR1, FGFR2, FGFR3 and FGFR4 (PubMed:19088846). Involved in food tolerance in small intestine: associates with the Gasdermin-D, p13 cleavage product (13 kDa GSDMD) and promotes transcription of CIITA, inducing type 1 regulatory T (Tr1) cells in upper small intestine (By similarity).
messages: Sumoylated with SUMO1, SUMO2 and SUMO3. Sumoylation is enhanced by IFN-gamma-induced phosphorylation on Ser-727, and by interaction with PIAS proteins. Enhances the transactivation activity.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The disease is caused by variants affecting the gene represented in this entry. STAT1 mutations in patients with autosomal dominant candidiasis lead to defective responses of type 1 and type 17 helper T-cells, characterized by reduced production of interferon-alpha, interleukin-17, and interleukin-22. These cytokines are crucial for the antifungal defense of skin and mucosa (PubMed:21714643).

9606:TACR3
gene id: 9606:TACR3
uniprot id: P29371
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: The anchoring of this receptor to the plasma membrane is probably mediated by the palmitoylation of a cysteine residue.
messages: The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry. The genetics of hypogonadotropic hypogonadism involves various modes of transmission. Oligogenic inheritance has been reported in some patients carrying mutations in TACR3 as well as in other HH-associated genes including FGFR1, SPRY4 and KAL1 (PubMed:23643382).
messages: This is a receptor for the tachykinin neuropeptide neuromedin-K (neurokinin B). It is associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of affinity of this receptor to tachykinins is: neuromedin-K > substance K > substance P.

9606:SLC25A21
gene id: 9606:SLC25A21
uniprot id: Q9BQT8
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the mitochondrial carrier (TC 2.A.29) family.
messages: Expressed in placenta, gall bladder and colon.
messages: Mitochondrion inner membrane
messages: The disease may be caused by variants affecting the gene represented in this entry.
messages: Transports dicarboxylates across the inner membranes of mitochondria by a counter-exchange mechanism (PubMed:11083877). Can transport 2-oxoadipate (2-oxohexanedioate), 2-oxoglutarate, adipate (hexanedioate), glutarate, and to a lesser extent, pimelate (heptanedioate), 2-oxopimelate (2-oxoheptanedioate), 2-aminoadipate (2-aminohexanedioate), oxaloacetate, and citrate (PubMed:11083877). Plays a central role in catabolism of lysine, hydroxylysine, and tryptophan, by transporting common metabolite intermediates (such as 2-oxoadipate) into the mitochondria, where it is converted into acetyl-CoA and can enter the citric acid (TCA) cycle (Probable).

9606:POP7
gene id: 9606:POP7
uniprot id: O75817
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the histone-like Alba family.
messages: Component of nuclear RNase P and RNase MRP complexes (PubMed:9630247, PubMed:15096576, PubMed:16723659, PubMed:20215441, PubMed:30454648). RNase P consists of a catalytic RNA moiety and 10 different protein chains; POP1, POP4, POP5, POP7, RPP14, RPP21, RPP25, RPP30, RPP38 and RPP40 (PubMed:9630247, PubMed:16723659, PubMed:30454648). Within the RNase P complex, POP1, POP7 and RPP25 form the 'finger' subcomplex, POP5, RPP14, RPP40 and homodimeric RPP30 form the 'palm' subcomplex, and RPP21, POP4 and RPP38 form the 'wrist' subcomplex. All subunits of the RNase P complex interact with the catalytic RNA (PubMed:30454648). Several subunits of RNase P are also part of the RNase MRP complex. RNase MRP consists of a catalytic RNA moiety and about 8 protein subunits; POP1, POP7, RPP25, RPP30, RPP38, RPP40 and possibly also POP4 and POP5 (PubMed:15096576, PubMed:16723659, PubMed:28115465). Interacts with SMN1 (PubMed:14715275). POP7 forms a heterodimer with RPP25 that binds to the P3 stem loop of the catalytic RNA (PubMed:15096576, PubMed:20215441, PubMed:29625199).
messages: Component of ribonuclease P, a ribonucleoprotein complex that generates mature tRNA molecules by cleaving their 5'-ends (PubMed:9630247, PubMed:30454648). Also a component of the MRP ribonuclease complex, which cleaves pre-rRNA sequences (PubMed:28115465).
messages: Cytoplasm
messages: Cytoplasmic granule
messages: nucleolus

9606:TEAD4
gene id: 9606:TEAD4
uniprot id: Q15561
names: Function
names: Sequence Caution
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Interacts with YAP1 and WWTR1/TAZ.
messages: Nucleus
messages: Preferentially expressed in skeletal muscle. Lower levels in pancreas, placenta, and heart.
messages: Transcription factor which plays a key role in the Hippo signaling pathway, a pathway involved in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein MST1/MST2, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Acts by mediating gene expression of YAP1 and WWTR1/TAZ, thereby regulating cell proliferation, migration and epithelial mesenchymal transition (EMT) induction. Binds specifically and non-cooperatively to the Sph and GT-IIC 'enhansons' (5'-GTGGAATGT-3') and activates transcription. Binds to the M-CAT motif.
messages: Unusual initiator. The initiator methionine is coded by a non-canonical ATA isoleucine codon.

9606:HERC5
gene id: 9606:HERC5
uniprot id: B4DXV3
uniprot id: Q9UII4
names: Caution
names: Function
names: Induction
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Functions as an E3 ligase for ISGylation of hepatitis B virus protein X leading to enhanced viral replication due to increased interferon resistance.
messages: Binds to CCNA1, CCNB1, CCND1 and CCNE1. Interacts with UBE2L6. Interacts with IRF3, this interaction is marginal in resting cells but enhanced upon viral infection. Interacts with influenza A virus NS1.
messages: By IFNB1/IFN-beta. In endothelial cells, by TNF, IL1B/interleukin-1B and by bacterial lipopolysaccharides (LPS), hardly induced in other cells of the vascular wall such as primary smooth muscle cells and fibroblasts. By viral infection.
messages: Cytoplasm
messages: Expressed in testis and to a lesser degree in brain, ovary and placenta. Found in most tissues at low levels.
messages: ISGylated.
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: Major E3 ligase for ISG15 conjugation (PubMed:27534820, PubMed:34572049, PubMed:37279284). Acts as a positive regulator of innate antiviral response in cells induced by interferon. Functions as part of the ISGylation machinery that recognizes target proteins in a broad and relatively non-specific manner. Catalyzes ISGylation of IRF3 which results in sustained activation, it attenuates IRF3-PIN1 interaction, which antagonizes IRF3 ubiquitination and degradation, and boosts the antiviral response. Mediates ISGylation of the phosphatase PTEN leading to its degradation, thus alleviating its suppression of the PI3K-AKT signaling pathway and promoting the production of cytokines that facilitate bacterial clearance (PubMed:37279284). Interferes with the function of key viral structural proteins such as ebolavirus structural protein VP40 or HIV-1 protein GAG (PubMed:22093708, PubMed:34572049). Catalyzes ISGylation of influenza A viral NS1 which attenuates virulence; ISGylated NS1 fails to form homodimers and thus to interact with its RNA targets. Catalyzes ISGylation of papillomavirus type 16 L1 protein which results in dominant-negative effect on virus infectivity. Physically associated with polyribosomes, broadly modifies newly synthesized proteins in a cotranslational manner. In an interferon-stimulated cell, newly translated viral proteins are primary targets of ISG15. Promotes parkin/PRKN ubiquitin E3 ligase activity by suppressing the intramolecular interaction that maintains its autoinhibited conformation (PubMed:27534820).
messages: Was thought to be a ubiquitin ligase ubiquitinated by UBE2D1, but was confirmed by numerous studies that it's main function is as E3 ISG15 ligase.
messages: perinuclear region

9606:ZSWIM6
gene id: 9606:ZSWIM6
uniprot id: Q9HCJ5
names: Disease Annotation
names: Function
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: involved in nervous system development, important for striatal morphology and motor regulation.

9606:SPO11
gene id: 9606:SPO11
uniprot id: Q9Y5K1
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the TOP6A family.
messages: Component of a topoisomerase 6 complex specifically required for meiotic recombination. Together with TOP6BL, mediates DNA cleavage that forms the double-strand breaks (DSB) that initiate meiotic recombination. The complex promotes relaxation of negative and positive supercoiled DNA and DNA decatenation through cleavage and ligation cycles. Essential for the phosphorylation of SMC3, HORMAD1 and HORMAD2.
messages: Heterotetramer of SPO11 and 2 TOP6BL chains. Interacts with TOP6BL.
messages: Highly expressed in testis.
messages: Nucleus

9606:ZWINT
gene id: 9606:ZWINT
uniprot id: O95229
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Interacts with ZW10 and MIS12. Interacts with the NDC80 subunit of the NDC80 complex specifically during mitosis. Also interacts with KNL1, CETN3, DSN1 and PMF1.
messages: Nucleus
messages: Part of the MIS12 complex, which is required for kinetochore formation and spindle checkpoint activity. Required to target ZW10 to the kinetochore at prometaphase.
messages: kinetochore

9606:GPX4
gene id: 9606:GPX4
uniprot id: P36969
uniprot id: Q6PI42
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the glutathione peroxidase family.
messages: Cytoplasm
messages: Essential antioxidant peroxidase that directly reduces phospholipid hydroperoxide even if they are incorporated in membranes and lipoproteins (By similarity). Can also reduce fatty acid hydroperoxide, cholesterol hydroperoxide and thymine hydroperoxide (By similarity). Plays a key role in protecting cells from oxidative damage by preventing membrane lipid peroxidation (By similarity). Required to prevent cells from ferroptosis, a non-apoptotic cell death resulting from an iron-dependent accumulation of lipid reactive oxygen species (PubMed:24439385). The presence of selenocysteine (Sec) versus Cys at the active site is essential for life: it provides resistance to overoxidation and prevents cells against ferroptosis (By similarity). The presence of Sec at the active site is also essential for the survival of a specific type of parvalbumin-positive interneurons, thereby preventing against fatal epileptic seizures (By similarity). May be required to protect cells from the toxicity of ingested lipid hydroperoxides (By similarity). Required for normal sperm development and male fertility (By similarity). Essential for maturation and survival of photoreceptor cells (By similarity). Plays a role in a primary T-cell response to viral and parasitic infection by protecting T-cells from ferroptosis and by supporting T-cell expansion (By similarity). Plays a role of glutathione peroxidase in platelets in the arachidonic acid metabolism (PubMed:11115402). Reduces hydroperoxy ester lipids formed by a 15-lipoxygenase that may play a role as down-regulator of the cellular 15-lipoxygenase pathway (By similarity).
messages: Mitochondrion
messages: Monomer. Has a tendency to form higher mass oligomers.
messages: Present primarily in testis. Expressed in platelets (at protein level) (PubMed:11115402).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:PPM1N
gene id: 9606:PPM1N
uniprot id: Q8N819
names: Cofactor
names: Similarity
messages: Belongs to the PP2C family.
messages: Binds 2 magnesium or manganese ions per subunit.

9606:GABRB1
gene id: 9606:GABRB1
uniprot id: P18505
uniprot id: X5DNL6
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the ligand-gated ion channel (TC 1.A.9) family.
messages: Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRB1 sub-subfamily.
messages: Binds UBQLN1 (By similarity). Heteropentamer, formed by a combination of alpha, beta, gamma, delta and rho chains. Interacts with KCTD8, KCTD12 and KCTD16; this interaction determines the pharmacology and kinetics of the receptor response, the KCTD proteins markedly accelerating the GABA-B response, although to different extents (By similarity).
messages: Cell membrane
messages: Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel.
messages: Membrane
messages: Postsynaptic cell membrane
messages: Synaptic cell membrane
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:CDK5RAP1
gene id: 9606:CDK5RAP1
uniprot id: A0A0S2Z5J9
uniprot id: Q53H36
uniprot id: Q96SZ6
names: Caution
names: Cofactor
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Absence of the mitochondrial target sequence which may lead to miss-localization.
messages: Belongs to the methylthiotransferase family. MiaB subfamily.
messages: Binds 2 [4Fe-4S] clusters. One cluster is coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine.
messages: CDK5RAP1 was proposed to act on both nuclear and mitochondrial RNA (PubMed:22422838). However, another study shows that ms2i6A is a mitochondrial tRNA specific modification and is absent from nuclear encoded RNA species, implying that there is no methylthiotransferase activity on nuclear RNA (PubMed:28981754).
messages: Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas (PubMed:10721722). Expressed in neurons of central nervous tissue (PubMed:10721722, PubMed:11882646).
messages: High expression in placenta and lung.
messages: Interacts with CDK5R1 (p35 form). CDK5RAP1, CDK5RAP2 and CDK5RAP3 show competitive binding to CDK5R1. Forms a complex with CDK5R1 and CDK5.
messages: Mainly expressed in brain, placenta and testis.
messages: May be due to intron retention.
messages: Methylthiotransferase that catalyzes the conversion of N6-(dimethylallyl)adenosine (i(6)A) to 2-methylthio-N6-(dimethylallyl)adenosine (ms(2)i(6)A) at position 37 (adjacent to the 3'-end of the anticodon) of four mitochondrial DNA-encoded tRNAs (Ser(UCN), Phe, Tyr and Trp) (PubMed:22422838, PubMed:25738458, PubMed:28981754). Essential for efficient and highly accurate protein translation by the ribosome (PubMed:22422838, PubMed:25738458, PubMed:28981754). Specifically inhibits CDK5 activation by CDK5R1 (PubMed:11882646). Essential for efficient mitochondrial protein synthesis and respiratory chain; shows pathological consequences in mitochondrial disease (PubMed:25738458).
messages: Mitochondrion

9606:GOLGA8H
gene id: 9606:GOLGA8H
uniprot id: P0CJ92
names: Similarity
messages: Belongs to the GOLGA8 family.

9606:KRTAP10-7
gene id: 9606:KRTAP10-7
uniprot id: P60409
names: Function
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Belongs to the KRTAP type 10 family.
messages: In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.
messages: Interacts with hair keratins.
messages: Restricted to a narrow region of the hair fiber cuticle, lying approximately 20 cell layers above the apex of the dermal papilla of the hair root; not detected in any other tissues.

9606:COLGALT1
gene id: 9606:COLGALT1
uniprot id: Q8NBJ5
names: Caution
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the glycosyltransferase 25 family.
messages: Beta-galactosyltransferase that transfers beta-galactose to hydroxylysine residues of type I collagen (PubMed:19075007, PubMed:22216269, PubMed:27402836). By acting on collagen glycosylation, facilitates the formation of collagen triple helix (PubMed:27402836). Also involved in the biosynthesis of collagen type IV (PubMed:30412317).
messages: Endoplasmic reticulum lumen
messages: Has no glucosyltransferase activity.
messages: N-glycosylated.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitous with higher levels in placenta, heart, lung and spleen.

9606:NHERF2
gene id: 9606:NHERF2
uniprot id: Q15599
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Apical cell membrane
messages: Endomembrane system
messages: Homodimer, and heterodimer with NHERF1. Binds PDZK1. Found in a complex with EZR, PODXL and NHERF2 (By similarity). Interacts (via the PDZ domains) with PODXL (via the C-terminal PDZ-binding motif DTHL); interaction is detected in glomerular epithelium cells (By similarity). Binds ADRB2, SLC9A3, P2RY1, P2YR2, SRY, RDX and LPAR2. Interacts with MCC and PODXL. Interacts with SGK1 and KCNJ1/ROMK1. Interacts (via the PDZ domains) with SLC26A6 isoform 4 and isoform 5.
messages: Nucleus
messages: Scaffold protein that connects plasma membrane proteins with members of the ezrin/moesin/radixin family and thereby helps to link them to the actin cytoskeleton and to regulate their surface expression. Necessary for cAMP-mediated phosphorylation and inhibition of SLC9A3 (PubMed:18829453). May also act as scaffold protein in the nucleus.
messages: Widely expressed.

9606:HNRNPR
gene id: 9606:HNRNPR
uniprot id: B4DMB1
uniprot id: B4DMD1
uniprot id: B4DT28
uniprot id: O43390
uniprot id: Q0VGD6
uniprot id: Q6MZS5
names: Disease Annotation
names: Function
names: Miscellaneous
names: Subcellular Location Annotation
names: Subunit
messages: Component of ribonucleosomes, which are complexes of at least 20 other different heterogeneous nuclear ribonucleoproteins (hnRNP). hnRNP play an important role in processing of precursor mRNA in the nucleus.
messages: Cytoplasm
messages: Expression is low and neural-specific.
messages: Identified in the spliceosome C complex. Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Interacts with GTPBP1.
messages: Microsome
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: nucleoplasm

9606:STEAP1
gene id: 9606:STEAP1
uniprot id: Q9UHE8
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the STEAP family.
messages: Cell membrane
messages: Does not function as a metalloreductase due to the absence of binding sites for the electron-donating substrate NADPH. Promotes Fe(3+) reduction when fused to the NADPH-binding domain of STEAP4.
messages: Endosome membrane
messages: Homotrimer.
messages: Ubiquitously expressed. Highly expressed in prostate tumors.

9606:TRPV4
gene id: 9606:TRPV4
uniprot id: Q9HBA0
names: Activity Regulation
names: Disease Annotation
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Facilitates Dengue virus (DENV) replication, possibly through its action on DDX3X.
messages: (Microbial infection) Facilitates Zika virus (ZIKV) replication, possibly through its action on DDX3X.
messages: (Microbial infection) Facilitates hepatitis C virus (HCV) replication, possibly through its action on DDX3X.
messages: Apical cell membrane
messages: Belongs to the transient receptor (TC 1.A.4) family. TrpV subfamily. TRPV4 sub-subfamily.
messages: Cell membrane
messages: Channel activation is inhibited by binding to phosphatidylinositol-4,5-bisphosphate, and to a much lesser degree by phosphatidylinositol-3,4,5-trisphosphate. Not inhibited by phosphatidylinositol-3,4-bisphosphate and phosphatidylinositol-3,5-bisphosphate.
messages: Endoplasmic reticulum
messages: Forms active ion channels.
messages: Found in the synoviocytes from patients with (RA) and without (CTR) rheumatoid arthritis (at protein level).
messages: Genetic variations in TRPV4 determine the sodium serum level quantitative trait locus 1 (SSQTL1) [MIM:613508]. In some populations, variant Pro19Ser has been shown to be significantly associated with hyponatremia defined as serum sodium concentration below or equal to 135 mEq/L.
messages: Homotetramer (Probable). Self-associates in an isoform-specific manner (PubMed:16293632). Isoform 1 and isoform 5 can oligomerize, but isoform 2, isoform 4 and isoform 6 cannot oligomerize (PubMed:16293632). Interacts with calmodulin (PubMed:12724311). Interacts with Map7 and Src family Tyr protein kinases LYN, SRC, FYN, HCK, LCK and YES (By similarity). Interacts with CTNNB1 (By similarity). The TRPV4 and CTNNB1 complex can interact with CDH1 (By similarity). Interacts with PACSIN1, PACSIN2 and PACSIN3 (via SH3 domain) (By similarity). Part of a complex containing MLC1, AQP4, HEPACAM and ATP1B1 (PubMed:22328087). Interacts with ITPR3 (PubMed:18826956). Interacts with AQP5; the interaction is probably indirect and regulates TRPV4 activation by hypotonicity (By similarity). Interacts with ANO1 (By similarity). Interacts (via C-terminus) with PKD2 (via C-terminus) (PubMed:18695040). Interacts with DDX3X; this interaction is decreased when the channel is activated (PubMed:29899501).
messages: Lacks channel activity, due to impaired oligomerization and intracellular retention.
messages: N-glycosylated.
messages: Non-selective calcium permeant cation channel involved in osmotic sensitivity and mechanosensitivity. Activation by exposure to hypotonicity within the physiological range exhibits an outward rectification (PubMed:18826956, PubMed:18695040, PubMed:29899501). Also activated by heat, low pH, citrate and phorbol esters (PubMed:16293632, PubMed:18826956, PubMed:18695040, PubMed:25256292, PubMed:20037586, PubMed:21964574). Increase of intracellular Ca(2+) potentiates currents. Channel activity seems to be regulated by a calmodulin-dependent mechanism with a negative feedback mechanism (PubMed:12724311, PubMed:18826956). Promotes cell-cell junction formation in skin keratinocytes and plays an important role in the formation and/or maintenance of functional intercellular barriers (By similarity). Acts as a regulator of intracellular Ca(2+) in synoviocytes (PubMed:19759329). Plays an obligatory role as a molecular component in the nonselective cation channel activation induced by 4-alpha-phorbol 12,13-didecanoate and hypotonic stimulation in synoviocytes and also regulates production of IL-8 (PubMed:19759329). Together with PKD2, forms mechano- and thermosensitive channels in cilium (PubMed:18695040). Negatively regulates expression of PPARGC1A, UCP1, oxidative metabolism and respiration in adipocytes (By similarity). Regulates expression of chemokines and cytokines related to pro-inflammatory pathway in adipocytes (By similarity). Together with AQP5, controls regulatory volume decrease in salivary epithelial cells (By similarity). Required for normal development and maintenance of bone and cartilage (PubMed:26249260). In its inactive state, may sequester DDX3X at the plasma membrane. When activated, the interaction between both proteins is affected and DDX3X relocalizes to the nucleus (PubMed:29899501).
messages: Non-selective calcium permeant cation channel involved in osmotic sensitivity and mechanosensitivity. Activation by exposure to hypotonicity within the physiological range exhibits an outward rectification. Also activated by phorbol esters. Has the same channel activity as isoform 1, and is activated by the same stimuli.
messages: The ANK repeat region mediates interaction with Ca(2+)-calmodulin and ATP binding (By similarity). The ANK repeat region mediates interaction with phosphatidylinositol-4,5-bisphosphate and related phosphatidylinositides (PubMed:25256292).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: adherens junction
messages: cilium

9606:ATP10D
gene id: 9606:ATP10D
uniprot id: Q9P241
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Autophosphorylated at the conserved aspartate of the P-type ATPase signature sequence.
messages: Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IV subfamily.
messages: Catalytic component of a P4-ATPase flippase complex, which catalyzes the hydrolysis of ATP coupled to the transport of glucosylceramide (GlcCer) from the outer to the inner leaflet of the plasma membrane.
messages: Cell membrane
messages: Component of a P4-ATPase flippase complex which consists of a catalytic alpha subunit ATP10A and an accessory beta subunit TMEM30A.
messages: Endoplasmic reticulum membrane
messages: Expressed in placenta and, to a lesser extent, in kidney.

9606:GPHB5
gene id: 9606:GPHB5
uniprot id: A0A0F7RPU1
uniprot id: Q86YW7
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the glycoprotein hormones subunit beta family.
messages: Functions as a heterodimeric glycoprotein hormone with GPHA2 able to bind and activate the thyroid-stimulating hormone receptor (TSHR), leading to increased cAMP production. Plays a central role in controlling thyroid cell metabolism.
messages: Heterodimer with GPHA2; this heterodimer interacts with thyroid-stimulating hormone receptor (TSHR), and hence stimulates cAMP production.
messages: Highly expressed in brain and at low levels in pituitary. Also found in retina, testis and skin but not in pancreas, parotid, kidney, stomach, liver, colon, small intestine, thyroid, brain or adrenal gland. In pituitary, colocalizes with ACTH, suggesting that it is located in corticotrophs.
messages: N-glycosylated.
messages: Secreted

9606:CHRNE
gene id: 9606:CHRNE
uniprot id: Q04844
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.
messages: Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Epsilon/CHRNE sub-subfamily.
messages: Cell membrane
messages: Pentamer of two alpha chains, and one each of the beta, delta, and gamma (in immature muscle) or epsilon (in mature muscle) chains. The muscle heteropentamer composed of alpha-1, beta-1, delta, epsilon subunits interacts with the alpha-conotoxin ImII (PubMed:15609996).
messages: Postsynaptic cell membrane
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The muscle AChR is the major target antigen in the autoimmune disease myasthenia gravis. Myasthenia gravis is characterized by sporadic muscular fatigability and weakness, occurring chiefly in muscles innervated by cranial nerves, and characteristically improved by cholinesterase-inhibiting drugs.

9606:MGMT
gene id: 9606:MGMT
uniprot id: B4DEE8
uniprot id: P16455
names: Cofactor
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the MGMT family.
messages: Binds 1 zinc ion.
messages: Involved in the cellular defense against the biological effects of O6-methylguanine (O6-MeG) and O4-methylthymine (O4-MeT) in DNA. Repairs the methylated nucleobase in DNA by stoichiometrically transferring the methyl group to a cysteine residue in the enzyme. This is a suicide reaction: the enzyme is irreversibly inactivated.
messages: Nucleus
messages: This enzyme catalyzes only one turnover and therefore is not strictly catalytic. According to one definition, an enzyme is a biocatalyst that acts repeatedly and over many reaction cycles.

9606:CACNA2D2
gene id: 9606:CACNA2D2
uniprot id: Q9NY47
names: Disease Annotation
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the calcium channel subunit alpha-2/delta family.
messages: Binds gabapentin, an antiepileptic drug.
messages: Dimer formed of alpha-2-2 and delta-2 chains; disulfide-linked. Voltage-dependent calcium channels are multisubunit complexes, consisting of alpha-1 (CACNA1), alpha-2 (CACNA2D), beta (CACNB) and delta (CACNA2D) subunits in a 1:1:1:1 ratio (By similarity).
messages: May be proteolytically processed into subunits alpha-2-2 and delta-2 that are disulfide-linked. It is however unclear whether such cleavage really takes place in vivo and has a functional role (By similarity).
messages: Membrane
messages: Predominantly present in cerebellar cortex. Present in various lung tumor cell lines, while it is absent in normal lung (at protein level). Highly expressed in heart, lung, testis, pancreas and skeletal muscle. Also expressed in kidney, liver, placenta and brain.
messages: The MIDAS-like motif in the VWFA domain binds divalent metal cations and is required to promote trafficking of the alpha-1 (CACNA1) subunit to the plasma membrane by an integrin-like switch.
messages: The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Acts as a regulatory subunit for P/Q-type calcium channel (CACNA1A), N-type (CACNA1B), L-type (CACNA1C OR CACNA1D) and possibly T-type (CACNA1G) (PubMed:15111129, PubMed:23339110). Overexpression induces apoptosis.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:CRX
gene id: 9606:CRX
uniprot id: O43186
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the paired homeobox family.
messages: Interacts (via the homeobox) with NRL (via the leucine-zipper domain). Interacts with PDC, RAX2, RORB and SCA7.
messages: Nucleus
messages: Retina.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Transcription factor that binds and transactivates the sequence 5'-TAATC[CA]-3' which is found upstream of several photoreceptor-specific genes, including the opsin genes. Acts synergistically with other transcription factors, such as NRL, RORB and RAX, to regulate photoreceptor cell-specific gene transcription. Essential for the maintenance of mammalian photoreceptors.

9606:DEFB103B
gene id: 9606:DEFB103B
uniprot id: P81534
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the beta-defensin family.
messages: By bacterial infection and by IFNG/IFN-gamma.
messages: Exhibits antimicrobial activity against Gram-positive bacteria S.aureus and S.pyogenes, Gram-negative bacteria P.aeruginosa and E.coli and the yeast C.albicans. Kills multiresistant S.aureus and vancomycin-resistant E.faecium. No significant hemolytic activity was observed.
messages: Highly expressed in skin and tonsils, and to a lesser extent in trachea, uterus, kidney, thymus, adenoid, pharynx and tongue. Low expression in salivary gland, bone marrow, colon, stomach, polyp and larynx. No expression in small intestine.
messages: Secreted

9606:NPHS1
gene id: 9606:NPHS1
uniprot id: O60500
names: Developmental Stage
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the immunoglobulin superfamily.
messages: Cell membrane
messages: In 23-week-old embryo found in epithelial podocytes of the periphery of mature and developing glomeruli.
messages: Interacts with CD2AP (via C-terminal domain). Interacts with MAGI1 (via PDZ 2 and 3 domains) forming a tripartite complex with IGSF5/JAM4. Interacts with DDN; the interaction is direct. Self-associates (via the Ig-like domains). Also interacts (via the Ig-like domains) with KIRREL1/NEPH1 and KIRREL2; the interaction with KIRREL1 is dependent on KIRREL1 glycosylation. Interacts with KIRREL3. Forms a complex with ACTN4, CASK, IQGAP1, MAGI2, SPTAN1 and SPTBN1 (By similarity). Interacts with NPHS2 (PubMed:11562357). Interacts with phosphatidylinositol 3-kinase regulatory subunit PIK3R1; the interaction is reduced by high glucose levels (PubMed:28955049).
messages: Phosphorylated at Tyr-1193 by FYN, leading to the recruitment and activation of phospholipase C-gamma-1/PLCG1 (By similarity). Tyrosine phosphorylation is reduced by high glucose levels (PubMed:28955049). Dephosphorylated by tensin TNS2 which leads to reduced binding of NPHN1 to PIK3R1 (PubMed:28955049).
messages: Seems to play a role in the development or function of the kidney glomerular filtration barrier. Regulates glomerular vascular permeability. May anchor the podocyte slit diaphragm to the actin cytoskeleton. Plays a role in skeletal muscle formation through regulation of myoblast fusion (By similarity).
messages: Specifically expressed in podocytes of kidney glomeruli.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:TDRKH
gene id: 9606:TDRKH
uniprot id: Q9Y2W6
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the Tdrkh family.
messages: Cytoplasm
messages: Interacts with (symmetrically methylated) PIWIL1, PIWIL2 and PIWIL4.
messages: Mitochondrion
messages: Participates in the primary piRNA biogenesis pathway and is required during spermatogenesis to repress transposable elements and prevent their mobilization, which is essential for the germline integrity. The piRNA metabolic process mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and govern the methylation and subsequent repression of transposons. Required for the final steps of primary piRNA biogenesis by participating in the processing of 31-37 nt intermediates into mature piRNAs. May act in pi-bodies and piP-bodies by transferring piRNA precursors or intermediates to or between these granules.
messages: Ubiquitinated by PRKN during mitophagy, leading to its degradation and enhancement of mitophagy. Deubiquitinated by USP30.

9606:ADAM17
gene id: 9606:ADAM17
uniprot id: B2RNB2
uniprot id: P78536
names: Caution
names: Cofactor
names: Disease Annotation
names: Domain
names: Function
names: Induction
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Binds 1 zinc ion per subunit.
messages: Cleaves the membrane-bound precursor of TNF-alpha to its mature soluble form (PubMed:9034191). Responsible for the proteolytical release of soluble JAM3 from endothelial cells surface (PubMed:20592283). Responsible for the proteolytic release of several other cell-surface proteins, including p75 TNF-receptor, interleukin 1 receptor type II, p55 TNF-receptor, transforming growth factor-alpha, L-selectin, growth hormone receptor, MUC1 and the amyloid precursor protein (PubMed:12441351). Acts as an activator of Notch pathway by mediating cleavage of Notch, generating the membrane-associated intermediate fragment called Notch extracellular truncation (NEXT) (PubMed:24226769). Plays a role in the proteolytic processing of ACE2 (PubMed:24227843). Plays a role in hemostasis through shedding of GP1BA, the platelet glycoprotein Ib alpha chain (By similarity). Mediates the proteolytic cleavage of LAG3, leading to release the secreted form of LAG3 (By similarity). Mediates the proteolytic cleavage of IL6R, leading to the release of secreted form of IL6R (PubMed:26876177, PubMed:28060820). Mediates the proteolytic cleavage and shedding of FCGR3A upon NK cell stimulation, a mechanism that allows for increased NK cell motility and detachment from opsonized target cells.
messages: In arthritis-affected cartilage.
messages: Interacts with MAD2L1, MAPK14 and MUC1 (PubMed:12441351, PubMed:20188673). Interacts with iRhom1/RHBDF1 and iRhom2/RHBDF2 (PubMed:29897333). Interacts with FRMD8 via its interaction with iRhom1/RHBDF1 and iRhom2/RHBDF2 (PubMed:29897333).
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: Membrane
messages: Must be membrane anchored to cleave the different substrates. The cytoplasmic domain is not required for the this activity. Only the catalytic domain is essential to shed TNF and p75 TNFR (By similarity).
messages: Phosphorylated. Stimulation by growth factor or phorbol 12-myristate 13-acetate induces phosphorylation of Ser-819 but decreases phosphorylation of Ser-791. Phosphorylation at Thr-735 by MAPK14 is required for ADAM17-mediated ectodomain shedding.
messages: The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The precursor is cleaved by a furin endopeptidase.
messages: Ubiquitously expressed. Expressed at highest levels in adult heart, placenta, skeletal muscle, pancreas, spleen, thymus, prostate, testes, ovary and small intestine, and in fetal brain, lung, liver and kidney. Expressed in natural killer cells (at protein level) (PubMed:24337742).

9606:NLRP5
gene id: 9606:NLRP5
uniprot id: P59047
names: Developmental Stage
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: As a member of the subcortical maternal complex (SCMC), plays an essential role for zygotes to progress beyond the first embryonic cell divisions via regulation of actin dynamics (By similarity). Required for the formation of F-actin cytoplasmic lattices (CPL) in oocytes, which in turn are responsible for symmetric division of zygotes via the regulation of mitotic spindle formation and positioning (By similarity). Required for the localization of cortical granules to the cortex of oocytes, via association with the cortical actin scaffold (By similarity). Required for cortical actin clearance prior to oocyte exocytosis (By similarity). Involved in regulating post-fertilization Ca(2+) release and endoplasmic reticulum (ER) storage via regulation of ER localization (By similarity). May be involved in the localization of mitochondria to the cytoplasm and perinuclear region in oocytes and early stage embryos, independent of its role in CPL formation (By similarity).
messages: Belongs to the NLRP family.
messages: Component of the subcortical maternal complex (SCMC), at least composed of NLRP5, KHDC3, OOEP, and TLE6 isoform 1 (PubMed:25542835). Within the complex, interacts with OOEP, KHDC3L and TLE6 (PubMed:25542835). The SCMC may facilitate translocation of its components between the nuclear and cytoplasmic compartments (PubMed:25542835). As part of the SCMC interacts with the SCMC-associated protein ZBED3 (By similarity). As part of the SCMC interacts with the SCMC-associated protein CFL1/Cofilin-1 (By similarity). Interacts with PRKCE (PubMed:19542546). Interacts with TUBB3 at cytoskeleton microtubules (PubMed:24374158).
messages: Cortical granule
messages: Cytoplasm
messages: Expressed at all stages during oocyte maturation, additionally expressed in granulosa cells and cumulus oophorus cells (PubMed:19192343). Expressed primarily with other SCMC components in the subcortex of oocytes and early embryos (PubMed:25542835). Expression is excluded from cell-cell contact regions after the 2-cell stage (PubMed:25542835).
messages: Expressed in cumulus cells (at protein level) (PubMed:19542546). Highly abundant in oocytes and early embryos, however poorly expressed in somatic tissues such as the liver and spinal cord (PubMed:11925379, PubMed:30877238).
messages: Golgi apparatus
messages: Mitochondrion
messages: NLRP5 variants have been found in a spectrum of phenotypes characterized by aberrant methylation of multiple imprinted loci, a condition known as multi-locus imprinting defect or multi-locus imprinting disturbance (MLID). MLID-related phenotype spectrum ranges from intrauterine death to different types of imprinting disorders, including Beckwith-Wiedemann syndrome (BWS), Silver-Russell syndrome (SRS), and non-specific developmental and behavioral manifestations. MLID has also been observed in individuals without overt clinical manifestations. Recurrent pregnancy loss has been reported in healthy women carrying NLRP5 variants.
messages: Phosphorylated by PRKCE.
messages: nucleolus

9606:AIM2
gene id: 9606:AIM2
uniprot id: O14862
names: Activity Regulation
names: Caution
names: Domain
names: Function
names: Induction
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: According to a report, AIM2 is autoinhibited in absence of double-stranded DNA (dsDNA) due to an interaction between the pyrin and HIN-200 domains that induce a closed conformation (PubMed:22483801). However, it was later shown that AIM2 is not autoinhibited and that dsDNA acts as a molecular ruler to promote its homooligomerization (PubMed:26197926).
messages: Also acts as a tumor suppressor independently of its role in inflammatory response (PubMed:16432157). Able to suppress overt cell proliferation in enterocytes: restricts stem cell proliferation in the intestinal mucosa in an inflammasome-independent manner, contributing to a decrease in the likelihood of colorectal cancer development (By similarity). AIM2 suppresses cell proliferation by inhibiting phosphorylation of AKT1 at 'Ser-473', preventing AKT1 activation and AKT-mTOR signaling pathway (By similarity). Inhibits AKT1 phosphorylation both by inhibiting the activity of PRKDC/DNA-PK kinase and promoting dephosphorylation by PP2A phosphatase (By similarity). Also acts as a key regulator of regulatory T-cells (Treg) homeostasis by promoting their stability: acts by preventing AKT1 activation (By similarity). Its role in Treg homeostasis is important to restain autoimmune diseases (By similarity).
messages: Belongs to the HIN-200 family.
messages: By IFNG/IFN-gamma and IFNB1/IFN-beta.
messages: Cytoplasm
messages: Defects in AIM2 may be a cause of microsatellite unstable colon cancers.
messages: Degraded via selective autophagy following interaction with TRIM11.
messages: Expressed in spleen, small intestine, peripheral blood leukocytes, and testis.
messages: Inactive in absence of double-stranded DNA (dsDNA) (PubMed:26197926, PubMed:22483801). Homooligomerizes upon binding to dsDNA, dsDNA serving as an oligomerization platform (PubMed:26197926, PubMed:33980849). AIM2 requires large dsDNA to generate a structural template that couples dsDNA ligand-binding and homooligomerization (PubMed:26197926). Homooligomerization is followed by recruitment of PYCARD/ASC to initiate speck formation (nucleation) (PubMed:26197926, PubMed:29440442, PubMed:22483801, PubMed:33980849). AIM2 and PYCARD/ASC homooligomer filaments assemble bidirectionally and the recognition between AIM2 and PYCARD/ASC oligomers occurs in a head-to-tail manner (PubMed:33980849). Clustered PYCARD/ASC nucleates the formation of CASP1 filaments through the interaction of their respective CARD domains, acting as a platform for CASP1 polymerization and activation (PubMed:19158675, PubMed:19158676). Active CASP1 then specifically processes protein precursors, such as gasdermin-D (GSDMD), IL1B and IL18, leading to the release of mature cytokines in the extracellular milieu or pyroptosis, depending on cell type (PubMed:16432157, PubMed:19158676, PubMed:19158675). AIM2 can be activated in response to events that cause genomic DNA (HIV protease inhibitor nelfinavir) or mitochondrial DNA release in the cytoplasm (such as Perfluoroalkyl substance pollutants or cholesterol overload) (By similarity). Activation of the AIM2 inflammasome is inhibited by isoform IFI16-beta of IFI16, which prevents the interaction between AIM2 and PYCARD/ASC (PubMed:30104205). Activation of the AIM2 inflammasome is inhibited by TRIM11, which promotes autophagy-dependent degradation of AIM2 (PubMed:27498865).
messages: Inflammasome
messages: Nucleus
messages: Self-associates; forms homooligomers in response to cytosolic double-stranded DNA (dsDNA) and the dsDNA seems to serve as oligomerization platform (PubMed:15582594, PubMed:19158676, PubMed:26197926, PubMed:29440442, PubMed:24406744, PubMed:26583071, PubMed:33980849). Component of AIM2 inflammasome, which consists of a signal sensor component (AIM2), an adapter (PYCARD/ASC), which recruits an effector pro-inflammatory caspase (CASP1) (PubMed:22869553, PubMed:22483801, PubMed:33980849). Interacts (via pyrin domain) with PYCARD/ASC (via pyrin domain); interaction is direct (PubMed:19158675, PubMed:19158679, PubMed:29440442, PubMed:23530044, PubMed:33980849). Component of the AIM2 PANoptosome complex, a multiprotein complex that drives inflammatory cell death (PANoptosis) (By similarity). Interacts with PYDC5; disrupts assembly of the AIM2 inflammasome complex (PubMed:24531343). Interacts with EIF2AK2/PKR (PubMed:22801494). Interacts with MAPRE1 (PubMed:22869553). Interacts with IFI16 (PubMed:22046441). Interacts with isoform IFI16-beta of IFI16; preventing the interaction between AIM2 and PYCARD/ASC (PubMed:30104205). Interacts with RACK1; promoting association with PP2A phosphatase and dephosphorylation of AKT1 (By similarity). Interacts with TRIM11; promoting AIM2 recruitment to autophagosomes and autophagy-dependent degradation (PubMed:27498865).
messages: Sensor component of the AIM2 inflammasome, which mediates inflammasome activation in response to the presence of double-stranded DNA (dsDNA) in the cytosol, leading to subsequent pyroptosis (PubMed:17726700, PubMed:19158675, PubMed:19158676, PubMed:19158679, PubMed:20566831, PubMed:26197926, PubMed:29440442, PubMed:23530044, PubMed:26583071, PubMed:33980849). Inflammasomes are supramolecular complexes that assemble in the cytosol in response to pathogens and other damage-associated signals and play critical roles in innate immunity and inflammation (PubMed:17726700, PubMed:19158675, PubMed:19158676, PubMed:19158679, PubMed:20566831, PubMed:26197926, PubMed:29440442, PubMed:33980849). Acts as a recognition receptor (PRR): specifically recognizes and binds dsDNA in the cytosol, and mediates the formation of the inflammasome polymeric complex composed of AIM2, CASP1 and PYCARD/ASC (PubMed:17726700, PubMed:19158675, PubMed:19158676, PubMed:19158679, PubMed:20566831, PubMed:26197926, PubMed:29440442, PubMed:33980849). Recruitment of pro-caspase-1 (proCASP1) to the AIM2 inflammasome promotes caspase-1 (CASP1) activation, which subsequently cleaves and activates inflammatory cytokines IL1B and IL18 and gasdermin-D (GSDMD), promoting cytokine secretion (PubMed:17726700, PubMed:19158675, PubMed:19158676, PubMed:19158679, PubMed:20566831). In some cells, CASP1 activation mediates cleavage and activation of GSDMD, triggering pyroptosis without promoting cytokine secretion (PubMed:19158675, PubMed:19158676). Detects cytosolic dsDNA of viral and bacterial origin in a non-sequence-specific manner (PubMed:17726700, PubMed:19158675, PubMed:19158676, PubMed:19158679, PubMed:20566831, PubMed:26197926, PubMed:29440442, PubMed:26583071, PubMed:33980849). Involved in the DNA damage response caused by acute ionizing radiation by mediating pyroptosis of intestinal epithelial cells and bone marrow cells in response to double-strand DNA breaks (By similarity). Mechanistically, AIM2 senses D…
messages: The HIN-200 domain mediates dsDNA binding via electrostatic interactions.
messages: The pyrin domain mediates homotypic interaction with PYCARD/ASC (PubMed:19158676, PubMed:19158675).

9606:OR56B4
gene id: 9606:OR56B4
uniprot id: Q8NH76
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Odorant receptor.

9606:COL6A1
gene id: 9606:COL6A1
uniprot id: P12109
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: A mutation in COL6A1 is the cause of autosomal recessive limb-girdle muscular dystrophy. The affected individual with a homozygous recessive COL6A1 mutation showed progressive muscle weakness with an onset at the age of 4 years and loss of ambulation at the age of 15 years. Muscle biopsy showed end stage dystrophy.
messages: Belongs to the type VI collagen family.
messages: Collagen VI acts as a cell-binding protein.
messages: Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Trimers composed of three different chains: alpha-1(VI), alpha-2(VI), and alpha-3(VI) or alpha-5(VI) or alpha-6(VI).
messages: extracellular matrix

9606:TSSK1B
gene id: 9606:TSSK1B
uniprot id: A0ZT98
uniprot id: Q9BXA7
names: Activity Regulation
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Autophosphorylated.
messages: Belongs to the protein kinase superfamily.
messages: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.
messages: Cytoplasm
messages: Interacts with TSSK2. Interacts with HSP90; this interaction stabilizes TSSK1 (By similarity).
messages: Kinase activity is specifically inhibited by 2 classes of compounds: biphenyl compounds (1,1'-(biphenyl-4,4'-diyl)bis(2,2-dihydroxyethanone)) and 1,2,7-trialky-1H-imidazo[4,5-g]quinoxalin-6-one. Activated by phosphorylation on Thr-174 and potentially by autophosphorylation.
messages: TSSK1B might be used as a target for male contraception or and intra-vaginal spermicides.
messages: Testis-specific serine/threonine-protein kinase required during spermatid development. Phosphorylates 'Ser-288' of TSKS. Involved in the late stages of spermatogenesis, during the reconstruction of the cytoplasm. During spermatogenesis, required for the transformation of a ring-shaped structure around the base of the flagellum originating from the chromatoid body.
messages: Testis-specific. Present in sperm (at protein level).
messages: Ubiquitinated; HSP90 activity negatively regulates ubiquitination and degradation.
messages: acrosome
messages: flagellum

9606:SURF1
gene id: 9606:SURF1
uniprot id: A0A087WYS9
uniprot id: E5KRX5
uniprot id: Q15526
names: Developmental Stage
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the SURF1 family.
messages: Component of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex, that regulates cytochrome c oxidase assembly.
messages: Component of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex, the core components of this complex being COA3/MITRAC12 and COX14. Interacts with COA3.
messages: Expressed in the fetus (at protein level).
messages: Mitochondrion inner membrane
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:LIMCH1
gene id: 9606:LIMCH1
uniprot id: Q9UPQ0
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Actin stress fibers-associated protein that activates non-muscle myosin IIa. Activates the non-muscle myosin IIa complex by promoting the phosphorylation of its regulatory subunit MRLC/MYL9. Through the activation of non-muscle myosin IIa, positively regulates actin stress fibers assembly and stabilizes focal adhesions. It therefore negatively regulates cell spreading and cell migration.
messages: Belongs to the LIMCH1 family.
messages: Interacts with MYH9; independently of the integration of MYH9 into the myosin complex.
messages: stress fiber

9606:PADI2
gene id: 9606:PADI2
uniprot id: Q9Y2J8
names: Cofactor
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the protein arginine deiminase family.
messages: Binding of Ca(2+) triggers a conformation change that is essential for catalytic activity.
messages: Catalyzes the deimination of arginine residues of proteins.
messages: Cytoplasm
messages: Detected in keratinocytes in epidermis (at protein level).
messages: Homodimer.

9606:SLC2A6
gene id: 9606:SLC2A6
uniprot id: Q9UGQ3
names: Caution
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the major facilitator superfamily. Sugar transporter (TC 2.A.1.1) family. Glucose transporter subfamily.
messages: By lipopolysaccharide (LPS).
messages: Highly expressed in brain, spleen and peripheral blood leukocytes.
messages: Lysosome membrane
messages: Probable sugar transporter that acts as a regulator of glycolysis in macrophages (Probable). Does not transport glucose (PubMed:30431159).
messages: Was initially thought to act as a glucose transporter (PubMed:10970791). However, later studies demonstrated that it does not transport glucose (PubMed:30431159).
messages: Was named GLUT9 by a report, but this gene name has already been used for SLC2A9.

9606:BEGAIN
gene id: 9606:BEGAIN
uniprot id: Q9BUH8
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Cytoplasm
messages: Interacts with DLG4 and DLGAP1 and forms a ternary complex.
messages: May sustain the structure of the postsynaptic density (PSD).
messages: Membrane

9606:SPRED1
gene id: 9606:SPRED1
uniprot id: Q7Z699
names: Disease Annotation
names: Function
names: PTM
names: Sequence Caution
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cell membrane
messages: Contaminating sequence. Potential poly-A sequence.
messages: Homodimer and heterodimer (PubMed:15683364). Able to interact with SPRED2 to form heterodimers (PubMed:15683364). Interacts (via C-terminus) with TAOK1/MARKK (via C-terminus); the interaction does not affect TAOK1 kinase activity (PubMed:18216281). Interacts (via C-terminus) with TESK1 (via C-terminus); the interaction inhibits TESK1 kinase activity (PubMed:18216281). Interacts with CAV1 (PubMed:16115197). Interacts with RAS (By similarity). Interacts with palmitoyltransferase ZDHHC17/HIP14; the interaction leads to palmitoylation of SPRED1 (PubMed:24705354).
messages: Nucleus
messages: Palmitoylated by ZDHHC17/HIP14.
messages: Phosphorylated on tyrosine.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Tyrosine kinase substrate that inhibits growth-factor-mediated activation of MAP kinase (By similarity). Negatively regulates hematopoiesis of bone marrow (By similarity). Inhibits fibroblast growth factor (FGF)-induced retinal lens fiber differentiation, probably by inhibiting FGF-mediated phosphorylation of ERK1/2 (By similarity). Attenuates actin stress fiber formation via inhibition of TESK1-mediated phosphorylation of cofilin (PubMed:18216281). Inhibits TGFB-induced epithelial-to-mesenchymal transition in lens epithelial cells (By similarity).
messages: Ubiquitinated.
messages: Weakly expressed in embryonic cell line HEK293.
messages: caveola

9606:BORCS8-MEF2B
gene id: 9606:BORCS8-MEF2B
uniprot id: Q02080
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the MEF2 family.
messages: Expressed in skeletal and cardiac muscle and brain.
messages: Interacts with HDAC7 (By similarity). Heterodimer. Interacts with HDAC9.
messages: Nucleus
messages: Transcriptional activator which binds specifically to the MEF2 element, 5'-YTA[AT](4)TAR-3', found in numerous muscle-specific genes. Activates transcription via this element. May be involved in muscle-specific and/or growth factor-related transcription.

9606:ADPRM
gene id: 9606:ADPRM
uniprot id: Q3LIE5
uniprot id: W0NWJ0
names: Function
names: Miscellaneous
names: Similarity
names: Subunit
messages: Belongs to the ADPRibase-Mn family.
messages: Hydrolyzes ADP-ribose, IDP-ribose, CDP-glycerol, CDP-choline and CDP-ethanolamine, but not other non-reducing ADP-sugars or CDP-glucose. May be involved in immune cell signaling as suggested by the second-messenger role of ADP-ribose, which activates TRPM2 as a mediator of oxidative/nitrosative stress (By similarity).
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Monomer.

9606:PPP2R5E
gene id: 9606:PPP2R5E
uniprot id: Q16537
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the phosphatase 2A regulatory subunit B56 family.
messages: Cytoplasm
messages: Found in a complex with at least ARL2, PPP2CB; PPP2R1A, PPP2R2A, PPP2R5E and TBCD (By similarity). PP2A consists of a common heterodimeric core enzyme, composed of a 36 kDa catalytic subunit (subunit C) and a 65 kDa constant regulatory subunit (PR65 or subunit A), that associates with a variety of regulatory subunits. Proteins that associate with the core dimer include three families of regulatory subunits B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56 families), the 48 kDa variable regulatory subunit, viral proteins, and cell signaling molecules. Interacts with SGO1.
messages: Phosphorylated on serine residues.
messages: The B regulatory subunit might modulate substrate selectivity and catalytic activity, and also might direct the localization of the catalytic enzyme to a particular subcellular compartment.

9606:OR10G4
gene id: 9606:OR10G4
uniprot id: A0A126GWS5
uniprot id: Q8NGN3
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Membrane
messages: Odorant receptor.

9606:UCMA
gene id: 9606:UCMA
uniprot id: A0A067XJP8
uniprot id: A0A067XJX6
uniprot id: A0A067XKV3
uniprot id: Q8WVF2
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the UCMA family.
messages: May be involved in the negative control of osteogenic differentiation of osteochondrogenic precursor cells in peripheral zones of fetal cartilage and at the cartilage-bone interface.
messages: Predominantly expressed in resting chondrocytes.
messages: Proteolytically cleaved by a furin-like convertase to generate a persistent C-terminal fragment found in almost the entire cartilage matrix, and affecting osteoblast differentiation.
messages: Sulfated on tyrosine residues.
messages: extracellular matrix

9606:IFNG
gene id: 9606:IFNG
uniprot id: A0A7R8GUN6
uniprot id: P01579
names: Disease Annotation
names: Function
names: Induction
names: PTM
names: Pharmaceutical
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Available under the name Actimmune (Genentech). Used for reducing the frequency and severity of serious infections associated with chronic granulomatous disease (CGD).
messages: Belongs to the type II (or gamma) interferon family.
messages: By cytokines, most notably interleukin IL-12, secreted by professional antigen-presenting cells such as monocytes/macrophages and dendritic cells.
messages: Disease susceptibility may be associated with variants affecting the gene represented in this entry.
messages: Homodimer (PubMed:1902591). Interacts with IFNGR1 (via extracellular domain); this interaction promotes IFNGR1 dimerization (PubMed:8349687).
messages: Homodimer.
messages: Proteolytic processing produces C-terminal heterogeneity, with proteins ending alternatively at Gly-150, Met-157 or Gly-161.
messages: Released primarily from activated T lymphocytes.
messages: Secreted
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Type II interferon produced by immune cells such as T-cells and NK cells that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing antigen presentation (PubMed:16914093, PubMed:8666937). Primarily signals through the JAK-STAT pathway after interaction with its receptor IFNGR1 to affect gene regulation (PubMed:8349687). Upon IFNG binding, IFNGR1 intracellular domain opens out to allow association of downstream signaling components JAK2, JAK1 and STAT1, leading to STAT1 activation, nuclear translocation and transcription of IFNG-regulated genes. Many of the induced genes are transcription factors such as IRF1 that are able to further drive regulation of a next wave of transcription (PubMed:16914093). Plays a role in class I antigen presentation pathway by inducing a replacement of catalytic proteasome subunits with immunoproteasome subunits (PubMed:8666937). In turn, increases the quantity, quality, and repertoire of peptides for class I MHC loading (PubMed:8163024). Increases the efficiency of peptide generation also by inducing the expression of activator PA28 that associates with the proteasome and alters its proteolytic cleavage preference (PubMed:11112687). Up-regulates as well MHC II complexes on the cell surface by promoting expression of several key molecules such as cathepsins B/CTSB, H/CTSH, and L/CTSL (PubMed:7729559). Participates in the regulation of hematopoietic stem cells during development and under homeostatic conditions by affecting their development, quiescence, and differentiation (By similarity).
messages: Type II interferon produced by immune cells such as T-cells and NK cells that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing antigen presentation. Primarily signals through the JAK-STAT pathway after interaction with its receptor IFNGR1 to affect gene regulation. Upon IFNG binding, IFNGR1 intracellular domain opens out to allow association of downstream signaling components JAK2, JAK1 and STAT1, leading to STAT1 activation, nuclear translocation and transcription of IFNG-regulated genes. Many of the induced genes are transcription factors such as IRF1 that are able to further drive regulation of a next wave of transcription. Plays a role in class I antigen presentation pathway by inducing a replacement of catalytic proteasome subunits with immunoproteasome subunits. In turn, increases the quantity, quality, and repertoire of peptides for class I MHC loading. Increases the efficiency of peptide generation also by inducing the expression of activator PA28 that associates with the proteasome and alters its proteolytic cleavage preference. Up-regulates as well MHC II complexes on the cell surface by promoting expression of several key molecules such as cathepsins B/CTSB, H/CTSH, and L/CTSL. Participates in the regulation of hematopoietic stem cells during development and under homeostatic conditions by affecting their development, quiescence, and differentiation.

9606:TUFM
gene id: 9606:TUFM
uniprot id: A0A384ME17
uniprot id: P49411
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Interacts with Hantaan hantavirus glycoprotein N; this interaction contributes to the virus-induced degradation of mitochondria by autophagy, which leads to degradation of MAVS and inhibition of type I interferon (IFN) responses.
messages: (Microbial infection) Interacts with human parainfluenza virus 3 matrix protein; this interaction inhibits RLR-mediated type I interferon production while promoting autophagy.
messages: Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. EF-Tu/EF-1A subfamily.
messages: Interacts with NLRX1 (PubMed:22749352). Interacts with ATG16L1 (PubMed:22749352).
messages: Mitochondrion
messages: Promotes the GTP-dependent binding of aminoacyl-tRNA to the A-site of ribosomes during protein biosynthesis. Also plays a role in the regulation of autophagy and innate immunity. Recruits ATG5-ATG12 and NLRX1 at mitochondria and serves as a checkpoint of the RIGI-MAVS pathway. In turn, inhibits RLR-mediated type I interferon while promoting autophagy.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: This protein promotes the GTP-dependent binding of aminoacyl-tRNA to the A-site of ribosomes during protein biosynthesis.

9606:TMCO5A
gene id: 9606:TMCO5A
uniprot id: A0A024R9I9
uniprot id: Q8N6Q1
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the TMCO5 family.
messages: Membrane

9606:SPAG16
gene id: 9606:SPAG16
uniprot id: Q8N0X2
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cytoplasm
messages: Interacts with SPAG6 and STK36.
messages: Isoform 1 is detected in testis. Isoform 4 is detected in testis and brain, and at lower levels in kidney, heart, pancreas, thyroid, ovary, adrenal gland, spinal cord, trachea and liver.
messages: Necessary for sperm flagellar function. Plays a role in motile ciliogenesis. May help to recruit STK36 to the cilium or apical surface of the cell to initiate subsequent steps of construction of the central pair apparatus of motile cilia (By similarity).
messages: Phosphorylated by TSSK2.
messages: cilium axoneme
messages: flagellum
messages: flagellum axoneme

9606:C5AR2
gene id: 9606:C5AR2
uniprot id: Q9P296
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Frontal cortex, hippocampus, hypothalamus, pons and liver.
messages: Interacts with C3 (the anaphylatoxin peptide C3a and the adipogenic hormone ASP); the interaction occurs with higher affinity for ASP, enhancing the phosphorylation and activation of GPR77, recruitment of ARRB2 to the cell surface and endocytosis of GRP77.
messages: Receptor for the chemotactic and inflammatory C3a, C4a and C5a anaphylatoxin peptides and also for their dearginated forms ASP/C3adesArg, C4adesArg and C5adesArg respectively. Couples weakly to G(i)-mediated signaling pathways.

9606:RIC1
gene id: 9606:RIC1
uniprot id: Q4ADV7
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the RIC1 family.
messages: Forms a complex with RGP1; the interaction enhances RAB6A GTPase activity (PubMed:16112082). Interacts (via central domain) with RGP1 (PubMed:16112082). Interacts with RAB6A; the interaction is direct with a preference for RAB6A-GDP (PubMed:16112082). Interacts (via C-terminus domain) with RAB33B; the interaction is direct with a preference for RAB33B-GTP (PubMed:16112082). Interacts with GJA1 (PubMed:23091056).
messages: Membrane
messages: Present in kidney and various cell lines (at protein level). Widely expressed at low level.
messages: The RIC1-RGP1 complex acts as a guanine nucleotide exchange factor (GEF), which activates RAB6A by exchanging bound GDP for free GTP, and may thereby be required for efficient fusion of endosome-derived vesicles with the Golgi compartment (PubMed:23091056). The RIC1-RGP1 complex participates in the recycling of mannose-6-phosphate receptors (PubMed:23091056). Required for phosphorylation and localization of GJA1 (PubMed:16112082). Is a regulator of procollagen transport and secretion, and is required for correct cartilage morphogenesis and development of the craniofacial skeleton (PubMed:31932796).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: cytosol

9606:IRS1
gene id: 9606:IRS1
uniprot id: P35568
names: Disease Annotation
names: Function
names: PTM
names: Polymorphism
names: Subunit
messages: Interacts with UBTF and PIK3CA (By similarity). Interacts (via phosphorylated YXXM motifs) with PIK3R1 (By similarity). Interacts with ROCK1 and FER (By similarity). Interacts (via PH domain) with PHIP (By similarity). Interacts with GRB2 (By similarity). Interacts with SOCS7 (PubMed:16127460). Interacts (via IRS-type PTB domain) with IGF1R and INSR (via the tyrosine-phosphorylated NPXY motif) (PubMed:7541045, PubMed:7559478, PubMed:7537849). Interacts with ALK (PubMed:15226403, PubMed:16878150). Interacts with EIF2AK2/PKR (By similarity). Interacts with GKAP1 (By similarity). Interacts with DGKZ in the absence of insulin; insulin stimulation decreases this interaction (By similarity). Found in a ternary complex with DGKZ and PIP5K1A in the absence of insulin stimulation (By similarity). Interacts with SQSTM1; the interaction is disrupted by the presence of tensin TNS2 (PubMed:25101860).
messages: May mediate the control of various cellular processes by insulin. When phosphorylated by the insulin receptor binds specifically to various cellular proteins containing SH2 domains such as phosphatidylinositol 3-kinase p85 subunit or GRB2. Activates phosphatidylinositol 3-kinase when bound to the regulatory p85 subunit (By similarity).
messages: Serine phosphorylation of IRS1 is a mechanism for insulin resistance. Ser-312 phosphorylation inhibits insulin action through disruption of IRS1 interaction with the insulin receptor (By similarity). Phosphorylation of Tyr-896 is required for GRB2-binding (By similarity). Phosphorylated by ALK. Phosphorylated at Ser-270, Ser-307, Ser-636 and Ser-1101 by RPS6KB1; phosphorylation induces accelerated degradation of IRS1 (PubMed:18952604). Phosphorylated on tyrosine residues in response to insulin (PubMed:23401856). In skeletal muscles, dephosphorylated on Tyr-612 by TNS2 under anabolic conditions; dephosphorylation results in the proteasomal degradation of IRS1 (PubMed:23401856).
messages: The Arg-971 polymorphism impairs the ability of insulin to stimulate glucose transport, glucose transporter translocation, and glycogen synthesis by affecting the PI3K/AKT1/GSK3 signaling pathway. The polymorphism at Arg-971 may contribute to the in vivo insulin resistance observed in carriers of this variant. Arg-971 could contribute to the risk for atherosclerotic cardiovascular diseases associated with non-insulin-dependent diabetes mellitus (NIDDM) by producing a cluster of insulin resistance-related metabolic abnormalities. In insulin-stimulated human endothelial cells from carriers of the Arg-971 polymorphism, genetic impairment of the IRS1/PI3K/PDPK1/AKT1 insulin signaling cascade results in impaired insulin-stimulated nitric oxide (NO) release and suggested that this may be a mechanism through which the Arg-971 polymorphism contributes to the genetic predisposition to develop endothelial dysfunction and cardiovascular disease. The Arg-971 polymorphism not only reduces phosphorylation of the substrate but allows IRS1 to act as an inhibitor of PI3K, producing global insulin resistance.
messages: The gene represented in this entry may be involved in disease pathogenesis.
messages: Ubiquitinated by the Cul7-RING(FBXW8) complex in a mTOR-dependent manner, leading to its degradation: the Cul7-RING(FBXW8) complex recognizes and binds IRS1 previously phosphorylated by S6 kinase (RPS6KB1 or RPS6KB2).

9606:PIGP
gene id: 9606:PIGP
uniprot id: P57054
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the PIGP family.
messages: Component of the glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex composed at least by PIGA, PIGC, PIGH, PIGP, PIGQ, PIGY and DPM2 (PubMed:16162815). Interacts directly with PIGA and PIGQ (PubMed:10944123).
messages: Membrane
messages: Part of the glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex that catalyzes the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to phosphatidylinositol and participates in the first step of GPI biosynthesis.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitous.

9606:TP53I3
gene id: 9606:TP53I3
uniprot id: Q53FA7
names: Function
names: Induction
names: Miscellaneous
names: Similarity
names: Subunit
messages: Belongs to the zinc-containing alcohol dehydrogenase family. Quinone oxidoreductase subfamily.
messages: Catalyzes the NADPH-dependent reduction of quinones (PubMed:19349281). Exhibits a low enzymatic activity with beta-naphthoquinones, with a strong preference for the ortho-quinone isomer (1,2-beta-naphthoquinone) over the para isomer (1,4-beta-naphthoquinone). Also displays a low reductase activity for non-quinone compounds such as diamine and 2,6-dichloroindophenol (in vitro) (PubMed:19349281). Involved in the generation of reactive oxygen species (ROS) (PubMed:19349281).
messages: Homodimer.
messages: Isoform 1 and isoform 2 are both activated by p53/TP53, doxorubicin, etoposide and ionizing radiation. Isoform 2 is highly activated by UV radiation.
messages: Major isoform under UV light exposure. Undergoes rapid proteolytic degradation by the proteasome.
messages: Major isoform under normal light conditions.

9606:DDHD2
gene id: 9606:DDHD2
uniprot id: O94830
names: Caution
names: Disease Annotation
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the PA-PLA1 family.
messages: Endoplasmic reticulum-Golgi intermediate compartment
messages: Forms homooligomers and, to a much smaller extent, heterooligomers with DDHD1.
messages: It is uncertain whether Met-1 or Met-31 is the initiator.
messages: Phospholipase that hydrolyzes preferentially phosphatidic acid, including 1,2-dioleoyl-sn-phosphatidic acid, and phosphatidylethanolamine. Specifically binds to phosphatidylinositol 3-phosphate (PI(3)P), phosphatidylinositol 4-phosphate (PI(4)P), phosphatidylinositol 5-phosphate (PI(5)P) and possibly phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2). May be involved in the maintenance of the endoplasmic reticulum and/or Golgi structures. May regulate the transport between Golgi apparatus and plasma membrane.
messages: SAM and DDHD domains together are required for phospholipid binding.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Widely expressed (at protein level).
messages: cis-Golgi network
messages: cytosol

9606:RECQL5
gene id: 9606:RECQL5
uniprot id: B3KQK2
uniprot id: O94762
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the helicase family. RecQ subfamily.
messages: Cytoplasm
messages: DNA helicase that plays an important role in DNA replication, transcription and repair (PubMed:20643585, PubMed:22973052). Binds to the RNA polymerase II subunit POLR2A during transcription elongation and suppresses transcription-associated genomic instability (PubMed:20231364). Associates also with POLR1A and enforces the stability of ribosomal DNA arrays (PubMed:27502483). Plays an important role in mitotic chromosome separation after cross-over events and cell cycle progress (PubMed:22013166). Mechanistically, removes RAD51 filaments protecting stalled replication forks at common fragile sites and stimulates MUS81-EME1 endonuclease leading to mitotic DNA synthesis (PubMed:28575661). Required for efficient DNA repair, including repair of inter-strand cross-links (PubMed:23715498). Stimulates DNA decatenation mediated by TOP2A. Prevents sister chromatid exchange and homologous recombination.
messages: Monomer. Interacts with TOP2A, TOP3A and TOP3B (PubMed:20231364, PubMed:10710432). Isoform beta interacts with RNA polymerase II subunit POLR2A (PubMed:20348101, PubMed:20231364, PubMed:23748380). Identified in a complex with the RNA polymerase II core bound to DNA (PubMed:20348101, PubMed:20231364). Interacts (via C-terminus) with POLR1A (PubMed:27502483). Isoform beta interacts with RAD51 (PubMed:20348101, PubMed:20231364). Interacts with WRN; this interaction stimulates WRN helicase activity on DNA fork duplexes (PubMed:23180761). Interacts with MUS1; this interaction promotes MUS81-dependent mitotic DNA synthesis (PubMed:28575661).
messages: Nucleus
messages: Phosphorylated by CDK1 at Ser-727; this phosphorylation is required for RECQL5-mediated disruption of RAD51 filaments on stalled replication forks.
messages: Ubiquitous.
messages: nucleoplasm

9606:DDX3Y
gene id: 9606:DDX3Y
uniprot id: O15523
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the DEAD box helicase family. DDX3/DED1 subfamily.
messages: Cytoplasm
messages: Located in the 'azoospermia factor a' (AZFa) region on chromosome Y which is deleted in Sertoli cell-only syndrome. This is an infertility disorder in which no germ cells are visible in seminiferous tubules leading to azoospermia.
messages: Nucleus
messages: Probable ATP-dependent RNA helicase. During immune response, may enhance IFNB1 expression via IRF3/IRF7 pathway (By similarity).
messages: Widely expressed at the mRNA level, with highest levels in testis (PubMed:9381176). Testis-specific (at protein level). Expressed predominantly in spermatogonia, but occasionally detected in some pre-leptotene/leptotene spermatocytes (PubMed:15294876).

9606:SLC17A8
gene id: 9606:SLC17A8
uniprot id: Q8NDX2
names: Activity Regulation
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the major facilitator superfamily. Sodium/anion cotransporter family. VGLUT subfamily.
messages: Cell membrane
messages: Expressed in amygdala, cerebellum, hippocampus, medulla, spinal cord and thalamus.
messages: Multifunctional transporter that transports L-glutamate as well as multiple ions such as chloride, sodium and phosphate (PubMed:33440152, PubMed:12151341). At the synaptic vesicle membrane, mainly functions as an uniporter that mediates the uptake of L-glutamate into synaptic vesicles at presynaptic nerve terminals of excitatory neural cells (PubMed:12151341). The L-glutamate uniporter activity is electrogenic and is driven by the proton electrochemical gradient, mainly by the electrical gradient established by the vacuolar H(+)-ATPase across the synaptic vesicle membrane (PubMed:12151341). In addition, functions as a chloride channel that allows a chloride permeation through the synaptic vesicle membrane that affects the proton electrochemical gradient and promotes synaptic vesicles acidification (By similarity). At the plasma membrane, following exocytosis, functions as a symporter of Na(+) and phosphate from the extracellular space to the cytoplasm allowing synaptic phosphate homeostasis regulation (Probable). The symporter activity is electrogenic (PubMed:33440152). Moreover, operates synergistically with SLC18A3/VACHT under a constant H(+) gradient, thereby allowing striatal vesicular acetylcholine uptake (By similarity).
messages: The L-glutamate uniporter activity exhibits a biphasic dependence on chloride concentration. Chloride channel activity is allosterically activated by lumenal H(+) and Cl(-) leading to synaptic vesicles acidification. The glutamate transport activity is allosterically activated by lumenal H(+) and Cl(-), preventing non-vesicular L-glutamate release.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: synaptic vesicle membrane
messages: synaptosome

9606:CDH7
gene id: 9606:CDH7
uniprot id: Q9ULB5
names: Domain
names: Function
names: Subcellular Location Annotation
messages: Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types.
messages: Cell membrane
messages: Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain.

9606:ATP1B2
gene id: 9606:ATP1B2
uniprot id: P14415
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the X(+)/potassium ATPases subunit beta family.
messages: Cell membrane
messages: Mediates cell adhesion of neurons and astrocytes, and promotes neurite outgrowth.
messages: The C-terminal lobe folds into an immunoglobulin-like domain and mediates cell adhesion properties.
messages: The sodium/potassium-transporting ATPase is composed of a catalytic alpha subunit, an auxiliary non-catalytic beta subunit and an additional regulatory subunit. Interacts with isoform 2 of BSG (By similarity).
messages: This is the non-catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of Na(+) and K(+) ions across the plasma membrane. The exact function of the beta-2 subunit is not known.

9606:RPAP1
gene id: 9606:RPAP1
uniprot id: A8K2F9
uniprot id: Q9BWH6
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the RPAP1 family.
messages: Forms an interface between the RNA polymerase II enzyme and chaperone/scaffolding protein, suggesting that it is required to connect RNA polymerase II to regulators of protein complex formation. Required for interaction of the RNA polymerase II complex with acetylated histone H3.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Nucleus
messages: Part of an RNA polymerase II complex that contains POLR2A, POLR2B, POLR2C, POLR2D, POLR2E, POLR2F, POLR2G, POLR2H, POLR2I, POLR2J, POLR2K, POLR2L, RPAP1, FCP1 plus the general transcription factors TFIIB and TFIIF.

9606:ITGA6
gene id: 9606:ITGA6
uniprot id: P23229
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the integrin alpha chain family.
messages: Cell membrane
messages: Heterodimer of an alpha and a beta subunit. The alpha subunit is composed of a heavy and a light chain linked by a disulfide bond (By similarity). Alpha-6 associates with either beta-1 (ITGB1) or beta-4 (ITGB4) to form ITGA6:ITGB1 and ITGA6:ITGB4, respectively (By similarity). ITGA6:ITGB1 is found in a complex with CD9; interaction takes place in oocytes and is involved in sperm-egg fusion (By similarity). ITGA6:ITGB4 is found in a ternary complex with NRG1 and ERBB3 (PubMed:20682778). ITGA6:ITGB4 is found in a ternary complex with IGF1 and IGF1R (PubMed:22351760). ITGA6:ITGB4 interacts with IGF2 (PubMed:28873464). Interacts with ADAM9 (By similarity). Interacts with RAB21 (PubMed:16754960). Interacts with MDK (PubMed:15466886). ITGA6:ITGB1 interacts with MDK; this interaction mediates MDK-induced neurite outgrowth (PubMed:15466886).
messages: Integrin alpha-6/beta-1 (ITGA6:ITGB1) is a receptor for laminin on platelets (By similarity). Integrin alpha-6/beta-1 (ITGA6:ITGB1) is present in oocytes and is involved in sperm-egg fusion (By similarity). Integrin alpha-6/beta-4 (ITGA6:ITGB4) is a receptor for laminin in epithelial cells and it plays a critical structural role in the hemidesmosome (By similarity). ITGA6:ITGB4 binds to NRG1 (via EGF domain) and this binding is essential for NRG1-ERBB signaling (PubMed:20682778). ITGA6:ITGB4 binds to IGF1 and this binding is essential for IGF1 signaling (PubMed:22351760). ITGA6:ITGB4 binds to IGF2 and this binding is essential for IGF2 signaling (PubMed:28873464).
messages: Integrin alpha-6/beta-4 is predominantly expressed by epithelia. Isoforms containing segment X1 are ubiquitously expressed. Isoforms containing segment X1X2 are expressed in heart, kidney, placenta, colon, duodenum, myoblasts and myotubes, and in a limited number of cell lines; they are always coexpressed with the ubiquitous isoform containing segment X1. In some tissues (e.g. Salivary gland), isoforms containing cytoplasmic segment A and isoforms containing segment B are detected while in others, only isoforms containing one cytoplasmic segment are found (segment A in epidermis and segment B in kidney). Processed integrin alpha-6: Expressed at low levels in normal prostate tissue with elevated levels in prostate cancer tissue (at protein level) (PubMed:15023541).
messages: Isoforms containing segment A, but not segment B, are the major targets for PMA-induced phosphorylation. Phosphorylation occurs on 'Ser-1103' of isoform alpha-6X1X2A. Phosphorylation is not required for the induction of integrin alpha-6A/beta-1 high affinity but may reduce the affinity for ligand.
messages: Palmitoylation by DHHC3 enhances stability and cell surface expression.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Undergoes PLAU-mediated cleavage at residues Arg-634-635-Arg in a time-dependent manner to produce processed integrin alpha-6 (alpha6p) (PubMed:11359780, PubMed:15023541, PubMed:17303120). Production of alpha6p enhances prostate cancer cell invasion and migration (PubMed:17303120).

9606:ELF2
gene id: 9606:ELF2
uniprot id: B7Z720
uniprot id: Q15723
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the ETS family.
messages: Expressed in all fetal and adult tissues examined. Among fetal tissues, highest levels of expression detected in heart, lung, liver and kidney, and lower levels in brain. Among adult tissues, highest levels of expression detected in heart, placenta, lung, skeletal muscle, spleen, thymus, testis and ovary. Moderate expression in prostate, small intestine, kidney, liver and pancreas, and weak expression in colon, brain and peripheral blood lymphocytes.
messages: Interacts with the LIM domains of LMO2 (By similarity). Interacts via its N-terminal region with RUNX1.
messages: Isoform 1 transcriptionally activates the LYN and BLK promoters and acts synergistically with RUNX1 to transactivate the BLK promoter.
messages: Isoform 2 may function in repression of RUNX1-mediated transactivation.
messages: Nucleus

9606:ZNF546
gene id: 9606:ZNF546
uniprot id: Q86UE3
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:USP15
gene id: 9606:USP15
uniprot id: Q9Y4E8
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts with human papillomavirus type 16 protein E6.
messages: (Microbial infection) Protects APC and human papillomavirus type 16 protein E6 against degradation via the ubiquitin proteasome pathway.
messages: A homodimer structure has been reported; however it is unclear whether the protein form a homodimer in vivo (PubMed:22001210). Identified in a complex with the COP9 signalosome complex (CSN) (PubMed:16005295). Interacts with SMAD1, SMAD2 and SMAD3; the interaction is direct (PubMed:21947082). Forms a complex with SMURF2 and SMAD7 (PubMed:22344298). Interacts with TGFBR1 (PubMed:22344298). Interacts with SART3; the interaction is direct (PubMed:24526689). May interact with RNF20 and RNF40 (PubMed:24526689). May interact with PRKN (PubMed:24852371). Interacts with INCA1 (PubMed:21750715).
messages: Belongs to the peptidase C19 family.
messages: Cytoplasm
messages: Expressed in skeletal muscle, kidney, heart, placenta, liver, thymus, lung, and ovary, with little or no expression in other tissues.
messages: Hydrolase that removes conjugated ubiquitin from target proteins and regulates various pathways such as the TGF-beta receptor signaling, NF-kappa-B and RNF41/NRDP1-PRKN pathways (PubMed:21947082, PubMed:22344298, PubMed:24852371, PubMed:16005295, PubMed:17318178, PubMed:19826004, PubMed:19576224). Acts as a key regulator of TGF-beta receptor signaling pathway, but the precise mechanism is still unclear: according to a report, acts by promoting deubiquitination of monoubiquitinated R-SMADs (SMAD1, SMAD2 and/or SMAD3), thereby alleviating inhibition of R-SMADs and promoting activation of TGF-beta target genes (PubMed:21947082). According to another reports, regulates the TGF-beta receptor signaling pathway by mediating deubiquitination and stabilization of TGFBR1, leading to an enhanced TGF-beta signal (PubMed:22344298). Able to mediate deubiquitination of monoubiquitinated substrates, 'Lys-27'-, 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains (PubMed:33093067). May also regulate gene expression and/or DNA repair through the deubiquitination of histone H2B (PubMed:24526689). Acts as an inhibitor of mitophagy by counteracting the action of parkin (PRKN): hydrolyzes cleavage of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains attached by parkin on target proteins such as MFN2, thereby reducing parkin's ability to drive mitophagy (PubMed:24852371). Acts as an associated component of COP9 signalosome complex (CSN) and regulates different pathways via this association: regulates NF-kappa-B by mediating deubiquitination of NFKBIA and deubiquitinates substrates bound to VCP (PubMed:16005295, PubMed:17318178, PubMed:19826004, PubMed:19576224). Involved in endosome organization by mediating deubiquitination of SQSTM1: ubiquitinated SQSTM1 forms a molecular bridge that restrains cognate vesicles in the perinuclear region and its deubiquitination releases target vesicles for fast transport into the cell periphery (PubMed:27368102). Acts as a negative regulator of antifungal…
messages: Mitochondrion
messages: Nucleus
messages: Phosphorylated. Phosphorylation protects against ubiquitination and subsequent degradation by the proteasome.
messages: Ubiquitinated, leading to degradation by the proteasome.

9606:RCN1
gene id: 9606:RCN1
uniprot id: Q15293
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the CREC family.
messages: Endoplasmic reticulum lumen
messages: May regulate calcium-dependent activities in the endoplasmic reticulum lumen or post-ER compartment.
messages: O-glycosylated. O-mannosylated by POMT1 and POMT2 and elongated by POMGNT1.
messages: This protein has four functional calcium-binding sites; potential sites II and VI have lost affinity for calcium.

9606:TJP3
gene id: 9606:TJP3
uniprot id: O95049
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the MAGUK family.
messages: Cell membrane
messages: Exhibits enhanced expression in matured epithelial layers (PubMed:23608536). Apical leptin, Staphylococcus aureus alpha-toxin and Pseudomonas aeruginosa acyl-homoserine lactone 3O-C12-HSl lower expression levels, altering junctional integrity in intestinal cells (PubMed:20434232, PubMed:22354024, PubMed:24314862).
messages: Interacts with occludin OCLN, claudins and TPJ1 (By similarity). Interacts with PATJ (By similarity). Interacts with UBN1 (PubMed:20434232). Interacts with FASLG (PubMed:19807924). Interacts with CCND1 (PubMed:21411630).
messages: Nucleus
messages: Phosphorylated (By similarity).
messages: TJP1, TJP2, and TJP3 are closely related scaffolding proteins that link tight junction (TJ) transmembrane proteins such as claudins, junctional adhesion molecules, and occludin to the actin cytoskeleton (PubMed:16129888). The tight junction acts to limit movement of substances through the paracellular space and as a boundary between the compositionally distinct apical and basolateral plasma membrane domains of epithelial and endothelial cells. Binds and recruits PATJ to tight junctions where it connects and stabilizes apical and lateral components of tight junctions (PubMed:16129888). Promotes cell-cycle progression through the sequestration of cyclin D1 (CCND1) at tight junctions during mitosis which prevents CCND1 degradation during M-phase and enables S-phase transition (PubMed:21411630). With TJP1 and TJP2, participates in the junctional retention and stability of the transcription factor DBPA, but is not involved in its shuttling to the nucleus (By similarity). Contrary to TJP2, TJP3 is dispensable for individual viability, embryonic development, epithelial differentiation, and the establishment of TJs, at least in the laboratory environment (By similarity).
messages: tight junction

9606:OR6N1
gene id: 9606:OR6N1
uniprot id: Q8NGY5
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Odorant receptor.

9606:NUTM2A
gene id: 9606:NUTM2A
uniprot id: Q8IVF1
names: Similarity
messages: Belongs to the NUT family.

9606:DNMT1
gene id: 9606:DNMT1
uniprot id: I6L9H2
uniprot id: P26358
uniprot id: Q59FP7
names: Disease Annotation
names: Domain
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acetylation on multiple lysines, mainly by KAT2B/PCAF, regulates cell cycle G(2)/M transition. Deacetylation of Lys-1349 and Lys-1415 by SIRT1 increases methyltransferase activity.
messages: Belongs to the class I-like SAM-binding methyltransferase superfamily. C5-methyltransferase family.
messages: Homodimer (PubMed:19173286). Forms a stable complex with E2F1, BB1 and HDAC1 (PubMed:10888886). Forms a complex with DMAP1 and HDAC2, with direct interaction (PubMed:10888872). Interacts with the PRC2/EED-EZH2 complex (PubMed:16357870). Probably part of a corepressor complex containing ZNF304, TRIM28, SETDB1 and DNMT1 (PubMed:24623306). Interacts with UHRF1; promoting its recruitment to hemimethylated DNA (PubMed:21745816). Interacts with USP7, promoting its deubiquitination (PubMed:21745816). Interacts with PCNA (PubMed:9302295). Interacts with MBD2 and MBD3 (PubMed:10947852). Interacts with DNMT3A and DNMT3B (PubMed:12145218). Interacts with UBC9 (PubMed:19450230). Interacts with CSNK1D (By similarity). Interacts with HDAC1 (By similarity). Interacts with BAZ2A/TIP5 (By similarity). Interacts with SIRT7 (By similarity). Interacts with ZNF263; recruited to the SIX3 promoter along with other proteins involved in chromatin modification and transcriptional corepression where it contributes to transcriptional repression (PubMed:32051553). Interacts with L3MBTL3 and DCAF5; the interaction requires DNMT1 methylation at Lys-142 and is necessary to target DNMT1 for ubiquitination by the CRL4-DCAF5 E3 ubiquitin ligase complex and proteasomal degradation (PubMed:29691401). Interacts with PHF20L1; the interaction requires DNMT1 methylation at Lys-142 and protects DNMT1 from ubiquitination and proteasomal degradation (PubMed:24492612).
messages: Its abundance is reduced to non detectable levels at the G0 phase of the cell cycle and is dramatically induced upon entrance into the S-phase of the cell cycle.
messages: Methylates CpG residues. Preferentially methylates hemimethylated DNA. Associates with DNA replication sites in S phase maintaining the methylation pattern in the newly synthesized strand, that is essential for epigenetic inheritance. Associates with chromatin during G2 and M phases to maintain DNA methylation independently of replication. It is responsible for maintaining methylation patterns established in development. DNA methylation is coordinated with methylation of histones. Mediates transcriptional repression by direct binding to HDAC2. In association with DNMT3B and via the recruitment of CTCFL/BORIS, involved in activation of BAG1 gene expression by modulating dimethylation of promoter histone H3 at H3K4 and H3K9. Probably forms a corepressor complex required for activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes in colorectal cancer (CRC) cells (PubMed:24623306). Also required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs) (PubMed:24623306). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing (PubMed:24623306). Promotes tumor growth (PubMed:24623306).
messages: Methylation at Lys-142 by SETD7 is necessary for the regulation of DNMT1 proteasomal degradation.
messages: Nucleus
messages: Phosphorylation of Ser-154 by CDKs is important for enzymatic activity and protein stability. Phosphorylation of Ser-143 by AKT1 prevents methylation by SETD7 therebye increasing DNMT1 stability.
messages: Sumoylated; sumoylation increases activity.
messages: The CXXC-type zinc finger specifically binds to unmethylated CpG dinucleotides, positioning the autoinhibitory linker between the DNA and the active site, thus providing a mechanism to ensure that only hemimethylated CpG dinucleotides undergo methylation.
messages: The N-terminal part is required for homodimerization and acts as a regulatory domain.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitinated by UHRF1; interaction with USP7 counteracts ubiquitination by UHRF1 by promoting deubiquitination and preventing degradation by the proteasome.
messages: Ubiquitous; highly expressed in fetal tissues, heart, kidney, placenta, peripheral blood mononuclear cells, and expressed at lower levels in spleen, lung, brain, small intestine, colon, liver, and skeletal muscle. Isoform 2 is less expressed than isoform 1.

9606:APC
gene id: 9606:APC
uniprot id: P25054
uniprot id: Q4LE70
names: Disease Annotation
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: APC mutations have led to some interesting observations. (1) the great majority of the mutations found to date would result in truncation of the APC product. (2) almost all the mutations have occurred within the first half of the coding sequence, and somatic mutations in colorectal tumors are further clustered in a particular region, called MCR (mutation cluster region). (3) most identified point mutations in the APC gene are transitions from cytosine to other nucleotides. (4) the location of germline mutations tends to correlate with the number of colorectal polyps in FAP1 patients. Inactivation of both alleles of the APC gene seems to be required as an early event to develop most adenomas and carcinomas in the colon and rectum as well as some of those in the stomach.
messages: Belongs to the adenomatous polyposis coli (APC) family.
messages: Cell membrane
messages: Cytoplasm
messages: Expressed in a variety of tissues: brain, small intestine, colon, thymus, skeletal muscle, heart, prostate, lung, spleen, ovary, testis kidney, placenta, blood and liver (PubMed:21643010, PubMed:27217144). Isoform 1A: Very strongly expressed in brain but has relatively low expression levels in other tissues (PubMed:19527921, PubMed:21643010, PubMed:27217144). Isoform 1B: Predominant form in all tissues except for brain, including gastric mucosa and blood (PubMed:19527921, PubMed:21643010, PubMed:27217144).
messages: Forms homooligomers (Probable). Found in a complex consisting of ARHGEF4, APC and CTNNB1 (PubMed:10947987). Found in a complex composed of MACF1, APC, AXIN1, CTNNB1 and GSK3B (By similarity). The complex composed, at least, of APC, CTNNB1 and GSK3B interacts with JPT1; the interaction requires the inactive form of GSK3B (phosphorylated at 'Ser-9') (PubMed:25169422). Interacts with APC2 (PubMed:11691822). Interacts with DLG1 (via PDZ domains) and DLG3 (via PDZ domains) (PubMed:8638125, PubMed:9188857). Interacts with alpha- and beta-catenins (PubMed:8259519). Interacts with AXIN1 (via RGS domain) (PubMed:10811618). Interacts with ARHGEF4 (via N-terminus) (PubMed:10947987). Interacts (via C-terminal residues 2674-2843) with MAPRE1 (via C-terminal residues 206-211); the interaction inhibits association with and bundling of F-actin (PubMed:17293347, PubMed:14514668, PubMed:19632184). Interacts with MAPRE2 and MAPRE3 (via C-terminus) (PubMed:14514668). Interacts with DIAPH1; DIAPH1 acts as a scaffold protein for MAPRE1 and APC to stabilize microtubules and promote cell migration (By similarity). Interacts with DIAPH2 (By similarity). Interacts with SCRIB; may mediate APC targeting to adherens junctions of epithelial cells (PubMed:16611247). Interacts with SPATA13 (via N-terminus and SH3 domain) (PubMed:17599059). Interacts with ASAP1 (via SH3 domain) (PubMed:20509626). Interacts (at the cell membrane) with AMER1 and AMER2 (via ARM repeats) (PubMed:21498506, PubMed:22128170). Interacts with KHDRBS1 (PubMed:22000517). Interacts with actin; binds both to F-actin and actin filament bundles (PubMed:17293347).
messages: Phosphorylated; phosphorylation enhances the F-actin bundling activity (PubMed:17293347). Phosphorylated by GSK3B.
messages: Produced by alternative promoter usage.
messages: The basic region (residues 2167-2674) mediates the association with both microtubule and actin proteins and promotes the bundling of F-actin.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The gene represented in this entry may be involved in disease pathogenesis.
messages: The microtubule tip localization signal (MtLS) motif; mediates interaction with MAPRE1 and targeting to the growing microtubule plus ends.
messages: Tumor suppressor. Promotes rapid degradation of CTNNB1 and participates in Wnt signaling as a negative regulator. APC activity is correlated with its phosphorylation state. Activates the GEF activity of SPATA13 and ARHGEF4. Plays a role in hepatocyte growth factor (HGF)-induced cell migration. Required for MMP9 up-regulation via the JNK signaling pathway in colorectal tumor cells. Associates with both microtubules and actin filaments, components of the cytoskeleton (PubMed:17293347). Plays a role in mediating the organization of F-actin into ordered bundles (PubMed:17293347). Functions downstream of Rho GTPases and DIAPH1 to selectively stabilize microtubules (By similarity). Acts as a mediator of ERBB2-dependent stabilization of microtubules at the cell cortex. It is required for the localization of MACF1 to the cell membrane and this localization of MACF1 is critical for its function in microtubule stabilization.
messages: Ubiquitinated, leading to its degradation by the proteasome. Ubiquitination is facilitated by Axin. Deubiquitinated by ZRANB1/TRABID.
messages: adherens junction
messages: cytoskeleton
messages: lamellipodium
messages: ruffle membrane

9606:ZNF35
gene id: 9606:ZNF35
uniprot id: P13682
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: May be involved in transcriptional regulation. Involved in cell differentiation and/or proliferation.
messages: Nucleus

9606:KBTBD13
gene id: 9606:KBTBD13
uniprot id: C9JR72
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Autoubiquitinated.
messages: Component of the BCR(KBTBD13) E3 ubiquitin ligase complex, at least composed of CUL3 and KBTBD13 and RBX1. Interacts with CUL3.
messages: Cytoplasm
messages: Expressed in skeletal muscle.
messages: Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex.
messages: The BCB domain mediates the interaction with CUL3.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:KRTAP4-1
gene id: 9606:KRTAP4-1
uniprot id: Q9BYQ7
names: Function
names: Polymorphism
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Belongs to the KRTAP type 4 family.
messages: Expressed in the hair follicles.
messages: In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.
messages: Interacts with hair keratins.
messages: Numerous size polymorphism are present in KRTAP4 gene family, which are mainly due to variations in the sequence encoding cysteine-rich repeat segments (PubMed:15955084).

9606:IFT27
gene id: 9606:IFT27
uniprot id: Q9BW83
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the small GTPase superfamily. Rab family.
messages: Component of the IFT complex B, at least composed of IFT20, IFT25, IFT27, IFT52, IFT57, IFT74, IFT81, IFT88 and TRAF3IP1 (PubMed:25443296). Interacts with IFT25 (By similarity). Interacts with IFT70B (By similarity). Interacts with RABL2/RABL2A; binding is equal in the presence of GTP or GDP (By similarity). Interacts with ARL6; recognizes and binds with the GTP-free form of ARL6 (PubMed:25443296).
messages: Cytoplasm
messages: Small GTPase-like component of the intraflagellar transport (IFT) complex B that promotes the exit of the BBSome complex from cilia via its interaction with ARL6 (PubMed:25443296). Not involved in entry of the BBSome complex into cilium. Prevents aggregation of GTP-free ARL6 (PubMed:25443296). Required for hedgehog signaling. Forms a subcomplex within the IFT complex B with IFT25. Its role in intraflagellar transport is mainly seen in tissues rich in ciliated cells such as kidney and testis. Essential for male fertility, spermiogenesis and sperm flagella formation. Plays a role in the early development of the kidney. May be involved in the regulation of ureteric bud initiation (By similarity).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: cilium
messages: flagellum

9606:CCL15
gene id: 9606:CCL15
uniprot id: A0A0B4J2E2
uniprot id: Q16663
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the intercrine beta (chemokine CC) family.
messages: Chemotactic factor that attracts T-cells and monocytes, but not neutrophils, eosinophils, or B-cells. Acts mainly via CC chemokine receptor CCR1. Also binds to CCR3. CCL15(22-92), CCL15(25-92) and CCL15(29-92) are more potent chemoattractants than the CCL15.
messages: Monomer.
messages: Most abundant in heart, skeletal muscle and adrenal gland. Lower levels in placenta, liver, pancreas and bone marrow. CCL15(22-92), CCL15(25-92) and CCL15(29-92) are found in high levels in synovial fluids from rheumatoid patients.
messages: Secreted
messages: The N-terminal is proteolytically cleaved by proteases associated with inflammatory responses. The processed forms CCL15(22-92), CCL15(25-92) and CCL15(29-92) exhibit increase in CCR1-mediated signaling and chemotaxis assays in vitro.

9606:MPP7
gene id: 9606:MPP7
uniprot id: Q5T2T1
names: Domain
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Acts as an important adapter that promotes epithelial cell polarity and tight junction formation via its interaction with DLG1. Involved in the assembly of protein complexes at sites of cell-cell contact.
messages: Belongs to the MAGUK family.
messages: Cytoplasm
messages: Down-regulated in patients suffering of passive Heymann nephritis (at protein level).
messages: Heterodimer; able to heterodimerize via its C-terminal L27 domain with LIN7A, LIN7B and LIN7C. Forms a tripartite complex composed of DLG1, MPP7 and LIN7 (LIN7A or LIN7C). Interacts with DLG1 via its N-terminal L27 domain. Interacts with PALS1 and PATJ.
messages: Lateral cell membrane
messages: Membrane
messages: Phosphorylated by aPKC which promotes dissociation from the cell cortex.
messages: The phospho-regulated basic and hydrophobic (PRBH) motif is sufficient and important for interaction with phospholipids permitting cortical localization (PubMed:26481050). Phosphorylation of the PRBH motif by aPKC inhibits the association of the protein with the cortical membrane (PubMed:26481050).
messages: adherens junction
messages: cell cortex
messages: tight junction

9606:CELA3A
gene id: 9606:CELA3A
uniprot id: P09093
names: Function
names: Similarity
messages: Belongs to the peptidase S1 family. Elastase subfamily.
messages: Efficient protease with alanine specificity but only little elastolytic activity.

9606:CTTNBP2NL
gene id: 9606:CTTNBP2NL
uniprot id: Q9P2B4
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Interacts with CTTN/cortactin; this interaction may redistribute CTTN to stress fibers (By similarity). May form homomers. May interact with MOB4, PPP2R1A, PPP2CB, STK24, STK25, STK26, STRN4, STRIP1 and STRIP2.
messages: Regulates lamellipodial actin dynamics in a CTTN-dependent manner.
messages: lamellipodium
messages: stress fiber

9606:STAC3
gene id: 9606:STAC3
uniprot id: Q96MF2
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Cytoplasm
messages: Interacts (via SH3 domains) with the calcium channels CACNA1S and CACNA1C (PubMed:29078335). Component of a calcium channel complex with CACNA1S and CACNB1. Component of a calcium channel complex with CACNA1C and CACNB1 (By similarity).
messages: Required for normal excitation-contraction coupling in skeletal muscle and for normal muscle contraction in response to membrane depolarization. Required for normal Ca(2+) release from the sarcplasmic reticulum, which ultimately leads to muscle contraction. Probably functions via its effects on muscle calcium channels (PubMed:23736855, PubMed:29078335). Increases CACNA1S channel activity, in addition to its role in enhancing the expression of CACNA1S at the cell membrane. Has a redundant role in promoting the expression of the calcium channel CACNA1S at the cell membrane (By similarity). Slows down the inactivation rate of the calcium channel CACNA1C (PubMed:29078335).
messages: T-tubule
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: sarcolemma

9606:PIR
gene id: 9606:PIR
uniprot id: O00625
names: Activity Regulation
names: Cofactor
names: Function
names: Induction
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the pirin family.
messages: Binds 1 Fe cation per subunit.
messages: Cytoplasm
messages: Genetic variations in PIR might have a sex-specific influence on bone mineral density differences in some populations, as reported by PubMed:19766747. In a cohort of 4000 Chinese, a significant statistical association has been identified, in women but not in men, between the intronic SNP rs5935970 and lumbar spine bone mineral density, and between a haplotype composed of three SNPs with bone mineral density at other sites.
messages: Highly expressed in a subset of melanomas. Detected at very low levels in most tissues (at protein level). Expressed in all tissues, with highest level of expression in heart and liver.
messages: Inhibited by kojic acid, sodium diethyldithiocarbamate and 1,10-phenanthroline monohydrochloride.
messages: May interact with NF1/CTF1. Interacts with BCL3. Identified in a complex comprised of PIR, BLC3, NFKB1 and target DNA.
messages: Nucleus
messages: Transcriptional coregulator of NF-kappa-B which facilitates binding of NF-kappa-B proteins to target kappa-B genes in a redox-state-dependent manner. May be required for efficient terminal myeloid maturation of hematopoietic cells. Has quercetin 2,3-dioxygenase activity (in vitro).
messages: Up-regulated in CD34(+) cells upon myelomonocytic differentiation. Down-regulated in many acute myeloid leukemias. Up-regulated in primary bronchial epithelial cells exposed to cigarette smoke extract.

9606:AP3S2
gene id: 9606:AP3S2
uniprot id: P59780
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Adaptor protein complex 3 (AP-3) is a heterotetramer composed of two large adaptins (delta-type subunit AP3D1 and beta-type subunit AP3B1 or AP3B2), a medium adaptin (mu-type subunit AP3M1 or AP3M2) and a small adaptin (sigma-type subunit APS1 or AP3S2). Interacts with AGAP1. AP-3 associates with the BLOC-1 complex (By similarity).
messages: Belongs to the adaptor complexes small subunit family.
messages: Cytoplasmic vesicle membrane
messages: Golgi apparatus
messages: Part of the AP-3 complex, an adaptor-related complex which is not clathrin-associated. The complex is associated with the Golgi region as well as more peripheral structures. It facilitates the budding of vesicles from the Golgi membrane and may be directly involved in trafficking to lysosomes. In concert with the BLOC-1 complex, AP-3 is required to target cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals.
messages: Present in all adult tissues examined.

9606:RBM10
gene id: 9606:RBM10
uniprot id: A0A0S2Z4W4
uniprot id: A0A0S2Z4X1
uniprot id: P98175
uniprot id: Q7Z3D7
names: Disease Annotation
names: Function
names: Miscellaneous
names: Subcellular Location Annotation
names: Subunit
messages: Associates with the spliceosome. Component of a large chromatin remodeling complex, at least composed of MYSM1, PCAF, RBM10 and KIF11/TRIP5.
messages: May be involved in post-transcriptional processing, most probably in mRNA splicing. Binds to RNA homopolymers, with a preference for poly(G) and poly(U) and little for poly(A) (By similarity). May bind to specific miRNA hairpins (PubMed:28431233).
messages: Nucleus
messages: RBM10 transcripts also code for an alternative open reading frame (alt-ORF) coding for the MINAS-60 (AC P0DW28) protein (Probable). MINAS-60 and RBM10 ORFs are overlapping and are formed by shifting the reading frame (Probable).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:KLF5
gene id: 9606:KLF5
uniprot id: Q13887
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: Expressed only in testis and placenta.
messages: Interacts with WWP1. Interacts with ANP32B; this interaction induces promoter region-specific histone incorporation and inhibition of histone acetylation by ANP32B.
messages: Nucleus
messages: The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.
messages: Transcription factor that binds to GC box promoter elements. Activates the transcription of these genes.
messages: Ubiquitinated. Polyubiquitination involves WWP1 and leads to proteasomal degradation of this protein (PubMed:15735697). Deubiquitinated by ATXN3L (PubMed:26079537).

9606:TNK1
gene id: 9606:TNK1
uniprot id: Q13470
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Autophosphorylated on tyrosine residues.
messages: Belongs to the protein kinase superfamily. Tyr protein kinase family.
messages: Cytoplasm
messages: Expressed in all umbilical cord blood, bone marrow and adult blood cell sub-populations and in several leukemia cell lines. Highly expressed in fetal blood, brain, lung, liver and kidney. Detected at lower levels in adult prostate, testis, ovary, small intestine and colon. Not expressed in adult lung, liver, kidney or brain.
messages: Interacts with the SH3 domain of PLCG1 via its Pro-rich domain.
messages: Involved in negative regulation of cell growth. Has tumor suppressor properties. Plays a negative regulatory role in the Ras-MAPK pathway. May function in signaling pathways utilized broadly during fetal development and more selectively in adult tissues and in cells of the lymphohematopoietic system. Could specifically be involved in phospholipid signal transduction.
messages: Membrane

9606:DIP2A
gene id: 9606:DIP2A
uniprot id: Q14689
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the DIP2 family.
messages: Catalyzes the de novo synthesis of acetyl-CoA in vitro (By similarity). Promotes acetylation of CTTN, possibly by providing the acetyl donor, ensuring correct dendritic spine morphology and synaptic transmission (By similarity). Binds to follistatin-related protein FSTL1 and may act as a cell surface receptor for FSTL1, contributing to AKT activation and subsequent FSTL1-induced survival and function of endothelial cells and cardiac myocytes (PubMed:20054002).
messages: Cell membrane
messages: Interacts with FSTL1; DIP2A may act as a cell surface receptor for FSTL1 (PubMed:20860622, PubMed:20054002). Interacts (via N-terminus) with CTTN (via SH3 domain); the interaction promotes acetylation of CTTN and is required for proper synaptic transmission (By similarity). Interacts with SHANK3 (By similarity).
messages: Low expression in all tissues tested.
messages: Mitochondrion
messages: dendritic spine

9606:CATSPER3
gene id: 9606:CATSPER3
uniprot id: Q86XQ3
names: Activity Regulation
names: Caution
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the cation channel sperm-associated (TC 1.A.1.19) family.
messages: Component of the CatSper complex or CatSpermasome composed of the core pore-forming members CATSPER1, CATSPER2, CATSPER3 and CATSPER4 as well as auxiliary members CATSPERB, CATSPERG, CATSPERD, CATSPERE, CATSPERZ, C2CD6/CATSPERT, TMEM249, TMEM262 and EFCAB9 (By similarity). HSPA1 may be an additional auxiliary complex member (By similarity). The core complex members CATSPER1, CATSPER2, CATSPER3 and CATSPER4 form a heterotetrameric channel. The auxiliary CATSPERB, CATSPERG, CATSPERD and CATSPERE subunits form a pavilion-like structure over the pore which stabilizes the complex through interactions with CATSPER4, CATSPER3, CATSPER1 and CATSPER2 respectively (By similarity). TMEM262/CATSPERH interacts with CATSPERB, further stabilizing the complex. C2CD6/CATSPERT interacts at least with CATSPERD and is required for targeting the CatSper complex in the flagellar membrane (By similarity).
messages: In mouse, Slco6c1 is an additional auxiliary subunit of the CatSper complex. It is unclear if the related SLCO6A1 protein performs the same role in non-rodent species.
messages: Testis-specific.
messages: The CatSper calcium channel is indirectly activated by extracellular progesterone and prostaglandins following the sequence: progesterone > PGF1-alpha = PGE1 > PGA1 > PGE2 >> PGD2 (PubMed:21412338, PubMed:21412339, PubMed:26989199). The CatSper calcium channel is directly inhibited by endocannabinoid 2-arachidonoylglycerol (2AG) (PubMed:26989199). Indirect activation by progesterone takes place via the following mechanism: progesterone binds and activates the acylglycerol lipase ABHD2, which in turn mediates hydrolysis of 2AG inhibitor, relieving inhibition of the CatSper channel (PubMed:26989199). The primary effect of progesterone activation is to shift voltage dependence towards more physiological, negative membrane potentials; it is not mediated by metabotropic receptors and second messengers (PubMed:21412338, PubMed:21412339). Sperm capacitation enhances the effect of progesterone by providing additional negative shift. Also activated by the elevation of intracellular pH (PubMed:21412338, PubMed:21412339).
messages: Voltage-gated calcium channel that plays a central role in calcium-dependent physiological responses essential for successful fertilization, such as sperm hyperactivation, acrosome reaction and chemotaxis towards the oocyte.
messages: flagellum membrane

9606:OR2J2
gene id: 9606:OR2J2
uniprot id: A0A126GWS4
uniprot id: O76002
names: Function
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Membrane
messages: Odorant receptor.
messages: Three OR2J2 alleles are known: 6M1-6*01, 6M1-6*02 and 6M1-6*03. The sequence shown is that of allele 6M1-6*01.

9606:MAT2B
gene id: 9606:MAT2B
uniprot id: A0A140VJP2
uniprot id: Q9NZL9
names: Function
names: Miscellaneous
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Belongs to the dTDP-4-dehydrorhamnose reductase family. MAT2B subfamily.
messages: Heterotrimer; composed of a catalytic MAT2A homodimer that binds one regulatory MAT2B chain (PubMed:10644686, PubMed:23189196). Heterohexamer; composed of a central, catalytic MAT2A homotetramer flanked on either side by a regulatory MAT2B chain (PubMed:25075345). NADP binding increases the affinity for MAT2A (PubMed:23189196).
messages: Heterotrimer; composed of a catalytic MAT2A homodimer that binds one regulatory MAT2B chain. Heterohexamer; composed of a central, catalytic MAT2A homotetramer flanked on either side by a regulatory MAT2B chain. NADP binding increases the affinity for MAT2A.
messages: Its expression in hepatoma cell lines may lead to increase DNA synthesis and thereby participate in cell proliferation.
messages: Regulatory subunit of S-adenosylmethionine synthetase 2, an enzyme that catalyzes the formation of S-adenosylmethionine from methionine and ATP. Regulates MAT2A catalytic activity by changing its kinetic properties, increasing its affinity for L-methionine (PubMed:10644686, PubMed:23189196, PubMed:25075345). Can bind NADP (in vitro) (PubMed:23189196, PubMed:23425511).
messages: Regulatory subunit of S-adenosylmethionine synthetase 2, an enzyme that catalyzes the formation of S-adenosylmethionine from methionine and ATP. Regulates MAT2A catalytic activity by changing its kinetic properties, increasing its affinity for L-methionine.
messages: Widely expressed.

9606:SUN1
gene id: 9606:SUN1
uniprot id: O94901
names: Domain
names: Function
names: PTM
names: Sequence Caution
names: Subcellular Location Annotation
names: Subunit
messages: As a component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex involved in the connection between the nuclear lamina and the cytoskeleton (PubMed:18039933, PubMed:18396275). The nucleocytoplasmic interactions established by the LINC complex play an important role in the transmission of mechanical forces across the nuclear envelope and in nuclear movement and positioning (By similarity). Required for interkinetic nuclear migration (INM) and essential for nucleokinesis and centrosome-nucleus coupling during radial neuronal migration in the cerebral cortex and during glial migration (By similarity). Involved in telomere attachment to nuclear envelope in the prophase of meiosis implicating a SUN1/2:KASH5 LINC complex in which SUN1 and SUN2 seem to act at least partial redundantly (By similarity). Required for gametogenesis and involved in selective gene expression of coding and non-coding RNAs needed for gametogenesis (By similarity). Helps to define the distribution of nuclear pore complexes (NPCs) (By similarity). Required for efficient localization of SYNE4 in the nuclear envelope (By similarity). May be involved in nuclear remodeling during sperm head formation in spermatogenesis (By similarity). May play a role in DNA repair by suppressing non-homologous end joining repair to facilitate the repair of DNA cross-links (PubMed:24375709).
messages: Core component of the LINC complex which is composed of inner nuclear membrane SUN domain-containing proteins coupled to outer nuclear membrane KASH domain-containing nesprins. SUN and KASH domain-containing proteins seem to bind each other promiscuously; however, differentially expression of LINC complex constituents is giving rise to specific assemblies. At least SUN1/2-containing core LINC complexes are proposed to be hexameric composed of three protomers of each KASH and SUN domain-containing protein. Interacts with KASH5 (via the last 22 amino acids); this interaction mediates KASH5 telomere localization by forming a SUN1:KASH5 LINC complex. May interact with SYNE3. Interacts with SYNE2 and SYNE1; probably forming respective LINC complexes. Interacts with A-type lamin with a strong preference for unprocessed A-type lamin compared with the mature protein. Interaction with lamins B1 and C is hardly detectable. Interacts with NAT10. Interacts with EMD and TSNAX. Associates with the nuclear pore complex (NPC). Interacts with CCDC79/TERB1; promoting the accumulation of the LINC complex complexes at the telomere-nuclear envelope attachment sites. Interacts (via KASH domain) with TMEM258 (PubMed:28716842).
messages: Nucleus inner membrane
messages: Probable cloning artifact.
messages: The SUN domain may play a role in nuclear anchoring and/or migration.
messages: The coiled coil domains differentially mediate trimerization required for binding to nesprins and are proposed to dynamically regulate the oligomeric state by locking the SUN domain in an inactive confirmation. The coiled coil domains are proposed to be involved in load-bearing and force transmission from the cytoskeleton.
messages: The disulfide bond with KASH domain-containing nesprins is required for stability of the respective LINC complexes under tensile forces.

9606:P2RY4
gene id: 9606:P2RY4
uniprot id: P51582
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Pancreas.
messages: Phosphorylation of Ser-333 and Ser-334 is a key step in agonist-dependent desensitization and loss of surface P2RY4. This phosphorylation does not involve PKC, nor other calcium activated kinases.
messages: Receptor for UTP and UDP coupled to G-proteins that activate a phosphatidylinositol-calcium second messenger system. Not activated by ATP or ADP.

9606:DMAC2L
gene id: 9606:DMAC2L
uniprot id: Q99766
names: Caution
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the ATP synthase subunit s family.
messages: Homotetramer. Associates with ATP synthase.
messages: Involved in regulation of mitochondrial membrane ATP synthase. Necessary for H(+) conduction of ATP synthase. Facilitates energy-driven catalysis of ATP synthesis by blocking a proton leak through an alternative proton exit pathway.
messages: It is uncertain whether Met-1 or Met-16 is the initiator.
messages: Mitochondrion
messages: Mitochondrion inner membrane

9606:NINL
gene id: 9606:NINL
uniprot id: Q9Y2I6
names: Domain
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cytoplasm
messages: Expressed in KYSE-150 esophageal carcinoma, HeLa cervical carcinoma and U2OS osteosarcoma cells. Expression is regulated in a cell cycle-dependent manner and peaks during G2/M phase (at protein level). Expressed in fetal heart, skeletal muscle, liver, lung and cochlea, and in adult brain, testis, kidney and retina.
messages: Interacts with gamma-tubulin and TUBGCP4. Interacts with anaphase promoting complex/cyclosome (APC/C). Interacts with CDC20 and FZR1. Isoform 2 interacts with LCA5 and USH2A. Isoform 2 interacts with DZANK1 (PubMed:26485514).
messages: Involved in the microtubule organization in interphase cells. Overexpression induces the fragmentation of the Golgi, and causes lysosomes to disperse toward the cell periphery; it also interferes with mitotic spindle assembly. Involved in vesicle transport in photoreceptor cells (By similarity). May play a role in ovarian carcinogenesis.
messages: Phosphorylated by PLK1 which disrupts its centrosome association and interaction with gamma-tubulin.
messages: The KEN and D (destructive) boxes are required for the cell cycle-controlled NINL degradation by the APC/C pathway.
messages: Ubiquitinated by the APC/C complex leading to its degradation.
messages: centrosome

9606:PPAN
gene id: 9606:PPAN
uniprot id: A8MV53
uniprot id: Q9NQ55
names: Function
names: Miscellaneous
names: Subcellular Location Annotation
names: Tissue Specificity
messages: A chimeric transcript, characterized by the first third of PPAN exon 12 joined to P2RY11 exon 2, has been detected. It is possibly produced by trans-splicing. The chimeric transcript is widely expressed and can be induced by retinoic acid during the granulocytic differentiation of the HL-60 cell line. The resulting chimeric protein shows a much lower activity than the non-chimeric P2RY11 gene product, but qualitatively indistinguishable (PubMed:11278528).
messages: May have a role in cell growth.
messages: Widely expressed.
messages: nucleolus

9606:AS3MT
gene id: 9606:AS3MT
uniprot id: Q9HBK9
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the methyltransferase superfamily. Arsenite methyltransferase family.
messages: Catalyzes the transfer of a methyl group from AdoMet to trivalent arsenicals producing methylated and dimethylated arsenicals (PubMed:16407288, PubMed:25997655). It methylates arsenite to form methylarsonate, Me-AsO(3)H(2), which is reduced by methylarsonate reductase to methylarsonite, Me-As(OH)2 (PubMed:16407288, PubMed:25997655). Methylarsonite is also a substrate and it is converted into the much less toxic compound dimethylarsinate (cacodylate), Me(2)As(O)-OH (PubMed:16407288, PubMed:25997655).
messages: Devoid of methyltransferase activity.
messages: cytosol

9606:XKR5
gene id: 9606:XKR5
uniprot id: Q6UX68
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the XK family.
messages: Cell membrane
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

9606:C2orf88
gene id: 9606:C2orf88
uniprot id: Q9BSF0
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the small membrane AKAP family.
messages: Binds to type I regulatory subunits of protein kinase A (PKA-RI) and may anchor/target them to the plasma membrane.
messages: Cell membrane
messages: Expressed in heart (at protein level).
messages: Interacts with PRKAR1A and PRKAR1B.
messages: May be palmitoylated at Cys-3.

9606:ISYNA1
gene id: 9606:ISYNA1
uniprot id: A0A140VK73
uniprot id: Q9NPH2
names: Activity Regulation
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the myo-inositol 1-phosphate synthase family.
messages: By glucose and lovastain. Up-regulation is prevented by mevalonic acid, farnesol, and geranylgeraniol. Up-regulated by E2F1.
messages: Cytoplasm
messages: Highly expressed in testis, ovary, heart, placenta and pancreas. Weakly expressed in blood leukocyte, thymus, skeletal muscle and colon.
messages: Inhibited by mood-stabilizing drugs such as valproate (VPA) and lithium.
messages: Key enzyme in myo-inositol biosynthesis pathway that catalyzes the conversion of glucose 6-phosphate to 1-myo-inositol 1-phosphate in a NAD-dependent manner (PubMed:15024000, PubMed:23902760). Rate-limiting enzyme in the synthesis of all inositol-containing compounds (PubMed:15024000).
messages: Phosphorylation at Ser-279 and Ser-357 may be associated with a decrease in activity.

9606:DDX42
gene id: 9606:DDX42
uniprot id: Q86XP3
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: ATP-dependent RNA helicase. Binds to partially double-stranded RNAs (dsRNAs) in order to unwind RNA secondary structures. Unwinding is promoted in the presence of single-strand binding proteins. Mediates also RNA duplex formation thereby displacing the single-strand RNA binding protein. ATP and ADP modulate its activity: ATP binding and hydrolysis by DDX42 triggers RNA strand separation, whereas the ADP-bound form of the protein triggers annealing of complementary RNA strands. Involved in the survival of cells by interacting with TP53BP2 and thereby counteracting the apoptosis-stimulating activity of TP53BP2. Relocalizes TP53BP2 to the cytoplasm.
messages: Belongs to the DEAD box helicase family. DDX42 subfamily.
messages: Cajal body
messages: Component of splicing factor SF3B complex which is composed of at least eight subunits; SF3B1, SF3B2, SF3B3, SF3B4, SF3B5, SF3B6, PHF5A/SF3B14B, and DDX42/SF3B125. Interacts (via the C-terminus) with TP53BP2; the interaction is not inhibitied by TP53BP2 ubiquitination and is independent of p53/TP53.
messages: Cytoplasm
messages: Expressed in several cell lines (at protein level). Expressed in liver, lung, tonsil, thymus, muscle and pancreatic islets.
messages: Nucleus
messages: Nucleus speckle

9606:NAT16
gene id: 9606:NAT16
uniprot id: Q8N8M0
names: Function
names: Miscellaneous
messages: NAT16 is the ortholog of the ectothermic vertebrates enzyme HISAT (AC I3J7Q8) responsible for the synthesis of N-acetyl-histidine (NAH). NAT16 protein, unlike fish HISAT, has only trace enzyme activity for NAH synthesis.
messages: Probable N-acetyltransferase. Shows only trace activity toward L-His and no N-acetyltransferase activity toward other amino acids. The physiological substrate of this enzyme is unknown.

9606:THEM5
gene id: 9606:THEM5
uniprot id: Q8N1Q8
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the THEM4/THEM5 thioesterase family.
messages: Has acyl-CoA thioesterase activity towards long-chain (C16 and C18) fatty acyl-CoA substrates, with a preference for linoleoyl-CoA and other unsaturated long-chain fatty acid-CoA esters (PubMed:22586271). Plays an important role in mitochondrial fatty acid metabolism, and in remodeling of the mitochondrial lipid cardiolipin (PubMed:22586271). Required for normal mitochondrial function (PubMed:22586271).
messages: Homodimer.
messages: Mitochondrion matrix

9606:MYOT
gene id: 9606:MYOT
uniprot id: Q9UBF9
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the myotilin/palladin family.
messages: Component of a complex of multiple actin cross-linking proteins. Involved in the control of myofibril assembly and stability at the Z lines in muscle cells.
messages: Expressed in skeletal muscle (at protein level). Expressed in skeletal muscle, heart, bone marrow and thyroid gland.
messages: Homodimer. Interacts with ACTA1, ACTN1, FLNA, FLNB, FLNC and MYOZ2. Interacts with the C-terminal region of MYOZ1.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Z line
messages: cytoskeleton
messages: sarcolemma

9606:EIF5B
gene id: 9606:EIF5B
uniprot id: O60841
uniprot id: Q8N5A0
names: Cofactor
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Cleaved and inactivated by the protease 3C of poliovirus, Coxsackievirus B3 and Human rhinovirus 14, allowing the virus to shutoff the host cell translation.
messages: Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. IF-2 subfamily.
messages: Binds 1 monovalent cation per monomer in the active site. Structural cofactor that stabilizes the GTP-bound 'on' state. May also act as a transition state stabilizer of the hydrolysis reaction.
messages: Cytoplasm
messages: Interacts through its C-terminal domain (CTD) with the CTD of eIF1A (EIF1AX) or with the CTD of EIF5 (mutually exclusive) through a common binding site (PubMed:30211544). Interacts with eIF1A (EIF1AX) from the location of the start codon by the 43S complex until the formation of the 80S complex (PubMed:12569173, PubMed:35732735). Interacts with ANXA5 in a calcium and phospholipid-dependent manner (By similarity).
messages: Plays a role in translation initiation (PubMed:10659855, PubMed:35732735). Ribosome-dependent GTPase that promotes the joining of the 60S ribosomal subunit to the pre-initiation complex to form the 80S initiation complex with the initiator methionine-tRNA in the P-site base paired to the start codon (PubMed:10659855, PubMed:35732735). Together with eIF1A (EIF1AX), actively orients the initiator methionine-tRNA in a conformation that allows 60S ribosomal subunit joining to form the 80S initiation complex (PubMed:12569173, PubMed:35732735). Is released after formation of the 80S initiation complex (PubMed:35732735). Its GTPase activity is not essential for ribosomal subunits joining, but GTP hydrolysis is needed for eIF1A (EIF1AX) ejection quickly followed by EIF5B release to form elongation-competent ribosomes (PubMed:10659855, PubMed:35732735). In contrast to its procaryotic homolog, does not promote recruitment of Met-rRNA to the small ribosomal subunit (PubMed:10659855).

9606:DDX41
gene id: 9606:DDX41
uniprot id: B3KRK2
uniprot id: Q9UJV9
names: Disease Annotation
names: Function
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the DEAD box helicase family. DDX41 subfamily.
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry.
messages: Identified in the spliceosome C complex (PubMed:11991638, PubMed:25920683). Interacts with ERCC6 (PubMed:26030138). Interacts with FAM50A (PubMed:32703943).
messages: Intron retention.
messages: Nucleus
messages: Probable ATP-dependent RNA helicase. Is required during post-transcriptional gene expression. May be involved in pre-mRNA splicing.

9606:CENPN
gene id: 9606:CENPN
uniprot id: Q96H22
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the CENP-N/CHL4 family.
messages: Component of the CENPA-NAC (nucleosome-associated) complex, a complex that plays a central role in assembly of kinetochore proteins, mitotic progression and chromosome segregation. The CENPA-NAC complex recruits the CENPA-CAD (nucleosome distal) complex and may be involved in incorporation of newly synthesized CENPA into centromeres. CENPN is the first protein to bind specifically to CENPA nucleosomes and the direct binding of CENPA nucleosomes by CENPN is required for centromere assembly. Required for chromosome congression and efficiently align the chromosomes on a metaphase plate.
messages: Component of the CENPA-NAC complex, at least composed of CENPA, CENPC, CENPH, CENPM, CENPN, CENPT and CENPU (PubMed:16622420, PubMed:16622419). The CENPA-NAC complex interacts with the CENPA-CAD complex, composed of CENPI, CENPK, CENPL, CENPO, CENPP, CENPQ, CENPR and CENPS. Interacts directly with CENPA (PubMed:19543270). Identified in a centromere complex containing histones H2A, H2B and H4, and at least CENPA, CENPB, CENPC, CENPT, CENPN, HJURP, SUPT16H, SSRP1 and RSF1 (PubMed:27499292).
messages: Nucleus
messages: kinetochore

9606:TMEM184A
gene id: 9606:TMEM184A
uniprot id: Q6ZMB5
names: Function
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Acts as a heparin receptor in vascular cells (By similarity). May be involved in vesicle transport in exocrine cells and Sertoli cells (By similarity).
messages: Belongs to the TMEM184 family.
messages: Cell membrane
messages: Cytoplasmic vesicle membrane
messages: Early endosome membrane
messages: Endosome
messages: Expressed in vascular cells (at protein level).
messages: Probable cloning artifact. Aberrant splice sites.
messages: perinuclear region
messages: secretory vesicle membrane

9606:P2RY11
gene id: 9606:P2RY11
uniprot id: Q96G91
names: Function
names: Induction
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: A chimeric transcript, characterized by the first third of PPAN exon 12 joined to P2RY11 exon 2, has been detected. It is possibly produced by trans-splicing. The chimeric transcript is widely expressed and can be induced by retinoic acid during the granulocytic differentiation of the HL-60 cell line. The resulting chimeric protein shows a much lower activity than the non-chimeric P2RY11 gene product, but qualitatively indistinguishable (PubMed:11278528).
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Highest expression in liver and spleen.
messages: Increased by DMSO and retinoic acid.
messages: Receptor for ATP and ADP coupled to G-proteins that activate both phosphatidylinositol-calcium and adenylyl cyclase second messenger systems. Not activated by UTP or UDP.

9606:WBP11
gene id: 9606:WBP11
uniprot id: Q9Y2W2
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Activates pre-mRNA splicing. May inhibit PP1 phosphatase activity.
messages: Cytoplasm
messages: Interacts with PPP1CA, PPP1CB and PPP1CC (By similarity). Interacts via the PGR motif with PQBP1 in the nucleus. Interacts with the WW domains of WBP4.
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitous. Highly expressed in the heart, pancreas, kidney skeletal muscle, placenta and brain (at protein level). Weakly expressed in liver and lung.

9606:POLR2J
gene id: 9606:POLR2J
uniprot id: P52435
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the archaeal Rpo11/eukaryotic RPB11/RPC19 RNA polymerase subunit family.
messages: Component of the RNA polymerase II (Pol II) complex consisting of 12 subunits. Interacts with AATF.
messages: DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB11 is part of the core element with the central large cleft (By similarity).
messages: Nucleus
messages: Ubiquitously expressed. High expression was found in heart and skeletal muscle.

9606:TTC4
gene id: 9606:TTC4
uniprot id: O95801
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the TTC4 family.
messages: Cytoplasm
messages: Highly expressed in proliferating tissue and tumor cell lines but not in normal cell lines.
messages: Interacts (via TPR repeats) with HSP90AB1 (PubMed:18320024). Interacts with HSPA8 and CDC6 (PubMed:18320024). Interacts with TBK1 (PubMed:29251827). Interacts with MSL1 (By similarity).
messages: May act as a co-chaperone for HSP90AB1 (PubMed:18320024). Promotes Sendai virus (SeV)-induced host cell innate immune responses (PubMed:29251827).
messages: Nucleus
messages: nucleoplasm

9606:COIL
gene id: 9606:COIL
uniprot id: P38432
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the coilin family.
messages: Cajal body
messages: Component of nuclear coiled bodies, also known as Cajal bodies or CBs, which are involved in the modification and assembly of nucleoplasmic snRNPs.
messages: Found in all the cell types examined.
messages: Interacts with ANKS1B (PubMed:15862129). Interacts with SMN1 (via Tudor domain) (PubMed:11641277). Interacts (via C-terminus) with AK6 (PubMed:16079131). Interacts with WRAP53/TCAB1 (PubMed:21072240). Interacts with HMBOX1 (PubMed:23685356). Interacts with PSME3; the interaction is inhibited by PSME3IP1 (PubMed:29934401). Interacts wit UBL5 (PubMed:23726919).
messages: Nucleus
messages: Phosphorylation during mitosis is associated with disassembly of CBs.
messages: Symmetrical dimethylation of arginine residues within the RG repeat region enhances affinity for SMN, and thus localization of SMN complexes to CBs.
messages: The atypical Tudor domain at the C-terminus contains two large unstructured loops, and does not bind methylated residues.

9606:ZCCHC18
gene id: 9606:ZCCHC18
uniprot id: P0CG32
names: Similarity
messages: Belongs to the ZCCHC12 family.

9606:FNDC4
gene id: 9606:FNDC4
uniprot id: Q9H6D8
names: Function
names: Induction
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Acts as an anti-inflammatory factor in the intestine and colon. Binds to and acts on macrophages to down-regulate pro-inflammatory gene expression. Affects key macrophage functions, including phagocytosis, by down-regulating many key pathways for macrophage activation, partly via by STAT3 activation and signaling. May be required to dampen the immunological response in colitis.
messages: Induced by TGFB1.
messages: Membrane
messages: Secreted
messages: Up-regulated in colon cells of patients with inflammatory bowel disease (IBD).

9606:EARS2
gene id: 9606:EARS2
uniprot id: Q5JPH6
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the class-I aminoacyl-tRNA synthetase family. Glutamate--tRNA ligase type 1 subfamily.
messages: Catalyzes the attachment of glutamate to tRNA(Glu) in a two-step reaction: glutamate is first activated by ATP to form Glu-AMP and then transferred to the acceptor end of tRNA(Glu).
messages: Mitochondrion matrix
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:MIPOL1
gene id: 9606:MIPOL1
uniprot id: Q8TD10
names: Disease Annotation
names: Miscellaneous
names: Tissue Specificity
messages: A chromosomal aberration involving MIPOL1 is found in a patient with mirror-image polydactyly of hands and feet without other anomalies (MIP). Translocation t(2;14)(p23.3;q13). MIP is a very rare congenital anomaly characterized by mirror-image duplication of digits. MIP is occasionally associated with dimelia of the ulna and fibula, tibial and/or fibular hypoplasia, nasal abnormality and other malformations. Most MIP cases are sporadic, but very rare parent-child transmissions observed in familial cases suggest an autosomal mode of inheritance.
messages: Expressed very weakly in heart, liver, skeletal muscle, kidney, pancreas and fetal kidney. Not detected in brain, placenta and lung.
messages: May be due to a competing acceptor splice site.

9606:KDELR2
gene id: 9606:KDELR2
uniprot id: P33947
names: Disease Annotation
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the ERD2 family.
messages: Binds the C-terminal sequence motif K-D-E-L in a hydrophilic cavity between the transmembrane domains. This triggers a conformation change that exposes a Lys-rich patch on the cytosolic surface of the protein (By similarity). This patch mediates recycling from the Golgi to the endoplasmic reticulum, probably via COPI vesicles (By similarity).
messages: COPI-coated vesicle membrane
messages: Endoplasmic reticulum membrane
messages: Golgi apparatus membrane
messages: Membrane receptor that binds the K-D-E-L sequence motif in the C-terminal part of endoplasmic reticulum resident proteins and maintains their localization in that compartment by participating to their vesicle-mediated recycling back from the Golgi (PubMed:1325562, PubMed:18086916, PubMed:33053334). Binding is pH dependent, and is optimal at pH 5-5.4 (By similarity).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:ZNF589
gene id: 9606:ZNF589
uniprot id: Q86UQ0
names: Domain
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: Interacts with TRIM28.
messages: Isoform 2 is widely expressed. Isoform 3 is only expressed in CD34(+) cells.
messages: May play a role in hematopoietic stem/progenitor cell differentiation. May play a role as a DNA binding-dependent transcriptional repressor.
messages: Nucleus
messages: Probable target of nonsense-mediated mRNA decay. The proposed CDS is dubious.
messages: Probable target of nonsense-mediated mRNA decay. The proposed CDS is dubious. Isoform produced through aberrant splice sites.
messages: The KRAB domain mediates interaction with TRIM28.

9606:KCNJ10
gene id: 9606:KCNJ10
uniprot id: P78508
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Basolateral cell membrane
messages: Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ10 subfamily.
messages: Expressed in kidney (at protein level).
messages: Heterodimer with Kir5.1/KCNJ16; this interaction is required for KCNJ16 localization to the basolateral membrane in kidney cells. Interacts with MAGI1, alone and possibly as a heterodimer with KCNJ16; this interaction may facilitate KCNJ10/KCNJ16 potassium channel expression at the basolateral membrane in kidney cells (PubMed:24561201). Interacts with PATJ (By similarity).
messages: May be responsible for potassium buffering action of glial cells in the brain. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by extracellular barium and cesium (By similarity). In the kidney, together with KCNJ16, mediates basolateral K(+) recycling in distal tubules; this process is critical for Na(+) reabsorption at the tubules.
messages: Membrane
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:NOTCH2NLA
gene id: 9606:NOTCH2NLA
uniprot id: Q7Z3S9
names: Developmental Stage
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the NOTCH family.
messages: Cleaved by ELANE.
messages: Cytoplasm
messages: Defects in NOTCH2NLA may be a cause of chromosome 1q21.1 deletion/duplication syndrome (PubMed:29856954). Deletions of NOTCH2NL (NOTCH2NLA, NOTCH2NLB and/or NOTCH2NLC) are present in patients affected by microcephaly, whereas macrocephaly is observed in patients with NOTCH2NL duplications (PubMed:29856954).
messages: Expressed at low levels at 7-9 gestational weeks and then increases at later stages, including in the non-cortical plate region at gestational week 21, containing the outer-subventricular zone (PubMed:29856955). Expressed at lower level than NOTCH2NLB (PubMed:29856955).
messages: Human-specific protein that promotes neural progenitor proliferation and evolutionary expansion of the brain neocortex by regulating the Notch signaling pathway (PubMed:29856954, PubMed:29856955, PubMed:29561261). Able to promote neural progenitor self-renewal, possibly by down-regulating neuronal differentiation genes, thereby delaying the differentiation of neuronal progenitors and leading to an overall final increase in neuronal production (PubMed:29856954). Acts by enhancing the Notch signaling pathway via two different mechanisms that probably work in parallel to reach the same effect (PubMed:29856954). Enhances Notch signaling pathway in a non-cell-autonomous manner via direct interaction with NOTCH2 (PubMed:29856954). Also promotes Notch signaling pathway in a cell-autonomous manner through inhibition of cis DLL1-NOTCH2 interactions, which promotes neuronal differentiation (By similarity).
messages: Interacts with ELANE (PubMed:14673143). Interacts with NOTCH2 (PubMed:29856954). Interacts with DLL1; the interaction is direct (By similarity).
messages: Secreted
messages: Widely expressed with higher levels in leukocytes and lymph nodes (PubMed:14673143). Expressed in radial glia neural stem cells during cortical development (PubMed:29856954).

9606:KLK11
gene id: 9606:KLK11
uniprot id: Q9UBX7
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: About 40% of KLK11 is inactivated by internal cleavage after Arg-188. This proteolytic inactivation may be effected by plasminogen.
messages: Belongs to the peptidase S1 family. Kallikrein subfamily.
messages: Expressed in brain, skin and prostate. Isoform 1 is expressed preferentially in brain. Isoform 2 is expressed in prostate. Present in seminal plasma at concentrations ranging from 2 to 37 microg/mL (at protein level).
messages: Golgi apparatus
messages: Localized in the prostate secretory epithelium.
messages: Possible multifunctional protease. Efficiently cleaves 'bz-Phe-Arg-4-methylcoumaryl-7-amide', a kallikrein substrate, and weakly cleaves other substrates for kallikrein and trypsin. Cleaves synthetic peptides after arginine but not lysine residues.
messages: Secreted

9606:SCAP
gene id: 9606:SCAP
uniprot id: B7Z6H0
uniprot id: Q12770
names: Domain
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the WD repeat SCAP family.
messages: By androgen-bound AR and glucocorticoid-bound NR3C1 in a prostate cancer cell line (LNCaP).
messages: COPII-coated vesicle membrane
messages: Cholesterol bound to SSD domain of SCAP or oxysterol bound to INSIG (INSIG1 or INSIG2) leads to masking of an ER export signal (also named MELADL motif) on SCAP possibly by moving the signal further away from the ER membrane.
messages: Endoplasmic reticulum membrane
messages: Escort protein required for cholesterol as well as lipid homeostasis (By similarity). Regulates export of the SCAP-SREBP complex from the endoplasmic reticulum to the Golgi upon low cholesterol, thereby regulating the processing of sterol regulatory element-binding proteins (SREBPs) SREBF1/SREBP1 and SREBF2/SREBP2 (By similarity). At high sterol concentrations, formation of a ternary complex with INSIG (INSIG1 or INSIG2) leads to mask the ER export signal in SCAP, promoting retention of the complex in the endoplasmic reticulum (By similarity). Low sterol concentrations trigger release of INSIG, a conformational change in the SSD domain of SCAP, unmasking of the ER export signal, promoting recruitment into COPII-coated vesicles and transport of the SCAP-SREBP to the Golgi: in the Golgi, SREBPs are then processed, releasing the transcription factor fragment of SREBPs from the membrane, its import into the nucleus and up-regulation of LDLR, INSIG1 and the mevalonate pathway (By similarity). Binds cholesterol via its SSD domain (By similarity).
messages: Golgi apparatus membrane
messages: Loop-1 binds to loop-7, enabling interaction with COPII-coated vesicles. When levels of cholesterol in the endoplasmic reticulum increase, Loop-1 binds to cholesterol instead, thereby disrupting direct binding between the two loops and preventing the SCAP-SREBP complex from exiting the endoplasmic reticulum.
messages: Membrane region forms a homotetramer (By similarity). Component of the SCAP-SREBP complex (composed of SCAP and SREBF1/SREBP1 or SREBF2/SREBP2); interacts with SREBF1/SREBP1 or SREBF2/SREBP2 through its C-terminal cytoplasmic domain (By similarity). Forms a ternary complex with INSIG1 or INSIG2 through its transmembrane domains at high sterol concentrations (PubMed:17428920, PubMed:26160948). Interacts with the SEC23-SEC24 complex in a SAR1-GTP-dependent manner through an ER export signal in its third cytoplasmic loop (By similarity). Interacts with RNF139; the interaction inhibits the interaction of SCAP with SEC24B and hampering the ER to Golgi transport of the SCAP-SREBP complex (PubMed:19706601). Interacts with SPRING1 (PubMed:32111832).
messages: Ubiquitinated at Lys-454 and Lys-466. RNF145 triggers ubiquitination of SCAP, likely inhibiting SCAP-SREBP complex transport to the Golgi apparatus and the subsequent processing/maturation of SREBF2/SREBP2.

9606:PDE11A
gene id: 9606:PDE11A
uniprot id: Q9HCR9
names: Activity Regulation
names: Cofactor
names: Disease Annotation
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the cyclic nucleotide phosphodiesterase family.
messages: Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions.
messages: Inhibited by 3-isobutyl-1-methylxanthine (IBMX), zaprinast and dipyridamole. cGMP acts as an allosteric activator. Weakly inhibited by Sildenafil (Viagra) and Tadalafil (Cialis); however, the fact that the protein is probably absent from testis, suggests that it is not biologically relevant and is not related with erectile dysfunction.
messages: Isoform 1 is present in prostate, pituitary, heart and liver. It is however not present in testis nor in penis, suggesting that weak inhibition by Tadalafil (Cialis) is not relevant (at protein level). Isoform 2 may be expressed in testis. Isoform 4 is expressed in adrenal cortex.
messages: Plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides cAMP and cGMP (PubMed:10725373, PubMed:10906126, PubMed:11050148, PubMed:16330539). Catalyzes the hydrolysis of both cAMP and cGMP to 5'-AMP and 5'-GMP, respectively (PubMed:10725373, PubMed:10906126, PubMed:11050148).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The tandem GAF domains bind cGMP, and regulate enzyme activity. The binding of cGMP stimulates enzyme activity.
messages: cytosol

9606:NUDT6
gene id: 9606:NUDT6
uniprot id: B4DG76
uniprot id: P53370
names: Caution
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the Nudix hydrolase family.
messages: Cytoplasm
messages: Detected in liver, kidney and esophagus (at protein level). Ubiquitous.
messages: May contribute to the regulation of cell proliferation.
messages: Mitochondrion
messages: Monomer and homodimer.
messages: Nucleus
messages: The rat protein was reported to play a role in DNA repair (PubMed:9406864), based on its ability to complement E.coli deficient in the DNA repair enzyme mutT that hydrolyzes oxidized guanine nucleotides. PubMed:17569023 found no such activity, neither for the human nor the rat protein.
messages: This protein is coded from a FGF2 (BFGF) gene antisense transcript.

9606:SAP130
gene id: 9606:SAP130
uniprot id: A0A2R8YDB8
uniprot id: H7BXF5
uniprot id: Q96DP1
uniprot id: Q9H0E3
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acetylated.
messages: Acts as a transcriptional repressor. May function in the assembly and/or enzymatic activity of the mSin3A corepressor complex or in mediating interactions between the complex and other regulatory complexes.
messages: Belongs to the SAP130 family.
messages: Component of a mSin3A corepressor complex that contains SIN3A, SAP130, SUDS3/SAP45, ARID4B/SAP180, HDAC1 and HDAC2. Interacts (released by dead or dying cells) with CLEC4E (By similarity).
messages: Expressed in various cancer cell ines.
messages: Nucleus
messages: Sumoylated with SUMO1.
messages: The C-terminus may interact with HDAC-dependent and HDAC-independent corepressors.
messages: The N-terminus may interact with a transcriptional coactivator.

9606:FUCA1
gene id: 9606:FUCA1
uniprot id: P04066
names: Disease Annotation
names: Function
names: Polymorphism
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Alpha-L-fucosidase is responsible for hydrolyzing the alpha-1,6-linked fucose joined to the reducing-end N-acetylglucosamine of the carbohydrate moieties of glycoproteins.
messages: Belongs to the glycosyl hydrolase 29 family.
messages: Homotetramer.
messages: Lysosome
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: There are two common alleles of FUCA1; FUCA1*1; also known as Fu1; has Arg-281 and FUCA1*2; also known as Fu2; has Gln-281.
messages: Translation of X01390 sequence produces a larger peptide than that shown in CAA25646.1.

9606:PTP4A2
gene id: 9606:PTP4A2
uniprot id: Q12974
names: Activity Regulation
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: A processed pseudogene with 96% sequence identity was found in the BRCA1 (113705) region of 17q21.
messages: Belongs to the protein-tyrosine phosphatase family.
messages: Cell membrane
messages: Cytoplasm
messages: Early endosome
messages: Farnesylated. Farnesylation is required for membrane targeting and for interaction with RABGGTB. Unfarnesylated forms are redirected to the nucleus and cytosol.
messages: In contrast to PTP4A1 and PTP4A3, does not interact with tubulin. Interacts with RABGGTB.
messages: Inhibited by sodium orthovanadate and pentamidine.
messages: Protein tyrosine phosphatase which stimulates progression from G1 into S phase during mitosis. Promotes tumors. Inhibits geranylgeranyl transferase type II activity by blocking the association between RABGGTA and RABGGTB.
messages: Ubiquitously expressed, with highest levels in skeletal muscle, heart and thymus. Overexpressed in prostate tumor tissue.

9606:EHD1
gene id: 9606:EHD1
uniprot id: A0A024R571
uniprot id: B2R5U3
uniprot id: Q9H4M9
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: ATP- and membrane-binding protein that controls membrane reorganization/tubulation upon ATP hydrolysis. In vitro causes vesiculation of endocytic membranes (PubMed:24019528). Acts in early endocytic membrane fusion and membrane trafficking of recycling endosomes (PubMed:15020713, PubMed:17233914, PubMed:20801876). Recruited to endosomal membranes upon nerve growth factor stimulation, indirectly regulates neurite outgrowth (By similarity). Plays a role in myoblast fusion (By similarity). Involved in the unidirectional retrograde dendritic transport of endocytosed BACE1 and in efficient sorting of BACE1 to axons implicating a function in neuronal APP processing (By similarity). Plays a role in the formation of the ciliary vesicle (CV), an early step in cilium biogenesis. Proposed to be required for the fusion of distal appendage vesicles (DAVs) to form the CV by recruiting SNARE complex component SNAP29. Is required for recruitment of transition zone proteins CEP290, RPGRIP1L, TMEM67 and B9D2, and of IFT20 following DAV reorganization before Rab8-dependent ciliary membrane extension. Required for the loss of CCP110 form the mother centriole essential for the maturation of the basal body during ciliogenesis (PubMed:25686250).
messages: Belongs to the TRAFAC class dynamin-like GTPase superfamily. Dynamin/Fzo/YdjA family. EHD subfamily.
messages: Cell membrane
messages: Early endosome membrane
messages: Endosome membrane
messages: Highly expressed in testis.
messages: Homooligomer, and heterooligomer with EHD2, EHD3 and EHD4, ATP-binding is required for heterooligomerization (PubMed:16251358, PubMed:17233914, PubMed:18331452). Interacts (via EH domain) with MICALL1 (via NPF1 motif); the interaction is direct and recruits EHD1 to membranes (PubMed:19864458, PubMed:20106972). Interacts with RAB35; the interaction is indirect through MICALL1 and recruits EHD1 to membranes (By similarity). Interacts (via EH domain) with PACSIN2 (via NPF motifs); regulates localization to tubular recycling endosome membranes (PubMed:23596323). Interacts with PACSIN1 (By similarity). Interacts with RAB8A (PubMed:19864458). Interacts with FER1L5 (via second C2 domain) (By similarity). Interacts with MYOF (By similarity). Interacts with ZFYVE20 (PubMed:15020713). Interacts (via EH domain) with RAB11FIP2 (PubMed:16251358).
messages: Membrane
messages: Recycling endosome membrane
messages: The EH domain interacts with Asn-Pro-Phe (NPF) motifs of target proteins.
messages: cilium membrane

9606:DPEP3
gene id: 9606:DPEP3
uniprot id: A0A140VK16
uniprot id: Q9H4B8
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the metallo-dependent hydrolases superfamily. Peptidase M19 family.
messages: Homodimer; disulfide-linked (PubMed:32325220). Interacts with TEX101; co-localized on the cell surface of spermatocytes, spermatids, and testicular spermatozoa, co-localized only in cytoplasmic droplets of caput and corpus epididymal sperm (By similarity).
messages: Lacks dipeptidase activity and is unable to hydrolyze cystinyl-bis-glycine, leukotriene D4 and the beta-lactam antibiotic imipenem (PubMed:32325220). The absence of activity may be due to the inability of asparagine (instead of aspartate found in DPEP1/2) at position 359 to function as the acid/base catalyst and activate the nucleophilic water/hydroxide (PubMed:32325220). A tyrosine (instead of histidine) at position 269 reduces affinity for the beta zinc and may cause substrate steric hindrance (PubMed:32325220).
messages: Membrane

9606:TWF2
gene id: 9606:TWF2
uniprot id: Q6IBS0
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Actin-binding protein involved in motile and morphological processes. Inhibits actin polymerization, likely by sequestering G-actin. By capping the barbed ends of filaments, it also regulates motility. Seems to play an important role in clathrin-mediated endocytosis and distribution of endocytic organelles. May play a role in regulating the mature length of the middle and short rows of stereocilia (By similarity).
messages: Belongs to the actin-binding proteins ADF family. Twinfilin subfamily.
messages: In vitro, phosphorylated by PRKCZ, CK2 and SRC.
messages: Interacts with G-actin; ADP-actin form and capping protein (CP). May also be able to interact with TWF1 and phosphoinositides, PI(4,5)P2. When bound to PI(4,5)P2, it is down-regulated. Interacts with MYO7A (By similarity).
messages: Ubiquitously expressed (at protein level).
messages: cytoskeleton
messages: perinuclear region
messages: stereocilium

9606:HNRNPL
gene id: 9606:HNRNPL
uniprot id: P14866
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: Cytoplasm
messages: Excess hnRNP L activates NMD of its own mRNA by promoting the inclusion of a 'poison exon' containing a premature stop codon and leading to nonsense-mediated decay. It also cross-regulates inclusion of an analogous 'poison exon' in the hnRNP L-like pre-mRNA (PubMed:19124611).
messages: Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs (PubMed:17289661). Interacts with HNRNPLL (PubMed:18669861). Interacts with APEX1; the interaction is DNA-dependent (PubMed:11809897). Component of a complex with SETD2 (PubMed:19332550, PubMed:36537238). Interacts with ELAVL1 (PubMed:18161049). Part of a transcription inhibitory ribonucleoprotein complex composed at least of the circular RNA circZNF827, ZNF827 and HNRNPK (PubMed:33174841). Interacts with CHD8 in an RNA-dependent manner.
messages: Phosphorylation at Ser-544 by CaMK4 enhances interaction with a CaMK4-responsive RNA element (CaRRE1), and prevents inclusion of the stress axis-regulated exon (STREX) of the KCNMA1 potassium channel transcripts upon membrane depolarization.
messages: RRM domain 2 has moderate RNA-binding affinity. RRM domains 3 and 4 may facilitate RNA looping when binding to two appropriately separated binding sites within the same target pre-mRNA (PubMed:23782695).
messages: Several isoelectric forms of the L protein are probably the results of post-translational modifications.
messages: Splicing factor binding to exonic or intronic sites and acting as either an activator or repressor of exon inclusion. Exhibits a binding preference for CA-rich elements (PubMed:11809897, PubMed:22570490, PubMed:24164894, PubMed:25623890, PubMed:26051023). Component of the heterogeneous nuclear ribonucleoprotein (hnRNP) complexes and associated with most nascent transcripts (PubMed:2687284). Associates, together with APEX1, to the negative calcium responsive element (nCaRE) B2 of the APEX2 promoter (PubMed:11809897). As part of a ribonucleoprotein complex composed at least of ZNF827, HNRNPK and the circular RNA circZNF827 that nucleates the complex on chromatin, may negatively regulate the transcription of genes involved in neuronal differentiation (PubMed:33174841). Regulates alternative splicing of a core group of genes involved in neuronal differentiation, likely by mediating H3K36me3-coupled transcription elongation and co-transcriptional RNA processing via interaction with CHD8.
messages: nucleoplasm

9606:TSPAN8
gene id: 9606:TSPAN8
uniprot id: P19075
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the tetraspanin (TM4SF) family.
messages: Gastric, colon, rectal, and pancreatic carcinomas.
messages: Membrane

9606:GRPR
gene id: 9606:GRPR
uniprot id: P30550
uniprot id: X5D7H2
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Highly expressed in pancreas (PubMed:11245983). Also expressed in stomach, adrenal cortex and brain (PubMed:11245983). In brain, expressed in cells throughout the cortex (PubMed:34610277).
messages: Membrane
messages: Receptor for gastrin-releasing peptide (GRP) (PubMed:1655761). Signals via association with G proteins that activate a phosphatidylinositol-calcium second messenger system, resulting in Akt phosphorylation. Contributes to the regulation of food intake. Contributes to the perception of prurient stimuli and transmission of itch signals in the spinal cord that promote scratching behavior, but does not play a role in the perception of pain. Contributes primarily to nonhistaminergic itch sensation. In one study, shown to act in the amygdala as part of an inhibitory network which inhibits memory specifically related to learned fear (By similarity). In another study, shown to contribute to disinhibition of glutamatergic cells in the auditory cortex via signaling on vasoactive intestinal peptide-expressing cells which leads to enhanced auditory fear memories (By similarity). Contributes to the induction of sighing through signaling in the pre-Botzinger complex, a cluster of several thousand neurons in the ventrolateral medulla responsible for inspiration during respiratory activity (By similarity).

9606:TROAP
gene id: 9606:TROAP
uniprot id: Q12815
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Could be involved with bystin and trophinin in a cell adhesion molecule complex that mediates an initial attachment of the blastocyst to uterine epithelial cells at the time of the embryo implantation.
messages: Cytoplasm
messages: Directly binds bystin, and indirectly trophinin.
messages: Strong expression at implantation sites. Was exclusively localized to the apical side of the syncytiotrophoblast. Also found in macrophages.

9606:PAQR8
gene id: 9606:PAQR8
uniprot id: B3KXW6
uniprot id: Q8TEZ7
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the ADIPOR family.
messages: Cell membrane
messages: Highly expressed in the hypothalamus (PubMed:23161870). Also expressed in spinal cord, kidney and testis.
messages: Membrane
messages: Non-classical progesterone receptors involved in extranuclear signaling are classified in 2 groups: the class II progestin and adipoQ receptor (PAQR) family (also called mPRs) (PAQR5, PAQR6, PAQR7, PAQR8 and PAQR9) and the b5-like heme/steroid-binding protein family (also called MAPRs) (PGRMC1, PGRMC2, NENF and CYB5D2).
messages: Plasma membrane progesterone (P4) receptor coupled to G proteins (PubMed:23763432). Seems to act through a G(i) mediated pathway (PubMed:23763432). May be involved in oocyte maturation (By similarity). Also binds dehydroepiandrosterone (DHEA), pregnanolone, pregnenolone and allopregnanolone (PubMed:23161870).

9606:CKS1B
gene id: 9606:CKS1B
uniprot id: P61024
uniprot id: Q5T178
names: Function
names: Similarity
names: Subunit
messages: Belongs to the CKS family.
messages: Binds to the catalytic subunit of the cyclin dependent kinases and is essential for their biological function.
messages: Forms a homohexamer that can probably bind six kinase subunits.

9606:KLK13
gene id: 9606:KLK13
uniprot id: Q9UKR3
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the peptidase S1 family. Kallikrein subfamily.
messages: Expressed in prostate, breast, testis and salivary gland.
messages: Secreted

9606:ZNF219
gene id: 9606:ZNF219
uniprot id: Q9P2Y4
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: C2H2-type zinc-finger domains 5 and 6 are important for the interaction with SOX9.
messages: Interacts with SOX9 (via C-terminus).
messages: Nucleus
messages: Transcriptional regulator (PubMed:14621294, PubMed:19549071). Recognizes and binds 2 copies of the core DNA sequence motif 5'-GGGGG-3' (PubMed:14621294). Binds to the HMGN1 promoter and may repress HMGN1 expression (PubMed:14621294). Regulates SNCA expression in primary cortical neurons (PubMed:19549071). Binds to the COL2A1 promoter and activates COL2A1 expression, as part of a complex with SOX9 (By similarity). Plays a role in chondrocyte differentiation (By similarity).
messages: Ubiquitous.

9606:ADAMTS16
gene id: 9606:ADAMTS16
uniprot id: Q2XQZ0
uniprot id: Q8TE57
names: Caution
names: Cofactor
names: Domain
names: PTM
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Binds 1 zinc ion per subunit.
messages: Expressed in fetal lung and kidney and in adult prostate and ovary.
messages: Glycosylated. Can be O-fucosylated by POFUT2 on a serine or a threonine residue found within the consensus sequence C1-X(2)-(S/T)-C2-G of the TSP type-1 repeat domains where C1 and C2 are the first and second cysteine residue of the repeat, respectively. Fucosylated repeats can then be further glycosylated by the addition of a beta-1,3-glucose residue by the glucosyltransferase, B3GALTL. Fucosylation mediates the efficient secretion of ADAMTS family members. Can also be C-glycosylated with one or two mannose molecules on tryptophan residues within the consensus sequence W-X-X-W of the TPRs, and N-glycosylated. These other glycosylations can also facilitate secretion (By similarity).
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.
messages: The precursor is cleaved by a furin endopeptidase.
messages: The spacer domain and the TSP type-1 domains are important for a tight interaction with the extracellular matrix.
messages: extracellular matrix

9606:DDX1
gene id: 9606:DDX1
uniprot id: A3RJH1
uniprot id: Q92499
names: Caution
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts with Rev of HIV-1.
messages: (Microbial infection) Interacts with Severe acute respiratory syndrome coronavirus (SARS-CoV) (via N-terminus) (PubMed:20573827). Interacts (via C-terminus) with the replicase polyprotein 1ab Nsp14 of the Avian infectious bronchitis virus (IBV).
messages: (Microbial infection) Interacts with Venezuelan equine encephalitis virus non-structural protein 3.
messages: (Microbial infection) Required for Coronavirus IBV replication.
messages: (Microbial infection) Required for HIV-1 Rev function as well as for HIV-1 and coronavirus IBV replication. Binds to the RRE sequence of HIV-1 mRNAs.
messages: According to some authors the unwinding activity is ADP-dependent and not ATP-dependent.
messages: Acts as an ATP-dependent RNA helicase, able to unwind both RNA-RNA and RNA-DNA duplexes. Possesses 5' single-stranded RNA overhang nuclease activity. Possesses ATPase activity on various RNA, but not DNA polynucleotides. May play a role in RNA clearance at DNA double-strand breaks (DSBs), thereby facilitating the template-guided repair of transcriptionally active regions of the genome. Together with RELA, acts as a coactivator to enhance NF-kappa-B-mediated transcriptional activation. Acts as a positive transcriptional regulator of cyclin CCND2 expression. Binds to the cyclin CCND2 promoter region. Associates with chromatin at the NF-kappa-B promoter region via association with RELA. Binds to poly(A) RNA. May be involved in 3'-end cleavage and polyadenylation of pre-mRNAs. Component of the tRNA-splicing ligase complex required to facilitate the enzymatic turnover of catalytic subunit RTCB: together with archease (ZBTB8OS), acts by facilitating the guanylylation of RTCB, a key intermediate step in tRNA ligation (PubMed:24870230). Component of a multi-helicase-TICAM1 complex that acts as a cytoplasmic sensor of viral double-stranded RNA (dsRNA) and plays a role in the activation of a cascade of antiviral responses including the induction of pro-inflammatory cytokines via the adapter molecule TICAM1. Specifically binds (via helicase ATP-binding domain) on both short and long poly(I:C) dsRNA (By similarity).
messages: Belongs to the DEAD box helicase family. DDX1 subfamily.
messages: Cytoplasm
messages: Cytoplasmic granule
messages: Found in a multi-helicase-TICAM1 complex at least composed of DHX36, DDX1, DDX21 and TICAM1; this complex exists in resting cells with or without poly(I:C) RNA ligand stimulation. Interacts with DHX36. Interacts (via B30.2/SPRY domain) with DDX21 (via N-terminus); this interaction serves as bridges to TICAM1 (By similarity). Interacts with FAM98A (via N- and C-terminus) (PubMed:28040436). Interacts with MBNL1 (PubMed:18335541). Interacts with CSTF2 (PubMed:11598190). Interacts with HNRNPK (PubMed:12183465). Interacts with ATM (PubMed:18710941). Interacts with RELA (via C-terminus) (PubMed:19058135). Component of the tRNA-splicing ligase complex (PubMed:21311021, PubMed:24870230). Interacts with PQBP1 (PubMed:21933836). Interacts with PHF5A (via C-terminus) (By similarity). Interacts with ERCC6 (PubMed:26030138).
messages: Highest levels of transcription in 2 retinoblastoma cell lines and in tissues of neuroectodermal origin including the retina, brain, and spinal cord.
messages: Mitochondrion
messages: Nucleus
messages: Phosphorylated by ATM kinase; phosphorylation is increased in response to ionizing radiation (IR).
messages: RNA helicase.
messages: The helicase domain is involved in the stimulation of RELA transcriptional activity.
messages: cytosol

9606:WWOX
gene id: 9606:WWOX
uniprot id: A0A411HBC7
uniprot id: Q9NZC7
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the short-chain dehydrogenases/reductases (SDR) family.
messages: Cytoplasm
messages: Defects in WWOX may be involved in several cancer types. The gene spans the second most common chromosomal fragile site (FRA16D) which is frequently altered in cancers (PubMed:10861292). Alteration of the expression and expression of some isoforms is associated with cancers. However, it is still unclear if alteration of WWOX is directly implicated in cancerogenesis or if it corresponds to a secondary effect (PubMed:10861292, PubMed:11572989, PubMed:15266310, PubMed:15073125, PubMed:15131042).
messages: Golgi apparatus
messages: Interacts with TP53, p73/TP73 and MAPK8. Interacts with MAPT/TAU, RUNX2 and HYAL2 (By similarity). Forms a ternary complex with TP53 and MDM2. Interacts with ERBB4, LITAF and WBP1. Interacts with DVL1, DVL2 and DVL3. May interact with FAM189B and SCOTIN. Interacts with TNK2. Interacts with TMEM207. Interacts (via WW domain) with VOPP1 (PubMed:30285739).
messages: Lysosome
messages: Mitochondrion
messages: Nucleus
messages: Phosphorylated upon genotoxic stress. Phosphorylation of Tyr-33 regulates interaction with TP53, TP73 and MAPK8. May also regulate proapoptotic activity. Phosphorylation by TNK2 is associated with polyubiquitination and degradation.
messages: Putative oxidoreductase. Acts as a tumor suppressor and plays a role in apoptosis. Required for normal bone development (By similarity). May function synergistically with p53/TP53 to control genotoxic stress-induced cell death. Plays a role in TGFB1 signaling and TGFB1-mediated cell death. May also play a role in tumor necrosis factor (TNF)-mediated cell death. Inhibits Wnt signaling, probably by sequestering DVL2 in the cytoplasm.
messages: The WW 1 domain mediates interaction with TP53, and probably TP73, TFAP2C, LITAF and WBP1.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The disease may be caused by variants affecting the gene represented in this entry.
messages: Ubiquitinated when phosphorylated by TNK2, leading to its degradation.
messages: Widely expressed. Strongly expressed in testis, prostate, and ovary. Overexpressed in cancer cell lines. Isoform 5 and isoform 6 may only be expressed in tumor cell lines.

9606:FBF1
gene id: 9606:FBF1
uniprot id: Q8TES7
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cell junction
messages: Keratin-binding protein required for epithelial cell polarization. Involved in apical junction complex (AJC) assembly via its interaction with PARD3. Required for ciliogenesis.
messages: May interact with FAS cytoplasmic domain (By similarity). Interacts with PARD3 (By similarity) (PubMed:18838552). Interacts with TRAPPC14 (PubMed:31467083).
messages: Present in various epithelial cells (at protein level).
messages: centriole
messages: spindle pole

9606:TOR1A
gene id: 9606:TOR1A
uniprot id: B3KPA1
uniprot id: O14656
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the ClpA/ClpB family. Torsin subfamily.
messages: Cytoplasmic vesicle membrane
messages: Endoplasmic reticulum lumen
messages: Homohexamer. Interacts with TOR1B; the interaction may be specific of neural tissues. Interacts (ATP-bound) with TOR1AIP1 and TOR1AIP2; the interactions induce ATPase activity. Interacts with KLHL14; preferentially when ATP-free. Interacts with KLC1 (via TPR repeats); the interaction associates TOR1A with the kinesin oligomeric complex. Interacts with COPS4; the interaction associates TOR1A with the CSN complex. Interacts with SNAPIN; the interaction is direct and associates SNAPIN with the CSN complex. Interacts with STON2. Interacts (ATP-bound) with SYNE3 (via KASH domain); the interaction is required for SYNE3 nuclear envelope localization. Interacts with VIM; the interaction associates TOR1A with the cytoskeleton. Interacts with PLEC. Interacts (ATP-bound) with SLC6A3; regulates SLC6A3 transport to the plasma membrane.
messages: N-glycosylated.
messages: Nucleus membrane
messages: Protein with chaperone functions important for the control of protein folding, processing, stability and localization as well as for the reduction of misfolded protein aggregates. Involved in the regulation of synaptic vesicle recycling, controls STON2 protein stability in collaboration with the COP9 signalosome complex (CSN). In the nucleus, may link the cytoskeleton with the nuclear envelope, this mechanism seems to be crucial for the control of nuclear polarity, cell movement and, specifically in neurons, nuclear envelope integrity. Participates in the cellular trafficking and may regulate the subcellular location of multipass membrane proteins such as the dopamine transporter SLC6A3, leading to the modulation of dopamine neurotransmission. In the endoplasmic reticulum, plays a role in the quality control of protein folding by increasing clearance of misfolded proteins such as SGCE variants or holding them in an intermediate state for proper refolding. May have a redundant function with TOR1B in non-neural tissues.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Widely expressed. Highest levels in kidney and liver. In the brain, high levels found in the dopaminergic neurons of the substantia nigra pars compacta, as well as in the neocortex, hippocampus and cerebellum. Also highly expressed in the spinal cord.
messages: cytoskeleton
messages: growth cone
messages: secretory vesicle
messages: synaptic vesicle

9606:MTRF1L
gene id: 9606:MTRF1L
uniprot id: B4DMX1
uniprot id: Q9UGC7
names: Caution
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the prokaryotic/mitochondrial release factor family.
messages: Expressed in skeletal muscle (at protein level).
messages: Methylation of glutamine in the GGQ triplet by HEMK1 is conserved from bacteria to mammals.
messages: Mitochondrial peptide chain release factor that directs the termination of translation in response to the peptide chain termination codons UAA and UAG.
messages: Mitochondrion
messages: The GGQ domain interacts with the peptidyltransferase center (PTC) of the large ribosomal subunit to trigger nascent chain hydrolysis.
messages: Was initially thought to promote the termination of non-canonical termination stop codons AGG and AGA in addition to canonical termination codons UAA and UAG (PubMed:20075246). However, it was later shown that termination of non-canonical termination stop codons AGG and AGA is mediated by MTRF1 (PubMed:37141370).

9606:CAVIN3
gene id: 9606:CAVIN3
uniprot id: Q969G5
names: Domain
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the CAVIN family.
messages: Component of the CAVIN complex composed of CAVIN1, CAVIN2, CAVIN3 and CAVIN4. Interacts with PRKCD and with phosphatidylserine. Phosphatidylserine may form a bridge between PKC and PKC-binding partners and stabilize the binding. Interacts with PER2. Interacts with CAVIN1 (By similarity). Interacts (via leucine-zipper domain) with CAV1 in a cholesterol-sensitive manner (PubMed:19262564). Interacts with EPS15L1 (PubMed:19262564).
messages: Cytoplasm
messages: Down-regulated in breast and lung cancer cell lines.
messages: In vitro, phosphorylated by PRKCD.
messages: Regulates the traffic and/or budding of caveolae (PubMed:19262564). Plays a role in caveola formation in a tissue-specific manner. Required for the formation of caveolae in smooth muscle but not in the lung and heart endothelial cells. Regulates the equilibrium between cell surface-associated and cell surface-dissociated caveolae by promoting the rapid release of caveolae from the cell surface. Plays a role in the regulation of the circadian clock. Modulates the period length and phase of circadian gene expression and also regulates expression and interaction of the core clock components PER1/2 and CRY1/2 (By similarity).
messages: Skeletal muscle, liver, stomach, lung, kidney and heart (at protein level). Strongly expressed in mammary and epithelial cells.
messages: The leucine-zipper domain is essential for its localization in the caveolae and for its interaction with CAV1 and EPS15L1.
messages: caveola
messages: cytosol

9606:FAM81B
gene id: 9606:FAM81B
uniprot id: Q96LP2
names: Caution
names: Similarity
messages: Belongs to the FAM81 family.
messages: It is uncertain whether Met-1 or Met-39 is the initiator. Met-1 does not seem to exist in orthologs.

9606:EEF2K
gene id: 9606:EEF2K
uniprot id: O00418
names: Activity Regulation
names: Function
names: PTM
names: Similarity
names: Subunit
messages: Autophosphorylated at multiple residues, Thr-348 being the major site. Phosphorylated by AMP-activated protein kinase AMPK at Ser-398 leading to EEF2K activation and protein synthesis inhibition. Phosphorylated by TRPM7 at Ser-78 resulting in improved protein stability, higher EE2F phosphorylated and subsequently reduced rate of protein synthesis. Phosphorylation by other kinases such as CDK1 and MAPK13 at Ser-359 or RPS6KA1 and RPS6KB1 at Ser-366 instead decrease EEF2K activity and promote protein synthesis.
messages: Belongs to the protein kinase superfamily. Alpha-type protein kinase family.
messages: Monomer or homodimer (Probable). Interacts with Calmodulin/CALM1; this interaction is strictly required for phosphorylation activity (PubMed:11015200).
messages: Threonine kinase that regulates protein synthesis by controlling the rate of peptide chain elongation. Upon activation by a variety of upstream kinases including AMPK or TRPM7, phosphorylates the elongation factor EEF2 at a single site, renders it unable to bind ribosomes and thus inactive. In turn, the rate of protein synthesis is reduced.
messages: Undergoes calcium/calmodulin-dependent intramolecular autophosphorylation, and this results in it becoming partially calcium/calmodulin-independent.

9606:CCDC180
gene id: 9606:CCDC180
uniprot id: Q9P1Z9
names: Sequence Caution
messages: Intron retention.
messages: Readthrough transcript which is the product of an upstream read-through pseudogene (SUGT1P4-STRA6LP) with CCDC180.

9606:SENP2
gene id: 9606:SENP2
uniprot id: Q9HC62
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the peptidase C48 family.
messages: Binds to SUMO2 and SUMO3 (PubMed:15296745). Interacts with the C-terminal domain of NUP153 via its N-terminus (PubMed:11896061, PubMed:12192048). Interacts with MTA1 (PubMed:21965678).
messages: Cytoplasm
messages: Nucleus membrane
messages: Polyubiquitinated; which leads to proteasomal degradation.
messages: Protease that catalyzes two essential functions in the SUMO pathway (PubMed:11896061, PubMed:12192048, PubMed:20194620, PubMed:21965678, PubMed:15296745). The first is the hydrolysis of an alpha-linked peptide bond at the C-terminal end of the small ubiquitin-like modifier (SUMO) propeptides, SUMO1, SUMO2 and SUMO3 leading to the mature form of the proteins (PubMed:15296745). The second is the deconjugation of SUMO1, SUMO2 and SUMO3 from targeted proteins, by cleaving an epsilon-linked peptide bond between the C-terminal glycine of the mature SUMO and the lysine epsilon-amino group of the target protein (PubMed:20194620, PubMed:21965678, PubMed:15296745). May down-regulate CTNNB1 levels and thereby modulate the Wnt pathway (By similarity). Deconjugates SUMO2 from MTA1 (PubMed:21965678). Plays a dynamic role in adipogenesis by desumoylating and promoting the stabilization of CEBPB (PubMed:20194620). Acts as a regulator of the cGAS-STING pathway by catalyzing desumoylation of CGAS and STING1 during the late phase of viral infection (By similarity).
messages: The N-terminus is necessary and sufficient for nuclear envelope targeting.
messages: nuclear pore complex

9606:RNMT
gene id: 9606:RNMT
uniprot id: A8K946
uniprot id: O43148
names: Activity Regulation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the class I-like SAM-binding methyltransferase superfamily. mRNA cap 0 methyltransferase family.
messages: Catalytic subunit of the mRNA-capping methyltransferase RNMT:RAMAC complex that methylates the N7 position of the added guanosine to the 5'-cap structure of mRNAs (PubMed:9790902, PubMed:9705270, PubMed:10347220, PubMed:11114884, PubMed:22099306, PubMed:27422871). Binds RNA containing 5'-terminal GpppC (PubMed:11114884).
messages: In the N-terminal section; belongs to the dsDNA virus mRNA guanylyltransferase family.
messages: Interacts with importin alpha, leading to stimulate both RNA-binding and methyltransferase activity (PubMed:11114884). Interaction with importin alpha and beta is required for its nuclear localization, importin beta dissociating in response to RanGTP, allowing RNMT-importin alpha to bind RNA substrates (PubMed:11114884). Interacts with elongating form of polymerase II and RNGTT (PubMed:9705270). Interacts with RAMAC, this interaction significantly enhances RNA-binding and cap methyltransferase activity (PubMed:22099306, Ref.14).
messages: Methyltransferase activity is activated by RAMAC (PubMed:27422871).
messages: Nucleus
messages: Widely expressed.

9606:LRIG2
gene id: 9606:LRIG2
uniprot id: O94898
names: Disease Annotation
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Cell membrane
messages: Cytoplasm
messages: Detected in all tissues analyzed.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:ANGEL1
gene id: 9606:ANGEL1
uniprot id: Q9UNK9
names: Similarity
messages: Belongs to the CCR4/nocturin family.

9606:PECR
gene id: 9606:PECR
uniprot id: Q9BY49
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the short-chain dehydrogenases/reductases (SDR) family.
messages: Interacts with PEX5, probably required to target it into peroxisomes.
messages: Not induced by IR.
messages: Participates in chain elongation of fatty acids. Catalyzes the reduction of trans-2-enoyl-CoAs of varying chain lengths from 6:1 to 16:1, having maximum activity with 10:1 CoA. Has no 2,4-dienoyl-CoA reductase activity.
messages: Peroxisome

9606:HOOK1
gene id: 9606:HOOK1
uniprot id: Q9UJC3
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the hook family.
messages: Component of the FTS/Hook/FHIP complex (FHF complex) (PubMed:18799622, PubMed:32073997). The FHF complex may function to promote vesicle trafficking and/or fusion via the homotypic vesicular protein sorting complex (the HOPS complex) (PubMed:18799622). FHF complex promotes the distribution of AP-4 complex to the perinuclear area of the cell (PubMed:32073997). Required for spermatid differentiation. Probably involved in the positioning of the microtubules of the manchette and the flagellum in relation to the membrane skeleton (By similarity).
messages: Cytoplasm
messages: Self-associates (PubMed:18799622, PubMed:32073997). Component of the FTS/Hook/FHIP complex (FHF complex), composed of AKTIP/FTS, FHIP1B, and one or more members of the Hook family of proteins HOOK1, HOOK2, and HOOK3 (PubMed:18799622, PubMed:32073997). Interacts directly with AKTIP/FTS, HOOK2 and HOOK3 (PubMed:18799622, PubMed:32073997). Associates with several subunits of the homotypic vesicular sorting complex (the HOPS complex) including VPS16, VPS18, VPS39 and VPS41; these interactions may be indirect (PubMed:18799622). Interacts with CCDC181 (By similarity). Interacts (via coiled-coil region) with RIMBP3 (via C-terminus) (By similarity). Interacts with LRGUK (via guanylate kinase-like domain) (By similarity). Interacts with microtubules (PubMed:11238449). May interact with CLN3 (PubMed:15471887). Interacts with AP4M1; the interaction is direct, mediates the interaction between FTS-Hook-FHIP (FHF) complex and AP-4 and the perinuclear distribution of AP-4 (PubMed:32073997).
messages: cytoskeleton

9606:ARNT2
gene id: 9606:ARNT2
uniprot id: Q9HBZ2
names: Disease Annotation
names: Function
names: Sequence Caution
names: Subcellular Location Annotation
names: Subunit
messages: Efficient DNA binding requires dimerization with another bHLH protein (By similarity). Heterodimer with NPAS4 (PubMed:24465693). Heterodimer with SIM1 (By similarity). Heterodimer with the aryl hydrocarbon receptor (AHR) or the SIM1 protein (By similarity). Interacts with TACC3 (By similarity).
messages: Nucleus
messages: Probable cloning artifact.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Transcription factor that plays a role in the development of the hypothalamo-pituitary axis, postnatal brain growth, and visual and renal function (PubMed:24022475). Specifically recognizes the xenobiotic response element (XRE).

9606:PDSS2
gene id: 9606:PDSS2
uniprot id: B4DKU5
uniprot id: Q86YH6
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the FPP/GGPP synthase family.
messages: Heterotetramer composed of 2 PDSS1/DPS1 and 2 PDSS2/DLP1 subunits.
messages: Heterotetrameric enzyme that catalyzes the condensation of farnesyl diphosphate (FPP), which acts as a primer, and isopentenyl diphosphate (IPP) to produce prenyl diphosphates of varying chain lengths and participates in the determination of the side chain of ubiquinone (PubMed:16262699). Supplies nona and decaprenyl diphosphate, the precursors for the side chain of the isoprenoid quinones ubiquinone-9 (Q9) and ubiquinone-10 (Q10) respectively (PubMed:16262699). The enzyme adds isopentenyl diphosphate molecules sequentially to farnesyl diphosphate with trans stereochemistry (PubMed:16262699). May play a role during cerebellar development (By similarity). May regulate mitochondrial respiratory chain function (By similarity).
messages: Mitochondrion
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:HNRNPA0
gene id: 9606:HNRNPA0
uniprot id: Q13151
names: Function
names: PTM
names: Subcellular Location Annotation
messages: Arg-291 is dimethylated, probably to asymmetric dimethylarginine.
messages: Nucleus
messages: Phosphorylated at Ser-84 by MAPKAPK2 in response to LPS treatment, promoting stabilization of GADD45A mRNA.
messages: mRNA-binding component of ribonucleosomes. Specifically binds AU-rich element (ARE)-containing mRNAs. Involved in post-transcriptional regulation of cytokines mRNAs.

9606:GPR108
gene id: 9606:GPR108
uniprot id: Q9NPR9
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: (Microbial infection) N- and C-terminal domains are required for AAV transduction.
messages: (Microbial infection) Plays an essential function in adeno-associated virus (AAV) transduction across multiple serotypes except AAV5. May play a critical role in mediating the endosomal virus escape or in the AAV virions trafficking from endosomes to the nucleus.
messages: Belongs to the LU7TM family.
messages: Golgi apparatus membrane
messages: May play a role in intracellular immune modulation by activating NF-kappaB response and attenuating Toll-like-receptor response.
messages: cis-Golgi network membrane
messages: trans-Golgi network membrane

9606:ADH1B
gene id: 9606:ADH1B
uniprot id: D6RHZ6
uniprot id: P00325
uniprot id: V9HW50
names: Cofactor
names: Function
names: Miscellaneous
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the zinc-containing alcohol dehydrogenase family.
messages: Binds 2 Zn(2+) ions per subunit.
messages: Catalyzes the NAD-dependent oxidation of all-trans-retinol and its derivatives such as all-trans-4-hydroxyretinol and may participate in retinoid metabolism (PubMed:15369820, PubMed:16787387). In vitro can also catalyzes the NADH-dependent reduction of all-trans-retinal and its derivatives such as all-trans-4-oxoretinal (PubMed:15369820, PubMed:16787387). Catalyzes in the oxidative direction with higher efficiency (PubMed:16787387). Has the same affinity for all-trans-4-hydroxyretinol and all-trans-4-oxoretinal (PubMed:15369820).
messages: Cytoplasm
messages: Dimer of identical or non-identical chains of three types; alpha, beta and gamma.
messages: There are 7 different ADH's isozymes in human: three belongs to class-I: alpha, beta, and gamma, one to class-II: pi, one to class-III: chi, one to class-IV: ADH7 and one to class-V: ADH6.
messages: Three alleles are known: ADH1B*1 (ADH2*1) corresponding to variant beta-1, ADH1B*2 (ADH2*2) corresponding to variant beta-2, ADH1B*3 (ADH2*3) corresponding to variant beta-3. The sequence shown is that of allele ADH1B*2. The ADH1B*2 allele frequency in orientals is approximately 75%, whereas it is less than 5% in most Caucasian populations. The ADH1B*2 allele is associated with a lower risk of alcoholism. ADH1B variations have been associated with protection against alcohol dependence and alcohol-related aerodigestive tract cancer [MIM:103720].

9606:SFRP2
gene id: 9606:SFRP2
uniprot id: A0A140VJU3
uniprot id: B3KSM5
uniprot id: Q96HF1
names: Caution
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the secreted frizzled-related protein (sFRP) family.
messages: Expressed in adipose tissue, heart, brain, skeletal muscle, pancreas, thymus, prostate, testis, ovary, small intestine and colon. Highest levels in adipose tissue, small intestine and colon.
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: Secreted
messages: Soluble frizzled-related proteins (sFRPS) function as modulators of Wnt signaling through direct interaction with Wnts. They have a role in regulating cell growth and differentiation in specific cell types. SFRP2 may be important for eye retinal development and for myogenesis.
messages: The FZ domain is involved in binding with Wnt ligands.

9606:TMEM225B
gene id: 9606:TMEM225B
uniprot id: P0DP42
names: Subcellular Location Annotation
messages: Membrane

9606:OSGEPL1
gene id: 9606:OSGEPL1
uniprot id: Q9H4B0
names: Cofactor
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the KAE1 / TsaD family.
messages: Binds 1 divalent metal cation per subunit.
messages: Mitochondrion
messages: Monomer.
messages: Required for the formation of a threonylcarbamoyl group on adenosine at position 37 (t(6)A37) in mitochondrial tRNAs that read codons beginning with adenine. Probably involved in the transfer of the threonylcarbamoyl moiety of threonylcarbamoyl-AMP (TC-AMP) to the N6 group of A37. Involved in mitochondrial genome maintenance.
messages: Widely expressed, with maximum expression in pituitary gland, prostate, rectum and uterus.

9606:PPIP5K1
gene id: 9606:PPIP5K1
uniprot id: Q6PFW1
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the histidine acid phosphatase family. VIP1 subfamily.
messages: Bifunctional inositol kinase that acts in concert with the IP6K kinases IP6K1, IP6K2 and IP6K3 to synthesize the diphosphate group-containing inositol pyrophosphates diphosphoinositol pentakisphosphate, PP-InsP5, and bis-diphosphoinositol tetrakisphosphate, (PP)2-InsP4. PP-InsP5 and (PP)2-InsP4, also respectively called InsP7 and InsP8, regulate a variety of cellular processes, including apoptosis, vesicle trafficking, cytoskeletal dynamics, exocytosis, insulin signaling and neutrophil activation. Phosphorylates inositol hexakisphosphate (InsP6) at position 1 to produce PP-InsP5 which is in turn phosphorylated by IP6Ks to produce (PP)2-InsP4. Alternatively, phosphorylates PP-InsP5 at position 1, produced by IP6Ks from InsP6, to produce (PP)2-InsP4. Activated when cells are exposed to hyperosmotic stress.
messages: Cell membrane
messages: The C-terminal acid phosphatase-like domain binds PtdIns(3,4,5)P3 and InsP6. Despite its similarity with the phosphatase domain of histidine acid phosphatases, it has no phosphatase activity.
messages: Widely expressed, with a higher expression in skeletal muscle, heart and brain.
messages: cytosol

9606:CDCA8
gene id: 9606:CDCA8
uniprot id: Q53HL2
names: Developmental Stage
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the borealin family.
messages: Cell-cycle regulated. Increases during G2/M phase and then reduces after exit from M phase.
messages: Cells lacking CDCA8 display a slight decrease in histone H3 'Ser-10' phosphorylation, suggesting that the CPC complex mediates phosphorylation of 'Ser-10' of histone H3.
messages: Component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly. Major effector of the TTK kinase in the control of attachment-error-correction and chromosome alignment.
messages: Cytoplasm
messages: May form homooligomers and homodimers. Component of the chromosomal passenger complex (CPC) composed of at least BIRC5/survivin, CDCA8/borealin, INCENP, AURKB or AURKC; in the complex forms a triple-helix bundle-based subcomplex with INCENP and BIRC5 (PubMed:17956729). Interacts with SENP3, UBE2I and RANBP2. Interacts (phosphorylated) with SGO1 and SGO2; the association is dependent on CDK1.
messages: Phosphorylated by TTK, essentially at Thr-88, Thr94, Thr-169 and Thr-230. Phosphorylation (probably by CDK1) promotes targeting of the CPC to centromeric DNA.
messages: Sumoylated by UBE2I and RANBP2. Desumoylated by SENP3 through the removal of SUMO2 and SUMO3.
messages: The C-terminal region (aa 207-280) represents the dimerization motif.
messages: centromere
messages: nucleolus
messages: spindle

9606:APCS
gene id: 9606:APCS
uniprot id: P02743
uniprot id: V9HWP0
names: Cofactor
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the pentraxin family.
messages: Binds 2 calcium ions per subunit.
messages: Can interact with DNA and histones and may scavenge nuclear material released from damaged circulating cells. May also function as a calcium-dependent lectin.
messages: Found in serum and urine.
messages: Homopentamer. Pentaxin (or pentraxin) have a discoid arrangement of 5 non-covalently bound subunits.
messages: Homopentamer. Pentraxin (or pentaxin) have a discoid arrangement of 5 non-covalently bound subunits.
messages: N-glycosylated with a complex biantennary oligosaccharide chain with a sialic acid at the end (disialo-SAP). Monosialo-SAP as well as asioalo-SAP are also detected (PubMed:15174148).
messages: SAP is a precursor of amyloid component P which is found in basement membrane and associated with amyloid deposits.
messages: Secreted

9606:TMEM263
gene id: 9606:TMEM263
uniprot id: Q8WUH6
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the TMEM263 family.
messages: Defect in TMEM263 has been found in a fetus with severe lethal skeletal dysplasia. The homozygous frameshift mutation found in this fetus results in the creation of a premature stop codon at Lys-68.
messages: May play a role in bone development.
messages: Membrane

9606:NOTUM
gene id: 9606:NOTUM
uniprot id: Q6P988
names: Caution
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the pectinacetylesterase family. Notum subfamily.
messages: Carboxylesterase that acts as a key negative regulator of the Wnt signaling pathway by specifically mediating depalmitoleoylation of WNT proteins. Serine palmitoleoylation of WNT proteins is required for efficient binding to frizzled receptors (PubMed:25731175).
messages: Rarely expressed in adult normal tissues.
messages: Secreted
messages: The molecular function of NOTUM has remained unclear for many years. It was initially thought to hydrolyze glycosaminoglycan (GAG) chains of glypicans, thereby affecting glypicans ability to interact with Wnt ligands. It was later reported to trigger glypican shedding, by mediating cleavage of their GPI-anchor. However, while NOTUM specifically inhibit the Wnt signaling pathway, more pleiotropic effects would be expected from an enzyme affecting glypicans. It was finally shown that it requires glypicans to suppress Wnt signaling, but does not cleave their GPI-anchor. It acts by mediating depalmitoleoylation of WNT proteins, impairing WNT binding to frizzled receptors (PubMed:25731175).
messages: Up-regulated in hepatocellular carcinoma (HCC) with high intracellular beta-catenin.

9606:FAM120B
gene id: 9606:FAM120B
uniprot id: A0A0D9SEJ5
uniprot id: B4DG54
uniprot id: B4DSS4
uniprot id: F5GY05
uniprot id: Q96EK7
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the constitutive coactivator of PPAR-gamma family.
messages: Functions as a transactivator of PPARG and ESR1. Functions in adipogenesis through PPARG activation (By similarity).
messages: Interacts with ESR1 and RXRA. Interacts with PPARG; in a ligand-independent manner (By similarity).
messages: Nucleus
messages: Widely expressed.

9606:TFEC
gene id: 9606:TFEC
uniprot id: O14948
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the MiT/TFE family.
messages: Expressed moderately in spleen, kidney, bone marrow, small intestine and leukocytes. Expressed weakly in testis, trachea and colon.
messages: Homodimer. Forms heterodimers with TFE3. Forms heterodimers with MITF (By similarity). Interacts with MITF (By similarity).
messages: Nucleus
messages: Transcriptional regulator that acts as a repressor or an activator. Acts as a transcriptional repressor on minimal promoter containing element F (that includes an E-box sequence). Binds to element F in an E-box sequence-specific manner. Acts as a transcriptional transactivator on the proximal promoter region of the tartrate-resistant acid phosphatase (TRAP) E-box containing promoter (By similarity). Collaborates with MITF in target gene activation (By similarity). Acts as a transcriptional repressor on minimal promoter containing mu E3 enhancer sequence (By similarity). Binds to mu E3 DNA sequence of the immunoglobulin heavy-chain gene enhancer (By similarity). Binds DNA in a homo- or heterodimeric form.

9606:SEC16B
gene id: 9606:SEC16B
uniprot id: Q96JE7
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the SEC16 family.
messages: Endoplasmic reticulum membrane
messages: Golgi apparatus membrane
messages: Plays a role in the organization of the endoplasmic reticulum exit sites (ERES), also known as transitional endoplasmic reticulum (tER). Required for secretory cargo traffic from the endoplasmic reticulum to the Golgi apparatus (PubMed:17192411, PubMed:21768384, PubMed:22355596). Involved in peroxisome biogenesis. Regulates the transport of peroxisomal biogenesis factors PEX3 and PEX16 from the ER to peroxisomes (PubMed:21768384).
messages: SEC16A and SEC16B are each present in multiple copies in a heteromeric complex (PubMed:17192411, PubMed:22355596). Interacts with TFG (PubMed:21478858). Interacts with SEC13 (PubMed:22355596).
messages: Ubiquitous.

9606:BRMS1
gene id: 9606:BRMS1
uniprot id: G5E9I4
uniprot id: Q9HCU9
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the BRMS1 family.
messages: Contains an N-terminal anti-parallel coiled coil formed by two BRMS1 chains; this region can form homohexamers.
messages: Cytoplasm
messages: Expression levels are higher in term placentas than in early placentas. Low levels of expression observed in normal pregnancies and in molar pregnancies.
messages: Homohexamer (Potential). Interacts with SNX6, HDAC1 and RELA. Interacts with ARID4A. Identified in mSin3A corepressor complexes together with SIN3A, SIN3B, RBBP4, RBBP7, SAP30, SUDS3, ARID4A, HDAC1 and HDAC2. Interacts with SPOP; this recruits the protein to a ubiquitin ligase complex containing SPOP and CUL3.
messages: Nucleus
messages: Transcriptional repressor. Down-regulates transcription activation by NF-kappa-B by promoting the deacetylation of RELA at 'Lys-310'. Promotes HDAC1 binding to promoter regions. Down-regulates expression of anti-apoptotic genes that are controlled by NF-kappa-B. Promotes apoptosis in cells that have inadequate adherence to a substrate, a process called anoikis, and may thereby inhibit metastasis. May be a mediator of metastasis suppression in breast carcinoma.
messages: Ubiquitinated by a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex containing SPOP, leading to proteasomal degradation.

9606:UCP1
gene id: 9606:UCP1
uniprot id: P25874
uniprot id: Q4KMT7
names: Activity Regulation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the mitochondrial carrier (TC 2.A.29) family.
messages: Brown adipose tissue.
messages: Has no constitutive proton transporter activity and has to be activated by long-chain fatty acids/LCFAs (PubMed:28781081). Inhibited by purine nucleotides (PubMed:28781081). Both purine nucleotides and LCFAs bind the cytosolic side of the transporter and directly compete to activate or inhibit it (PubMed:28781081). Activated by noradrenaline and reactive oxygen species. Despite lacking canonical translational encoding for selenocysteine, a small pool of the protein has been observed to selectively incorporate selenocysteine at 'Cys-254'. Selenocysteine-modified protein is highly sensitive to redox modification and may constitute a pool of protein highly sensitive to activation by elevated levels of reactive oxygen species (ROS).
messages: May undergo sulfenylation upon cold exposure. May increase the sensitivity of UCP1 thermogenic function to the activation by noradrenaline probably through structural effects.
messages: May undergo ubiquitin-mediated proteasomal degradation.
messages: Membrane
messages: Mitochondrial protein responsible for thermogenic respiration, a specialized capacity of brown adipose tissue and beige fat that participates in non-shivering adaptive thermogenesis to temperature and diet variations and more generally to the regulation of energy balance (By similarity). Functions as a long-chain fatty acid/LCFA and proton symporter, simultaneously transporting one LCFA and one proton through the inner mitochondrial membrane (PubMed:24196960, PubMed:28781081). However, LCFAs remaining associated with the transporter via their hydrophobic tails, it results in an apparent transport of protons activated by LCFAs. Thereby, dissipates the mitochondrial proton gradient and converts the energy of substrate oxydation into heat instead of ATP. Regulates the production of reactive oxygen species/ROS by mitochondria (By similarity).
messages: Mitochondrial protein responsible for thermogenic respiration, a specialized capacity of brown adipose tissue and beige fat that participates in non-shivering adaptive thermogenesis to temperature and diet variations and more generally to the regulation of energy balance. Functions as a long-chain fatty acid/LCFA and proton symporter, simultaneously transporting one LCFA and one proton through the inner mitochondrial membrane. However, LCFAs remaining associated with the transporter via their hydrophobic tails, it results in an apparent transport of protons activated by LCFAs. Thereby, dissipates the mitochondrial proton gradient and converts the energy of substrate oxydation into heat instead of ATP. Regulates the production of reactive oxygen species/ROS by mitochondria.
messages: Mitochondrion inner membrane
messages: Most probably functions as a monomer. Binds one purine nucleotide per monomer (By similarity). However, has also been suggested to function as a homodimer or a homotetramer (PubMed:24196960). Tightly associates with cardiolipin in the mitochondrion inner membrane; may stabilize and regulate its activity (PubMed:24196960).

9606:RAB3IP
gene id: 9606:RAB3IP
uniprot id: Q96QF0
names: Activity Regulation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the SEC2 family.
messages: Cytoplasm
messages: Expressed in brain, kidney, heart, pancreas and placenta. Not detected in skeletal muscle or liver.
messages: Guanine nucleotide exchange factor (GEF) which may activate RAB8A and RAB8B (PubMed:12221131, PubMed:26824392). Promotes the exchange of GDP to GTP, converting inactive GDP-bound Rab proteins into their active GTP-bound form (PubMed:12221131, PubMed:26824392). Mediates the release of GDP from RAB8A and RAB8B but not from RAB3A or RAB5 (PubMed:20937701, PubMed:26824392). Modulates actin organization and promotes polarized transport of RAB8A-specific vesicles to the cell surface (PubMed:12221131). Together with RAB11A, RAB8A, the exocyst complex, PARD3, PRKCI, ANXA2, CDC42 and DNMBP promotes transcytosis of PODXL to the apical membrane initiation sites (AMIS), apical surface formation and lumenogenesis (PubMed:20890297). Part of the ciliary targeting complex containing Rab11, ASAP1, RAB3IP and RAB11FIP3 and ARF4 that promotes RAB3IP preciliary vesicle trafficking to mother centriole and ciliogenesis initiation (PubMed:31204173, PubMed:25673879).
messages: Homodimer (PubMed:26258637). Interacts with the N-terminal region of SSX2 (PubMed:12007189). Interacts with the GDP-bound forms of RAB8A and RAB8B (PubMed:26824392, PubMed:12221131). The interaction with RAB8A is prevented by phosphorylation of RAB8A at 'Thr-72' (PubMed:26824392). Interacts with the GDP-bound forms of RAB3A and RAB3D (PubMed:12221131). Interacts with DCDC1 (PubMed:22159412, PubMed:12007189, PubMed:12221131, PubMed:26824392). Interacts (via the N-terminal region) with TRAPPC14; this interaction mediates RAB3IP association with the TRAPP II complex (PubMed:31467083). Forms a heterotetramer with RAB11A where RAB3IP homodimer binds two RAB11A subunits (PubMed:26258637). Forms a complex with RAB11A and RAB11FIP3, probably a heterohexamer with two of each protein subunit, where Rabin8/RAB3IP and RAB11FIP3 simultaneously bind to RAB11A; the complex promotes preciliary trafficking (PubMed:26258637, PubMed:31204173). Forms a complex containing RAB11A, ASAP1, RAB3IP, RAP11FIP3 and ARF4; the complex promotes preciliary trafficking; the complex binds to RHO in photoreceptor cells and promotes RHO ciliary transport (PubMed:25673879).
messages: Nucleus
messages: Phosphorylated by AKT1; the phosphorylation alters its GEF activity.
messages: Phosphorylation by ATK1 alters its GEF activity (PubMed:31204173). Complex formation with RAB11A and RAB11FIP3 and ciliogenesis function are competitively inhibited by RAB11A-WDR44 interaction (PubMed:31204173).
messages: Vesicle
messages: centrosome
messages: cytoskeleton
messages: lamellipodium

9606:OMP
gene id: 9606:OMP
uniprot id: P47874
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the olfactory marker protein family.
messages: Cytoplasm
messages: Interacts with BEX1 and BEX2.
messages: May act as a modulator of the olfactory signal-transduction cascade.
messages: Uniquely associated with mature olfactory receptor neurons.

9606:SHOX2
gene id: 9606:SHOX2
uniprot id: A6NLG4
uniprot id: O60902
names: Developmental Stage
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the paired homeobox family. Bicoid subfamily.
messages: Expressed during cranofacial development as well as in heart.
messages: Expressed in heart, skeletal muscle, liver, lung, bone marrow fibroblast, pancreas and placenta.
messages: May be a growth regulator and have a role in specifying neural systems involved in processing somatosensory information, as well as in face and body structure formation.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Nucleus

9606:NDUFA8
gene id: 9606:NDUFA8
uniprot id: B7Z768
uniprot id: P51970
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis (PubMed:27626371, PubMed:32385911, PubMed:33153867). Complex I functions in the transfer of electrons from NADH to the respiratory chain (PubMed:27626371). The immediate electron acceptor for the enzyme is believed to be ubiquinone (PubMed:27626371).
messages: Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone.
messages: Belongs to the complex I NDUFA8 subunit family.
messages: Complex I is composed of 45 different subunits.
messages: Contains four C-X9-C motifs that are predicted to form a helix-coil-helix structure, permitting the formation of intramolecular disulfide bonds.
messages: May contain intrachain disulfide bonds, as evidenced by its electrophoretic mobility under reducing vs non-reducing conditions.
messages: Mitochondrion
messages: Mitochondrion inner membrane
messages: Mitochondrion intermembrane space
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:DDX39B
gene id: 9606:DDX39B
uniprot id: Q13838
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Interacts with human cytomegalovirus/HHV-5 protein UL69.
messages: (Microbial infection) The TREX complex is essential for the export of Kaposi's sarcoma-associated herpesvirus (KSHV) intronless mRNAs and infectious virus production.
messages: Belongs to the DEAD box helicase family. DECD subfamily.
messages: Cytoplasm
messages: Homodimer, and heterodimer with DDX39A (PubMed:11675789, PubMed:15833825, PubMed:14667819). Component of the transcription/export (TREX) complex at least composed of ALYREF/THOC4, DDX39B, SARNP/CIP29, CHTOP and the THO subcomplex; TREX seems to have dynamic structure involving ATP-dependent remodeling; in the complex bridges ALYREF/THOC4 and the THO complex, and, in a ATP-dependent manner, ALYREF/THOC4 and SARNP/CIP29 (PubMed:11675789, PubMed:15833825, PubMed:14667819, PubMed:15998806, PubMed:17984224, PubMed:20844015, PubMed:23299939). Component of the spliceosome. Interacts directly with U2AF2 (PubMed:9242493). Interacts with RBM8A, RNPS1 and SRRM1, FYTTD1/UIF, THOC1, MX1 and POLDIP3 (PubMed:12944400, PubMed:15870275, PubMed:19836239, PubMed:21859714, PubMed:22928037). Interacts with LUZP4 (PubMed:25662211).
messages: Involved in nuclear export of spliced and unspliced mRNA. Assembling component of the TREX complex which is thought to couple mRNA transcription, processing and nuclear export, and specifically associates with spliced mRNA and not with unspliced pre-mRNA. TREX is recruited to spliced mRNAs by a transcription-independent mechanism, binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5' end of the mRNA where it functions in mRNA export to the cytoplasm via the TAP/NFX1 pathway. May undergo several rounds of ATP hydrolysis during assembly of TREX to drive subsequent loading of components such as ALYREF/THOC and CHTOP onto mRNA. Also associates with pre-mRNA independent of ALYREF/THOC4 and the THO complex. Involved in the nuclear export of intronless mRNA; the ATP-bound form is proposed to recruit export adapter ALYREF/THOC4 to intronless mRNA; its ATPase activity is cooperatively stimulated by RNA and ALYREF/THOC4 and ATP hydrolysis is thought to trigger the dissociation from RNA to allow the association of ALYREF/THOC4 and the NXF1-NXT1 heterodimer. Involved in transcription elongation and genome stability.
messages: Nucleus
messages: Nucleus speckle
messages: Splice factor that is required for the first ATP-dependent step in spliceosome assembly and for the interaction of U2 snRNP with the branchpoint. Has both RNA-stimulated ATP binding/hydrolysis activity and ATP-dependent RNA unwinding activity. Even with the stimulation of RNA, the ATPase activity is weak. Can only hydrolyze ATP but not other NTPs. The RNA stimulation of ATPase activity does not have a strong preference for the sequence and length of the RNA. However, ssRNA stimulates the ATPase activity much more strongly than dsRNA. Can unwind 5' or 3' overhangs or blunt end RNA duplexes in vitro. The ATPase and helicase activities are not influenced by U2AF2; the effect of ALYREF/THOC4 is reported conflictingly with [PubMed:23299939] reporting a stimulatory effect.
messages: The helicase C-terminal domain mediates interaction with ALYREF/THOC4.

9606:TLL1
gene id: 9606:TLL1
uniprot id: B7ZLW3
uniprot id: O43897
names: Caution
names: Cofactor
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
messages: Binds 1 zinc ion per subunit.
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: Protease which processes procollagen C-propeptides, such as chordin, pro-biglycan and pro-lysyl oxidase. Required for the embryonic development. Predominant protease, which in the development, influences dorsal-ventral patterning and skeletogenesis.
messages: Secreted
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:ST3GAL2
gene id: 9606:ST3GAL2
uniprot id: B3KXG9
uniprot id: Q16842
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: A beta-galactoside alpha2-3 sialyltransferase primarily involved in terminal sialylation of ganglio and globo series glycolipids (PubMed:8920913, PubMed:9266697). Catalyzes the transfer of sialic acid (N-acetyl-neuraminic acid; Neu5Ac) from the nucleotide sugar donor CMP-Neu5Ac onto acceptor Galbeta-(1->3)-GalNAc-terminated glycoconjugates through an alpha2-3 linkage (PubMed:8920913, PubMed:9266697, PubMed:25916169). Sialylates GM1/GM1a, GA1/asialo-GM1 and GD1b gangliosides to form GD1a, GM1b and GT1b, respectively (PubMed:8920913, PubMed:9266697). Together with ST3GAL3, primarily responsible for biosynthesis of brain GD1a and GT1b that function as ligands for myelin-associated glycoprotein MAG on axons, regulating MAG expression and axonal myelin stability and regeneration (By similarity). Via GT1b regulates TLR2 signaling in spinal cord microglia in response to nerve injury (By similarity). Responsible for the sialylation of the pluripotent stem cell- and cancer stem cell-associated antigen SSEA3, forming SSEA4 (PubMed:12716912). Sialylates with low efficiency asialofetuin, presumably onto O-glycosidically linked Galbeta-(1->3)-GalNAc-O-Ser (PubMed:9266697, PubMed:25916169).
messages: Belongs to the glycosyltransferase 29 family.
messages: Golgi stack membrane
messages: Highly expressed in skeletal muscle and heart and to a much lesser extent in brain, placenta, liver and pancreas. Scarcely detectable in lung and kidney.
messages: Homodimer; disulfide-linked. Homodimer formation occurs in the endoplasmic reticulum.
messages: Membrane
messages: N-glycosylated; necessary for proper exit from endoplasmic reticulum and trafficking to the Golgi apparatus.
messages: Secreted
messages: The soluble form derives from the membrane form by proteolytic processing.

9606:ASPRV1
gene id: 9606:ASPRV1
uniprot id: Q53RT3
names: Caution
names: Disease Annotation
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Expressed primarily in the granular layer of the epidermis and inner root sheath of hair follicles. In psoriatic skin, expressed throughout the stratum corneum. In ulcerated skin, expressed in the stratum granulosum of intact epidermis but almost absent from ulcerated regions. Expressed in differentiated areas of squamous cell carcinomas but not in undifferentiated tumors.
messages: Homodimer.
messages: It is uncertain whether Met-1 or Met-85 is the initiator.
messages: Membrane
messages: Protease responsible for filaggrin processing, essential for the maintenance of a proper epidermis organization.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Undergoes autocleavage which is necessary for activation of the protein.

9606:S100A3
gene id: 9606:S100A3
uniprot id: P33764
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the S-100 family.
messages: Binds both calcium and zinc. May be involved in calcium-dependent cuticle cell differentiation, hair shaft and hair cuticular barrier formation.
messages: Cytoplasm
messages: Homodimer and homotetramer for the citrullinated form.
messages: More than half of the arginine residues undergo citrullination by PAD1 and PAD2. Arg-51 is specifically citrullinated by PAD3 and promotes tetramerization.
messages: Skin specific, specifically expressed at the inner endocuticle of hair fibers.

9606:BLM
gene id: 9606:BLM
uniprot id: B7ZKN7
uniprot id: H0YNU5
uniprot id: P54132
names: Cofactor
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Eliminates nuclear HIV-1 cDNA, thereby suppressing immune sensing and proviral hyper-integration.
messages: (Microbial infection) Sumoylation of BLM is decreased by HIV-1 Vpu protein, unleashing end degradation of viral cDNA.
messages: ATP-dependent DNA helicase that unwinds single- and double-stranded DNA in a 3'-5' direction (PubMed:9388193, PubMed:24816114, PubMed:25901030). Participates in DNA replication and repair (PubMed:12019152, PubMed:21325134, PubMed:23509288, PubMed:34606619). Involved in 5'-end resection of DNA during double-strand break (DSB) repair: unwinds DNA and recruits DNA2 which mediates the cleavage of 5'-ssDNA (PubMed:21325134). Negatively regulates sister chromatid exchange (SCE) (PubMed:25901030). Stimulates DNA 4-way junction branch migration and DNA Holliday junction dissolution (PubMed:25901030). Binds single-stranded DNA (ssDNA), forked duplex DNA and DNA Holliday junction (PubMed:20639533, PubMed:24257077, PubMed:25901030). Recruited by the KHDC3L-OOEP scaffold to DNA replication forks where it is retained by TRIM25 ubiquitination, it thereby promotes the restart of stalled replication forks (By similarity).
messages: Belongs to the helicase family. RecQ subfamily.
messages: Binds 1 zinc ion per subunit.
messages: Monomer (PubMed:28228481). Homodimer (via N-terminus) (PubMed:28228481). Homotetramer (via N-terminus); dimer of dimers (PubMed:28228481). Homohexamer (via N-terminus) (PubMed:28228481). Self-association negatively regulates DNA unwinding amplitude and rate. Oligomeric complexes dissociate into monomer in presence of ATP (PubMed:28228481). Part of the BRCA1-associated genome surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the RAD50-MRE11-NBS1 protein complex. This association could be a dynamic process changing throughout the cell cycle and within subnuclear domains. Interacts with RMI complex. Interacts directly with RMI1 (via N-terminal region) component of RMI complex. Found in a complex, at least composed of BLM, RAD51 and SPIDR; the complex formation is mediated by SPIDR. Interacts with the KHDC3L/FILIA-OOEP/FLOPED scaffold complex and TRIM25 at DNA replication forks (By similarity). Interacts with ubiquitinated FANCD2 (PubMed:15257300). Interacts with SUPV3L1 (PubMed:17961633). Interacts with TOP3A (via N-terminal region). Interacts with SPIDR (via C-terminal region); the interaction is direct and required to target BLM to sites of DNA damage.
messages: Nucleus
messages: Phosphorylated in response to DNA damage. Phosphorylation requires the FANCA-FANCC-FANCE-FANCF-FANCG protein complex, as well as the presence of RMI1.
messages: Poly-ubiquitinated by TRIM25 at Lys-259 (By similarity). Deubiquitinated by USP37; leading to stabilization in order to sustain the DNA damage response (PubMed:34606619).
messages: The N-terminal region mediates dimerization and homooligomerization (PubMed:28228481). Both the helicase ATP-binding domain and the helicase C-terminal domain form intramolecular interactions with the HRDC domain in a ATP-dependent manner (PubMed:25901030). The HRDC domain is required for single-stranded DNA (ssDNA) and DNA Holliday junction binding (PubMed:20639533).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:WDR4
gene id: 9606:WDR4
uniprot id: P57081
names: Disease Annotation
names: Function
names: Induction
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Amplified and overexpressed in a number of cancers (at protein level).
messages: Belongs to the WD repeat TRM82 family.
messages: Chromosome
messages: In the context of cancer, overexpression of the METTL1-WDR4 methyltransferase complex promotes cancer progression by driving oncogenic transformation (PubMed:34352207, PubMed:34352206, PubMed:34371184). The METTL1-WDR4 methyltransferase complex drives oncogenesis by mediating the formation of N(7)-methylguanine at position 46 (m7G46) in some tRNAs, in particular Arg-TCT-4-1 (TRR-TCT4-1), leading to increased translation of mRNAs, including cell cycle regulators that are enriched in the corresponding AGA codon (PubMed:34352207, PubMed:34352206, PubMed:34371184).
messages: Non-catalytic component of the METTL1-WDR4 complex, composed of METTL1 and WDR4 (PubMed:12403464, PubMed:26751069, PubMed:36599982, PubMed:36599985, PubMed:37379838). Interacts with FEN1; the interaction is direct (PubMed:26751069).
messages: Non-catalytic component of the METTL1-WDR4 methyltransferase complex required for the formation of N(7)-methylguanine in a subset of RNA species, such as tRNAs, mRNAs and microRNAs (miRNAs) (PubMed:12403464, PubMed:31031084, PubMed:31031083, PubMed:36599982, PubMed:36599985, PubMed:37369656). In the METTL1-WDR4 methyltransferase complex, WDR4 acts as a scaffold for tRNA-binding (PubMed:36599982, PubMed:36599985, PubMed:37369656). Required for the formation of N(7)-methylguanine at position 46 (m7G46) in a large subset of tRNAs that contain the 5'-RAGGU-3' motif within the variable loop (PubMed:12403464, PubMed:34352207, PubMed:34352206, PubMed:36599982, PubMed:36599985, PubMed:37369656). M7G46 interacts with C13-G22 in the D-loop to stabilize tRNA tertiary structure and protect tRNAs from decay (PubMed:36599982, PubMed:36599985). Also required for the formation of N(7)-methylguanine at internal sites in a subset of mRNAs (PubMed:31031084, PubMed:37379838). Also required for methylation of a specific subset of miRNAs, such as let-7 (PubMed:31031083). Independently of METTL1, also plays a role in genome stability: localizes at the DNA replication site and regulates endonucleolytic activities of FEN1 (PubMed:26751069).
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:NALF1
gene id: 9606:NALF1
uniprot id: B1AL88
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Auxillary component of the NALCN sodium channel complex, a channel that regulates the resting membrane potential and controls neuronal excitability.
messages: Belongs to the NALF family.
messages: Cell membrane
messages: Component of the NALCN channel complex. NALCN complex consists of NALCN and auxiliary subunits, UNC79, UNC80 and NACL1. These auxiliary subunits are essential for the NALCN channel function.

9606:PAICS
gene id: 9606:PAICS
uniprot id: P22234
names: Disease Annotation
names: Function
names: Similarity
names: Subunit
messages: Bifunctional phosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazole succinocarboxamide synthetase catalyzing two reactions of the de novo purine biosynthetic pathway.
messages: Homooctamer.
messages: In the C-terminal section; belongs to the AIR carboxylase family. Class II subfamily.
messages: In the N-terminal section; belongs to the SAICAR synthetase family.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:SAA2
gene id: 9606:SAA2
uniprot id: P0DJI9
names: Disease Annotation
names: Function
names: Induction
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Apolipoprotein of the HDL complex.
messages: At least 2 different SAA2 alleles have been described: SAA2.1 (SAA2alpha) and SAA2.2 (SAA2beta). We use here the revised nomenclature described in PubMed:10211414. The sequence shown is that of SAA2.2.
messages: Belongs to the SAA family.
messages: Expressed by the liver; secreted in plasma.
messages: Major acute phase reactant.
messages: Reactive, secondary amyloidosis is characterized by the extracellular accumulation in various tissues of the SAA2 protein. These deposits are highly insoluble and resistant to proteolysis; they disrupt tissue structure and compromise function.
messages: Secreted
messages: Upon cytokine stimulation.

9606:STMN3
gene id: 9606:STMN3
uniprot id: Q9NZ72
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the stathmin family.
messages: Exhibits microtubule-destabilizing activity, which is antagonized by STAT3.
messages: Golgi apparatus
messages: Interacts with STAT3. Interacts with CLU (secreted form); this interaction may act as an important modulator during neuronal differentiation (By similarity).
messages: N-terminal palmitoylation promotes specific anchoring to the cytosolic leaflet of Golgi membranes and subsequent vesicular trafficking along dendrites and axons. Neuronal Stathmins are substrates for palmitoyltransferases ZDHHC3, ZDHHC7 and ZDHHC15.
messages: Neuron specific.
messages: axon
messages: cytosol
messages: growth cone

9606:CAPN14
gene id: 9606:CAPN14
uniprot id: A8MX76
uniprot id: B7Z467
names: Function
names: Similarity
names: Tissue Specificity
messages: Belongs to the peptidase C2 family.
messages: Calcium-regulated non-lysosomal thiol-protease.
messages: Not expressed in tissues tested.

9606:OR8G5
gene id: 9606:OR8G5
uniprot id: A0A126GVX5
uniprot id: A0A126GW95
uniprot id: Q8NG78
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Membrane
messages: Odorant receptor.

9606:OR4C46
gene id: 9606:OR4C46
uniprot id: A6NHA9
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Odorant receptor.

9606:MC3R
gene id: 9606:MC3R
uniprot id: P41968
names: Function
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Brain, placental, and gut tissues.
messages: Cell membrane
messages: Genetic variations in MC3R define the body mass index quantitative trait locus 9 (BMIQ9) [MIM:602025]. Variance in body mass index is a susceptibility factor for obesity.
messages: Receptor for MSH (alpha, beta and gamma) and ACTH. This receptor is mediated by G proteins which activate adenylate cyclase. Required for expression of anticipatory patterns of activity and wakefulness during periods of limited nutrient availability and for the normal regulation of circadian clock activity in the brain.

9606:EXTL2
gene id: 9606:EXTL2
uniprot id: F5GZK1
uniprot id: Q8N8F1
uniprot id: Q9UBQ6
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the glycosyltransferase 47 family.
messages: Endoplasmic reticulum membrane
messages: Glycosyltransferase required for the biosynthesis of heparan-sulfate and responsible for the alternating addition of beta-1-4-linked glucuronic acid (GlcA) and alpha-1-4-linked N-acetylglucosamine (GlcNAc) units to nascent heparan sulfate chains.
messages: Membrane
messages: Secreted
messages: The soluble form derives from the membrane form by proteolytic processing.
messages: Ubiquitous.

9606:FER1L5
gene id: 9606:FER1L5
uniprot id: A0AVI2
uniprot id: Q2NNQ7
names: Cofactor
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the ferlin family.
messages: Binds 3 Ca(2+) ions per C2 domain.
messages: Cell membrane
messages: Gene prediction based on partial mRNA data.
messages: Interacts (via second C2 domain) with EHD1 and EHD2.
messages: Membrane
messages: Plays a role in myoblast fusion; probable mediator of endocytic recycling for membrane trafficking events during myotube formation.

9606:RTRAF
gene id: 9606:RTRAF
uniprot id: Q549M8
uniprot id: Q9Y224
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) In case of infection by influenza virus A (IVA), is involved in viral replication (PubMed:21900157).
messages: (Microbial infection) Interacts with influenza A virus (IAV) RNA polymerase subunits PA, PB1 and PB2, and nucleocapsid NP (PubMed:21900157, PubMed:26864902). Associates with IAV polymerase complexes both in the nucleus and cytosol (PubMed:26864902). Associates with IAV ribonucleoproteins (vRNP) packaged in virions (PubMed:26864902). Interacts with hepatitis C virus core protein p19 (PubMed:21823664).
messages: (Microbial infection) Up-regulated specifically following influenza A virus (IAV) infection in a viral replication-dependent manner (at protein level) (PubMed:26864902).
messages: Belongs to the RTRAF family.
messages: Cytoplasm
messages: Homodimer (Probable). Interacts with FAM98A (via N- and C-terminus) (PubMed:28040436). Interacts with NIN; which may prevent phosphorylation of NIN (PubMed:15147888). Interacts with POLR2A (PubMed:16950395). Component of a tRNA-splicing ligase complex with FAM98B, DDX1 and RTCB (PubMed:21311021, PubMed:24870230, PubMed:24608264).
messages: Nucleus
messages: RNA-binding protein involved in modulation of mRNA transcription by Polymerase II (PubMed:16950395). Component of the tRNA-splicing ligase complex and is required for tRNA ligation (PubMed:24870230). May be required for RNA transport (PubMed:24608264).
messages: Widely expressed. Expressed at high level in heart and skeletal muscle. Expressed at intermediate level in liver, pancreas, fetal brain and fetal lung. Weakly expressed in adult brain, adult lung, placenta, fetal liver and fetal kidney. Overexpressed in many brain tumors.
messages: centrosome
messages: cytosol
messages: perinuclear region

9606:ACOT11
gene id: 9606:ACOT11
uniprot id: Q8WXI4
names: Function
names: Induction
names: Subcellular Location Annotation
names: Tissue Specificity
messages: By cold exposure and repressed by heat exposure.
messages: Cytoplasm
messages: Has an acyl-CoA thioesterase activity with a preference for the long chain fatty acyl-CoA thioesters hexadecanoyl-CoA/palmitoyl-CoA and tetradecanoyl-CoA/myristoyl-CoA which are the main substrates in the mitochondrial beta-oxidation pathway.
messages: Isoform 1 is predominantly expressed in skeletal muscle, liver, testis, stomach, spleen, lung and brain. Isoform 2 is predominantly expressed in kidney, uterus, hibernoma and white adipose tissue.
messages: Mitochondrion matrix

9606:PRR4
gene id: 9606:PRR4
uniprot id: Q16378
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Abundantly expressed in lacrimal gland where it is found in the acinar cells but not in the intralobular ducts. Also found in the submandibular gland, the parotid and sublingual glands.
messages: Secreted

9606:CREB5
gene id: 9606:CREB5
uniprot id: Q02930
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the bZIP family.
messages: Binds DNA as a homodimer or as a heterodimer with JUN or ATF2/CREBP1.
messages: Binds to the cAMP response element and activates transcription.
messages: Nucleus

9606:FAXC
gene id: 9606:FAXC
uniprot id: Q5TGI0
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the FAX family.
messages: May play a role in axonal development.
messages: Membrane

9606:EFCC1
gene id: 9606:EFCC1
uniprot id: Q9HA90
names: Caution
messages: It is uncertain whether Met-1 or Met-12 is the initiator.

9606:PEX26
gene id: 9606:PEX26
uniprot id: Q7Z412
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the peroxin-26 family.
messages: Interacts (via its cytoplasmic domain) with PEX6; interaction is direct and is ATP-dependent (PubMed:12717447, PubMed:21362118). Interacts with PEX1; interaction is indirect and is mediated via interaction with PEX6 (PubMed:12717447).
messages: Peroxisomal docking factor that anchors PEX1 and PEX6 to peroxisome membranes (PubMed:12717447, PubMed:12851857, PubMed:16854980, PubMed:21362118, PubMed:16763195, PubMed:16257970). PEX26 is therefore required for the formation of the PEX1-PEX6 AAA ATPase complex, a complex that mediates the extraction of the PEX5 receptor from peroxisomal membrane (PubMed:12717447, PubMed:12851857, PubMed:16854980, PubMed:21362118, PubMed:16763195, PubMed:16257970).
messages: Peroxisome membrane
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Widely expressed (PubMed:12851857). Highly expressed in kidney, liver, brain and skeletal muscles (PubMed:12851857). Expressed at intermediate level in pancreas, placenta and heart (PubMed:12851857). Weakly expressed in lung (PubMed:12851857).

9606:EPB41L1
gene id: 9606:EPB41L1
uniprot id: Q9H4G0
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Highest expression in brain, lower in heart, kidney, pancreas, placenta, lung and skeletal muscle.
messages: Interacts with AGAP2.
messages: May function to confer stability and plasticity to neuronal membrane via multiple interactions, including the spectrin-actin-based cytoskeleton, integral membrane channels and membrane-associated guanylate kinases.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: cytoskeleton

9606:PANK2
gene id: 9606:PANK2
uniprot id: Q9BZ23
names: Activity Regulation
names: Disease Annotation
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the type II pantothenate kinase family.
messages: Cytoplasm
messages: Cytoplasmic isoform that catalyzes the phosphorylation of pantothenate to generate 4'-phosphopantothenate in the first and rate-determining step of coenzyme A (CoA) synthesis.
messages: Expressed in the brain (at protein level) (PubMed:15659606, PubMed:17825826). Ubiquitous (PubMed:11479594). Highly expressed in the testis (PubMed:17825826). Expressed in the umbilical vein endothelial cells (HUVEC) (PubMed:30221726).
messages: Homodimer.
messages: May be produced by alternative initiation at Leu-111 of isoform 1.
messages: Mitochondrial isoform that catalyzes the phosphorylation of pantothenate to generate 4'-phosphopantothenate in the first and rate-determining step of coenzyme A (CoA) synthesis (PubMed:15659606, PubMed:17825826, PubMed:17242360, PubMed:16272150). Required for angiogenic activity of umbilical vein of endothelial cells (HUVEC) (PubMed:30221726).
messages: Mitochondrion
messages: Mitochondrion intermembrane space
messages: Nucleus
messages: Produced by alternative initiation at Met-124 of isoform 1.
messages: Strongly inhibited by acetyl-CoA and its thioesters (PubMed:15659606, PubMed:17825826, PubMed:17242360, PubMed:16272150). Activated by palmitoylcarnitine (PubMed:17825826, PubMed:17242360).
messages: Synthesized as a 62-kDa precursor which is proteolytically processed by the mitochondrial-processing peptidase (MPP) via a 59-kDa intermediate to yield the mature mitochondrial 48-kDa subunit.
messages: The HSS syndrome has been proposed to be renamed because of the unethical activities of Julius Hallervorden and Hugo Spatz during world war II.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:AARS2
gene id: 9606:AARS2
uniprot id: Q5JTZ9
names: Cofactor
names: Disease Annotation
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the class-II aminoacyl-tRNA synthetase family.
messages: Binds 1 zinc ion per subunit.
messages: Catalyzes the attachment of alanine to tRNA(Ala) in a two-step reaction: alanine is first activated by ATP to form Ala-AMP and then transferred to the acceptor end of tRNA(Ala). Also edits incorrectly charged tRNA(Ala) via its editing domain.
messages: Consists of three domains; the N-terminal catalytic domain, the editing domain and the C-terminal C-Ala domain. The editing domain removes incorrectly charged amino acids, while the C-Ala domain, along with tRNA(Ala), serves as a bridge to cooperatively bring together the editing and aminoacylation centers thus stimulating deacylation of misacylated tRNAs.
messages: Mitochondrion
messages: Monomer.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:IKBIP
gene id: 9606:IKBIP
uniprot id: Q70UQ0
names: Function
names: Induction
names: Miscellaneous
names: PTM
names: Subcellular Location Annotation
names: Tissue Specificity
messages: By X-ray irradiation.
messages: Endoplasmic reticulum membrane
messages: Expressed in vein endothelial cells. Isoform 4 is expressed in lung, kidney, spleen, thymus and skeletal muscle.
messages: N-glycosylated. Isoform 4 is glycosylated at Asn-154.
messages: Shares a common promoter with APAF1 from which the 2 genes are transcribed in opposite directions.
messages: Target of p53/TP53 with pro-apoptotic function.

9606:CDC42
gene id: 9606:CDC42
uniprot id: P60953
names: Activity Regulation
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) AMPylation at Tyr-32 and Thr-35 are mediated by bacterial enzymes in case of infection by H.somnus and V.parahaemolyticus, respectively. AMPylation occurs in the effector region and leads to inactivation of the GTPase activity by preventing the interaction with downstream effectors, thereby inhibiting actin assembly in infected cells. It is unclear whether some human enzyme mediates AMPylation; FICD has such ability in vitro but additional experiments remain to be done to confirm results in vivo.
messages: (Microbial infection) Glucosylated at Thr-35 by C.difficile toxins TcdA and TcdB in the colonic epithelium (PubMed:7777059, PubMed:7775453, PubMed:24905543). Monoglucosylation completely prevents the recognition of the downstream effector, blocking the GTPases in their inactive form, leading to actin cytoskeleton disruption and cell death, resulting in the loss of colonic epithelial barrier function (PubMed:7777059, PubMed:7775453).
messages: (Microbial infection) Glycosylated (O-GlcNAcylated) at Thr-35 by C.novyi toxin TcdA (PubMed:8810274). O-GlcNAcylation completely prevents the recognition of the downstream effector, blocking the GTPases in their inactive form, leading to actin cytoskeleton disruption (PubMed:8810274).
messages: (Microbial infection) Glycosylated at Tyr-32 by Photorhabdus asymbiotica toxin PAU_02230. Mono-O-GlcNAcylation by PAU_02230 inhibits downstream signaling by an impaired interaction with diverse regulator and effector proteins of CDC42 and leads to actin disassembly.
messages: Belongs to the small GTPase superfamily. Rho family. CDC42 subfamily.
messages: Cell membrane
messages: Interacts with CDC42EP1, CDC42EP2, CDC42EP3, CDC42EP4, CDC42EP5, CDC42SE1, CDC42SE2, PARD6A, PARD6B and PARD6G (in a GTP-dependent manner) (PubMed:10490598, PubMed:10816584, PubMed:10954424, PubMed:11260256). Interacts with activated CSPG4 and with BAIAP2 (PubMed:10587647, PubMed:11130076). Interacts with activated CSPG4 and with BAIAP2 (By similarity). Interacts with DOCK11/Zizimin2; the interaction activates CDC42 by exchanging GDP for GTP (By similarity). Interacts with DOCK9; the interaction activates CDC42 by exchanging GDP for GTP (PubMed:12172552, PubMed:19745154). Interacts with DOCK8 (via DHR-2 domain); the interaction activates CDC42 by exchanging GDP for GTP (PubMed:12172552). Interacts with IQGAP1 (By similarity). Interacts with NET1 and ARHGAP33/TCGAP (By similarity). Part of a complex with PARD3, PARD6A or PARD6B and PRKCI or PRKCZ (PubMed:11260256). The GTP-bound form interacts with CCPG1 (By similarity). Interacts with USP6 (PubMed:12612085). Interacts with NEK6 (PubMed:20873783). Part of a collagen stimulated complex involved in cell migration composed of CDC42, CRK, TNK2 and BCAR1/p130cas (PubMed:17038317). Interacts with ITGB1BP1 (PubMed:11807099). Interacts with ARHGDIA; this interaction inactivates and stabilizes CDC42 (PubMed:23434736). Interacts with ARHGDIB; this maintains CDC42 in the inactive, GDP-bound form (PubMed:7512369). Interacts (in GTP-bound form) with FNBP1L and ABI1, but only in the presence of FNBP1L (PubMed:19798448). May interact with ARHGEF16; responsible for the activation of CDC42 by the viral protein HPV16 E6 (PubMed:21139582).
messages: Midbody
messages: Phosphorylated by SRC in an EGF-dependent manner, this stimulates the binding of the Rho-GDP dissociation inhibitor RhoGDI.
messages: Plasma membrane-associated small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state. In active state binds to a variety of effector proteins to regulate cellular responses. Involved in epithelial cell polarization processes. Regulates the bipolar attachment of spindle microtubules to kinetochores before chromosome congression in metaphase (PubMed:15642749). Regulates cell migration (PubMed:17038317). In neurons, plays a role in the extension and maintenance of the formation of filopodia, thin and actin-rich surface projections (PubMed:14978216). Required for DOCK10-mediated spine formation in Purkinje cells and hippocampal neurons. In podocytes, facilitates filopodia and podosomes formation upon DOCK11-activation (PubMed:33523862). Upon activation by CaMKII, modulates dendritic spine structural plasticity by relaying CaMKII transient activation to synapse-specific, long-term signaling (By similarity). Also plays a role in phagocytosis through organization of the F-actin cytoskeleton associated with forming phagocytic cups (PubMed:26465210).
messages: Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP, GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity, and GDP dissociation inhibitors which inhibit the dissociation of the nucleotide from the GTPase.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: centrosome
messages: dendrite
messages: spindle

9606:SCRIB
gene id: 9606:SCRIB
uniprot id: A0A0G2JNZ2
uniprot id: A0A0G2JPP5
uniprot id: Q14160
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts (via fourth PDZ domain) with tick-borne encephalitis virus RNA-directed RNA polymerase NS5; this interaction targets viral NS5 to the cell membrane periphery and nucleus and prevents STAT1 phosphorylation, and thus, the activation of the JAK-STAT signaling pathway (PubMed:18042258). Interacts with HPV E6 (PubMed:11027293).
messages: Belongs to the LAP (LRR and PDZ) protein family.
messages: Cell junction
messages: Cell membrane
messages: Cytoplasm
messages: Expressed in kidney, skeletal muscles, liver, lung, breast, intestine, placenta and skin mainly in epithelial cells (at protein level).
messages: Interacts with UBE3A (PubMed:11027293). Interacts with PAK1 and PAK2 (PubMed:18716323). Interacts (via PDZ domains) with VANGL2 (By similarity). Interacts (via PDZ domains) with LPP and TRIP6; the interaction is direct (PubMed:15649318, PubMed:16137684). Interacts (via PDZ domains) with TJP2 (PubMed:15975580). Interacts (via PDZ domains) with APC; may mediate APC targeting to adherens junctions of epithelial cells (PubMed:16611247). Interacts (via PDZ domains) with TSHR; regulates TSHR trafficking and function (PubMed:15775968). Interacts with ARHGEF7 and GIT1; interacts directly with ARHGEF7 (PubMed:15182672). Interacts with CTNNB1 (By similarity). Interacts with MAPK12 (By similarity). Interacts (via PDZ domains 1 and 3) with MCC (PubMed:19555689, PubMed:22480440). Interacts with DLG5 (PubMed:28169360). Interacts with STK4/MST1 and LATS1 in the presence of DLG5 (PubMed:28169360). Interacts (via PDZ domain 3) with CRTAM (via PDZ-binding motif); the interaction promotes CRTAM and SCRIB polarization in a subset of CD4+ T-cells (By similarity).
messages: Palmitoylated (PubMed:27380321). Could be depalmitoylated by LYPLA1 and/or LYPLA2 (PubMed:27380321). Palmitoylation of SCRIB by ZDHHC7 is required for its localization to cell-cell junctions, function in the establishement of epithelial cell polarity and the regulation of downstream signaling pathways important for epithelial cell differentiation (PubMed:27380321).
messages: Postsynapse
messages: Presynapse
messages: Scaffold protein involved in different aspects of polarized cell differentiation regulating epithelial and neuronal morphogenesis and T-cell polarization (PubMed:15182672, PubMed:16344308, PubMed:19041750, PubMed:18716323, PubMed:18641685, PubMed:16965391, PubMed:27380321). Via its interaction with CRTAM, required for the late phase polarization of a subset of CD4+ T-cells, which in turn regulates TCR-mediated proliferation and IFNG and IL22 production (By similarity). Most probably functions in the establishment of apico-basal cell polarity (PubMed:16344308, PubMed:19041750). May function in cell proliferation regulating progression from G1 to S phase and as a positive regulator of apoptosis for instance during acinar morphogenesis of the mammary epithelium (PubMed:16965391, PubMed:19041750). May also function in cell migration and adhesion and hence regulate cell invasion through MAPK signaling (PubMed:18716323, PubMed:18641685). May play a role in exocytosis and in the targeting of synaptic vesicles to synapses (PubMed:15182672). Functions as an activator of Rac GTPase activity.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitinated; targeted for UBE3A-dependent multiubiquitination in the presence of high-risk HPV E6 proteins and degraded.
messages: adherens junction
messages: lamellipodium

9606:DIO2
gene id: 9606:DIO2
uniprot id: A8K845
uniprot id: Q92813
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the iodothyronine deiodinase family.
messages: Has a Sec in position 37.
messages: Has a Sec in positions 90, 169 and 302.
messages: Interacts with USP20 and USP33. Interacts with MARCHF6.
messages: Isoform 1 is expressed in the lung, trachea, kidney, heart, skeletal muscle, placenta, fetal brain and several regions of the adult brain (PubMed:8755651, PubMed:11165050). Isoform 2 is expressed in the brain, heart, kidney and trachea (PubMed:11165050).
messages: Membrane
messages: Responsible for the deiodination of T4 (3,5,3',5'-tetraiodothyronine) into T3 (3,5,3'-triiodothyronine). Essential for providing the brain with appropriate levels of T3 during the critical period of development.
messages: Responsible for the deiodination of T4 (3,5,3',5'-tetraiodothyronine).
messages: Ubiquitinated by MARCHF6, leading to its degradation by the proteasome. Deubiquitinated by USP20 and USP33.

9606:RNF157
gene id: 9606:RNF157
uniprot id: Q96PX1
names: Domain
names: Function
names: Induction
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: Cytoplasm
messages: E3 ubiquitin ligase that ubiquitinates APBB1 for its degradation by the proteasome and thus prevents apoptosis and promotes survival of neurons (PubMed:25342469). Has a dual role in neurons as it is also required for dendrite growth and maintenance for which its ligase activity is not critical (PubMed:25342469). May act as a scaffold molecule to regulate this process (PubMed:25342469). Acts as a downstream effector of the interconnected PI3K and MAPK signaling pathways and thus participates in the regulation of the cell cycle (PubMed:28655764).
messages: Expression is cell cycle-specific with higher levels in cells arrested in G1/S and G2/M (PubMed:28655764).
messages: Interacts with APBB1 (PubMed:25342469). Interacts with CHD1; CHD1-binding controls RNF157 stability (PubMed:28655764). Interacts with ATRN, MEGF8, TECR, MSI2, PLRG1, BYSL, MTERF3, PSMA1, MRPS18B, PRPF4, FASTKD2, SLC25A1, SMU1, CNOT9, MRPS2, MAGT1, FXR2, EMD, PSMD8, HDAC1, RAN, HSD17B12, TXNDC5 and MRPL19 (PubMed:28655764).
messages: Phosphorylation at Ser-660, Ser-661, Ser-662 and Ser-663 downstream of the PI3K and MAPK pathways influences the E3 ligase activity and stability of RNF157 during the cell cycle in an anaphase-promoting complex/cyclosome-CDH1-dependent manner (PubMed:28655764).
messages: The D-box motifs play a key role in RNF157 stabilization (PubMed:28655764).

9606:MAPK13
gene id: 9606:MAPK13
uniprot id: A0A024RD04
uniprot id: O15264
names: Activity Regulation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Activated by phosphorylation on threonine and tyrosine by dual specificity kinases, MAP2K3/MKK3, MAP2K6/MKK6, MAP2K4/MKK4 and MAP2K7/MKK7. Activation by ultraviolet radiation, hyperosmotic shock, anisomycin or by TNF-alpha is mediated by MAP2K3/MKK3. Inhibited by dual specificity phosphatase DUSP1.
messages: Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.
messages: Dually phosphorylated on Thr-180 and Tyr-182 by MAP2K3/MKK3, MAP2K4/MKK4, MAP2K6/MKK6 and MAP2K7/MKK7, which activates the enzyme. Dephosphorylated by dual specificity phosphatase DUSP1.
messages: Expressed in testes, pancreas, small intestine, lung and kidney. Abundant in macrophages, also present in neutrophils, CD4+ T-cells, and endothelial cells.
messages: Interacts with MAPK8IP2.
messages: Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK13 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as pro-inflammatory cytokines or physical stress leading to direct activation of transcription factors such as ELK1 and ATF2. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. MAPK13 is one of the less studied p38 MAPK isoforms. Some of the targets are downstream kinases such as MAPKAPK2, which are activated through phosphorylation and further phosphorylate additional targets. Plays a role in the regulation of protein translation by phosphorylating and inactivating EEF2K. Involved in cytoskeletal remodeling through phosphorylation of MAPT and STMN1. Mediates UV irradiation induced up-regulation of the gene expression of CXCL14. Plays an important role in the regulation of epidermal keratinocyte differentiation, apoptosis and skin tumor development. Phosphorylates the transcriptional activator MYB in response to stress which leads to rapid MYB degradation via a proteasome-dependent pathway. MAPK13 also phosphorylates and down-regulates PRKD1 during regulation of insulin secretion in pancreatic beta cells.
messages: The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.

9606:MRPL49
gene id: 9606:MRPL49
uniprot id: Q13405
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the mitochondrion-specific ribosomal protein mL49 family.
messages: Component of the mitochondrial large ribosomal subunit (mt-LSU) (PubMed:28892042, PubMed:25838379, PubMed:25278503). Mature mammalian 55S mitochondrial ribosomes consist of a small (28S) and a large (39S) subunit. The 28S small subunit contains a 12S ribosomal RNA (12S mt-rRNA) and 30 different proteins. The 39S large subunit contains a 16S rRNA (16S mt-rRNA), a copy of mitochondrial valine transfer RNA (mt-tRNA(Val)), which plays an integral structural role, and 52 different proteins (PubMed:11551941, PubMed:25278503, PubMed:25838379). Interacts with OXA1L (By similarity).
messages: Mitochondrion
messages: Ubiquitous.

9606:DPY19L2
gene id: 9606:DPY19L2
uniprot id: Q6NUT2
names: Disease Annotation
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the dpy-19 family.
messages: Interacts with FAM209.
messages: It has been suggested that DPY19L2P1 is an inactive pseudogene from which DPY19L2 has evolved by duplication. However, expressed transcript sequences derived from the DPY19L2P1 locus are known to exist.
messages: Nucleus inner membrane
messages: Probable C-mannosyltransferase that mediates C-mannosylation of tryptophan residues on target proteins.
messages: Required during spermatogenesis for sperm head elongation and acrosome formation (PubMed:21397063, PubMed:21397064). Also plays a role in acrosome attachment to the nuclear envelope (By similarity).
messages: The disease is caused by variants affecting the gene represented in this entry. Deletions in DPY19L2 are probably the major cause of SPGF9.
messages: Widely expressed with high expression in testis. Not detectable in ejaculated sperm (at protein level).

9606:STK32B
gene id: 9606:STK32B
uniprot id: B2R9M8
uniprot id: Q9NY57
names: Miscellaneous
names: Similarity
messages: Belongs to the protein kinase superfamily.
messages: Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.
messages: It is unsure whether Met-1 or Met-3 is the initiator.

9606:ZSCAN31
gene id: 9606:ZSCAN31
uniprot id: B3KTA4
uniprot id: Q96LW9
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: Expressed at high levels in the lung, liver, and kidney, while weakly expressed in intestine, brain, muscle, cholecyst, heart, and pancreas.
messages: May function as a transcription factor. May be involved in the development of multiple embryonic organs.
messages: Nucleus

9606:WDR5B
gene id: 9606:WDR5B
uniprot id: Q86VZ2
names: Function
names: Similarity
names: Subunit
messages: Belongs to the WD repeat WDR5/wds family.
messages: May function as a substrate receptor for CUL4-DDB1 ubiquitin E3 ligase complex.
messages: Probable part of a cullin-RING E3 protein ligase complex containing CUL4B-DDB1 and a substrate-recruiting component (DCAF). Interacts with CUL4B and DDB1 (By similarity).

9606:DLGAP5
gene id: 9606:DLGAP5
uniprot id: Q15398
names: Caution
names: Developmental Stage
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Abundantly expressed in fetal liver. Expressed at lower levels in bone marrow, testis, colon, and placenta.
messages: Belongs to the SAPAP family.
messages: Cytoplasm
messages: Decreased phosphorylation levels are associated with the differentiation of intestinal epithelial cells.
messages: Elevated levels of expression detected in the G2/M phase of synchronized cultures of HeLa cells.
messages: Interacts with CDK1. Interacts with the C-terminal proline-rich region of FBXO7. Recruited by FBXO7 to a SCF (SKP1-CUL1-F-box) protein complex in a CDK1/Cyclin B-phosphorylation dependent manner. Interacts with CDH1.
messages: It was localized to the spindle and the spindle pole (PubMed:12527899) but was later found to be localized to the spindle and to be excluded from the spindle pole (PubMed:15561729).
messages: Nucleus
messages: Potential cell cycle regulator that may play a role in carcinogenesis of cancer cells. Mitotic phosphoprotein regulated by the ubiquitin-proteasome pathway. Key regulator of adherens junction integrity and differentiation that may be involved in CDH1-mediated adhesion and signaling in epithelial cells.
messages: Ubiquitinated, leading to its degradation.
messages: spindle

9606:CYP26C1
gene id: 9606:CYP26C1
uniprot id: Q6V0L0
names: Disease Annotation
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: A cytochrome P450 monooxygenase involved in the metabolism of retinoates (RAs), the active metabolites of vitamin A, and critical signaling molecules in animals (PubMed:14532297). RAs exist as at least four different isomers: all-trans-RA (atRA), 9-cis-RA, 13-cis-RA, and 9,13-dicis-RA, where atRA is considered to be the biologically active isomer, although 9-cis-RA and 13-cis-RA also have activity (Probable). Catalyzes the oxidation of atRA primarily at C-4 (PubMed:14532297). Oxidation of atRA limits its biological activity and initiates a degradative process leading to its eventual elimination, thereby contributes to the regulation of atRA homeostasis and signaling (Probable). Able to metabolize other RAs such as 9-cis with high efficiency (PubMed:14532297). Can oxidize all-trans-13,14-dihydroretinoate (DRA) to metabolites which could include all-trans-4-oxo-DRA, all-trans-4-hydroxy-DRA, all-trans-5,8-epoxy-DRA, and all-trans-18-hydroxy-DRA (By similarity). Shares sequence similarity with other CYP26 family members, but has higher affinity to 9-cis-RA and is much less sensitive to the inhibitory effects of ketoconazole (PubMed:14532297). In cooperation with Cyp26a1, contributes to the CNS patterning and the development of regions of higher visual acuity (By similarity).
messages: Belongs to the cytochrome P450 family.
messages: By retinoic acid.
messages: Detected in most tissues at very low level.
messages: Membrane
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:RPE65
gene id: 9606:RPE65
uniprot id: Q16518
names: Cofactor
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the carotenoid oxygenase family.
messages: Binds 1 Fe(2+) ion per subunit.
messages: Cell membrane
messages: Critical isomerohydrolase in the retinoid cycle involved in regeneration of 11-cis-retinal, the chromophore of rod and cone opsins. Catalyzes the cleavage and isomerization of all-trans-retinyl fatty acid esters to 11-cis-retinol which is further oxidized by 11-cis retinol dehydrogenase to 11-cis-retinal for use as visual chromophore (PubMed:16116091). Essential for the production of 11-cis retinal for both rod and cone photoreceptors (PubMed:17848510). Also capable of catalyzing the isomerization of lutein to meso-zeaxanthin an eye-specific carotenoid (PubMed:28874556). The soluble form binds vitamin A (all-trans-retinol), making it available for LRAT processing to all-trans-retinyl ester. The membrane form, palmitoylated by LRAT, binds all-trans-retinyl esters, making them available for IMH (isomerohydrolase) processing to all-cis-retinol. The soluble form is regenerated by transferring its palmitoyl groups onto 11-cis-retinol, a reaction catalyzed by LRAT (By similarity).
messages: Cytoplasm
messages: Interacts with MYO7A; this mediates light-dependent intracellular transport of RPE65.
messages: Microsome membrane
messages: Palmitoylation by LRAT regulates ligand binding specificity; the palmitoylated form (membrane form) specifically binds all-trans-retinyl-palmitate, while the soluble unpalmitoylated form binds all-trans-retinol (vitamin A) (By similarity).
messages: Retina (at protein level). Retinal pigment epithelium specific.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:MTMR7
gene id: 9606:MTMR7
uniprot id: B7Z9Q7
uniprot id: B7ZAG8
uniprot id: Q9Y216
names: Activity Regulation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the protein-tyrosine phosphatase family. Non-receptor class myotubularin subfamily.
messages: Cytoplasm
messages: Endomembrane system
messages: Expressed specifically in brain.
messages: Heterodimer (via C-terminus) with MTMR9 (via coiled coil domain); the interaction enhances MTMR7 catalytic activity (By similarity). Does not homodimerize (By similarity). Interacts with RAB1B (in GDP-bound form) (By similarity).
messages: Interaction with MTMR9 increases phosphatase activity.
messages: Phosphatase that specifically dephosphorylates phosphatidylinositol 3-phosphate (PtdIns(3)P) and inositol 1,3-bisphosphate (Ins(1,3)P2).

9606:FFAR4
gene id: 9606:FFAR4
uniprot id: Q5NUL3
names: Developmental Stage
names: Function
names: PTM
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Abundant expression in the intestinal tract. Expressed in colonic intraepithelial neuroendocrine cells.
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Endosome membrane
messages: G-protein-coupled receptor for long-chain fatty acids (LCFAs) with a major role in adipogenesis, energy metabolism and inflammation. Signals via G-protein and beta-arrestin pathways (PubMed:22282525, PubMed:24742677, PubMed:27852822, PubMed:24817122, PubMed:22343897). LCFAs sensing initiates activation of phosphoinositidase C-linked G proteins GNAQ and GNA11 (G(q)/G(11)), inducing a variety of cellular responses via second messenger pathways such as intracellular calcium mobilization, modulation of cyclic adenosine monophosphate (cAMP) production, and mitogen-activated protein kinases (MAPKs) (PubMed:27852822, PubMed:22343897, PubMed:22282525, PubMed:24742677). After LCFAs binding, associates with beta-arrestin ARRB2 that acts as an adapter protein coupling the receptor to specific downstream signaling pathways, as well as mediating receptor endocytosis (PubMed:22282525, PubMed:24817122). In response to dietary fats, plays an important role in the regulation of adipocyte proliferation and differentiation (By similarity). Acts as a receptor for omega-3 polyunsaturated fatty acids (PUFAs) at primary cilium of perivascular preadipocytes, initiating an adipogenic program via cAMP and CTCF-dependent chromatin remodeling that ultimately results in transcriptional activation of adipogenic genes and cell cycle entry (By similarity). Induces differentiation of brown adipocytes probably via autocrine and endocrine functions of FGF21 hormone (By similarity). Activates brown adipocytes by initiating intracellular calcium signaling that leads to mitochondrial depolarization and fission, and overall increased mitochondrial respiration (By similarity). Consequently stimulates fatty acid uptake and oxidation in mitochondria together with UCP1-mediated thermogenic respiration, eventually reducing fat mass (By similarity). Regulates bi-potential differentiation of bone marrow mesenchymal stem cells toward osteoblasts or adipocytes likely by up-regulating distinct integrins (By simila…
messages: Genetic variations in FFAR4 define the body mass index quantitative trait locus 10 (BMIQ10) [MIM:607514]. Variance in body mass index is a susceptibility factor for obesity.
messages: Interacts (via C-terminus) with ARRB2 following LCFAs stimulation.
messages: Low expression is detected in preadipocytes, mainly localized in primary cilium.
messages: Lysosome membrane
messages: Phosphorylated at two clusters of Ser and Thr residues located in the intracellular C-terminus, a prerequisite for FFAR4 internalization via an ARRB2-dependent pathway.
messages: Receptor for LCFAs decoupled from G-protein signaling. May signal through beta-arrestin pathway. After LCFAs binding, associates with beta-arrestin ARRB2 that may act as an adapter protein coupling the receptor to specific downstream signaling pathways, as well as mediating receptor endocytosis.
messages: The predominant isoform in human tissues. Expressed in adipose tissue, pancreatic islets, lung and brain. Expressed in alpha cells of pancreatic islets (PubMed:24742677). Expressed in primary cilia of perivascular preadipocytes of white adipose tissue (at protein level) (PubMed:31761534).
messages: cilium membrane

9606:CDH8
gene id: 9606:CDH8
uniprot id: P55286
names: Domain
names: Function
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types.
messages: Cell membrane
messages: Mainly expressed in brain. Found in certain nerve cell lines, such as retinoblasts, glioma cells and neuroblasts.
messages: Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain.

9606:RXRB
gene id: 9606:RXRB
uniprot id: A0A0G2JKR7
uniprot id: A0A0S2Z570
uniprot id: B7Z7J5
uniprot id: P28702
uniprot id: Q5STP9
names: Domain
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the nuclear hormone receptor family. NR2 subfamily.
messages: Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.
messages: Cytoplasm
messages: Down-regulated by aging.
messages: Expressed in aortic endothelial cells (at protein level) (PubMed:28167758). Expressed in monocytes (PubMed:26463675). Expressed in a variety of tumor cell lines.
messages: Homodimer (in vitro) (PubMed:11782480). Heterodimer with other retinoic acid receptor family members. Binds DNA preferentially as a RAR/RXR heterodimer (PubMed:1310259). Interacts with NR1H3 (PubMed:12970175). Interacts with AKAP13 (By similarity).
messages: Nucleus
messages: Receptor for retinoic acid. Retinoic acid receptors bind as heterodimers to their target response elements in response to their ligands, all-trans or 9-cis retinoic acid, and regulate gene expression in various biological processes. The RAR/RXR heterodimers bind to the retinoic acid response elements (RARE).

9606:CIMAP3
gene id: 9606:CIMAP3
uniprot id: Q8TCI5
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Cytoplasm
messages: Cytoplasmic vesicle
messages: During primary cilia disassembly, involved in cilia disassembly. Required specifically to control cilia retraction as well as the liberation and duplication of the basal body/centrosome. May act by stimulating AURKA activity at the basal body in a cell cycle-dependent manner.
messages: Interacts with proteins involved in ciliary transport, including ARL13B, CETN1, KIF3A, RAB6A, RAB8A, TUBB1 and TUBG1. Interacts with AURKA.
messages: trans-Golgi network

9606:ST8SIA2
gene id: 9606:ST8SIA2
uniprot id: B2R9U8
uniprot id: C6G488
uniprot id: Q4VAY9
uniprot id: Q92186
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the glycosyltransferase 29 family.
messages: Golgi apparatus membrane
messages: Highly expressed in fetal brain, kidney and heart and to a much lesser extent in adult heart and thymus.
messages: May transfer sialic acid through alpha-2,8-linkages to the alpha-2,3-linked and alpha-2,6-linked sialic acid of N-linked oligosaccharides of glycoproteins and may be involved in PSA (polysialic acid) expression.
messages: Membrane

9606:MMP2
gene id: 9606:MMP2
uniprot id: P08253
names: Activity Regulation
names: Cofactor
names: Disease Annotation
names: Domain
names: Function
names: Induction
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Aspirin appears to inhibit expression.
messages: Belongs to the peptidase M10A family.
messages: Binds 2 Zn(2+) ions per subunit.
messages: Binds 4 Ca(2+) ions per subunit.
messages: Cytoplasm
messages: Induced by oxidative stress.
messages: Inhibited by histatin-3 1/24 (histatin-5).
messages: Interacts (via the C-terminal hemopexin-like domains-containing region) with the integrin alpha-V/beta-3; the interaction promotes vascular invasion in angiogenic vessels and melamoma cells. Interacts (via the C-terminal PEX domain) with TIMP2 (via the C-terminal); the interaction inhibits the degradation activity. Interacts with GSK3B.
messages: Mediates the proteolysis of CHUK/IKKA and initiates a primary innate immune response by inducing mitochondrial-nuclear stress signaling with activation of the pro-inflammatory NF-kappaB, NFAT and IRF transcriptional pathways.
messages: Membrane
messages: Mitochondrion
messages: Nucleus
messages: PEX, the C-terminal non-catalytic fragment of MMP2, posseses anti-angiogenic and anti-tumor properties and inhibits cell migration and cell adhesion to FGF2 and vitronectin. Ligand for integrinv/beta3 on the surface of blood vessels.
messages: Phosphorylation on multiple sites modulates enzymatic activity. Phosphorylated by PKC in vitro.
messages: Produced by normal skin fibroblasts. PEX is expressed in a number of tumors including gliomas, breast and prostate.
messages: The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The propeptide is processed by MMP14 (MT-MMP1) and MMP16 (MT-MMP3). Autocatalytic cleavage in the C-terminal produces the anti-angiogenic peptide, PEX. This processing appears to be facilitated by binding integrinv/beta3.
messages: Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque rupture. As well as degrading extracellular matrix proteins, can also act on several nonmatrix proteins such as big endothelial 1 and beta-type CGRP promoting vasoconstriction. Also cleaves KISS at a Gly-|-Leu bond. Appears to have a role in myocardial cell death pathways. Contributes to myocardial oxidative stress by regulating the activity of GSK3beta. Cleaves GSK3beta in vitro. Involved in the formation of the fibrovascular tissues in association with MMP14.
messages: extracellular matrix

9606:COL11A2
gene id: 9606:COL11A2
uniprot id: P13942
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: A disulfide-bonded peptide called proline/arginine-rich protein or PARP is released from the N-terminus during extracellular processing and is subsequently retained in the cartilage matrix from which it can be isolated in significant amounts.
messages: Belongs to the fibrillar collagen family.
messages: May play an important role in fibrillogenesis by controlling lateral growth of collagen II fibrils.
messages: Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.
messages: The C-terminal propeptide, also known as COLFI domain, have crucial roles in tissue growth and repair by controlling both the intracellular assembly of procollagen molecules and the extracellular assembly of collagen fibrils. It binds a calcium ion which is essential for its function (By similarity).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Trimers composed of three different chains: alpha 1(XI), alpha 2(XI), and alpha 3(XI). Alpha 3(XI) is a post-translational modification of alpha 1(II). Alpha 1(V) can also be found instead of alpha 3(XI)=1(II).
messages: extracellular matrix

9606:BTNL8
gene id: 9606:BTNL8
uniprot id: Q6UX41
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the immunoglobulin superfamily. BTN/MOG family.
messages: Down-regulated in neutrophils after treatment with LPS and TNF.
messages: Expressed in neutrophils. Isoforms 1 and 5 are expressed at high levels in the colon, lung,testis, lymph nodes and thyroid tissue. Isoform 5, but not isoform 1, is detected in spleen.
messages: May stimulate primary immune response. Acts on T-cell stimulated sub-optimally through the TCR/CD3 complex stimulating their proliferation and cytokine production.
messages: Membrane

9606:PDCD1LG2
gene id: 9606:PDCD1LG2
uniprot id: Q9BQ51
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the immunoglobulin superfamily. BTN/MOG family.
messages: Cell membrane
messages: Endomembrane system
messages: Highly expressed in heart, placenta, pancreas, lung and liver and weakly expressed in spleen, lymph nodes and thymus.
messages: Interacts with PDCD1.
messages: Involved in the costimulatory signal, essential for T-cell proliferation and IFNG production in a PDCD1-independent manner. Interaction with PDCD1 inhibits T-cell proliferation by blocking cell cycle progression and cytokine production (By similarity).
messages: Secreted
messages: Up-regulated by IFNG/IFN-gamma stimulation in monocytes and induced on dendritic cells grown from peripheral blood mononuclear cells with CSF2 and IL4/interleukin-4.

9606:MDH1B
gene id: 9606:MDH1B
uniprot id: C9JER5
uniprot id: Q5I0G3
names: Similarity
messages: Belongs to the LDH/MDH superfamily. MDH type 2 family.

9606:GH1
gene id: 9606:GH1
uniprot id: B1A4G6
uniprot id: B1A4G7
uniprot id: P01241
names: Disease Annotation
names: Function
names: Miscellaneous
names: Pharmaceutical
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Available under the names Nutropin or Protropin (Genentech), Norditropin (Novo Nordisk), Genotropin (Pharmacia Upjohn), Humatrope (Eli Lilly) and Saizen or Serostim (Serono). Used for the treatment of growth hormone deficiency and for Turner's syndrome.
messages: Belongs to the somatotropin/prolactin family.
messages: Circulating GH shows a great heterogeneity due to alternative splicing, differential post-translational modifications of monomeric forms, oligomerization, optional binding to 2 different GH-binding proteins, and potentially proteolytic processing.
messages: Monomer, dimer, trimer, tetramer and pentamer, disulfide-linked or non-covalently associated, in homomeric and heteromeric combinations. Can also form a complex either with GHBP or with the alpha2-macroglobulin complex.
messages: Plays an important role in growth control. Its major role in stimulating body growth is to stimulate the liver and other tissues to secrete IGF-1. It stimulates both the differentiation and proliferation of myoblasts. It also stimulates amino acid uptake and protein synthesis in muscle and other tissues.
messages: Secreted
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:TMEM14B
gene id: 9606:TMEM14B
uniprot id: A0A087WU83
uniprot id: C9JCY4
uniprot id: Q9NUH8
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the TMEM14 family.
messages: Interacts with IQGAP1; this interaction promotes phosphorylation and nuclear translocation of IQGAP1.
messages: Mainly expressed in the outer subventricular zone (OSVZ) of the fetal brains.
messages: Membrane
messages: Primate-specific protein involved in cortical expansion and folding in the developing neocortex. May drive neural progenitor proliferation through nuclear translocation of IQGAP1, which in turn promotes G1/S cell cycle transitions.
messages: When expressed in embryonic mouse neocortex, induces intermediate progenitor cells and outer radial glia expansion, cortical thickening and induces gyrification (PubMed:29033352).

9606:EOMES
gene id: 9606:EOMES
uniprot id: B7Z4K0
uniprot id: O95936
names: Caution
names: Developmental Stage
names: Disease Annotation
names: Function
names: Induction
names: Miscellaneous
names: Subcellular Location Annotation
names: Tissue Specificity
messages: A translocation t(3;10)(p24;q23) located 215 kb 3' to the EOMES gene but leading to loss of its expression was identified in a large consanguineous family. Homozygous silencing produces microcephaly associated with corpus callosum agenesis, bilateral polymicrogyria, ventricular dilatation and a small cerebellum.
messages: Detected at 7 weeks of development in the forebrain floorplate of the CNS. Expressed within the mantle layer and migrating neuroblasts of the telencephalon at 12.5 weeks of development.
messages: Dubious isoform produced through aberrant splice sites.
messages: Expressed in CD8+ T-cells.
messages: Functions as a transcriptional activator playing a crucial role during development. Functions in trophoblast differentiation and later in gastrulation, regulating both mesoderm delamination and endoderm specification. Plays a role in brain development being required for the specification and the proliferation of the intermediate progenitor cells and their progeny in the cerebral cortex. Also involved in the differentiation of CD8+ T-cells during immune response regulating the expression of lytic effector genes.
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: Nucleus
messages: Up-regulated in CD8+ T-cells simultaneously stimulated with TGFB1 and IL4/interleukin-4.

9606:CTPS2
gene id: 9606:CTPS2
uniprot id: Q9NRF8
names: Function
names: Similarity
messages: Belongs to the CTP synthase family.
messages: Catalyzes the ATP-dependent amination of UTP to CTP with either L-glutamine or ammonia as the source of nitrogen. Constitutes the rate-limiting enzyme in the synthesis of cytosine nucleotides.

9606:ARIH1
gene id: 9606:ARIH1
uniprot id: Q9Y4X5
names: Activity Regulation
names: Caution
names: Disease Annotation
names: Domain
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Autoinhibited by the ariadne domain, which masks the second RING-type zinc finger that contains the active site and inhibits the E3 activity (PubMed:23707686). Inhibition is relieved upon binding to neddylated cullin-RING ubiquitin ligase complexes, which activate the E3 ligase activity of ARIH1 (PubMed:24076655, PubMed:27565346).
messages: Belongs to the RBR family. Ariadne subfamily.
messages: Cajal body
messages: Cytoplasm
messages: Defects in ARIH1 have been found in several individuals with thoracic aortic aneurysms and cerebrovascular disease.
messages: E3 ubiquitin-protein ligase, which catalyzes ubiquitination of target proteins together with ubiquitin-conjugating enzyme E2 UBE2L3 (PubMed:15236971, PubMed:21532592, PubMed:24076655, PubMed:27565346, PubMed:23707686). Acts as an atypical E3 ubiquitin-protein ligase by working together with cullin-RING ubiquitin ligase (CRL) complexes and initiating ubiquitination of CRL substrates: associates with CRL complexes and specifically mediates addition of the first ubiquitin on CRLs targets (PubMed:27565346). The initial ubiquitin is then elongated by CDC34/UBE2R1 and UBE2R2 (PubMed:27565346). E3 ubiquitin-protein ligase activity is activated upon binding to neddylated cullin-RING ubiquitin ligase complexes (PubMed:24076655, PubMed:27565346). Plays a role in protein translation in response to DNA damage by mediating ubiquitination of EIF4E2, the consequences of EIF4E2 ubiquitination are however unclear (PubMed:25624349). According to a report, EIF4E2 ubiquitination leads to promote EIF4E2 cap-binding and protein translation arrest (PubMed:25624349). According to another report EIF4E2 ubiquitination leads to its subsequent degradation (PubMed:14623119). Acts as the ligase involved in ISGylation of EIF4E2 (PubMed:17289916). In vitro, controls the degradation of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex member SUN2 and may therefore have a role in the formation and localization of the LINC complex, and as a consequence, nuclear subcellular localization and nuclear morphology (PubMed:29689197).
messages: Interacts (via the first RING-type zinc finger) with UBE2L3 (PubMed:11278816, PubMed:21532592, PubMed:24076655, PubMed:23707686). Associates with cullin-RING ubiquitin ligase (CRL) complexes containing CUL1, CUL2 and CUL3 (PubMed:24076655, PubMed:27565346). Interacts with neddylated CUL1 (PubMed:24076655, PubMed:27565346). Interacts with neddylated CUL2 (PubMed:24076655, PubMed:27565346). Interacts with neddylated CUL3 (PubMed:24076655, PubMed:27565346). Interacts with neddylated CUL4A (PubMed:24076655).
messages: Members of the RBR family are atypical E3 ligases. They interact with the E2 conjugating enzyme UBE2L3 and function like HECT-type E3 enzymes: they bind E2s via the first RING-type zinc finger, but require an obligate trans-thiolation step during the ubiquitin transfer, requiring a conserved active site Cys residue in the second RING-type zinc finger (PubMed:21532592, PubMed:23707686). The active site probably forms a thioester intermediate with ubiquitin taken from the active-site cysteine of the E2 before ultimately transferring it to a Lys residue on the substrate (PubMed:21532592, PubMed:23707686).
messages: Nucleus
messages: The Ariadne domain inhibits activity by masking the second RING-type zinc finger that contains the active site (PubMed:23707686).
messages: The RING-type 2 zinc finger was initially reported to only bind 1 zinc ion instead of 2 compared to classical RING-types (PubMed:15236971). But it was later shown that it is not the case and binds 2 zinc ions (PubMed:24058416, PubMed:23707686).
messages: Up-regulated following DNA damage (PubMed:25624349).
messages: Widely expressed.

9606:CPVL
gene id: 9606:CPVL
uniprot id: Q9H3G5
names: Function
names: Similarity
names: Tissue Specificity
messages: Belongs to the peptidase S10 family.
messages: Expressed in macrophages but not in other leukocytes. Abundantly expressed in heart and kidney. Also expressed in spleen, leukocytes, and placenta.
messages: May be involved in the digestion of phagocytosed particles in the lysosome, participation in an inflammatory protease cascade, and trimming of peptides for antigen presentation.

9606:IGLL5
gene id: 9606:IGLL5
uniprot id: B9A064
names: Miscellaneous
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Contrary to IGLL1, not expressed in pre-B-cells.
messages: Located within the immunoglobulin lambda locus, but does not require somatic rearrangement for expression.
messages: Secreted

9606:CD52
gene id: 9606:CD52
uniprot id: P31358
uniprot id: V9HWN9
names: Function
names: Subcellular Location Annotation
messages: Cell membrane
messages: May play a role in carrying and orienting carbohydrate, as well as having a more specific role.
messages: Membrane

9606:CNDP2
gene id: 9606:CNDP2
uniprot id: Q96KP4
names: Activity Regulation
names: Cofactor
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the peptidase M20A family.
messages: Binds 2 manganese ions per subunit.
messages: Broadly expressed in fetal tissues. Expressed in adult liver and placenta.
messages: Catalyzes the peptide bond hydrolysis in dipeptides, displaying a non-redundant activity toward threonyl dipeptides (By similarity). Mediates threonyl dipeptide catabolism in a tissue-specific way (By similarity). Has high dipeptidase activity toward cysteinylglycine, an intermediate metabolite in glutathione metabolism (PubMed:19346245, PubMed:12473676). Metabolizes N-lactoyl-amino acids, both through hydrolysis to form lactic acid and amino acids, as well as through their formation by reverse proteolysis (PubMed:25964343). Plays a role in the regulation of cell cycle arrest and apoptosis (PubMed:17121880, PubMed:24395568).
messages: Cytoplasm
messages: Homodimer.
messages: Inhibited by p-hydroxymercurybenzoate. The inhibitory concentration 50% (IC(50)) is 13 uM. Inhibited by bestatin. The inhibitory concentration 50% (IC(50)) is 7 nM at pH 9.5.
messages: Lacks a part of the catalytic domain.
messages: The reverse proteolysis is not negligible in vivo as long as the substrates are present in considerable concentrations, such as upon physical exercice. N-lac-Phe plasma levels are increased in patients with PKU with increased plasma Phe levels. N-lactoyl-amino acids are present in many tissues.
messages: Ubiquitously expressed with higher levels in kidney and liver (at protein level). Expressed in peripheral blood leukocytes (PubMed:12473676). Expressed in gastric mucosa and down-regulated in gastric cancer mucosal tissues (at protein level) (PubMed:24395568).

9606:CALN1
gene id: 9606:CALN1
uniprot id: Q9BXU9
names: Domain
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Brain specific.
messages: Cell membrane
messages: Interacts with PI4KB. This binding competes with FREQ/NCS1 binding in a calcium-dependent manner.
messages: Negatively regulates Golgi-to-plasma membrane trafficking by interacting with PI4KB and inhibiting its activity. May play a role in the physiology of neurons and is potentially important in memory and learning.
messages: The C-terminal transmembrane domain (TMD) is necessary and sufficient for membrane targeting.
messages: perinuclear region
messages: trans-Golgi network membrane

9606:ACE2
gene id: 9606:ACE2
uniprot id: Q9BYF1
names: Activity Regulation
names: Biotechnology
names: Cofactor
names: Domain
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Acts as a receptor for human coronaviruses SARS-CoV and SARS-CoV-2, as well as human coronavirus NL63/HCoV-NL63.
messages: (Microbial infection) In airway epithelial cells, expression is increased upon influenza A virus infection (PubMed:32413319).
messages: (Microbial infection) In airway epithelial cells, expression is induced by viruses such rhinoviruses and influenza virus.
messages: (Microbial infection) Induced by human coronavirus SARS-CoV-2.
messages: (Microbial infection) Interacts with SARS coronavirus-2/SARS-CoV-2 spike protein (via RBD domain).
messages: (Microbial infection) Interacts with SARS coronavirus-2/SARS-CoV-2 spike protein; the interaction is increased by AVP/Arg-vasopressin with which they may form a complex.
messages: (Microbial infection) Interacts with SARS coronavirus/SARS-CoV spike protein.
messages: (Microbial infection) Interacts with human coronavirus NL63 spike protein.
messages: (Microbial infection) Interacts with human coronavirus NL63/HCoV-NL63 spike glycoprotein.
messages: (Microbial infection) Non-functional as a receptor for human coronavirus SARS-CoV-2.
messages: An engeneered stable, dimeric and secreted receptor with combined mutations that increase the affinity for human coronavirus SARS-CoV-2 spike protein shows potent SARS-CoV and SARS-CoV-2 neutralization in vitro.
messages: Apical cell membrane
messages: Belongs to the peptidase M2 family.
messages: Binds 1 Cl(-) ion per subunit.
messages: Binds 1 zinc ion per subunit.
messages: Cell membrane
messages: Cytoplasm
messages: Essential counter-regulatory carboxypeptidase of the renin-angiotensin hormone system that is a critical regulator of blood volume, systemic vascular resistance, and thus cardiovascular homeostasis (PubMed:27217402). Converts angiotensin I to angiotensin 1-9, a nine-amino acid peptide with anti-hypertrophic effects in cardiomyocytes, and angiotensin II to angiotensin 1-7, which then acts as a beneficial vasodilator and anti-proliferation agent, counterbalancing the actions of the vasoconstrictor angiotensin II (PubMed:10969042, PubMed:10924499, PubMed:11815627, PubMed:19021774, PubMed:14504186). Also removes the C-terminal residue from three other vasoactive peptides, neurotensin, kinetensin, and des-Arg bradykinin, but is not active on bradykinin (PubMed:10969042, PubMed:11815627). Also cleaves other biological peptides, such as apelins (apelin-13, [Pyr1]apelin-13, apelin-17, apelin-36), casomorphins (beta-casomorphin-7, neocasomorphin) and dynorphin A with high efficiency (PubMed:11815627, PubMed:27217402, PubMed:28293165). In addition, ACE2 C-terminus is homologous to collectrin and is responsible for the trafficking of the neutral amino acid transporter SL6A19 to the plasma membrane of gut epithelial cells via direct interaction, regulating its expression on the cell surface and its catalytic activity (PubMed:18424768, PubMed:19185582).
messages: Expressed in endothelial cells from small and large arteries, and in arterial smooth muscle cells (at protein level) (PubMed:15141377). Expressed in enterocytes of the small intestine, Leydig cells and Sertoli cells (at protein level) (PubMed:15141377). Expressed in the renal proximal tubule and the small intestine (at protein level) (PubMed:18424768). Expressed in heart, kidney, testis, and gastrointestinal system (at protein level) (PubMed:10969042, PubMed:10924499, PubMed:15231706, PubMed:12459472, PubMed:15671045, PubMed:32715618, PubMed:32170560). In lung, expressed at low levels in some alveolar type 2 cells, the expression seems to be individual-specific (at protein level) (PubMed:32425701, PubMed:15141377, PubMed:32715618, PubMed:32170560, PubMed:33432184). Expressed in nasal epithelial cells (at protein level) (PubMed:33432184, PubMed:32333915). Coexpressed with TMPRSS2 within some lung alveolar type 2 cells, ileal absorptive enterocytes, intestinal epithelial cells, cornea, gallbladder and nasal goblet secretory cells (PubMed:32413319, PubMed:32327758, PubMed:32358202). Coexpressed with TMPRSS4 within mature enterocytes (PubMed:32404436).
messages: Expressed in nasal and bronchial epithelial cells (at protein level).
messages: Expression is induced by interferons such as IFNA, IFNB and IFNG. It seems that isoform 2 is an interferon-stimulated gene (ISG) but not isoform 1.
messages: Homodimer (PubMed:32132184). Interacts with the catalytically active form of TMPRSS2 (PubMed:21068237). Interacts with SLC6A19; this interaction is essential for expression and function of SLC6A19 in intestine (By similarity). Interacts with ITGA5:ITGB1 (PubMed:15276642, PubMed:33102950). Probably interacts (via endocytic sorting signal motif) with AP2M1; the interaction is inhibited by phosphorylation of Tyr-781 (PubMed:33436498). Interacts (via PDZ-binding motif) with NHERF1 (via PDZ domains); the interaction may enhance ACE2 membrane residence (PubMed:34189428).
messages: N-glycosylation on Asn-90 may limit SARS infectivity.
messages: Non-functional as a carboxypeptidase.
messages: Not induced by interferons such as IFNA, IFNB and IFNG.
messages: Phosphorylated. Phosphorylation at Tyr-781 probably inhibits interaction with AP2M1 and enables interactions with proteins containing SH2 domains.
messages: Proteolytic cleavage by ADAM17 generates a secreted form (PubMed:15983030, PubMed:33713620). Also cleaved by serine proteases: TMPRSS2, TMPRSS11D and HPN/TMPRSS1.
messages: Regulated by chloride and fluoride, but not bromide (PubMed:11815627). Chloride increases angiotensin I and decreases angiotensin II cleavage (PubMed:19021774). Inhibited by MLN-4760, cFP_Leu, and EDTA (PubMed:15231706, PubMed:10924499), but not by the ACE inhibitors lisinopril, captopril and enalaprilat (PubMed:10969042, PubMed:10924499). Highly potent and selective in vitro ACE2 inhibitors were identified (PubMed:12358520).
messages: Secreted
messages: The cytoplasmic tail contains several linear motifs such as LIR, PDZ-binding, PTB and endocytic sorting signal motifs that would allow interaction with proteins that mediate endocytic trafficking and autophagy.
messages: The extracellular region of the ACE2 enzyme is composed of two domains. The first is a zinc metallopeptidase domain (residues 19-611). The second domain is located at the C-terminus (residues 612-740) and is 48% identical to human collectrin.
messages: Up-regulated in failing heart (PubMed:14504186, PubMed:15151696, PubMed:15671045). Expression is induced by IFNA and IFNG (PubMed:32413319, PubMed:32425701). Exposure to cigarette smoke increases expression in lungs (PubMed:32425701). Expression is decreased in nasal and bronchial epithelium of individuals with allergy after allergen challenge (PubMed:32333915). IL13 stimulation decreases expression in nasal and bronchial epithelium (PubMed:32333915).
messages: cilium

9606:SKIC8
gene id: 9606:SKIC8
uniprot id: Q9GZS3
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the SKI8 family.
messages: Component of the PAF1 complex (PAF1C) which has multiple functions during transcription by RNA polymerase II and is implicated in regulation of development and maintenance of embryonic stem cell pluripotency (PubMed:16307923, PubMed:19952111, PubMed:20178742). PAF1C associates with RNA polymerase II through interaction with POLR2A CTD non-phosphorylated and 'Ser-2'- and 'Ser-5'-phosphorylated forms and is involved in transcriptional elongation, acting both independently and synergistically with TCEA1 and in cooperation with the DSIF complex and HTATSF1 (PubMed:16307923, PubMed:19952111, PubMed:20178742). PAF1C is required for transcription of Hox and Wnt target genes (PubMed:16307923, PubMed:19952111, PubMed:20178742). PAF1C is involved in hematopoiesis and stimulates transcriptional activity of KMT2A/MLL1; it promotes leukemogenesis through association with KMT2A/MLL1-rearranged oncoproteins, such as KMT2A/MLL1-MLLT3/AF9 and KMT2A/MLL1-MLLT1/ENL (PubMed:16307923, PubMed:19952111, PubMed:20178742). PAF1C is involved in histone modifications such as ubiquitination of histone H2B and methylation on histone H3 'Lys-4' (H3K4me3) (PubMed:16307923, PubMed:19952111, PubMed:20178742). PAF1C recruits the RNF20/40 E3 ubiquitin-protein ligase complex and the E2 enzyme UBE2A or UBE2B to chromatin which mediate monoubiquitination of 'Lys-120' of histone H2B (H2BK120ub1); UB2A/B-mediated H2B ubiquitination is proposed to be coupled to transcription (PubMed:16307923, PubMed:19952111, PubMed:20178742). PAF1C is involved in mRNA 3' end formation probably through association with cleavage and poly(A) factors (PubMed:16307923, PubMed:19952111, PubMed:20178742). In case of infection by influenza A strain H3N2, PAF1C associates with viral NS1 protein, thereby regulating gene transcription (PubMed:16307923, PubMed:19952111, PubMed:20178742). Required for mono- and trimethylation on histone H3 'Lys-4' (H3K4me3), dimethylation on histone H3 'Lys-79' (H3K4me3). Required for Hox gene transcr…
messages: Component of the PAF1 complex, which consists of CDC73, PAF1, LEO1, CTR9, RTF1 and SKIC8 (PubMed:16024656, PubMed:19952111, PubMed:20178742). The PAF1 complex interacts with PHF5A (By similarity). Within the PAF1 complex interacts directly with PHF5A (By similarity). Component of the SKI complex which consists of SKIC2, SKIC3 and SKIC8 (PubMed:16024656, PubMed:32006463, PubMed:35120588).
messages: Cytoplasm
messages: Nucleus

9606:CAAP1
gene id: 9606:CAAP1
uniprot id: Q9H8G2
names: Function
names: Tissue Specificity
messages: Anti-apoptotic protein that modulates a caspase-10 dependent mitochondrial caspase-3/9 feedback amplification loop.
messages: Ubiquitous.

9606:SLC25A41
gene id: 9606:SLC25A41
uniprot id: Q8N5S1
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the mitochondrial carrier (TC 2.A.29) family.
messages: Calcium-independent ATP-Mg/Pi exchanger that catalyzes the electroneutral exchange of Mg-ATP or free ADP against an hydrogenphosphate and participates in the net transport of adenine nucleotides across the mitochondria inner membrane.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Mitochondrion inner membrane

9606:CDRT4
gene id: 9606:CDRT4
uniprot id: Q8N9R6
names: Tissue Specificity
messages: Expressed in fetal skeletal muscle and kidney.

9606:NAB1
gene id: 9606:NAB1
uniprot id: A8K8T1
uniprot id: B8ZZS2
uniprot id: Q13506
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acts as a transcriptional repressor for zinc finger transcription factors EGR1 and EGR2.
messages: Belongs to the NAB family.
messages: Homomultimers may associate with EGR1 bound to DNA.
messages: Isoform Short is found in myeloid leukemia cell line KG-1.
messages: Nucleus
messages: The NAB conserved domain 1 (NCD1) interacts with EGR1 inhibitory domain and mediates multimerization.
messages: The NAB conserved domain 2 (NCD2) is necessary for transcriptional repression.

9606:ABHD6
gene id: 9606:ABHD6
uniprot id: Q9BV23
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the AB hydrolase superfamily.
messages: Late endosome membrane
messages: Lipase that preferentially hydrolysis medium-chain saturated monoacylglycerols including 2-arachidonoylglycerol (PubMed:22969151). Through 2-arachidonoylglycerol degradation may regulate endocannabinoid signaling pathways (By similarity). Also has a lysophosphatidyl lipase activity with a preference for lysophosphatidylglycerol among other lysophospholipids (By similarity). Also able to degrade bis(monoacylglycero)phosphate (BMP) and constitutes the major enzyme for BMP catabolism (PubMed:26491015). BMP, also known as lysobisphosphatidic acid, is enriched in late endosomes and lysosomes and plays a key role in the formation of intraluminal vesicles and in lipid sorting (PubMed:26491015).
messages: Lysosome membrane
messages: Mitochondrion membrane

9606:AMBRA1
gene id: 9606:AMBRA1
uniprot id: Q9C0C7
names: Domain
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the WD repeat AMBRA1 family.
messages: Component of the DCX(AMBRA1) E3 ubiquitin ligase complex, also named CRL4(AMBRA1), at least composed of CUL4 (CUL4A or CUL4B), DDB1, AMBRA1 and RBX1 (PubMed:25499913, PubMed:16949367, PubMed:30166453, PubMed:33854232, PubMed:33854239). Interacts with BECN1 (PubMed:21358617, PubMed:25438055). Probably forms a complex with BECN1 and PIK3C3 (By similarity). Interacts with BECN2 (PubMed:23954414). Interacts with BCL2; leading to prevent interaction with BCN1 and autophagy, interaction is disrupted upon autophagy induction (PubMed:21358617). Interacts with ULK1 (PubMed:25438055). Interacts (via PxP motifs) with PPP2CA; enhancing interaction between PPP2CA and MYC or FOXO3 (PubMed:25438055, PubMed:30513302). Forms a complex with PPP2CA and BECN1; AMBRA1 and BECN1 components of the complex regulate MYC stability via different pathways (PubMed:25803737). Interacts (TQT motifs) with DYNLL1 and DYNLL2; tethering AMBRA1 and the BECN1-PIK3C3 complex in absence of autophagy (PubMed:20921139). Interacts with TRAF6; interaction is required to mediate 'Lys-63'-linked ubiquitination of ULK1 (PubMed:23524951). Interacts with TRIM32; promoting activation of ULK1 by TRIM32 via unanchored 'Lys-63'-linked polyubiquitin chains (PubMed:31123703). Interacts with PRKN (By similarity). Interacts (via LIR motif) with LC3 (MAP1LC3A, MAP1LC3B or MAP1LC3C) (PubMed:25215947, PubMed:30217973). Interacts with HUWE1 (PubMed:30217973). Interacts with PTK2/FAK (By similarity). Interacts with SRC; required for SRC trafficking to autophagosomes (By similarity).
messages: Endoplasmic reticulum
messages: Mitochondrion
messages: Negatively regulated by microRNA 7-3HG (miR7-3HG), which targets the 3' untranslated (3'-UTR) region of AMBRA1 transcripts, leading to a decrease of AMBRA1 mRNA and protein levels, thereby inhibiting autophagy (PubMed:28059583). Strongly up-regulated during egulatory T-cells (Treg) differentiation (PubMed:30513302).
messages: Nucleus
messages: Phosphorylation at Ser-52 by MTOR inhibits its ability to regulate autophagy and mediate ubiquitination of ULK1 (PubMed:23524951). Phosphorylation by ULK1 in response to autophagy induction abolishes interaction with DYNLL1 and DYNLL2, releasing AMBRA1 from the cytoskeletal docking site to induce autophagosome nucleation (PubMed:20921139). Phosphorylation by MTOR inhibits interaction with PPP2CA and subsequent dephosphorylation of MYC (PubMed:25438055). Phosphorylation at Ser-1043 by CHUK/IKKA promotes its interaction with ATG8 family proteins GABARAP and MAP1LC3B and its mitophagic activity (PubMed:30217973).
messages: Substrate-recognition component of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex involved in cell cycle control and autophagy (PubMed:20921139, PubMed:23524951, PubMed:24587252, PubMed:33854232, PubMed:33854235, PubMed:33854239, PubMed:32333458). The DCX(AMBRA1) complex specifically mediates the polyubiquitination of target proteins such as BECN1, CCND1, CCND2, CCND3, ELOC and ULK1 (PubMed:23524951, PubMed:33854232, PubMed:33854235, PubMed:33854239). Acts as an upstream master regulator of the transition from G1 to S cell phase: AMBRA1 specifically recognizes and binds phosphorylated cyclin-D (CCND1, CCND2 and CCND3), leading to cyclin-D ubiquitination by the DCX(AMBRA1) complex and subsequent degradation (PubMed:33854232, PubMed:33854235, PubMed:33854239). By controlling the transition from G1 to S phase and cyclin-D degradation, AMBRA1 acts as a tumor suppressor that promotes genomic integrity during DNA replication and counteracts developmental abnormalities and tumor growth (PubMed:33854232, PubMed:33854235, PubMed:33854239). AMBRA1 also regulates the cell cycle by promoting MYC dephosphorylation and degradation independently of the DCX(AMBRA1) complex: acts via interaction with the catalytic subunit of protein phosphatase 2A (PPP2CA), which enhances interaction between PPP2CA and MYC, leading to MYC dephosphorylation and degradation (PubMed:25803737, PubMed:25438055). Acts as a regulator of Cul5-RING (CRL5) E3 ubiquitin-protein ligase complexes by mediating ubiquitination and degradation of Elongin-C (ELOC) component of CRL5 complexes (PubMed:25499913, PubMed:30166453). Acts as a key regulator of autophagy by modulating the BECN1-PIK3C3 complex: controls protein turnover during neuronal development, and regulates normal cell survival and proliferation (PubMed:21358617). In normal conditions, AMBRA1 is tethered to the cytoskeleton via interaction with dyneins DYNLL1 and DYNLL2 (PubMed:20921139). Upon autophagy induction, AMBRA1 is released from the…
messages: The LIR motif (LC3-interacting region) is required for the interaction with the ATG8 family proteins GABARAP and MAP1LC3B.
messages: The PxP motifs mediate interaction with the catalytic subunit of protein phosphatase 2A (PPP2CA).
messages: The TQT motifs mediate interaction with the dynein light chain proteins DYNLL1 and DYNLL2, tethering AMBRA1 to the cytoskeleton in absence of autophagy.
messages: Ubiquitinated by RNF2 via 'Lys-48'-linkage in unstressed cells, leading to its degradation by the proteasome (PubMed:25499913). Induction of autophagy promotes stabilization via interaction with CUL4 (CUL4A or CUL4B) and DDB1 (PubMed:25499913). Upon prolonged starvation, ubiquitinated and degraded, terminating the autophagy response (PubMed:25499913).
messages: Undergoes proteolytic processing by caspase-6 (CASP6), caspase-7 (CASP7) and caspase-8 (CASP8) during apoptosis, resulting in the dismantling of the autophagic machinery and the accomplishment of the programmed cell death program (PubMed:22441670). Also cleaved by calpains during apoptosis, which mediate a complete proteolytic degradation (PubMed:22441670).
messages: autophagosome
messages: cytoskeleton
messages: cytosol
messages: focal adhesion

9606:PTPN2
gene id: 9606:PTPN2
uniprot id: A8K3N4
uniprot id: K7EQG9
uniprot id: P17706
uniprot id: Q59F91
names: Function
names: Induction
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the protein-tyrosine phosphatase family. Non-receptor class 1 subfamily.
messages: Cell membrane
messages: Cytoplasm
messages: Endoplasmic reticulum
messages: Endoplasmic reticulum-Golgi intermediate compartment
messages: Interacts with RMDN3. Isoform 1 interacts with TMED9. Isoform 1 interacts with STX17; dephosphorylates STX17. Interacts with ITGA1 (via cytoplasmic domain); activates the phosphatase activity towards EGFR. Interacts with TRAF2; probably involved in tumor necrosis factor-mediated signaling. Interacts with MET.
messages: Major isoform. Contains a nuclear location signal at positions 377-381 (PubMed:7593185) and an autoinhibitory region acting through intramolecular interactions is found at positions 353-387.
messages: Minor isoform.
messages: Non-receptor type tyrosine-specific phosphatase that dephosphorylates receptor protein tyrosine kinases including INSR, EGFR, CSF1R, PDGFR. Also dephosphorylates non-receptor protein tyrosine kinases like JAK1, JAK2, JAK3, Src family kinases, STAT1, STAT3 and STAT6 either in the nucleus or the cytoplasm. Negatively regulates numerous signaling pathways and biological processes like hematopoiesis, inflammatory response, cell proliferation and differentiation, and glucose homeostasis. Plays a multifaceted and important role in the development of the immune system. Functions in T-cell receptor signaling through dephosphorylation of FYN and LCK to control T-cells differentiation and activation. Dephosphorylates CSF1R, negatively regulating its downstream signaling and macrophage differentiation. Negatively regulates cytokine (IL2/interleukin-2 and interferon)-mediated signaling through dephosphorylation of the cytoplasmic kinases JAK1, JAK3 and their substrate STAT1, that propagate signaling downstream of the cytokine receptors. Also regulates the IL6/interleukin-6 and IL4/interleukin-4 cytokine signaling through dephosphorylation of STAT3 and STAT6 respectively. In addition to the immune system, it is involved in anchorage-dependent, negative regulation of EGF-stimulated cell growth. Activated by the integrin ITGA1/ITGB1, it dephosphorylates EGFR and negatively regulates EGF signaling. Dephosphorylates PDGFRB and negatively regulates platelet-derived growth factor receptor-beta signaling pathway and therefore cell proliferation. Negatively regulates tumor necrosis factor-mediated signaling downstream via MAPK through SRC dephosphorylation. May also regulate the hepatocyte growth factor receptor signaling pathway through dephosphorylation of the hepatocyte growth factor receptor MET. Also plays an important role in glucose homeostasis. For instance, negatively regulates the insulin receptor signaling pathway through the dephosphorylation of INSR and control gluconeogene…
messages: Nucleus
messages: Specifically phosphorylated in a cell cycle-dependent manner by cyclin-dependent kinases CDK1 and CDK2. Probably activated through phosphorylation by PKR.
messages: Ubiquitously expressed. Isoform 2 is probably the major isoform. Isoform 1 is expressed in T-cells and in placenta.
messages: Up-regulated by IL4/interleukin-4 (at protein level).

9606:DHRS1
gene id: 9606:DHRS1
uniprot id: Q96LJ7
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the short-chain dehydrogenases/reductases (SDR) family.
messages: Detected in heart, liver, adrenal glands, and at low levels in skeletal muscle, kidney, pancreas and brain.
messages: Endoplasmic reticulum
messages: May be attached to the ER membrane by its C-terminus segment.
messages: NADPH-dependent oxidoreductase which catalyzes the reduction of steroids (estrone, androstene-3,17-dione and cortisone) as well as prostaglandin E1, isatin and xenobiotics in vitro (PubMed:30031147). May have a role in steroid and/or xenobiotic metabolism (PubMed:30031147).

9606:KRTAP5-2
gene id: 9606:KRTAP5-2
uniprot id: Q701N4
names: Function
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Belongs to the KRTAP type 5 family.
messages: In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated protein (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.
messages: Interacts with hair keratins.
messages: Restricted to hair root, not detected in any other tissues.

9606:S100Z
gene id: 9606:S100Z
uniprot id: Q8WXG8
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Belongs to the S-100 family.
messages: Highest level of expression in spleen and leukocytes.
messages: Homodimer (PubMed:28074300). Interacts with S100P (PubMed:11747429).

9606:ST14
gene id: 9606:ST14
uniprot id: Q9Y5Y6
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the peptidase S1 family.
messages: Exhibits trypsin-like activity as defined by cleavage of synthetic substrates with Arg or Lys as the P1 site (PubMed:10373424). Involved in the terminal differentiation of keratinocytes through prostasin (PRSS8) activation and filaggrin (FLG) processing (PubMed:18843291). Proteolytically cleaves and therefore activates TMPRSS13 (PubMed:28710277).
messages: Interacts with CDCP1. May interact with TMEFF1.
messages: Membrane
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:ZFYVE26
gene id: 9606:ZFYVE26
uniprot id: Q68DK2
names: Disease Annotation
names: Domain
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Interacts with AP5Z1, AP5B1, AP5S1 and SPG11. Interacts with TTC19 and KIF13A.
messages: Midbody
messages: Phosphatidylinositol 3-phosphate-binding protein required for the abcission step in cytokinesis: recruited to the midbody during cytokinesis and acts as a regulator of abcission. May also be required for efficient homologous recombination DNA double-strand break repair.
messages: Strongest expression in the adrenal gland, bone marrow, adult brain, fetal brain, lung, placenta, prostate, skeletal muscle, testis, thymus, and retina. Intermediate levels are detected in other structures, including the spinal cord.
messages: The FYVE-type zinc finger mediates binding to phosphatidylinositol 3-phosphate and recruitment to the midbody during cytokinesis.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: centrosome

9606:OR52K1
gene id: 9606:OR52K1
uniprot id: A0A126GVF2
uniprot id: Q8NGK4
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Membrane
messages: Odorant receptor.

9606:PRKAG2
gene id: 9606:PRKAG2
uniprot id: Q9UGJ0
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subunit
names: Tissue Specificity
messages: AMP/ATP-binding subunit of AMP-activated protein kinase (AMPK), an energy sensor protein kinase that plays a key role in regulating cellular energy metabolism. In response to reduction of intracellular ATP levels, AMPK activates energy-producing pathways and inhibits energy-consuming processes: inhibits protein, carbohydrate and lipid biosynthesis, as well as cell growth and proliferation. AMPK acts via direct phosphorylation of metabolic enzymes, and by longer-term effects via phosphorylation of transcription regulators. Also acts as a regulator of cellular polarity by remodeling the actin cytoskeleton; probably by indirectly activating myosin. Gamma non-catalytic subunit mediates binding to AMP, ADP and ATP, leading to activate or inhibit AMPK: AMP-binding results in allosteric activation of alpha catalytic subunit (PRKAA1 or PRKAA2) both by inducing phosphorylation and preventing dephosphorylation of catalytic subunits. ADP also stimulates phosphorylation, without stimulating already phosphorylated catalytic subunit. ATP promotes dephosphorylation of catalytic subunit, rendering the AMPK enzyme inactive.
messages: AMPK is a heterotrimer of an alpha catalytic subunit (PRKAA1 or PRKAA2), a beta (PRKAB1 or PRKAB2) and a gamma non-catalytic subunits (PRKAG1, PRKAG2 or PRKAG3). Interacts with FNIP1 and FNIP2.
messages: Belongs to the 5'-AMP-activated protein kinase gamma subunit family.
messages: Isoform B is ubiquitously expressed except in liver and thymus. The highest level is detected in heart with abundant expression in placenta and testis.
messages: Phosphorylated by ULK1; leading to negatively regulate AMPK activity and suggesting the existence of a regulatory feedback loop between ULK1 and AMPK.
messages: The 4 CBS domains mediate binding to nucleotides. Of the 4 potential nucleotide-binding sites, 3 are occupied, designated as sites 1, 3, and 4 based on the CBS modules that provide the acidic residue for coordination with the 2'- and 3'-hydroxyl groups of the ribose of AMP. Of these, site 4 appears to be a structural site that retains a tightly held AMP molecule (AMP 3). The 2 remaining sites, 1 and 3, can bind either AMP, ADP or ATP. Site 1 (AMP, ADP or ATP 1) is the high-affinity binding site and likely accommodates AMP or ADP. Site 3 (AMP, ADP or ATP 2) is the weakest nucleotide-binding site on the gamma subunit, yet it is exquisitely sensitive to changes in nucleotide levels and this allows AMPK to respond rapidly to changes in cellular energy status. Site 3 is likely to be responsible for protection of a conserved threonine in the activation loop of the alpha catalytic subunit through conformational changes induced by binding of AMP or ADP.
messages: The AMPK pseudosubstrate motif resembles the sequence around sites phosphorylated on target proteins of AMPK, except the presence of a non-phosphorylatable residue in place of Ser. In the absence of AMP this pseudosubstrate sequence may bind to the active site groove on the alpha subunit (PRKAA1 or PRKAA2), preventing phosphorylation by the upstream activating kinase STK11/LKB1.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:CNOT9
gene id: 9606:CNOT9
uniprot id: D5MQE1
uniprot id: Q92600
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the CNOT9 family.
messages: Component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. Involved in down-regulation of MYB- and JUN-dependent transcription. May play a role in cell differentiation (By similarity). Can bind oligonucleotides, such as poly-G, poly-C or poly-T (in vitro), but the physiological relevance of this is not certain. Does not bind poly-A. Enhances ligand-dependent transcriptional activity of nuclear hormone receptors, including RARA, expect ESR1-mediated transcription that is not only slightly increased, if at all.
messages: Detected in spleen, thymus, prostate, testis, ovary and intestine.
messages: Homodimer. Component of the CCR4-NOT complex; distinct complexes seem to exist that differ in the participation of probably mutually exclusive catalytic subunits. Interacts with MYB, ATF2, RARA, RARB, RARG, RXRA, RXRB and RXRG. Identified in a complex with ATF2 bound to target DNA (By similarity). Interacts with NANOS2 (By similarity). Directly interacts with ZNF335.
messages: Nucleus
messages: P-body

9606:EFHD1
gene id: 9606:EFHD1
uniprot id: Q9BUP0
names: Function
names: Subcellular Location Annotation
messages: Acts as a calcium sensor for mitochondrial flash (mitoflash) activation, an event characterized by stochastic bursts of superoxide production (PubMed:26975899). May play a role in neuronal differentiation (By similarity).
messages: Mitochondrion inner membrane

9606:TBC1D10A
gene id: 9606:TBC1D10A
uniprot id: Q9BXI6
names: Domain
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: Acts as GTPase-activating protein for RAB27A, but not for RAB2A, RAB3A, nor RAB4A.
messages: Binds to the first PDZ domain of NHERF1 and NHERF2.
messages: Exists in both phosphorylated and non-phosphorylated state.
messages: The arginine and glutamine fingers are critical for the GTPase-activating mechanism, they pull out Rab's 'switch 2' glutamine and insert in Rab's active site.
messages: microvillus

9606:PCDH20
gene id: 9606:PCDH20
uniprot id: Q8N6Y1
names: Function
names: Subcellular Location Annotation
messages: Cell membrane
messages: Potential calcium-dependent cell-adhesion protein.

9606:SYNE3
gene id: 9606:SYNE3
uniprot id: Q6ZMZ3
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: As a component of the LINC (LInker of Nucleoskeleton and Cytoskeleton) complex involved in the connection between the nuclear lamina and the cytoskeleton. The nucleocytoplasmic interactions established by the LINC complex play an important role in the transmission of mechanical forces across the nuclear envelope and in nuclear movement and positioning. Probable anchoring protein which tethers the nucleus to the cytoskeleton by binding PLEC which can associate with the intermediate filament system. Plays a role in the regulation of aortic epithelial cell morphology, and is required for flow-induced centrosome polarization and directional migration in aortic endothelial cells.
messages: Belongs to the nesprin family.
messages: Core component of LINC complexes which are composed of inner nuclear membrane SUN domain-containing proteins coupled to outer nuclear membrane KASH domain-containing nesprins. SUN and KASH domain-containing proteins seem to bind each other promiscuously; however, differentially expression of LINC complex constituents can give rise to specific assemblies. Interacts with SUN1 and SUN2; probably forming respective LINC complexes. Interacts with PLEC (via actin-binding domain). Interacts with DST. Interacts with SYNE1 via spectrin repeats. Interacts (via KASH domain) with TOR1A (ATP-bound); the interaction is required for SYNE3 nuclear envelope localization.
messages: Expressed in aortic endothelial cells (at protein level).
messages: Nucleus envelope
messages: Nucleus outer membrane
messages: Rough endoplasmic reticulum
messages: The KASH domain is involved in the binding to SUN1 and SUN2 through recognition of their SUN domains.
messages: The disulfid bond with SUN1 or SUN2 is required for stability of the respective LINC complex under tensile forces.

9606:ABCD1
gene id: 9606:ABCD1
uniprot id: P33897
names: Activity Regulation
names: Caution
names: Disease Annotation
names: Domain
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: ATP-dependent transporter of the ATP-binding cassette (ABC) family involved in the transport of very long chain fatty acid (VLCFA)-CoA from the cytosol to the peroxisome lumen (PubMed:11248239, PubMed:15682271, PubMed:16946495, PubMed:18757502, PubMed:21145416, PubMed:23671276, PubMed:29397936, PubMed:33500543). Coupled to the ATP-dependent transporter activity has also a fatty acyl-CoA thioesterase activity (ACOT) and hydrolyzes VLCFA-CoA into VLCFA prior their ATP-dependent transport into peroxisomes, the ACOT activity is essential during this transport process (PubMed:33500543, PubMed:29397936). Thus, plays a role in regulation of VLCFAs and energy metabolism namely, in the degradation and biosynthesis of fatty acids by beta-oxidation, mitochondrial function and microsomal fatty acid elongation (PubMed:23671276, PubMed:21145416). Involved in several processes; namely, controls the active myelination phase by negatively regulating the microsomal fatty acid elongation activity and may also play a role in axon and myelin maintenance. Controls also the cellular response to oxidative stress by regulating mitochondrial functions such as mitochondrial oxidative phosphorylation and depolarization. And finally controls the inflammatory response by positively regulating peroxisomal beta-oxidation of VLCFAs (By similarity).
messages: Belongs to the ABC transporter superfamily. ABCD family. Peroxisomal fatty acyl CoA transporter (TC 3.A.1.203) subfamily.
messages: Can form homodimers and heterodimers with ABCD2 and ABCD3. Dimerization is necessary to form an active transporter (PubMed:17609205, PubMed:10551832) (Probable). The minimal functional unit is a homodimer but the major oligomeric form in peroxisomal membrane is a homotetramer (By similarity). Forms heterotramers with ABCD2 (By similarity). Interacts with PEX19; facilitates ABCD1 insertion into the peroxisome membrane (PubMed:10777694, PubMed:10704444).
messages: Endoplasmic reticulum membrane
messages: Lysosome membrane
messages: Mitochondrion membrane
messages: Peroxisome membrane
messages: The NH2-terminal transmembrane domaine (TMD) is involved in the recognition of substrates, and undergoes a conformational change upon ATP binding to the COOH-terminal nucleotide binding domain (NBD).
messages: The cysteine-reactive reagent p-chloromercuribenzoic acid (pCMB) strongly decreased the ACOT activity. The serine esterase inhibitors phenylmethylsulfonyl fluoride (PMSF), diisopropylfluorophosphate (DFP) and bis-(4-nitrophenyl)phosphate (BNPP) moderately reduced the ACOT activity. The histidine-reacting reagent diethyl pyrocarbonate (DEPC) has no effect on the ACOT activity.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The promoter region of ABCD1 is deleted in the chromosome Xq28 deletion syndrome which involves ABCD1 and the neighboring gene BCAP31.
messages: Tyrosine-phosphorylated.
messages: Up-regulated by degradation or export of cholesterol.
messages: Variants Trp-88, Cys-152, Cys-181, Ser-343, Pro-503, Arg-514 and His-554 have original been associated with ALD. However this paper was retracted due to inconsistencies in a confirmation immunoblot that could not be validated from the originally published data.

9606:SLC5A10
gene id: 9606:SLC5A10
uniprot id: A0PJK1
names: Activity Regulation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Apical cell membrane
messages: Appears to have no transporter activity.
messages: Belongs to the sodium:solute symporter (SSF) (TC 2.A.21) family.
messages: Electrogenic Na+-coupled sugar symporter that actively transports D-mannose or D-fructose at the plasma membrane, with a Na+ to sugar coupling ratio of 1:1. Transporter activity is driven by a transmembrane Na+ electrochemical gradient set by the Na+/K+ pump. Exclusively recognizes sugar substrates having a pyranose ring with an axial hydroxyl group on carbon 2 (PubMed:24573086, PubMed:22212718, PubMed:23451068). Has likely evolved to enable renal reabsorption of D-mannose, an important constituent of oligosaccharide chains of glycoproteins. Contributes to dietary D-fructose reabsorption from glomerular filtrate across the brush border of the kidney (PubMed:22212718, PubMed:23451068).
messages: Expressed in kidney.
messages: Inhibited by phlorizin.
messages: Predominantly expressed at high levels in kidney. Very low expression is detected in testes.
messages: The most abundant isoform expressed in kidney.

9606:OR5M11
gene id: 9606:OR5M11
uniprot id: A0A126GVL9
uniprot id: Q96RB7
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Membrane
messages: Odorant receptor.

9606:SPINK13
gene id: 9606:SPINK13
uniprot id: Q1W4C9
names: Function
names: Subcellular Location Annotation
messages: May be a serine protease inhibitor (By similarity). Essential for sperm maturation and fertility. Inhibits sperm acrosome reaction, protecting sperm from premature reaction (By similarity).
messages: Secreted

9606:TOR3A
gene id: 9606:TOR3A
uniprot id: Q9H497
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the ClpA/ClpB family. Torsin subfamily.
messages: Cytoplasm
messages: Endoplasmic reticulum lumen
messages: May not form homohexamers.
messages: N-glycosylated.
messages: Ubiquitously expressed. Highest expression in stomach, salivary glands and lymph nodes. Isoform 2 is expressed in placenta.

9606:MATN2
gene id: 9606:MATN2
uniprot id: A0A140VKH7
uniprot id: O00339
uniprot id: Q8N2G3
names: Caution
names: Function
names: Subcellular Location Annotation
messages: Involved in matrix assembly.
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: Secreted

9606:GPR68
gene id: 9606:GPR68
uniprot id: A1A5B2
uniprot id: Q15743
names: Caution
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Found at low level in a wide range of tissues, but significantly expressed in lung, kidney, bone and nervous system.
messages: Proton-sensing receptor involved in pH homeostasis. May represents an osteoblastic pH sensor regulating cell-mediated responses to acidosis in bone. Mediates its action by association with G proteins that stimulates inositol phosphate (IP) production or Ca(2+) mobilization. The receptor is almost silent at pH 7.8 but fully activated at pH 6.8. Also functions as a metastasis suppressor gene in prostate cancer (By similarity).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Was originally (PubMed:10806476) thought to be a receptor for sphingosylphosphorylcholine (SPC). However, this work has been retracted (PubMed:16508674).

9606:QDPR
gene id: 9606:QDPR
uniprot id: P09417
names: Disease Annotation
names: Function
names: Similarity
names: Subunit
messages: Belongs to the short-chain dehydrogenases/reductases (SDR) family.
messages: Catalyzes the conversion of quinonoid dihydrobiopterin into tetrahydrobiopterin.
messages: Homodimer.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:CEP131
gene id: 9606:CEP131
uniprot id: Q9UPN4
names: Function
names: Induction
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the CEP131 family.
messages: Component of centriolar satellites contributing to the building of a complex and dynamic network required to regulate cilia/flagellum formation (PubMed:17954613, PubMed:24185901). In proliferating cells, MIB1-mediated ubiquitination induces its sequestration within centriolar satellites, precluding untimely cilia formation initiation (PubMed:24121310). In contrast, during normal and ultraviolet or heat shock cellular stress-induced ciliogenesis, its non-ubiquitinated form is rapidly displaced from centriolar satellites and recruited to centrosome/basal bodies in a microtubule- and p38 MAPK-dependent manner (PubMed:24121310, PubMed:26616734). Acts also as a negative regulator of BBSome ciliary trafficking (PubMed:24550735). Plays a role in sperm flagellar formation; may be involved in the regulation of intraflagellar transport (IFT) and/or intramanchette (IMT) trafficking, which are important for axoneme extension and/or cargo delivery to the nascent sperm tail (By similarity). Required for optimal cell proliferation and cell cycle progression; may play a role in the regulation of genome stability in non-ciliogenic cells (PubMed:22797915, PubMed:26297806). Involved in centriole duplication (By similarity). Required for CEP152, WDR62 and CEP63 centrosomal localization and promotes the centrosomal localization of CDK2 (PubMed:26297806). Essential for maintaining proper centriolar satellite integrity (PubMed:30804208).
messages: MAPKAPK2-dependent phosphorylation at Ser-47 and Ser-78 occurs in response to cellular stress such as exposure to ultraviolet irradiation and promotes binding to 14-3-3 proteins which leads to cytoplasmic sequestration of CEP131 and blocks formation of new centriolar satellites (PubMed:26616734). Phosphorylation at Ser-78 mediated by PLK4 is essential for proper organization and integrity of centriolar satellites but is dispensable for its localization to centrioles and its function in ciliogenesis (PubMed:30804208).
messages: Self-associates. Associates with the centriolar satellite BBSome protein complex. Interacts with BBS4; the interaction limits BBS4 availability for association with the BBSome complex, and hence negatively regulates ciliary localization of the BBSome complex (PubMed:24550735). Interacts with MIB1 (PubMed:24121310). Interacts with PCM1; the interaction increases in response to ultraviolet light (UV) radiation (PubMed:22797915, PubMed:24121310). Associates with microtubules; association with microtubules is reduced in response to cellular stress, such as UV stimulation, in a process that requires p38 MAP kinase signaling (PubMed:24121310). Interacts with CEP290, DCTN1, PCNT, PCM1 and CEP152. Interacts with 14-3-3 proteins following UV-induced phosphorylation by MAPKAPK2; this inhibits formation of novel centriolar satellites (PubMed:26616734). Interacts with SDCCAG8 (PubMed:27224062). Interacts with CCDC61 (PubMed:31789463). Interacts with PLK4 (PubMed:30804208).
messages: Transient cell cultured-based knock-down (by RNAi) of CEP131 leads to a reduction in ciliogenesis (PubMed:17954613, PubMed:24121310). However, analysis of mice with chronic absence of CEP131 following genetic deletion (knockout) shows that cilia develop and function normally in vivo. This suggests that CEP131 is not essential for ciliogenesis, except for the modified cilia of the developing sperm flagella, and that there is an alternative mechanism to compensate for the lack of CEP131.
messages: Ubiquitinated. Undergoes monoubiquitination catalyzed by the E3 ubiquitin-protein ligase MIB1 in proliferating cells, preventing cilia formation. Monoubiquitination by MIB1 is inhibited in response to cellular stress, such as ultraviolet light (UV) radiation or heat shock, resulting in cilia formation initiation.
messages: Up-regulated by the transcription factor SP1.
messages: acrosome
messages: centriolar satellite
messages: centriole
messages: centrosome
messages: cilium basal body

9606:SEC23A
gene id: 9606:SEC23A
uniprot id: Q15436
names: Disease Annotation
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the SEC23/SEC24 family. SEC23 subfamily.
messages: COPII is composed of at least five proteins: the Sec23/24 complex, the Sec13/31 complex and Sar1 (PubMed:17499046). Interacts with SEC23IP. Interacts with HTR4 (By similarity). Interacts with SEC16A (PubMed:17192411). Interacts with SLC6A4 (By similarity). Interacts (as part of the Sec23/24 complex) with SEC22B; recruits SEC22B into COPII-coated vesicles and allows the transport of this cargo from the endoplasmic reticulum to the Golgi (PubMed:17499046). Interacts (via Gelsolin-like repeat) with MIA2 and MIA3; specifically involved in the transport of large cargos like the collagen COL7A1 (PubMed:27551091, PubMed:28442536). Interacts with DDHD1 (By similarity). Interacts with TMEM39A (PubMed:31806350). Interacts with SACM1L; this interaction is reduced in the absence of TMEM39A (PubMed:31806350). Interacts with kinase FAM20C; transport of FAM20C from the endoplasmic reticulum to the Golgi is likely to be mediated by COPII vesicles (PubMed:34349020).
messages: COPII-coated vesicle membrane
messages: Component of the coat protein complex II (COPII) which promotes the formation of transport vesicles from the endoplasmic reticulum (ER). The coat has two main functions, the physical deformation of the endoplasmic reticulum membrane into vesicles and the selection of cargo molecules for their transport to the Golgi complex. Required for the translocation of insulin-induced glucose transporter SLC2A4/GLUT4 to the cell membrane (By similarity).
messages: Endoplasmic reticulum membrane
messages: The Gelsolin-like repeat mediates interaction with proteins containing PPP motifs that include MIA2, MIA3 but also SEC31A. These interactions are probably competitive.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitously expressed.
messages: cytosol

9606:AMY1B
gene id: 9606:AMY1B
uniprot id: P0DTE7
uniprot id: P0DTE8
uniprot id: P0DUB6
names: Caution
names: Cofactor
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the glycosyl hydrolase 13 family.
messages: Binds 1 Ca(2+) ion per subunit.
messages: Binds 1 Cl(-) ion per subunit.
messages: Calcium-binding enzyme that initiates starch digestion in the oral cavity (PubMed:12527308). Catalyzes the hydrolysis of internal (1->4)-alpha-D-glucosidic bonds, yielding a mixture of maltose, isomaltose, small amounts of glucose as well as small linear and branched oligosaccharides called dextrins (PubMed:12527308).
messages: Monomer.
messages: Secreted
messages: Three distinct genes (AMY1A, AMY1B and AMY1C), located in a gene cluster on 1p21, encode proteins sharing the same peptidic sequence.

9606:GPR75-ASB3
gene id: 9606:GPR75-ASB3
uniprot id: Q9Y575
names: Domain
names: Function
names: Similarity
names: Subunit
messages: Belongs to the ankyrin SOCS box (ASB) family.
messages: Interacts with ELOB and TNFRSF1B.
messages: Probable substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Recognizes TNFRSF1B.
messages: The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin-protein ligase complexes.

9606:DEFB118
gene id: 9606:DEFB118
uniprot id: A0A384MTK2
uniprot id: Q96PH6
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the beta-defensin family.
messages: Has antibacterial activity.
messages: High-level and epididymis-specific expression (PubMed:12600824). Most abundant in the epithelium of the caput and present in the epididymis lumen and bound to sperm (PubMed:12600824). Also expressed in pancreas (PubMed:12600824).
messages: Host defense peptide that exhibits antimicrobial activity against both Gram-negative bacteria, such as E.coli and S.typhimurium, and Gram-positive bacteria, such as S.aureus and B.subtilis (PubMed:15033915, PubMed:33224970). Inhibits cell adhesion of E.coli on intestinal epithelial enterocytes (PubMed:33224970). Causes rapid permeabilization of both the outer and inner membrane of E.coli, leading to morphological alterations on the bacterial surface (PubMed:15033915). Binds to bacterial lipopolysaccharides (LPS) with high affinity, and may thereby be involved in immunoregulation through LPS neutralization (PubMed:33181266). May contribute to epididymal innate immunity and protect the sperm against attack by microorganisms (PubMed:15033915).
messages: Secreted
messages: The three-dimensional structure formed by the three intramolecular disulfide bridges is indispensable for antimicrobial activity.

9606:OR6Q1
gene id: 9606:OR6Q1
uniprot id: A0A126GVP6
uniprot id: Q8NGQ2
names: Function
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
messages: A single nucleotide deletion at position Leu-229 in the gene coding for this protein is responsible for functional diversity thus producing a pseudogene. The deletion is more frequent in African-Americans than in non-Africans.
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Membrane
messages: Odorant receptor.

9606:BBS5
gene id: 9606:BBS5
uniprot id: A0A0S2Z626
uniprot id: Q8N3I7
names: Disease Annotation
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: BBS5 may interact genetically with BBS1.
messages: Belongs to the BBS5 family.
messages: Cytoplasm
messages: Membrane
messages: Part of BBSome complex, that contains BBS1, BBS2, BBS4, BBS5, BBS7, BBS8/TTC8, BBS9 and BBIP10. Binds to phosphoinositides. Interacts with CCDC28B. Interacts with SMO; the interaction is indicative for the association of SMO with the BBsome complex to facilitate ciliary localization of SMO. Interacts with PKD1 (PubMed:24939912). Interacts with DLEC1 (PubMed:33144677).
messages: The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia. The BBSome complex is required for ciliogenesis but is dispensable for centriolar satellite function. This ciliogenic function is mediated in part by the Rab8 GDP/GTP exchange factor, which localizes to the basal body and contacts the BBSome. Rab8(GTP) enters the primary cilium and promotes extension of the ciliary membrane. Firstly the BBSome associates with the ciliary membrane and binds to RAB3IP/Rabin8, the guanosyl exchange factor (GEF) for Rab8 and then the Rab8-GTP localizes to the cilium and promotes docking and fusion of carrier vesicles to the base of the ciliary membrane. The BBSome complex, together with the LTZL1, controls SMO ciliary trafficking and contributes to the sonic hedgehog (SHH) pathway regulation. Required for BBSome complex ciliary localization but not for the proper complex assembly.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: centriolar satellite
messages: cilium basal body
messages: cilium membrane

9606:SIGLEC10
gene id: 9606:SIGLEC10
uniprot id: Q96LC7
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the immunoglobulin superfamily. SIGLEC (sialic acid binding Ig-like lectin) family.
messages: Cell membrane
messages: Contains 1 copy of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases.
messages: Expressed by peripheral blood leukocytes (eosinophils, monocytes and a natural killer cell subpopulation). Isoform 5 is found to be the most abundant isoform. Found in lymph node, lung, ovary and appendix. Isoform 1 is found at high levels and isoform 2 at lower levels in bone marrow, spleen and spinal chord. Isoform 2 is also found in brain. Isoform 4 is specifically found in natural killer cells.
messages: Interacts with PTPN6/SHP-1 upon phosphorylation (PubMed:12163025). Interacts with NCF1 (By similarity). Interacts with CD24; the probable CD24:SIGLEC10 complex is proposed to inhibit HGMB1-mediated tissue damage immune response. Interacts with HMGB1; the interaction is dependent on CD24 (PubMed:19264983). Interacts with RIGI, CBL and PTPN11 (By similarity).
messages: Phosphorylation of Tyr-667 is involved in binding to PTPN6.
messages: Putative adhesion molecule that mediates sialic-acid dependent binding to cells. Preferentially binds to alpha-2,3- or alpha-2,6-linked sialic acid (By similarity). The sialic acid recognition site may be masked by cis interactions with sialic acids on the same cell surface. In the immune response, seems to act as an inhibitory receptor upon ligand induced tyrosine phosphorylation by recruiting cytoplasmic phosphatase(s) via their SH2 domain(s) that block signal transduction through dephosphorylation of signaling molecules (PubMed:11284738, PubMed:12163025). Involved in negative regulation of B-cell antigen receptor signaling. The inhibition of B cell activation is dependent on PTPN6/SHP-1 (By similarity). In association with CD24 may be involved in the selective suppression of the immune response to danger-associated molecular patterns (DAMPs) such as HMGB1, HSP70 and HSP90 (By similarity). In association with CD24 may regulate the immune repsonse of natural killer (NK) cells (PubMed:25450598). Plays a role in the control of autoimmunity (By similarity). During initiation of adaptive immune responses by CD8-alpha(+) dendritic cells inhibits cross-presentation by impairing the formation of MHC class I-peptide complexes. The function seems to implicate recruitment of PTPN6/SHP-1, which dephosphorylates NCF1 of the NADPH oxidase complex consequently promoting phagosomal acidification (By similarity).
messages: Secreted

9606:LRIT2
gene id: 9606:LRIT2
uniprot id: A6NDA9
names: Subcellular Location Annotation
messages: Membrane

9606:FRAT1
gene id: 9606:FRAT1
uniprot id: Q92837
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the GSK-3-binding protein family.
messages: Binds DVL1. Binds GSK-3 and prevent GSK-3-dependent phosphorylation.
messages: Cytoplasm
messages: Phosphorylated.
messages: Positively regulates the Wnt signaling pathway by stabilizing beta-catenin through the association with GSK-3. May play a role in tumor progression and collaborate with PIM1 and MYC in lymphomagenesis.

9606:HPSE
gene id: 9606:HPSE
uniprot id: Q9Y251
names: Activity Regulation
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the glycosyl hydrolase 79 family.
messages: Endoglycosidase that cleaves heparan sulfate proteoglycans (HSPGs) into heparan sulfate side chains and core proteoglycans. Participates in extracellular matrix (ECM) degradation and remodeling. Selectively cleaves the linkage between a glucuronic acid unit and an N-sulfo glucosamine unit carrying either a 3-O-sulfo or a 6-O-sulfo group. Can also cleave the linkage between a glucuronic acid unit and an N-sulfo glucosamine unit carrying a 2-O-sulfo group, but not linkages between a glucuronic acid unit and a 2-O-sulfated iduronic acid moiety. It is essentially inactive at neutral pH but becomes active under acidic conditions such as during tumor invasion and in inflammatory processes. Facilitates cell migration associated with metastasis, wound healing and inflammation. Enhances shedding of syndecans, and increases endothelial invasion and angiogenesis in myelomas. Acts as procoagulant by increasing the generation of activation factor X in the presence of tissue factor and activation factor VII. Increases cell adhesion to the extracellular matrix (ECM), independent of its enzymatic activity. Induces AKT1/PKB phosphorylation via lipid rafts increasing cell mobility and invasion. Heparin increases this AKT1/PKB activation. Regulates osteogenesis. Enhances angiogenesis through up-regulation of SRC-mediated activation of VEGF. Implicated in hair follicle inner root sheath differentiation and hair homeostasis.
messages: Escapes proteolytic cleavage, devoid of HS degradation activity.
messages: Heterodimer; heterodimer formation between the 8 kDa and the 50 kDa subunits is required for enzyme activity. Interacts with TF; the interaction, inhibited by heparin, enhances the generation of activated factor X and activates coagulation. Interacts with HRG; the interaction is enhanced at acidic pH, partially inhibits binding of HPSE to cell surface receptors and modulates its enzymatic activity. Interacts with SDC1; the interaction enhances the shedding of SDC1. Interacts with HPSE2.
messages: Highly expressed in placenta and spleen and weakly expressed in lymph node, thymus, peripheral blood leukocytes, bone marrow, endothelial cells, fetal liver and tumor tissues. Also expressed in hair follicles, specifically in both Henle's and Huxley's layers of inner the root sheath (IRS) at anagen phase.
messages: Inhibited by EDTA, laminarin sulfate and, to a lower extent, by heparin and sulfamin and activated by calcium and magnesium.
messages: Lysosome membrane
messages: N-glycosylated. Glycosylation of the 50 kDa subunit appears to be essential for its solubility.
messages: Nucleus
messages: Proteolytically processed. The cleavage of the 65 kDa form leads to the generation of a linker peptide, and 8 kDa and 50 kDa products. The active form, the 8/50 kDa heterodimer, is resistant to degradation. Complete removal of the linker peptide appears to be a prerequisite to the complete activation of the enzyme.
messages: Secreted

9606:SATB2
gene id: 9606:SATB2
uniprot id: B3KPQ9
uniprot id: Q59FT3
uniprot id: Q9UPW6
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: A chromosomal aberration involving SATB2 is found in a patient with classical features of Toriello-Carey syndrome. Translocation t(2;14)(q33;q22).
messages: Belongs to the CUT homeobox family.
messages: Binds to DNA, at nuclear matrix- or scaffold-associated regions. Thought to recognize the sugar-phosphate structure of double-stranded DNA. Transcription factor controlling nuclear gene expression, by binding to matrix attachment regions (MARs) of DNA and inducing a local chromatin-loop remodeling. Acts as a docking site for several chromatin remodeling enzymes and also by recruiting corepressors (HDACs) or coactivators (HATs) directly to promoters and enhancers. Required for the initiation of the upper-layer neurons (UL1) specific genetic program and for the inactivation of deep-layer neurons (DL) and UL2 specific genes, probably by modulating BCL11B expression. Repressor of Ctip2 and regulatory determinant of corticocortical connections in the developing cerebral cortex. May play an important role in palate formation. Acts as a molecular node in a transcriptional network regulating skeletal development and osteoblast differentiation.
messages: Chromosomal aberrations involving SATB2 are found in isolated cleft palate. Translocation t(2;7); translocation t(2;11).
messages: High expression in adult brain, moderate expression in fetal brain, and weak expression in adult liver, kidney, and spinal cord and in select brain regions, including amygdala, corpus callosum, caudate nucleus, and hippocampus.
messages: Interacts with ATF4 and RUNX2; resulting in enhanced DNA binding and transactivation by these transcription factors (By similarity). Interacts with PIAS1.
messages: Nucleus
messages: Nucleus matrix
messages: Sumoylated by PIAS1. Sumoylation promotes nuclear localization, but represses transcription factor activity.
messages: The disease may be caused by variants affecting the gene represented in this entry.

9606:MYO5B
gene id: 9606:MYO5B
uniprot id: Q7Z7A5
uniprot id: Q9ULV0
names: Caution
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.
messages: Component of the CART complex, at least composed of ACTN4, HGS/HRS, MYO5B and TRIM3. Interacts with RAB11FIP2, RAB11A, and RAB8A. Found in a complex with CFTR and RAB11A. Interacts with NPC1L1; (PubMed:19542231). Interacts with LIMA1 (PubMed:29880681).
messages: Cytoplasm
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: May be involved in vesicular trafficking via its association with the CART complex. The CART complex is necessary for efficient transferrin receptor recycling but not for EGFR degradation. Required in a complex with RAB11A and RAB11FIP2 for the transport of NPC1L1 to the plasma membrane. Together with RAB11A participates in CFTR trafficking to the plasma membrane and TF (transferrin) recycling in nonpolarized cells. Together with RAB11A and RAB8A participates in epithelial cell polarization. Together with RAB25 regulates transcytosis. Required for proper localization of bile salt export pump ABCB11 at the apical/canalicular plasma membrane of hepatocytes (PubMed:34816459).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:RAG1
gene id: 9606:RAG1
uniprot id: P15918
names: Cofactor
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Autoubiquitinated in the presence of CDC34/UBCH3.
messages: Belongs to the RAG1 family.
messages: Binds 1 divalent metal cation per subunit. Mg(2+) or Mn(2+).
messages: Catalytic component of the RAG complex, a multiprotein complex that mediates the DNA cleavage phase during V(D)J recombination. V(D)J recombination assembles a diverse repertoire of immunoglobulin and T-cell receptor genes in developing B and T-lymphocytes through rearrangement of different V (variable), in some cases D (diversity), and J (joining) gene segments. In the RAG complex, RAG1 mediates the DNA-binding to the conserved recombination signal sequences (RSS) and catalyzes the DNA cleavage activities by introducing a double-strand break between the RSS and the adjacent coding segment. RAG2 is not a catalytic component but is required for all known catalytic activities. DNA cleavage occurs in 2 steps: a first nick is introduced in the top strand immediately upstream of the heptamer, generating a 3'-hydroxyl group that can attack the phosphodiester bond on the opposite strand in a direct transesterification reaction, thereby creating 4 DNA ends: 2 hairpin coding ends and 2 blunt, 5'-phosphorylated ends. The chromatin structure plays an essential role in the V(D)J recombination reactions and the presence of histone H3 trimethylated at 'Lys-4' (H3K4me3) stimulates both the nicking and haipinning steps. The RAG complex also plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and monospecific recognition by the B-cell antigen receptor (BCR) expressed on individual B-lymphocytes. The introduction of DNA breaks by the RAG complex on one immunoglobulin allele induces ATM-dependent repositioning of the other allele to pericentromeric heterochromatin, preventing accessibility to the RAG complex and recombination of the second allele. In addition to its endonuclease activity, RAG1 also acts as an E3 ubiquitin-protein ligase that mediates monoubiquitination of histone H3. Histone H3 monoubiquitination is required for the joining step of V(D)J recombination. Mediates polyubiquitinat…
messages: Homodimer. Component of the RAG complex composed of core components RAG1 and RAG2, and associated component HMGB1 or HMGB2. Interacts with DCAF1, leading to recruitment of the CUL4A-RBX1-DDB1-DCAF1/VPRBP complex to ubiquitinate proteins and limit error-prone repair during V(D)J recombination (By similarity).
messages: Maturing lymphoid cells.
messages: Nucleus
messages: The NBD (nonamer binding) DNA-binding domain mediates the specific binding to the nonamer RSS motif by forming a tightly interwoven homodimer that binds and synapses 2 nonamer elements, with each NBD making contact with both DNA molecules. Each RSS is composed of well-conserved heptamer (consensus 5'-CACAGTG-3') and nonamer (consensus 5'-ACAAAAACC-3') sequences separated by a spacer of either 12 bp or 23 bp.
messages: The RING-type zinc finger mediates the E3 ubiquitin-protein ligase activity.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:H2AC12
gene id: 9606:H2AC12
uniprot id: A3KPC7
uniprot id: Q96KK5
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the histone H2A family.
messages: Chromosome
messages: Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
messages: Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.
messages: Deiminated on Arg-4 in granulocytes upon calcium entry.
messages: Glutamine methylation at Gln-105 (H2AQ104me) by FBL is specifically dedicated to polymerase I. It is present at 35S ribosomal DNA locus and impairs binding of the FACT complex (PubMed:24352239).
messages: Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.
messages: Monoubiquitination of Lys-120 (H2AK119Ub) by RING1, TRIM37 and RNF2/RING2 complex gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. It is involved in the initiation of both imprinted and random X inactivation. Ubiquitinated H2A is enriched in inactive X chromosome chromatin. Ubiquitination of H2A functions downstream of methylation of 'Lys-27' of histone H3 (H3K27me). H2AK119Ub by RNF2/RING2 can also be induced by ultraviolet and may be involved in DNA repair. Monoubiquitination of Lys-120 (H2AK119Ub) by TRIM37 may promote transformation of cells in a number of breast cancers (PubMed:25470042). Following DNA double-strand breaks (DSBs), it is ubiquitinated through 'Lys-63' linkage of ubiquitin moieties by the E2 ligase UBE2N and the E3 ligases RNF8 and RNF168, leading to the recruitment of repair proteins to sites of DNA damage. Ubiquitination at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) in response to DNA damage is initiated by RNF168 that mediates monoubiquitination at these 2 sites, and 'Lys-63'-linked ubiquitin are then conjugated to monoubiquitin; RNF8 is able to extend 'Lys-63'-linked ubiquitin chains in vitro. Deubiquitinated by USP51 at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) after damaged DNA is repaired (PubMed:27083998). H2AK119Ub and ionizing radiation-induced 'Lys-63'-linked ubiquitination (H2AK13Ub and H2AK15Ub) are distinct events.
messages: Nucleus
messages: Phosphorylation on Ser-2 (H2AS1ph) is enhanced during mitosis. Phosphorylation on Ser-2 by RPS6KA5/MSK1 directly represses transcription. Acetylation of H3 inhibits Ser-2 phosphorylation by RPS6KA5/MSK1. Phosphorylation at Thr-121 (H2AT120ph) by DCAF1 is present in the regulatory region of many tumor suppresor genes and down-regulates their transcription.
messages: Symmetric dimethylation on Arg-4 by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage.
messages: The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.

9606:PCDHB1
gene id: 9606:PCDHB1
uniprot id: Q9Y5F3
names: Function
names: Subcellular Location Annotation
messages: Cell membrane
messages: Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain.

9606:CCL2
gene id: 9606:CCL2
uniprot id: P13500
names: Function
names: Induction
names: PTM
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acts as a ligand for C-C chemokine receptor CCR2 (PubMed:9837883, PubMed:10587439, PubMed:10529171). Signals through binding and activation of CCR2 and induces a strong chemotactic response and mobilization of intracellular calcium ions (PubMed:9837883, PubMed:10587439). Exhibits a chemotactic activity for monocytes and basophils but not neutrophils or eosinophils (PubMed:8627182, PubMed:9792674, PubMed:8195247). May be involved in the recruitment of monocytes into the arterial wall during the disease process of atherosclerosis (PubMed:8107690).
messages: Belongs to the intercrine beta (chemokine CC) family.
messages: Expressed in the seminal plasma, endometrial fluid and follicular fluid (at protein level) (PubMed:23765988). Expressed in monocytes (PubMed:2513477).
messages: Genetic variations in CCL2 determine Mycobacterium tuberculosis susceptibility [MIM:607948].
messages: Monomer or homodimer; in equilibrium (PubMed:8898111, PubMed:9837883, PubMed:15033992, PubMed:8989326). Is tethered on endothelial cells by glycosaminoglycan (GAG) side chains of proteoglycans (PubMed:9792674). Interacts with TNFAIP6 (via Link domain).
messages: N-Glycosylated.
messages: Processing at the N-terminus can regulate receptor and target cell selectivity (PubMed:8627182). Deletion of the N-terminal residue converts it from an activator of basophil to an eosinophil chemoattractant (PubMed:8627182).
messages: Secreted
messages: Up-regulated upon hypertonic conditions (PubMed:23233732). In pancreatic islets, secretion is stimulated by IL1B (PubMed:23955712).

9606:PKD2
gene id: 9606:PKD2
uniprot id: Q13563
names: Activity Regulation
names: Disease Annotation
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Basolateral cell membrane
messages: Belongs to the polycystin family.
messages: Cell membrane
messages: Channel activity is regulated by phosphorylation (PubMed:16551655, PubMed:20881056, PubMed:26269590). Channel activity is regulated by intracellular Ca(2+) (PubMed:11854751).
messages: Component of a heteromeric calcium-permeable ion channel formed by PKD1 and PKD2 that is activated by interaction between PKD1 and a Wnt family member, such as WNT3A and WNT9B (PubMed:27214281). Can also form a functional, homotetrameric ion channel (PubMed:29899465). Functions as a cation channel involved in fluid-flow mechanosensation by the primary cilium in renal epithelium (PubMed:18695040). Functions as outward-rectifying K(+) channel, but is also permeable to Ca(2+), and to a much lesser degree also to Na(+) (PubMed:11854751, PubMed:15692563, PubMed:27071085, PubMed:27991905). May contribute to the release of Ca(2+) stores from the endoplasmic reticulum (PubMed:11854751, PubMed:20881056). Together with TRPV4, forms mechano- and thermosensitive channels in cilium (PubMed:18695040). PKD1 and PKD2 may function through a common signaling pathway that is necessary to maintain the normal, differentiated state of renal tubule cells. Acts as a regulator of cilium length, together with PKD1. The dynamic control of cilium length is essential in the regulation of mechanotransductive signaling. The cilium length response creates a negative feedback loop whereby fluid shear-mediated deflection of the primary cilium, which decreases intracellular cAMP, leads to cilium shortening and thus decreases flow-induced signaling. Also involved in left-right axis specification via its role in sensing nodal flow; forms a complex with PKD1L1 in cilia to facilitate flow detection in left-right patterning. Detection of asymmetric nodal flow gives rise to a Ca(2+) signal that is required for normal, asymmetric expression of genes involved in the specification of body left-right laterality (By similarity).
messages: Cytoplasmic vesicle membrane
messages: Detected in fetal and adult kidney (PubMed:10770959). Detected at the thick ascending limb of the loop of Henle, at distal tubules, including the distal convoluted tubule and cortical collecting tubules, with weak staining of the collecting duct (PubMed:10770959). Detected on placenta syncytiotrophoblasts (at protein level) (PubMed:26269590). Strongly expressed in ovary, fetal and adult kidney, testis, and small intestine. Not detected in peripheral leukocytes.
messages: Endoplasmic reticulum membrane
messages: Golgi apparatus
messages: Homotetramer (PubMed:20881056, PubMed:27768895, PubMed:27991905, PubMed:28092368, PubMed:29899465). Heterotetramer with PKD1, giving rise to a complex formed by one PKD1 chain and three PKD2 chains (PubMed:20881056, PubMed:19556541, PubMed:27214281, PubMed:30093605). Interaction with PKD1 is required for ciliary localization (By similarity) Isoform 1 interacts with PKD1 while isoform 3 does not (By similarity). Interacts with PKD1L1. Interacts with CD2AP (PubMed:10913159). Interacts with HAX1 (PubMed:10760273). Interacts with NEK8 (By similarity). Part of a complex containing AKAP5, ADCY5, ADCY6 and PDE4C (By similarity). Interacts (via C-terminus) with TRPV4 (via C-terminus) (PubMed:18695040). Interacts (via C-terminal acidic region) with PACS1 and PACS2; these interactions retain the protein in the endoplasmic reticulum and prevent trafficking to the cell membrane (PubMed:15692563). Interacts with TMEM33 (By similarity).
messages: Minor isoform.
messages: N-glycosylated. The four subunits in a tetramer probably differ in the extent of glycosylation; simultaneous glycosylation of all experimentally validated sites would probably create steric hindrance. Thus, glycosylation at Asn-305 is not compatible with glycosylation at Asn-328; only one of these two residues is glycosylated at a given time.
messages: Phosphorylated. Phosphorylation is important for protein function; a mutant that lacks the N-terminal phosphorylation sites cannot complement a zebrafish pkd2-deficient mutant (PubMed:16551655). PKD-mediated phosphorylation at the C-terminus regulates its function in the release of Ca(2+) stores from the endoplasmic reticulum (PubMed:20881056). PKA-mediated phosphorylation at a C-terminal site strongly increases the open probability of the channel, but does not increase single channel conductance (PubMed:26269590).
messages: The C-terminal coiled-coil domain is involved in oligomerization and the interaction with PKD1 (PubMed:18694932, PubMed:19556541). The isolated coiled-coil domain forms a homotrimer in vitro; the homotrimer interacts with a single PKD1 chain (PubMed:19556541). The coiled-coil domain binds calcium and undergoes a calcium-induced conformation change (in vitro) (PubMed:18694932).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The mechanisms that govern channel opening are complex and still under debate; heterologous expression of PKD2 by itself or together with PKD1 gives rise to very low or undetectable spontaneous ion channel activity, in spite of its presence at the cell membrane.
messages: cilium membrane

9606:SIDT2
gene id: 9606:SIDT2
uniprot id: Q8NBJ9
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the SID1 family.
messages: Cell membrane
messages: Glycosylated.
messages: Interacts with adapter protein complex 1 (AP-1) and AP-2, but not AP-3 and AP-4 (By similarity). Interacts with LAMP2 (PubMed:27046251).
messages: Lysosome membrane
messages: Mediates the translocation of RNA and DNA across the lysosomal membrane during RNA and DNA autophagy (RDA), a process in which RNA or DNA is directly imported into lysosomes in an ATP-dependent manner, and degraded (PubMed:27046251, PubMed:27846365). Involved in the uptake of single-stranded oligonucleotides by living cells, a process called gymnosis (PubMed:28277980). In vitro, mediates the uptake of linear DNA more efficiently than that of circular DNA, but exhibits similar uptake efficacy toward RNA and DNA. Binds long double-stranded RNA (dsRNA) (500 - 700 base pairs), but not dsRNA shorter than 100 bp (By similarity).

9606:OR12D2
gene id: 9606:OR12D2
uniprot id: A0A126GV87
uniprot id: P58182
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Membrane
messages: Odorant receptor.

9606:CDKN2D
gene id: 9606:CDKN2D
uniprot id: P55273
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the CDKN2 cyclin-dependent kinase inhibitor family.
messages: Cytoplasm
messages: Interacts strongly with CDK4 and CDK6 and inhibits them.
messages: Interacts with CDK6.
messages: Nucleus

9606:MPEG1
gene id: 9606:MPEG1
uniprot id: Q2M385
names: Activity Regulation
names: Disease Annotation
names: Domain
names: Function
names: Induction
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the MPEG1 family.
messages: By wounding; increased levels are observed in hematopoietic cells 48 hours after wounding (PubMed:30609079). Following wounding, repressed by infection with S.aureus (PubMed:30609079). Isoform 1: By lipopolysaccharide and TNF (PubMed:28705375). Isoform 2: By lipopolysaccharide and TNF (PubMed:28705375).
messages: Cytoplasmic vesicle membrane
messages: Expressed constitutively in a variety of cell types including macrophages, natural killer cells, neutrophils, keratinocytes and monocytes (PubMed:26402460, PubMed:28705375, PubMed:7888681). In skin, expressed in both hematopoietic and non-hematopoietic cells with expression detected in a variety of cell types including keratinocytes, fibroblasts and endothelial cells (PubMed:30609079).
messages: Forms arc- and ring-shaped pre-pores on top of the membrane at neutral to slightly acidic pH conditions and converts to pores upon acidification (PubMed:31537793). Undergoes transition from the pre-pore to the pore in a processive clockwise hand-over-hand process (By similarity). In the pore state, 2 alpha-helical regions refold into transmembrane hairpins (TMH1 and TMH2) in each protomer that form in the ensemble complex giant beta-barrel transmembrane pores (PubMed:31537793).
messages: Homooligomer (PubMed:31537793). Predominantly forms a homooligomeric arc-shaped pore complex instead of complete rings of 16 subunits (By similarity).
messages: Lacks the C-terminal transmembrane domain.
messages: Monoubiquitinated in response to bacterial infection; ubiquitination is required for vesicular localization and antibacterial activity and can be blocked by bacterial cell cycle inhibiting factor (cif) (By similarity).
messages: Pore-forming protein involved in both innate and adaptive immunity (PubMed:23753625, PubMed:26402460, PubMed:28422754, PubMed:30609079, PubMed:31537793, PubMed:33224153). Plays a central role in antigen cross-presentation in dendritic cells by forming a pore in antigen-containing compartments, thereby promoting delivery of antigens for cross-presentation (By similarity). Also involved in innate immune response following bacterial infection; shows antibacterial activity against a wide spectrum of Gram-positive, Gram-negative and acid-fast bacteria (PubMed:23753625, PubMed:26402460, PubMed:28422754, PubMed:30609079, PubMed:33224153). Reduces the viability of the intracytosolic pathogen L.monocytogenes by inhibiting acidification of the phagocytic vacuole of host cells which restricts bacterial translocation from the vacuole to the cytosol (By similarity). Required for the antibacterial activity of reactive oxygen species and nitric oxide (By similarity).
messages: Pore-forming protein that plays a central role in antigen cross-presentation in dendritic cells by mediating delivery of antigens for cross-presentation (By similarity). Dendritic cells bridge innate and adaptive immunity by capturing exogenous antigens on MHC class-I molecules and presenting them to naive CD8(+) T-cells (By similarity). Acts by forming a pore in antigen-containing compartments, promoting the release of antigens into the cytosol, enabling generation of MHCI:peptide complexes and T-cell priming (By similarity).
messages: Proteolytically processed in two steps to generate the Macrophage-expressed gene 1 protein, processed form: cleaved by trypsin in proximity of the helical transmembrane domain releases the ectodomain into the lysosomal lumen to orient the pore-forming domain toward the endogenous membranes, and processed by the asparagine endopeptidase (LGMN).
messages: Secreted
messages: The MACPF domain includes the central machinery of pore formation: acidification causes a significant structural rearrangement, leading to oligomerization and deployment of the transmembrane beta-strands (named TMH1 and TMH2) that enter the membrane as amphipathic beta-hairpins.
messages: The P2 region contains beta-hairpins to interact with target membranes.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: phagosome membrane

9606:SOWAHA
gene id: 9606:SOWAHA
uniprot id: Q2M3V2
names: Similarity
messages: Belongs to the SOWAH family.

9606:SLC25A53
gene id: 9606:SLC25A53
uniprot id: Q5H9E4
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the mitochondrial carrier (TC 2.A.29) family.
messages: Mitochondrion inner membrane

9606:NUAK2
gene id: 9606:NUAK2
uniprot id: Q9H093
names: Activity Regulation
names: Disease Annotation
names: Function
names: PTM
names: Similarity
messages: Activated by phosphorylation on Thr-208.
messages: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.
messages: Phosphorylated at Thr-208 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39 (PubMed:14976552). Autophosphorylation is also possible at Thr-208 (PubMed:32845958).
messages: Stress-activated kinase involved in tolerance to glucose starvation. Induces cell-cell detachment by increasing F-actin conversion to G-actin. Expression is induced by CD95 or TNF-alpha, via NF-kappa-B. Protects cells from CD95-mediated apoptosis and is required for the increased motility and invasiveness of CD95-activated tumor cells. Phosphorylates LATS1 and LATS2. Plays a key role in neural tube closure during embryonic development through LATS2 phosphorylation and regulation of the nuclear localization of YAP1 a critical downstream regulatory target in the Hippo signaling pathway (PubMed:32845958).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:SLX4
gene id: 9606:SLX4
uniprot id: Q8IY92
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the SLX4 family.
messages: Forms a heterodimer with SLX1A/GIYD1. Interacts with ERCC4/XPF; catalytic subunit of the ERCC4-ERCC1 endonuclease. Interacts with MUS81; catalytic subunit of the MUS81-EME1 endonuclease. Interacts with MSH2; component of the MSH2-MSH3 mismatch repair complex. Interacts with TERF2-TERF2IP. Interacts with PLK1 and SLX4IP.
messages: Nucleus
messages: Regulatory subunit that interacts with and increases the activity of different structure-specific endonucleases. Has several distinct roles in protecting genome stability by resolving diverse forms of deleterious DNA structures originating from replication and recombination intermediates and from DNA damage. Component of the SLX1-SLX4 structure-specific endonuclease that resolves DNA secondary structures generated during DNA repair and recombination. Has endonuclease activity towards branched DNA substrates, introducing single-strand cuts in duplex DNA close to junctions with ss-DNA. Has a preference for 5'-flap structures, and promotes symmetrical cleavage of static and migrating Holliday junctions (HJs). Resolves HJs by generating two pairs of ligatable, nicked duplex products. Interacts with the structure-specific ERCC4-ERCC1 endonuclease and promotes the cleavage of bubble structures. Interacts with the structure-specific MUS81-EME1 endonuclease and promotes the cleavage of 3'-flap and replication fork-like structures. SLX4 is required for recovery from alkylation-induced DNA damage and is involved in the resolution of DNA double-strand breaks.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:FAM167A
gene id: 9606:FAM167A
uniprot id: Q96KS9
names: Similarity
names: Tissue Specificity
messages: Belongs to the FAM167 (SEC) family.
messages: Expressed in skin, including primary keratinocytes, spleen, kidney, leukocytes, testis, lung, small intestine and prostate.

9606:UMODL1
gene id: 9606:UMODL1
uniprot id: Q5DID0
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Cell membrane
messages: Cytoplasm
messages: Isoform 4 is expressed at low level in kidney, testis and fetal thymus. Isoform 3 is expressed at low level in prostate, testis and fetal thymus.

9606:EED
gene id: 9606:EED
uniprot id: O75530
names: Caution
names: Developmental Stage
names: Disease Annotation
names: Domain
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) May interact with the MA protein of HIV-1.
messages: Belongs to the WD repeat ESC family.
messages: Chromosome
messages: Component of the PRC2/EED-EZH2 complex, which includes EED, EZH2, SUZ12, RBBP4 and RBBP7 and possibly AEBP2. The minimum components required for methyltransferase activity of the PRC2/EED-EZH2 complex are EED, EZH2 and SUZ12. Component of the PRC2/EED-EZH1 complex, which includes EED, EZH1, SUZ12, RBBP4 and AEBP2. The PRC2 complex may also interact with DNMT1, DNMT3A, DNMT3B and PHF1 via the EZH2 subunit and with SIRT1 via the SUZ12 subunit. Interacts with HDAC, HDAC2, histone H1 and YY1. May interact with ITGA4, ITGAE and ITGB7. Interacts with CDYL. Interacts with BMAL1. Interacts with KMT2A/MLL1 (By similarity).
messages: Expressed in brain, colon, heart, kidney, liver, lung, muscle, ovary, peripheral blood leukocytes, pancreas, placenta, prostate, spleen, small intestine, testis, thymus and uterus. Appears to be overexpressed in breast and colon cancer.
messages: Expression is induced by E2F1, E2F2 and E2F3.
messages: Expression peaks at the G1/S phase boundary.
messages: Methylated. Binding to histone H1 'Lys-26' promotes mono-, di-, and trimethylation of internal lysines.
messages: Nucleus
messages: Polycomb group (PcG) protein. Component of the PRC2/EED-EZH2 complex, which methylates 'Lys-9' and 'Lys-27' of histone H3, leading to transcriptional repression of the affected target gene. Also recognizes 'Lys-26' trimethylated histone H1 with the effect of inhibiting PRC2 complex methyltransferase activity on nucleosomal histone H3 'Lys-27', whereas H3 'Lys-27' recognition has the opposite effect, enabling the propagation of this repressive mark. The PRC2/EED-EZH2 complex may also serve as a recruiting platform for DNA methyltransferases, thereby linking two epigenetic repression systems. Genes repressed by the PRC2/EED-EZH2 complex include HOXC8, HOXA9, MYT1 and CDKN2A.
messages: The WD repeat domain mediates recognition of trimethylated histone peptides at the consensus sequence Ala-Arg-Lys-Ser. This is achieved through an aromatic cage encircling the methyllysine, and involving Phe-97, Tyr-148 and Tyr-365.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Two variants of the PRC2 complex have been described, termed PRC3 and PRC4. Each of the three complexes may include a different complement of EED isoforms, although the precise sequences of the isoforms in each complex have not been determined. The PRC2 and PRC4 complexes may also methylate 'Lys-26' of histone H1 in addition to 'Lys-27' of histone H3 (PubMed:15099518, PubMed:15684044), although other studies have demonstrated no methylation of 'Lys-26' of histone H1 by PRC2 (PubMed:16431907).

9606:METTL8
gene id: 9606:METTL8
uniprot id: A8K7U3
uniprot id: B3KW44
uniprot id: B4DLT0
uniprot id: Q9H825
names: Caution
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: A publication reported some nucleolar localization (PubMed:32199293). However, the protein used in this publication used a N-terminal tag, which possibly interferes with the mitochondrial targeting (PubMed:34774131).
messages: Belongs to the methyltransferase superfamily. METL family.
messages: Interacts with EP300.
messages: Mitochondrial S-adenosyl-L-methionine-dependent methyltransferase that mediates N(3)-methylcytidine modification of residue 32 of the tRNA anticodon loop of mitochondrial tRNA(Ser)(UCN) and tRNA(Thr) (PubMed:34774131, PubMed:35017528). N(3)-methylcytidine methylation modification regulates mitochondrial translation efficiency and is required for activity of the respiratory chain (PubMed:34774131, PubMed:35017528). N(3)-methylcytidine methylation of mitochondrial tRNA(Ser)(UCN) requires the formation of N(6)-dimethylallyladenosine(37) (i6A37) by TRIT1 as prerequisite (PubMed:34774131, PubMed:35017528). May also mediate N(3)-methylcytidine modification of mRNAs (PubMed:28655767). The existence of N(3)-methylcytidine modification on mRNAs is however unclear, and additional evidences are required to confirm the role of the N(3)-methylcytidine-specific mRNA methyltransferase activity of METTL8 in vivo (PubMed:34774131, PubMed:33313824).
messages: Mitochondrion
messages: S-adenosyl-L-methionine-dependent methyltransferase.
messages: The existence of N(3)-methylcytidine on mRNA is unclear (PubMed:34774131, PubMed:33313824). A report was unable to detect N(3)-methylcytidine formation in mammalian mRNAs using a nucleotide-resolution sequencing approach (PubMed:33313824). According to another publication, METTL8 has no activity on mRNAs and specifically methylates mitochondrial tRNAs (PubMed:34774131).

9606:MMP24
gene id: 9606:MMP24
uniprot id: Q86VV6
uniprot id: Q9Y5R2
names: Cofactor
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the peptidase M10A family.
messages: Binds 1 zinc ion per subunit.
messages: Binds 2 Zn(2+) ions per subunit.
messages: Can bind about 5 Ca(2+) ions per subunit.
messages: Cell membrane
messages: Cleaved by a furin endopeptidase in the trans-Golgi network.
messages: Interacts (via PDZ-binding motif) with APBA3 (via PDZ domain). Interacts with GRIP1 and GRIP2 (By similarity).
messages: Metalloprotease that mediates cleavage of N-cadherin (CDH2) and acts as a regulator of neuro-immune interactions and neural stem cell quiescence. Involved in cell-cell interactions between nociceptive neurites and mast cells, possibly by mediating cleavage of CDH2, thereby acting as a mediator of peripheral thermal nociception and inflammatory hyperalgesia. Key regulator of neural stem cells quiescence by mediating cleavage of CDH2, affecting CDH2-mediated anchorage of neural stem cells to ependymocytes in the adult subependymal zone, leading to modulate their quiescence. May play a role in axonal growth. Able to activate progelatinase A. May also be a proteoglycanase involved in degradation of proteoglycans, such as dermatan sulfate and chondroitin sulfate proteoglycans. Cleaves partially fibronectin, but not collagen type I, nor laminin (By similarity).
messages: Predominantly expressed in brain, kidney, pancreas and lung. Overexpressed in a series of brain tumors, including astrocytomas and glioblastomas.
messages: The PDZ-binding motif (also named EWV motif) is required for interaction with PDZ domains of APBA3 and recycling through the trans-Golgi network.
messages: The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.
messages: extracellular matrix
messages: trans-Golgi network membrane

9606:ARHGEF2
gene id: 9606:ARHGEF2
uniprot id: Q92974
names: Disease Annotation
names: Domain
names: Function
names: Induction
names: PTM
names: Sequence Caution
names: Subcellular Location Annotation
names: Subunit
messages: Activates Rho-GTPases by promoting the exchange of GDP for GTP. May be involved in epithelial barrier permeability, cell motility and polarization, dendritic spine morphology, antigen presentation, leukemic cell differentiation, cell cycle regulation, innate immune response, and cancer. Binds Rac-GTPases, but does not seem to promote nucleotide exchange activity toward Rac-GTPases, which was uniquely reported in PubMed:9857026. May stimulate instead the cortical activity of Rac. Inactive toward CDC42, TC10, or Ras-GTPases. Forms an intracellular sensing system along with NOD1 for the detection of microbial effectors during cell invasion by pathogens. Required for RHOA and RIP2 dependent NF-kappaB signaling pathways activation upon S.flexneri cell invasion. Involved not only in sensing peptidoglycan (PGN)-derived muropeptides through NOD1 that is independent of its GEF activity, but also in the activation of NF-kappaB by Shigella effector proteins (IpgB2 and OspB) which requires its GEF activity and the activation of RhoA. Involved in innate immune signaling transduction pathway promoting cytokine IL6/interleukin-6 and TNF-alpha secretion in macrophage upon stimulation by bacterial peptidoglycans; acts as a signaling intermediate between NOD2 receptor and RIPK2 kinase. Contributes to the tyrosine phosphorylation of RIPK2 through Src tyrosine kinase leading to NF-kappaB activation by NOD2. Overexpression activates Rho-, but not Rac-GTPases, and increases paracellular permeability (By similarity). Involved in neuronal progenitor cell division and differentiation (PubMed:28453519). Involved in the migration of precerebellar neurons (By similarity).
messages: Cytoplasm
messages: Cytoplasmic vesicle
messages: Found in a complex composed at least of ARHGEF2, NOD2 and RIPK2. Interacts with RIPK2; the interaction mediates tyrosine phosphorylation of RIPK2 by Src kinase CSK. Interacts with RIPK1 and RIPK3. Interacts with YWHAZ/14-3-3 zeta; when phosphorylated at Ser-886. Interacts with the kinases PAK4, AURKA and MAPK1. Interacts with RHOA and RAC1. Interacts with NOD1. Interacts (via the N-terminal zinc finger) with CAPN6 (via domain II). Interacts with DYNLT1 (By similarity).
messages: Golgi apparatus
messages: Phosphorylation of Ser-886 by PAK1 induces binding to protein YWHAZ, promoting its relocation to microtubules and the inhibition of its activity. Phosphorylated by AURKA and CDK1 during mitosis, which negatively regulates its activity. Phosphorylation by MAPK1 or MAPK3 increases nucleotide exchange activity. Phosphorylation by PAK4 releases GEF-H1 from the microtubules. Phosphorylated on serine, threonine and tyrosine residues in a RIPK2-dependent manner.
messages: Sequence differs at a large extent from the sequence shown in the paper.
messages: The DH (DBL-homology) domain interacts with and promotes loading of GTP on RhoA. Promotes tyrosine phosphorylation of RIPK2.
messages: The PH domain has no affinity for phosphoinositides suggesting that it does not interact directly with membranes.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The phorbol-ester/DAG-type zinc-finger and the C-terminal coiled-coil domains (606-986) are both important for association with microtubules.
messages: Up-regulated by bacterial peptidoglycans stimulation, such as muramyl dipeptide and in biopsies from inflamed mucosal areas of Crohn's disease patients.
messages: cytoskeleton
messages: ruffle membrane
messages: spindle
messages: tight junction

9606:SFTA2
gene id: 9606:SFTA2
uniprot id: Q6UW10
names: Function
names: PTM
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Golgi apparatus
messages: N-glycosylated.
messages: Predominantly expressed in lung, where it is detected in type II pneumocytes in the alveolus, and in nonciliated epithelium in bronchioli (at protein level). Also detected at lower levels in cervix, esophagus, stomach, testis and kidney.
messages: Putative surfactant protein.
messages: Secreted
messages: secretory vesicle

9606:PRAG1
gene id: 9606:PRAG1
uniprot id: Q86YV5
names: Caution
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the protein kinase superfamily.
messages: Catalytically inactive protein kinase that acts as a scaffold protein. Functions as an effector of the small GTPase RND2, which stimulates RhoA activity and inhibits NGF-induced neurite outgrowth (By similarity). Promotes Src family kinase (SFK) signaling by regulating the subcellular localization of CSK, a negative regulator of these kinases, leading to the regulation of cell morphology and motility by a CSK-dependent mechanism (By similarity). Acts as a critical coactivator of Notch signaling (By similarity).
messages: Cytoplasm
messages: Despite of the presence of a putative ATP-binding motif, this protein does not bind ATP, suggesting that it has no protein kinase activity.
messages: Homodimer (PubMed:29079850). Dimerization leads to the catalytic activation of CSK (By similarity). Interacts (via C-terminus) with RND2 (By similarity). Interacts with CSK (via SH2 domain) in a Tyr-413 phosphorylation-dependent manner; this interaction potentiates kinase activity of CSK (By similarity). Interacts with PEAK1 (PubMed:29079850). Interacts with NOTCH1 intracellular domain (N1ICD) (By similarity). Forms a complex with N1ICD and MAML1, in a MAML1-dependent manner (By similarity).
messages: Nucleus
messages: Phosphorylated by CSK on Tyr-253, Tyr-365, and Tyr-413; Tyr-413 is a primary site of phosphorylation.
messages: The dimerization region encompasses helices both from the N- and C-terminal of the protein kinase domain.
messages: focal adhesion

9606:B4GALNT2
gene id: 9606:B4GALNT2
uniprot id: Q8NHY0
names: Disease Annotation
names: Function
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the glycosyltransferase 2 family.
messages: Golgi apparatus membrane
messages: Involved in the synthesis of the Sd(a) antigen (Sia-alpha2,3-[GalNAc-beta1,4]Gal-beta1,4-GlcNAc), a carbohydrate determinant expressed on erythrocytes, the colonic mucosa and other tissues. Transfers a beta-1,4-linked GalNAc to the galactose residue of an alpha-2,3-sialylated chain.
messages: The Sd(a) antigen on red blood cells defines the SID blood group system. There is considerable variability in the strength of antigen expression, ranging from ordinary Sd(a+) to strong Sd(a++) expression [MIM:615018]. Lack of Sd(a) antigen results in the Sd(a-) phenotype, due to genetic variants in B4GALNT2.
messages: The gene represented in this entry is involved in disease pathogenesis.
messages: Widely expressed. Highly expressed in colon and to a lesser extent in kidney, stomach, ileum and rectum.

9606:PKD1L1
gene id: 9606:PKD1L1
uniprot id: Q8TDX9
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the polycystin family.
messages: Component of a ciliary calcium channel that controls calcium concentration within primary cilia without affecting cytoplasmic calcium concentration. Forms a heterodimer with PKD2L1 in primary cilia and forms a calcium-permeant ciliary channel that regulates sonic hedgehog/SHH signaling and GLI2 transcription. Does not constitute the pore-forming subunit. Also involved in left/right axis specification downstream of nodal flow: forms a complex with PKD2 in cilia to facilitate flow detection in left/right patterning.
messages: Detected in testis and in fetal and adult heart.
messages: Heterodimer; heterodimerizes with PKD2 proteins to form a calcium channel. Interacts with PKD2L1; to form ciliary calcium channel. Interacts with PKD2.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: cilium membrane

9606:NUTM2F
gene id: 9606:NUTM2F
uniprot id: A1L443
names: Similarity
messages: Belongs to the NUT family.

9606:ARMC1
gene id: 9606:ARMC1
uniprot id: Q9NVT9
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Cytoplasm
messages: In association with mitochondrial contact site and cristae organizing system (MICOS) complex components and mitochondrial outer membrane sorting assembly machinery (SAM) complex components may regulate mitochondrial dynamics playing a role in determining mitochondrial length, distribution and motility.
messages: Interacts with mitochondrial contact site and cristae organizing system (MICOS) complex components IMMT/MIC60 and MICOS10/MIC10 (PubMed:31644573). Interacts with mitochondrial outer membrane sorting assembly machinery (SAM) complex components SAMM50 and MTX1 (PubMed:31644573).
messages: Mitochondrion
messages: Mitochondrion outer membrane

9606:TRIM71
gene id: 9606:TRIM71
uniprot id: Q2Q1W2
names: Biotechnology
names: Disease Annotation
names: Domain
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Autoubiquitinated.
messages: Belongs to the TRIM/RBCC family.
messages: E3 ubiquitin-protein ligase that cooperates with the microRNAs (miRNAs) machinery and promotes embryonic stem cells proliferation and maintenance (Probable). Binds to miRNAs and associates with AGO2, participating in post-transcriptional repression of transcripts such as CDKN1A (By similarity). In addition, participates in post-transcriptional mRNA repression in a miRNA independent mechanism (PubMed:23125361). Facilitates the G1-S transition to promote rapid embryonic stem cell self-renewal by repressing CDKN1A expression. Required to maintain proliferation and prevent premature differentiation of neural progenitor cells during early neural development: positively regulates FGF signaling by controlling the stability of SHCBP1 (By similarity). Specific regulator of miRNA biogenesis. Binds to miRNA MIR29A hairpin and postranscriptionally modulates MIR29A levels, which indirectly regulates TET proteins expression (PubMed:28431233).
messages: Interacts (via NHL repeats) with AGO2; the interaction increases in presence of RNA (PubMed:23125361). Interacts with HSP90AA1. Interacts (via NHL repeats) with MOV10, PABPC1, PUM1, PUM2, STAU2, XRN1 and XRN2 in an RNA-dependent manner (PubMed:23125361). Interacts with SHCBP1; leading to enhance its stability (By similarity).
messages: Negatively regulated by the microRNA (miRNA) let-7 which causes degradation of the mRNA encoding this protein. This requires a let-7 complementary site (LCS) in the 3'-UTR of the mRNA encoding this protein (PubMed:17890240, PubMed:24239284). Down-regulated by retinoic acid in Tera-2 cells (PubMed:15722555).
messages: P-body
messages: Promotes reprogramming of differentiated cells to an embryonic-like state designated iPS (induced pluripotent stem) cells. iPS cells exhibit the morphology and growth properties of ES cells and express ES cell marker genes. Inhibits translation of the prodifferentiation transcription factor EGR1 through binding to its mRNA and regulates a broad array of differentiation genes.
messages: Specifically expressed in testis.
messages: The NHL domain, containing the 6 NHL repeats, is necessary and sufficient to target RNA but not to repress mRNA. The minimal region needed to execute repression consists of the coiled coil domain and the Filamin repeat. The RING-type domain is dispensable for mRNA repression.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:CCN1
gene id: 9606:CCN1
uniprot id: O00622
uniprot id: Q6FI18
names: Caution
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the CCN family.
messages: Interaction with integrins is heparin- and cell-type-dependent and promotes cell adhesion. In skin fibroblasts it binds ITGA6/ITGB1, in endothelial cells, binds ITGAV/ITGB3 and in platelets, ITGA2B/ITGB3. Binds, in vitro, ITGAV/ITGB5.
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: Promotes cell proliferation, chemotaxis, angiogenesis and cell adhesion. Appears to play a role in wound healing by up-regulating, in skin fibroblasts, the expression of a number of genes involved in angiogenesis, inflammation and matrix remodeling including VEGA-A, VEGA-C, MMP1, MMP3, TIMP1, uPA, PAI-1 and integrins alpha-3 and alpha-5. CCN1-mediated gene regulation is dependent on heparin-binding. Down-regulates the expression of alpha-1 and alpha-2 subunits of collagen type-1. Promotes cell adhesion and adhesive signaling through integrin alpha-6/beta-1, cell migration through integrin alpha-v/beta-5 and cell proliferation through integrin alpha-v/beta-3.
messages: Secreted

9606:PALMD
gene id: 9606:PALMD
uniprot id: A0A0S2Z5E7
uniprot id: Q9NP74
names: PTM
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the paralemmin family.
messages: Contaminating sequence. Potential poly-A sequence.
messages: Cytoplasm
messages: Interacts with GLUL.
messages: Phosphorylated.
messages: Ubiquitous. Most abundant in cardiac and skeletal muscle.
messages: dendrite
messages: dendritic spine

9606:TMEM130
gene id: 9606:TMEM130
uniprot id: Q8N3G9
names: Subcellular Location Annotation
messages: Golgi apparatus membrane

9606:TUBA3D
gene id: 9606:TUBA3D
uniprot id: P0DPH8
uniprot id: Q1ZYQ1
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acetylation of alpha chains at Lys-40 is located inside the microtubule lumen. This modification has been correlated with increased microtubule stability, intracellular transport and ciliary assembly.
messages: Belongs to the tubulin family.
messages: Detyrosination is involved in metaphase plate congression by guiding chromosomes during mitosis: detyrosination promotes interaction with CENPE, promoting pole-proximal transport of chromosomes toward the equator (PubMed:25908662). Detyrosination increases microtubules-dependent mechanotransduction in dystrophic cardiac and skeletal muscle. In cardiomyocytes, detyrosinated microtubules are required to resist to contractile compression during contraction: detyrosination promotes association with desmin (DES) at force-generating sarcomeres, leading to buckled microtubules and mechanical resistance to contraction (By similarity).
messages: Dimer of alpha and beta chains. A typical microtubule is a hollow water-filled tube with an outer diameter of 25 nm and an inner diameter of 15 nM. Alpha-beta heterodimers associate head-to-tail to form protofilaments running lengthwise along the microtubule wall with the beta-tubulin subunit facing the microtubule plus end conferring a structural polarity. Microtubules usually have 13 protofilaments but different protofilament numbers can be found in some organisms and specialized cells.
messages: Expressed in the cornea, sclera, and peripheral blood (PubMed:29051577).
messages: Methylation of alpha chains at Lys-40 is found in mitotic microtubules and is required for normal mitosis and cytokinesis contributing to genomic stability.
messages: Nitration of Tyr-450 is irreversible and interferes with normal dynein intracellular distribution.
messages: Some glutamate residues at the C-terminus are monoglycylated but not polyglycylated due to the absence of functional TTLL10 in human. Monoglycylation is mainly limited to tubulin incorporated into cilia and flagella axonemes, which is required for their stability and maintenance. Flagella glycylation controls sperm motility. Both polyglutamylation and monoglycylation can coexist on the same protein on adjacent residues, and lowering glycylation levels increases polyglutamylation, and reciprocally.
messages: Some glutamate residues at the C-terminus are polyglutamylated, resulting in polyglutamate chains on the gamma-carboxyl group (PubMed:26875866). Polyglutamylation plays a key role in microtubule severing by spastin (SPAST). SPAST preferentially recognizes and acts on microtubules decorated with short polyglutamate tails: severing activity by SPAST increases as the number of glutamates per tubulin rises from one to eight, but decreases beyond this glutamylation threshold (PubMed:26875866). Glutamylation is also involved in cilia motility (By similarity).
messages: The MREC motif may be critical for tubulin autoregulation.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin.
messages: Tyrosination promotes microtubule interaction with CAP-Gly domain-containing proteins such as CLIP1, CLIP2 and DCTN1 (By similarity). Tyrosination regulates the initiation of dynein-dynactin motility via interaction with DCTN1, which brings the dynein-dynactin complex into contact with microtubules (PubMed:26972003). In neurons, tyrosinated tubulins mediate the initiation of retrograde vesicle transport (By similarity).
messages: Undergoes a tyrosination/detyrosination cycle, the cyclic removal and re-addition of a C-terminal tyrosine residue by the enzymes tubulin tyrosine carboxypeptidase (KIAA0895L/MATCAP, VASH1 or VASH2) and tubulin tyrosine ligase (TTL), respectively.
messages: cytoskeleton

9606:TUT4
gene id: 9606:TUT4
uniprot id: A0A0C4DFM7
uniprot id: Q5TAX3
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the DNA polymerase type-B-like family.
messages: Cytoplasm
messages: Cytoplasmic ribonucleoprotein granule
messages: Interacts with LIN28A in the presence of pre-let-7 RNA (PubMed:19703396, PubMed:22118463, PubMed:31036859). Interacts with T2BP (PubMed:16643855). Interacts with MOV10; the interaction is RNA-dependent (PubMed:30122351).
messages: Nucleus
messages: Uridylyltransferase that mediates the terminal uridylation of mRNAs with short (less than 25 nucleotides) poly(A) tails, hence facilitating global mRNA decay (PubMed:25480299, PubMed:31036859). Essential for both oocyte maturation and fertility. Through 3' terminal uridylation of mRNA, sculpts, with TUT7, the maternal transcriptome by eliminating transcripts during oocyte growth (By similarity). Involved in microRNA (miRNA)-induced gene silencing through uridylation of deadenylated miRNA targets. Also functions as an integral regulator of microRNA biogenesis using 3 different uridylation mechanisms (PubMed:25979828). Acts as a suppressor of miRNA biogenesis by mediating the terminal uridylation of some miRNA precursors, including that of let-7 (pre-let-7), miR107, miR-143 and miR-200c. Uridylated miRNAs are not processed by Dicer and undergo degradation. Degradation of pre-let-7 contributes to the maintenance of embryonic stem (ES) cell pluripotency (By similarity). Also catalyzes the 3' uridylation of miR-26A, a miRNA that targets IL6 transcript. This abrogates the silencing of IL6 transcript, hence promoting cytokine expression (PubMed:19703396). In the absence of LIN28A, TUT7 and TUT4 monouridylate group II pre-miRNAs, which includes most of pre-let7 members, that shapes an optimal 3' end overhang for efficient processing (PubMed:25979828). Adds oligo-U tails to truncated pre-miRNAS with a 5' overhang which may promote rapid degradation of non-functional pre-miRNA species (PubMed:25979828). May also suppress Toll-like receptor-induced NF-kappa-B activation via binding to T2BP (PubMed:16643855). Does not play a role in replication-dependent histone mRNA degradation (PubMed:18172165). Due to functional redundancy between TUT4 and TUT7, the identification of the specific role of each of these proteins is difficult (PubMed:25979828, PubMed:25480299, PubMed:16643855, PubMed:19703396, PubMed:18172165) (By similarity). TUT4 and TUT7 restrict retrotransposition of long i…
messages: Utilizes two multidomain functional modules during the switch from monouridylation to oligouridylation. The catalytic module (containing the 3 CCHC-type Zinc finger domains) is essential for both activities while the Lin28-interacting module (LIM) at the N-termail part is indispensable for oligouridylation.

9606:TANC2
gene id: 9606:TANC2
uniprot id: Q9HCD6
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the TANC family.
messages: Defects in TANC2 has been found in a patient with isolated coloboma, a defect of the eye characterized by the absence of ocular structures due to abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure). Isolated colobomas may be associated with an abnormally small eye (microphthalmia) or small cornea.
messages: Interacts with KIF1A; the interaction decreases in presence of calcium.
messages: Scaffolding protein in the dendritic spines which acts as immobile postsynaptic posts able to recruit KIF1A-driven dense core vesicles to dendritic spines.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: dendritic spine

9606:KCTD6
gene id: 9606:KCTD6
uniprot id: Q8NC69
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Highly expressed in cerebellum and brain. Expression is down-regulated in medulloblastoma.
messages: Homopentamer. Interacts with KCTD11; KCTD6 and KCTD11 may associate in pentameric assemblies. Interacts (via BTB domain) with CUL3; initially a 4:4 stoichiometry has been reported, however, electron microscopy revealed pentameric states with a five-pointed pinwheel shape. The interaction with CUL3 is indicative for a participation in a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex. Interacts with HDAC1; probably indirect as the interaction is requires the presence of KCTD11 (PubMed:21472142, PubMed:24307990, PubMed:25974686, PubMed:27152988). Interacts with USP21 (preferentially catalytic inactive form) (PubMed:27621083). Interacts with ANK1 isoform Mu17; detected in striated muscle (PubMed:22573887). Interacts with USP11 (PubMed:29293652).
messages: M line
messages: Probable substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex mediating the ubiquitination and subsequent proteasomal degradation of target proteins. Promotes the ubiquitination of HDAC1; the function seems to depend on KCTD11:KCTD6 oligomerization. Can function as antagonist of the Hedgehog pathway by affecting the nuclear transfer of transcription factor GLI1; the function probably occurs via HDAC1 down-regulation, keeping GLI1 acetylated and inactive. Inhibits cell growth and tumorigenicity of medulloblastoma (MDB) (PubMed:21472142). Involved in regulating protein levels of ANK1 isoform Mu17 probably implicating CUL3-dependent proteasomal degradation (PubMed:22573887).

9606:MRPL20
gene id: 9606:MRPL20
uniprot id: Q9BYC9
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the bacterial ribosomal protein bL20 family.
messages: Component of the mitochondrial large ribosomal subunit (mt-LSU) (PubMed:28892042, PubMed:25838379). Mature mammalian 55S mitochondrial ribosomes consist of a small (28S) and a large (39S) subunit. The 28S small subunit contains a 12S ribosomal RNA (12S mt-rRNA) and 30 different proteins. The 39S large subunit contains a 16S rRNA (16S mt-rRNA), a copy of mitochondrial valine transfer RNA (mt-tRNA(Val)), which plays an integral structural role, and 52 different proteins (PubMed:25278503, PubMed:25838379). Interacts with OXA1L (By similarity).
messages: Mitochondrion

9606:PRKACB
gene id: 9606:PRKACB
uniprot id: A0A087WVC4
uniprot id: B1APF9
uniprot id: B1APG3
uniprot id: B2RB89
uniprot id: B7ZA00
uniprot id: P22694
names: Activity Regulation
names: Disease Annotation
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: A number of inactive tetrameric holoenzymes are produced by the combination of homo- or heterodimers of the different regulatory subunits associated with two catalytic subunits. cAMP causes the dissociation of the inactive holoenzyme into a dimer of regulatory subunits bound to four cAMP and two free monomeric catalytic subunits (By similarity). Interacts with PRKAR1A and PRKAR2B (PubMed:33058759). The cAMP-dependent protein kinase catalytic subunit binds PJA2 (PubMed:21423175). Interacts with GPKOW (PubMed:21880142).
messages: Activated by cAMP.
messages: Asn-3 is partially deaminated to Asp giving rise to 2 major isoelectric variants, called CB and CA respectively.
messages: Belongs to the protein kinase superfamily.
messages: Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. cAMP subfamily.
messages: Cell membrane
messages: Cytoplasm
messages: Incomplete sequence.
messages: Isoform 1 is most abundant in the brain, with low level expression in kidney. Isoform 2 is predominantly expressed in thymus, spleen and kidney. Isoform 3 and isoform 4 are only expressed in the brain.
messages: Mediates cAMP-dependent signaling triggered by receptor binding to GPCRs (PubMed:12420224, PubMed:21423175, PubMed:31112131). PKA activation regulates diverse cellular processes such as cell proliferation, the cell cycle, differentiation and regulation of microtubule dynamics, chromatin condensation and decondensation, nuclear envelope disassembly and reassembly, as well as regulation of intracellular transport mechanisms and ion flux (PubMed:12420224, PubMed:21423175). Regulates the abundance of compartmentalized pools of its regulatory subunits through phosphorylation of PJA2 which binds and ubiquitinates these subunits, leading to their subsequent proteolysis (PubMed:12420224, PubMed:21423175). Phosphorylates GPKOW which regulates its ability to bind RNA (PubMed:21880142). Acts as a negative regulator of mTORC1 by mediating phosphorylation of RPTOR (PubMed:31112131).
messages: Membrane
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:RNF38
gene id: 9606:RNF38
uniprot id: Q9H0F5
names: Function
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Acts as an E3 ubiquitin-protein ligase able to ubiquitinate p53/TP53 which promotes its relocalization to discrete foci associated with PML nuclear bodies. Exhibits preference for UBE2D2 as a E2 enzyme.
messages: Nucleus
messages: Widely expressed with highest levels in testis.

9606:FOXR2
gene id: 9606:FOXR2
uniprot id: Q6PJQ5
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Expressed in breast cancer cell lines and primary cancer.
messages: Nucleus

9606:KIAA1217
gene id: 9606:KIAA1217
uniprot id: Q5T5P2
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Cytoplasm
messages: Interacts with CPNE4 (via VWFA domain).
messages: Required for normal development of intervertebral disks.
messages: centrosome

9606:UTP3
gene id: 9606:UTP3
uniprot id: Q9NQZ2
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the SAS10 family.
messages: Citrullinated by PADI4.
messages: Essential for gene silencing: has a role in the structure of silenced chromatin. Plays a role in the developing brain (By similarity). Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (PubMed:34516797).
messages: Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3.
messages: nucleolus

9606:CFHR5
gene id: 9606:CFHR5
uniprot id: Q9BXR6
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Defects in CFHR5 have been found in patients with atypical hemolytic uremic syndrome and may contribute to the disease. Atypical hemolytic uremic syndrome is a complex genetic disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, renal failure and absence of episodes of enterocolitis and diarrhea. In contrast to typical hemolytic uremic syndrome, atypical forms have a poorer prognosis, with higher death rates and frequent progression to end-stage renal disease. Susceptibility to the development of atypical hemolytic uremic syndrome can be conferred by mutations in various components of or regulatory factors in the complement cascade system. Other genes may play a role in modifying the phenotype.
messages: Expressed by the liver and secreted in plasma.
messages: Head-to-tail homodimer and heterodimer with CFHR1 or CFHR2. Binds C3b in vitro.
messages: Involved in complement regulation. The dimerized forms have avidity for tissue-bound complement fragments and efficiently compete with the physiological complement inhibitor CFH.
messages: Secreted
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:EBLN2
gene id: 9606:EBLN2
uniprot id: Q6P2I7
names: Function
names: Miscellaneous
messages: Bornavirus is a non-retroviral RNA virus that does not generate DNA forms during viral replication. Therefore, integration of EBLN-2 must have occur through a mechanism relying on an endogenous reverse transcriptase activity.
messages: May act as an RNA-binding protein. The C-terminal region is highly homologous to the bornavirus nucleocapsid N protein that binds viral RNA and oligomerizes. The viral protein also possesses a nuclear import and a nuclear export signal. These 2 signals seem absent in EBLN-2 supporting an unrelated function in Human.

9606:LSR
gene id: 9606:LSR
uniprot id: Q86X29
names: Caution
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the immunoglobulin superfamily. LISCH7 family.
messages: Cell membrane
messages: Defects in LSR may be the cause of familial intrahepatic cholestasis.
messages: Homotrimer or homotetramer (By similarity). Assembles into cell-cell contacts. Interacts (via the cytoplasmic domain) with MARVELD2 (via C-terminal cytoplasmic domain); the interaction is required to recruit MARVELD2 to tricellular contacts. Interacts with OCLN (By similarity).
messages: In contrast to the rodent orthologous protein, it is longer in N-terminus and no signal sequence is detected by any prediction method.
messages: Phosphorylation at Ser-365 by MAPK8/JNK1 and MAPK9/JNK2 may be required for exclusive localization at tricellular tight junstions.
messages: Probable role in the clearance of triglyceride-rich lipoprotein from blood. Binds chylomicrons, LDL and VLDL in presence of free fatty acids and allows their subsequent uptake in the cells (By similarity). Maintains epithelial barrier function by recruiting MARVELD2/tricellulin to tricellular tight junctions (By similarity).
messages: tight junction

9606:CDH2
gene id: 9606:CDH2
uniprot id: C9J126
uniprot id: P19022
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: Cadherins are calcium-dependent cell adhesion proteins.
messages: Calcium-dependent cell adhesion protein; preferentially mediates homotypic cell-cell adhesion by dimerization with a CDH2 chain from another cell. Cadherins may thus contribute to the sorting of heterogeneous cell types. Acts as a regulator of neural stem cells quiescence by mediating anchorage of neural stem cells to ependymocytes in the adult subependymal zone: upon cleavage by MMP24, CDH2-mediated anchorage is affected, leading to modulate neural stem cell quiescence. Plays a role in cell-to-cell junction formation between pancreatic beta cells and neural crest stem (NCS) cells, promoting the formation of processes by NCS cells (By similarity). Required for proper neurite branching. Required for pre- and postsynaptic organization (By similarity). CDH2 may be involved in neuronal recognition mechanism. In hippocampal neurons, may regulate dendritic spine density.
messages: Cell junction
messages: Cell membrane
messages: Cell surface
messages: Cleaved by MMP24. Ectodomain cleavage leads to the generation of a soluble 90 kDa N-terminal soluble fragment and a 45 kDa membrane-bound C-terminal fragment 1 (CTF1), which is further cleaved by gamma-secretase into a 35 kDa (By similarity). Cleavage in neural stem cells by MMP24 affects CDH2-mediated anchorage of neural stem cells to ependymocytes in the adult subependymal zone, leading to modulate neural stem cell quiescence (By similarity).
messages: Homodimer (via extracellular region). Can also form heterodimers with other cadherins (via extracellular region). Dimerization occurs in trans, i.e. with a cadherin chain from another cell (By similarity). Interacts with CDCP1 (PubMed:16007225). Interacts with PCDH8; this complex may also include TAOK2 (By similarity). The interaction with PCDH8 may lead to internalization through TAOK2/p38 MAPK pathway (By similarity). Identified in a complex containing FGFR4, NCAM1, CDH2, PLCG1, FRS2, SRC, SHC1, GAP43 and CTTN. May interact with OBSCN (via protein kinase domain 2) (By similarity). Interacts with FBXO45 (PubMed:32341084).
messages: May be phosphorylated by OBSCN.
messages: Membrane
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The disease may be caused by variants affecting the gene represented in this entry.
messages: Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain. Calcium-binding sites are occupied sequentially in the order of site 3, then site 2 and site 1.
messages: adherens junction
messages: desmosome
messages: sarcolemma

9606:DBF4
gene id: 9606:DBF4
uniprot id: Q9UBU7
names: Function
names: Induction
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Forms a complex with CDC7. Note that CDC7 forms distinct complex either with DBF4A or DBF4B. Such complexes are stable upon replication stress. Interacts with MEN1, MCM2, ORC2, ORC4 and ORC6. Interacts (via IBM motifs) with PSIP1 (via IBD domain); phosphorylation increases its affinity for PSIP1 (PubMed:29997176).
messages: Highly expressed in testis and thymus. Expressed also in most cancer cells lines.
messages: Induced in G1 phase at low level, increased during G1-S phase and remain high during S and G2-M phase.
messages: Nucleus
messages: Phosphorylation increases its interaction with PSIP1.
messages: Regulatory subunit for CDC7 which activates its kinase activity thereby playing a central role in DNA replication and cell proliferation. Required for progression of S phase. The complex CDC7-DBF4A selectively phosphorylates MCM2 subunit at 'Ser-40' and 'Ser-53' and then is involved in regulating the initiation of DNA replication during cell cycle.

9606:SYK
gene id: 9606:SYK
uniprot id: P43405
names: Activity Regulation
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts with Epstein-Barr virus LMP2A.
messages: Autoinhibited. Intramolecular binding of the interdomains A and B (also called linker region) to parts of the catalytic domain keep the catalytic center in an inactive conformation. The phosphorylation of the interdomains or the binding of the SH2 domains with dually phosphorylated ITAM domains on transmembrane proteins disrupt those intramolecular interactions allowing the kinase domain to adopt an active conformation. The phosphorylation of SYK and of the ITAM domains which is responsible for SYK activation is essentially mediated by SRC subfamily kinases, like LYN, upon transmembrane receptors engagement. May also be negatively regulated by PTPN6 through dephosphorylation. Downstream signaling adapters and intermediates like BLNK or RHOH may mediate positive and/or negative feedback regulation. Negatively regulated by CBL and CBLB through ubiquitination and probable degradation. Phosphorylates SH3BP2 which in turn may regulate SYK through LYN (By similarity).
messages: Autophosphorylated. Phosphorylated on tyrosine residues by LYN following receptors engagement. Phosphorylation on Tyr-323 creates a binding site for CBL, an adapter protein that serves as a negative regulator of BCR-stimulated calcium ion signaling. Phosphorylation at Tyr-348 creates a binding site for VAV1. Phosphorylation on Tyr-348 and Tyr-352 enhances the phosphorylation and activation of phospholipase C-gamma and the early phase of calcium ion mobilization via a phosphoinositide 3-kinase-independent pathway (By similarity). Phosphorylated on tyrosine residues in response to IL15 (PubMed:15123770). Phosphorylation on Ser-297 is very common, it peaks 5 minutes after BCR stimulation, and creates a binding site for YWHAG. Phosphorylation at Tyr-630 creates a binding site for BLNK. Dephosphorylated by PTPN6.
messages: Belongs to the protein kinase superfamily. Tyr protein kinase family. SYK/ZAP-70 subfamily.
messages: Cell membrane
messages: Interacts with LYN; phosphorylates SYK (By similarity). Interacts with RHOH (phosphorylated); regulates mast cells activation (By similarity). Interacts with NFAM1 (phosphorylated); probably involved in BCR signaling (By similarity). Interacts with VAV1 (via SH2 domain); phosphorylates VAV1 upon BCR activation. Interacts with GAB2 (phosphorylated); probably involved in IgE Fc receptor signaling (By similarity). Interacts (via its SH2 domains) with CD79A (via its phosphorylated ITAM domain); the interaction stimulates SYK autophosphorylation and activation (By similarity). Interacts with FCRL3 (PubMed:19843936, PubMed:11162587). Interacts (via SH2 domains) with FCER1G (via ITAM domain); activates SYK and mediates neutrophils and macrophages integrin-mediated activation (By similarity). Interaction with FCER1G in basophils triggers IL3-induced IL4 production (By similarity). Interacts with ITGB2 and FGR; involved in ITGB2 downstream signaling (By similarity). Interacts with ITGB3; upon activation by ITGB3 promotes platelet adhesion. Interacts (via SH2 domains) with TYROBP (via ITAM domain); involved in neutrophils and macrophages integrin-mediated activation (By similarity). Interacts with MSN and SELPLG; mediates the selectin-dependent activation of SYK by SELPLG. Interacts with BLNK (via SH2 domain). Interacts (via the second SH2 domain) with USP25 (via C-terminus); phosphorylates USP25 and regulates USP25 intracellular levels. Interacts (via SH2 domains) with CLEC1B (dimer). Interacts with CLEC7A; participates in leukocyte activation in presence of fungal pathogens. Interacts (phosphorylated) with SLA; may regulate SYK through CBL recruitment. Interacts with YWHAG; attenuates BCR-induced membrane translocation and activation of SYK. Interacts (via SH2 domains) with GCSAM; the interaction increases after B-cell receptor stimulation, resulting in enhanced SYK autophosphorylation and activity. Interacts with TNS2; leading to the phosphorylation of SYK (PubMed:22019427…
messages: Non-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immunoreceptors like the B-cell receptor (BCR). Regulates several biological processes including innate and adaptive immunity, cell adhesion, osteoclast maturation, platelet activation and vascular development (PubMed:12387735, PubMed:33782605). Assembles into signaling complexes with activated receptors at the plasma membrane via interaction between its SH2 domains and the receptor tyrosine-phosphorylated ITAM domains. The association with the receptor can also be indirect and mediated by adapter proteins containing ITAM or partial hemITAM domains. The phosphorylation of the ITAM domains is generally mediated by SRC subfamily kinases upon engagement of the receptor. More rarely signal transduction via SYK could be ITAM-independent. Direct downstream effectors phosphorylated by SYK include DEPTOR, VAV1, PLCG1, PI-3-kinase, LCP2 and BLNK (PubMed:12456653, PubMed:15388330, PubMed:8657103, PubMed:34634301). Initially identified as essential in B-cell receptor (BCR) signaling, it is necessary for the maturation of B-cells most probably at the pro-B to pre-B transition (PubMed:12456653). Activated upon BCR engagement, it phosphorylates and activates BLNK an adapter linking the activated BCR to downstream signaling adapters and effectors. It also phosphorylates and activates PLCG1 and the PKC signaling pathway. It also phosphorylates BTK and regulates its activity in B-cell antigen receptor (BCR)-coupled signaling. In addition to its function downstream of BCR also plays a role in T-cell receptor signaling. Plays also a crucial role in the innate immune response to fungal, bacterial and viral pathogens. It is for instance activated by the membrane lectin CLEC7A. Upon stimulation by fungal proteins, CLEC7A together with SYK activates immune cells inducing the production of ROS. Also activates the inflammasome and NF-kappa-B-mediated transcr…
messages: The SH2 domains mediate the interaction of SYK with the phosphorylated ITAM domains of transmembrane proteins. Some proteins like CLEC1B have a partial ITAM domain (also called hemITAM) containing a single YxxL motif. The interaction with SYK requires CLEC1B homodimerization.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitinated by CBLB after BCR activation; which promotes proteasomal degradation.
messages: Widely expressed in hematopoietic cells (at protein level) (PubMed:8163536). Expressed in neutrophils (at protein level) (PubMed:15123770). Within the B-cell compartment, expressed from pro- and pre-B cells to plasma cells (PubMed:8163536).
messages: cytosol

9606:ASMTL
gene id: 9606:ASMTL
uniprot id: O95671
names: Cofactor
names: Function
names: Miscellaneous
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Homodimer.
messages: In the C-terminal section; belongs to the class I-like SAM-binding methyltransferase superfamily. Cation-independent O-methyltransferase family.
messages: In the N-terminal section; belongs to the Maf family. YhdE subfamily.
messages: Nucleoside triphosphate pyrophosphatase that hydrolyzes dTTP and UTP. Can also hydrolyze CTP and the modified nucleotides pseudo-UTP, 5-methyl-UTP (m(5)UTP) and 5-methyl-CTP (m(5)CTP). Has weak activity with dCTP, 8-oxo-GTP and N(4)-methyl-dCTP (PubMed:24210219). May have a dual role in cell division arrest and in preventing the incorporation of modified nucleotides into cellular nucleic acids (PubMed:24210219). In addition, the presence of the putative catalytic domain of S-adenosyl-L-methionine binding in the C-terminal region argues for a methyltransferase activity (Probable).
messages: Pyrophosphatase activity requires a divalent metal cation.
messages: The gene coding for this protein is located in the pseudoautosomal region 1 (PAR1) of X and Y chromosomes. It represents a unique fusion product of 2 different genes of different evolutionary origin and function. The N-terminus is homologous to the bacterial maf/orfE genes and the C-terminus is homologous to ASMT. Exon duplication, exon shuffling and gene fusion seem to be common characteristics of the PAR1 region.
messages: Widely expressed. In adult, highly expressed in pancreas, placenta, fibroblast, thymus, prostate, testis, ovary and colon. Expressed at lower levels in spleen, small intestine and leukocytes. In fetus, expressed at high levels in the lung and kidney and at lower level in brain and liver.

9606:MNAT1
gene id: 9606:MNAT1
uniprot id: A0A024R688
uniprot id: P51948
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Associates primarily with CDK7 and cyclin H to form the CAK complex. CAK can further associate with the core-TFIIH to form the TFIIH basal transcription factor.
messages: Associates with CDK7 and cyclin H.
messages: Highest levels in colon and testis. Moderate levels are present thymus, prostate, ovary, and small intestine. The lowest levels are found in spleen and leukocytes.
messages: Nucleus
messages: Stabilizes the cyclin H-CDK7 complex to form a functional CDK-activating kinase (CAK) enzymatic complex.
messages: Stabilizes the cyclin H-CDK7 complex to form a functional CDK-activating kinase (CAK) enzymatic complex. CAK activates the cyclin-associated kinases CDK1, CDK2, CDK4 and CDK6 by threonine phosphorylation. CAK complexed to the core-TFIIH basal transcription factor activates RNA polymerase II by serine phosphorylation of the repetitive C-terminal domain (CTD) of its large subunit (POLR2A), allowing its escape from the promoter and elongation of the transcripts. Involved in cell cycle control and in RNA transcription by RNA polymerase II.

9606:ZNF410
gene id: 9606:ZNF410
uniprot id: Q86VK4
names: Domain
names: Function
names: Induction
names: Miscellaneous
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Chromosome
messages: During fibroblast senescence.
messages: Interacts with CDKN2A/p14ARF.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Nucleus
messages: O-glycosylated (PubMed:30078215). O-GlcNAcylation may occur in response to increasing glucose levels and affect transcription factor activity (PubMed:30078215).
messages: Sumoylated (PubMed:12370286). Sumoylation increases its half-life, possibly by blocking ubiquitin-mediated degradation (PubMed:12370286).
messages: The five zinc finger domains are necessary and sufficient to bind to DNA.
messages: Transcription factor that binds to the sequence motif 5'-CATCCCATAATA-3', and is specifically required to silence expression of fetal hemoglobin in adult erythroid cells (PubMed:33859416, PubMed:33301730). Prevents expression of fetal hemoglobin genes HBG1 and HBG2 through CHD4: acts as a direct transcriptional activator of CHD4, a central component of the NuRD complex that represses transcription of fetal hemoglobin genes HBG1 and HBG2 in erythroid cells (PubMed:33859416, PubMed:33301730). May also activate transcription of matrix-remodeling genes such as MMP1 during fibroblast senescence (PubMed:12370286). May activate transcription of the gap junction gene GJC1, perhaps in response to increasing glucose (PubMed:30078215). However, recent studies suggest that ZNF410 is dedicated to regulate expression of a single gene: CHD4 (PubMed:33859416, PubMed:33301730).
messages: Widely expressed.

9606:C6orf132
gene id: 9606:C6orf132
uniprot id: Q5T0Z8
names: Sequence Caution
messages: Contaminating sequence. Sequence of unknown origin in the C-terminal part.
messages: Contaminating sequence. Sequence of unknown origin in the N-terminal part.

9606:NAP1L1
gene id: 9606:NAP1L1
uniprot id: B7Z2V4
uniprot id: F5H4R6
uniprot id: F8W543
uniprot id: P55209
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts with Chikungunya virus non-structural protein 3 (via C-terminus).
messages: (Microbial infection) Interacts with hepatitis virus protein NS5A (via C-terminus); this interaction sequesters NAP1L1 in the cytoplasm, blocking its nuclear translocation.
messages: (Microbial infection) Interacts with human herpesvirus 8 protein LANA1 (via N-terminus); this interaction is required for LANA1-dependent DNA replication.
messages: (Microbial infection) Positively regulates Epstein-Barr virus reactivation in epithelial cells through the induction of viral BZLF1 expression.
messages: (Microbial infection) Together with human herpesvirus 8 protein LANA1, assists the proper assembly of the nucleosome on the replicated viral DNA.
messages: Belongs to the nucleosome assembly protein (NAP) family.
messages: Cytoplasm
messages: Histone chaperone that plays a role in the nuclear import of H2A-H2B and nucleosome assembly (PubMed:20002496, PubMed:21211722, PubMed:26841755). Participates also in several important DNA repair mechanisms: greatly enhances ERCC6-mediated chromatin remodeling which is essential for transcription-coupled nucleotide excision DNA repair (PubMed:28369616). Stimulates also homologous recombination (HR) by RAD51 and RAD54 which is essential in mitotic DNA double strand break (DSB) repair (PubMed:24798879). Plays a key role in the regulation of embryonic neurogenesis (By similarity). Promotes the proliferation of neural progenitors and inhibits neuronal differentiation during cortical development (By similarity). Regulates neurogenesis via the modulation of RASSF10; regulates RASSF10 expression by promoting SETD1A-mediated H3K4 methylation at the RASSF10 promoter (By similarity).
messages: Homodimer (PubMed:26841755). The dimer binds strongly and sequentially to single and double H2A-H2B heterodimers (PubMed:26841755). Interacts with ERCC6; this interaction increases ERCC6 processivity (PubMed:28369616). Interacts with RAD54 (PubMed:24798879). Interacts with SETD1A (By similarity).
messages: Melanosome
messages: Monoglycylated on glutamate residues. Cannot be polyglycylated due to the absence of functional TTLL10 in human (By similarity).
messages: Nucleus
messages: Polyglutamylated by TTLL4 on glutamate residues, resulting in polyglutamate chains on the gamma-carboxyl group. Both polyglutamylation and monoglycylation modifications can coexist on the same protein on adjacent residues, and lowering polyglycylation levels increases polyglutamylation, and reciprocally.
messages: The NAP1L motif is required for the histone chaperone activity.
messages: The acidic domains are probably involved in the interaction with histones.
messages: Ubiquitously expressed.

9606:S100A2
gene id: 9606:S100A2
uniprot id: P29034
names: Caution
names: Developmental Stage
names: Function
names: Induction
names: Miscellaneous
names: Similarity
names: Subunit
names: Tissue Specificity
messages: A subset of epithelial cells including normal human mammary epithelial cells and keratinocytes.
messages: Belongs to the S-100 family.
messages: By growth factors in early G1 phase and probably by cell-cycle regulation in S phase. DNA methylation probably plays a direct negative role in suppressing S100L gene expression in tumor cells.
messages: Homodimer. Interacts with FKBP4. Interacts with PPP5C (via TPR repeats); the interaction is calcium-dependent and modulates PPP5C activity. Interacts with TPPP; this interaction inhibits TPPP dimerization (PubMed:33831707).
messages: It is uncertain whether Met-1 or Met-2 is the initiator.
messages: May function as calcium sensor and modulator, contributing to cellular calcium signaling. May function by interacting with other proteins, such as TPR-containing proteins, and indirectly play a role in many physiological processes. May also play a role in suppressing tumor cell growth.
messages: Preferentially expressed in normal human mammary epithelial cells as opposed to tumor-derived ones. The level of S100L was shown to correlate inversely with tumor progression.
messages: This protein binds two calcium ions.

9606:MMP13
gene id: 9606:MMP13
uniprot id: P45452
uniprot id: Q53H33
names: Activity Regulation
names: Cofactor
names: Disease Annotation
names: Domain
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the peptidase M10A family.
messages: Binds 2 Zn(2+) ions per subunit.
messages: Can bind about 5 Ca(2+) ions per subunit.
messages: Detected in fetal cartilage and calvaria, in chondrocytes of hypertrophic cartilage in vertebrae and in the dorsal end of ribs undergoing ossification, as well as in osteoblasts and periosteal cells below the inner periosteal region of ossified ribs. Detected in chondrocytes from in joint cartilage that have been treated with TNF and IL1B, but not in untreated chondrocytes. Detected in T lymphocytes. Detected in breast carcinoma tissue.
messages: Inhibited by TIMP1, TIMP2 and TIMP3. Inhibited by acetohydroxamic acid and other zinc chelators.
messages: Monomer. Interacts with TIMP1, TIMP2 and TIMP3. Binds (via the C-terminal region) to collagen.
messages: N-glycosylated.
messages: Plays a role in the degradation of extracellular matrix proteins including fibrillar collagen, fibronectin, TNC and ACAN. Cleaves triple helical collagens, including type I, type II and type III collagen, but has the highest activity with soluble type II collagen. Can also degrade collagen type IV, type XIV and type X. May also function by activating or degrading key regulatory proteins, such as TGFB1 and CCN2. Plays a role in wound healing, tissue remodeling, cartilage degradation, bone development, bone mineralization and ossification. Required for normal embryonic bone development and ossification. Plays a role in the healing of bone fractures via endochondral ossification. Plays a role in wound healing, probably by a mechanism that involves proteolytic activation of TGFB1 and degradation of CCN2. Plays a role in keratinocyte migration during wound healing. May play a role in cell migration and in tumor cell invasion.
messages: Secreted
messages: The C-terminal region binds to collagen.
messages: The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme (By similarity).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The proenzyme is activated by removal of the propeptide; this cleavage can be effected by other matrix metalloproteinases, such as MMP2, MMP3 and MMP14 and may involve several cleavage steps. Cleavage can also be autocatalytic, after partial maturation by another protease or after treatment with 4-aminophenylmercuric acetate (APMA) (in vitro).
messages: Tyrosine phosphorylated by PKDCC/VLK.
messages: Up-regulated by TNF and IL1B.
messages: extracellular matrix

9606:HABP4
gene id: 9606:HABP4
uniprot id: Q5JVS0
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Able to bind hyaluronan. However, its intracellular localization suggests that this interaction may not be relevant in vivo.
messages: Associates with ribosomes; promoting ribosome stabilization (PubMed:21771594). Interacts with EEF2/eEF2; promoting ribosome stabilization (By similarity). Interacts with FMR1 (PubMed:21771594). Interacts with FXR1 and FXR2 (PubMed:21771594). Interacts with CHD3 (via C-terminus) (PubMed:12505151). Interacts (via C-terminus) with RACK1 (PubMed:14699138). Interacts with p53/TP53 (PubMed:16455055). Interacts (via N-terminus) with SRSF9; this interaction is direct (PubMed:19523114). Interacts with SYNCRIP; this interaction is direct (PubMed:19523114). Interacts with MEF2C (via N-terminus); this interaction decreases DNA-binding activity of MEF2C in myocardial cells in response to mechanical stress (PubMed:15862299). Interacts with PRMT1 (via N-terminus) (PubMed:16879614). Interacts with SPIN1 (By similarity).
messages: Belongs to the SERBP1-HABP4 family.
messages: Cajal body
messages: Cytoplasm
messages: Highly expressed in brain, heart, and kidney, and moderately expressed in skeletal muscle. Also expressed in a variety of tumor cell lines and in activated but not resting leukocytes.
messages: Methylated (PubMed:16879614). Methylation is decreased by phorbol 12-myristate 13-acetate (PMA)-activated PKC, in vitro (PubMed:16879614).
messages: Nucleus
messages: Nucleus speckle
messages: Phosphorylated by phorbol 12-myristate 13-acetate (PMA)-activated PKC isoforms at Thr-354 and Thr-375.
messages: Ribosome-binding protein that promotes ribosome hibernation, a process during which ribosomes are stabilized in an inactive state and preserved from proteasomal degradation (By similarity). Acts via its association with EEF2/eEF2 factor at the A-site of the ribosome, promoting ribosome stabilization in an inactive state compatible with storage (By similarity). Plays a key role in ribosome hibernation in the mature oocyte by promoting ribosome stabilization (By similarity). Ribosomes, which are produced in large quantities during oogenesis, are stored and translationally repressed in the oocyte and early embryo (By similarity). Also binds RNA, regulating transcription and pre-mRNA splicing (PubMed:14699138, PubMed:16455055, PubMed:21771594, PubMed:19523114). Binds (via C-terminus) to poly(U) RNA (PubMed:19523114). Seems to play a role in PML-nuclear bodies formation (PubMed:28695742). Negatively regulates DNA-binding activity of the transcription factor MEF2C in myocardial cells in response to mechanical stress (By similarity).
messages: Stress granule
messages: The C-terminal region is necessary for nucleus and cytoplasmic localization (PubMed:19523114). The N-terminal region is necessary for nucleus and nuclear bodies localization (PubMed:19523114). Regions containing Arg-Gly-Gly repeats (RGG/RXR-box) may be preferentially methylated by PRMT1 (PubMed:16879614).
messages: The interaction with RACK1 is abolished upon activation of L540 tumor cells with PMA, which results in phosphorylation and exit of HABP4 from the nucleus.
messages: gem
messages: nuclear body
messages: nucleolus
messages: sarcoplasm

9606:GALNT14
gene id: 9606:GALNT14
uniprot id: B7Z5C5
uniprot id: Q96FL9
names: Domain
names: Function
names: Miscellaneous
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the glycosyltransferase 2 family. GalNAc-T subfamily.
messages: Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor. Displays activity toward mucin-derived peptide substrates such as Muc2, Muc5AC, Muc7, and Muc13 (-58). May be involved in O-glycosylation in kidney.
messages: Chimeric at the C-terminus.
messages: Detected in renal tubules (at protein level). Highly expressed in fetal and adult kidney. Widely expressed at low level. Weakly expressed in whole brain, cerebellum, thymus, lung, mammary gland, liver, stomach, small intestine, colon, pancreas, spleen, bladder, uterus, placenta, testis, ovary, skeletal muscle, leukocyte, B-cell, bone marrow, fetal brain, fetal thymus, fetal lung, fetal liver, fetal small intestine, fetal spleen, fetal skeletal and fetus. Detected in renal tubules (at protein level).
messages: Golgi apparatus membrane
messages: Major isoform.
messages: Membrane
messages: Minor isoform.
messages: The ricin B-type lectin domain binds to GalNAc and contributes to the glycopeptide specificity.
messages: There are two conserved domains in the glycosyltransferase region: the N-terminal domain (domain A, also called GT1 motif), which is probably involved in manganese coordination and substrate binding and the C-terminal domain (domain B, also called Gal/GalNAc-T motif), which is probably involved in catalytic reaction and UDP-Gal binding.

9606:TMEM255B
gene id: 9606:TMEM255B
uniprot id: Q8WV15
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the TMEM255 family.
messages: Membrane

9606:MOG
gene id: 9606:MOG
uniprot id: Q16653
uniprot id: Q5SSB8
names: Caution
names: Disease Annotation
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Acts as a receptor for rubella virus.
messages: (Microbial infection) Interacts with rubella virus E2 glycoprotein.
messages: Belongs to the immunoglobulin superfamily. BTN/MOG family.
messages: Cell membrane
messages: Do not confuse myelin-oligodendrocyte glycoprotein (MOG) with oligodendrocyte-myelin glycoprotein (OMG).
messages: Found exclusively in the CNS, where it is localized on the surface of myelin and oligodendrocyte cytoplasmic membranes.
messages: Homodimer (By similarity). May form heterodimers between the different isoforms (By similarity).
messages: Homodimer.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Mediates homophilic cell-cell adhesion (By similarity). Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication.
messages: Membrane
messages: Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication. Mediates homophilic cell-cell adhesion.
messages: Not functionally active. May be expressed at low level in the adult.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:USP6NL
gene id: 9606:USP6NL
uniprot id: Q92738
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acts as a GTPase-activating protein for RAB5A and RAB43. Involved in receptor trafficking. In complex with EPS8 inhibits internalization of EGFR. Involved in retrograde transport from the endocytic pathway to the Golgi apparatus. Involved in the transport of Shiga toxin from early and recycling endosomes to the trans-Golgi network. Required for structural integrity of the Golgi complex.
messages: Cytoplasmic vesicle
messages: Golgi apparatus
messages: Interacts with EPS8.
messages: Widely expressed.

9606:GIGYF2
gene id: 9606:GIGYF2
uniprot id: Q6Y7W6
names: Disease Annotation
names: Function
names: Sequence Caution
names: Similarity
names: Subunit
messages: (Microbial infection) Interacts with SARS coronavirus-2/SARS-CoV-2 non-structural protein 2 (nsp2); the interaction enhances GIGYF2 binding to EIF4E2.
messages: (Microbial infection) Upon SARS coronavirus-2/SARS-CoV-2 infection, the interaction with non-structural protein 2 (nsp2) enhances GIGYF2 binding to EIF4E2 and increases repression of translation initiation of genes involved in antiviral innate immune response such as IFNB1.
messages: Belongs to the GIGYF family.
messages: Component of the 4EHP-GYF2 complex, at least composed of EIF4E2, GIGYF2 and ZNF598 (PubMed:22751931, PubMed:31439631, PubMed:32726578). Interacts (via the 4EHP-binding motif) with EIF4E2; the interaction is direct (PubMed:22751931, PubMed:31439631, PubMed:32726578). Interacts with ZFP36/TTP (via P-P-P-P-G repeats); the interaction is direct (PubMed:31439631). Interacts with GRB10 (By similarity). Interacts (via DDX6 motif) with DDX6 (via RecA-like domain 2) (PubMed:31439631).
messages: Disease susceptibility may be associated with variants affecting the gene represented in this entry. Its association with Parkinson disease is however unclear. According to a number of studies, variations affecting this gene are not a frequent cause of Parkinson disease, suggesting that GIGYF2 does not play a major role in Parkinson disease etiology (PubMed:19279319, PubMed:19429085, PubMed:19638301, PubMed:19482505, PubMed:20004041, PubMed:19321232, PubMed:20060621).
messages: Key component of the 4EHP-GYF2 complex, a multiprotein complex that acts as a repressor of translation initiation (PubMed:22751931, PubMed:31439631, PubMed:35878012). In the 4EHP-GYF2 complex, acts as a factor that bridges EIF4E2 to ZFP36/TTP, linking translation repression with mRNA decay (PubMed:31439631). Also recruits and bridges the association of the 4EHP complex with the decapping effector protein DDX6, which is required for the ZFP36/TTP-mediated down-regulation of AU-rich mRNA (PubMed:31439631). May act cooperatively with GRB10 to regulate tyrosine kinase receptor signaling, including IGF1 and insulin receptors (PubMed:12771153). In association with EIF4E2, assists ribosome-associated quality control (RQC) by sequestering the mRNA cap, blocking ribosome initiation and decreasing the translational load on problematic messages. Part of a pathway that works in parallel to RQC-mediated degradation of the stalled nascent polypeptide (PubMed:32726578). GIGYF2 and EIF4E2 work downstream and independently of ZNF598, which seems to work as a scaffold that can recruit them to faulty mRNA even if alternative recruitment mechanisms may exist (PubMed:32726578).
messages: Unlikely isoform.

9606:LPGAT1
gene id: 9606:LPGAT1
uniprot id: Q92604
names: Caution
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the 1-acyl-sn-glycerol-3-phosphate acyltransferase family.
messages: Endoplasmic reticulum membrane
messages: Highly expressed in liver and placenta. Also expressed in peripheral blood, lung, kidney and brain. Detected at lower levels in colon. High expression is detected in brain and testis.
messages: Lysophospholipid acyltransferase involved in fatty acyl chain remodeling of glycerophospholipids in the endoplasmic reticulum membrane (By similarity). Selectively catalyzes the transfer and esterification of saturated long-chain fatty acids from acyl-CoA to the sn-1 position of 1-lyso-2-acyl phosphatidylethanolamines (1-lyso-PE, LPE), with a preference for stearoyl CoA over palmitoyl CoA as acyl donor (PubMed:36049524). Acts in concert with an unknown phospholipase A1 to convert palmitate phosphatidylethanolamine (PE) species into stearate ones. Provides substrates to the PE methylation pathway, controlling stearate/palmitate composition of PE and phosphatidylcholine (PC) species with an overall impact on de novo hepatic lipid synthesis, body fat content and life span (By similarity). Can acylate lysophosphatidylglycerols (LPG) using various saturated fatty acyl-CoAs as acyl donors (PubMed:15485873). Can also acylate monoacylglycerols with a preference for 2-monoacylglycerols over 1-monoacylglycerols (By similarity). Has no activity toward lysophosphatidic acids (LPA) (By similarity).
messages: The HXXXXD motif is essential for acyltransferase activity and may constitute the binding site for the phosphate moiety of the glycerol-3-phosphate.
messages: The role in phosphatidylglycerols remodeling and cardiolipin synthesis is questioned as both processes occur in mitochondria. The monoacylglycerol acyltransferase activity is also weak and a direct role in triacylglycerol synthesis appears unlikely.

9606:NHS
gene id: 9606:NHS
uniprot id: Q6T4R5
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Apical cell membrane
messages: Belongs to the NHS family.
messages: Cytoplasm
messages: Detected at low levels in all tissues analyzed. Detected in fetal and adult brain, lens, retina, retinal pigment epithelium, placenta, lymphocytes and fibroblasts. Levels in retinal pigment epithelium, placenta, lymphocytes, and fibroblasts are very low. Expressed also in kidney, lung and thymus.
messages: Interacts with the tight junction protein TJP1/ZO-1. Associates with actin-rich structures. Interacts with BRK1 and with all three members of the WAVE protein family, WASF1, WASF2 and WASF3.
messages: May function in cell morphology by maintaining the integrity of the circumferential actin ring and controlling lamellipod formation. Involved in the regulation eye, tooth, brain and craniofacial development.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The disease is caused by variants affecting the gene represented in this entry. Caused by copy number variations predicted to result in altered transcriptional regulation of the NHS gene: a 0.8 Mb segmental duplication-triplication encompassing the NHS, SCML1 and RAI2 genes, and an 4.8 kb intragenic deletion in NHS intron 1.
messages: focal adhesion
messages: lamellipodium
messages: tight junction

9606:PRAC2
gene id: 9606:PRAC2
uniprot id: D3DTV9
names: Caution
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Highly expressed in prostate and testis. Also detected in placenta, muscle, colon, peripheral blood leukocytes and skin.
messages: Nucleus
messages: Product of a dubious CDS prediction.

9606:MYRF
gene id: 9606:MYRF
uniprot id: Q9Y2G1
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the MRF family.
messages: Constitutes a precursor of the transcription factor. Mediates the autocatalytic cleavage that releases the Myelin regulatory factor, N-terminal component that specifically activates transcription of central nervous system (CNS) myelin genes (PubMed:23966832).
messages: Cytoplasm
messages: Endoplasmic reticulum membrane
messages: Expressed in lung, ARPE-19 cell line, brainstem, uterus and, to a lesser extent, in basal ganglion and liver. Weakly expressed in cerebellum and retina.
messages: Follows autocatalytic cleavage via the peptidase S74 domain. Autoprocessing is apparently constitutive and is essential for transcriptional activity (PubMed:23966832). Autocatalytic cleavage is inhibited by interaction with TMEM98 (By similarity).
messages: Glycosylated.
messages: Homotrimer (PubMed:23966832). Interacts (via C-terminal region) with TMEM98; the interaction inhibits MYRF self-cleavage (By similarity).
messages: Membrane-bound part that has no transcription factor activity and remains attached to the endoplasmic reticulum membrane following cleavage.
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The disease may be caused by variants affecting the gene represented in this entry.
messages: The nuclear localization signals mediate translocation to the nucleus.
messages: The peptidase S74 domain, also named Intramolecular Chaperone Auto-processed (ICA) domain or Intramolecular Chaperone Domain (ICD), has protease activity and mediates autocatalytic processing of the protein to generate the Myelin regulatory factor, N-terminal active transcription factor and the Myelin regulatory factor, C-terminal components.
messages: Transcription factor that specifically activates expression of myelin genes such as MBP, MOG, MAG, DUSP15 and PLP1 during oligodendrocyte (OL) maturation, thereby playing a central role in oligodendrocyte maturation and CNS myelination. Specifically recognizes and binds DNA sequence 5'-CTGGYAC-3' in the regulatory regions of myelin-specific genes and directly activates their expression. Not only required during oligodendrocyte differentiation but is also required on an ongoing basis for the maintenance of expression of myelin genes and for the maintenance of a mature, viable oligodendrocyte phenotype (PubMed:23966832).

9606:SPRR2B
gene id: 9606:SPRR2B
uniprot id: P35325
names: Developmental Stage
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the cornifin (SPRR) family.
messages: By UV irradiation and carcinogenic agents. During squamous differentiation of epidermal keratinocytes.
messages: Cross-linked envelope protein of keratinocytes. It is a keratinocyte protein that first appears in the cell cytosol, but ultimately becomes cross-linked to membrane proteins by transglutaminase. All that results in the formation of an insoluble envelope beneath the plasma membrane.
messages: Cytoplasm
messages: Expressed during differentiation of squamous cells.
messages: Suprabasal layers of squamous-differentiated tissues such as epidermis, esophagus, tongue and trachea.

9606:ZDHHC17
gene id: 9606:ZDHHC17
uniprot id: Q8IUH5
names: Caution
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Autopalmitoylated (PubMed:15603740, PubMed:18794299). Autopalmitoylation has a regulatory role in ZDHHC17-mediated Mg(2+) transport (PubMed:18794299).
messages: Belongs to the DHHC palmitoyltransferase family. AKR/ZDHHC17 subfamily.
messages: Cytoplasmic vesicle membrane
messages: Expressed in all brain regions. Expression is highest in the cortex, cerebellum, occipital lobe and caudate and lowest in the spinal cord. Expression is also seen in testis, pancreas, heart and kidney.
messages: Golgi apparatus membrane
messages: Interacts (via ANK repeats) with numerous proteins (via the consensus sequence motif [VIAP]-[VIT]-x-x-Q-P) (PubMed:28882895). Interacts (via ANK repeats) with CLIP3 (PubMed:26198635, PubMed:28882895). Interacts (via ANK repeats) with HTT; this interaction is inversely correlated to the length of the polyglutamine tract added to the huntingtin protein in Huntington disease (PubMed:12393793, PubMed:9700202, PubMed:26198635, PubMed:28882895, PubMed:28757145). Interacts (via ANK repeats) with DNAJC5 (via C-terminus) (PubMed:28882895). Interacts (via ANK repeats) with MAP6 (PubMed:26198635). Interacts (via ANK repeats) with SNAP23 (PubMed:28882895). Interacts (via ANK repeats) with SNAP25 (PubMed:28882895, PubMed:28757145). Interacts (via ANK repeats) with EVL (PubMed:28882895). Interacts with SPRED1 and SPRED3 (PubMed:24705354). Interacts with GPM6A and OPTN (PubMed:24705354). May interact (via ANK repeats) with SPRED2 (By similarity). May interact with NTRK1; may regulate its localization and function (By similarity).
messages: Palmitoyltransferase that catalyzes the addition of palmitate onto various protein substrates and is involved in a variety of cellular processes (PubMed:15489887, PubMed:15603740, PubMed:24705354, PubMed:27911442, PubMed:28757145). Has no stringent fatty acid selectivity and in addition to palmitate can also transfer onto target proteins myristate from tetradecanoyl-CoA and stearate from octadecanoyl-CoA (By similarity). Palmitoyltransferase specific for a subset of neuronal proteins, including SNAP25, DLG4/PSD95, GAD2, SYT1 and HTT (PubMed:15603740, PubMed:15489887, PubMed:19139280, PubMed:28757145). Also palmitoylates neuronal protein GPM6A as well as SPRED1 and SPRED3 (PubMed:24705354). Could also play a role in axonogenesis through the regulation of NTRK1 and the downstream ERK1/ERK2 signaling cascade (By similarity). May be involved in the sorting or targeting of critical proteins involved in the initiating events of endocytosis at the plasma membrane (PubMed:12393793). May play a role in Mg(2+) transport (PubMed:18794299). Could also palmitoylate DNAJC5 and regulate its localization to the Golgi membrane (By similarity). Palmitoylates CASP6, thereby preventing its dimerization and subsequent activation (PubMed:27911442).
messages: Presynaptic cell membrane
messages: The DHHC domain is required for palmitoyltransferase activity.
messages: Thought to palmitoylate MPP1 (PubMed:22496366). This work was later retracted due to image manipulation.

9606:TMEM41B
gene id: 9606:TMEM41B
uniprot id: Q5BJD5
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Critical host factor required for infection by human coronaviruses SARS-CoV-2, HCoV-OC43, HCoV-NL63, and HCoV-229E, as well as all flaviviruses tested such as Zika virus and Yellow fever virus (PubMed:33382968, PubMed:33338421). Required post-entry of the virus to facilitate the ER membrane remodeling necessary to form replication organelles (PubMed:33382968).
messages: (Microbial infection) Interacts with Zika virus NS4A protein and Yellow fever virus NS4B protein.
messages: (Microbial infection) VTT domain is required for flavivirus infection.
messages: Belongs to the TMEM41 family.
messages: Cytoplasm
messages: Endomembrane system
messages: Endoplasmic reticulum membrane
messages: Interacts with VMP1 (PubMed:30093494). Interacts with COPA, COPB1, VDAC1 and ERLIN2 (PubMed:30352685). Interacts with ATG2A (PubMed:33850023). Interacts with SURF4 (PubMed:34015269).
messages: Phospholipid scramblase involved in lipid homeostasis and membrane dynamics processes (PubMed:34015269, PubMed:33929485, PubMed:33850023). Has phospholipid scramblase activity toward cholesterol and phosphatidylserine, as well as phosphatidylethanolamine and phosphatidylcholine (PubMed:34015269, PubMed:33929485, PubMed:33850023). Required for autophagosome formation: participates in early stages of autophagosome biogenesis at the endoplasmic reticulum (ER) membrane by reequilibrating the leaflets of the ER as lipids are extracted by ATG2 (ATG2A or ATG2B) to mediate autophagosome assembly (PubMed:30093494, PubMed:30126924, PubMed:30933966, PubMed:34015269, PubMed:33929485, PubMed:34043740, PubMed:33850023). In addition to autophagy, involved in other processes in which phospholipid scramblase activity is required (PubMed:33850023). Required for normal motor neuron development (By similarity).
messages: The VTT domain was previously called the SNARE-assoc domain. As there is no evidence that this domain associates with SNARE proteins, it was renamed as VMP1, TMEM41, and TVP38 (VTT) domain.

9606:VPS53
gene id: 9606:VPS53
uniprot id: B3KS06
uniprot id: Q5VIR6
names: Disease Annotation
names: Function
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Acts as component of the GARP complex that is involved in retrograde transport from early and late endosomes to the trans-Golgi network (TGN). The GARP complex is required for the maintenance of the cycling of mannose 6-phosphate receptors between the TGN and endosomes, this cycling is necessary for proper lysosomal sorting of acid hydrolases such as CTSD (PubMed:15878329, PubMed:18367545). Acts as component of the EARP complex that is involved in endocytic recycling. The EARP complex associates with Rab4-positive endosomes and promotes recycling of internalized transferrin receptor (TFRC) to the plasma membrane (PubMed:25799061).
messages: Belongs to the VPS53 family.
messages: Component of the Golgi-associated retrograde protein (GARP) complex, also called VFT (VPS fifty-three) complex, composed of VPS51, VPS52, VPS53 and VPS54 (PubMed:27440922, PubMed:15878329). Component of the endosome-associated retrograde protein (EARP) complex, composed of VPS51, VPS52, VPS53 and VPS50/Syndetin (PubMed:25799061, PubMed:27440922). EIPR1 interacts with both EARP and GARP complexes and mediates the recruitment of the GARP complex to the trans-Golgi network (PubMed:27440922). Interacts with VPS50 in an EIPR1-independent manner (PubMed:31721635).
messages: Endosome membrane
messages: Membrane
messages: Probable cloning artifact.
messages: Recycling endosome
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: trans-Golgi network membrane

9606:AMY2A
gene id: 9606:AMY2A
uniprot id: P04746
uniprot id: Q53F26
names: Cofactor
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the glycosyl hydrolase 13 family.
messages: Binds 1 Ca(2+) ion per subunit.
messages: Binds 1 Cl(-) ion per subunit.
messages: Detected in pancreas (at protein level).
messages: Monomer. Binds to the sea anemone inhibitor helianthamide (PubMed:27066537).
messages: extracellular space

9606:SIPA1L3
gene id: 9606:SIPA1L3
uniprot id: O60292
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
messages: A chromosomal translocation involving SIPA1L3 is found in a patient with bilateral severe ocular abnormalities including congenital cataracts, corneal clouding, iridocorneal and lenticular adhesions and microphthalmia. Chromosomal translocation t(2;19)(q37.3;q13.1). In addition to translocation, missense variant has been found in patient with bilateral congenital cataracts (PubMed:26231217).
messages: Apical cell membrane
messages: Plays a critical role in epithelial cell morphogenesis, polarity, adhesion and cytoskeletal organization in the lens (PubMed:26231217).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:TMEM176B
gene id: 9606:TMEM176B
uniprot id: A0A090N7V7
uniprot id: Q3YBM2
names: Caution
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the TMEM176 family.
messages: Expressed in lung and dermal fibroblasts.
messages: May play a role in the process of maturation of dendritic cells. Required for the development of cerebellar granule cells (By similarity).
messages: Nucleus membrane
messages: The sequence shown here is derived from an EMBL/GenBank/DDBJ whole genome shotgun (WGS) entry which is preliminary data.
messages: Up-regulated in fibrotic lung. Down-regulated in activated dendritic cells.

9606:AQP2
gene id: 9606:AQP2
uniprot id: P41181
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Apical cell membrane
messages: Aquaporins contain two tandem repeats each containing three membrane-spanning domains and a pore-forming loop with the signature motif Asn-Pro-Ala (NPA).
messages: Basolateral cell membrane
messages: Belongs to the MIP/aquaporin (TC 1.A.8) family.
messages: Cell membrane
messages: Cytoplasmic vesicle membrane
messages: Expressed in collecting tubules in kidney medulla (at protein level) (PubMed:7510718). Detected in kidney (PubMed:7510718).
messages: Forms a water-specific channel that provides the plasma membranes of renal collecting duct with high permeability to water, thereby permitting water to move in the direction of an osmotic gradient (PubMed:8140421, PubMed:7524315, PubMed:7510718, PubMed:15509592). Plays an essential role in renal water homeostasis (PubMed:8140421, PubMed:7524315, PubMed:15509592).
messages: Homotetramer (PubMed:24733887). Interacts with micropeptide MIAC; the interaction leads to a reduction of filamentous actin fibers and inhibition of the EREG/EGFR signaling pathway (PubMed:32176498, PubMed:36117171).
messages: N-glycosylated.
messages: Ser-256 phosphorylation is necessary and sufficient for expression at the apical membrane. Endocytosis is not phosphorylation-dependent.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: trans-Golgi network membrane

9606:TMEM169
gene id: 9606:TMEM169
uniprot id: Q96HH4
names: Subcellular Location Annotation
messages: Membrane

9606:TRIM44
gene id: 9606:TRIM44
uniprot id: Q96DX7
names: Disease Annotation
names: Function
names: Subunit
names: Tissue Specificity
messages: Highly expressed in testis.
messages: Interacts (via coiled coil) with TRIM17 (via coiled coil).
messages: May play a role in the process of differentiation and maturation of neuronal cells (By similarity). May regulate the activity of TRIM17. Is a negative regulator of PAX6 expression (PubMed:26394807).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:RANGRF
gene id: 9606:RANGRF
uniprot id: Q9HD47
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the MOG1 family.
messages: Cell membrane
messages: Cytoplasm
messages: Isoform 1 and isoform 2 are ubiquitously expressed (PubMed:11290418). Detected in heart and brain (PubMed:21621375).
messages: May regulate the intracellular trafficking of RAN (PubMed:11290418). Promotes guanine nucleotide release from RAN and inhibits binding of new GTP by preventing the binding of the RAN guanine nucleotide exchange factor RCC1 (PubMed:29040603). Regulates the levels of GTP-bound RAN in the nucleus, and thereby plays a role in the regulation of RAN-dependent mitotic spindle dynamics (PubMed:29040603). Enhances the expression of SCN5A at the cell membrane in cardiomyocytes (PubMed:18184654, PubMed:23420830, PubMed:21621375).
messages: Monomer. Interacts with RAN, both RAN-GTP and RAN-GDP (PubMed:11290418, PubMed:29040603). Competes with RCC1 for a common binding site on RAN and thereby inhibits RCC1-mediated nucleotide exchange (PubMed:29040603). Forms a complex with RAN-GTP and RANBP1 (By similarity). Interacts with the cytoplasmic loop 2 of SCN5A (PubMed:18184654).
messages: Nucleus
messages: Overexpression can rescue the trafficking defect caused by some SCN5A mutations that impair trafficking to the cell membrane.
messages: perinuclear region

9606:TMPRSS13
gene id: 9606:TMPRSS13
uniprot id: Q9BYE2
names: Activity Regulation
names: Caution
names: Function
names: PTM
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the peptidase S1 family.
messages: Cell membrane
messages: Cleavage of HGF is inhibited by SPINT1/HAI-1 via the BPTI/Kunitz inhibitor 1 domain.
messages: Cytoplasm
messages: Expressed in lung, placenta, pancreas, and prostate (PubMed:11267681). Weakly expressed in testis and peripheral blood lymphocytes (PubMed:11267681).
messages: Expressed in placenta.
messages: Interacts with SPINT1/HAI-1; the interaction promotes the phosphorylation and cell membrane localization of TMPRSS13 (PubMed:28710277). Interacts with SPINT2/HAI-2; the interaction promotes the phosphorylation and cell membrane localization of TMPRSS13 (PubMed:28710277, PubMed:34562451).
messages: N-glycosylation of Asn-405 and Asn-445 is required for exit from the endoplasmic reticulum and trafficking to the cell surface (PubMed:28710277, PubMed:34562451). Also required for autocleavage of the zymogen, activation and secretion of the mature protein (PubMed:34562451).
messages: Phosphorylation is required for localization at the cell surface (PubMed:28710277, PubMed:34562451). Phosphorylation increases following inhibition of protease activity by SPINT2/HAI-2 (PubMed:35796294).
messages: Predominantly expressed in lung, placenta, pancreas, and prostate.
messages: Secreted
messages: Serine protease (PubMed:20977675, PubMed:28710277, PubMed:34562451). Cleaves the proform of PRSS8/prostasin to form the active protein (PubMed:34562451). Cleaves the proform of HGF to form the active protein which promotes MAPK signaling (PubMed:20977675). Promotes the formation of the stratum corneum and subsequently the epidermal barrier in embryos (By similarity).
messages: The inactive zymogen is post-translationally modified and then trafficked to the cell surface, whereby it undergoes autocatalytic cleavage resulting in an activated form that is released extracellularly.
messages: The repeat A-S-P-A-[GLQR] is polymorphic and the number of copies varies between 12 to 14.
messages: Was termed TMPRSS6 (Ref.3).

9606:INO80D
gene id: 9606:INO80D
uniprot id: Q53TQ3
names: Function
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the INO80D family.
messages: Component of the chromatin remodeling INO80 complex; specifically part of a complex module associated with the N-terminus of INO80.
messages: Contaminating sequence. Potential poly-A sequence.
messages: Nucleus
messages: Putative regulatory component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair.

9606:PLAGL2
gene id: 9606:PLAGL2
uniprot id: Q9UPG8
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: Nucleus
messages: Shows weak transcriptional activatory activity.

9606:SERPINB4
gene id: 9606:SERPINB4
uniprot id: P48594
uniprot id: Q9BYF7
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the serpin family.
messages: Belongs to the serpin family. Ov-serpin subfamily.
messages: Cytoplasm
messages: May act as a protease inhibitor to modulate the host immune response against tumor cells.
messages: Squamous cells.

9606:TSPY3
gene id: 9606:TSPY3
uniprot id: F2Z2I4
uniprot id: P0CV98
uniprot id: P0CW01
uniprot id: Q01534
names: Developmental Stage
names: Disease Annotation
names: Function
names: Induction
names: PTM
names: Polymorphism
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the nucleosome assembly protein (NAP) family.
messages: Cytoplasm
messages: Detected in 22-week old testis.
messages: Maps to a tandemly repeated region on chromosome Yp11; additionally at least one copy is reported originating from Yq. The gene is thought to be present with an inter-individual variation in copy number and between 20 and 60 copies per Y chromosome are expected. 35 tandemly repeated gene copies on Yp11 originating from one individual have been reported (PubMed:12815422).
messages: Maps to a tandemly repeated region on chromosome Yp11; additionally at least one copy is reported originating from Yq. The gene is thought to be present with an inter-individual variation in copy number and between 20 and 60 copies per Y chromosome are expected. PubMed:12815422 reports 35 tandemly repeated gene copies on Yp11 originating from one individual.
messages: May be involved in sperm differentiation and proliferation.
messages: Nucleus
messages: Phosphorylated.
messages: Probable unspliced transcript.
messages: Sequence of unknown origin inserted in the coding sequence.
messages: Specifically expressed in testicular tissues. Isoform 1 and isoform 2 are expressed in spermatogonia and spermatocytes. Found in early testicular carcinoma in situ, spermatogonial cells in testicular tissues of 46,X,Y female and in prostate cancer cell lines.
messages: TSPY is located in the gonadoblastoma critical region and is preferentially expressed in tumor germ cells of gonadoblastoma specimens. Expression also correlates with testicular seminoma and tumorigenesis of the prostate gland.
messages: Up-regulated by androgen in a prostate cancer cell line.
messages: Variants Val-Glu-Val-Val-Ala-Glu-79 Ins and Arg-195 are shown to be present in a number of TSPY1 copies of the Yp11 loci. Variant Arg-195 is shown to be present at least in one TSPY1 copy of the Yq locus.

9606:COA3
gene id: 9606:COA3
uniprot id: Q9Y2R0
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Along with COX14, core component of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex (Probable) (PubMed:23260140). Interacts with MT-CO1/COX1, SMIM20, SURF1 and TIMM21 (PubMed:26321642).
messages: Belongs to the COA3 family.
messages: Core component of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex, that regulates cytochrome c oxidase assembly. MITRAC complexes regulate both translation of mitochondrial encoded components and assembly of nuclear-encoded components imported in mitochondrion. Required for efficient translation of MT-CO1 and mitochondrial respiratory chain complex IV assembly.
messages: Mitochondrion inner membrane
messages: The disease may be caused by variants affecting the gene represented in this entry.

9606:GAS7
gene id: 9606:GAS7
uniprot id: O60861
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
messages: A chromosomal aberration involving GAS7 is found in acute myeloid leukemia. Translocation t(11;17)(q23;p13) with KMT2A/MLL1.
messages: Cytoplasm
messages: May play a role in promoting maturation and morphological differentiation of cerebellar neurons.

9606:LRRTM1
gene id: 9606:LRRTM1
uniprot id: Q86UE6
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the LRRTM family.
messages: Cell membrane
messages: Exhibits strong synaptogenic activity, restricted to excitatory presynaptic differentiation, acting at both pre- and postsynaptic level.
messages: Postsynaptic cell membrane
messages: Predominantly expressed in forebrain regions including thalamus and cerebral cortex.
messages: This gene is imprinted, being predominantly expressed from the paternal allele and showing a variable pattern of maternal down-regulation. May be associated paternally with handedness and schizophrenia.

9606:KIAA0586
gene id: 9606:KIAA0586
uniprot id: Q9BVV6
names: Developmental Stage
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the TALPID3 family.
messages: Expressed as early as 6 weeks of gestation (Carnegie stage 16). Ubiquitously expressed during fetal development and postnatally in all adult tissues tested.
messages: Interacts with CCP110, CEP290, CEP97, KIF24.
messages: Photoreceptor inner segment
messages: Required for ciliogenesis and sonic hedgehog/SHH signaling. Required for the centrosomal recruitment of RAB8A and for the targeting of centriole satellite proteins to centrosomes such as of PCM1. May play a role in early ciliogenesis in the disappearance of centriolar satellites that preceeds ciliary vesicle formation (PubMed:24421332). Involved in regulation of cell intracellular organization. Involved in regulation of cell polarity (By similarity). Required for asymmetrical localization of CEP120 to daughter centrioles (By similarity).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The disease is caused by variants affecting the gene represented in this entry. Some patients with biallelic KIAA0586 mutations manifest a disease phenotype with features of Joubert syndrome and additional findings of a small thorax and respiratory problems consistent with Jeune syndrome (Joubert-Jeune ciliopathy).
messages: Ubiquitously expressed (PubMed:26386044). Expressed in photoreceptor cells (at protein level) (PubMed:26386247).
messages: centriole
messages: centrosome
messages: cilium basal body

9606:CLEC4F
gene id: 9606:CLEC4F
uniprot id: Q8N1N0
names: Function
names: Subcellular Location Annotation
messages: Membrane
messages: Receptor with an affinity for galactose and fucose. Could be involved in endocytosis (By similarity).

9606:C6orf15
gene id: 9606:C6orf15
uniprot id: Q6UXA7
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Binds to numerous extracellular matrix proteins.
messages: Expressed in skin and tonsils.
messages: extracellular matrix

9606:ANKRD37
gene id: 9606:ANKRD37
uniprot id: Q7Z713
names: PTM
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Cytoplasm
messages: Mainly expressed in testis, small intestine, colon, blood leukocytes and in pancreatic adenocarcinoma cells.
messages: Nucleus
messages: Ubiquitinated by the CRL2(FEM1B) complex, leading to its degradation.

9606:NT5DC3
gene id: 9606:NT5DC3
uniprot id: Q86UY8
names: Cofactor
names: Similarity
names: Tissue Specificity
messages: Belongs to the 5'(3')-deoxyribonucleotidase family.
messages: Binds 1 Mg(2+) ion per subunit.
messages: Expressed in brain, placenta, skeletal muscle, pancreas, testis, uterus, and small intestine. Reduced expression in pancreatic cancer cells.

9606:IL3
gene id: 9606:IL3
uniprot id: P08700
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Activated T-cells, mast cells, natural killer cells.
messages: Belongs to the IL-3 family.
messages: Cytokine secreted predominantly by activated T-lymphocytes as well as mast cells and osteoblastic cells that controls the production and differentiation of hematopoietic progenitor cells into lineage-restricted cells (PubMed:2556442). Stimulates also mature basophils, eosinophils, and monocytes to become functionally activated (PubMed:10779277, PubMed:32889153). In addition, plays an important role in neural cell proliferation and survival (PubMed:23226269). Participates as well in bone homeostasis and inhibits osteoclast differentiation by preventing NF-kappa-B nuclear translocation and activation (PubMed:12816992). Mechanistically, exerts its biological effects through a receptor composed of IL3RA subunit and a signal transducing subunit IL3RB (PubMed:29374162). Receptor stimulation results in the rapid activation of JAK2 kinase activity leading to STAT5-mediated transcriptional program (By similarity). Alternatively, contributes to cell survival under oxidative stress in non-hematopoietic systems by activating pathways mediated by PI3K/AKT and ERK (PubMed:27862234).
messages: Interacts with IL3RA (PubMed:29374162).
messages: Secreted
messages: Upon activation of the T-cell receptor/CD3 pathway and can be augmented by coactivation of the CD3 and CD28 pathways.

9606:MTHFS
gene id: 9606:MTHFS
uniprot id: P49914
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the 5-formyltetrahydrofolate cyclo-ligase family.
messages: Contributes to tetrahydrofolate metabolism. Helps regulate carbon flow through the folate-dependent one-carbon metabolic network that supplies carbon for the biosynthesis of purines, thymidine and amino acids. Catalyzes the irreversible conversion of 5-formyltetrahydrofolate (5-FTHF) to yield 5,10-methenyltetrahydrofolate.
messages: Cytoplasm
messages: Monomer.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:ARL5C
gene id: 9606:ARL5C
uniprot id: A6NH57
names: Function
names: Similarity
messages: Belongs to the small GTPase superfamily. Arf family.
messages: Binds and exchanges GTP and GDP.

9606:EDF1
gene id: 9606:EDF1
uniprot id: O60869
names: Developmental Stage
names: Domain
names: Function
names: Induction
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cytoplasm
messages: Down-regulated by HIV-1 Tat or phorbol ester (TPA) treatment in endothelial cells (at mRNA and protein levels).
messages: Expressed in brain, liver, lung, kidney and heart (at protein level). Ubiquitously expressed. More abundant in heart, pancreas, liver, intestine and adipose tissues.
messages: Expressed in fetal tissues. More abundant in kidney.
messages: Interacts with TBP and the transcription factor IID (TFIID) complex, NR5A2, NR1H3 and PPARG. Interaction with TBP is regulated by phosphorylation. Binds NR5A1, ATF1, FOS and JUN via their conserved basic region. Binding to calmodulin is regulated by calcium and phosphorylation of the IQ motif.
messages: Nucleus
messages: Phosphorylated (by PKA and PKC).
messages: The IQ motif, which is involved in calmodulin binding, overlaps with the binding domain for nuclear receptors and transcription factors. Its phosphorylation probably allows a switch between the two activities of the protein (By similarity).
messages: Transcriptional coactivator stimulating NR5A1 and ligand-dependent NR1H3/LXRA and PPARG transcriptional activities. Enhances the DNA-binding activity of ATF1, ATF2, CREB1 and NR5A1. Regulates nitric oxid synthase activity probably by sequestering calmodulin in the cytoplasm. May function in endothelial cells differentiation, hormone-induced cardiomyocytes hypertrophy and lipid metabolism.

9606:AKTIP
gene id: 9606:AKTIP
uniprot id: Q9H8T0
names: Caution
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the ubiquitin-conjugating enzyme family. FTS subfamily.
messages: Cell membrane
messages: Component of the FTS/Hook/FHIP complex (FHF complex) (PubMed:32073997). The FHF complex may function to promote vesicle trafficking and/or fusion via the homotypic vesicular protein sorting complex (the HOPS complex). Regulates apoptosis by enhancing phosphorylation and activation of AKT1. Increases release of TNFSF6 via the AKT1/GSK3B/NFATC1 signaling cascade. FHF complex promotes the distribution of AP-4 complex to the perinuclear area of the cell (PubMed:32073997).
messages: Component of the FTS/Hook/FHIP complex (FHF complex), composed of AKTIP/FTS, FHIP1B, and one or more members of the Hook family of proteins HOOK1, HOOK2, and HOOK3. Interacts directly with HOOK1, HOOK2 and HOOK3 (PubMed:18799622, PubMed:32073997). The FHF complex associates with the homotypic vesicular sorting complex (the HOPS complex) (PubMed:18799622). Also interacts with AKT1. May interact with FHIP1A (PubMed:32073997).
messages: Cytoplasm
messages: Lacks the conserved Cys residue necessary for ubiquitin-conjugating enzyme E2 activity.

9606:GLRX
gene id: 9606:GLRX
uniprot id: P35754
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the glutaredoxin family.
messages: Cytoplasm
messages: Has a glutathione-disulfide oxidoreductase activity in the presence of NADPH and glutathione reductase. Reduces low molecular weight disulfides and proteins.

9606:MUC13
gene id: 9606:MUC13
uniprot id: Q9H3R2
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Apical cell membrane
messages: Cell membrane
messages: Cleaved into two subunits, alpha and beta, probably between the first EGF domain and the SEA domain. Beta subunit contains the cytoplasmic tail and alpha subunit the extracellular tail. The homooligomerization into dimers is dependent on intrachain disulfide bonds.
messages: Epithelial and hemopoietic transmembrane mucin that may play a role in cell signaling.
messages: Highly N-glycosylated.
messages: Highly expressed in epithelial tissues, particularly those of the gastrointestinal and respiratory tracts, such as large intestine and trachea, followed by kidney, small intestine, appendix and stomach.
messages: Homodimer of beta subunits.
messages: Secreted

9606:DYNC1I1
gene id: 9606:DYNC1I1
uniprot id: A4D1I7
uniprot id: O14576
uniprot id: Q8N542
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. The intermediate chains mediate the binding of dynein to dynactin via its 150 kDa component (p150-glued) DCTN1. May play a role in mediating the interaction of cytoplasmic dynein with membranous organelles and kinetochores.
messages: Belongs to the dynein intermediate chain family.
messages: Cytoplasm
messages: Homodimer (By similarity). The cytoplasmic dynein 1 complex consists of two catalytic heavy chains (HCs) and a number of non-catalytic subunits presented by intermediate chains (ICs), light intermediate chains (LICs) and light chains (LCs); the composition seems to vary in respect to the IC, LIC and LC composition. The heavy chain homodimer serves as a scaffold for the probable homodimeric assembly of the respective non-catalytic subunits. The ICs and LICs bind directly to the HC dimer and the LCs assemble on the IC dimer. Interacts with DYNC1H1. Interacts with DYNLT1 and DYNLT3. Interacts with DCTN1 (By similarity).
messages: kinetochore
messages: spindle pole

9606:NKD2
gene id: 9606:NKD2
uniprot id: Q969F2
names: Developmental Stage
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the NKD family.
messages: Cell autonomous antagonist of the canonical Wnt signaling pathway. May activate a second Wnt signaling pathway that controls planar cell polarity (By similarity). Required for processing of TGFA and for targeting of TGFA to the basolateral membrane of polarized epithelial cells.
messages: Cell membrane
messages: Cytoplasm
messages: Cytoplasmic vesicle
messages: Expressed in fetal kidney and lung.
messages: Expressed in kidney, lung, pancreas and spleen.
messages: Interacts with DVL1, DVL2, DVL3 and PPP2R3A (By similarity). Interacts with RNF25 and TGFA (via cytoplasmic domain).
messages: The N-terminal domain comprising the first 217 amino acid residues is mostly unstructured.
messages: Ubiquitinated, leading to rapid proteasomal degradation. Interaction with TGFA interferes with RNF25 binding and protects against ubiquitination mediated by RNF25.

9606:INF2
gene id: 9606:INF2
uniprot id: Q27J81
names: Activity Regulation
names: Disease Annotation
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the formin homology family.
messages: Interacts with actin at the FH2 domain. Interacts with DAAM2 (PubMed:33232676).
messages: Phosphate inhibits both the depolymerization and severing activities.
messages: Regulated by autoinhibition due to intramolecular GBD-DAD binding.
messages: Severs actin filaments and accelerates their polymerization and depolymerization.
messages: The WH2 domain acts as the DAD (diaphanous autoregulatory) domain and binds to actin monomers.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The severing activity is dependent on covalent attachment of the FH2 domain to the C-terminus.
messages: Widely expressed. In the kidney, expression is apparent in podocytes and some tubule cells.
messages: perinuclear region

9606:KCNJ18
gene id: 9606:KCNJ18
uniprot id: B7U540
names: Disease Annotation
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ12 subfamily.
messages: Cell membrane
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry.
messages: Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium.
messages: Probably phosphorylated by PKC; decreases single-channel open probability.
messages: Specifically expressed in skeletal muscle.
messages: Up-regulated by triiodothyronine.

9606:SMCO2
gene id: 9606:SMCO2
uniprot id: A6NFE2
names: Subcellular Location Annotation
messages: Membrane

9606:CD47
gene id: 9606:CD47
uniprot id: A0A0A1TSG4
uniprot id: Q08722
names: Function
names: Induction
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Adhesive protein that mediates cell-to-cell interactions (PubMed:11509594, PubMed:15383453). Acts as receptor for thrombospondin THBS1 and as modulator of integrin signaling through the activation of heterotrimeric G proteins (PubMed:19004835, PubMed:8550562, PubMed:7691831). Involved in signal transduction, cardiovascular homeostasis, inflammation, apoptosis, angiogenesis, cellular self-renewal, and immunoregulation (PubMed:27742621, PubMed:19004835, PubMed:8550562, PubMed:11509594, PubMed:7691831, PubMed:32679764, PubMed:15383453). Plays a role in modulating pulmonary endothelin EDN1 signaling (PubMed:27742621). Modulates nitrous oxide (NO) signaling, in response to THBS1, hence playing a role as a pressor agent, supporting blood pressure (By similarity). Plays an important role in memory formation and synaptic plasticity in the hippocampus (By similarity). Receptor for SIRPA, binding to which prevents maturation of immature dendritic cells and inhibits cytokine production by mature dendritic cells (PubMed:11509594). Interaction with SIRPG mediates cell-cell adhesion, enhances superantigen-dependent T-cell-mediated proliferation and costimulates T-cell activation (PubMed:15383453). Positively modulates FAS-dependent apoptosis in T-cells, perhaps by enhancing FAS clustering (By similarity). Plays a role in suppressing angiogenesis and may be involved in metabolic dysregulation during normal aging (PubMed:32679764). In response to THBS1, negatively modulates wound healing (By similarity). Inhibits stem cell self-renewal, in response to THBS1, probably by regulation of the stem cell transcription factors POU5F1/OCT4, SOX2, MYC/c-Myc and KLF4 (By similarity). May play a role in membrane transport and/or integrin dependent signal transduction (PubMed:7691831). May prevent premature elimination of red blood cells (By similarity).
messages: Cell membrane
messages: Induced in pulmonary artery and lung parenchyma following injury or stress (PubMed:27742621). Expression in arteries increases in normal aging (PubMed:32679764).
messages: Membrane
messages: Monomer (PubMed:18657508). Interacts with THBS1 (via the C-terminal domain) (PubMed:8550562, PubMed:19004835). Interacts with SIRPA (PubMed:11509594). Interacts with FAS/CD95; interaction may be enhanced by functional activation (PubMed:15917238). Interacts with SIRPG, UBQLN1 and UBQLN2 (PubMed:10549293, PubMed:15383453, PubMed:18657508). May interact with fibrinogen (PubMed:22079249).
messages: Very broadly distributed on normal adult tissues, as well as ovarian tumors, being especially abundant in some epithelia and the brain.

9606:TACC3
gene id: 9606:TACC3
uniprot id: Q9Y6A5
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the TACC family.
messages: Cytoplasm
messages: Interacts with microtubules. Interacts with CKAP5 independently of clathrin. Interacts with CKAP5 and clathrin forming the TACC3/ch-TOG/clathrin complex located at spindle inter-microtubules bridges; TACC3 (phosphorylated at Ser-558 by AURKA) and CLTC are proposed to form a composite microtubule interaction surface (PubMed:21297582, PubMed:23918938, PubMed:25596274). Interacts with CCDC100/CEP120. The coiled coil C-terminal region interacts with AH receptor nuclear translocator protein (ARNT) and ARNT2 (By similarity). Interacts with GCN5L2 and PCAF (PubMed:14767476).
messages: Plays a role in the microtubule-dependent coupling of the nucleus and the centrosome. Involved in the processes that regulate centrosome-mediated interkinetic nuclear migration (INM) of neural progenitors (By similarity). Acts as component of the TACC3/ch-TOG/clathrin complex proposed to contribute to stabilization of kinetochore fibers of the mitotic spindle by acting as inter-microtubule bridge. The TACC3/ch-TOG/clathrin complex is required for the maintenance of kinetochore fiber tension (PubMed:21297582, PubMed:23532825). May be involved in the control of cell growth and differentiation. May contribute to cancer (PubMed:14767476).
messages: Up-regulated in various cancer cell lines.
messages: centrosome
messages: spindle
messages: spindle pole

9606:IKBKE
gene id: 9606:IKBKE
uniprot id: A0A075B7B4
uniprot id: Q14164
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: 'Lys-63'-linked polyubiquitinated at Lys-30 and Lys-401 by TRAF2:BIRC2 and TRAF2:BIRC3 complexes. Ubiquitination is induced by LPS, TNFA and interleukin-1 and required for full kinase activity and KF-kappa-B pathway activation.
messages: (Microbial infection) Interacts (via Protein kinase domain) with arenavirus protein N; the interaction inhibits IKBKE kinase function.
messages: (Microbial infection) Interacts with Ebola virus protein VP35; the interaction leads to inhibition of cellular antiviral response by blocking necessary interactions between the IKBKE and MAVS/IPS as well as its substrates IRF3 and IRF7.
messages: (Microbial infection) Interacts with Epstein-Barr virus (EBV) protein NEC2/BFRF1; this interaction inhibits IKBKE kinase activity and IRF3 nuclear translocation.
messages: (Microbial infection) Interacts with Severe fever with thrombocytopenia virus (SFTSV) NSs; this interaction this interaction sequesters IKBKE in NSs-induced cytoplasmic inclusion bodies thereby inhibiting the IFN responses.
messages: (Microbial infection) Interacts with human T-cell leukemia virus 1/HTLV-1 protein HBZ.
messages: Autophosphorylated and phosphorylated by IKBKB/IKKB. Phosphorylation at Ser-172 is enhanced by the interaction with DDX3X. Phosphorylated at Thr-501 upon IFN activation.
messages: Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. I-kappa-B kinase subfamily.
messages: Cytoplasm
messages: Highly expressed in spleen followed by thymus, peripheral blood leukocytes, pancreas, placenta. Weakly expressed in lung, kidney, prostate, ovary and colon.
messages: Homodimer. Interacts with MAVS/IPS1 (PubMed:16177806, PubMed:28011935, PubMed:27980081). Interacts (via protein kinase domain) with TTLL12 (via N-terminus); the interaction prevents MAVS binding to IKBKE (PubMed:28011935). Interacts with the adapter proteins AZI2/NAP1, TANK and TBKBP1/SINTBAD (PubMed:17568778). Interacts with SIKE1 (PubMed:16281057, PubMed:14560022). Interacts with TICAM1/TRIF, IRF3 and RIGI; interactions are disrupted by the interaction between IKBKE and SIKE1 (PubMed:14739303, PubMed:16281057, PubMed:23478265). Interacts with TOPORS; induced by DNA damage (PubMed:20188669). Interacts with CYLD (PubMed:18636086). Interacts (when polyubiquitinated) with IKBKB, IKBKG and MYD88 (PubMed:23453969). Interacts with IFIH1 (PubMed:17600090). Interacts with DDX3X; the interaction may be induced upon virus infection (PubMed:18636090, PubMed:20657822, PubMed:23478265, PubMed:27980081). Interacts with TRIM6 (via SPRY box) (PubMed:24882218). Interacts with unanchored K48-linked polyubiquitin chains; this leads to IKBKE activation (PubMed:24882218). Interacts with TBK1 (PubMed:29251827). Interacts with FKBP5 (PubMed:26101251, PubMed:31434731).
messages: Induced by lipopolysaccharide (LPS) and TNFA.
messages: Nucleus
messages: PML body
messages: Serine/threonine kinase that plays an essential role in regulating inflammatory responses to viral infection, through the activation of the type I IFN, NF-kappa-B and STAT signaling. Also involved in TNFA and inflammatory cytokines, like Interleukin-1, signaling. Following activation of viral RNA sensors, such as RIG-I-like receptors, associates with DDX3X and phosphorylates interferon regulatory factors (IRFs), IRF3 and IRF7, as well as DDX3X. This activity allows subsequent homodimerization and nuclear translocation of the IRF3 leading to transcriptional activation of pro-inflammatory and antiviral genes including IFNB. In order to establish such an antiviral state, IKBKE forms several different complexes whose composition depends on the type of cell and cellular stimuli. Thus, several scaffolding molecules including IPS1/MAVS, TANK, AZI2/NAP1 or TBKBP1/SINTBAD can be recruited to the IKBKE-containing-complexes. Activated by polyubiquitination in response to TNFA and interleukin-1, regulates the NF-kappa-B signaling pathway through, at least, the phosphorylation of CYLD. Phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. In addition, is also required for the induction of a subset of ISGs which displays antiviral activity, may be through the phosphorylation of STAT1 at 'Ser-708'. Phosphorylation of STAT1 at 'Ser-708' seems also to promote the assembly and DNA binding of ISGF3 (STAT1:STAT2:IRF9) complexes compared to GAF (STAT1:STAT1) complexes, in this way regulating the balance between type I and type II IFN responses. Protects cells against DNA damage-induced cell death. Also plays an important role in energy balance regulation by sustaining a state of chronic, low-grade inflammation in obesity, wich leads to a negative impact on insulin sensitivity. Phosphorylates AKT1.
messages: Sumoylation by TOPORS upon DNA damage is required for protection of cells against DNA damage-induced cell death. Desumoylated by SENP1.

9606:ECHS1
gene id: 9606:ECHS1
uniprot id: P30084
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the enoyl-CoA hydratase/isomerase family.
messages: Converts unsaturated trans-2-enoyl-CoA species ((2E)-enoyl-CoA) to the corresponding (3S)-3hydroxyacyl-CoA species through addition of a water molecule to the double bond (PubMed:25125611, PubMed:26251176). Catalyzes the hydration of medium- and short-chained fatty enoyl-CoA thioesters from 4 carbons long (C4) up to C16 (PubMed:26251176). Has high substrate specificity for crotonyl-CoA ((2E)-butenoyl-CoA) and moderate specificity for acryloyl-CoA, 3-methylcrotonyl-CoA (3-methyl-(2E)-butenoyl-CoA) and methacrylyl-CoA ((2E)-2-methylpropenoyl-CoA) (PubMed:26251176). Can bind tiglyl-CoA (2-methylcrotonoyl-CoA), but hydrates only a small amount of this substrate (PubMed:26251176). Plays a key role in the beta-oxidation spiral of short- and medium-chain fatty acid oxidation (PubMed:25125611, PubMed:26251176). At a lower rate than the hydratase reaction, catalyzes the isomerase reaction of trans-3-enoyl-CoA species (such as (3E)-hexenoyl-CoA) to trans-2-enoyl-CoA species (such as (2E)-hexenoyl-CoA), which are subsequently hydrated to 3(S)-3-hydroxyacyl-CoA species (such as (3S)-hydroxyhexanoyl-CoA) (By similarity).
messages: Homohexamer; dimer of trimers.
messages: Liver, fibroblast, muscle. Barely detectable in spleen and kidney.
messages: Mitochondrion matrix
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:ADRB3
gene id: 9606:ADRB3
uniprot id: A8KAG8
uniprot id: P13945
names: Function
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRB3 sub-subfamily.
messages: Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. Beta-3 is involved in the regulation of lipolysis and thermogenesis.
messages: Cell membrane
messages: Expressed mainly in adipose tissues.
messages: Interacts with ARRDC3.
messages: Membrane
messages: The variant Arg-64 seems to be associated with weight gain (obesity) and is also associated with susceptibility to non-insulin-dependent diabetes mellitus (NIDDM).

9606:MTX3
gene id: 9606:MTX3
uniprot id: Q5HYI7
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the metaxin family.
messages: Could function in transport of proteins into the mitochondrion.
messages: Mitochondrion
messages: Mitochondrion outer membrane
messages: Part of a large protein complex spanning both mitochondrial membranes termed the mitochondrial intermembrane space bridging (MIB) complex.

9606:MS4A14
gene id: 9606:MS4A14
uniprot id: Q96JA4
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the MS4A family.
messages: May be involved in signal transduction as a component of a multimeric receptor complex.
messages: Membrane

9606:KRTAP2-2
gene id: 9606:KRTAP2-2
uniprot id: Q9BYT5
names: Function
names: Sequence Caution
names: Similarity
names: Subunit
messages: Belongs to the KRTAP type 2 family.
messages: Chimeric cDNA. The N-terminal part is identical to the product of the KRTAP2-3 gene.
messages: In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins (By similarity).
messages: Interacts with hair keratins.

9606:SVBP
gene id: 9606:SVBP
uniprot id: Q8N300
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the SVBP family.
messages: Cytoplasm
messages: Enhances the tyrosine carboxypeptidase activity of VASH1 and VASH2, thereby promoting the removal of the C-terminal tyrosine residue of alpha-tubulin (PubMed:29146869, PubMed:31270470, PubMed:31235911, PubMed:31324789, PubMed:31171830, PubMed:31235910). This activity is critical for spindle function and accurate chromosome segregation during mitosis since microtubule detyronisation regulates mitotic spindle length and postioning (PubMed:31171830). Also required to enhance the solubility and secretion of VASH1 and VASH2 (PubMed:20736312, PubMed:27879017, PubMed:30607023). Plays a role in axon and excitatory synapse formation (PubMed:31235911).
messages: Interacts with VASH1 and VASH2.
messages: Secreted
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: cytoskeleton

9606:RUFY2
gene id: 9606:RUFY2
uniprot id: Q8WXA3
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Expressed in brain, lung and testis.
messages: Interacts with BMX.
messages: Nucleus

9606:GRIP2
gene id: 9606:GRIP2
uniprot id: Q9C0E4
names: Domain
names: Function
names: Miscellaneous
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the GRIP2 family.
messages: Cytoplasm
messages: Due to intron retention.
messages: Interacts with EFNB1, EFNB3, GRIA2, GRIA3, CSPG4 and GRIPAP1. Can form homomultimers and heteromultimers with GRIP1 (By similarity). Interacts with the C-terminal tail of PRLHR.
messages: May play a role as a localized scaffold for the assembly of a multiprotein signaling complex and as mediator of the trafficking of its binding partners at specific subcellular location in neurons.
messages: Membrane
messages: PDZ 5 mediates the C-terminal binding of GRIA2 and GRIA3. PDZ 6 mediates interaction with the PDZ recognition motif of EFNB1. PDZ 7 mediates interaction with CSPG4 (By similarity).
messages: Probable cloning artifact.

9606:RUNDC3A
gene id: 9606:RUNDC3A
uniprot id: Q59EK9
names: Function
names: Similarity
names: Subunit
messages: Belongs to the RUNDC3 family.
messages: Interacts with the GTP-bound form of RAP2A.
messages: May act as an effector of RAP2A in neuronal cells.

9606:RXYLT1
gene id: 9606:RXYLT1
uniprot id: Q9Y2B1
names: Disease Annotation
names: Function
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Acts as a UDP-D-xylose:ribitol-5-phosphate beta1,4-xylosyltransferase, which catalyzes the transfer of UDP-D-xylose to ribitol 5-phosphate (Rbo5P) to form the Xylbeta1-4Rbo5P linkage on O-mannosyl glycan (PubMed:27733679, PubMed:29477842) (Probable). Participates in the biosynthesis of the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-beta-3-N-acetylglucosamine-beta-4-(phosphate-6-)mannose), a carbohydrate structure present in alpha-dystroglycan (DAG1), which is required for binding laminin G-like domain-containing extracellular proteins with high affinity (PubMed:25279699, PubMed:27601598, PubMed:27733679) (Probable).
messages: Belongs to the RXYLT1 family.
messages: Contaminating sequence. Potential poly-A sequence.
messages: Forms a complex composed of FKTN/fukutin, FKRP and RXYLT1/TMEM5.
messages: Golgi apparatus membrane
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:CMYA5
gene id: 9606:CMYA5
uniprot id: Q8N3K9
names: Domain
names: Function
names: Induction
names: PTM
names: Sequence Caution
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Amphipathic helix regions act as an anchoring domain for PKA, and appear to be responsible of the interaction between myospryn and PRKAR2A.
messages: Contaminating sequence. Potential poly-A sequence.
messages: Cytoplasm
messages: Down-regulated in muscle cell lines derived from patients with Duchenne muscular dystrophy (DMD).
messages: Expressed in skeletal muscle; at a strong level and in heart.
messages: Interacts with PRKAR2A. Interacts with ACTN2 and DTNBP1/dysbindin (By similarity). Interacts with DES (PubMed:17872945). Interacts with DMD/dystrophin (By similarity). Interacts with the calcineurin catalytic subunit PPP3CA (By similarity). Interacts with TTN (PubMed:20634290). Interacts with CAPN3; this interaction, which results in CMYA5 proteolysis, may protect CAPN3 from autolysis (PubMed:20634290). Interacts with FSD2 (By similarity). Identified in a complex composed of FSD2, CMYA5 and RYR2 (By similarity).
messages: M line
messages: May serve as an anchoring protein that mediates the subcellular compartmentation of protein kinase A (PKA) via binding to PRKAR2A (By similarity). May function as a repressor of calcineurin-mediated transcriptional activity. May attenuate calcineurin ability to induce slow-fiber gene program in muscle and may negatively modulate skeletal muscle regeneration (By similarity). Plays a role in the assembly of ryanodine receptor (RYR2) clusters in striated muscle (By similarity).
messages: Nucleus
messages: Phosphorylated by PKA.
messages: Sarcoplasmic reticulum
messages: perinuclear region

9606:WNT5B
gene id: 9606:WNT5B
uniprot id: Q9H1J7
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the Wnt family.
messages: Interacts with PORCN.
messages: Ligand for members of the frizzled family of seven transmembrane receptors. Probable developmental protein. May be a signaling molecule which affects the development of discrete regions of tissues. Is likely to signal over only few cell diameters (By similarity).
messages: Palmitoleoylation is required for efficient binding to frizzled receptors. Depalmitoleoylation leads to Wnt signaling pathway inhibition.
messages: extracellular matrix

9606:A4GNT
gene id: 9606:A4GNT
uniprot id: Q9UNA3
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the glycosyltransferase 32 family.
messages: Catalyzes the transfer of N-acetylglucosamine (GlcNAc) to core 2 branched O-glycans (PubMed:10430883). Necessary for the synthesis of type III mucin which is specifically produced in the stomach, duodenum, and pancreatic duct (PubMed:10430883). May protect against inflammation-associated gastric adenocarcinomas (By similarity).
messages: Detected in stomach and pancreas.
messages: Golgi apparatus membrane
messages: The conserved DXD motif is involved in enzyme activity.

9606:KRTAP9-1
gene id: 9606:KRTAP9-1
uniprot id: A8MXZ3
names: Function
names: Similarity
names: Subunit
messages: Belongs to the KRTAP type 9 family.
messages: In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins (By similarity).
messages: Interacts with hair keratins.

9606:CCL27
gene id: 9606:CCL27
uniprot id: Q5VZ77
uniprot id: Q9Y4X3
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the intercrine beta (chemokine CC) family.
messages: Chemotactic factor that attracts skin-associated memory T-lymphocytes. May play a role in mediating homing of lymphocytes to cutaneous sites. Binds to CCR10.
messages: Monomer, dimer, and tetramer. Heparin avidly promotes oligomerization. Interacts with TNFAIP6 (via Link domain).
messages: Secreted
messages: Testis, thymus, placenta, ovary and skin.

9606:OLFML2B
gene id: 9606:OLFML2B
uniprot id: B4DWE8
uniprot id: F2Z3N3
uniprot id: Q68BL8
names: Caution
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: Homodimer. Binds to heparin and chondroitin sulfate E (By similarity).
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: O-glycosylated and N-glycosylated.
messages: Secreted

9606:GSTZ1
gene id: 9606:GSTZ1
uniprot id: A0A0C4DFM0
uniprot id: O43708
names: Cofactor
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the GST superfamily. Zeta family.
messages: Bifunctional enzyme showing minimal glutathione-conjugating activity with ethacrynic acid and 7-chloro-4-nitrobenz-2-oxa-1,3-diazole and maleylacetoacetate isomerase activity. Has also low glutathione peroxidase activity with T-butyl and cumene hydroperoxides. Is able to catalyze the glutathione dependent oxygenation of dichloroacetic acid to glyoxylic acid.
messages: Cytoplasm
messages: Glutathione is required for the MAAI activity.
messages: Homodimer.
messages: Mostly expressed in liver followed by kidney, skeletal muscle and brain. Also expressed in melanocytes, synovium, placenta, breast and fetal liver and heart.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:RGS16
gene id: 9606:RGS16
uniprot id: O15492
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Abundantly expressed in retina with lower levels of expression in most other tissues.
messages: Interacts with GNAI1 and GNAQ (PubMed:18434541). Interacts with GNAI2, GNAI3 and GNAO1 (By similarity).
messages: Membrane
messages: Palmitoylated on Cys-2 and/or Cys-12.
messages: Phosphorylated. Phosphorylation at Tyr-168 by EGFR enhances GTPase accelerating (GAP) activity toward GNAI1.
messages: Regulates G protein-coupled receptor signaling cascades. Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form (PubMed:11602604, PubMed:18434541). Plays an important role in the phototransduction cascade by regulating the lifetime and effective concentration of activated transducin alpha. May regulate extra and intracellular mitogenic signals (By similarity).

9606:FBXO40
gene id: 9606:FBXO40
uniprot id: Q9UH90
names: Function
names: Miscellaneous
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cytoplasm
messages: Directly interacts with SKP1 and CUL1.
messages: Expressed only in heart and skeletal muscle.
messages: Probable substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex that may function in myogenesis.
messages: The expression decreases in the dystrophic muscle of Limb-girdle muscular dystrophy (LGMD) patient.

9606:LMBR1L
gene id: 9606:LMBR1L
uniprot id: A0A024R0Y9
uniprot id: A0A0S2Z6E3
uniprot id: Q6UX01
names: Developmental Stage
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the LIMR family.
messages: Cell membrane
messages: Dimer (PubMed:23964685). Can also form higher oligomers (PubMed:23964685). Interacts with LCN1; this interaction mediates the endocytosis of LCN1 (PubMed:11287427, PubMed:12591932, PubMed:23964685). Interacts with UBAC2, FAF2, VCP, AMFR, ZNRF3, CTNNB1, LRP6, GSK3A and GSK3B (PubMed:31073040). Interacts with DVL2 and RNF43 (By similarity). Interaction with SCGB1A1 has been observed in PubMed:16423471, but not in PubMed:23964685 (PubMed:16423471, PubMed:23964685). Interaction with LGB which mediates the endocytosis of LGB has been observed in PubMed:17991420, but not in PubMed:23964685 (PubMed:17991420, PubMed:23964685).
messages: Endoplasmic reticulum membrane
messages: Expressed in fetal kidney and lung.
messages: Expressed in testis, pituitary gland, adrenal gland, trachea, placenta, thymus, cerebellum, stomach, mammary gland, spinal cord. A weaker expression is detected in colon, pancreas, and prostate.
messages: Plays an essential role in lymphocyte development by negatively regulating the canonical Wnt signaling pathway (By similarity). In association with UBAC2 and E3 ubiquitin-protein ligase AMFR, promotes the ubiquitin-mediated degradation of CTNNB1 and Wnt receptors FZD6 and LRP6 (By similarity). LMBR1L stabilizes the beta-catenin destruction complex that is required for regulating CTNNB1 levels (By similarity). Acts as a LCN1 receptor and can mediate its endocytosis (PubMed:11287427, PubMed:12591932, PubMed:23964685).

9606:UGT1A9
gene id: 9606:UGT1A9
uniprot id: O60656
uniprot id: Q5DSZ5
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the UDP-glycosyltransferase family.
messages: Endoplasmic reticulum membrane
messages: Expressed in liver, kidney, colon, esophagus and small intestine.
messages: Homodimer (PubMed:17179145). Homooligomer (Probable). Interacts with UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A7, UGT1A8 and UGT1A10 to form heterodimers (PubMed:17179145). Isoform 1 interacts with isoform 2/i2 suggesting that oligomerization is involved in negative regulation of transferase activity by isoform 2. Isoform 1 also interacts with respective i2 isoforms of UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A7, UGT1A8 and UGT1A10 (PubMed:20610558).
messages: Lacks UGT glucuronidation activity but acts as a negative regulator of isoform 1.
messages: Membrane
messages: UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:12181437, PubMed:15472229, PubMed:15470161, PubMed:18004212, PubMed:18052087, PubMed:18674515, PubMed:19545173). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:12181437, PubMed:18004212). Catalyzes the glucuronidation of endogenous estrogen hormones such as estradiol and estrone (PubMed:15472229). Also catalyzes the glucuronidation of the isoflavones genistein, daidzein, glycitein, formononetin, biochanin A and prunetin, which are phytoestrogens with anticancer and cardiovascular properties (PubMed:18052087, PubMed:19545173). Involved in the glucuronidation of the AGTR1 angiotensin receptor antagonist caderastan, a drug which can inhibit the effect of angiotensin II (PubMed:18674515). Involved in the biotransformation of 7-ethyl-10-hydroxycamptothecin (SN-38), the pharmacologically active metabolite of the anticancer drug irinotecan (PubMed:12181437, PubMed:20610558). Also metabolizes mycophenolate, an immunosuppressive agent (PubMed:15470161, PubMed:18004212).
messages: UGT1A9 isoform is part of the UGT1A complex locus which displays alternative use of promoters, first exons and terminal exons. The locus is defined by 13 first exons, which are alternatively spliced to 3 other common exons and 2 alternative terminal exons 5. From the 27 possible mRNA isoforms, 9 produce functionally active polypeptides (UGT1A1, 1A3, 1A4, 1A5, 1A6, 1A7, 1A8, 1A9 and 1A10) called isoforms 1 (i1). Use of an alternative exon 5 (5b) as terminal exon is leading to 9 additional alternatively spliced products termed isoforms i2 and which lack transferase activity.

9606:KRTAP25-1
gene id: 9606:KRTAP25-1
uniprot id: Q3LHN0
names: Function
names: Similarity
names: Subunit
messages: Belongs to the PMG family.
messages: In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins (By similarity).
messages: Interacts with hair keratins.

9606:LHFPL7
gene id: 9606:LHFPL7
uniprot id: A0A0C4DG04
uniprot id: Q6ICI0
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the TMEM211 family.
messages: Membrane

9606:PEA15
gene id: 9606:PEA15
uniprot id: B1AKZ4
uniprot id: Q15121
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Binds RPS6KA3, MAPK3 and MAPK1. Transient interaction with PLD1 and PLD2 (By similarity). Interacts with CASP8 and FADD.
messages: Blocks Ras-mediated inhibition of integrin activation and modulates the ERK MAP kinase cascade. Inhibits RPS6KA3 activities by retaining it in the cytoplasm (By similarity). Inhibits both TNFRSF6- and TNFRSF1A-mediated CASP8 activity and apoptosis. Regulates glucose transport by controlling both the content of SLC2A1 glucose transporters on the plasma membrane and the insulin-dependent trafficking of SLC2A4 from the cell interior to the surface.
messages: Cytoplasm
messages: Phosphorylated by protein kinase C and calcium-calmodulin-dependent protein kinase. These phosphorylation events are modulated by neurotransmitters or hormones.
messages: Ubiquitously expressed. Most abundant in tissues such as heart, brain, muscle and adipose tissue which utilize glucose as an energy source. Lower expression in glucose-producing tissues. Higher levels of expression are found in tissues from individuals with type 2 diabetes than in controls.

9606:EMC6
gene id: 9606:EMC6
uniprot id: Q9BV81
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the EMC6 family.
messages: Component of the ER membrane protein complex (EMC).
messages: Endoplasmic reticulum membrane
messages: Part of the endoplasmic reticulum membrane protein complex (EMC) that enables the energy-independent insertion into endoplasmic reticulum membranes of newly synthesized membrane proteins (PubMed:30415835, PubMed:29809151, PubMed:29242231, PubMed:32459176, PubMed:32439656). Preferentially accommodates proteins with transmembrane domains that are weakly hydrophobic or contain destabilizing features such as charged and aromatic residues (PubMed:30415835, PubMed:29809151, PubMed:29242231). Involved in the cotranslational insertion of multi-pass membrane proteins in which stop-transfer membrane-anchor sequences become ER membrane spanning helices (PubMed:30415835, PubMed:29809151). It is also required for the post-translational insertion of tail-anchored/TA proteins in endoplasmic reticulum membranes (PubMed:29809151, PubMed:29242231). By mediating the proper cotranslational insertion of N-terminal transmembrane domains in an N-exo topology, with translocated N-terminus in the lumen of the ER, controls the topology of multi-pass membrane proteins like the G protein-coupled receptors (PubMed:30415835). By regulating the insertion of various proteins in membranes, it is indirectly involved in many cellular processes (Probable).

9606:CDX1
gene id: 9606:CDX1
uniprot id: P47902
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the Caudal homeobox family.
messages: Intestinal epithelium.
messages: Nucleus
messages: Plays a role in transcriptional regulation (PubMed:24623306). Involved in activated KRAS-mediated transcriptional activation of PRKD1 in colorectal cancer (CRC) cells (PubMed:24623306). Binds to the PRKD1 promoter in colorectal cancer (CRC) cells (PubMed:24623306). Could play a role in the terminal differentiation of the intestine. Binds preferentially to methylated DNA (PubMed:28473536).

9606:BTAF1
gene id: 9606:BTAF1
uniprot id: O14981
uniprot id: Q2M1V9
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Associates with TBP to form B-TFIID. Binds DRAP1.
messages: Belongs to the SNF2/RAD54 helicase family.
messages: Nucleus
messages: Regulates transcription in association with TATA binding protein (TBP). Removes TBP from the TATA box in an ATP-dependent manner.

9606:STIMATE-MUSTN1
gene id: 9606:STIMATE-MUSTN1
uniprot id: A8MSY1
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the MUSTANG family.
messages: Nucleus

9606:OR11H6
gene id: 9606:OR11H6
uniprot id: A0A126GVP4
uniprot id: Q8NGC7
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Membrane
messages: Odorant receptor.

9606:PAN3
gene id: 9606:PAN3
uniprot id: Q58A45
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the protein kinase superfamily. PAN3 family.
messages: Contains a pseudokinase domain. The protein kinase domain is predicted to be catalytically inactive because some of the residues important for catalytic activity are substituted and it lacks the equivalent of the binding site for a peptide substrate. However, it has retained an ATP-binding site and ATP-binding is required for mRNA degradation, stimulating the activity of the PAN2 nuclease in vitro. The nucleotide-binding site is juxtaposed to the RNase active site of PAN2 in the complex and may actually bind nucleosides of a poly(A) RNA rather than ATP, feeding the poly(A)-tail to the active site of the deadenylase and thus increasing the efficiency with which this distributive enzyme degrades oligo(A) RNAs.
messages: Cytoplasm
messages: Decreases PAN2-mediated deadenylation, possibly by preventing progression into the second CCR4-NOT mediated stage of biphasic deadenylation. Has a significant effect on mRNA stability, generally stabilizing a subset of the transcriptome. Stabilizes mRNAs degraded by the AU-rich element (ARE)-mediated mRNA decay pathway but promotes degradation of mRNAs by the microRNA-mediated pathway (PubMed:28559491). Its activity influences mRNP remodeling, specifically reducing formation of a subset of P-bodies containing GW220, an isoform of TNRC6A (PubMed:28559491).
messages: Enhances PAN2 deadenylase activity and has an extensive effect on mRNA stability, generally enhancing mRNA decay across the transcriptome by multiple pathways, including the AU-rich element (ARE)-mediated pathway, microRNA-mediated pathway and the nonsense-mediated pathway (NMD) (PubMed:28559491). Its activity is required for efficient P-body formation (PubMed:28559491). May be involved in regulating mRNAs of genes involved in cell cycle progression and cell proliferation (PubMed:28559491).
messages: Homodimer (PubMed:23932717). Forms a heterotrimer with a catalytic subunit PAN2 to form the poly(A)-nuclease (PAN) deadenylation complex (PubMed:14583602, PubMed:23932717). Interacts (via PAM-2 motif) with poly(A)-binding protein PABPC1 (via PABC domain), conferring substrate specificity of the enzyme complex (PubMed:17595167, PubMed:18056425). Interacts with the GW182 family proteins TNRC6A, TNRC6B and TNRC6 (PubMed:21981923). Interacts with YTHDF3 (By similarity).
messages: Interacts with PAN2 (PubMed:28559491). Interacts (via N-terminus) with PABPC1 at higher efficiency than isoform 1 (PubMed:28559491).
messages: Interacts with PAN2 (PubMed:28559491). Interacts (via N-terminus) with PABPC1 at lower efficiency than isoform 3 (PubMed:28559491).
messages: Nucleus
messages: P-body
messages: Regulatory subunit of the poly(A)-nuclease (PAN) deadenylation complex, one of two cytoplasmic mRNA deadenylases involved in general and miRNA-mediated mRNA turnover. PAN specifically shortens poly(A) tails of RNA and the activity is stimulated by poly(A)-binding protein (PABP). PAN deadenylation is followed by rapid degradation of the shortened mRNA tails by the CCR4-NOT complex. Deadenylated mRNAs are then degraded by two alternative mechanisms, namely exosome-mediated 3'-5' exonucleolytic degradation, or deadenylation-dependent mRNA decapping and subsequent 5'-3' exonucleolytic degradation by XRN1. PAN3 acts as a regulator for PAN activity, recruiting the catalytic subunit PAN2 to mRNA via its interaction with RNA and PABP, and to miRNA targets via its interaction with GW182 family proteins.
messages: The N-terminal zinc finger binds to poly(A) RNA.
messages: The pseudokinase domain, the coiled-coil (CC), and C-terminal knob domain (CK) form a structural unit (PKC) that forms an extensive high-affinity interaction surface for PAN2.

9606:P2RY6
gene id: 9606:P2RY6
uniprot id: Q15077
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Receptor for extracellular UDP > UTP > ATP. The activity of this receptor is mediated by G proteins which activate a phosphatidylinositol-calcium second messenger system.

9606:FHOD3
gene id: 9606:FHOD3
uniprot id: Q2V2M9
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Actin-organizing protein that may cause stress fiber formation together with cell elongation (By similarity). Isoform 4 may play a role in actin filament polymerization in cardiomyocytes.
messages: Belongs to the formin homology family.
messages: Expressed in the heart, kidney and brain. May be down-regulated in various types of heart diseases, including idiopathic dilated, ventricular dilated, familial dilated and perinatal dilated cardiomyopathies, as well as ischemic heart disease (at protein level).
messages: Interacts with nestin/NES-based interfilament (IF) (By similarity). Interacts with SQSTM1; isoform 4 threonine phosphorylation disrupts SQSTM1-binding.
messages: Phosphorylated on Thr-1474 and Thr-1476 by CK2.
messages: The DAD domain regulates activation via by an autoinhibitory interaction with the GBD/FH3 domain. This autoinhibition is released upon competitive binding of an activated GTPase. The release of DAD allows the FH2 domain to then nucleate and elongate nonbranched actin filaments (By similarity).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Z line
messages: cytoskeleton

9606:STOML3
gene id: 9606:STOML3
uniprot id: Q8TAV4
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the band 7/mec-2 family.
messages: Cell membrane
messages: Homodimer. Interacts with PIEZO1 and PIEZO2.
messages: Required for the function of many mechanoreceptors. Modulate mechanotransduction channels and acid-sensing ion channels (ASIC) proteins. Potentiates PIEZO1 and PIEZO2 function by increasing their sensitivity to mechanical stimulations.

9606:SYN2
gene id: 9606:SYN2
uniprot id: B3KRB3
uniprot id: Q59GM1
uniprot id: Q86VA8
uniprot id: Q92777
names: Caution
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the synapsin family.
messages: Can form oligomers with SYN1 (PubMed:23406870). Interacts with CAPON.
messages: Central and peripheral nervous systems.
messages: Disease susceptibility may be associated with variants affecting the gene represented in this entry.
messages: Neuronal phosphoprotein that coats synaptic vesicles, binds to the cytoskeleton, and is believed to function in the regulation of neurotransmitter release. May play a role in noradrenaline secretion by sympathetic neurons (By similarity).
messages: Phosphorylation at Ser-10 dissociates synapsins from synaptic vesicles. Phosphorylation at Ser-425 by MAPK1/ERK2 and/or MAPK3/ERK1 may play a role in noradrenaline secretion by sympathetic neurons (By similarity).
messages: Several in-frame stop codons.
messages: Synapse
messages: The A region binds phospholipids with a preference for negatively charged species.
messages: There are several mRNAs and ESTs supporting this gene model. However, the genome sequence encoding the N-terminal part contains several sequence discrepancies.

9606:AIMP1
gene id: 9606:AIMP1
uniprot id: Q12904
names: Disease Annotation
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: Cleaved by caspase-7 in response to apoptosis to produce EMAP-II.
messages: Endoplasmic reticulum
messages: Golgi apparatus
messages: Homodimer. Part of the multisynthetase complex (MSC), a multisubunit complex that groups tRNA ligases for Arg (RARS1), Asp (DARS1), Gln (QARS1), Ile (IARS1), Leu (LARS1), Lys (KARS1), Met (MARS1) the bifunctional ligase for Glu and Pro (EPRS1) and the auxiliary subunits AIMP1/p43, AIMP2/p38 and EEF1E1/p18 (PubMed:24312579, PubMed:19131329, PubMed:19289464). Interacts (via N-terminus) with RARS1 (via N-terminus) (PubMed:10358004, PubMed:17443684). Part of a complex composed of RARS1, QARS1 and AIMP1 (PubMed:25288775). Interacts (via C-terminus) with SMURF2. Interacts (via N-terminus) with HSP90B1/gp96 (via C-terminus) (By similarity). Interacts with PSMA7 (PubMed:19362550). Interacts with TARS3 (PubMed:24312579).
messages: Non-catalytic component of the multisynthase complex. Stimulates the catalytic activity of cytoplasmic arginyl-tRNA synthase (PubMed:10358004). Binds tRNA. Possesses inflammatory cytokine activity (PubMed:11306575). Negatively regulates TGF-beta signaling through stabilization of SMURF2 by binding to SMURF2 and inhibiting its SMAD7-mediated degradation (By similarity). Involved in glucose homeostasis through induction of glucagon secretion at low glucose levels (By similarity). Promotes dermal fibroblast proliferation and wound repair (PubMed:16472771). Regulates KDELR1-mediated retention of HSP90B1/gp96 in the endoplasmic reticulum (By similarity). Plays a role in angiogenesis by inducing endothelial cell migration at low concentrations and endothelian cell apoptosis at high concentrations (PubMed:12237313). Induces maturation of dendritic cells and monocyte cell adhesion (PubMed:11818442). Modulates endothelial cell responses by degrading HIF-1A through interaction with PSMA7 (PubMed:19362550).
messages: Nucleus
messages: Secreted
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: cytosol

9606:NUBP2
gene id: 9606:NUBP2
uniprot id: Q9Y5Y2
names: Cofactor
names: Developmental Stage
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the Mrp/NBP35 ATP-binding proteins family. NUBP2/CFD1 subfamily.
messages: Binds 4 [4Fe-4S] clusters per heterotetramer. Contains two stable clusters in the N-termini of NUBP1 and two labile, bridging clusters between subunits of the NUBP1-NUBP2 heterotetramer.
messages: Component of the cytosolic iron-sulfur (Fe/S) protein assembly (CIA) machinery. Required for maturation of extramitochondrial Fe-S proteins. The NUBP1-NUBP2 heterotetramer forms a Fe-S scaffold complex, mediating the de novo assembly of an Fe-S cluster and its transfer to target apoproteins. Negatively regulates cilium formation and structure.
messages: Cytoplasm
messages: Expressed in fetal brain, lung, liver and kidney.
messages: Heterotetramer of 2 NUBP1 and 2 NUBP2 chains (By similarity). Interacts with KIFC1 (By similarity). Interacts with NUBP1 (PubMed:18573874).
messages: Nucleus
messages: Widely expressed with highest expression in skeletal muscle.
messages: centriole
messages: centrosome
messages: cilium axoneme
messages: microtubule organizing center

9606:NEIL3
gene id: 9606:NEIL3
uniprot id: Q8TAT5
names: Caution
names: Developmental Stage
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the FPG family.
messages: Chromosome
messages: DNA glycosylase which prefers single-stranded DNA (ssDNA), or partially ssDNA structures such as bubble and fork structures, to double-stranded DNA (dsDNA) (PubMed:12433996, PubMed:19170771, PubMed:22569481, PubMed:23755964). Mediates interstrand cross-link repair in response to replication stress: acts by mediating DNA glycosylase activity, cleaving one of the two N-glycosyl bonds comprising the interstrand cross-link, which avoids the formation of a double-strand break but generates an abasic site that is bypassed by translesion synthesis polymerases (By similarity). In vitro, displays strong glycosylase activity towards the hydantoin lesions spiroiminodihydantoin (Sp) and guanidinohydantoin (Gh) in both ssDNA and dsDNA; also recognizes FapyA, FapyG, 5-OHU, 5-OHC, 5-OHMH, Tg and 8-oxoA lesions in ssDNA (PubMed:12433996, PubMed:19170771, PubMed:22569481, PubMed:23755964). No activity on 8-oxoG detected (PubMed:12433996, PubMed:19170771, PubMed:22569481, PubMed:23755964). Also shows weak DNA-(apurinic or apyrimidinic site) lyase activity (PubMed:12433996, PubMed:19170771, PubMed:22569481, PubMed:23755964). In vivo, appears to be the primary enzyme involved in removing Sp and Gh from ssDNA in neonatal tissues (PubMed:12433996, PubMed:19170771, PubMed:22569481, PubMed:23755964).
messages: Expressed in keratinocytes and embryonic fibroblasts (at protein level). Also detected in thymus, testis and fetal lung primary fibroblasts.
messages: Nucleus
messages: The N-terminal region (2-281) contains the glycosylase and lyase activities.
messages: The RanBP2-type zinc-finger, also named NZF zinc finger, recognizes and binds ubiquitinated CMG helicase complex. The GRF-type zinc-fingers recognize single-stranded DNA (ssDNA), possibly on the lagging strand template.
messages: Up-regulated during early S phase of the cell cycle, and sustained through G/M phase. Low expression levels in quiescent cells.
messages: Was originally thought to be inactive as a glycosylase (PMID:12200441,PMID:19121397), but recent reports (PMID:22569481, PMID:20185759) demonstrate that cleavage of the initiator methionine is essential for catalytic activity.

9606:TP73
gene id: 9606:TP73
uniprot id: A0A0C4DFW9
uniprot id: O15350
names: Cofactor
names: Disease Annotation
names: Domain
names: Function
names: Induction
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts with Epstein-Barr virus protein EBNA6; this interaction inhibits TP73-mediated apoptotic pathway.
messages: Activated and stabilized by interaction with RANBP9.
messages: Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type. Involved in cell cycle regulation as a trans-activator that acts to negatively regulate cell division by controlling a set of genes required for this process. One of the activated genes is an inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression.
messages: Belongs to the p53 family.
messages: Binds 1 zinc ion per subunit.
messages: Binds DNA as a homotetramer.
messages: Cytoplasm
messages: Expressed in striatal neurons of patients with Huntington disease (at protein level). Brain, kidney, placenta, colon, heart, liver, spleen, skeletal muscle, prostate, thymus and pancreas. Highly expressed in fetal tissue. Expressed in the respiratory epithelium (PubMed:34077761).
messages: Found in a complex with p53/TP53 and CABLES1. The C-terminal oligomerization domain binds to the ABL1 tyrosine kinase SH3 domain. Interacts with HECW2. Isoform Beta interacts homotypically and with p53/TP53, whereas isoform Alpha does not. Isoform Gamma interacts homotypically and with all p73 isoforms. Isoform Delta interacts with isoform Gamma, isoform Alpha, and homotypically. Isoforms Alpha and Beta interact with HIPK2. Isoform Alpha interacts with RANBP9. Isoform Beta interacts with WWOX. Interacts (via SAM domain) with FBXO45 (via B30.2/SPRY domain). Interacts with YAP1 (phosphorylated form). Interacts with HCK (via SH3 domain); this inhibits TP73 activity and degradation. Interacts (via SAM domain) with NQO1; this interaction is NADH-dependent, stabilizes TP73 in response to oxidative stress and protects it from ubiquitin-independent degradation by the 20S proteasome.
messages: Higher levels of phosphorylation seen in the brain from patients with Huntington disease.
messages: Isoform alpha (but not isoform beta) is sumoylated on Lys-627, which potentiates proteasomal degradation but does not affect transcriptional activity. Phosphorylation by PLK1 and PLK3 inhibits the transcription regulator activity and pro-apoptotic function.
messages: Maps to a chromosome region frequently mutated in diverse cell lines of human cancer. Appears not to be frequently mutated in human cancers, in contrast to p53/TP53. Hemizygosity is observed in neuroblastoma and oligodendroglioma.
messages: Not induced by DNA damage. Isoforms lacking the transactivation domain block gene induction.
messages: Nucleus
messages: Participates in the apoptotic response to DNA damage. Isoforms containing the transactivation domain are pro-apoptotic, isoforms lacking the domain are anti-apoptotic and block the function of p53 and transactivating p73 isoforms. May be a tumor suppressor protein. Is an activator of FOXJ1 expression (By similarity). It is an essential factor for the positive regulation of lung ciliated cell differentiation (PubMed:34077761).
messages: Polyubiquitinated by RCHY1/PIRH2; leading to its degradation by the proteasome.
messages: Possesses an acidic transactivation domain, a central DNA binding domain and a C-terminal oligomerization domain that binds to the ABL1 tyrosine kinase SH3 domain.
messages: Produced by alternative promoter usage.
messages: Produced by alternative splicing of isoform Alpha.
messages: Produced by alternative splicing of isoform Alpha. The splicing of exon 11 results in a frameshift from the original reading frame.
messages: Produced by alternative splicing of isoform Alpha. The splicing of exon 11 results in a frameshift from the original reading frame. The splicing of exon 13 reverts the reading frame to the sequence of isoform Alpha.
messages: Produced by alternative splicing of isoform dN-Alpha.
messages: The PPxY motif mediates interaction with WWOX.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:BLTP3B
gene id: 9606:BLTP3B
uniprot id: A0JNW5
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Early endosome
messages: Monomer. Homodimer (via N-terminus). Associates with the Golgi-associated retrograde protein (GARP) complex. Interacts with GARP complex component VPS52 (PubMed:20163565). Interacts (via C-terminal coiled-coil domain) with STX6 (PubMed:20163565, PubMed:35499567).
messages: Tube-forming lipid transport protein which mediates the transfer of lipids between membranes at organelle contact sites (PubMed:35499567). Required for retrograde traffic of vesicle clusters in the early endocytic pathway to the Golgi complex (PubMed:35499567, PubMed:20163565).
messages: cytosol

9606:GABBR1
gene id: 9606:GABBR1
uniprot id: A0A1U9X7R0
uniprot id: C9J342
uniprot id: Q59HG8
uniprot id: Q5SUJ9
uniprot id: Q8IW08
uniprot id: Q9UBS5
names: Caution
names: Domain
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Alpha-helical parts of the C-terminal intracellular region mediate heterodimeric interaction with GABBR2 (PubMed:9872744). The linker region between the transmembrane domain 3 (TM3) and the transmembrane domain 4 (TM4) probably plays a role in the specificity for G-protein coupling (PubMed:9844003).
messages: Belongs to the G-protein coupled receptor 3 family. GABA-B receptor subfamily.
messages: Cell membrane
messages: Component of a heterodimeric G-protein coupled receptor for GABA, formed by GABBR1 and GABBR2 (PubMed:9872316, PubMed:9872744, PubMed:15617512, PubMed:18165688, PubMed:22660477, PubMed:24305054). Within the heterodimeric GABA receptor, only GABBR1 seems to bind agonists, while GABBR2 mediates coupling to G proteins (PubMed:18165688). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase (PubMed:10906333, PubMed:10773016, PubMed:10075644, PubMed:9872744, PubMed:24305054). Signaling inhibits adenylate cyclase, stimulates phospholipase A2, activates potassium channels, inactivates voltage-dependent calcium-channels and modulates inositol phospholipid hydrolysis (PubMed:10075644). Calcium is required for high affinity binding to GABA (By similarity). Plays a critical role in the fine-tuning of inhibitory synaptic transmission (PubMed:9844003). Pre-synaptic GABA receptor inhibits neurotransmitter release by down-regulating high-voltage activated calcium channels, whereas postsynaptic GABA receptor decreases neuronal excitability by activating a prominent inwardly rectifying potassium (Kir) conductance that underlies the late inhibitory postsynaptic potentials (PubMed:9844003, PubMed:9872316, PubMed:10075644, PubMed:9872744, PubMed:22660477). Not only implicated in synaptic inhibition but also in hippocampal long-term potentiation, slow wave sleep, muscle relaxation and antinociception (Probable). Activated by (-)-baclofen, cgp27492 and blocked by phaclofen (PubMed:9844003, PubMed:9872316, PubMed:24305054).
messages: Heterodimer of GABBR1 and GABBR2 (PubMed:9872316, PubMed:10773016, PubMed:9872744, PubMed:15617512, PubMed:18165688, PubMed:22660477, PubMed:24305054). Homodimers may form, but are inactive (PubMed:9872316, PubMed:15617512). Isoform 1E (without C-terminal intracellular domain) is unable to dimerize via a coiled-coil interaction with GABBR2 (PubMed:10906333). Interacts (via C-terminus) with ATF4 (via leucine zipper domain) (By similarity). Interacts with JAKMIP1 (PubMed:14718537).
messages: Highly expressed in brain (PubMed:9844003, PubMed:9753614, PubMed:9872744). Weakly expressed in heart, small intestine and uterus. Isoform 1A: Mainly expressed in granular cell and molecular layer (PubMed:9844003). Isoform 1B: Mainly expressed in Purkinje cells (PubMed:9844003). Isoform 1E: Predominantly expressed in peripheral tissues as kidney, lung, trachea, colon, small intestine, stomach, bone marrow, thymus and mammary gland (PubMed:10906333).
messages: Isoform 1E may regulate the formation of functional GABBR1/GABBR2 heterodimers by competing for GABBR2 binding. This could explain the observation that certain small molecule ligands exhibit differential affinity for central versus peripheral sites.
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: Major isoform in almost all peripheral tissues, although containing a premature stop codon in the mRNA and thus being a potential target for nonsense-mediated mRNA decay. May act as an antagonist of GABA-B receptors, being able to disrupt the normal association between isoform 1A and GABBR2.
messages: Membrane
messages: Postsynaptic cell membrane
messages: Secreted
messages: dendrite

9606:ZNF160
gene id: 9606:ZNF160
uniprot id: Q9HCG1
names: Function
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: Dubious alternative splicing.
messages: May be involved in transcriptional regulation.
messages: Nucleus
messages: Ubiquitous.

9606:YIPF2
gene id: 9606:YIPF2
uniprot id: K7ENM8
uniprot id: Q9BWQ6
names: Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the YIP1 family.
messages: Endosome membrane
messages: Golgi apparatus membrane
messages: Interacts with YIPF6; this interaction may stabilize YIPF2. May also form a ternary complex with YIPF1 and YIPF6.
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: Late endosome membrane
messages: Membrane
messages: cis-Golgi network membrane
messages: trans-Golgi network membrane

9606:CBX1
gene id: 9606:CBX1
uniprot id: P83916
uniprot id: Q6IBN6
names: Caution
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Component of heterochromatin. Recognizes and binds histone H3 tails methylated at 'Lys-9', leading to epigenetic repression. Interaction with lamin B receptor (LBR) can contribute to the association of the heterochromatin with the inner nuclear membrane.
messages: Expressed in all adult and embryonic tissues.
messages: Homodimer (By similarity). Interacts directly with CHAF1A, EMSY, LBR, TIF1/TIF1A and TRIM28/TIF1B PXVXL motif via the chromoshadow domain (PubMed:14651845, PubMed:16615912). Interacts directly with histone H3 methylated at 'Lys-9' via the chromo domain (By similarity). Interacts with SUV39H1 and SETDB1, KMT5B and KMT5C (PubMed:10202156, PubMed:15899859). Interacts with PRDM6 (By similarity). Interacts with POGZ (PubMed:20850016, PubMed:20562864). Interacts with CHAMP1 (PubMed:20850016). Interacts with INCENP (PubMed:21346195). Interacts with SGO1; the CBX1 homodimer binds to one molecule of SGO1 (PubMed:21346195). Interacts with LRIF1 (via PxVxL motif) (PubMed:23542155). Interacts with HDGFL2 (PubMed:26721387). Interacts with CHD3 (PubMed:28977666). Interacts with CHD4 (PubMed:28977666).
messages: Not phosphorylated.
messages: Nucleus
messages: Ubiquitinated.
messages: Was previously reported to interact with ASXL1. However, this publication has been retracted.

9606:LRGUK
gene id: 9606:LRGUK
uniprot id: Q96M69
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Interacts (via guanylate kinase-like domain) with RIMBP3 (via coiled-coil region). Interacts (via guanylate kinase-like domain) with HOOK2. Interacts (via LRRCT domain) with KLC3. Interacts with HOOK1 and HOOK3.
messages: Involved in multiple aspects of sperm assembly including acrosome attachment, shaping of the sperm head and in the early aspects of axoneme development. Not essential for primary cilium biogenesis.
messages: acrosome
messages: cilium basal body
messages: cytoskeleton

9606:SLC47A1
gene id: 9606:SLC47A1
uniprot id: Q96FL8
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Apical cell membrane
messages: Belongs to the multi antimicrobial extrusion (MATE) (TC 2.A.66.1) family.
messages: Cell membrane
messages: Mediates the efflux of cationic compounds such as the model cations, tetraethylammonium (TEA), the neurotoxin 1-methyl-4-phenylpyridinium (MPP), the platinum-based drugs cisplatin and oxaliplatin, the drugs procainamide, acyclovir and topotecan, or weak bases that are positively charged at physiological pH, such as cimetidine or the antidiabetic drug metformin.
messages: Multidrug efflux pump that functions as a H(+)/organic cation antiporter (PubMed:16330770, PubMed:17509534). Plays a physiological role in the excretion of cationic compounds including endogenous metabolites, drugs, toxins through the kidney and liver, into urine and bile respectively (PubMed:16330770, PubMed:17495125, PubMed:17509534, PubMed:17582384, PubMed:18305230, PubMed:19158817, PubMed:21128598, PubMed:24961373). Mediates the efflux of endogenous compounds such as creatinine, vitamin B1/thiamine, agmatine and estrone-3-sulfate (PubMed:16330770, PubMed:17495125, PubMed:17509534, PubMed:17582384, PubMed:18305230, PubMed:19158817, PubMed:21128598, PubMed:24961373). May also contribute to regulate the transport of cationic compounds in testis across the blood-testis-barrier (Probable).
messages: Widely expressed. The highest expression is found in adrenal gland, and to a lower extent in liver, skeletal muscle and kidney. In testis, primarily localized throughout the adluminal compartment of the seminiferous tubules with expression at the peritubular myoid cells and Leydig cells (PubMed:35307651).

9606:PURB
gene id: 9606:PURB
uniprot id: Q96QR8
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the PUR DNA-binding protein family.
messages: Defects in PURB may be a cause of progression of myelodysplastic syndrome (MDS) towards acute myelogenous leukemia (AML). MDS refers to a heterogeneous group of closely related hematopoietic disorders. All are characterized by a cellular marrow with impaired morphology and maturation (dysmyelopoiesis) and peripheral blood cytopenias, resulting from ineffective blood cell production. Some patients with MDS develop acute myelogenous leukemia (AML), a malignant disease in which hematopoietic precursors are arrested in an early stage of development.
messages: Expressed in myocardium of heart failure patients.
messages: Has capacity to bind repeated elements in single-stranded DNA such as the purine-rich single strand of the PUR element located upstream of the MYC gene. Plays a role in the control of vascular smooth muscle (VSM) alpha-actin gene transcription as repressor in myoblasts and fibroblasts. Participates in transcriptional and translational regulation of alpha-MHC expression in cardiac myocytes by binding to the purine-rich negative regulatory (PNR) element. Modulates constitutive liver galectin-3 gene transcription by binding to its promoter. May play a role in the dendritic transport of a subset of mRNAs (By similarity).
messages: Homodimer, heterodimer with PURA and heterotrimer with PURA and YBX1/Y-box protein 1.
messages: Nucleus

9606:RNF24
gene id: 9606:RNF24
uniprot id: Q9Y225
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Golgi apparatus membrane
messages: Interacts with TRPC1, TRPC3, TRPC4, TRPC5, TRPC6 and TRPC7.
messages: May play a role in TRPCs intracellular trafficking.

9606:AMMECR1
gene id: 9606:AMMECR1
uniprot id: Q9Y4X0
names: Disease Annotation
names: Subcellular Location Annotation
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The gene represented in this entry may be involved in disease pathogenesis.

9606:AAGAB
gene id: 9606:AAGAB
uniprot id: Q6PD74
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Associated with AP-1 and AP-2 complexes.
messages: May be involved in endocytic recycling of growth factor receptors such as EGFR.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Widely expressed, including in skin and keratinocytes, with highest levels in adrenal gland, rectum and thymus.
messages: cytosol

9606:CYTH4
gene id: 9606:CYTH4
uniprot id: Q9UIA0
names: Domain
names: Function
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Autoinhibited by its C-terminal basic region.
messages: Binds via its PH domain to the inositol head group of phosphatidylinositol 3,4,5-trisphosphate.
messages: Cell membrane
messages: Expressed predominantly in peripheral blood leukocytes.
messages: Promotes guanine-nucleotide exchange on ARF1 and ARF5. Promotes the activation of ARF factors through replacement of GDP with GTP.

9606:ABCA3
gene id: 9606:ABCA3
uniprot id: Q4LE27
uniprot id: Q99758
names: Activity Regulation
names: Disease Annotation
names: Domain
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the ABC transporter superfamily. ABCA family.
messages: Catalyzes the ATP-dependent transport of phospholipids such as phosphatidylcholine and phosphoglycerol from the cytoplasm into the lumen side of lamellar bodies, in turn participates in the lamellar bodies biogenesis and homeostasis of pulmonary surfactant (PubMed:16959783, PubMed:17574245, PubMed:28887056, PubMed:31473345, PubMed:27177387). Transports preferentially phosphatidylcholine containing short acyl chains (PubMed:27177387). In addition plays a role as an efflux transporter of miltefosine across macrophage membranes and free cholesterol (FC) through intralumenal vesicles by removing FC from the cell as a component of surfactant and protects cells from free cholesterol toxicity (PubMed:26903515, PubMed:25817392, PubMed:27177387).
messages: Cytoplasmic vesicle membrane
messages: Expressed in brain, pancreas, skeletal muscle and heart (PubMed:8706931). Highly expressed in the lung in an AT2-cell-specific manner (PubMed:11718719, PubMed:8706931). Weakly expressed in placenta, kidney and liver (PubMed:8706931). Also expressed in medullary thyroid carcinoma cells (MTC) and in C-cell carcinoma (PubMed:8706931).
messages: Homooligomer; disulfide-linked.
messages: Late endosome membrane
messages: Lysosome membrane
messages: Membrane
messages: Multifunctional polypeptide with two homologous halves, each containing a hydrophobic membrane-anchoring domain and an ATP binding cassette (ABC) domain.
messages: N-glycosylated (PubMed:16959783, PubMed:24142515, PubMed:27177387). Localization at intracellular vesicles is accompanied by processing of oligosaccharide from high mannose type to complex type (PubMed:16959783, PubMed:27177387). N-linked glycosylation at Asn-124 and Asn-140 is required for stability and efficient anterograde trafficking and prevents from proteasomal degradation (PubMed:24142515).
messages: Proteolytically cleaved by CTSL and to a lower extent by CTSB within multivesicular bodies (MVB) and lamellar bodies (LB) leading to a mature form of 150 kDa.
messages: The ATP-dependent phosphatidylcholine transport is competitively inhibited by miltefosine.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Up-regulated in Leishmania Viannia (L.V.) panamensis-infected macrophages exposed to miltefosine (PubMed:26903515). Down-regulated by L. V. panamensis infection (PubMed:26903515).
messages: multivesicular body membrane

9606:AHRR
gene id: 9606:AHRR
uniprot id: A9YTQ3
names: Function
names: Induction
names: Polymorphism
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: By 3-methylcholanthrene (3-MC) in MNCs from adults. By the heterodimer AHR/ARNT.
messages: Cytoplasm
messages: Highly expressed in testis, lung, ovary, spleen and pancreas. Highly expressed in mononuclear cells (MNCs) from umbilical cord blood. Isoform 3 is highly expressed in lung, kidney, spleen and thymus. Down-regulated malignant tissue from different anatomical origins, including colon, breast, lung, stomach, cervix, and ovary.
messages: Interacts with ANKRA2, HDAC4 and HDAC5. Interacts with ARNT; forms a heterodimer with ARNT (PubMed:28904176).
messages: Mediates dioxin toxicity and is involved in regulation of cell growth and differentiation. Represses the transcription activity of AHR by competing with this transcription factor for heterodimer formation with the ARNT and subsequently binding to the xenobiotic response element (XRE) sequence present in the promoter regulatory region of variety of genes. Represses CYP1A1 by binding the XRE sequence and recruiting ANKRA2, HDAC4 and/or HDAC5. Autoregulates its expression by associating with its own XRE site.
messages: Nucleus
messages: The Ala-189 allele may be a susceptibility factor for dioxin-related male infertility. Homozygosity for Ala-189 is observed in azoospermic individuals at higher frequency than in normozoospermic individuals (PubMed:15474075, PubMed:17559847). Might also be associated with susceptibility to and severity of endometriosis.

9606:MACROH2A2
gene id: 9606:MACROH2A2
uniprot id: Q9P0M6
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Chromosome
messages: Nucleus
messages: The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers.
messages: Variant histone H2A which replaces conventional H2A in a subset of nucleosomes where it represses transcription. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. May be involved in stable X chromosome inactivation.

9606:TCP11
gene id: 9606:TCP11
uniprot id: B7ZAT8
uniprot id: Q8WWU5
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the TCP11 family.
messages: Constitutively phosphorylated on serine, threonine and tyrosine residues within the head and tail regions of noncapacitated spermatozoa. Phosphorylation on tyrosine residues increases upon sperm capacitation within the acrosomal region in a protein kinase A (PKA)-dependent signaling pathway.
messages: Found in a complex at least composed of MROH2B, PRKACA isoform 2 and TCP11. Interacts with MROH2B. Interacts with PRKACA isoform 2 (By similarity). Isoform 2 and isoform 3 interact with ODF1 (via leucine zipper motif) (PubMed:21597245).
messages: Isoform 2 and isoform 3 are expressed in sperm. Isoform 1 is not detected in sperm (at protein level) (PubMed:21597245). Testis-specific (PubMed:11756566). Isoform 1, isoform 2 and isoform 3 are expressed in sperm (PubMed:21597245).
messages: Membrane
messages: Plays a role in the process of sperm capacitation and acrosome reactions. Probable receptor for the putative fertilization-promoting peptide (FPP) at the sperm membrane that may modulate the activity of the adenylyl cyclase cAMP pathway.
messages: acrosome
messages: flagellum

9606:PLEK2
gene id: 9606:PLEK2
uniprot id: Q9NYT0
names: Function
names: Subcellular Location Annotation
messages: May help orchestrate cytoskeletal arrangement. Contribute to lamellipodia formation.
messages: cytoskeleton
messages: lamellipodium membrane

9606:BDH1
gene id: 9606:BDH1
uniprot id: A0A384MTY4
uniprot id: Q02338
names: Activity Regulation
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the short-chain dehydrogenases/reductases (SDR) family.
messages: Homotetramer.
messages: Mitochondrion inner membrane
messages: Mitochondrion matrix
messages: Requires phosphatidylcholine as an allosteric activator for enzymatic activity.

9606:GPRASP2
gene id: 9606:GPRASP2
uniprot id: B3KW05
uniprot id: Q96D09
names: Disease Annotation
names: Function
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Belongs to the GPRASP family.
messages: Expressed in the brain.
messages: Interacts with cytoplasmic tails of a variety of G-protein coupled receptors such as muscarinic acetylcholine receptor M1/CHRM1 and calcitonin receptor/CALCR.
messages: May play a role in regulation of a variety of G-protein coupled receptors.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:SYNCRIP
gene id: 9606:SYNCRIP
uniprot id: A0A7I2YQN2
uniprot id: B7Z645
uniprot id: O60506
uniprot id: Q59GL1
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Sequence Caution
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts with herpes virus 8/HHV-8 protein vIRF-1; this interaction induces ubiquitination and degradation of SYNCRIP.
messages: (Microbial infection) Interacts with minute virus of mice (MVM) NS1 protein.
messages: Contaminating sequence. Potential poly-A sequence starting in position 413.
messages: Cytoplasm
messages: Endoplasmic reticulum
messages: Heterogenous nuclear ribonucleoprotein (hnRNP) implicated in mRNA processing mechanisms. Component of the CRD-mediated complex that promotes MYC mRNA stability. Isoform 1, isoform 2 and isoform 3 are associated in vitro with pre-mRNA, splicing intermediates and mature mRNA protein complexes. Isoform 1 binds to apoB mRNA AU-rich sequences. Isoform 1 is part of the APOB mRNA editosome complex and may modulate the postranscriptional C to U RNA-editing of the APOB mRNA through either by binding to A1CF (APOBEC1 complementation factor), to APOBEC1 or to RNA itself. May be involved in translationally coupled mRNA turnover. Implicated with other RNA-binding proteins in the cytoplasmic deadenylation/translational and decay interplay of the FOS mRNA mediated by the major coding-region determinant of instability (mCRD) domain. Interacts in vitro preferentially with poly(A) and poly(U) RNA sequences. Isoform 3 may be involved in cytoplasmic vesicle-based mRNA transport through interaction with synaptotagmins. Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes. Upon interferon-gamma activation assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation; seems not to be essential for GAIT complex function.
messages: Isoform 1 is a component of the APOB mRNA editosome complex and interacts with APOBEC1 and A1CF (APOBEC1 complementation factor). Part of a complex associated with the FOS mCRD domain and consisting of PABPC1, PAIP1, CSDE1/UNR, HNRPD and SYNCRIP. Isoform 3 interacts with HNRPR. Interacts with POLR2A hyperphosphorylated C-terminal domain. Isoform 1, isoform 2 and isoform 3 interact with SMN. Isoform 3 interacts through its C-terminal domain with SYT7, SYT8 and SYT9 (By similarity). The non-phosphorylated and phosphorylated forms are colocalized with PAIP1 in polysomes (By similarity). Interacts with HABP4 (PubMed:19523114). Identified in a histone pre-mRNA complex, at least composed of ERI1, LSM11, SLBP, SNRPB, SYNCRIP and YBX1 (By similarity). Identified in the spliceosome C complex. Component of the coding region determinant (CRD)-mediated complex, composed of DHX9, HNRNPU, IGF2BP1, SYNCRIP and YBX1. Identified in a mRNP complex, at least composed of DHX9, DDX3X, ELAVL1, HNRNPU, IGF2BP1, ILF3, PABPC1, PCBP2, PTBP2, STAU1, STAU2, SYNCRIP and YBX1. Identified in a mRNP granule complex, at least composed of ACTB, ACTN4, DHX9, ERG, HNRNPA1, HNRNPA2B1, HNRNPAB, HNRNPD, HNRNPL, HNRNPR, HNRNPU, HSPA1, HSPA8, IGF2BP1, ILF2, ILF3, NCBP1, NCL, PABPC1, PABPC4, PABPN1, RPLP0, RPS3, RPS3A, RPS4X, RPS8, RPS9, SYNCRIP, YBX1 and untranslated mRNAs. Interacts with GTPBP1. Component of the GAIT complex; in humans the complex assembly seems to be a two-step process in which EPRS1 first associates with SYNCRIP to form a pre-GAIT complex which is deficient in GAIT element binding.
messages: May be due to a competing donor splice site and to an exon inclusion.
messages: May be due to a competing donor splice site.
messages: Microsome
messages: Nucleus
messages: Phosphorylated on tyrosine. The membrane-bound form found in microsomes is phosphorylated in vitro by insulin receptor tyrosine kinase (INSR). Phosphorylation is inhibited upon binding to RNA, whereas the cytoplasmic form is poorly phosphorylated (By similarity).
messages: The domain containing eight Arg-Gly-Gly repeats (RGG/RXR-box) may be involved in RNA-binding and protein-protein interactions. It is methylated by PRMT1, and essential for nuclear localization.
messages: Ubiquitously expressed. Detected in heart, brain, pancreas, placenta, spleen, lung, liver, skeletal muscle, kidney, thymus, prostate, uterus, small intestine, colon, peripheral blood and testis.
messages: nucleoplasm

9606:ZNF529
gene id: 9606:ZNF529
uniprot id: Q6P280
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:TECPR2
gene id: 9606:TECPR2
uniprot id: O15040
names: Disease Annotation
names: Function
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Belongs to the WD repeat KIAA0329 family.
messages: Detected in skin fibroblast (at protein level).
messages: Interacts with the ATG8 family members GABARAP, GABARAPL1, GABARAPL2, MAP1LC3B and MAP1LC3C.
messages: Probably plays a role as positive regulator of autophagy.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:PCYT1B
gene id: 9606:PCYT1B
uniprot id: Q9Y5K3
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the cytidylyltransferase family.
messages: Catalyzes the key rate-limiting step in the CDP-choline pathway for phosphatidylcholine biosynthesis.
messages: Cytoplasm
messages: Endoplasmic reticulum
messages: Expressed in brain, liver and fetal lung.
messages: Extensively phosphorylated.
messages: Highly expressed in testis, placenta, brain, ovary, liver and fetal lung.
messages: Homodimer.
messages: Phosphorylated.

9606:VWA3B
gene id: 9606:VWA3B
uniprot id: Q502W6
names: Disease Annotation
names: Subcellular Location Annotation
messages: Cytoplasm
messages: The disease may be caused by variants affecting the gene represented in this entry.

9606:COMMD2
gene id: 9606:COMMD2
uniprot id: Q86X83
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cytoplasm
messages: Interacts (via COMM domain) with COMMD1 (via COMM domain) (PubMed:15799966). Interacts with RELA, RELB, NFKB1/p105, NFKB2/p100. Interacts with CCDC22, CCDC93, SCNN1B, CUL3, CUL4B, CUL5, CUL7 (PubMed:28892079, PubMed:15799966, PubMed:21778237, PubMed:23563313, PubMed:23637203, PubMed:25355947).
messages: May modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes (PubMed:21778237). May down-regulate activation of NF-kappa-B (PubMed:15799966).
messages: Ubiquitous.

9606:CLIP3
gene id: 9606:CLIP3
uniprot id: Q96DZ5
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: Cell membrane
messages: Cytoplasm
messages: Functions as a cytoplasmic linker protein. Involved in TGN-endosome dynamics. May modulate the cellular compartmentalization of AKT kinase family and promote its cell membrane localization, thereby playing a role in glucose transport in adipocytes.
messages: Golgi stack
messages: Homodimer. Interacts with AKT1 and AKT2; when AKT1 and AKT2 are phosphorylated and activated, affinity is higher for AKT2 (PubMed:19139280). Interacts with ZDHHC13 (via ANK repeats) (PubMed:26198635). Interacts with ZDHHC17 (via ANK repeats) (PubMed:26198635, PubMed:28882895).
messages: Microtubule association is inhibited by the ANK repeats and the Golgi localization region (GoLD).
messages: Palmitoylation by ZDHHC17 regulates association with the plasma membrane.
messages: The N-terminal half is dispensable for proper Golgi targeting, whereas the GoLD region is required.

9606:SPRING1
gene id: 9606:SPRING1
uniprot id: Q9H741
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the SPRING family.
messages: Golgi apparatus membrane
messages: Interacts with SCAP.
messages: Positively regulates hepatic SREBP signaling pathway by modulating the proper localization of SCAP (SREBP cleavage-activating protein) to the endoplasmic reticulum, thereby controlling the level of functional SCAP.

9606:MAD2L1
gene id: 9606:MAD2L1
uniprot id: Q13257
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the MAD2 family.
messages: Component of the spindle-assembly checkpoint that prevents the onset of anaphase until all chromosomes are properly aligned at the metaphase plate (PubMed:29162720, PubMed:15024386). In the closed conformation (C-MAD2) forms a heterotetrameric complex with MAD1L1 at unattached kinetochores during prometaphase, the complex recruits open conformation molecules of MAD2L1 (O-MAD2) and then promotes the conversion of O-MAD2 to C-MAD2 (PubMed:29162720). Required for the execution of the mitotic checkpoint which monitors the process of kinetochore-spindle attachment and inhibits the activity of the anaphase promoting complex by sequestering CDC20 until all chromosomes are aligned at the metaphase plate (PubMed:10700282, PubMed:11804586, PubMed:15024386).
messages: Cytoplasm
messages: Monomer and homodimer (PubMed:18022367, PubMed:18318601). Heterodimerizes with MAD2L1 in order to form a tetrameric MAD1L1-MAD2L1 core complex (PubMed:12574116, PubMed:18981471, PubMed:12006501, PubMed:15024386). In the closed and open conformation, interacts with MAD1L1 (PubMed:29162720). Formation of a heterotetrameric core complex containing two molecules each of MAD1L1 and of MAD2L1 promotes binding of another molecule of MAD2L1 to each MAD2L1, resulting in a heterohexamer (PubMed:12006501). Interacts with MAD2L1BP (PubMed:12456649, PubMed:18022368). Interacts with ADAM17/TACE (PubMed:10527948). Interacts with CDC20 (PubMed:9637688, PubMed:12574116, PubMed:18981471, PubMed:10700282). Dimeric MAD2L1 in the closed conformation interacts with CDC20 (PubMed:29162720). Monomeric MAD2L1 in the open conformation does not interact with CDC20 (PubMed:11804586). CDC20 competes with MAD1L1 for MAD2L1 binding (PubMed:11804586). In the closed conformation, interacts with BUB1B (PubMed:29162720). Interacts with TTK (PubMed:29162720). Interacts with TPR (PubMed:18981471). Binds to UBD (via ubiquitin-like 1 domain) during mitosis (PubMed:16495226, PubMed:25422469). Interacts with isoform 1 and isoform 2 of NEK2 (PubMed:20034488). Interacts with HSF1; this interaction occurs in mitosis (PubMed:18794143). Interacts with isoform 3 of MAD1L1; this interaction leads to the cytoplasmic sequestration of MAD2L1 (PubMed:19010891).
messages: Nucleus
messages: Phosphorylated on multiple serine residues. The level of phosphorylation varies during the cell cycle and is highest during mitosis. Phosphorylation abolishes interaction with MAD1L1 and reduces interaction with CDC20. Phosphorylated by NEK2.
messages: The protein has two highly different native conformations, an inactive open conformation that cannot bind CDC20 and that predominates in cytosolic monomers, and an active closed conformation. The protein in the closed conformation preferentially dimerizes with another molecule in the open conformation, but can also form a dimer with a molecule in the closed conformation. Formation of a heterotetrameric core complex containing two molecules of MAD1L1 and of MAD2L1 in the closed conformation promotes binding of another molecule of MAD2L1 in the open conformation and the conversion of the open to the closed form, and thereby promotes interaction with CDC20.
messages: kinetochore
messages: spindle pole

9606:ENKUR
gene id: 9606:ENKUR
uniprot id: A0A087WUX1
uniprot id: Q8TC29
names: Domain
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Adapter that functions to localize a calcium-sensitive signal transduction machinery in sperm to a calcium-permeable ion channel (By similarity). Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating (PubMed:36191189).
messages: Binds calmodulin via its IQ domain. Interacts with TRPC1, TRPC2, TRPC5, but not TRPC3 (By similarity). Interacts with CFAP45 (PubMed:33139725).
messages: Expressed in airway epithelial cells.
messages: The IQ motif is involved in calmodulin binding.
messages: cilium axoneme
messages: flagellum

9606:ICMT
gene id: 9606:ICMT
uniprot id: B3KS61
uniprot id: O60725
names: Activity Regulation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the class VI-like SAM-binding methyltransferase superfamily. Isoprenylcysteine carboxyl methyltransferase family.
messages: Catalyzes the post-translational methylation of isoprenylated C-terminal cysteine residues.
messages: Competitively inhibited by N-acetyl-S-trans,trans-farnesyl-l-cysteine (AFC).
messages: Endoplasmic reticulum membrane
messages: Membrane
messages: Ubiquitously expressed. Expressed at higher levels in the cerebellum and putamen than in other brain regions. Abundant expression seen in the Purkinje cells and pontine neurons.

9606:SLC11A1
gene id: 9606:SLC11A1
uniprot id: P49279
names: Function
names: Induction
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the NRAMP family.
messages: Genetic variation in SLC11A1 is associated with susceptibility to infection with Mycobacterium ulcerans [MIM:610446].
messages: Genetic variations in SLC11A1 determine Mycobacterium tuberculosis susceptibility [MIM:607948].
messages: In response to lymphokine or bacterial products.
messages: Late endosome membrane
messages: Lysosome membrane
messages: Macrophage-specific antiporter that fluxes metal ions in either direction against a proton gradient. Localized to late endosomal lysosomal membranes, delivers bivalent cations from the cytosol into these acidic compartments where they may directly affect antimicrobial activity (PubMed:11237855). Involved in iron metabolism and host natural resistance to infection with intracellular parasites. Pathogen resistance involves sequestration of Fe(2+) and Mn(2+), cofactors of both prokaryotic and eukaryotic catalases and superoxide dismutases, not only to protect the macrophage against its own generation of reactive oxygen species, but to deny the cations to the pathogen for synthesis of its protective enzymes (Probable).
messages: Macrophages; peripheral blood leukocytes, lung, spleen and liver.

9606:ADAMTS1
gene id: 9606:ADAMTS1
uniprot id: B2RB33
uniprot id: Q9UHI8
names: Caution
names: Cofactor
names: Domain
names: Function
names: PTM
names: Subcellular Location Annotation
messages: Binds 1 zinc ion per subunit.
messages: Cleaves aggrecan, a cartilage proteoglycan, at the '1938-Glu-|-Leu-1939' site (within the chondroitin sulfate attachment domain), and may be involved in its turnover (By similarity). Has angiogenic inhibitor activity. Active metalloprotease, which may be associated with various inflammatory processes as well as development of cancer cachexia. May play a critical role in follicular rupture.
messages: Glycosylated. Can be O-fucosylated by POFUT2 on a serine or a threonine residue found within the consensus sequence C1-X(2)-(S/T)-C2-G of the TSP type-1 repeat domains where C1 and C2 are the first and second cysteine residue of the repeat, respectively. Fucosylated repeats can then be further glycosylated by the addition of a beta-1,3-glucose residue by the glucosyltransferase, B3GALTL. Fucosylation mediates the efficient secretion of ADAMTS family members. Can also be C-glycosylated with one or two mannose molecules on tryptophan residues within the consensus sequence W-X-X-W of the TPRs, and N-glycosylated. These other glycosylations can also facilitate secretion (By similarity).
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.
messages: The precursor is cleaved by a furin endopeptidase.
messages: The spacer domain and the TSP type-1 domains are important for a tight interaction with the extracellular matrix.
messages: extracellular matrix

9606:BMP7
gene id: 9606:BMP7
uniprot id: A8K571
uniprot id: P18075
names: Developmental Stage
names: Function
names: PTM
names: Pharmaceutical
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Available under the name Osigraft (Stryker). Its use is indicated in the treatment of tibial non-union of at least 9 months duration, secondary to trauma, in skeletally mature patients, in cases where autograft has failed or is unfeasible.
messages: Belongs to the TGF-beta family.
messages: Expressed in the developing eye, brain and ear during embryogenesis.
messages: Expressed in the kidney and bladder. Lower levels seen in the brain.
messages: Growth factor of the TGF-beta superfamily that plays important role in various biological processes, including embryogenesis, hematopoiesis, neurogenesis and skeletal morphogenesis (PubMed:31208997). Initiates the canonical BMP signaling cascade by associating with type I receptor ACVR1 and type II receptor ACVR2A (PubMed:9748228, PubMed:12667445). Once all three components are bound together in a complex at the cell surface, ACVR2A phosphorylates and activates ACVR1. In turn, ACVR1 propagates signal by phosphorylating SMAD1/5/8 that travel to the nucleus and act as activators and repressors of transcription of target genes (PubMed:12478285). For specific functions such as growth cone collapse in developing spinal neurons and chemotaxis of monocytes, uses also BMPR2 as type II receptor (PubMed:31208997). Can also signal through non-canonical pathways such as P38 MAP kinase signaling cascade that promotes brown adipocyte differentiation through activation of target genes, including members of the SOX family of transcription factors (PubMed:27923061). Promotes the expression of HAMP, this is repressed by its interaction with ERFE (PubMed:30097509).
messages: Homodimer; disulfide-linked (PubMed:8570652). Interacts with SOSTDC1 (PubMed:15020244). Interacts with TWSG1 (By similarity). Interacts with FBN1 (via N-terminal domain) and FBN2 (PubMed:18339631). Interacts with type I receptor ACVR1 (PubMed:9748228). Interacts with type II receptor ACVR2A (PubMed:12667445). Interacts with NOG; this interaction inhibits canonical BMP signaling (PubMed:12478285). Interacts with SCUBE3 (PubMed:33308444). Interacts with ERFE; the interaction inhibits BMP-induced transcription of HAMP (PubMed:30097509).
messages: Secreted
messages: Several N-termini starting at positions 293, 300, 315 and 316 have been identified by direct sequencing resulting in secretion of different mature forms.

9606:CPEB1
gene id: 9606:CPEB1
uniprot id: B4DWY2
uniprot id: Q9BZB8
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the RRM CPEB family.
messages: Cytoplasm
messages: Cytoplasmic granule
messages: Interacts with kinesin, dynein, APLP1, APLP2, TENT2/GLD2 and APP. Both phosphorylated and non phosphorylated forms interact with APLP1 (By similarity). Interacts with TENT4B; the interaction is required for TENT4B-mediated translational control (PubMed:28383716).
messages: Isoform 1 is expressed in immature oocytes, ovary, brain and heart. Isoform 2 is expressed in brain and heart. Isoform 3 and isoform 4 are expressed in brain. Expressed in breast tumors and several tumor cell lines.
messages: Membrane
messages: Nucleus
messages: P-body
messages: Phosphorylated on serine/threonine residues by AURKA within positions 166 and 197. Phosphorylation and dephosphorylation on Thr-172 regulates cytoplasmic polyadenylation and translation of CPE-containing mRNAs. Phosphorylation on Thr-172 by AURKA and CAMK2A activates CPEB1. Phosphorylation on Thr-172 may be promoted by APLP1. Phosphorylation increases binding to RNA (By similarity).
messages: Postsynaptic density
messages: Sequence-specific RNA-binding protein that regulates mRNA cytoplasmic polyadenylation and translation initiation during oocyte maturation, early development and at postsynapse sites of neurons. Binds to the cytoplasmic polyadenylation element (CPE), an uridine-rich sequence element (consensus sequence 5'-UUUUUAU-3') within the mRNA 3'-UTR. RNA binding results in a clear conformational change analogous to the Venus fly trap mechanism (PubMed:24990967). In absence of phosphorylation and in association with TACC3 is also involved as a repressor of translation of CPE-containing mRNA; a repression that is relieved by phosphorylation or degradation (By similarity). Involved in the transport of CPE-containing mRNA to dendrites; those mRNAs may be transported to dendrites in a translationally dormant form and translationally activated at synapses (By similarity). Its interaction with APLP1 promotes local CPE-containing mRNA polyadenylation and translation activation (By similarity). Induces the assembly of stress granules in the absence of stress. Required for cell cycle progression, specifically for prophase entry (PubMed:26398195).
messages: Synapse
messages: The 2 RRM domains and the C-terminal region mediate interaction with CPE-containing RNA (PubMed:24990967). The interdomain linker (411-429) acts as a hinge to fix the relative orientation of the 2 RRMs (PubMed:24990967). The ZZ domain (509-566) coordinates 2 Zn ions and is probably implicated in mediating interactions with other proteins in addition to increasing the affinity of the RRMs for the CPEs (PubMed:23500490, PubMed:24990967). A continuous hydrophobic interface is formed between the 2 RRMs (PubMed:24990967).
messages: dendrite

9606:PDHA1
gene id: 9606:PDHA1
uniprot id: P08559
names: Activity Regulation
names: Disease Annotation
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acetylation alters the phosphorylation pattern. Deacetylated by SIRT3 (By similarity).
messages: Heterotetramer of two PDHA1 and two PDHB subunits. The heterotetramer interacts with DLAT, and is part of the multimeric pyruvate dehydrogenase complex that contains multiple copies of pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (DLAT, E2) and lipoamide dehydrogenase (DLD, E3). These subunits are bound to an inner core composed of about 48 DLAT and 12 PDHX molecules.
messages: Mitochondrion matrix
messages: Phosphorylation at Ser-232, Ser-293 and Ser-300 by PDK family kinases inactivates the enzyme; for this phosphorylation at a single site is sufficient. Dephosphorylation at all three sites, i.e. at Ser-232, Ser-293 and Ser-300, is required for reactivation.
messages: Pyruvate dehydrogenase activity is inhibited by phosphorylation of PDHA1; it is reactivated by dephosphorylation.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.
messages: Ubiquitous.

9606:DKC1
gene id: 9606:DKC1
uniprot id: A0A8Q3SIY6
uniprot id: O60832
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the pseudouridine synthase TruB family.
messages: Cajal body
messages: Catalytic subunit of H/ACA small nucleolar ribonucleoprotein (H/ACA snoRNP) complex, which catalyzes pseudouridylation of rRNA (PubMed:25219674). This involves the isomerization of uridine such that the ribose is subsequently attached to C5, instead of the normal N1 (PubMed:25219674). Each rRNA can contain up to 100 pseudouridine ('psi') residues, which may serve to stabilize the conformation of rRNAs. Required for ribosome biogenesis and telomere maintenance (PubMed:19179534, PubMed:25219674). Also required for correct processing or intranuclear trafficking of TERC, the RNA component of the telomerase reverse transcriptase (TERT) holoenzyme (PubMed:19179534).
messages: Cytoplasm
messages: Part of the H/ACA small nucleolar ribonucleoprotein (H/ACA snoRNP) complex, which contains NHP2/NOLA2, GAR1/NOLA1, NOP10/NOLA3, and DKC1/NOLA4, which is presumed to be the catalytic subunit (PubMed:15044956). The complex contains a stable core formed by binding of one or two NOP10-DKC1 heterodimers to NHP2; GAR1 subsequently binds to this core via DKC1 (PubMed:15044956). The complex binds a box H/ACA small nucleolar RNA (snoRNA), which may target the specific site of modification within the RNA substrate (PubMed:15044956). During assembly, the complex contains NAF1 instead of GAR1/NOLA1 (PubMed:16601202, PubMed:16618814). The complex also interacts with TERC, which contains a 3'-terminal domain related to the box H/ACA snoRNAs. Specific interactions with snoRNAs or TERC are mediated by GAR1 and NHP2. Associates with NOLC1/NOPP140 (PubMed:15044956). H/ACA snoRNPs interact with the SMN complex, consisting of SMN1 or SMN2, GEMIN2/SIP1, DDX20/GEMIN3, and GEMIN4. This is mediated by interaction between GAR1 and SMN1 or SMN2. The SMN complex may be required for correct assembly of the H/ACA snoRNP complex (PubMed:15044956). Component of the telomerase holoenzyme complex composed of one molecule of TERT, one molecule of WRAP53/TCAB1, two molecules of H/ACA ribonucleoprotein complex subunits DKC1, NOP10, NHP2 and GAR1, and a telomerase RNA template component (TERC) (PubMed:11074001, PubMed:19179534, PubMed:20351177, PubMed:29695869). The telomerase holoenzyme complex is associated with TEP1, SMG6/EST1A and POT1 (PubMed:19179534). Interacts with SHQ1; this interaction may lead to the stabilization of DKC1, from the time of its synthesis until its association with NOP10, NHP2, and NAF1 at the nascent H/ACA RNA (PubMed:19734544, PubMed:19383767). Interacts with HMBOX1 (PubMed:23685356). Interacts with DHX36 (PubMed:21846770).
messages: Promotes cell to cell and cell to substratum adhesion, increases the cell proliferation rate and leads to cytokeratin hyper-expression.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The disease is caused by variants affecting the gene represented in this entry. Reduced rRNA pseudouridine levels in cells from patients (PubMed:25219674).
messages: Ubiquitously expressed.
messages: nucleolus

9606:FNDC1
gene id: 9606:FNDC1
uniprot id: Q4ZHG4
names: Caution
names: Function
names: Induction
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Almost absent from healthy skin; especially in epidermal keratinocytes, skin fibroblasts or endothelial cells and is barely detectable in benign melanocytic naevi. Expressed in the stroma close to skin tumors, in the tumor cells themselves and in the epidermis of psoriasis.
messages: By TGFB1 present in the melanoma cell conditioned medium (MCCM).
messages: It is uncertain whether Met-1 or Met-53 is the initiator.
messages: May be an activator of G protein signaling.
messages: Secreted

9606:S1PR4
gene id: 9606:S1PR4
uniprot id: O95977
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Receptor for the lysosphingolipid sphingosine 1-phosphate (S1P). S1P is a bioactive lysophospholipid that elicits diverse physiological effect on most types of cells and tissues. May be involved in cell migration processes that are specific for lymphocytes.
messages: Specifically expressed in fetal and adult lymphoid and hematopoietic tissue as well as in lung. Considerable level of expression in adult and fetal spleen as well as adult peripheral leukocytes and lung. Lower expression in adult thymus, lymph node, bone marrow, and appendix as well as in fetal liver, thymus, and lung.

9606:F2
gene id: 9606:F2
uniprot id: P00734
names: Activity Regulation
names: Disease Annotation
names: Function
names: Miscellaneous
names: PTM
names: Pharmaceutical
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the peptidase S1 family.
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry.
messages: Expressed by the liver and secreted in plasma.
messages: Heterodimer (named alpha-thrombin) of a light and a heavy chain; disulfide-linked. Forms a heterodimer with SERPINA5. In plasma, interacts (via N-terminus) with alpha-1-microglobulin with molar ratio 1:2 and 1:1; this interaction does not prevent the activation of prothrombin to thrombin.
messages: In the penultimate step of the coagulation cascade, prothrombin is converted to thrombin by the prothrombinase complex composed of factor Xa (F10), cofactor Va (F5), and phospholipids. This activation requires factor Xa-catalyzed sequential cleavage at 2 sites, Arg-314 and Arg-363, along 2 possible pathways. In the first pathway, the first cleavage occurs at Arg-314, leading to the formation of the inactive intermediate prethrombin-2. This pathway preferentially occurs on platelets and in the absence of cofactor Va. In the second pathway, the first cleavage occurs at Arg-363, which separates protease domain into 2 chains that remain connected through a disulfide bond and generates the active intermediate meizothrombin. The presence of cofactor Va directs activation along the meizothrombin pathway and greatly accelerates the rate of cleavage at Arg-363, but has a smaller effect on the cleavage of meizothrombin at Arg-314. Meizothrombin accumulates as an intermediate when prothrombinase is assembled on the membrane of red blood cells.
messages: Inhibited by SERPINA5.
messages: It is not known whether 1 or 2 smaller activation peptides, with additional cleavage after Arg-314, are released in natural blood clotting.
messages: N-glycosylated. N-glycan heterogeneity at Asn-121: Hex3HexNAc3 (minor), Hex4HexNAc3 (minor) and Hex5HexNAc4 (major). At Asn-143: Hex4HexNAc3 (minor) and Hex5HexNAc4 (major).
messages: The cleavage after Arg-198, observed in vitro, does not occur in plasma.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The disease is caused by variants affecting the gene represented in this entry. A common genetic variation in the 3-prime untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increased risk of venous thrombosis.
messages: The gamma-carboxyglutamyl residues, which bind calcium ions, result from the carboxylation of glutamyl residues by a microsomal enzyme, the vitamin K-dependent carboxylase. The modified residues are necessary for the calcium-dependent interaction with a negatively charged phospholipid surface, which is essential for the conversion of prothrombin to thrombin.
messages: The peptide TP508 also known as Chrysalin (Orthologic) could be used to accelerate repair of both soft and hard tissues.
messages: Thrombin can itself cleave the N-terminal fragment (fragment 1) of the prothrombin, prior to its activation by factor Xa.
messages: Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing.
messages: extracellular space

9606:KAT6B
gene id: 9606:KAT6B
uniprot id: B2RWN8
uniprot id: Q8WYB5
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: A chromosomal aberration involving KAT6B may be a cause acute myeloid leukemias. Translocation t(10;16)(q22;p13) with CREBBP.
messages: Autoacetylated (PubMed:10497217, PubMed:11965546). Autoacetylation at Lys-815 is required for proper function.
messages: Belongs to the MYST (SAS/MOZ) family.
messages: Component of the MOZ/MORF complex composed at least of ING5, KAT6A, KAT6B, MEAF6 and one of BRPF1, BRD1/BRPF2 and BRPF3. Interacts with RUNX1 and RUNX2.
messages: Contaminating sequence. Potential poly-A sequence.
messages: Histone acetyltransferase which may be involved in both positive and negative regulation of transcription. Required for RUNX2-dependent transcriptional activation. May be involved in cerebral cortex development. Component of the MOZ/MORF complex which has a histone H3 acetyltransferase activity.
messages: Nucleus
messages: The N-terminus is involved in transcriptional activation while the C-terminus is involved in transcriptional repression.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitously expressed, with high levels in heart, pancreas, testis and ovary.

9606:LCE3E
gene id: 9606:LCE3E
uniprot id: Q5T5B0
names: Function
names: Induction
names: Miscellaneous
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Belongs to the LCE cluster present on 1q21.
messages: Belongs to the LCE family.
messages: By UVB.
messages: Interacts with CYSRT1.
messages: Precursors of the cornified envelope of the stratum corneum.
messages: Skin-specific. Expression was readily detected in adult trunk skin, adult arm skin, fetal skin, penal skin, vulva, esophagus and tongue. Not expressed in the cervix, rectum, lung, colon, or placenta.

9606:C14orf119
gene id: 9606:C14orf119
uniprot id: Q9NWQ9
names: Subcellular Location Annotation
messages: Mitochondrion

9606:TERB2
gene id: 9606:TERB2
uniprot id: Q8NHR7
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the TERB2 family.
messages: Component of the MAJIN-TERB1-TERB2 complex, composed of MAJIN, TERB1 and TERB2.
messages: Meiosis-specific telomere-associated protein involved in meiotic telomere attachment to the nucleus inner membrane, a crucial step for homologous pairing and synapsis. Component of the MAJIN-TERB1-TERB2 complex, which promotes telomere cap exchange by mediating attachment of telomeric DNA to the inner nuclear membrane and replacement of the protective cap of telomeric chromosomes: in early meiosis, the MAJIN-TERB1-TERB2 complex associates with telomeric DNA and the shelterin/telosome complex. During prophase, the complex matures and promotes release of the shelterin/telosome complex from telomeric DNA.
messages: Nucleus inner membrane
messages: The disease may be caused by variants affecting the gene represented in this entry.
messages: telomere

9606:RETN
gene id: 9606:RETN
uniprot id: Q9HD89
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the resistin/FIZZ family.
messages: Expressed in white adipose tissue (at protein level) (PubMed:11201732). Widely expressed, with particularly strong expression in lung, bone marrow, breast and peripheral blood (PubMed:15248836). Expressed strongly in bone marrow and at lower levels in lung, but not detected in other tissues (PubMed:15064728). Isoform 2 is detected in adipose tissue, bone marrow, brain, lung, peripheral blood, placenta and thymus (PubMed:15248836).
messages: Homodimer; disulfide-linked (By similarity). Interacts with DEFA1 (PubMed:15064728).
messages: Hormone that seems to suppress insulin ability to stimulate glucose uptake into adipose cells (By similarity). Potentially links obesity to diabetes (By similarity). Promotes chemotaxis in myeloid cells (PubMed:15064728).
messages: Secreted

9606:KRT7
gene id: 9606:KRT7
uniprot id: P08729
names: Function
names: Induction
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts with human papillomavirus 16/HPV16 protein E7.
messages: Arg-20 is dimethylated, probably to asymmetric dimethylarginine.
messages: Belongs to the intermediate filament family.
messages: Blocks interferon-dependent interphase and stimulates DNA synthesis in cells. Involved in the translational regulation of the human papillomavirus type 16 E7 mRNA (HPV16 E7).
messages: Cytoplasm
messages: Expressed in cultured epidermal, bronchial and mesothelial cells but absent in colon, ectocervix and liver. Observed throughout the glandular cells in the junction between stomach and esophagus but is absent in the esophagus.
messages: Heterotetramer of two type I and two type II keratins. Interacts with eukaryotic translation initiator factor 3 (eIF3) subunit EIF3S10. Interacts with GPER1.
messages: There are two types of cytoskeletal and microfibrillar keratin: I (acidic; 40-55 kDa) and II (neutral to basic; 56-70 kDa).
messages: Up-regulated by retinoic acid.

9606:REEP6
gene id: 9606:REEP6
uniprot id: A0A1L5BXV2
uniprot id: Q96HR9
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the DP1 family.
messages: Endoplasmic reticulum membrane
messages: Expressed in circumvallate papillae and testis (PubMed:16720576). Expressed in the retina. Isoform 1 is predominantly present in mature optic cups. Isoform 1 expression is confined to the cell body and inner segment of developing rod photoreceptor cells (PubMed:27889058).
messages: Interacts with STX3 (By similarity). Interacts with clathrin (By similarity).
messages: Membrane
messages: Required for correct function and survival of retinal photoreceptors (PubMed:27889058). Required for retinal development (By similarity). In rod photoreceptors, facilitates stability and/or trafficking of guanylate cyclases and is required to maintain endoplasmic reticulum and mitochondrial homeostasis (By similarity). May play a role in clathrin-coated intracellular vesicle trafficking of proteins from the endoplasmic reticulum to the retinal rod plasma membrane (By similarity).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: clathrin-coated vesicle membrane

9606:IKZF2
gene id: 9606:IKZF2
uniprot id: Q9UKS7
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Associates with Ikaros at centromeric heterochromatin.
messages: Belongs to the Ikaros C2H2-type zinc-finger protein family.
messages: Interacts with IKZF4 and IKZF5.
messages: Nucleus

9606:CDC40
gene id: 9606:CDC40
uniprot id: O60508
names: Disease Annotation
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: Component of the pre-catalytic and catalytic spliceosome complexes (PubMed:11991638, PubMed:28502770, PubMed:28076346, PubMed:29361316, PubMed:29360106, PubMed:29301961). Component of the postcatalytic spliceosome P complex (PubMed:30705154). Interacts with PPIL1; this interaction leads to CDC40 isomerization (PubMed:33220177).
messages: Nucleus
messages: Nucleus speckle
messages: Required for pre-mRNA splicing as component of the activated spliceosome (PubMed:33220177). Plays an important role in embryonic brain development; this function does not require proline isomerization (PubMed:33220177).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Undergoes isomerization of the peptide bond between Gly-94 and Pro-95. The reaction is catalyzed by PPIL1.

9606:ZP1
gene id: 9606:ZP1
uniprot id: P60852
uniprot id: V9HWI9
names: Caution
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the ZP domain family. ZPB subfamily.
messages: Cell membrane
messages: Component of the zona pellucida, an extracellular matrix surrounding oocytes which mediates sperm binding, induction of the acrosome reaction and prevents post-fertilization polyspermy. The zona pellucida is composed of 3 to 4 glycoproteins, ZP1, ZP2, ZP3, and ZP4. ZP1 ensures the structural integrity of the zona pellucida.
messages: Expressed in oocytes (at protein level).
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: Membrane
messages: O-glycosylated.
messages: Polymers of ZP2 and ZP3 organized into long filaments cross-linked by ZP1 homodimers (By similarity). Interacts with ZP3 (PubMed:28886344).
messages: Proteolytically cleaved before the transmembrane segment to yield the secreted ectodomain incorporated in the zona pellucida.
messages: The ZP domain is involved in the polymerization of the ZP proteins to form the zona pellucida.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Zona pellucida

9606:KDM6B
gene id: 9606:KDM6B
uniprot id: O15054
names: Disease Annotation
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the UTX family.
messages: By 12-O-tetradecanoylphorbol-13-acetate (TPA) in myeloid leukemia cells.
messages: Histone demethylase that specifically demethylates 'Lys-27' of histone H3, thereby playing a central role in histone code (PubMed:17825402, PubMed:17851529, PubMed:17713478, PubMed:18003914). Demethylates trimethylated and dimethylated H3 'Lys-27' (PubMed:17825402, PubMed:17851529, PubMed:17713478, PubMed:18003914). Plays a central role in regulation of posterior development, by regulating HOX gene expression (PubMed:17851529). Involved in inflammatory response by participating in macrophage differentiation in case of inflammation by regulating gene expression and macrophage differentiation (PubMed:17825402). Plays a demethylase-independent role in chromatin remodeling to regulate T-box family member-dependent gene expression by acting as a link between T-box factors and the SMARCA4-containing SWI/SNF remodeling complex (By similarity).
messages: Interacts with TLE1 (By similarity). Component of the MLL4 complex, at least composed of KMT2B/MLL4, ASH2L, RBBP5, WDR5, and KDM6B (PubMed:17825402). Interacts with TBX21, SMARCA4, SMARCC1 and SMARCC2 (By similarity).
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:LYRM2
gene id: 9606:LYRM2
uniprot id: Q9NU23
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the complex I LYR family.
messages: Involved in efficient integration of the N-module into mitochondrial respiratory chain complex I.
messages: Mitochondrion

9606:PDZD8
gene id: 9606:PDZD8
uniprot id: Q8NEN9
names: Caution
names: Disease Annotation
names: Domain
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Interacts with HIV-1 Gag polyprotein p55.
messages: (Microbial infection) Was initially reported to enhance infectivity of retroviruses, such as HIV-1, by stabilizing the capsid of retroviruses (PubMed:20573829, PubMed:24554657). However, it was later shown that PDZD8 is not absolutely required for HIV-1 infection, suggesting that its role in retroviral infection is probably indirect (PubMed:25771112).
messages: Endoplasmic reticulum membrane
messages: Interacts with MSN.
messages: Molecular tethering protein that connects endoplasmic reticulum and mitochondria membranes (PubMed:29097544). PDZD8-dependent endoplasmic reticulum-mitochondria membrane tethering is essential for endoplasmic reticulum-mitochondria Ca(2+) transfer (PubMed:29097544). In neurons, involved in the regulation of dendritic Ca(2+) dynamics by regulating mitochondrial Ca(2+) uptake in neurons (PubMed:29097544). Plays an indirect role in the regulation of cell morphology and cytoskeletal organization (PubMed:21834987). May inhibit herpes simplex virus 1 infection at an early stage (PubMed:21549406).
messages: The SMP-LTD domain is a barrel-like domain that binds phospholipids.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:GARIN4
gene id: 9606:GARIN4
uniprot id: Q8IYT1
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the GARIN family.
messages: Golgi apparatus
messages: Interacts (via N-terminus) with RAB2B (in GTP-bound form).
messages: RAB2B effector protein required for the compacted Golgi morphology, probably through interaction with small GTPase RAB2B.

9606:CKM
gene id: 9606:CKM
uniprot id: B2R892
uniprot id: P06732
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the ATP:guanido phosphotransferase family.
messages: Cytoplasm
messages: Dimer of identical or non-identical chains, which can be either B (brain type) or M (muscle type). With MM being the major form in skeletal muscle and myocardium, MB existing in myocardium, and BB existing in many tissues, especially brain.
messages: Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate). Creatine kinase isoenzymes play a central role in energy transduction in tissues with large, fluctuating energy demands, such as skeletal muscle, heart, brain and spermatozoa.

9606:EDN1
gene id: 9606:EDN1
uniprot id: P05305
uniprot id: Q6FH53
names: Disease Annotation
names: Function
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the endothelin/sarafotoxin family.
messages: EDN1 genetic variants may influence high density lipoprotein cholesterol (HDLC) levels in some populations and in a sex-specific manner, defining the high density lipoprotein cholesterol level quantitative trait locus 7 (HDLCQ7) [MIM:618979].
messages: Endothelins are endothelium-derived vasoconstrictor peptides (By similarity). Probable ligand for G-protein coupled receptors EDNRA and EDNRB which activates PTK2B, BCAR1, BCAR3 and, GTPases RAP1 and RHOA cascade in glomerular mesangial cells (PubMed:19086031). Also binds the DEAR/FBXW7-AS1 receptor (PubMed:17446437).
messages: Expressed in lung, placental stem villi vessels and in cultured placental vascular smooth muscle cells.
messages: Secreted
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:POMC
gene id: 9606:POMC
uniprot id: P01189
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: ACTH and MSH are produced by the pituitary gland.
messages: Anorexigenic peptide. Increases the pigmentation of skin by increasing melanin production in melanocytes.
messages: Belongs to the POMC family.
messages: Disease susceptibility may be associated with variants affecting the gene represented in this entry.
messages: Endogenous opiate.
messages: Endogenous orexigenic opiate.
messages: Increases the pigmentation of skin by increasing melanin production in melanocytes.
messages: O-glycosylated; reducing sugar is probably N-acetylgalactosamine.
messages: Secreted
messages: Specific enzymatic cleavages at paired basic residues yield the different active peptides.
messages: Stimulates the adrenal glands to release cortisol.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:TLN1
gene id: 9606:TLN1
uniprot id: Q9Y490
names: Domain
names: Function
names: Induction
names: Miscellaneous
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts with human cytomegalovirus protein UL135.
messages: By a combination of TGFB and EGF.
messages: Cell surface
messages: Consists of an N-terminal FERM domain linked via a short unstructured region to a large flexible C-terminal rod which contains 13 amphipathic helical bundles (R1-R13). The rod begins with a five-helix bundle (R1) followed by three four-helix bundles (R2-R4). These are followed by a series of eight five-helix bundles (R5-R7 and R9-R13) in which the N- and C-termini are positioned at opposite ends of the bundle, creating a linear chain. The four-helix bundle R8 does not disrupt the chain because it is inserted into a loop in the R7 five-helix bundle. The uneven distribution of four- and five-helix bundles creates two distinctly different zones: a compact N-terminal region sensitive to stretch and a linear C-terminal region that is optimal for force transmission.
messages: Expressed at low to non-detectable levels in many tissues but highly expressed in skin and pancreas with other tissues including kidney cortex, endocervix, testis, pituitary, liver, and spleen also showing robust expression.
messages: Expression in cancer cells is associated with altered drug responses. Cells show increased sensitivity to EGFR inhibitors but are resistant to drugs targeting PI3K signaling and cytoskeleton regulation.
messages: High molecular weight cytoskeletal protein concentrated at regions of cell-substratum contact and, in lymphocytes, at cell-cell contacts (By similarity). Involved in connections of major cytoskeletal structures to the plasma membrane (By similarity).
messages: Interacts with VCL; shows enhanced VCL binding compared to isoform 1 (PubMed:36880935). Interacts with APBB1IP; shows similar level of binding compared to isoform 1 (PubMed:36880935).
messages: Interacts with VCL; shows reduced VCL binding compared to isoform 2 (PubMed:36880935). Interacts with APBB1IP; shows similar level of binding compared to isoform 2 (PubMed:36880935).
messages: Part of a complex composed of THSD1, PTK2/FAK1, TLN1 and VCL (PubMed:29069646). Interacts with THSD1 (PubMed:27895300, PubMed:29069646); this promotes interaction with PTK2/FAK1 and VCL. Binds with high affinity to VCL and with low affinity to integrins (PubMed:15070891). Interacts with APBB1IP; this inhibits VCL binding. Interacts with PTK2/FAK1 (By similarity). Interacts with PIP5K1C and NRAP (PubMed:10320340, PubMed:12422220). Interacts with LAYN (By similarity). Interacts with SYNM (PubMed:18342854). Interacts with ITGB1; the interaction is prevented by competitive binding of ITGB1BP1 (PubMed:21768292, PubMed:12473654).
messages: Shows reduced mechanical stability compared to isoform 1 (PubMed:36880935). Shows altered focal adhesion formation compared to isoform 1 with cells having a greater number of small adhesions compared to those expressing isoform 1 (PubMed:36880935).
messages: cytoskeleton
messages: focal adhesion
messages: ruffle membrane

9606:PGAP2
gene id: 9606:PGAP2
uniprot id: A0A024RCD5
uniprot id: A0A0A0MS75
uniprot id: A0A0S2Z568
uniprot id: A8MYS5
uniprot id: H0YDQ4
uniprot id: Q9UHJ9
names: Disease Annotation
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the PGAP2 family.
messages: Endoplasmic reticulum membrane
messages: Golgi apparatus membrane
messages: Interacts with PGAP2IP.
messages: Involved in the lipid remodeling steps of GPI-anchor maturation. Required for stable expression of GPI-anchored proteins at the cell surface.
messages: Membrane
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: This isoform is predicted to contain an additional transmembrane domain at position 85-105. If this domain exists, the topology of the protein would be modified, possibly challenging the GPI-anchor remodeling function of the protein.
messages: Ubiquitously expressed, with highest levels in testis and pancreas.

9606:BAHD1
gene id: 9606:BAHD1
uniprot id: Q8TBE0
names: Domain
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: Chromosome
messages: Heterochromatin protein that acts as a transcription repressor and has the ability to promote the formation of large heterochromatic domains. May act by recruiting heterochromatin proteins such as CBX5 (HP1 alpha), HDAC5 and MBD1. Represses IGF2 expression by binding to its CpG-rich P3 promoter and recruiting heterochromatin proteins. At specific stages of Listeria infection, in complex with TRIM28, corepresses interferon-stimulated genes, including IFNL1, IFNL2 and IFNL3.
messages: Interacts with CBX5 (HP1 alpha), HDAC5, MBD1 and SP1. Forms a transcription silencing complex with at least CBX3 (HP1 gamma), HDAC1, HDAC2 and TRIM28. Interacts with L.monocytogenes LntA; this interaction, occurring at a late Listeria infection stage, relieves transcription repression, mostly that of interferon-stimulated genes. Interacts with FBXO11 (PubMed:33156908).
messages: Nucleus
messages: The BAH domain is required for localization at H3K27me3.
messages: Ubiquitinated in a FBXO11-dependent manner; leading to degradation.

9606:MEIOC
gene id: 9606:MEIOC
uniprot id: A2RUB1
names: Developmental Stage
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cytoplasm
messages: Expressed in fetal ovaries (PubMed:26742488). Expressed in testis (PubMed:28380054).
messages: Expression first detected in wpf (week post-fertilization) 11 and is highest in wpf 22.
messages: Interacts with YTHDC2; binds transcript that regulate the mitotic cell cycle inhibiting progression into metaphase, thereby allowing meiotic prophase to proceed normally. Interacts with RBM46.
messages: Is required for meiosis completion in both male and female germ cells. Confers stability to numerous meiotic mRNAs in gonads allowing proper initiation and progression into meiosis prophase I. The function may involve YTHDC2 and is independent of induction by retinoic acid (RA). Maintains an extended meiotic prophase I by properly promoting the transition from a mitotic to a meiotic cell cycle program by binding transcripts through its interaction with YTHDC2 that regulate the mitotic cell cycle.
messages: Nucleus

9606:NRP2
gene id: 9606:NRP2
uniprot id: O60462
uniprot id: Q7Z3T9
names: Caution
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Acts as a receptor for human cytomegalovirus pentamer-dependent entry in epithelial and endothelial cells.
messages: (Microbial infection) Interacts with human cytomegalovirus proteins gL, UL128, UL130 and UL131A.
messages: Belongs to the neuropilin family.
messages: Heterodimer with NRP1. Binds PLXNB1.
messages: High affinity receptor for semaphorins 3C, 3F, VEGF-165 and VEGF-145 isoforms of VEGF, and the PLGF-2 isoform of PGF.
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: Membrane
messages: Secreted
messages: The tandem CUB domains mediate binding to semaphorin, while the tandem F5/8 domains are responsible for heparin and VEGF binding.

9606:SARS1
gene id: 9606:SARS1
uniprot id: P49591
uniprot id: Q0VGA5
uniprot id: Q5T5C7
names: Disease Annotation
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: A splice site deletion resulting in a five amino acid in-frame insertion in SARS1, is associated with autosomal dominant complex spastic paraplegia with ataxia, intellectual disability, developmental delay and seizures, but without microcephaly.
messages: Belongs to the class-II aminoacyl-tRNA synthetase family. Type-1 seryl-tRNA synthetase subfamily.
messages: Brain.
messages: Catalyzes the attachment of serine to tRNA(Ser) in a two-step reaction: serine is first activated by ATP to form Ser-AMP and then transferred to the acceptor end of tRNA(Ser) (PubMed:22353712, PubMed:24095058, PubMed:9431993, PubMed:26433229, PubMed:28236339, PubMed:34570399, PubMed:36041817). Is probably also able to aminoacylate tRNA(Sec) with serine, to form the misacylated tRNA L-seryl-tRNA(Sec), which will be further converted into selenocysteinyl-tRNA(Sec) (PubMed:9431993, PubMed:26433229, PubMed:28236339, PubMed:34570399). In the nucleus, binds to the VEGFA core promoter and prevents MYC binding and transcriptional activation by MYC (PubMed:24940000). Recruits SIRT2 to the VEGFA promoter, promoting deacetylation of histone H4 at 'Lys-16' (H4K16). Thereby, inhibits the production of VEGFA and sprouting angiogenesis mediated by VEGFA (PubMed:19423848, PubMed:19423847, PubMed:24940000).
messages: Consists of two distinct domains, a catalytic core and a N-terminal extension that is involved in tRNA binding.
messages: Cytoplasm
messages: Homodimer (PubMed:22353712, PubMed:26433229). The tRNA molecule may bind across the dimer (PubMed:26433229). Interacts with SIRT2 (PubMed:24940000). Interacts with METTL6; interaction is required for the tRNA N(3)-methylcytidine methyltransferase activity of METTL6 (PubMed:28655767, PubMed:34268557).
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:CCL17
gene id: 9606:CCL17
uniprot id: Q92583
names: Caution
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Although CCL17 was shown to bind to CCR8, additional studies demonstrated that CCR4, not CCR8, was the bona fide CCL17 receptor.
messages: Belongs to the intercrine beta (chemokine CC) family.
messages: Chemokine, which displays chemotactic activity for T lymphocytes, preferentially Th2 cells, but not monocytes or granulocytes. Therefore plays an important role in a wide range of inflammatory and immunological processes (PubMed:8702936, PubMed:9169480). Acts by binding to CCR4 at T-cell surface (PubMed:9169480, PubMed:10540332). Mediates GM-CSF/CSF2-driven pain and inflammation (PubMed:27525438). In the brain, required to maintain the typical, highly branched morphology of hippocampal microglia under homeostatic conditions. May be important for the appropriate adaptation of microglial morphology and synaptic plasticity to acute lipopolysaccharide (LPS)-induced neuroinflammation (By similarity). Plays a role in wound healing, mainly by inducing fibroblast migration into the wound (By similarity).
messages: Constitutively expressed in thymus. Detected at lower levels in the lung, colon and small intestine (PubMed:8702936). Expressed in stimulated peripheral blood mononuclear cells, but not in resting cells (PubMed:8702936).
messages: In monocytes, up-regulated by IL4 and by GM-CSF/CSF2 in an IRF4-dependent manner (at protein level).
messages: Secreted
messages: Was originally thought to be a ligand for CCR8.

9606:OR5T3
gene id: 9606:OR5T3
uniprot id: Q8NGG3
names: Caution
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: It is uncertain whether Met-1 or Met-19 is the initiator.
messages: Odorant receptor.

9606:COX7B2
gene id: 9606:COX7B2
uniprot id: Q8TF08
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the cytochrome c oxidase VIIb family.
messages: Component of the cytochrome c oxidase (complex IV, CIV), a multisubunit enzyme composed of 14 subunits. The complex is composed of a catalytic core of 3 subunits MT-CO1, MT-CO2 and MT-CO3, encoded in the mitochondrial DNA, and 11 supernumerary subunits COX4I, COX5A, COX5B, COX6A, COX6B, COX6C, COX7A, COX7B, COX7C, COX8 and NDUFA4, which are encoded in the nuclear genome. The complex exists as a monomer or a dimer and forms supercomplexes (SCs) in the inner mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), resulting in different assemblies (supercomplex SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)).
messages: Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. Cytochrome c oxidase is the component of the respiratory chain that catalyzes the reduction of oxygen to water. Electrons originating from reduced cytochrome c in the intermembrane space (IMS) are transferred via the dinuclear copper A center (CU(A)) of subunit 2 and heme A of subunit 1 to the active site in subunit 1, a binuclear center (BNC) formed by heme A3 and copper B (CU(B)). The BNC reduces molecular oxygen to 2 water molecules using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix.
messages: Mitochondrion inner membrane

9606:UBE2D4
gene id: 9606:UBE2D4
uniprot id: Q9Y2X8
names: Function
names: Similarity
messages: Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro able to promote polyubiquitination using all 7 ubiquitin Lys residues, but may prefer 'Lys-11' and 'Lys-48'-linked polyubiquitination.
messages: Belongs to the ubiquitin-conjugating enzyme family.

9606:RPP38
gene id: 9606:RPP38
uniprot id: P78345
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Autoantibodies against RPP38 are found in sera from scleroderma patients.
messages: Belongs to the eukaryotic ribosomal protein eL8 family.
messages: Component of nuclear RNase P and RNase MRP ribonucleoproteins (PubMed:9037013, PubMed:10444065, PubMed:9630247, PubMed:16723659, PubMed:30454648). RNase P consists of a catalytic RNA moiety and about 10 protein subunits; POP1, POP4, POP5, POP7, RPP14, RPP21, RPP25, RPP30, RPP38 and RPP40 (PubMed:9037013, PubMed:9630247, PubMed:10444065, PubMed:16723659, PubMed:30454648). Within the RNase P complex, POP1, POP7 and RPP25 form the 'finger' subcomplex, POP5, RPP14, RPP40 and homodimeric RPP30 form the 'palm' subcomplex, and RPP21, POP4 and RPP38 form the 'wrist' subcomplex. All subunits of the RNase P complex interact with the catalytic RNA (PubMed:30454648). Several subunits of RNase P are also part of the RNase MRP complex. RNase MRP consists of a catalytic RNA moiety and about 8 protein subunits; POP1, POP7, RPP25, RPP30, RPP38, RPP40 and possibly also POP4 and POP5 (PubMed:16723659, PubMed:28115465).
messages: Component of ribonuclease P, a ribonucleoprotein complex that generates mature tRNA molecules by cleaving their 5'-ends (PubMed:9037013, PubMed:9630247, PubMed:10444065, PubMed:30454648). Also a component of the MRP ribonuclease complex, which cleaves pre-rRNA sequences (PubMed:28115465).
messages: nucleolus

9606:CMPK2
gene id: 9606:CMPK2
uniprot id: Q5EBM0
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the thymidylate kinase family.
messages: By interferon-alpha (PubMed:30083606). IRF1 is crucial for the transcriptional activation of CMPK2 (PubMed:36930652).
messages: High levels are observed in myeloid, lymphoid and mesenchymal tissues.
messages: Mitochondrial nucleotide monophosphate kinase needed for salvage dNTP synthesis that mediates immunomodulatory and antiviral activities through IFN-dependent and IFN-independent pathways (PubMed:17999954, PubMed:30083606, PubMed:36930652, PubMed:37075076). Restricts the replication of multiple viruses including flaviviruses or coronaviruses (PubMed:30083606, PubMed:36930652, PubMed:37075076). Together with viperin/RSAD2 and ddhCTP, suppresses the replication of several coronaviruses through inhibition of the viral RNA-dependent RNA polymerase activities (PubMed:36930652). Concerning flaviviruses, restricts RNA translation when localized to the mitochondria independently of its kinase activity (PubMed:37075076). Is able to phosphorylate dUMP, dCMP, CMP, UMP and monophosphates of the pyrimidine nucleoside analogs ddC, dFdC, araC, BVDU and FdUrd with ATP as phosphate donor. Efficacy is highest for dUMP followed by dCMP while CMP and UMP are poor substrates. Controls therefore mitochondrial DNA synthesis by supplying required deoxyribonucleotides (By similarity). CMPK2-dependent mitochondrial DNA synthesis is necessary for the production of oxidized mitochondrial DNA fragments after exposure to NLRP3 activators (By similarity). In turn, cytosolic oxidized mtDNA associates with the NLRP3 inflammasome complex and is required for its activation (By similarity).
messages: Mitochondrion

9606:C19orf38
gene id: 9606:C19orf38
uniprot id: A8MVS5
names: Subcellular Location Annotation
messages: Membrane

9606:LIAT1
gene id: 9606:LIAT1
uniprot id: Q6ZQX7
names: Domain
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: Cytoplasm
messages: LIAT1 proteins of some primates, from macaques to humans, contain tandem repeats of a 10-residue sequence, whereas LIAT1 proteins of other mammals contain a single copy of this motif. Quantities of these repeats are, in general, different in LIAT1 of different primates. For example, there are 1, 4, 13, 13, 17, and 17 repeats in the gibbon, gorilla, orangutan, bonobo, neanderthal, and human LIAT1, respectively.
messages: Participates in nucleolar liquid-liquid phase separation (LLPS) through its N-terminal intrinsically disordered region (IDR). May be involved in ATE1-mediated N-terminal arginylation.
messages: Post-translationally modified by JMJD6 lysyl-hydroxylase activity at its Lys-rich domain, which inhibits its self-association and nucleolar localization.
messages: Self-associates (via Lys-rich domain); targets LIAT1 to the nucleolus. Interacts with ATE1; it is not a substrate of ATE1, the interaction takes place in the cytoplasm and seems to increase ATE1 arginyltransferase activity. Interacts with JMJD6 and MRPS14.
messages: The N-terminal intrinsically disordered region (IDR) facilitates its liquid-liquid phase separation (LLPS) in the nucleolus. In the IDR, the lysine-rich domain mediates self-association and targeting to the nucleolus.
messages: nucleolus

9606:ELP6
gene id: 9606:ELP6
uniprot id: Q0PNE2
names: Caution
names: Function
names: Similarity
names: Subunit
messages: Belongs to the ELP6 family.
messages: Component of the elongator complex which consists of ELP1, ELP2, ELP3, ELP4, ELP5 and ELP6.
messages: Component of the elongator complex which is required for multiple tRNA modifications, including mcm5U (5-methoxycarbonylmethyl uridine), mcm5s2U (5-methoxycarbonylmethyl-2-thiouridine), and ncm5U (5-carbamoylmethyl uridine) (PubMed:29332244). The elongator complex catalyzes formation of carboxymethyluridine in the wobble base at position 34 in tRNAs (PubMed:22854966, PubMed:29332244). Involved in cell migration (By similarity).
messages: The elongator complex was originally thought to play a role in transcription elongation. However, it is no longer thought to play a direct role in this process and its primary function is thought to be in tRNA modification.

9606:RIPK2
gene id: 9606:RIPK2
uniprot id: O43353
names: Activity Regulation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Acetylation of Ser-174, Ser-176 and Ser-178 by Yersinia YopJ prevents phosphorylation and activation, thereby promoting cell death.
messages: Autophosphorylated (PubMed:16824733, PubMed:21123652, PubMed:29452636, PubMed:28545134). Phosphorylated at Ser-176, either via autophosphorylation or by LRRK2, enhancing activity (PubMed:16824733, PubMed:27830463). Autophosphorylation at Tyr-474 is required for effective NOD2 signaling (PubMed:21123652). Autophosphorylation is however not essential for NOD2 signaling (PubMed:29452636). Phosphorylation at Tyr-381 by Src kinase CSK occurs in a ARHGEF2-dependent manner and is required for NOD2-dependent innate immune activation (PubMed:21887730).
messages: Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.
messages: Cell membrane
messages: Contains an N-terminal kinase domain and a C-terminal caspase activation and recruitment domain (CARD) that mediates the recruitment of CARD-containing proteins.
messages: Cytoplasm
messages: Degraded via selective autophagy following interaction with IRGM (PubMed:36221902). IRGM promotes NOD1/NOD2-RIPK2 RIPosome recruitment to autophagosome membranes (PubMed:36221902). RIPK2 biquitinated via 'Lys-63'-linked chains is then recognized by SQSTM1/p62, leading to the SQSTM1/p62-dependent autophagic degradation of the NOD1/NOD2-RIPK2 RIPosome (PubMed:36221902).
messages: Detected in heart, brain, placenta, lung, peripheral blood leukocytes, spleen, kidney, testis, prostate, pancreas and lymph node.
messages: Endoplasmic reticulum
messages: In the inactive state, the helix alphaC is packed against the helical, non-phosphorylated activation segment (AS) (PubMed:28545134). Upon activation, helix alphaC is displaced and the phosphorylated AS becomes disordered (PubMed:28545134). Specifically inhibited by GSK583, which blocks NOD2 signaling by interfering with XIAP binding to RIPK2 (PubMed:29452636). Specifically inhibited by CSLP37 and CSLP43, which blocks NOD2 signaling by interfering with XIAP binding to RIPK2 (PubMed:30026309).
messages: Interacts (via CARD domain) with NOD2 (via CARD domain) (PubMed:15044951, PubMed:17355968, PubMed:19592251, PubMed:21887730, PubMed:27812135, PubMed:30279485, PubMed:30478312). Interacts (via CARD domain) with NOD1 (via CARD domain) (PubMed:17054981, PubMed:30478312). Homooligomer; following interaction with NOD1 or NOD2, homooligomerizes via its CARD domain and forms long filaments named RIPosomes (PubMed:30279485, PubMed:30478312). Found in a signaling complex consisting of at least ARHGEF2, NOD2 and RIPK2 (PubMed:21887730). Interacts with ARHGEF2; the interaction mediates tyrosine phosphorylation of RIPK2 by Src kinase CSK (PubMed:21887730). Interacts with MAP3K4; this interaction sequesters RIPK2 from the NOD2 signaling pathway (PubMed:18775659). Interacts with IKBKG/NEMO (PubMed:18079694). The polyubiquitinated protein interacts with MAP3K7/TAK1; interaction is indirect and is mediated by TAB2 and TAB3 that bind to polyubiquitin chains attached to RIPK2 (PubMed:18079694). Binds to CFLAR/CLARP and CASP1 via their CARD domains (PubMed:9575181). Binds to BIRC3/c-IAP1 and BIRC2/c-IAP2, TRAF1, TRAF2, TRAF5 and TRAF6 (PubMed:21931591). Interacts with NLRP10 (PubMed:22672233). Interacts with CARD9 (By similarity). Interacts with INAVA; the interaction takes place upon PRR stimulation (PubMed:28436939). Interacts (via CARD domain) with NGFR (via death domain) (PubMed:26646181). Interacts with IRGM; promoting RIPK2 degradation (PubMed:36221902).
messages: Polyubiquitinated via both 'Lys-63'- and 'Met-1'-linked polyubiquitin following recruitment by NOD1 or NOD2, creating docking sites for downstream effectors, triggering activation of the NF-kappa-B and MAP kinases signaling (PubMed:22607974, PubMed:29452636, PubMed:30026309). 'Lys-63'-linked polyubiquitination by XIAP is essential for NOD2 signaling and promotes recruitment of the LUBAC complex (PubMed:22607974, PubMed:29452636, PubMed:30026309). Also polyubiquitinated with 'Lys-63'-linked chains by PELI3, BIRC2/c-IAP1 and BIRC3/c-IAP2 (PubMed:19464198, PubMed:21931591). Ubiquitinated on Lys-209 via 'Lys-63'-linked by ITCH (PubMed:18079694, PubMed:19592251). Undergoes 'Lys-63'-linked deubiquitination by MYSM1 to attenuate NOD2-mediated inflammation and tissue damage (By similarity). Polyubiquitinated with 'Lys-63'-linked chains in response to Shigella infection, promoting its SQSTM1/p62-dependent autophagic degradation (PubMed:36221902). Undergoes 'Met-1'-linked polyubiquitination; the head-to-tail linear polyubiquitination is mediated by the LUBAC complex in response to NOD2 stimulation 'Met-1'-linked polyubiquitination (PubMed:23806334). 'Lys-63'-linked polyubiquitination by XIAP is required for recruimtent of the LUBAC complex and subsequent (PubMed:22607974). Linear polyubiquitination is restricted by FAM105B/otulin, probably to limit NOD2-dependent pro-inflammatory signaling activation of NF-kappa-B (PubMed:23806334). Ubiquitination at Lys-503 by ZNRF4 via 'Lys-48'-linked polyubiquitination promotes RIPK2 degradation by the proteasome; ubiquitination by ZNRF4 takes place during both acute and NOD2 tolerance conditions (PubMed:28656966).
messages: Serine/threonine/tyrosine-protein kinase that plays an essential role in modulation of innate and adaptive immune responses (PubMed:9575181, PubMed:9642260, PubMed:14638696, PubMed:21123652, PubMed:17054981, PubMed:28656966). Acts as a key effector of NOD1 and NOD2 signaling pathways: upon activation by bacterial peptidoglycans, NOD1 and NOD2 oligomerize and recruit RIPK2 via CARD-CARD domains, leading to the formation of RIPK2 filaments (PubMed:17562858, PubMed:21123652, PubMed:17054981, PubMed:22607974, PubMed:28656966, PubMed:29452636, PubMed:30026309). Once recruited, RIPK2 autophosphorylates and undergoes 'Lys-63'-linked polyubiquitination by E3 ubiquitin ligases XIAP, BIRC2 and BIRC3, as well as 'Met-1'-linked (linear) polyubiquitination by the LUBAC complex, becoming a scaffolding protein for downstream effectors (PubMed:22607974, PubMed:29452636, PubMed:28545134, PubMed:30279485, PubMed:30478312, PubMed:30026309). 'Met-1'-linked polyubiquitin chains attached to RIPK2 recruit IKBKG/NEMO, which undergoes 'Lys-63'-linked polyubiquitination in a RIPK2-dependent process (PubMed:22607974, PubMed:17562858, PubMed:29452636, PubMed:30026309). 'Lys-63'-linked polyubiquitin chains attached to RIPK2 serve as docking sites for TAB2 and TAB3 and mediate the recruitment of MAP3K7/TAK1 to IKBKG/NEMO, inducing subsequent activation of IKBKB/IKKB (PubMed:18079694). In turn, NF-kappa-B is released from NF-kappa-B inhibitors and translocates into the nucleus where it activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis (PubMed:18079694). The protein kinase activity is dispensable for the NOD1 and NOD2 signaling pathways (PubMed:29452636, PubMed:30026309). Contributes to the tyrosine phosphorylation of the guanine exchange factor ARHGEF2 through Src tyrosine kinase leading to NF-kappa-B activation by NOD2 (PubMed:21887730). Also involved in adaptive immunity: plays a role during engagement of the T-cell rec…

9606:NRN1L
gene id: 9606:NRN1L
uniprot id: Q496H8
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the neuritin family.
messages: Cell membrane

9606:RAC3
gene id: 9606:RAC3
uniprot id: P60763
names: Activity Regulation
names: Disease Annotation
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Glycosylated at Tyr-32 by Photorhabdus asymbiotica toxin PAU_02230. Mono-O-GlcNAcylation by PAU_02230 inhibits downstream signaling by an impaired interaction with diverse regulator and effector proteins of Rac and leads to actin disassembly.
messages: Belongs to the small GTPase superfamily. Rho family.
messages: Cell membrane
messages: Cytoplasm
messages: Endomembrane system
messages: Expression down-regulated in quiescent fibroblasts and clearly induced by serum stimulation.
messages: Highest levels in brain, also detected in heart, placenta and pancreas.
messages: Interacts with the GEF protein DOCK7, which promotes the exchange between GDP and GTP, and therefore activates it (PubMed:16982419). Interacts with C1D (PubMed:9852280). Interacts (via C-terminal region) with CIB1; the interaction induces their association with the cytoskeleton upon alpha-IIb/beta3 integrin-mediated adhesion (PubMed:11756406). Interacts with NRBP (PubMed:11956649).
messages: Plasma membrane-associated small GTPase which cycles between an active GTP-bound and inactive GDP-bound state. In active state binds to a variety of effector proteins to regulate cellular responses, such as cell spreading and the formation of actin-based protusions including lamellipodia and membrane ruffles. Promotes cell adhesion and spreading on fibrinogen in a CIB1 and alpha-IIb/beta3 integrin-mediated manner.
messages: Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP, GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity, and GDP dissociation inhibitors which inhibit the dissociation of the nucleotide from the GTPase. Regulated by the GEF protein DOCK7.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitinated at Lys-166 in a FBXL19-mediated manner; leading to proteasomal degradation.
messages: cytoskeleton
messages: lamellipodium
messages: perinuclear region

9606:DCX
gene id: 9606:DCX
uniprot id: O43602
names: Disease Annotation
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: A chromosomal aberration involving DCX is found in lissencephaly. Translocation t(X;2)(q22.3;p25.1).
messages: Cytoplasm
messages: Highly expressed in neuronal cells of fetal brain (in the majority of cells of the cortical plate, intermediate zone and ventricular zone), but not expressed in other fetal tissues. In the adult, highly expressed in the brain frontal lobe, but very low expression in other regions of brain, and not detected in heart, placenta, lung, liver, skeletal muscles, kidney and pancreas.
messages: Interacts with tubulin (PubMed:27292316). Interacts with USP9X (PubMed:24607389).
messages: Microtubule-associated protein required for initial steps of neuronal dispersion and cortex lamination during cerebral cortex development. May act by competing with the putative neuronal protein kinase DCLK1 in binding to a target protein. May in that way participate in a signaling pathway that is crucial for neuronal interaction before and during migration, possibly as part of a calcium ion-dependent signal transduction pathway. May be part with PAFAH1B1/LIS-1 of overlapping, but distinct, signaling pathways that promote neuronal migration.
messages: Phosphorylation by MARK1, MARK2 and PKA regulates its ability to bind microtubules (By similarity). Phosphorylation at Ser-265 and Ser-297 seems to occur only in neonatal brain, the levels falling precipitously by postnatal day 21 (By similarity).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitinated by MDM2, leading to its degradation by the proteasome. Ubiquitinated by MDM2 and subsequent degradation leads to reduce the dendritic spine density of olfactory bulb granule cells.
messages: neuron projection

9606:KLK10
gene id: 9606:KLK10
uniprot id: O43240
names: Developmental Stage
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the peptidase S1 family. Kallikrein subfamily.
messages: Down-regulated during breast cancer progression.
messages: Expressed in breast, ovary and prostate.
messages: Has a tumor-suppressor role for NES1 in breast and prostate cancer.
messages: Secreted

9606:CD1E
gene id: 9606:CD1E
uniprot id: P15812
names: Function
names: PTM
names: Polymorphism
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Early endosome
messages: Expressed on cortical thymocytes, dendritic cells, Langerhans cells, on certain T-cell leukemias, and in various other tissues.
messages: Golgi apparatus membrane
messages: Heterodimer with B2M (beta-2-microglobulin). The association with B2M appears to be facilitated by the presence of the propeptide.
messages: Late endosome
messages: Lysosome lumen
messages: Mono-ubiquitinated.
messages: Proteolytically cleaved in late endosomes to yield a soluble form.
messages: Six alleles of CD1E are known. CD1E*01 has His-102/Gln-106/Ser-149/Arg-164/Leu-194, CD1E*02 has His-102/Arg-106/Ser-149/Arg-164/Leu-194, CD1E*03 (9L) has His-102/Gln-106/Ser-149/Trp-164/Leu-194, CD1E*04 (15L) has His-102/Gln-106/Ser-149/Arg-164/Pro-194, CD1E*05 has Arg-102/Arg-106/Ser-149/Arg-164/Leu-194 and CD1E*06 has His-102/Arg-106/Asn-149/Arg-164/Leu-194 (PubMed:12144626, PubMed:11019917, PubMed:18325888). The sequence shown is that of allele CD1E*01.
messages: T-cell surface glycoprotein CD1e, soluble binds diacetylated lipids, including phosphatidyl inositides and diacylated sulfoglycolipids, and is required for the presentation of glycolipid antigens on the cell surface. The membrane-associated form is not active.

9606:CD70
gene id: 9606:CD70
uniprot id: A0A0U5JA32
uniprot id: P32970
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the tumor necrosis factor family.
messages: Cytokine which is the ligand for CD27. The CD70-CD27 pathway plays an important role in the generation and maintenance of T cell immunity, in particular during antiviral responses. Upon CD27 binding, induces the proliferation of costimulated T-cells and enhances the generation of cytolytic T-cells.
messages: Homotrimer.
messages: Membrane
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:OR2B2
gene id: 9606:OR2B2
uniprot id: A0A126GWD0
uniprot id: Q9GZK3
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Membrane
messages: Odorant receptor.

9606:GLOD5
gene id: 9606:GLOD5
uniprot id: A6NK44
names: Caution
names: Similarity
messages: Belongs to the glyoxalase I family.
messages: It is uncertain whether Met-1 or Met-13 is the initiator.

9606:SLC16A11
gene id: 9606:SLC16A11
uniprot id: Q8NCK7
names: Caution
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the major facilitator superfamily. Monocarboxylate porter (TC 2.A.1.13) family.
messages: Cell membrane
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry. A risk haplotype spanning SLC16A11 is associated with a 20% increased risk for T2D. The haplotype includes 5 SLC16A11 variants in strong linkage disequilibrium: variants Ile-113, Gly-127, Ser-340, Thr-443 and a silent variant. This risk haplotype probably derives from H.sapiens neanderthalensis (Neanderthal) introgression and is present at 50% frequency in Native-American samples, 10% in east Asian, while it is rare in European and African samples populations. The risk haplotype contains a cis-eQTL that is responsible for reduced SLC16A11 expression in liver (PubMed:28666119).
messages: Endoplasmic reticulum membrane
messages: Expressed in liver, salivary gland and thyroid.
messages: Interacts with isoform 2 of BSG.
messages: It is uncertain whether Met-1 or Met-25 is the initiator.
messages: Proton-linked monocarboxylate transporter. It catalyzes the transport of pyruvate across the plasma membrane (PubMed:28666119). Probably involved in hepatic lipid metabolism: overexpression results in an increase of triacylglycerol(TAG) levels, small increases in intracellular diacylglycerols and decreases in lysophosphatidylcholine, cholesterol ester and sphingomyelin lipids (PubMed:24390345).

9606:LCN15
gene id: 9606:LCN15
uniprot id: Q6UWW0
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the calycin superfamily. Lipocalin family.
messages: Secreted

9606:PMEL
gene id: 9606:PMEL
uniprot id: P40967
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the PMEL/NMB family.
messages: Endoplasmic reticulum membrane
messages: Extracellular vesicle
messages: Forms physiological amyloids that play a central role in melanosome morphogenesis and pigmentation. The maturation of unpigmented premelanosomes from stage I to II is marked by assembly of processed amyloidogenic fragments into parallel fibrillar sheets, which elongate the vesicle into a striated ellipsoidal shape. In pigmented stage III and IV melanosomes, the amyloid matrix serves as a platform where eumelanin precursors accumulate at high local concentrations for pigment formation. May prevent pigmentation-associated toxicity by sequestering toxic reaction intermediates of eumelanin biosynthesis pathway.
messages: Homodimer; disulfide-linked. Dimerization in the endoplasmic reticulum and early Golgi prevents premature fibril formation. The dimers are resolved to monomers in late- or post-Golgi compartments (PubMed:26694611). Heterooligomer; amyloid-type. Processed amyloidogenic fragments assemble into fibrils that further organize into beta-sheet quaternary amyloid structures (PubMed:28272432, PubMed:30988362). Interacts (via luminal C-terminal fragment) with CD63; this is important for sorting of the luminal fragment in tetraspanin rich microdomains in stage I melanosomes to prevent premature lysosomal degradation (PubMed:21962903). Interacts with APOE; this allows the loading of the luminal fragment on ILVs to induce fibril nucleation (PubMed:26387950). Interacts with MLANA (PubMed:15695812).
messages: Melanosome
messages: N- and O-glycosylated. A small amount of P1/P100 (major form) undergoes glycosylation in ER and Golgi compartments to yield P2/P120 (minor form). The mature P2 form leaves the trans-Golgi network and is mainly targeted to stage I melanosomes via the plasma membrane and clathrin-mediated endocytosis. Stage II melanosomes harbor only Golgi-modified fragments that are derived from M-alpha and that bear sialylated O-linked oligosaccharides. O-glycosylation of the RPT region is a conserved feature likely involved in amyloid sheet separation via electrostatic repulsion.
messages: Normally expressed at low levels in quiescent adult melanocytes but overexpressed by proliferating neonatal melanocytes and during tumor growth. Overexpressed in melanomas. Some expression was found in dysplastic nevi.
messages: Represents a potent melanoma-specific antigen. Among melanoma non-mutated self-peptides, G9-154 (KTWGQYWQV), G9-209 (ITDQVPFSV) and G9-280 (YLEPGPVTA), appear to act as immunodominant common epitopes that stimulate anti-tumor immune response mediated by HLA-A-restricted cytotoxic T cells.
messages: Secreted
messages: The Kringle-like domain (KLD) contains six highly conserved cysteine residues that are critical for dimer formation.
messages: The core amyloid fragment (CAF) represents the amyloidogenic unit of melanosomal fibrils. It is predicted to form a beta-solenoid structure comprising four coil right-handed beta strands with Tyr-151 and Trp-160 residues pi-stacking against each other to confer stability.
messages: The highly O-glycosylated repeat (RPT) domain drives the generation of the fibrillar amyloid sheet structures within melanosomes. The O-glycosylation sites rather than its primary amino acid sequence are conserved across species.
messages: Undergoes multiple proteolytic processing. In a post-Golgi prelysosomal compartment, P2 is cleaved by a furin-like proprotein convertase (PC) into two disulfide-linked subunits: a large lumenal subunit, M-alpha/ME20-S, and an integral membrane subunit, M-beta. Despite cleavage, only a small fraction of M-alpha is secreted, as most M-alpha and M-beta remain associated with each other intracellularly via a disulfide bond (PubMed:12732614, PubMed:11694580, PubMed:15695812, PubMed:15096515, PubMed:17991747). Once targeted to stage I melanosomes, beta-secretase BACE2 cleaves the M-beta fragment to release the amyloidogenic luminal fragment containing M-alpha and a small portion of M-beta N-terminus (PubMed:23754390). M-alpha is further cleaved by metalloproteinases, likely ADAM10 or ADAM17, and still unknown proteases to yield subfragments that ultimately assemble into amyloid fibrils (PubMed:19047044). The C-terminal fragment of M-beta is processed by the gamma-secretase complex to release a short intracytoplasmic domain (PubMed:19047044).
messages: cis-Golgi network membrane
messages: multivesicular body

9606:MEOX2
gene id: 9606:MEOX2
uniprot id: P50222
names: Domain
names: Function
names: Induction
names: Polymorphism
names: Subcellular Location Annotation
names: Subunit
messages: Expression is repressed by ZEB2.
messages: Interacts with RNF10 (PubMed:16335786). Interacts with TCF15 (By similarity).
messages: Mesodermal transcription factor that plays a key role in somitogenesis and somitogenesis and limb muscle differentiation (By similarity). Required during limb development for normal appendicular muscle formation and for the normal regulation of myogenic genes (By similarity). May have a regulatory role when quiescent vascular smooth muscle cells reenter the cell cycle (By similarity). Also acts as a negative regulator of angiogenesis (PubMed:17074759, PubMed:20516212, PubMed:22206000). Activates expression of CDKN1A and CDKN2A in endothelial cells, acting as a regulator of vascular cell proliferation (PubMed:17074759, PubMed:22206000). While it activates CDKN1A in a DNA-dependent manner, it activates CDKN2A in a DNA-independent manner (PubMed:22206000). Together with TCF15, regulates transcription in heart endothelial cells to regulate fatty acid transport across heart endothelial cells (By similarity).
messages: Nucleus
messages: Nucleus speckle
messages: The poly-His region of MEOX2 is polymorphic and the number of His varies in the population.
messages: The polyhistidine repeat may act as a targeting signal to nuclear speckles.

9606:CRB1
gene id: 9606:CRB1
uniprot id: A0A7D6VM04
uniprot id: A8K118
uniprot id: B7Z824
uniprot id: B7Z826
uniprot id: F5H0L2
uniprot id: P82279
names: Caution
names: Developmental Stage
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Apical cell membrane
messages: Belongs to the Crumbs protein family.
messages: CRB1 mutations have been found in various retinal dystrophies, chronic and disabling disorders of visual function. They predominantly involve the posterior portion of the ocular fundus, due to degeneration in the sensory layer of the retina, retinal pigment epithelium, Bruch membrane, choroid, or a combination of these tissues. Onset of inherited retinal dystrophies is painless, bilateral and typically progressive. Most people experience gradual peripheral vision loss or tunnel vision, and difficulties with poor illumination and night vision. Central vision is usually unaffected, so the person may still be able to read. However, it can also deteriorate to cause total blindness. Examples of retinal dystrophies are retinitis pigmentosa, Leber congenital amaurosis, cone-rod dystrophy among others.
messages: Component of a complex composed of PALS1, CRB1 and EPB41L5 (PubMed:17920587). Within the complex, interacts (via intracellular domain) with PALS1 and EPB41L5 (via FERM domain) (PubMed:17920587). Forms a complex with MPP4 and PALS1 (PubMed:15914641). Interacts with MPDZ/MUPP1 and MPP4 (By similarity).
messages: Expressed in the retinal layer of the optic vesicle, and weakly expressed in the retinal pigment epithelium at 12.5 dpc.
messages: Extensively glycosylated.
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: Photoreceptor inner segment
messages: Plays a role in photoreceptor morphogenesis in the retina (By similarity). May maintain cell polarization and adhesion (By similarity).
messages: Preferential expression in retina, also expressed in brain, testis, fetal brain and fetal eye (PubMed:15914641). Expressed at the outer limiting membrane and apical to adherens junctions in the retina (PubMed:15914641).
messages: Secreted
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: photoreceptor outer segment

9606:HSD17B8
gene id: 9606:HSD17B8
uniprot id: Q92506
names: Function
names: Induction
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the short-chain dehydrogenases/reductases (SDR) family.
messages: Heterotetramer with CBR4; contains two molecules of HSD17B8 and CBR4.
messages: Mitochondrion matrix
messages: Required for the solubility and assembly of the heterotetramer 3-ketoacyl-[acyl carrier protein] (ACP) reductase functional complex (KAR or KAR1) that forms part of the mitochondrial fatty acid synthase (mtFAS). Alpha-subunit of the KAR complex that acts as a scaffold protein required for the stability of carbonyl reductase type-4 (CBR4, beta-subunit of the KAR complex) and for its 3-ketoacyl-ACP reductase activity, thereby participating in mitochondrial fatty acid biosynthesis. Catalyzes the NAD-dependent conversion of (3R)-3-hydroxyacyl-CoA into 3-ketoacyl-CoA (3-oxoacyl-CoA) with no chain length preference; this enzymatic activity is not needed for the KAR function (PubMed:19571038, PubMed:25203508, PubMed:30508570). Prefers (3R)-3-hydroxyacyl-CoA over (3S)-3-hydroxyacyl-CoA and displays enzymatic activity only in the presence of NAD(+) (PubMed:19571038). Cooperates with enoyl-CoA hydratase 1 in mitochondria, together they constitute an alternative route to the auxiliary enzyme pathways for the breakdown of Z-PUFA (cis polyunsaturated fatty acid) enoyl-esters (Probable) (PubMed:30508570). NAD-dependent 17-beta-hydroxysteroid dehydrogenase with highest activity towards estradiol (17beta-estradiol or E2). Has very low activity towards testosterone and dihydrotestosterone (17beta-hydroxy-5alpha-androstan-3-one). Primarily an oxidative enzyme, it can switch to a reductive mode determined in the appropriate physiologic milieu and catalyze the reduction of estrone (E1) to form biologically active 17beta-estradiol (PubMed:17978863).
messages: The fatty acyl-CoA dehydrogenase activity is several thousand times higher than the estradiol and testosterone 17beta-hydroxysteroid dehydrogenase conversion.
messages: Up-regulated by estradiol.
messages: Widely expressed, particularly abundant in prostate, placenta and kidney (PubMed:17978863). Expressed at protein level in various tissues like brain, cerebellum, heart, lung, kidney, ovary, testis, adrenals and prostate (PubMed:30508570).

9606:URI1
gene id: 9606:URI1
uniprot id: O94763
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the RNA polymerase II subunit 5-mediating protein family.
messages: Cytoplasm
messages: Homodimer. Component of the PAQosome complex which is responsible for the biogenesis of several protein complexes and which consists of R2TP complex members RUVBL1, RUVBL2, RPAP3 and PIH1D1, URI complex members PFDN2, PFDN6, PDRG1, UXT and URI1 as well as ASDURF, POLR2E and DNAAF10/WDR92 (PubMed:31738558). Interacts with POLR2E/RPB5, RUVBL2 and RUVBL1 (PubMed:14615539, PubMed:9819440). Interacts with PFDN2, PFDN4 and STAP1; the interactions are phosphorylation-dependent and occur in a growth-dependent manner in the mitochondrion (PubMed:14615539). Interacts with UXT (PubMed:21730289). Interacts with PPP1CC; the interaction is phosphorylation-dependent and occurs in a growth factor-dependent manner (PubMed:21397856). Interacts (via the middle C-terminal region) with GTF2F1 and GTF2F2 (PubMed:12737519). Interacts with DMAP1 (PubMed:15367675). Interacts with TSC1 and TSC2 (PubMed:28561026). Interacts with PRPF8 and EFTUD2 in a ZNHIT2-dependent manner (PubMed:28561026).
messages: Involved in gene transcription regulation. Acts as a transcriptional repressor in concert with the corepressor UXT to regulate androgen receptor (AR) transcription. May act as a tumor suppressor to repress AR-mediated gene transcription and to inhibit anchorage-independent growth in prostate cancer cells. Required for cell survival in ovarian cancer cells. Together with UXT, associates with chromatin to the NKX3-1 promoter region. Antagonizes transcriptional modulation via hepatitis B virus X protein.
messages: Mitochondrion
messages: Nucleus
messages: Phosphorylated. Phosphorylation occurs essentially on serine residues. Phosphorylation occurs in response to androgen treatment in prostate cancer cells in a mTOR-dependent manner. Phosphorylated; hyperhosphorylated in mitochondria in a mTORC-dependent signaling pathway. Phosphorylated at Ser-372 by RPS6KB1 in a growth factor- and rapamycin-dependent manner. S6K1-mediated mitochondrial phosphorylation at Ser-372 disrupts the URI1-PPP1CC complex in the mitochondrion, relieves PPP1CC phosphatase inhibition activity and hence engages a negative feedback diminishing RPS6KB1 kinase activity, preventing sustained S6K1-dependent signaling.
messages: Plays a central role in maintaining S6K1 signaling and BAD phosphorylation under normal growth conditions thereby protecting cells from potential deleterious effects of sustained S6K1 signaling. The URI1-PPP1CC complex acts as a central component of a negative feedback mechanism that counteracts excessive S6K1 survival signaling to BAD in response to growth factors. Mediates inhibition of PPP1CC phosphatase activity in mitochondria. Coordinates the regulation of nutrient-sensitive gene expression availability in a mTOR-dependent manner. Seems to be a scaffolding protein able to assemble a prefoldin-like complex that contains PFDs and proteins with roles in transcription and ubiquitination.
messages: Ubiquitous. Expressed in ovarian cancers (at protein level). Expressed strongly in skeletal muscle. Expressed weakly in brain, heart, pancreas and in prostate epithelial cells.
messages: dendrite

9606:NLRC4
gene id: 9606:NLRC4
uniprot id: Q9NPP4
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cytoplasm
messages: Homooligomer; homooligomerizes to induce formation of the NLRC4 inflammasome (PubMed:25385754, PubMed:33420028). Homooligomerizes following activation by pathogenic proteins (By similarity). Component of the NLRC4 inflammasome, at least composed of NLRC4 and caspase-1 (CASP1) (By similarity). Some NLRC4 inflammasomes contain PYCARD/ASC, while some others directly contact and activate CASP1 (PubMed:25217959). Interacts (via CARD domain) with PYCARD/ASC, pro-caspase-1 (CASP1), NOD2, BCL10 and NALP1 (NAC) by CARD-CARD interaction (PubMed:15107016). Interacts with EIF2AK2/PKR (PubMed:22801494).
messages: In an autoinhibited form the C-terminal leucine-rich repeat (LRR) domain is positioned to sterically occlude one side of the NBD domain and consequently sequester NLRC4 in a monomeric state. An ADP-mediated interaction between the NBD and the WHD also contributes to the autoinhibition.
messages: Inflammasome
messages: Isoform 2 is expressed ubiquitously, although highly expressed in lung and spleen. Isoform 1 is highly expressed in lung, followed by leukocytes especially monocytes, lymph node, colon, brain, prostate, placenta, spleen, bone marrow and fetal liver. Isoform 4 is only detected in brain.
messages: Key component of inflammasomes that indirectly senses specific proteins from pathogenic bacteria and fungi and responds by assembling an inflammasome complex that promotes caspase-1 activation, cytokine production and macrophage pyroptosis (PubMed:15107016). The NLRC4 inflammasome is activated as part of the innate immune response to a range of intracellular bacteria (By similarity).
messages: Phosphorylated at Ser-533 following infection of macrophages with S.typhimurium (Salmonella). Phosphorylation is essential for NLRC4 inflammasome function to promote caspase-1 activation and pyroptosis. PRKCD phosphorylates Ser-533 in vitro.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: cytosol

9606:CLCF1
gene id: 9606:CLCF1
uniprot id: Q9UBD9
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the IL-6 superfamily.
messages: Expressed predominantly in lymph nodes, spleen, peripheral blood lymphocytes, bone marrow, and fetal liver.
messages: Forms a heteromeric complex with cardiotrophin-like cytokine CRLF1/CLF-1; the CRLF1-CLCF1 complex is a ligand for the ciliary neurotrophic factor receptor/CNTFR (PubMed:26858303). The CRLF1-CLCF1 heterodimer binds SORL1 (via N-terminal ectodomain); within this complex, the interaction is mediated predominantly by the CRLF1 moiety (PubMed:26858303). The tripartite signaling complex formed by CRLF1, CLCF1 and CNTFR also binds SORL1 (PubMed:26858303).
messages: In complex with CRLF1, forms a heterodimeric neurotropic cytokine that plays a crucial role during neuronal development (Probable). Also stimulates B-cells. Binds to and activates the ILST/gp130 receptor.
messages: Secreted
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:P4HB
gene id: 9606:P4HB
uniprot id: A0A024R8S5
uniprot id: P07237
names: Disease Annotation
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the protein disulfide isomerase family.
messages: Cell membrane
messages: Endoplasmic reticulum
messages: Endoplasmic reticulum lumen
messages: Heterodimer; heterodimerizes with the protein microsomal triglyceride transfer MTTP (PubMed:23475612, PubMed:26224785, PubMed:16478722). Homodimer. Monomers and homotetramers may also occur. Interacts with P4HA2, forming a heterotetramer consisting of 2 alpha subunits (P4HA2) and 2 beta (P4HB), where P4HB plays the role of a structural subunit; this tetramer catalyzes the formation of 4-hydroxyproline in collagen (PubMed:7753822). Also constitutes the structural subunit of the microsomal triacylglycerol transfer protein MTTP in mammalian cells. Stabilizes both enzymes and retain them in the ER without contributing to the catalytic activity (By similarity). Binds UBQLN1 (PubMed:12095988). Interacts with ERO1B (PubMed:11707400). Binds to CD4, and upon HIV-1 binding to the cell membrane, is part of a P4HB/PDI-CD4-CXCR4-gp120 complex. Interacts with ILDR2 (By similarity). Interacts with ERN1/IRE1A (via N-terminus); the interaction is enhanced by phosphorylation of P4HB by FAM20C in response to endoplasmic reticulum stress and results in attenuation of ERN1 activity (PubMed:32149426).
messages: Melanosome
messages: Phosphorylation of Ser-357 by FAM20C is induced by endoplasmic reticulum stress and results in a functional switch from oxidoreductase to molecular chaperone (PubMed:32149426). It also promotes interaction with ERN1 (PubMed:32149426).
messages: Reduces and may activate fusogenic properties of HIV-1 gp120 surface protein, thereby enabling HIV-1 entry into the cell.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: This multifunctional protein catalyzes the formation, breakage and rearrangement of disulfide bonds. At the cell surface, seems to act as a reductase that cleaves disulfide bonds of proteins attached to the cell. May therefore cause structural modifications of exofacial proteins. Inside the cell, seems to form/rearrange disulfide bonds of nascent proteins. At high concentrations and following phosphorylation by FAM20C, functions as a chaperone that inhibits aggregation of misfolded proteins (PubMed:32149426). At low concentrations, facilitates aggregation (anti-chaperone activity). May be involved with other chaperones in the structural modification of the TG precursor in hormone biogenesis. Also acts as a structural subunit of various enzymes such as prolyl 4-hydroxylase and microsomal triacylglycerol transfer protein MTTP. Receptor for LGALS9; the interaction retains P4HB at the cell surface of Th2 T helper cells, increasing disulfide reductase activity at the plasma membrane, altering the plasma membrane redox state and enhancing cell migration (PubMed:21670307).

9606:H1-2
gene id: 9606:H1-2
uniprot id: P16403
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: ADP-ribosylated on Ser-188 in response to DNA damage.
messages: Belongs to the histone H1/H5 family.
messages: Chromosome
messages: Citrullination at Arg-54 (H1R54ci) by PADI4 takes place within the DNA-binding site of H1 and results in its displacement from chromatin and global chromatin decondensation, thereby promoting pluripotency and stem cell maintenance.
messages: Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.
messages: H1 histones are progressively phosphorylated during the cell cycle, becoming maximally phosphorylated during late G2 phase and M phase, and being dephosphorylated sharply thereafter.
messages: Histone H1 protein binds to linker DNA between nucleosomes forming the macromolecular structure known as the chromatin fiber. Histones H1 are necessary for the condensation of nucleosome chains into higher-order structured fibers. Acts also as a regulator of individual gene transcription through chromatin remodeling, nucleosome spacing and DNA methylation (By similarity).
messages: Interacts with TSC22D1 isoforms 2 and 5.
messages: Nucleus
messages: The C-terminal domain is required for high-affinity binding to chromatin.

9606:RNF133
gene id: 9606:RNF133
uniprot id: Q8WVZ7
names: Function
names: PTM
names: Subcellular Location Annotation
messages: Auto-ubiquitinated.
messages: Endoplasmic reticulum membrane
messages: Has E3 ubiquitin-protein ligase activity.

9606:CAMK2D
gene id: 9606:CAMK2D
uniprot id: A0A8V8TN60
uniprot id: A0A8V8TN65
uniprot id: A0A8V8TN88
uniprot id: A0A8V8TNA1
uniprot id: A0A8V8TNA7
uniprot id: A0A8V8TPJ8
uniprot id: A0A8V8TPY4
uniprot id: A0A994J516
uniprot id: A0A994J5B0
uniprot id: D6R938
uniprot id: E9PBG7
uniprot id: E9PF82
uniprot id: Q13557
names: Activity Regulation
names: Domain
names: Function
names: Induction
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Activated by Ca(2+)/calmodulin. Binding of calmodulin results in conformational change that relieves intrasteric autoinhibition and allows autophosphorylation of Thr-287 which turns the kinase in a constitutively active form and confers to the kinase a Ca(2+)-independent activity.
messages: Activity is induced in skeletal muscle during exercise.
messages: Autophosphorylation of Thr-287 following activation by Ca(2+)/calmodulin. Phosphorylation of Thr-287 locks the kinase into an activated state.
messages: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily.
messages: CAMK2 is composed of 4 different chains: alpha (CAMK2A), beta (CAMK2B), gamma (CAMK2G), and delta (CAMK2D). The different isoforms assemble into homo- or heteromultimeric holoenzymes composed of 12 subunits with two hexameric rings stacked one on top of the other (PubMed:14722083). Interacts with RRAD and CACNB2 (By similarity).
messages: Calcium/calmodulin-dependent protein kinase involved in the regulation of Ca(2+) homeostatis and excitation-contraction coupling (ECC) in heart by targeting ion channels, transporters and accessory proteins involved in Ca(2+) influx into the myocyte, Ca(2+) release from the sarcoplasmic reticulum (SR), SR Ca(2+) uptake and Na(+) and K(+) channel transport. Targets also transcription factors and signaling molecules to regulate heart function. In its activated form, is involved in the pathogenesis of dilated cardiomyopathy and heart failure. Contributes to cardiac decompensation and heart failure by regulating SR Ca(2+) release via direct phosphorylation of RYR2 Ca(2+) channel on 'Ser-2808'. In the nucleus, phosphorylates the MEF2 repressor HDAC4, promoting its nuclear export and binding to 14-3-3 protein, and expression of MEF2 and genes involved in the hypertrophic program (PubMed:17179159). Is essential for left ventricular remodeling responses to myocardial infarction. In pathological myocardial remodeling acts downstream of the beta adrenergic receptor signaling cascade to regulate key proteins involved in ECC. Regulates Ca(2+) influx to myocytes by binding and phosphorylating the L-type Ca(2+) channel subunit beta-2 CACNB2. In addition to Ca(2+) channels, can target and regulate the cardiac sarcolemmal Na(+) channel Nav1.5/SCN5A and the K+ channel Kv4.3/KCND3, which contribute to arrhythmogenesis in heart failure. Phosphorylates phospholamban (PLN/PLB), an endogenous inhibitor of SERCA2A/ATP2A2, contributing to the enhancement of SR Ca(2+) uptake that may be important in frequency-dependent acceleration of relaxation (FDAR) and maintenance of contractile function during acidosis (PubMed:16690701). May participate in the modulation of skeletal muscle function in response to exercise, by regulating SR Ca(2+) transport through phosphorylation of PLN/PLB and triadin, a ryanodine receptor-coupling factor. In response to interferon-gamma (IFN-gamma) stimulation, catal…
messages: Expressed in cardiac muscle and skeletal muscle. Isoform Delta 3, isoform Delta 2, isoform Delta 8 and isoform Delta 9 are expressed in cardiac muscle. Isoform Delta 11 is expressed in skeletal muscle.
messages: Expression of CAMK2D is significantly increased in patients suffering from dilated cardiomyopathy in PubMed:10189359.
messages: Sarcoplasmic reticulum membrane
messages: The CAMK2 protein kinases contain a unique C-terminal subunit association domain responsible for oligomerization.
messages: sarcolemma

9606:CLDN8
gene id: 9606:CLDN8
uniprot id: A0A0K0K1I9
uniprot id: P56748
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: A protein of the expected size has been detected by antibody binding and Western blot in at least one of the analyzed tissues or cells.
messages: Belongs to the claudin family.
messages: Cell membrane
messages: Directly interacts with TJP1/ZO-1, TJP2/ZO-2 and TJP3/ZO-3. Interacts with CLDN4. Interacts with KLHL3.
messages: Expressed in the epididymis, mainly in the caput segment.
messages: Membrane
messages: Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity.
messages: Tight-junction protein required for paracellular chloride transport in the kidney. Mediates recruitment of CLDN4 to tight junction in the kidney. Claudins play a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity.
messages: Ubiquitinated by the BCR(KLHL3) E3 ubiquitin ligase complex in the kidney, leading to its degradation.
messages: tight junction

9606:CT45A8
gene id: 9606:CT45A8
uniprot id: P0DMV1
uniprot id: P0DMV2
uniprot id: Q5DJT8
names: Similarity
names: Tissue Specificity
messages: Belongs to the CT45 family.
messages: Testis specific. Expressed in cancer cell lines.

9606:LZTFL1
gene id: 9606:LZTFL1
uniprot id: Q9NQ48
names: Developmental Stage
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the LZTFL1 family.
messages: Cytoplasm
messages: Expressed in brain, lung, liver, and kidney.
messages: Expressed in prostate, ovary, stomach, pancreas, esophagus, breast, liver, bladder, kidney, thyroid, colon and lung (at protein level). Down-regulated in multiple primary tumors (at protein level). Detected in testis, heart, skeletal muscle, thymus, spleen, small intestine, and peripheral blood leukocytes.
messages: Regulates ciliary localization of the BBSome complex. Together with the BBSome complex, controls SMO ciliary trafficking and contributes to the sonic hedgehog (SHH) pathway regulation. May play a role in neurite outgrowth. May have tumor suppressor function.
messages: Self-associates. Interacts with BBS9; the interaction mediates the association of LZTL1 with the BBsome complex and regulates BBSome ciliary trafficking.
messages: The disease is caused by variants affecting the gene represented in this entry. Patients carrying LZTFL1 mutations manifest mesoaxial polydactyly, a clinical feature very uncommon for Bardet-Biedl syndrome (PubMed:22510444, PubMed:23692385). Some patients manifest situs inversus (PubMed:22510444).

9606:C11orf24
gene id: 9606:C11orf24
uniprot id: Q96F05
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Cell membrane
messages: Highest expression in heart, placenta, liver, pancreas and colon. Also detected in brain, lung, skeletal muscle, kidney, spleen, prostate, testis, ovary and small intestine. Lowest expression in thymus and leukocytes.
messages: trans-Golgi network membrane

9606:SRD5A2
gene id: 9606:SRD5A2
uniprot id: P31213
names: Disease Annotation
names: Function
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the steroid 5-alpha reductase family.
messages: Converts testosterone (T) into 5-alpha-dihydrotestosterone (DHT) and progesterone or corticosterone into their corresponding 5-alpha-3-oxosteroids. It plays a central role in sexual differentiation and androgen physiology.
messages: Endoplasmic reticulum membrane
messages: Expressed in high levels in the prostate and many other androgen-sensitive tissues.
messages: Individuals with Thr-49 have an increased risk of prostate cancer (PubMed:10501358). The enzyme with Thr-49 has a higher in vitro V(max) than the Ala-49 enzyme (PubMed:10501358).
messages: Microsome membrane
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:LDAF1
gene id: 9606:LDAF1
uniprot id: I3L288
uniprot id: I3NI23
uniprot id: Q96B96
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the LDAF1 family.
messages: Endoplasmic reticulum membrane
messages: Expressed at high levels in the heart and skeletal muscle. Expressed at low levels in kidney, small intestine, lung and liver.
messages: Interacts with isoform 1 and isoform 3 of BSCL2/seipin to form an oligomeric complex.
messages: Lipid droplet
messages: Membrane
messages: Plays an important role in the formation of lipid droplets (LD) which are storage organelles at the center of lipid and energy homeostasis (PubMed:31708432). In association with BSCL2/seipin, defines the sites of LD formation in the endoplasmic reticulum (PubMed:31708432).

9606:NEK4
gene id: 9606:NEK4
uniprot id: P51957
uniprot id: Q05DF6
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the protein kinase superfamily.
messages: Belongs to the protein kinase superfamily. NEK Ser/Thr protein kinase family. NIMA subfamily.
messages: Cytoplasm
messages: Highest expression in adult heart, followed by pancreas, skeletal muscle, brain, testis, retina, liver, kidney, lung and placenta. Present in most primary carcinomas.
messages: Interacts with RPGRIP1 and RPGRIP1L.
messages: Protein kinase that seems to act exclusively upon threonine residues (By similarity). Required for normal entry into proliferative arrest after a limited number of cell divisions, also called replicative senescence. Required for normal cell cycle arrest in response to double-stranded DNA damage.
messages: cilium

9606:RAB25
gene id: 9606:RAB25
uniprot id: P57735
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the small GTPase superfamily. Rab family.
messages: Cell membrane
messages: Cytoplasmic vesicle
messages: Expressed in ovarian epithelium (NOE) and breast tissue. Expressed in ovarian cancer; expression is increased relative to NOE cells. Expression in ovarian cancer is stage dependent, with stage III and stage IV showing higher levels than early stage cancers. Expressed in breast cancer; expression is increased relative to normal breast tissue.
messages: Interacts with RAB11FIP1, RAB11FIP2, RAB11FIP3 and RAB11FIP4. Interacts (via the hypervariable C-terminal region) with ITGB1 (via the cytoplasmic region); the interaction is GTP-dependent. Interacts with ITGAV. Associates with the integrin alpha-V/beta-1 heterodimer. Interacts with VPS33B (PubMed:28017832).
messages: Involved in the regulation of cell survival. Promotes invasive migration of cells in which it functions to localize and maintain integrin alpha-V/beta-1 at the tips of extending pseudopodia (PubMed:17925226). Involved in the regulation of epithelial morphogenesis through the control of CLDN4 expression and localization at tight junctions (By similarity). May selectively regulate the apical recycling pathway. Together with MYO5B regulates transcytosis (By similarity).
messages: pseudopodium membrane

9606:TRPM6
gene id: 9606:TRPM6
uniprot id: Q9BX84
names: Disease Annotation
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cell membrane
messages: Essential ion channel and serine/threonine-protein kinase. Crucial for magnesium homeostasis. Has an important role in epithelial magnesium transport and in the active magnesium absorption in the gut and kidney. Isoforms of the type M6-kinase lack the ion channel region.
messages: Forms heterodimers with TRPM7. TRPM6 requires the presence of TRPM7 to be targeted to the cell membrane (in HEK 293 cells). Interacts (via kinase domain) with RACK1.
messages: Highly expressed in kidney and colon. Isoform TRPM6a and isoform TRPM6b, are coexpressed with TRPM7 in kidney, and testis, and are also found in several cell lines of lung origin. Isoform TRPM6c is detected only in testis and in NCI-H510A small cell lung carcinoma cells.
messages: In the C-terminal section; belongs to the protein kinase superfamily. Alpha-type protein kinase family. ALPK subfamily.
messages: In the N-terminal section; belongs to the transient receptor (TC 1.A.4) family. LTrpC subfamily. TRPM6 sub-subfamily.
messages: Lacks the ion channel region.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:CELA2A
gene id: 9606:CELA2A
uniprot id: P08217
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the peptidase S1 family. Elastase subfamily.
messages: Elastase that enhances insulin signaling and might have a physiologic role in cellular glucose metabolism. Circulates in plasma and reduces platelet hyperactivation, triggers both insulin secretion and degradation, and increases insulin sensitivity.
messages: Expressed in pancreas. Not detected in keratinocytes (PubMed:10620133). Detected in exocrine secretions of the pancreas (at protein level). Also expressed in a small fraction of cells in pancreatic islets, adrenal cortex, intestinal glands and colonic lymphoid follicles (at protein level) (PubMed:31358993). Detected in plasma (PubMed:31358993).
messages: Interacts with CPA1. Interacts with SERPINA1 (PubMed:31358993).
messages: Secreted
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:STMN2
gene id: 9606:STMN2
uniprot id: Q93045
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the stathmin family.
messages: Cytoplasm
messages: Endosome
messages: Golgi apparatus
messages: Interacts with MAPK8 (By similarity). Interacts with ITM2C. Interacts with KIFBP. Interacts (via the N-terminal region) with CIB1 (via C-terminal region); the interaction is direct, occurs in a calcium-dependent manner and attenuates the neurite outgrowth inhibition of STMN2.
messages: Membrane
messages: N-terminal palmitoylation promotes specific anchoring to the cytosolic leaflet of Golgi membranes and subsequent vesicular trafficking along dendrites and axons. Neuronal Stathmins are substrates for palmitoyltransferases ZDHHC3, ZDHHC7 and ZDHHC15.
messages: Neuron specific.
messages: Phosphorylated mostly by MAPK8, but also by MAPK9 and MAPK10 in the developing brain cortex.
messages: Regulator of microtubule stability. When phosphorylated by MAPK8, stabilizes microtubules and consequently controls neurite length in cortical neurons. In the developing brain, negatively regulates the rate of exit from multipolar stage and retards radial migration from the ventricular zone (By similarity).
messages: Sumoylated.
messages: axon
messages: growth cone
messages: lamellipodium
messages: perinuclear region

9606:RHOT2
gene id: 9606:RHOT2
uniprot id: Q8IXI1
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the mitochondrial Rho GTPase family.
messages: Interacts with the kinesin-binding proteins TRAK1/OIP106 and TRAK2/GRIF1, forming a link between mitochondria and the trafficking apparatus of the microtubules (PubMed:16630562). Interacts with ARMCX3 (By similarity). Found in a complex with KIF5B, OGT, RHOT1 and TRAK1 (PubMed:24995978).
messages: Mitochondrial GTPase involved in mitochondrial trafficking (PubMed:16630562, PubMed:22396657). Probably involved in control of anterograde transport of mitochondria and their subcellular distribution (PubMed:22396657).
messages: Mitochondrion outer membrane
messages: Ubiquitinated by PRKN in a PINK1-dependent manner, leading to its degradation.
messages: Ubiquitously expressed. Highly expressed in heart, liver, skeletal muscle, kidney and pancreas.

9606:UGDH
gene id: 9606:UGDH
uniprot id: O60701
names: Activity Regulation
names: Disease Annotation
names: Domain
names: Function
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Belongs to the UDP-glucose/GDP-mannose dehydrogenase family.
messages: Catalyzes the formation of UDP-alpha-D-glucuronate, a constituent of complex glycosaminoglycans (PubMed:21961565, PubMed:21502315, PubMed:23106432, PubMed:22123821, PubMed:25478983, PubMed:27966912, PubMed:30420606, PubMed:30457329). Required for the biosynthesis of chondroitin sulfate and heparan sulfate. Required for embryonic development via its role in the biosynthesis of glycosaminoglycans (By similarity). Required for proper brain and neuronal development (PubMed:32001716).
messages: Detected in heart, placenta, liver, pancreas, spleen, thymus, prostate, ovary, small intestine and colon (PubMed:9737970). Widely expressed (PubMed:9737970).
messages: Homohexamer.
messages: The allosteric switch region moves by about 5 Angstroms when UDP-xylose is bound, and occupies part of the UDP-glucose binding site. At the same time it promotes domain movements that disrupt the active hexameric ring structure and lead to the formation of a horseshoe-shaped, inactive hexamer.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The protein goes through several conformation states during the reaction cycle, giving rise to hysteresis. In the initial state, the ligand-free protein is in an inactive conformation (E*). Substrate binding triggers a change to the active conformation (E). UDP-xylose binding triggers the transition to a distinct, inhibited conformation. The presence of an intrinsically disordered C-terminus promotes a more dynamic protein structure and favors a conformation with high affinity for UPD-xylose.
messages: UDP-alpha-D-xylose (UDX) acts as a feedback inhibitor. It binds at the same site as the substrate, but functions as allosteric inhibitor by triggering a conformation change that disrupts the active hexameric ring structure and gives rise to an inactive, horseshoe-shaped hexamer.

9606:PFKFB2
gene id: 9606:PFKFB2
uniprot id: O60825
names: Activity Regulation
names: Function
names: PTM
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Heart.
messages: Homodimer (By similarity). Forms a heterodimer with PFKFB3 (PubMed:36402789).
messages: In the C-terminal section; belongs to the phosphoglycerate mutase family.
messages: Phosphorylation by AMPK stimulates activity.
messages: Phosphorylation results in the activation of the kinase activity.
messages: Synthesis and degradation of fructose 2,6-bisphosphate.

9606:C10orf53
gene id: 9606:C10orf53
uniprot id: Q8N6V4
names: Similarity
messages: Belongs to the UPF0728 family.

9606:MINDY3
gene id: 9606:MINDY3
uniprot id: Q9H8M7
names: Caution
names: Function
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the MINDY deubiquitinase family. FAM188 subfamily.
messages: Contaminating sequence. Potential poly-A sequence.
messages: Hydrolase that can remove 'Lys-48'-linked conjugated ubiquitin from proteins.
messages: Interacts with COPS5.
messages: Nucleus
messages: Was named CARP for 'CARD domain-containing protein' by PubMed:12054670. However, no CARD domain is detected by any prediction tool.
messages: Widely expressed with high levels in heart, skeletal muscle, and kidney, and low levels in liver and brain (PubMed:12054670). Also expressed in lung (at protein level) (PubMed:21499297).

9606:DPPA4
gene id: 9606:DPPA4
uniprot id: Q7L190
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Interacts with DPPA2 (By similarity). Interacts with PCGF1 (PubMed:26687479).
messages: May be involved in the maintenance of active epigenetic status of target genes. May inhibit differentiation of embryonic cells into a primitive ectoderm lineage.
messages: Nucleus

9606:GLRX2
gene id: 9606:GLRX2
uniprot id: Q9NS18
names: Activity Regulation
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the glutaredoxin family.
messages: Glutathione-dependent oxidoreductase that facilitates the maintenance of mitochondrial redox homeostasis upon induction of apoptosis by oxidative stress. Involved in response to hydrogen peroxide and regulation of apoptosis caused by oxidative stress. Acts as a very efficient catalyst of monothiol reactions because of its high affinity for protein glutathione-mixed disulfides. Can receive electrons not only from glutathione (GSH), but also from thioredoxin reductase supporting both monothiol and dithiol reactions. Efficiently catalyzes both glutathionylation and deglutathionylation of mitochondrial complex I, which in turn regulates the superoxide production by the complex. Overexpression decreases the susceptibility to apoptosis and prevents loss of cardiolipin and cytochrome c release.
messages: Mitochondrion
messages: Monomer; active form. Homodimer; inactive form. The homodimer is probably linked by 1 2Fe-2S cluster.
messages: Nucleus
messages: The 2Fe-2S present in the homodimer leads to inactivation of the enzyme. The 2Fe-2S may serve as a redox sensor: the presence of one-electron oxidants or reductants leading to the loss of the 2Fe-2S cluster, subsequent monomerization and activation of the enzyme. Unlike other glutaredoxins, it is not inhibited by oxidation of structural Cys residues.
messages: The absence of GLRX2 dramatically sensitizes cells to cell death induced by doxorubicin/adriamycin and phenylarsine oxide.
messages: Widely expressed. Expressed in brain, heart, skeletal muscle, colon, thymus, spleen, kidney, liver, small intestine, placenta and lung. Not expressed in peripheral blood leukocytes.

9606:GSC2
gene id: 9606:GSC2
uniprot id: O15499
names: Developmental Stage
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the paired homeobox family. Bicoid subfamily.
messages: Detected in adult testis and pituitary, and in 9-10 week fetal tissue (thorax). Probably expressed in other tissues at low levels.
messages: Expressed in early human development as well as in a limited number of adult tissues.
messages: May have a role in development. May regulate its own transcription. May bind the bicoid consensus sequence TAATCC.
messages: Nucleus

9606:RAB1B
gene id: 9606:RAB1B
uniprot id: Q9H0U4
names: Activity Regulation
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) AMPylation at Tyr-77 by L.pneumophila DrrA occurs in the switch 2 region and leads to moderate inactivation of the GTPase activity. It appears to prolong the lifetime of the GTP state of RAB1B by restricting access of GTPase effectors to switch 2 and blocking effector-stimulated GTP hydrolysis, thereby rendering RAB1B constitutively active. It is later de-AMPylated by L.pneumophila SidD, releasing RAB1B from bacterial phagosomes.
messages: (Microbial infection) Glycosylated by S.typhimurium protein Ssek3: arginine GlcNAcylation prevents GTPase activity, thereby disrupting vesicular protein transport from the endoplasmic reticulum (ER) to the Golgi compartment.
messages: (Microbial infection) Interacts with L.pneumophila AnkX (PubMed:21822290, PubMed:22307087). Interacts with L.pneumophila Lem3 (PubMed:22158903, PubMed:22307087). Interacts with L.pneumophila SidD (PubMed:21734656, PubMed:21680813). Interacts with L.pneumophila DrrA (PubMed:20064470, PubMed:20651120).
messages: (Microbial infection) Phosphocholinated at Ser-76 by L.pneumophila AnkX, leading to displace GDP dissociation inhibitors (GDI) (PubMed:21822290, PubMed:22307087). Both GDP-bound and GTP-bound forms can be phosphocholinated. Dephosphocholinated by L.pneumophila Lem3, restoring accessibility to L.pneumophila GTPase effector LepB (PubMed:22158903, PubMed:22307087).
messages: Belongs to the small GTPase superfamily. Rab family.
messages: Cytoplasm
messages: Interacts with MICAL1 and MICAL2 (PubMed:15694364, PubMed:27552051). Interacts (in GTP-bound form) with MICALCL, MICAL1 and MILCAL3 (PubMed:15694364, PubMed:27552051). Interacts with GDI1; the interaction requires the GDP-bound state (PubMed:8836150, PubMed:11389151). Interacts with CHM/REP1; the interaction requires the GDP-bound form and is necessary for prenylation by GGTase II (PubMed:9437002, PubMed:11389151). Interacts with RabGAP TBC1D20 (PubMed:23236136). Interacts (in GDP-bound form) with lipid phosphatase MTMR6 (via GRAM domain); the interaction regulates MTMR6 recruitment to the endoplasmic reticulum-Golgi intermediate compartment (PubMed:23188820). Interacts (in GDP-bound form) with lipid phosphatase MTMR7 (By similarity).
messages: Membrane
messages: Preautophagosomal structure membrane
messages: Prenylated; by GGTase II, only after interaction of the substrate with Rab escort protein 1 (REP1).
messages: Rab activation is generally mediated by a guanine exchange factor (GEF), while inactivation through hydrolysis of bound GTP is catalyzed by a GTPase activating protein (GAP).
messages: Rab-1B binds GTP and GDP and possesses low intrinsic GTPase activity.
messages: The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes (PubMed:20545908, PubMed:9437002). Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (PubMed:9437002). Plays a role in the initial events of the autophagic vacuole development which take place at specialized regions of the endoplasmic reticulum (PubMed:20545908). Regulates vesicular transport between the endoplasmic reticulum and successive Golgi compartments (By similarity). Required to modulate the compacted morphology of the Golgi (PubMed:26209634). Promotes the recruitment of lipid phosphatase MTMR6 to the endoplasmic reticulum-Golgi intermediate compartment (By similarity).
messages: perinuclear region

9606:ENPP2
gene id: 9606:ENPP2
uniprot id: E7EUF1
uniprot id: Q13822
names: Activity Regulation
names: Cofactor
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the nucleotide pyrophosphatase/phosphodiesterase family.
messages: Binds 1 Ca(2+) ion per subunit.
messages: Binds 2 Zn(2+) ions per subunit.
messages: Detected in blood plasma (at protein level) (PubMed:12176993, PubMed:26371182). Predominantly expressed in brain, placenta, ovary, and small intestine. Expressed in a number of carcinomas such as hepatocellular and prostate carcinoma, neuroblastoma and non-small-cell lung cancer. Expressed in body fluids such as plasma, cerebral spinal fluid (CSF), saliva, follicular and amniotic fluids. Not detected in leukocytes. Isoform 1 is more highly expressed in peripheral tissues than in the central nervous system (CNS). Adipocytes only express isoform 1. Isoform 3 is more highly expressed in the brain than in peripheral tissues.
messages: Hydrolyzes lysophospholipids to produce the signaling molecule lysophosphatidic acid (LPA) in extracellular fluids (PubMed:15769751, PubMed:26371182, PubMed:27754931, PubMed:14500380, PubMed:12354767). Major substrate is lysophosphatidylcholine (PubMed:12176993, PubMed:27754931, PubMed:14500380). Can also act on sphingosylphosphorylcholine producing sphingosine-1-phosphate, a modulator of cell motility (PubMed:14500380). Can hydrolyze, in vitro, bis-pNPP, to some extent pNP-TMP, and barely ATP (PubMed:15769751, PubMed:12176993). Involved in several motility-related processes such as angiogenesis and neurite outgrowth. Acts as an angiogenic factor by stimulating migration of smooth muscle cells and microtubule formation (PubMed:11559573). Stimulates migration of melanoma cells, probably via a pertussis toxin-sensitive G protein (PubMed:1733949). May have a role in induction of parturition (PubMed:12176993). Possible involvement in cell proliferation and adipose tissue development (Probable). Tumor cell motility-stimulating factor (PubMed:1733949, PubMed:11559573). Required for LPA production in activated platelets, cleaves the sn-1 lysophospholipids to generate sn-1 lysophosphatidic acids containing predominantly 18:2 and 20:4 fatty acids (PubMed:21393252). Shows a preference for the sn-1 to the sn-2 isomer of 1-O-alkyl-sn-glycero-3-phosphocholine (lyso-PAF) (PubMed:21393252).
messages: Inhibited by lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P). Inhibited by EDTA and EGTA (Probable).
messages: N-glycosylation, but not furin-cleavage, plays a critical role on secretion and on lysoPLD activity.
messages: Secreted
messages: The interdomain disulfide bond between Cys-414 and Cys-806 is essential for catalytic activity.
messages: Up-regulated in massively obese subjects with glucose intolerance, and during adipogenesis.

9606:SAMD9
gene id: 9606:SAMD9
uniprot id: Q5K651
names: Disease Annotation
names: Function
names: Induction
names: Sequence Caution
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts with myxoma virus protein M062.
messages: Contaminating sequence. Potential poly-A sequence.
messages: Cytoplasm
messages: Double-stranded nucleic acid binding that acts as a an antiviral factor by playing an essential role in the formation of cytoplasmic antiviral granules (PubMed:25428864, PubMed:28157624). May play a role in the inflammatory response to tissue injury and the control of extra-osseous calcification, acting as a downstream target of TNF-alpha signaling. Involved in the regulation of EGR1, in coordination with RGL2. May be involved in endosome fusion.
messages: Interacts with RGL2 (PubMed:21160498). Interacts with EEA1 (PubMed:24029230).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The disease is caused by variants affecting the gene represented in this entry. Germline mutations in SAMD9 with a suppressive effect on the cell cycle are associated with somatic loss of the chromosome 7 harboring the mutant allele. This results in the deletion of several genes and predisposes to the development of myelodysplastic syndrome and acute myelogenous leukemia.
messages: Unlikely isoform. Aberrant splice sites.
messages: Up-regulated by TNF-alpha through p38 MAPKs and NF-kappa-B. Up-regulated by osmotic shock. Induced by IFNG.
messages: Widely expressed. Very low levels are detected in skeletal muscle. Not detected in brain. Down-regulated in aggressive fibromatosis, as well as in breast and colon cancers. Up-regulated in fibroblasts from patients with normophosphatemic tumoral calcinosis (NFTC).

9606:FASTKD3
gene id: 9606:FASTKD3
uniprot id: Q14CZ7
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the FAST kinase family.
messages: Expression detected in spleen, thymus, testis, ovary, colon, heart, smooth muscle, kidney, brain, lung, liver and white adipose tissue with highest expression in liver and thyroid.
messages: Mitochondrion
messages: RAP domain is required for FASTKD3 function in mRNA stability and translation.
messages: Required for normal mitochondrial respiration (PubMed:20869947). Increases steady-state levels and half-lives of a subset of mature mitochondrial mRNAs MT-ND2, MT-ND3, MT-CYTB, MT-CO2, and MT-ATP8/6. Promotes MT-CO1 mRNA translation and increases mitochondrial complex IV assembly and activity (PubMed:27789713).

9606:GRM4
gene id: 9606:GRM4
uniprot id: A1L4F9
uniprot id: A8K0J8
uniprot id: B7ZLU9
uniprot id: Q14833
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor 3 family.
messages: Cell membrane
messages: G-protein coupled receptor for glutamate. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Signaling inhibits adenylate cyclase activity.
messages: Interacts with PICK1.
messages: Membrane
messages: Strongly expressed in the cerebellum. Expressed at low levels in hippocampus, hypothalamus and thalamus. No expression detected in liver.

9606:STK17A
gene id: 9606:STK17A
uniprot id: Q9UEE5
names: Activity Regulation
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Acts as a positive regulator of apoptosis. Also acts as a regulator of cellular reactive oxygen species.
messages: Autophosphorylated.
messages: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. DAP kinase subfamily.
messages: Directly regulated by p53/TP53: induced following cisplatin treatment in a p53/TP53-dependent manner. p53/TP53 activates expression by directly binding to its regulatory regions.
messages: Highly expressed in placenta. Lower levels in heart, lung, skeletal muscle, kidney and pancreas.
messages: Inhibited by thiazolidinedione-type compounds: inhibited by furan- and pyridone- thiazolidinediones.
messages: Nucleus

9606:CFP
gene id: 9606:CFP
uniprot id: P27918
names: Disease Annotation
names: Domain
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: A positive regulator of the alternate pathway (AP) of complement (PubMed:20382442, PubMed:28264884). It binds to and stabilizes the C3- and C5-convertase enzyme complexes (PubMed:20382442, PubMed:28264884). Inhibits CFI-CFH mediated degradation of Complement C3 beta chain (C3b) (PubMed:31507604).
messages: In plasma, properdin exists as dimers, trimers or tetramers in the relative proportions of 26:54:20 (PubMed:20382442, PubMed:15491616, PubMed:28264884, PubMed:31507604). Interacts with the pro-C3-convertase enzyme complex (C3b-Bb) comprised of Complement C3 beta chain (C3b) and the Complement factor B Bb fragment (Bb), where it binds (via its TSP type-1 5 domain) with C3b and Bb (PubMed:28264884, PubMed:31507604). This interaction stabilizes the complex and allows it to become the active C3-convertase enzyme complex (C3b-Bb-FP) (PubMed:28264884, PubMed:31507604). Interacts with C3b (PubMed:28264884, PubMed:31507604). Interacts with CFB (PubMed:31507604).
messages: Secreted
messages: TSP type-1 domain 0 binds to TSP type-1 domain 4, and TSP type-1 domain 1 binds to TSP type-1 domain 6 (PubMed:15491616, PubMed:28264884, PubMed:31507604). These interactions mediate multimerization (PubMed:15491616, PubMed:28264884, PubMed:31507604).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:PKIG
gene id: 9606:PKIG
uniprot id: Q549H9
uniprot id: Q9Y2B9
names: Function
names: Similarity
names: Tissue Specificity
messages: Belongs to the PKI family.
messages: Extremely potent competitive inhibitor of cAMP-dependent protein kinase activity, this protein interacts with the catalytic subunit of the enzyme after the cAMP-induced dissociation of its regulatory chains.
messages: Ubiquitous.

9606:RPE
gene id: 9606:RPE
uniprot id: C9IZU8
uniprot id: C9J9T0
uniprot id: Q96AT9
names: Cofactor
names: Function
names: Similarity
names: Subunit
messages: Belongs to the ribulose-phosphate 3-epimerase family.
messages: Binds 1 divalent metal cation per subunit.
messages: Binds 1 divalent metal cation per subunit. Active with Fe(2+), and probably also with Mn(2+), Zn(2+) and Co(2+).
messages: Catalyzes the reversible epimerization of D-ribulose 5-phosphate to D-xylulose 5-phosphate.
messages: Homodimer.

9606:PRKCA
gene id: 9606:PRKCA
uniprot id: L7RSM7
uniprot id: P17252
uniprot id: Q7Z727
names: Activity Regulation
names: Cofactor
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily.
messages: Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2 domain.
messages: Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in positive and negative regulation of cell proliferation, apoptosis, differentiation, migration and adhesion, tumorigenesis, cardiac hypertrophy, angiogenesis, platelet function and inflammation, by directly phosphorylating targets such as RAF1, BCL2, CSPG4, TNNT2/CTNT, or activating signaling cascade involving MAPK1/3 (ERK1/2) and RAP1GAP. Involved in cell proliferation and cell growth arrest by positive and negative regulation of the cell cycle. Can promote cell growth by phosphorylating and activating RAF1, which mediates the activation of the MAPK/ERK signaling cascade, and/or by up-regulating CDKN1A, which facilitates active cyclin-dependent kinase (CDK) complex formation in glioma cells. In intestinal cells stimulated by the phorbol ester PMA, can trigger a cell cycle arrest program which is associated with the accumulation of the hyper-phosphorylated growth-suppressive form of RB1 and induction of the CDK inhibitors CDKN1A and CDKN1B. Exhibits anti-apoptotic function in glioma cells and protects them from apoptosis by suppressing the p53/TP53-mediated activation of IGFBP3, and in leukemia cells mediates anti-apoptotic action by phosphorylating BCL2. During macrophage differentiation induced by macrophage colony-stimulating factor (CSF1), is translocated to the nucleus and is associated with macrophage development. After wounding, translocates from focal contacts to lamellipodia and participates in the modulation of desmosomal adhesion. Plays a role in cell motility by phosphorylating CSPG4, which induces association of CSPG4 with extensive lamellipodia at the cell periphery and polarization of the cell accompanied by increases in cell motility. During chemokine-induced CD4(+) T cell migration, phosphorylates CDC42-guanine exchange factor DOCK8 resulting in its dissociation from LRCH1 and the activation of GTPase CDC42 (PubMed:28028151). Is hig…
messages: Cell membrane
messages: Classical (or conventional) PKCs (PRKCA, PRKCB and PRKCG) are activated by calcium and diacylglycerol (DAG) in the presence of phosphatidylserine. Three specific sites; Thr-497 (activation loop of the kinase domain), Thr-638 (turn motif) and Ser-657 (hydrophobic region), need to be phosphorylated for its full activation.
messages: Cytoplasm
messages: Membrane
messages: Mitochondrion membrane
messages: Nucleus
messages: Recruited in a circadian manner into a nuclear complex which also includes BMAL1 and RACK1 (By similarity). Interacts with ADAP1/CENTA1 (PubMed:12893243). Interacts with CSPG4 (PubMed:15504744). Binds to CAVIN2 in the presence of phosphatidylserine (By similarity). Interacts with PRKCABP/PICK1 (via PDZ domain) (PubMed:15247289). Interacts with TRIM41 (PubMed:17893151). Interacts with PARD3 (PubMed:27925688). Interacts with SOCS2 (By similarity).

9606:GNG7
gene id: 9606:GNG7
uniprot id: O60262
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the G protein gamma family.
messages: Cell membrane
messages: Expressed in a variety of tissues. Down-regulated in pancreatic and esophageal cancer.
messages: G proteins are composed of 3 units, alpha, beta and gamma.
messages: Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction. Plays a role in the regulation of adenylyl cyclase signaling in certain regions of the brain. Plays a role in the formation or stabilzation of a G protein heterotrimer (G(olf) subunit alpha-beta-gamma-7) that is required for adenylyl cyclase activity in the striatum (By similarity).

9606:GEMIN6
gene id: 9606:GEMIN6
uniprot id: Q8WXD5
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Cytoplasm
messages: Part of the core SMN complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8 and STRAP/UNRIP (PubMed:18984161, PubMed:11748230, PubMed:15939020, PubMed:12065586, PubMed:16314521, PubMed:17178713). Part of the SMN-Sm complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8, STRAP/UNRIP and the Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG (PubMed:18984161, PubMed:16314521). Interacts with GEMIN7; the interaction is direct (PubMed:12065586, PubMed:15939020, PubMed:33754639, PubMed:17178713). Interacts with GEMIN8; the interaction is direct (PubMed:33754639). Interacts with SNRPB, SNRPD2, SNRPD3 and SNRPE; the interaction is direct (PubMed:11748230, PubMed:15939020).
messages: The SMN complex catalyzes the assembly of small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome, and thereby plays an important role in the splicing of cellular pre-mRNAs. Most spliceosomal snRNPs contain a common set of Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP (Sm core). In the cytosol, the Sm proteins SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG are trapped in an inactive 6S pICln-Sm complex by the chaperone CLNS1A that controls the assembly of the core snRNP. To assemble core snRNPs, the SMN complex accepts the trapped 5Sm proteins from CLNS1A forming an intermediate. Binding of snRNA inside 5Sm triggers eviction of the SMN complex, thereby allowing binding of SNRPD3 and SNRPB to complete assembly of the core snRNP.
messages: gem
messages: nucleoplasm

9606:FAM149A
gene id: 9606:FAM149A
uniprot id: A5PLN7
names: Similarity
messages: Belongs to the FAM149 family.

9606:WFDC8
gene id: 9606:WFDC8
uniprot id: Q8IUA0
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Expressed ubiquitously, the highest levels are found in the epididymis followed by testis and trachea.
messages: Secreted

9606:TMEM26
gene id: 9606:TMEM26
uniprot id: Q6ZUK4
names: Miscellaneous
names: Subcellular Location Annotation
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Membrane

9606:DCST1
gene id: 9606:DCST1
uniprot id: B4DXB8
uniprot id: B4DXE3
uniprot id: Q5T197
names: Domain
names: Function
names: Induction
names: Subcellular Location Annotation
names: Subunit
messages: Cell membrane
messages: E3 ubiquitin-protein ligase which mediates 'Lys-48'-linked ubiquitination of STAT2 and induces its proteasomal degradation thereby negatively regulating type-I-interferon signaling. Essential sperm cell-surface protein required for sperm-egg fusion and fertilization (By similarity).
messages: Induced by IFNB1.
messages: Interacts with STAT2; the interaction results in STAT2 'Lys-48'-linked ubiquitination leading to its proteasomal degradation. Interacts with DCST2 (By similarity).
messages: Membrane
messages: The RING-type zinc finger domain is responsible for E3 ubiquitin ligase activity.
messages: acrosome membrane

9606:ATP7A
gene id: 9606:ATP7A
uniprot id: B4DRW0
uniprot id: Q04656
names: Caution
names: Disease Annotation
names: Domain
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: ATP-driven copper (Cu(+)) ion pump that plays an important role in intracellular copper ion homeostasis (PubMed:10419525, PubMed:11092760, PubMed:28389643). Within a catalytic cycle, acquires Cu(+) ion from donor protein on the cytoplasmic side of the membrane and delivers it to acceptor protein on the lumenal side. The transfer of Cu(+) ion across the membrane is coupled to ATP hydrolysis and is associated with a transient phosphorylation that shifts the pump conformation from inward-facing to outward-facing state (PubMed:10419525, PubMed:19453293, PubMed:19917612, PubMed:31283225, PubMed:28389643). Under physiological conditions, at low cytosolic copper concentration, it is localized at the trans-Golgi network (TGN) where it transfers Cu(+) ions to cuproenzymes of the secretory pathway (PubMed:28389643, PubMed:11092760). Upon elevated cytosolic copper concentrations, it relocalizes to the plasma membrane where it is responsible for the export of excess Cu(+) ions (PubMed:10419525, PubMed:28389643). May play a dual role in neuron function and survival by regulating cooper efflux and neuronal transmission at the synapse as well as by supplying Cu(+) ions to enzymes such as PAM, TYR and SOD3 (PubMed:28389643) (By similarity). In the melanosomes of pigmented cells, provides copper cofactor to TYR to form an active TYR holoenzyme for melanin biosynthesis (By similarity).
messages: Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IB subfamily.
messages: Cell membrane
messages: Contains three di-leucine motifs in the C-terminus which are required for recycling from the plasma membrane to the TGN. The di-leucine 1487-Leu-Leu-1488 motif mediates endocytosis at the plasma membrane, whereas the di-leucine 1467-Leu-Leu-1468 motif is a sorting signal for retrograde trafficking to TGN via early endosomes.
messages: Early endosome membrane
messages: Endoplasmic reticulum
messages: Expressed in cerebellum and brain cortex.
messages: Lacks 6 transmembrane regions and 5 heavy-metal-associated (HMA) domains.
messages: Lacks all transmembrane regions and 5 heavy-metal-associated (HMA) domains, but has a putative nuclear localization signal attached at the N-terminus.
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: Lacks the transmembrane domains 3 and 4. Expressed at a low level in several tissues of normal individuals and is the only isoform found in patients with OHS.
messages: Melanosome membrane
messages: Membrane
messages: Monomer. Interacts with PDZD11 (PubMed:16051599). Interacts with ATOX1 and COMMD1 (PubMed:21667063, PubMed:19453293, PubMed:31283225). Interacts with TYRP1 (By similarity). Directly interacts with SOD3; this interaction is copper-dependent and is required for SOD3 activity.
messages: Postsynaptic density
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The heavy-metal-associated domain (HMA) coordinates a Cu(+) ion via the cysteine residues within the CXXC motif. The transfer of Cu(+) ion from ATOX1 to ATP7A involves the formation of a three-coordinate Cu(+)-bridged heterodimer where the metal is shared between the two metal binding sites of ATOX1 and ATP7A. The Cu(+) ion appears to switch between two coordination modes, forming two links with one protein and one with the other. Cisplatin, a chemotherapeutic drug, can bind the CXXC motif and hinder the release of Cu(+) ion.
messages: The nucleotide-binding domain consists of a twisted six-stranded antiparallel beta-sheet flanked by two pairs of alpha-helices, forming an hydrophobic pocket that interacts with the adenine ring of ATP. The ATP binding site comprises residues located in alpha-1 and alpha-2 helices and beta-2 and beta-3 strands, which are involved in van der Waal's interactions, and Glu-1081 which forms an hydrogen bond with the adenine ring.
messages: Widely expressed including in heart, brain, lung, muscle, kidney, pancreas, and to a lesser extent placenta (PubMed:8490646, PubMed:8490659). Expressed in fibroblasts, aortic smooth muscle cells, aortic endothelial cells and umbilical vein endothelial cells (at protein level) (PubMed:16371425).
messages: axon
messages: cytosol
messages: dendrite
messages: trans-Golgi network membrane

9606:ZFHX2
gene id: 9606:ZFHX2
uniprot id: A0A2P1H683
uniprot id: B7ZM83
uniprot id: B9EK48
uniprot id: Q9C0A1
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
messages: Nucleus
messages: The disease may be caused by variants affecting the gene represented in this entry.
messages: Transcriptional regulator that is critical for the regulation of pain perception and processing of noxious stimuli.

9606:ZNF593
gene id: 9606:ZNF593
uniprot id: O00488
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Associates with pre-60S ribosomal particles.
messages: Belongs to the ZNF593/BUD20 C2H2-type zinc-finger protein family.
messages: Cytoplasm
messages: Involved in pre-60S ribosomal particles maturation by promoting the nuclear export of the 60S ribosome (PubMed:32669547). Negatively modulates the DNA binding activity of Oct-2 and therefore its transcriptional regulatory activity (PubMed:9115366).
messages: The protein is largely disordered, with the exception of the zinc finger domain.
messages: Ubiquitous. Detected in spleen, prostate, testis, small intestine, colon and to a minor level in thymus and peripheral blood leukocytes.
messages: nucleolus

9606:NEU1
gene id: 9606:NEU1
uniprot id: Q5JQI0
uniprot id: Q99519
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: A C-terminal internalization signal (YGTL) appears to allow the targeting of plasma membrane proteins to endosomes.
messages: Belongs to the glycosyl hydrolase 33 family.
messages: Catalyzes the removal of sialic acid (N-acetylneuraminic acid) moieties from glycoproteins and glycolipids. To be active, it is strictly dependent on its presence in the multienzyme complex. Appears to have a preference for alpha 2-3 and alpha 2-6 sialyl linkage.
messages: Cell membrane
messages: Cytoplasmic vesicle
messages: Highly expressed in pancreas, followed by skeletal muscle, kidney, placenta, heart, lung and liver. Weakly expressed in brain.
messages: Interacts with cathepsin A (protective protein), beta-galactosidase and N-acetylgalactosamine-6-sulfate sulfatase in a multienzyme complex.
messages: Lysosome
messages: Lysosome lumen
messages: Lysosome membrane
messages: N-glycosylated.
messages: Phosphorylation of tyrosine within the internalization signal results in inhibition of sialidase internalization and blockage on the plasma membrane.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:ACSBG2
gene id: 9606:ACSBG2
uniprot id: Q5FVE4
names: Developmental Stage
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the ATP-dependent AMP-binding enzyme family. Bubblegum subfamily.
messages: Catalyzes the conversion of fatty acids such as long chain and very long-chain fatty acids to their active form acyl-CoAs for both synthesis of cellular lipids, and degradation via beta-oxidation. Can activate diverse saturated, monosaturated and polyunsaturated fatty acids (PubMed:16371355, PubMed:16762313). Has increased ability to activate oleic and linoleic acid (PubMed:16371355). May play a role in spermatogenesis (PubMed:15685348).
messages: Cytoplasm
messages: Membrane
messages: Testis-specific.
messages: Weakly or not expressed in fetal testis. Highly expressed in adult testis and moderately in elderly testis.

9606:ST6GALNAC2
gene id: 9606:ST6GALNAC2
uniprot id: Q9UJ37
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Aberrant O-galactosylation of IgA1 molecules plays a role in the development and progression of IgA nephropathy (IgAN). Genetic interactions of C1GALT1 and ST6GALNAC2 variants influence IgA1 O-glycosylation, disease predisposition, and disease severity, and may contribute to the polygenic nature of IgAN.
messages: Belongs to the glycosyltransferase 29 family.
messages: Catalyzes the transfer of N-acetylneuraminyl groups onto glycan chains in glycoproteins (PubMed:10742600, PubMed:29251719). Shows a preference for N-acetylgalactosamine (GalNAc) residues already modified by the addition of galactose or galactose followed by sialic acid in alpha-2,3 linkage (PubMed:10742600).
messages: Expressed in skeletal muscle, heart, kidney, placenta, lung and leukocytes.
messages: Golgi apparatus membrane

9606:ZMYM3
gene id: 9606:ZMYM3
uniprot id: Q14202
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: A chromosomal aberration involving ZMYM3 may be a cause of X-linked intellectual disability in Xq13.1. Translocation t(X;13)(q13.1;?).
messages: May be a component of a BHC histone deacetylase complex that contains HDAC1, HDAC2, HMG20B/BRAF35, KDM1A, RCOR1/CoREST, PHF21A/BHC80, ZMYM2, ZNF217, ZMYM3, GSE1 and GTF2I.
messages: Most abundant in brain, moderate in muscle and heart, low in other tissues except placenta.
messages: Nucleus
messages: Plays a role in the regulation of cell morphology and cytoskeletal organization.

9606:BBS9
gene id: 9606:BBS9
uniprot id: A0A090N8P4
uniprot id: Q3SYG4
names: Caution
names: Disease Annotation
names: Function
names: Induction
names: Sequence Caution
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: A chromosomal aberration involving PTHB1 has been found in Wilms tumor. Translocation t(1;7)(q42;p15) with OBSCN.
messages: Chimera.
messages: Cytoplasm
messages: Down-regulated by parathyroid hormone.
messages: Part of BBSome complex, that contains BBS1, BBS2, BBS4, BBS5, BBS7, BBS8/TTC8, BBS9 and BBIP10. Interacts with LZTL1; the interaction mediates the association of LZTL1 with the BBsome complex and regulates BBSome ciliary trafficking.
messages: The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia. The BBSome complex is required for ciliogenesis but is dispensable for centriolar satellite function. This ciliogenic function is mediated in part by the Rab8 GDP/GTP exchange factor, which localizes to the basal body and contacts the BBSome. Rab8(GTP) enters the primary cilium and promotes extension of the ciliary membrane. Firstly the BBSome associates with the ciliary membrane and binds to RAB3IP/Rabin8, the guanosyl exchange factor (GEF) for Rab8 and then the Rab8-GTP localizes to the cilium and promotes docking and fusion of carrier vesicles to the base of the ciliary membrane. Required for proper BBSome complex assembly and its ciliary localization.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The sequence shown here is derived from an EMBL/GenBank/DDBJ whole genome shotgun (WGS) entry which is preliminary data.
messages: Widely expressed. Expressed in adult heart, skeletal muscle, lung, liver, kidney, placenta and brain, and in fetal kidney, lung, liver and brain.
messages: centriolar satellite
messages: centrosome
messages: cilium membrane

9606:MS4A3
gene id: 9606:MS4A3
uniprot id: Q96HJ5
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the MS4A family.
messages: Endomembrane system
messages: Expressed specifically in hematopoietic cells and tissues.
messages: Hematopoietic modulator for the G1-S cell cycle transition. Modulates the level of phosphorylation of cyclin-dependent kinase 2 (CDK2) through its direct binding to cyclin-dependent kinase inhibitor 3 (CDKN3/KAP).
messages: Interacts with CDKN3. Interacts with CDKN3-CDK2 complexes through its binding to CDKN3; this interaction facilitates dissociation of cyclin A from CDKN3-CDK2 complexes.
messages: The C-terminal region is required for binding to CDKN3-CDK2 complexes and the modulation of CDKN3 activity.
messages: perinuclear region

9606:RPP14
gene id: 9606:RPP14
uniprot id: O95059
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the eukaryotic/archaeal RNase P protein component 2 family.
messages: Component of ribonuclease P, a ribonucleoprotein complex that generates mature tRNA molecules by cleaving their 5'-ends.
messages: RNase P consists of a catalytic RNA moiety and about 10 protein subunits; POP1, POP4, POP5, POP7, RPP14, RPP21, RPP25, RPP30, RPP38 and RPP40 (PubMed:10024167, PubMed:16723659, PubMed:30454648). Within the RNase P complex, POP1, POP7 and RPP25 form the 'finger' subcomplex, POP5, RPP14, RPP40 and homodimeric RPP30 form the 'palm' subcomplex, and RPP21, POP4 and RPP38 form the 'wrist' subcomplex. All subunits of the RNase P complex interact with the catalytic RNA (PubMed:30454648).
messages: This protein is produced by a bicistronic gene which also produces the HTD2 protein from an overlapping reading frame.
messages: nucleolus

9606:ZNF496
gene id: 9606:ZNF496
uniprot id: Q96IT1
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: DNA-binding transcription factor that can both act as an activator and a repressor.
messages: Interacts (via zinc-fingers) with JARID2. Interacts with NSD1 (By similarity).
messages: Nucleus
messages: The C2H2-type zinc finger 1, also named C2HR, mediates the interaction with NSD1.

9606:TGM2
gene id: 9606:TGM2
uniprot id: B4DIT7
uniprot id: B4DTN7
uniprot id: P21980
uniprot id: V9HWG3
names: Activity Regulation
names: Caution
names: Cofactor
names: Disease Annotation
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Acyltransferase activity is regulated by the binding of GTP and Ca(2+): inactivated by GTP, which stabilizes its closed structure, thereby obstructing the accessibility of substrates to the active sites (PubMed:2903073, PubMed:7592956, PubMed:18092889, PubMed:31991788). In contrast, Ca(2+) acts as a cofactor by inducing conformational change to the active open form (PubMed:2903073, PubMed:18092889, PubMed:31991788). In absence of Ca(2+), Mg(2+) may bind Ca(2+)-binding sites, promoting GTP-binding and subsequent inhibition of the acyltransferase activity (PubMed:31991788). Specifically inhibited by compound VA4 ((S)-Benzyl (6-Acrylamido-1-(4-((5-(dimethylamino)naphthalen-1-yl)sulfonyl)piperazin-1-yl)-1-oxohexan-2-yl)carbamate), which specifically abolishes both the transamidation and GTP-binding activities (PubMed:28858494).
messages: Auto-transglutaminated: Forms covalent cross-links mediated by transglutaminase between Gln-633 and the epsilon-amino group of a lysine residue of itself or HMGB1, forming homopolymers and heteropolymers, respectively.
messages: Belongs to the transglutaminase superfamily. Transglutaminase family.
messages: Binds 1 Ca(2+) ion per subunit.
messages: By retinoic acid.
messages: Calcium-dependent acyltransferase that catalyzes the formation of covalent bonds between peptide-bound glutamine and various primary amines, such as gamma-amino group of peptide-bound lysine, or mono- and polyamines, thereby producing cross-linked or aminated proteins, respectively (PubMed:9252372, PubMed:23941696, PubMed:31991788). Involved in many biological processes, such as bone development, angiogenesis, wound healing, cellular differentiation, chromatin modification and apoptosis (PubMed:1683874, PubMed:7935379, PubMed:9252372, PubMed:27270573). Acts as a protein-glutamine gamma-glutamyltransferase by mediating the cross-linking of proteins, such as ACO2, HSPB6, FN1, HMGB1, RAP1GDS1, SLC25A4/ANT1, SPP1 and WDR54 (PubMed:23941696, PubMed:24349085, PubMed:29618516, PubMed:30458214). Under physiological conditions, the protein cross-linking activity is inhibited by GTP; inhibition is relieved by Ca(2+) in response to various stresses (PubMed:7649299, PubMed:7592956, PubMed:18092889). When secreted, catalyzes cross-linking of proteins of the extracellular matrix, such as FN1 and SPP1 resulting in the formation of scaffolds (PubMed:12506096). Plays a key role during apoptosis, both by (1) promoting the cross-linking of cytoskeletal proteins resulting in condensation of the cytoplasm, and by (2) mediating cross-linking proteins of the extracellular matrix, resulting in the irreversible formation of scaffolds that stabilize the integrity of the dying cells before their clearance by phagocytosis, thereby preventing the leakage of harmful intracellular components (PubMed:7935379, PubMed:9252372). In addition to protein cross-linking, can use different monoamine substrates to catalyze a vast array of protein post-translational modifications: mediates aminylation of serotonin, dopamine, noradrenaline or histamine into glutamine residues of target proteins to generate protein serotonylation, dopaminylation, noradrenalinylation or histaminylation, respectively (PubMed:237…
messages: Cell membrane
messages: Chromosome
messages: Disulfide bond formation inactivates the calcium-dependent acyltransferase activity (PubMed:20547769). Cys-370 can form disulfide bonds with both Cys-230 and Cys-371: formation of a disulfide bond between Cys-230 and Cys-370 facilitates formation of the disulfide between Cys-370 and Cys-371, which promotes inactivation of the acyltransferase activity (PubMed:20547769). May also form interchain disulfids between Cys-230 and Cys-370 (PubMed:25192068). Ca(2+) protects against disulfide bond formation and inactivation (PubMed:20547769).
messages: Has cytotoxic activity: is able to induce apoptosis independently of its acyltransferase activity.
messages: Homooligomer.
messages: Initial enzymatic assays were performed with a protein sequence containing a Gly residue instead of a Val at position 224: such protein displays lower Ca(2+)-binding affinity and reduced transglutaminase activity.
messages: Mitochondrion
messages: Monomer (PubMed:25192068). Interacts with phospholipase C; promoting alpha-1 adrenergic receptor signaling (PubMed:7592956). Interacts with PLCD1 (By similarity).
messages: Nucleus
messages: S-nitrosylated, leading to inactivation of the acyltransferase activity.
messages: TGM2 constitutes the major autoantigen in celiac disease, a multifactorial chronic disorder of the small intestine caused by intolerance to gluten (PubMed:9212111, PubMed:9623982). Celiac disease is characterized by immune-mediated enteropathy associated with failed intestinal absorption and malnutrition: intestinal inflammation is precipitated by ingestion of the protein gliadin, a component of wheat gluten in the diet (PubMed:9212111, PubMed:9623982). TGM2 is the main target for celiac disease-associated anti-endomysium autoantibodies (PubMed:9212111). It mediates its effect by catalyzing specific deamidation of gliadin; this deamidation creates an epitope that binds efficiently to HLA-DQ2 and is recognized by gut-derived T-cells (PubMed:9623982).
messages: cytosol
messages: extracellular matrix
messages: perinuclear region

9606:LSS
gene id: 9606:LSS
uniprot id: B2R694
uniprot id: P48449
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the terpene cyclase/mutase family.
messages: Endoplasmic reticulum membrane
messages: Key enzyme in the cholesterol biosynthesis pathway. Catalyzes the cyclization of (S)-2,3 oxidosqualene to lanosterol, a reaction that forms the sterol nucleus (PubMed:14766201, PubMed:7639730, PubMed:26200341). Through the production of lanosterol may regulate lens protein aggregation and increase transparency (PubMed:26200341).
messages: Monomer.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Widely expressed. Expressed in the hair bulb, the outer root sheath and hair matrix of the hair follicle epithelium. Also detected in dermal papilla, epidermis, sweat glands, sebaceous glands, and blood vessels.

9606:CMTM6
gene id: 9606:CMTM6
uniprot id: Q9NX76
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the chemokine-like factor family.
messages: Cell membrane
messages: Early endosome membrane
messages: Expressed in the leukocytes, placenta and testis.
messages: Interacts with PD-L1/CD274 (via transmembrane domain); the interaction is direct (PubMed:28813417, PubMed:28813410). Interacts with CMTM4 (PubMed:28813410). Interacts with CD58, ARG1, ENO1 and TMPO (PubMed:28813417).
messages: Master regulator of recycling and plasma membrane expression of PD-L1/CD274, an immune inhibitory ligand critical for immune tolerance to self and antitumor immunity. Associates with both constitutive and IFNG-induced PD-L1/CD274 at recycling endosomes, where it protects PD-L1/CD274 from being targeted for lysosomal degradation, likely by preventing its STUB1-mediated ubiquitination. May stabilize PD-L1/CD274 expression on antigen presenting cells and potentiates inhibitory signaling by PDCD1/CD279, its receptor on T-cells, ultimately triggering T-cell anergy.
messages: Recycling endosome membrane

9606:RPL23A
gene id: 9606:RPL23A
uniprot id: P62750
names: Domain
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the universal ribosomal protein uL23 family.
messages: Citrullinated by PADI4.
messages: Component of the large ribosomal subunit (PubMed:23636399, PubMed:32669547). Interacts with LYAR and GNL2 (PubMed:26203195). Interacts with MDM2; this interaction may promote MDM2-mediated p53/TP53 polyubiquitination (PubMed:26203195). Directly interacts (via BIB domain) with IPO5, IPO7, KPNB1 and TNPO1; these interactions are involved in RPL23A nuclear import for the assembly of ribosomal subunits (PubMed:9687515, PubMed:11682607). Interacts with IPO8 (PubMed:11682607).
messages: Component of the large ribosomal subunit (PubMed:23636399, PubMed:32669547). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399, PubMed:32669547). Binds a specific region on the 26S rRNA (PubMed:23636399, PubMed:32669547). May promote p53/TP53 degradation possibly through the stimulation of MDM2-mediated TP53 polyubiquitination (PubMed:26203195).
messages: Cytoplasm
messages: May be down-regulated by GNL2 (at protein level).
messages: N-terminus is methylated by METTL11A/NTM1.
messages: Nucleus
messages: The N-terminal beta-like import receptor binding (BIB) domain mediates interaction with IPO5, IPO7, KPNB1 and TNPO1.

9606:BMS1
gene id: 9606:BMS1
uniprot id: Q14692
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the TRAFAC class translation factor GTPase superfamily. Bms1-like GTPase family. BMS1 subfamily.
messages: Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3.
messages: Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: nucleolus

9606:QPCTL
gene id: 9606:QPCTL
uniprot id: Q9NXS2
names: Caution
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the glutaminyl-peptide cyclotransferase family.
messages: Golgi apparatus membrane
messages: It is unclear whether this protein requires a metal cofactor for catalysis. It was originally proposed to be a Zn(2+)-dependent metalloenzyme based on structural similarities to bacterial aminopeptidases and the observation that it can bind Zn(2+) ions, typically in a 1:1 stoichiometry (PubMed:21288892). However, a recent study suggests a Zn(2+)-independent catalytic mechanism (By similarity).
messages: Responsible for the biosynthesis of pyroglutamyl peptides.

9606:IMPA2
gene id: 9606:IMPA2
uniprot id: O14732
names: Activity Regulation
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the inositol monophosphatase superfamily.
messages: Can use myo-inositol monophosphates, scylloinositol 1,4-diphosphate, glucose-1-phosphate, beta-glycerophosphate, and 2'-AMP as substrates. Has been implicated as the pharmacological target for lithium Li(+) action in brain.
messages: Cytoplasm
messages: Homodimer.
messages: Inhibited by high Li(+) and restricted Mg(2+) concentrations.
messages: Repressed by Li(+).

9606:TBC1D9
gene id: 9606:TBC1D9
uniprot id: Q6ZT07
names: Domain
names: Function
names: Sequence Caution
messages: Aberrant splicing.
messages: May act as a GTPase-activating protein for Rab family protein(s).
messages: The arginine and glutamine fingers are critical for the GTPase-activating mechanism, they pull out Rab's 'switch 2' glutamine and insert in Rab's active site.

9606:GABRA5
gene id: 9606:GABRA5
uniprot id: P31644
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRA5 sub-subfamily.
messages: Cell membrane
messages: Generally pentameric. There are five types of GABA(A) receptor subunits: alpha, beta, gamma, delta, and rho.
messages: Ligand-gated chloride channel subunit which is a component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the brain (PubMed:29961870, PubMed:31056671). May be involved in GABA-A receptor assembly, and GABA-A receptor immobilization and accumulation by gephyrin at the synapse (PubMed:31056671).
messages: Postsynaptic cell membrane
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:CFAP299
gene id: 9606:CFAP299
uniprot id: Q6V702
names: Function
names: Miscellaneous
names: Subcellular Location Annotation
messages: Cytoplasm
messages: May be involved in spermatogenesis.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Nucleus

9606:AQP8
gene id: 9606:AQP8
uniprot id: O94778
names: Activity Regulation
names: Domain
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Apical cell membrane
messages: Aquaporins contain two tandem repeats each containing three membrane-spanning domains and a pore-forming loop with the signature motif Asn-Pro-Ala (NPA).
messages: Basolateral cell membrane
messages: Belongs to the MIP/aquaporin (TC 1.A.8) family.
messages: Cell membrane
messages: Channel that allows the facilitated permeation of water and uncharged molecules, such as hydrogen peroxide and the neutral form of ammonia (NH3), through cellular membranes such as plasma membrane, inner mitochondrial membrane and endoplasmic reticulum membrane of several tissues (PubMed:26972385, PubMed:15948717, PubMed:18948439, PubMed:23541115, PubMed:29732408, PubMed:30579780). The transport of the ammonia neutral form induces a parallel transport of proton, at alkaline pH when the concentration of ammonia is high (By similarity). However, it is unclear whether the transport of proton takes place via the aquaporin or via an endogenous pathway (By similarity). Also, may transport ammonia analogs such as formamide and methylamine, a transport favourited at basic pH due to the increase of unprotonated (neutral) form, which is expected to favor diffusion (PubMed:15948717). Does not transport urea or glycerol (PubMed:15948717). The water transport mechanism is mercury- and copper-sensitive and passive in response to osmotic driving forces (PubMed:15948717). At the canicular plasma membrane, mediates the osmotic transport of water toward the bile canaliculus and facilitates the cAMP-induced bile canalicular water secretion, a process involved in bile formation (PubMed:18948439). In addition, mediates the hydrogen peroxide release from hepatocyte mitochondria that modulates the SREBF2-mediated cholesterol synthesis and facilitates the mitochondrial ammonia uptake which is metabolized into urea, mainly under glucagon stimulation (PubMed:30579780, PubMed:34292591). In B cells, transports the CYBB-generated hydrogen peroxide from the external leaflet of the plasma membrane to the cytosol to promote B cell activation and differentiation for signal amplification (By similarity). In the small intestine and colon system, mediates water transport through mitochondria and apical membrane of epithelial cells (By similarity). May play an important role in the adaptive response of…
messages: Detected in the sperm midpiece (at protein level) (PubMed:28042826). Expressed only in pancreas and colon.
messages: Mitochondrion inner membrane
messages: N-glycosylated.
messages: Persulfidation at Cys-53 is required to gate AQP8 channel; under stress condition, hydrogen peroxide accumulates in the cell leading to CBS activation that produces hydrogen sulfide inducing persulfidation of oxidized Cys-53 (C53-SOH).
messages: Regulated by osmotic stress (PubMed:20144166). Up-regulated in response to metabolic acidosis (PubMed:22622463).
messages: Reversibly gated by a two-step sulfenylation-persulfidation process in cells undergoing diverse stresses.
messages: Smooth endoplasmic reticulum membrane
messages: Sulfenylation at Cys-53(C53-SOH) when hydrogen peroxide flows through the AQP8 channel, making it susceptible to hydrogen sulfide produced by CBS.

9606:SERPINA12
gene id: 9606:SERPINA12
uniprot id: Q8IW75
names: Activity Regulation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Adipokine that modulates insulin action by specifically inhibiting its target protease KLK7 in white adipose tissues.
messages: Belongs to the serpin family.
messages: Expressed in visceral adipose tissues.
messages: Forms a stable complex with KLK7.
messages: Glycosylation slightly decreases affinity for heparin, but otherwise has no significant effect on KLK7 inhibitory activity or thermal stability of the protein.
messages: Inhibition of KLK7 is enhanced by heparin.
messages: Secreted
messages: The reactive center loop (RCL) extends out from the body of the protein and directs binding to the target protease. The protease cleaves the serpin at the reactive site within the RCL, establishing a covalent linkage between the carboxyl group of the serpin reactive site and the serine hydroxyl of the protease. The resulting inactive serpin-protease complex is highly stable.

9606:LUC7L2
gene id: 9606:LUC7L2
uniprot id: Q9Y383
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the Luc7 family.
messages: Interacts with SCNM1.
messages: May bind to RNA via its Arg/Ser-rich domain.
messages: Nucleus speckle
messages: nucleoplasm

9606:KRTAP9-7
gene id: 9606:KRTAP9-7
uniprot id: A8MTY7
names: Function
names: Similarity
names: Subunit
messages: Belongs to the KRTAP type 9 family.
messages: In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins (By similarity).
messages: Interacts with hair keratins.

9606:DYNLT2B
gene id: 9606:DYNLT2B
uniprot id: Q8WW35
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 2 complex (dynein-2 complex), a motor protein complex that drives the movement of cargos along microtubules within cilia and flagella in concert with the intraflagellar transport (IFT) system. Required for proper retrograde ciliary transport.
messages: Belongs to the dynein light chain Tctex-type family.
messages: Dynein axonemal particle
messages: Light chain of the cytoplasmic dynein complex 2, a multisubunit complex composed at least of eleven different proteins (PubMed:25205765, PubMed:26044572). The cytoplasmic dynein 2 complex consists of two catalytic heavy chains (HCs) and a number of non-catalytic subunits presented by intermediate chains (ICs), light intermediate chains (LICs) and light chains (LCs). Among them, a heavy chain (DYNC2H1), two intermediate chains (DYNC2I2 and DYNC2I1), a light intermediate chain (DYNC2LI1), and a light chain (DYNLT2B) are unique to the dynein-2 complex, but a subset of the light chains are also shared by dynein-1 and dynein-2 complexes (PubMed:25205765, PubMed:26044572). Interacts with DYNC2I1 (PubMed:26044572). The dimer DYNLT2B-DYNLT1/DYNLT3 interacts with DYNC2I1; this interaction is crucial for retrograde trafficking of ciliary proteins (PubMed:29742051, PubMed:26044572).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:NCBP3
gene id: 9606:NCBP3
uniprot id: Q53F19
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Associates with NCBP1/CBP80 to form an alternative cap-binding complex (CBC) which plays a key role in mRNA export. NCBP3 serves as adapter protein linking the capped RNAs (m7GpppG-capped RNA) to NCBP1/CBP80. Unlike the conventional CBC with NCBP2 which binds both small nuclear RNA (snRNA) and messenger (mRNA) and is involved in their export from the nucleus, the alternative CBC with NCBP3 does not bind snRNA and associates only with mRNA thereby playing a role in only mRNA export. The alternative CBC is particularly important in cellular stress situations such as virus infections and the NCBP3 activity is critical to inhibit virus growth (PubMed:26382858).
messages: Belongs to the NCBP3 family.
messages: Component of an alternative cap-binding complex (CBC) composed of NCBP1/CBP80 and NCBP3. Interacts with SRRT, KPNA3, THOC5 and EIF4A3.
messages: Cytoplasm
messages: Nucleus

9606:VDR
gene id: 9606:VDR
uniprot id: F1D8P8
uniprot id: P11473
names: Caution
names: Disease Annotation
names: Domain
names: Function
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the nuclear hormone receptor family. NR1 subfamily.
messages: Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.
messages: Cytoplasm
messages: Genetic variations in VDR may determine Mycobacterium tuberculosis susceptibility [MIM:607948].
messages: Homodimer in the absence of bound vitamin D3 (PubMed:11980721). Heterodimer with RXRA after vitamin D3 binding (PubMed:15225774, PubMed:11980721, PubMed:10678179). Interacts with MED1, NCOA1, NCOA2, NCOA3 and NCOA6 coactivators, leading to a strong increase of transcription of target genes (PubMed:10866662, PubMed:15728261, PubMed:28698609, PubMed:9267036). Interacts with the corepressor NCOR1 (PubMed:28698609). Interacts with SNW1 (PubMed:9632709). Interacts with IRX4, the interaction does not affect its transactivation activity (PubMed:22323358). Interacts with CRY1 (By similarity). Interacts with CRY2 in a ligand-dependent manner (By similarity).
messages: It is uncertain whether Met-1 or Met-4 is the initiator.
messages: Nuclear receptor for calcitriol, the active form of vitamin D3 which mediates the action of this vitamin on cells (PubMed:28698609, PubMed:16913708, PubMed:15728261, PubMed:10678179). Enters the nucleus upon vitamin D3 binding where it forms heterodimers with the retinoid X receptor/RXR (PubMed:28698609). The VDR-RXR heterodimers bind to specific response elements on DNA and activate the transcription of vitamin D3-responsive target genes (PubMed:28698609). Plays a central role in calcium homeostasis (By similarity). Also functions as a receptor for the secondary bile acid lithocholic acid (LCA) and its metabolites (PubMed:12016314, PubMed:32354638).
messages: Nucleus
messages: The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Was thought to be recruited to promoters via its interaction with BAZ1B/WSTF, but this work has later been retracted.

9606:OXTR
gene id: 9606:OXTR
uniprot id: B2R9L7
uniprot id: P30559
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family. Vasopressin/oxytocin receptor subfamily.
messages: Cell membrane
messages: Membrane
messages: Receptor for oxytocin. The activity of this receptor is mediated by G proteins which activate a phosphatidylinositol-calcium second messenger system.

9606:ISL1
gene id: 9606:ISL1
uniprot id: P61371
names: Developmental Stage
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: At neuronal promoters, displaces LDB1 from LHX3 LIM domain to form a ternary complex in which ISL1 contacts both LHX3 and LDB1; allosteric structural changes in the DNA binding domain of LHX3, induced by the ISL1:LHX3 interaction, may explain differences in sequence specificity of the different complexes. Interacts with LHX3. Interacts (via C-terminus) with POU4F2 (via C-terminus) isoform 1. Interacts with POU3F2. Interacts with POU4F3. Interacts (via N-terminal domain) with MLIP; the interaction represses ISL1 transactivator activity. Interacts with GCN5/KAT2A. Interactions of ISL1 with MLIP1 or KAT2A may be mutually exclusive (By similarity).
messages: DNA-binding transcriptional activator. Recognizes and binds to the consensus octamer binding site 5'-ATAATTAA-3' in promoter of target genes. Plays a fundamental role in the gene regulatory network essential for retinal ganglion cell (RGC) differentiation. Cooperates with the transcription factor POU4F2 to achieve maximal levels of expression of RGC target genes and RGC fate specification in the developing retina. Involved in the specification of motor neurons in cooperation with LHX3 and LDB1 (By similarity). Binds to insulin gene enhancer sequences (By similarity). Essential for heart development. Marker of one progenitor cell population that give rise to the outflow tract, right ventricle, a subset of left ventricular cells, and a large number of atrial cells as well, its function is required for these progenitors to contribute to the heart. Controls the expression of FGF and BMP growth factors in this cell population and is required for proliferation and survival of cells within pharyngeal foregut endoderm and adjacent splanchnic mesoderm as well as for migration of cardiac progenitors into the heart (By similarity).
messages: Expressed in subsets of neurons of the adrenal medulla and dorsal root ganglion, inner nuclear and ganglion cell layers in the retina, the pineal and some regions of the brain.
messages: Expressed in the forming heart in the stage 9 embryo, in the myocardial trough, and then at stages 10 to 11, in the nondifferentiated mesodermal cells at the venous and arterial poles, as well as cells of the dorsal coelomic wall and ruptured mesocardium (at protein level).
messages: Nucleus
messages: Phosphorylated.
messages: Ubiquitinated probably by WWP1 E3 ubiquitin ligase; ubiquitination is followed by protein degradation.

9606:ACSS3
gene id: 9606:ACSS3
uniprot id: A0A0B4J1R2
uniprot id: Q9H6R3
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the ATP-dependent AMP-binding enzyme family.
messages: Catalyzes the synthesis of acetyl-CoA from short-chain fatty acids (PubMed:28003429). Propionate is the preferred substrate (PubMed:28003429). Can utilize acetate and butyrate with a much lower affinity (By similarity).
messages: Mitochondrion matrix

9606:TPSG1
gene id: 9606:TPSG1
uniprot id: Q9NRR2
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the peptidase S1 family. Tryptase subfamily.
messages: Expressed in many tissues.
messages: Membrane
messages: There are two alleles; gamma-I and gamma-II which differ by 5 residues.

9606:BNIP1
gene id: 9606:BNIP1
uniprot id: Q12981
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts with adenovirus E1B 19K protein; plays a role in the suppression of cell apoptosis by the viral protein.
messages: As part of a SNARE complex may be involved in endoplasmic reticulum membranes fusion and be required for the maintenance of endoplasmic reticulum organization (PubMed:15272311). Also plays a role in apoptosis (PubMed:7954800, PubMed:15272311, PubMed:23896122). It is for instance required for endoplasmic reticulum stress-induced apoptosis (PubMed:23896122). As a substrate of RNF185 interacting with SQSTM1, might also be involved in mitochondrial autophagy (Probable).
messages: Belongs to the SEC20 family.
messages: Component of a SNARE complex consisting of STX18, USE1L, BNIP1/SEC20L and SEC22B (PubMed:15272311). Interacts directly with STX18, RINT1/TIP20L and NAPA (PubMed:15272311). Interacts with ZW10 through RINT1 (PubMed:15272311). Interacts with BCL2 (PubMed:7954800). Interacts with RNF186 (PubMed:23896122). Interacts with RNF185 (PubMed:21931693). Interacts with SQSTM1; increased by 'Lys-63'-linked polyubiquitination of BNIP1 (PubMed:21931693).
messages: Endoplasmic reticulum membrane
messages: Isoform 1 is highly expressed in heart, brain, liver skeletal muscle and pancreas. Isoform 3 is moderately expressed in placenta, lung and kidney. Isoform 4 is highly expressed in testis and small intestine.
messages: Mitochondrion membrane
messages: Polyubiquitinated (PubMed:21931693, PubMed:23896122). 'Lys-63'-linked polyubiquitination by RNF185 increases the interaction with the autophagy receptor SQSTM1 (PubMed:21931693). Undergoes 'Lys-29'- and 'Lys-63'-linked polyubiquitination by RNF186 that may regulate BNIP1 localization to the mitochondrion (PubMed:23896122).

9606:GIN1
gene id: 9606:GIN1
uniprot id: Q9NXP7
names: Miscellaneous
names: Sequence Caution
names: Tissue Specificity
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Widely expressed. Also found in tumors originating from parathyroid gland, colon, stomach, bladder, uterus and prostate.
messages: Wrong choice of CDS.

9606:EXTL1
gene id: 9606:EXTL1
uniprot id: Q92935
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the glycosyltransferase 47 family.
messages: Endoplasmic reticulum membrane
messages: Glycosyltransferase required for the biosynthesis of heparan-sulfate (HS) (PubMed:11390981). Transfers N-acetyl-alpha-D-glucosamine to the nascent HS chain (GlcNAcT-II activity) (PubMed:11390981). Appears to lack GlcNAcT I and GlcAT-II activities (PubMed:11390981).

9606:C14orf132
gene id: 9606:C14orf132
uniprot id: Q9NPU4
names: Subcellular Location Annotation
messages: Membrane

9606:RTBDN
gene id: 9606:RTBDN
uniprot id: K7ESG0
uniprot id: Q9BSG5
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the folate receptor family.
messages: Cell membrane
messages: Expressed in peripheral retina (at protein level).
messages: Not N-glycosylated.
messages: Riboflavin-binding protein which might have a role in retinal flavin transport.
messages: interphotoreceptor matrix

9606:TYW5
gene id: 9606:TYW5
uniprot id: A2RUC4
names: Cofactor
names: Function
names: Similarity
names: Subunit
messages: Belongs to the TYW5 family.
messages: Binds 1 Fe(2+) ion per subunit.
messages: Homodimer.
messages: tRNA hydroxylase that acts as a component of the wybutosine biosynthesis pathway. Wybutosine is a hyper modified guanosine with a tricyclic base found at the 3'-position adjacent to the anticodon of eukaryotic phenylalanine tRNA. Catalyzes the hydroxylation of 7-(a-amino-a-carboxypropyl)wyosine (yW-72) into undermodified hydroxywybutosine (OHyW*). OHyW* being further transformed into hydroxywybutosine (OHyW) by LCMT2/TYW4. OHyW is a derivative of wybutosine found in higher eukaryotes.

9606:ARHGAP32
gene id: 9606:ARHGAP32
uniprot id: A7KAX9
uniprot id: Q86T64
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the PX domain-containing GAP family.
messages: Endoplasmic reticulum membrane
messages: Endosome membrane
messages: GTPase-activating protein (GAP) promoting GTP hydrolysis on RHOA, CDC42 and RAC1 small GTPases. May be involved in the differentiation of neuronal cells during the formation of neurite extensions. Involved in NMDA receptor activity-dependent actin reorganization in dendritic spines. May mediate cross-talks between Ras- and Rho-regulated signaling pathways in cell growth regulation. Isoform 2 has higher GAP activity (By similarity).
messages: Golgi apparatus membrane
messages: Interacts with NTRK1 (via cytoplasmic domain); the interaction is independent of the phosphorylation state of NTRK1 (PubMed:12446789). Interacts with SHC3 (via SH2 domain) (PubMed:12446789). Interacts with RASA1 (via SH3 domain); the interaction is necessary for the Ras activation and cell transforming activities of ARHGAP32 (By similarity). Interacts with GAB1 and GAB2 (PubMed:12819203). Interacts with CRK and CRKL (PubMed:12819203, PubMed:12446789). Found in a complex with CRKL and BCAR1; upon EGF stimulation BCAR1 may be replaced by EGFR (PubMed:12446789, PubMed:12819203). Interacts with NCK1 (via SH3 domain); NCK1 recruits phosphorylated BCAR1 to the complex (PubMed:12819203). Isoform 2 interacts with FYN; the interaction appears to be dependent on tyrosine phosphorylation of ARHGAP32 (PubMed:12788081). Interacts with EGFR; the interaction requires EGF stimulation and is increased by SHC3 (PubMed:12446789). Interacts with CDC42; the interaction requires constitutively active CDC42. Interacts with CTNNB1 (PubMed:12531901). Interacts with GRIN2B (PubMed:12857875). Interacts with DLG4 and CDH2 (By similarity). Interacts with GPHN (By similarity).
messages: Isoform 1 and isoform 2 are highly expressed in brain and testis. Isoform 1 is also expressed in other tissues such as lung, liver and spleen.
messages: Isoform 2 is phosphorylated on multiple tyrosine residues by FYN. Phosphorylated tyrosine residues undergo dephosphorylation after stimulation of NMDA receptors (By similarity). Phosphorylated in vitro by CaMK2 in the presence of calmodulin and calcium; which inhibits GAP activity (By similarity).
messages: Membrane
messages: Postsynaptic density
messages: The N-terminal PX domain interacts specifically with phosphatidylinositides.
messages: cell cortex
messages: dendritic spine

9606:LAYN
gene id: 9606:LAYN
uniprot id: Q6UX15
names: Domain
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Interacts with NF2, RDX and TLN1.
messages: Membrane
messages: Receptor for hyaluronate.
messages: The C-terminal domain interacts with the N-terminal domain of RDX.

9606:NDUFB11
gene id: 9606:NDUFB11
uniprot id: Q9NX14
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone.
messages: Belongs to the complex I NDUFB11 subunit family.
messages: Complex I is composed of 45 different subunits (PubMed:12611891, PubMed:27626371). Interacts with BCAP31 (PubMed:31206022).
messages: Mitochondrion inner membrane
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The disease may be caused by variants affecting the gene represented in this entry.
messages: Ubiquitous.

9606:PCSK1N
gene id: 9606:PCSK1N
uniprot id: Q9UHG2
names: Domain
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Endogenous ligand for GPR171. Neuropeptide involved in the regulation of feeding.
messages: Expressed in brain and pancreas.
messages: Interacts via the C-terminal inhibitory domain with PCSK1 66 kDa form.
messages: May function in the control of the neuroendocrine secretory pathway. Proposed be a specific endogenous inhibitor of PCSK1. ProSAAS and Big PEN-LEN, both containing the C-terminal inhibitory domain, but not the further processed peptides reduce PCSK1 activity in the endoplasmic reticulum and Golgi. It reduces the activity of the 84 kDa form but not the autocatalytically derived 66 kDa form of PCSK1. Subsequent processing of proSAAS may eliminate the inhibition. Slows down convertase-mediated processing of proopiomelanocortin and proenkephalin. May control the intracellular timing of PCSK1 rather than its total level of activity (By similarity).
messages: O-glycosylated with a core 1 or possibly core 8 glycan.
messages: ProSAAS(1-180) increases secretion of enzymatically inactive PCSK1.
messages: Proteolytically cleaved in the Golgi.
messages: Secreted
messages: The C-terminal inhibitory domain is involved in inhibition of PCSK1. It corresponds to the probable processing intermediate Big PEN-LEN, binds to PCSK1 in vitro and contains the hexapeptide L-L-R-V-K-R, which, as a synthetic peptide, is sufficient for PCSK1 inhibition (By similarity).
messages: The four C-terminal amino acids of Big LEN are sufficient to bind and activate GPR171.
messages: trans-Golgi network

9606:ZC3HAV1L
gene id: 9606:ZC3HAV1L
uniprot id: Q96H79
names: Caution
messages: Despite its name, it does not contain a canonical C3H1-type zinc-finger.

9606:RENBP
gene id: 9606:RENBP
uniprot id: P51606
names: Activity Regulation
names: Function
names: Similarity
names: Subunit
messages: Belongs to the N-acylglucosamine 2-epimerase family.
messages: Catalyzes the interconversion of N-acetylglucosamine to N-acetylmannosamine (PubMed:9990133, PubMed:10502668, PubMed:12499362). Involved in the N-glycolylneuraminic acid (Neu5Gc) degradation pathway: although human is not able to catalyze formation of Neu5Gc due to the inactive CMAHP enzyme, Neu5Gc is present in food and must be degraded (PubMed:9990133).
messages: Homodimer (PubMed:1723410, PubMed:9990133). Forms a heterodimer with renin and inhibits its activity (PubMed:1723410, PubMed:9990133).
messages: Inhibited by N-ethylmaleimide, 5,5'-dithiobis-2-nitrobenzoate and iodoacetic acid.

9606:USH2A
gene id: 9606:USH2A
uniprot id: O75445
names: Disease Annotation
names: Domain
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Defects in USH2A has been found in a patient with a form of non-syndromic sensorineural hearing loss.
messages: Interacts with collagen IV and fibronectin via its laminin EGF-like domains. Interaction with collagen may be required for stable integration into the basement membrane (PubMed:14676276, PubMed:16114888). Interacts with NINL (PubMed:18826961). Interacts with USH1C (PubMed:16301216). Component of USH2 complex, composed of ADGRV1, PDZD7, USH2A and WHRN. Interacts with ADGRV1/MASS1 (via N-terminal PDZ domain). Interacts (via the cytoplasmic region) with WHRN (PubMed:16434480). Interacts (via the cytoplasmic region) with PDZD7 (PubMed:20440071). Interacts (via the cytoplasmic region) with VEZT and MYO7A (via MyTH4-FERM domains); the interaction associates VEZT with the USH2 complex at the stereocilia base (By similarity).
messages: Involved in hearing and vision as member of the USH2 complex. In the inner ear, required for the maintenance of the hair bundle ankle formation, which connects growing stereocilia in developing cochlear hair cells. In retina photoreceptors, the USH2 complex is required for the maintenance of periciliary membrane complex that seems to play a role in regulating intracellular protein transport.
messages: Present in the basement membrane of many, but not all tissues. Expressed in retina, cochlea, small and large intestine, pancreas, bladder, prostate, esophagus, trachea, thymus, salivary glands, placenta, ovary, fallopian tube, uterus and testis. Absent in many other tissues such as heart, lung, liver, kidney and brain. In the retina, it is present in the basement membranes in the Bruch's layer choroid capillary basement membranes, where it localizes just beneath the retinal pigment epithelial cells (at protein level). Weakly expressed. Isoform 2 is expressed in fetal eye, cochlea and heart, and at very low level in brain, CNS, intestine, skeleton, tongue, kidney and lung. Isoform 2 is not expressed in stomach and liver. In adult tissues, isoform 2 is expressed in neural retina and testis, and at low level in brain, heart, kidney and liver. Isoform 1 displays a similar pattern of expression but is expressed at very low level in fetal cochlea.
messages: Secreted
messages: The PDZ-binding motif probably mediates the association with some of the PDZ domains of USH1C and WHRN.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: stereocilium membrane

9606:ATP8B4
gene id: 9606:ATP8B4
uniprot id: Q6PG43
uniprot id: Q8TF62
names: Function
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IV subfamily.
messages: Cell membrane
messages: Component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and ensures the maintenance of asymmetric distribution of phospholipids. Phospholipid translocation seems also to be implicated in vesicle formation and in uptake of lipid signaling molecules (Probable).
messages: Component of a P4-ATPase flippase complex which consists of a catalytic alpha subunit and an accessory beta subunit (Probable). Interacts with beta subunits TMEM30A and TMEM30B.
messages: Contaminating sequence. Sequence of unknown origin inserted in the coding sequence.
messages: Golgi apparatus
messages: Membrane
messages: Ubiquitously expressed at moderate levels.

9606:ZNF805
gene id: 9606:ZNF805
uniprot id: Q5CZA5
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: Gene prediction based on similarity to orthologs.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:PPP2R2D
gene id: 9606:PPP2R2D
uniprot id: Q66LE6
uniprot id: Q6IN90
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: B regulatory subunit of protein phosphatase 2A (PP2A) that plays a key role in cell cycle by controlling mitosis entry and exit. The activity of PP2A complexes containing PPP2R2D (PR55-delta) fluctuate during the cell cycle: the activity is high in interphase and low in mitosis. During mitosis, activity of PP2A is inhibited via interaction with phosphorylated ENSA and ARPP19 inhibitors. Within the PP2A complexes, the B regulatory subunits modulate substrate selectivity and catalytic activity, and may also direct the localization of the catalytic enzyme to a particular subcellular compartment (By similarity).
messages: Belongs to the phosphatase 2A regulatory subunit B family.
messages: Cytoplasm
messages: PP2A consists of a common heterodimeric core enzyme, composed of a 36 kDa catalytic subunit (subunit C) and a 65 kDa constant regulatory subunit (PR65 or subunit A), that associates with a variety of regulatory subunits. Proteins that associate with the core dimer include three families of regulatory subunits B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56 families), the 48 kDa variable regulatory subunit, viral proteins, and cell signaling molecules. Interacts with ENSA (when phosphorylated at 'Ser-67') and ARPP19 (when phosphorylated at 'Ser-62'), leading to inhibit PP2A activity (By similarity). Interacts with IER5 (PubMed:25816751).

9606:DUOXA2
gene id: 9606:DUOXA2
uniprot id: Q1HG44
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the DUOXA family.
messages: Endoplasmic reticulum membrane
messages: Heterodimer with DUXA2; disulfide-linked (PubMed:25761904). Interacts with CSNK1G2 (PubMed:37099597).
messages: N-glycosylated.
messages: Required for the maturation and the transport from the endoplasmic reticulum to the plasma membrane of functional DUOX2. May play a role in thyroid hormone synthesis.
messages: Specifically expressed in thyroid. Also detected in salivary glands.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:BRD3
gene id: 9606:BRD3
uniprot id: Q15059
names: Disease Annotation
names: Domain
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: A chromosomal aberration involving BRD3 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;9)(q14;q34) with NUTM1 which produces a BRD3-NUTM1 fusion protein.
messages: Chromatin reader that recognizes and binds hyperacetylated chromatin and plays a role in the regulation of transcription, probably by chromatin remodeling and interaction with transcription factors (PubMed:18406326, PubMed:27105114). Regulates transcription by promoting the binding of the transcription factor GATA1 to its targets (By similarity).
messages: Interacts (via bromo domain 1) with GATA1 acetylated at 'Lys-312' and 'Lys-315'. Interacts (via bromo domain 1) with GATA2 acetylated on lysine residues (By similarity). Interacts (via bromo domains) with acetylated lysine residues on the N-terminus of histone H2A, H2B, H3 and H4 (in vitro).
messages: Nucleus
messages: The Bromo domains specifically recognize and bind acetylated histones.
messages: Ubiquitous.

9606:TAF9B
gene id: 9606:TAF9B
uniprot id: Q9HBM6
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the TAF9 family.
messages: Binds TAF5 and TAF6. Component of TFIID and the TATA-binding protein-free TAF complex (TFTC). TFIID is composed of TATA binding protein (TBP) and a number of TBP-associated factors (TAFs). Binds N-terminal domain of p53/TP53 which is essential for transcription.
messages: Essential for cell viability. TAF9 and TAF9B are involved in transcriptional activation as well as repression of distinct but overlapping sets of genes. May have a role in gene regulation associated with apoptosis. TAFs are components of the transcription factor IID (TFIID) complex, the TBP-free TAFII complex (TFTC), the PCAF histone acetylase complex and the STAGA transcription coactivator-HAT complex. TFIID or TFTC are essential for the regulation of RNA polymerase II-mediated transcription.
messages: Nucleus

9606:GOLGA2
gene id: 9606:GOLGA2
uniprot id: Q08379
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the GOLGA2 family.
messages: Cleaved by caspases at the onset of apoptosis.
messages: Endoplasmic reticulum-Golgi intermediate compartment membrane
messages: Extended rod-like protein with long coiled-coil domains.
messages: Homodimer, may assemble into homohexamers (PubMed:26363069). Homotetramer; forms a parallel homotetramer with a flexible rod-like structure that can give rise to I- and Y-shaped conformations (By similarity). Interacts with GORASP1/GRASP65 (PubMed:16489344, PubMed:18045989, PubMed:26363069). The homooligomer forms a complex with GORASP1 with a 1:1 stoichiometry (By similarity). Interacts with RAB1B that has been activated by GTP-binding (PubMed:11306556). Interacts with p115/USO1; interaction with p115/USO1 inhibits interaction with STX5 and/or RAB1B. Interacts with STX5 (By similarity). Interacts with ZFPL1 (PubMed:18323775). Interacts with AKAP450/AKAP9; leading to recruit AKAP450/AKAP9 to the cis-Golgi (PubMed:19242490).
messages: Methylation by PRMT5 is required for Golgi ribbon formation. While dimethylation at Arg-30 and Arg-35 are confirmed in vivo, it is unclear whether Arg-18 is methylated in vivo.
messages: Peripheral membrane component of the cis-Golgi stack that acts as a membrane skeleton that maintains the structure of the Golgi apparatus, and as a vesicle thether that facilitates vesicle fusion to the Golgi membrane (Probable) (PubMed:16489344). Required for normal protein transport from the endoplasmic reticulum to the Golgi apparatus and the cell membrane (By similarity). Together with p115/USO1 and STX5, involved in vesicle tethering and fusion at the cis-Golgi membrane to maintain the stacked and inter-connected structure of the Golgi apparatus. Plays a central role in mitotic Golgi disassembly: phosphorylation at Ser-37 by CDK1 at the onset of mitosis inhibits the interaction with p115/USO1, preventing tethering of COPI vesicles and thereby inhibiting transport through the Golgi apparatus during mitosis (By similarity). Also plays a key role in spindle pole assembly and centrosome organization (PubMed:26165940). Promotes the mitotic spindle pole assembly by activating the spindle assembly factor TPX2 to nucleate microtubules around the Golgi and capture them to couple mitotic membranes to the spindle: upon phosphorylation at the onset of mitosis, GOLGA2 interacts with importin-alpha via the nuclear localization signal region, leading to recruit importin-alpha to the Golgi membranes and liberate the spindle assembly factor TPX2 from importin-alpha. TPX2 then activates AURKA kinase and stimulates local microtubule nucleation. Upon filament assembly, nascent microtubules are further captured by GOLGA2, thus linking Golgi membranes to the spindle (PubMed:19242490, PubMed:26165940). Regulates the meiotic spindle pole assembly, probably via the same mechanism (By similarity). Also regulates the centrosome organization (PubMed:18045989, PubMed:19109421). Also required for the Golgi ribbon formation and glycosylation of membrane and secretory proteins (PubMed:16489344, PubMed:17314401).
messages: Phosphorylated at Ser-37 by CDK1 at the onset of mitosis, inhibiting the interaction with p115/USO1 and triggering Golgi disassembly (PubMed:20421892, PubMed:26165940). Phosphorylated at Ser-37 in prophase as the Golgi complex starts to break down, and remains phosphorylated during further breakdown and partitioning of the Golgi fragments in metaphase and anaphase. In telophase, GM130 is dephosphorylated by PP2A as the Golgi fragments start to reassemble (By similarity).
messages: Sequence differs from that shown after position 826 due to an internal deletion.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The nuclear localization signal (cNLS) mediates interaction with importin-alpha, recruiting importin-alpha to the Golgi membrane and liberating TPX2.
messages: cis-Golgi network membrane
messages: spindle pole

9606:CYP4B1
gene id: 9606:CYP4B1
uniprot id: B4DV41
uniprot id: P13584
uniprot id: Q8IZB0
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the cytochrome P450 family.
messages: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
messages: Detected in the liver and lung (at protein level).
messages: Endoplasmic reticulum membrane
messages: Microsome membrane
messages: P450 can be induced to high levels in liver and other tissues by various foreign compounds, including drugs, pesticides, and carcinogens.

9606:NXN
gene id: 9606:NXN
uniprot id: Q6DKJ4
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Associates with the phosphatase 2A holoenzyme. Interacts with PPP2CA; the interaction is direct. Interacts with DVL1 (via PDZ domain); the interaction is direct and regulated by oxidative stress (By similarity).
messages: Belongs to the nucleoredoxin family.
messages: Functions as a redox-dependent negative regulator of the Wnt signaling pathway, possibly by preventing ubiquitination of DVL3 by the BCR(KLHL12) complex. May also function as a transcriptional regulator act as a regulator of protein phosphatase 2A (PP2A) (By similarity).
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: cytosol

9606:ZNF333
gene id: 9606:ZNF333
uniprot id: Q96JL9
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: Highly expressed in heart.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:MMP19
gene id: 9606:MMP19
uniprot id: Q99542
names: Activity Regulation
names: Cofactor
names: Disease Annotation
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Activated by autolytic cleavage after Lys-97.
messages: Autoantigen anti-MMP19 are frequent in RA patients.
messages: Belongs to the peptidase M10A family.
messages: Binds 1 zinc ion per subunit.
messages: Endopeptidase that degrades various components of the extracellular matrix, such as aggrecan and cartilage oligomeric matrix protein (comp), during development, haemostasis and pathological conditions (arthritic disease). May also play a role in neovascularization or angiogenesis. Hydrolyzes collagen type IV, laminin, nidogen, nascin-C isoform, fibronectin, and type I gelatin.
messages: Expressed in mammary gland, placenta, lung, pancreas, ovary, small intestine, spleen, thymus, prostate, testis colon, heart and blood vessel walls. Not detected in brain and peripheral blood leukocytes. Also expressed in the synovial fluid of normal and rheumatoid patients (PubMed:8920941).
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Strongly inhibited by TIMP-2, TIMP-3 and TIMP-4, while TIMP-1 is less efficient.
messages: The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Tyrosine phosphorylated by PKDCC/VLK.
messages: extracellular matrix

9606:ZBTB37
gene id: 9606:ZBTB37
uniprot id: Q5TC79
names: Function
names: Subcellular Location Annotation
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:FSIP2
gene id: 9606:FSIP2
uniprot id: Q5CZC0
names: Disease Annotation
names: Function
names: Sequence Caution
names: Subunit
names: Tissue Specificity
messages: Aberrant splicing.
messages: May interact with AKAP4.
messages: Plays a role in spermatogenesis.
messages: Predominantly expressed in testis.
messages: The disease may be caused by variants affecting the gene represented in this entry.

9606:EPHX3
gene id: 9606:EPHX3
uniprot id: Q9H6B9
names: Activity Regulation
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the AB hydrolase superfamily. Epoxide hydrolase family.
messages: Catalyzes the hydrolysis of epoxide-containing fatty acids. Active in vitro against epoxyeicosatrienoic acids (EETs) including 8,9-EET, 9,10-EET, 11,12-EET and 14,15-EET and leukotoxin.
messages: Inhibited by 1-(1-acetylpiperidin-4-yl)-3-(4-(trifl uoromethoxy)phenyl)urea (TPAU), 1-cyclohexyl-3-dodecylurea (CDU), 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), 1-((3S, 5S, 7S)-adamantan-1-yl)-3-(5-(2-(2-ethoxyethoxy) ethoxy)pentyl)urea (AEPU) and to a lesser extent by 8-(3-((3S, 5S, 7S)-adamantan-1-yl)ureido) octanoic acid (AUOA).
messages: Microsome membrane

9606:TM7SF2
gene id: 9606:TM7SF2
uniprot id: O76062
names: Function
names: Induction
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the ERG4/ERG24 family.
messages: By sterol starvation.
messages: Catalyzes the reduction of the C14-unsaturated bond of lanosterol, as part of the metabolic pathway leading to cholesterol biosynthesis.
messages: Endoplasmic reticulum membrane
messages: Expressed in adult heart, brain, pancreas, lung, liver, skeletal muscle, kidney, ovary, prostate, testis and adrenal gland, but not detected in placenta, spleen, thymus, small intestine, colon (mucosal lining), or peripheral blood leukocytes.
messages: Microsome membrane
messages: Sequencing errors.

9606:RLIM
gene id: 9606:RLIM
uniprot id: Q9NVW2
names: Disease Annotation
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acts as a positive coregulator of ESR1-mediated transcription in breast cancer cells.
messages: Belongs to the RNF12 family.
messages: E3 ubiquitin-protein ligase. Acts as a negative coregulator for LIM homeodomain transcription factors by mediating the ubiquitination and subsequent degradation of LIM cofactors LDB1 and LDB2 and by mediating the recruitment the SIN3a/histone deacetylase corepressor complex. Ubiquitination and degradation of LIM cofactors LDB1 and LDB2 allows DNA-bound LIM homeodomain transcription factors to interact with other protein partners such as RLIM. Plays a role in telomere length-mediated growth suppression by mediating the ubiquitination and degradation of TERF1. By targeting ZFP42 for degradation, acts as an activator of random inactivation of X chromosome in the embryo, a stochastic process in which one X chromosome is inactivated to minimize sex-related dosage differences of X-encoded genes in somatic cells of female placental mammals.
messages: Expressed in many tissues.
messages: Interacts with LIM/homeobox factors such as LHX3. Interacts with LDB1, LDB2 and SIN3A (By similarity). Interacts with LIMK1 (By similarity). Interacts (via N-terminus) with TERF1. Interacts (via C-terminus) with ESR1.
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:RASGEF1C
gene id: 9606:RASGEF1C
uniprot id: Q8N431
names: Function
messages: Guanine nucleotide exchange factor (GEF).

9606:F7
gene id: 9606:F7
uniprot id: B4DPM2
uniprot id: F5H8B0
uniprot id: P08709
names: Caution
names: Disease Annotation
names: Function
names: PTM
names: Pharmaceutical
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Available under the names Niastase or Novoseven (Novo Nordisk). Used for the treatment of bleeding episodes in hemophilia A or B patients with antibodies to coagulation factors VIII or IX.
messages: Belongs to the peptidase S1 family.
messages: Can be either O-glucosylated or O-xylosylated at Ser-112 by POGLUT1 in vitro.
messages: Heterodimer of a light chain and a heavy chain linked by a disulfide bond.
messages: Initiates the extrinsic pathway of blood coagulation. Serine protease that circulates in the blood in a zymogen form. Factor VII is converted to factor VIIa by factor Xa, factor XIIa, factor IXa, or thrombin by minor proteolysis. In the presence of tissue factor and calcium ions, factor VIIa then converts factor X to factor Xa by limited proteolysis. Factor VIIa will also convert factor IX to factor IXa in the presence of tissue factor and calcium.
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: O- and N-glycosylated. N-glycosylation at Asn-205 occurs cotranslationally and is mediated by STT3A-containing complexes, while glycosylation at Asn-382 is post-translational and is mediated STT3B-containing complexes before folding. O-fucosylated by POFUT1 on a conserved serine or threonine residue found in the consensus sequence C2-X(4,5)-[S/T]-C3 of EGF domains, where C2 and C3 are the second and third conserved cysteines.
messages: Plasma.
messages: Secreted
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains.
messages: The vitamin K-dependent, enzymatic carboxylation of some glutamate residues allows the modified protein to bind calcium.

9606:CD74
gene id: 9606:CD74
uniprot id: P04233
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: A chromosomal aberration involving CD74 is found in a non-small cell lung tumor. Results in the formation of a CD74-ROS1 chimeric protein.
messages: Antiviral activity requires delivery of the thyroglobulin domain to the endosomal membrane.
messages: Binds to the peptide-binding site of MHC class II alpha/beta heterodimers forming an alpha-beta-CLIP complex, thereby preventing the loading of antigenic peptides to the MHC class II complex until its release by HLA-DM in the endosome.
messages: Cell membrane
messages: Detected in urine (at protein level).
messages: Endoplasmic reticulum membrane
messages: Endosome
messages: Homotrimer. In the endoplasmic reticulum (ER) it forms a heterononameric MHC II-Ii complex: 3 MHC class II molecules (heterodimers of an alpha and a beta subunit) bind to the CD74 homotrimer (also known as invariant chain or HLA class II histocompatibility antigen gamma chain). In the endosomal/lysosomal system, the CD74 component undergoes sequential degradation by various proteases, including CTSS and CTSL, leaving a small fragment termed CLIP (class-II-associated invariant chain peptide) attached to the MHC class II molecule (alpha-beta-CLIP complex). This processed complex interacts with HLA_DM and HLA_DO heterodimers in order to release CLIP and facilitate the binding of antigenic peptides to the MHC class II molecules. Interacts with CD44; this complex is essential for the MIF-induced signaling cascade that results in B cell survival.
messages: In B cells, represents 10% of total CD74 expression.
messages: In B cells, represents 70% of total CD74 expression.
messages: Interacts with the mature form of CTSL; the complex survive in neutral pH environment.
messages: Late endosome
messages: Lysosome
messages: O-glycosylated with core 1 or possibly core 8 glycans (PubMed:22171320, PubMed:23234360). Contains chondroitin sulfate (PubMed:25326458).
messages: Plays a critical role in MHC class II antigen processing by stabilizing peptide-free class II alpha/beta heterodimers in a complex soon after their synthesis and directing transport of the complex from the endoplasmic reticulum to the endosomal/lysosomal system where the antigen processing and binding of antigenic peptides to MHC class II takes place. Serves as cell surface receptor for the cytokine MIF.
messages: Secreted
messages: Stabilizes the conformation of mature CTSL by binding to its active site and serving as a chaperone to help maintain a pool of mature enzyme in endocytic compartments and extracellular space of antigen-presenting cells (APCs). Has antiviral activity by stymieing the endosomal entry of Ebola virus and coronaviruses, including SARS-CoV-2 (PubMed:32855215). Disrupts cathepsin-mediated Ebola virus glycoprotein processing, which prevents viral fusion and entry. This antiviral activity is specific to p41 isoform (PubMed:32855215).
messages: trans-Golgi network

9606:RAB11FIP4
gene id: 9606:RAB11FIP4
uniprot id: Q86YS3
names: Domain
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts with human cytomegalovirus/HHV-5 protein gM/UL100.
messages: Acts as a regulator of endocytic traffic by participating in membrane delivery. Required for the abcission step in cytokinesis, possibly by acting as an 'address tag' delivering recycling endosome membranes to the cleavage furrow during late cytokinesis. In case of infection by HCMV (human cytomegalovirus), may participate in egress of the virus out of nucleus; this function is independent of ARF6.
messages: Cleavage furrow
messages: Cytoplasmic vesicle
messages: Endosome
messages: Homodimer. Forms a complex with Rab11 (RAB11A or RAB11B) and ARF6. Interacts with RAB11A; the interaction is direct. Forms a heterooligomeric complex with RAB11FIP2, RAB11FIP3 and RAB11FIP5. Interacts with ECPAS.
messages: Midbody
messages: Present at high level in testis (at protein level). Weakly expressed in other tissues.
messages: Recycling endosome membrane
messages: The RBD-FIP domain mediates the interaction with Rab11 (RAB11A or RAB11B).
messages: centrosome
messages: spindle

9606:CBLB
gene id: 9606:CBLB
uniprot id: B3KSS7
uniprot id: B4DYP3
uniprot id: B7ZAG1
uniprot id: Q13191
names: Domain
names: Function
names: Induction
names: Miscellaneous
names: PTM
names: Sequence Caution
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Auto-ubiquitinated upon EGF-mediated cell activation or upon T-cell costimulation by CD28; which promotes proteasomal degradation.
messages: By serum starvation.
messages: Cytoplasm
messages: E3 ubiquitin-protein ligase which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and transfers it to substrates, generally promoting their degradation by the proteasome.
messages: E3 ubiquitin-protein ligase which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes, and transfers it to substrates, generally promoting their degradation by the proteasome. Negatively regulates TCR (T-cell receptor), BCR (B-cell receptor) and FCER1 (high affinity immunoglobulin epsilon receptor) signal transduction pathways. In naive T-cells, inhibits VAV1 activation upon TCR engagement and imposes a requirement for CD28 costimulation for proliferation and IL-2 production. Also acts by promoting PIK3R1/p85 ubiquitination, which impairs its recruitment to the TCR and subsequent activation. In activated T-cells, inhibits PLCG1 activation and calcium mobilization upon restimulation and promotes anergy. In B-cells, acts by ubiquitinating SYK and promoting its proteasomal degradation. Slightly promotes SRC ubiquitination. May be involved in EGFR ubiquitination and internalization. May be functionally coupled with the E2 ubiquitin-protein ligase UB2D3. In association with CBL, required for proper feedback inhibition of ciliary platelet-derived growth factor receptor-alpha (PDGFRA) signaling pathway via ubiquitination and internalization of PDGFRA (By similarity).
messages: Expressed in placenta, heart, lung, kidney, spleen, ovary and testis, as well as fetal brain and liver and hematopoietic cell lines, but not in adult brain, liver, pancreas, salivary gland, or skeletal muscle. Present in lymphocytes (at protein level).
messages: Interacts with SH3 domain-containing proteins LCK, CRK and SORBS1. Interacts with LCP2 and ZAP70. Interacts with CBL (PubMed:29237719). Interacts with SH3 domain-containing proteins VAV1, FYN, FGR, PLCG1, GRB2, CRKL, PIK3R1 and SH3KBP1/CIN85. Identified in heterotrimeric complexes with SH3KBP1/CIN85, CD2AP and ARHGEF7, where one CBLB peptide binds two copies of the other protein. Interacts with poly-ubiquitinated proteins. Dimerization is required for the binding of poly-ubiquitin, but not for the binding of mono-ubiquitin. Interacts with EGFR (phosphorylated). Interacts with IFT20 (PubMed:29237719).
messages: Phosphorylated on tyrosine and serine residues upon TCR or BCR activation, and upon various types of cell stimulation.
messages: Probable cloning artifact.
messages: The N-terminus is composed of the phosphotyrosine binding (PTB) domain, a short linker region and the RING-type zinc finger. The PTB domain, which is also called TKB (tyrosine kinase binding) domain, is composed of three different subdomains: a four-helix bundle (4H), a calcium-binding EF hand and a divergent SH2 domain.
messages: The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme.
messages: The UBA domain interacts with poly-ubiquitinated proteins.
messages: This protein has one functional calcium-binding site.

9606:CORO1A
gene id: 9606:CORO1A
uniprot id: P31146
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the WD repeat coronin family.
messages: Binds actin.
messages: Expressed in brain, thymus, spleen, bone marrow and lymph node. Low in lung and gut.
messages: May be a crucial component of the cytoskeleton of highly motile cells, functioning both in the invagination of large pieces of plasma membrane, as well as in forming protrusions of the plasma membrane involved in cell locomotion. In mycobacteria-infected cells, its retention on the phagosomal membrane prevents fusion between phagosomes and lysosomes.
messages: Polyubiquitinated by RNF128 with 'Lys-48'-linked chains, leading to proteasomal degradation.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: cell cortex
messages: cytoskeleton
messages: phagosome membrane
messages: phosphorylation at Thr-412 by PKC strongly down-regulates the association with actin.

9606:FGF5
gene id: 9606:FGF5
uniprot id: A0A7U3L5M4
uniprot id: P12034
uniprot id: Q8NBG6
names: Developmental Stage
names: Disease Annotation
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the heparin-binding growth factors family.
messages: Can transform NIH 3T3 cells.
messages: Expressed in neonatal brain.
messages: Interacts with FGFR1 and FGFR2. Affinity between fibroblast growth factors (FGFs) and their receptors is increased by heparan sulfate glycosaminoglycans that function as coreceptors.
messages: Plays an important role in the regulation of cell proliferation and cell differentiation. Required for normal regulation of the hair growth cycle. Functions as an inhibitor of hair elongation by promoting progression from anagen, the growth phase of the hair follicle, into catagen the apoptosis-induced regression phase (By similarity).
messages: Secreted
messages: Seems to have an antagonistic effect compared to that of the isoform Long.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:ACAD9
gene id: 9606:ACAD9
uniprot id: Q9H845
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: As part of the MCIA complex, primarily participates in the assembly of the mitochondrial complex I and therefore plays a role in oxidative phosphorylation (PubMed:20816094, PubMed:24158852, PubMed:32320651). This moonlighting protein has also a dehydrogenase activity toward a broad range of substrates with greater specificity for long-chain unsaturated acyl-CoAs (PubMed:12359260, PubMed:16020546, PubMed:21237683, PubMed:24158852). However, in vivo, it does not seem to play a primary role in fatty acid oxidation (PubMed:20816094, PubMed:24158852). In addition, the function in complex I assembly is independent of the dehydrogenase activity of the protein (PubMed:24158852).
messages: Belongs to the acyl-CoA dehydrogenase family.
messages: Homodimer (PubMed:16020546). Interacts with NDUFAF1 and ECSIT (PubMed:20816094). Part of the mitochondrial complex I assembly/MCIA complex that comprises at least the core subunits TMEM126B, NDUFAF1, ECSIT and ACAD9 and complement subunits such as COA1 and TMEM186 (PubMed:32320651). Interacts with TMEM70 and TMEM242 (PubMed:33753518).
messages: Mitochondrion inner membrane
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitously expressed in most normal human tissues and cancer cell lines with high level of expression in heart, skeletal muscles, brain, kidney and liver (PubMed:12359260). In the cerebellum uniquely expressed in the granular layer (at protein level) (PubMed:21237683).

9606:CRYGC
gene id: 9606:CRYGC
uniprot id: A0A0X8GLL6
uniprot id: P07315
names: Disease Annotation
names: Domain
names: Function
names: Similarity
names: Subunit
messages: Belongs to the beta/gamma-crystallin family.
messages: Crystallins are the dominant structural components of the vertebrate eye lens.
messages: Has a two-domain beta-structure, folded into four very similar Greek key motifs.
messages: Monomer.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:AMBN
gene id: 9606:AMBN
uniprot id: Q546D7
uniprot id: Q9NP70
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Ameloblast-specific. Located at the Tomes processes of secretory ameloblasts and in the sheath space between rod-interrod enamel.
messages: Belongs to the ameloblastin family.
messages: Involved in the mineralization and structural organization of enamel.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: extracellular matrix

9606:E2F8
gene id: 9606:E2F8
uniprot id: A0AVK6
names: Domain
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Atypical E2F transcription factor that participates in various processes such as angiogenesis and polyploidization of specialized cells. Mainly acts as a transcription repressor that binds DNA independently of DP proteins and specifically recognizes the E2 recognition site 5'-TTTC[CG]CGC-3'. Directly represses transcription of classical E2F transcription factors such as E2F1: component of a feedback loop in S phase by repressing the expression of E2F1, thereby preventing p53/TP53-dependent apoptosis. Plays a key role in polyploidization of cells in placenta and liver by regulating the endocycle, probably by repressing genes promoting cytokinesis and antagonizing action of classical E2F proteins (E2F1, E2F2 and/or E2F3). Required for placental development by promoting polyploidization of trophoblast giant cells. Acts as a promoter of sprouting angiogenesis, possibly by acting as a transcription activator: associates with HIF1A, recognizes and binds the VEGFA promoter, which is different from canonical E2 recognition site, and activates expression of the VEGFA gene.
messages: Belongs to the E2F/DP family.
messages: Following DNA damage (PubMed:18202719). Up-regulation in response to DNA damage is not confirmed by PubMed:22802528.
messages: Homodimer and heterodimer: mainly forms homodimers and, to a lesser extent, heterodimers with E2F8. Dimerization is important for DNA-binding. Interacts with HIF1A.
messages: In contrast to classical members of the E2F transcription factor, atypical members contain 2 DNA-binding domains and regulate transcription in a DP-independent manner. Both DNA-binding domains are required for DNA-binding and are proposed to form an intramolecular structure that is similar to the winged helix structure of the E2F-DP heterodimer (By similarity).
messages: Nucleus

9606:ZBTB33
gene id: 9606:ZBTB33
uniprot id: Q86T24
names: Function
names: Induction
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cytoplasm
messages: Expressed in vascular endothelium.
messages: Induced in vascular endothelium by wounding. This effect is potentiated by prior laminar shear stress, which enhances wound closure.
messages: Nucleus
messages: Self-associates. Interacts with CTNND2 (By similarity). Interacts with CTNND1, and this interaction inhibits binding to both methylated and non-methylated DNA. Interacts with NCOR1. Interacts with KPNA2/RCH1, which may mediate nuclear import of this protein. Interacts with CBFA2T3.
messages: Transcriptional regulator with bimodal DNA-binding specificity. Binds to methylated CpG dinucleotides in the consensus sequence 5'-CGCG-3' and also binds to the non-methylated consensus sequence 5'-CTGCNA-3' also known as the consensus kaiso binding site (KBS). Recruits the N-CoR repressor complex to promote histone deacetylation and the formation of repressive chromatin structures in target gene promoters. May contribute to the repression of target genes of the Wnt signaling pathway. May also activate transcription of a subset of target genes by the recruitment of CTNND2. Represses expression of MMP7 in conjunction with transcriptional corepressors CBFA2T3, CBFA2T2 and RUNX1T1 (PubMed:23251453).

9606:METTL13
gene id: 9606:METTL13
uniprot id: Q8N6R0
names: Activity Regulation
names: Disease Annotation
names: Function
names: Miscellaneous
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the methyltransferase superfamily.
messages: Cytoplasm
messages: Dual methyltransferase that catalyzes methylation of elongation factor 1-alpha (EEF1A1 and EEF1A2) at two different positions, and is therefore involved in the regulation of mRNA translation (PubMed:30612740, PubMed:30143613). Via its C-terminus, methylates EEF1A1 and EEF1A2 at the N-terminal residue 'Gly-2' (PubMed:30143613). Via its N-terminus dimethylates EEF1A1 and EEF1A2 at residue 'Lys-55' (PubMed:30612740, PubMed:30143613). Has no activity towards core histones H2A, H2B, H3 and H4 (PubMed:30612740). Negatively regulates cell proliferation at G1/S transition via transcriptional suppression of cell cycle regulatory genes such as CDK4 and CDK6 (PubMed:26763933).
messages: Forms a tripartite complex containing GAB1, METTL13 and SPRY2 (PubMed:29408807). Within the complex interacts with GAB1 and SPRY2 (PubMed:29408807).
messages: Genetic variants in METTL13 define the deafness modifier locus DFNB26M [MIM:605429]. The DFNB26M phenotype is characterized by normal hearing despite the presence of homozygosity for a causative deafness mutation in the GAB1 gene.
messages: METTL13 unregulation may be involved in tumorigenesis. High METTL13 expression has been observed in pancreatic and lung cancer tissues, correlates with overexpression of dimethylated elongation factor 1-alpha and is associated with poor clinical outcome. The disease mechanism involves dysregulation of mRNA translation and enhanced protein synthesis to sustain growth of malignant cells.
messages: Mitochondrion
messages: Nucleus
messages: Present in the circulating blood plasma of cancer patients, particularly in ovarian and non-small cell lung cancer patients, may potentially be used as a biomarker (PubMed:27659353). Acts as a tumor suppressor in bladder cancer suppressing cell migration and invasion (PubMed:26763933). Reduced expression is seen in later stages of the disease (PubMed:26763933).
messages: Protein N-terminal methyltransferase activity is inhibited by GTP and GDP.

9606:SH2B3
gene id: 9606:SH2B3
uniprot id: B7Z7K6
uniprot id: F5GYM4
uniprot id: Q59H48
uniprot id: Q9UQQ2
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Belongs to the SH2B adapter family.
messages: Binds to the tyrosine-phosphorylated TCR zeta chain via its SH2 domain.
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry.
messages: Disease susceptibility may be associated with variants affecting the gene represented in this entry.
messages: Links T-cell receptor activation signal to phospholipase C-gamma-1, GRB2 and phosphatidylinositol 3-kinase.
messages: Preferentially expressed by lymphoid cell lines.
messages: Tyrosine phosphorylated by LCK.

9606:TBC1D3L
gene id: 9606:TBC1D3L
uniprot id: B9A6J9
names: Function
names: Miscellaneous
names: PTM
names: Subcellular Location Annotation
messages: Acts as a GTPase activating protein for RAB5. Does not act on RAB4 or RAB11 (By similarity).
messages: Cell membrane
messages: Palmitoylation is required for membrane localization and protects TBC1D3 from ubiquitination.
messages: TBC1D3 is encoded by a collection of very similar paralogs with multiple copies of each paralog, some human genomes encoding well over 50 copies depending on ethnic origin of the donor.
messages: Ubiquitinated by a CUL7-based E3 ligase, which leads to proteasomal degradation.

9606:CERS1
gene id: 9606:CERS1
uniprot id: B4DE47
uniprot id: P27544
uniprot id: Q5XG75
names: Activity Regulation
names: Disease Annotation
names: Function
names: Miscellaneous
names: PTM
names: Subcellular Location Annotation
messages: Acetylated. Deacetylation by SIRT3 increases enzyme activity and promotes mitochondrial ceramide accumulation.
messages: Ceramide synthase that catalyzes the transfer of the acyl chain from acyl-CoA to a sphingoid base, with high selectivity toward stearoyl-CoA (octadecanoyl-CoA; C18:0-CoA) (PubMed:17977534, PubMed:23530041, PubMed:26887952, PubMed:31916624). N-acylates sphinganine and sphingosine bases to form dihydroceramides and ceramides in de novo synthesis and salvage pathways, respectively (PubMed:17977534, PubMed:23530041, PubMed:26887952, PubMed:31916624, PubMed:24782409). Plays a predominant role in skeletal muscle in regulating C18 ceramide and dihydroceramide levels with an impact on whole-body glucose metabolism and insulin sensitivity. Protects from diet-induced obesity by suppressing the uptake of glucose in multiple organs in a FGF21-dependent way (By similarity). Generates C18 ceramides in the brain, playing a critical role in cerebellar development and Purkinje cell function (By similarity). In response to cellular stress mediates mitophagy, a known defense mechanism against cell transformation and aging. Upon mitochondria fission, generates C18 ceramides that anchor lipidated MAP1LC3B/LC3B-II autophagolysosomes to outer mitochondrial membranes to eliminate damaged mitochondria (PubMed:22922758).
messages: Endoplasmic reticulum membrane
messages: Inhibited by fumonisin B1.
messages: Membrane
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: This protein is produced by a bicistronic gene which also produces the GDF1 protein from a non-overlapping reading frame.

9606:CCDC89
gene id: 9606:CCDC89
uniprot id: Q8N998
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the CCDC89 family.
messages: Cytoplasm
messages: Interacts with HEY1.
messages: Nucleus

9606:GLT1D1
gene id: 9606:GLT1D1
uniprot id: Q96MS3
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the glycosyltransferase group 1 family. Glycosyltransferase 4 subfamily.
messages: Secreted

9606:C16orf86
gene id: 9606:C16orf86
uniprot id: Q6ZW13
names: Sequence Caution
messages: Intron retention.

9606:MSL2
gene id: 9606:MSL2
uniprot id: Q9HCI7
names: Function
names: Similarity
names: Subunit
messages: Belongs to the MSL2 family.
messages: Component of a multisubunit histone acetyltransferase complex (MSL) at least composed of the KAT8/MOF/MYST1, MSL1/hampin, MSL2 and MSL3 (PubMed:16543150, PubMed:23084835). Forms a MSL heterotetrameric core with MSL1 (PubMed:16543150).
messages: Component of histone acetyltransferase complex responsible for the majority of histone H4 acetylation at lysine 16 which is implicated in the formation of higher-order chromatin structure. Acts as an E3 ubiquitin ligase that promotes monoubiquitination of histone H2B at 'Lys-35' (H2BK34Ub), but not that of H2A. This activity is greatly enhanced by heterodimerization with MSL1. H2B ubiquitination in turn stimulates histone H3 methylation at 'Lys-4' (H3K4me) and 'Lys-79' (H3K79me) and leads to gene activation, including that of HOXA9 and MEIS1.

9606:INTS10
gene id: 9606:INTS10
uniprot id: Q9NVR2
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the Integrator subunit 10 family.
messages: Belongs to the multiprotein complex Integrator, at least composed of INTS1, INTS2, INTS3, INTS4, INTS5, INTS6, INTS7, INTS8, INTS9/RC74, INTS10, INTS11/CPSF3L and INTS12. Interacts with POLR2A.
messages: Component of the Integrator (INT) complex, a complex involved in the small nuclear RNAs (snRNA) U1 and U2 transcription and in their 3'-box-dependent processing. The Integrator complex is associated with the C-terminal domain (CTD) of RNA polymerase II largest subunit (POLR2A) and is recruited to the U1 and U2 snRNAs genes (Probable). May be not involved in the recruitment of cytoplasmic dynein to the nuclear envelope by different components of the INT complex (PubMed:23904267).
messages: Nucleus

9606:CALHM5
gene id: 9606:CALHM5
uniprot id: Q8N5C1
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the CALHM family.
messages: Membrane
messages: Pore-forming subunit of a voltage-gated ion channel.

9606:VCX
gene id: 9606:VCX
uniprot id: Q9H320
names: Function
names: Similarity
names: Tissue Specificity
messages: Belongs to the VCX/VCY family.
messages: Expressed exclusively in testis.
messages: May mediate a process in spermatogenesis or may play a role in sex ratio distortion.

9606:LCTL
gene id: 9606:LCTL
uniprot id: Q6UWM7
names: Caution
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Although it belongs to the glycosyl hydrolase 1 family, Asp-201 is present instead of the conserved Glu which is an active site residue. It is therefore expected that this protein lacks glycosidase activity.
messages: Belongs to the glycosyl hydrolase 1 family. Klotho subfamily.
messages: Endoplasmic reticulum membrane
messages: May form dimers.
messages: Plays a role in formation of the lens suture in the eye, which is important for normal optical properties of the lens.

9606:BCKDHB
gene id: 9606:BCKDHB
uniprot id: P21953
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Heterotetramer of 2 alpha/BCKDHA and 2 beta chains/BCKDHB that forms the branched-chain alpha-keto acid decarboxylase (E1) component of the BCKD complex (PubMed:9582350, PubMed:10745006). The branched-chain alpha-ketoacid dehydrogenase is a large complex composed of three major building blocks E1, E2 and E3. It is organized around E2, a 24-meric cubic core composed of DBT, to which are associated 6 to 12 copies of E1, and approximately 6 copies of the dehydrogenase E3, a DLD dimer (PubMed:10745006).
messages: Mitochondrion matrix
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Together with BCKDHA forms the heterotetrameric E1 subunit of the mitochondrial branched-chain alpha-ketoacid dehydrogenase (BCKD) complex. The BCKD complex catalyzes the multi-step oxidative decarboxylation of alpha-ketoacids derived from the branched-chain amino-acids valine, leucine and isoleucine producing CO2 and acyl-CoA which is subsequently utilized to produce energy. The E1 subunit catalyzes the first step with the decarboxylation of the alpha-ketoacid forming an enzyme-product intermediate. A reductive acylation mediated by the lipoylamide cofactor of E2 extracts the acyl group from the E1 active site for the next step of the reaction.

9606:SLC7A1
gene id: 9606:SLC7A1
uniprot id: P30825
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the amino acid-polyamine-organocation (APC) superfamily. Cationic amino acid transporter (CAT) (TC 2.A.3.3) family.
messages: Cell membrane
messages: High-affinity, low capacity permease involved in the transport of the cationic amino acids (arginine, lysine and ornithine) in non-hepatic tissues.
messages: Interacts with TM4SF5; the interaction is negatively regulated by arginine (PubMed:30956113). Forms tissue-specific complexes with ASL, ASS1 and nitric oxide synthase NOS1 or NOS3; the complex regulates cell-autonomous L-arginine synthesis and citrulline recycling while channeling extracellular L-arginine to nitric oxide synthesis pathway (By similarity).
messages: Ubiquitous.

9606:DHX33
gene id: 9606:DHX33
uniprot id: Q9H6R0
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the DEAD box helicase family. DEAH subfamily.
messages: Cytoplasm
messages: Implicated in nucleolar organization, ribosome biogenesis, protein synthesis and cytoplasmic dsRNA sensing (By similarity) (PubMed:21930779, PubMed:23871209, PubMed:26100019). Stimulates RNA polymerase I transcription of the 47S precursor rRNA. Associates with ribosomal DNA (rDNA) loci where it is involved in POLR1A recruitment (PubMed:21930779). In the cytoplasm, promotes elongation-competent 80S ribosome assembly at the late stage of mRNA translation initiation (PubMed:26100019). Senses cytosolic dsRNA mediating NLRP3 inflammasome formation in macrophages and type I interferon production in myeloid dendritic cells (PubMed:23871209). Required for NLRP3 activation induced by viral dsRNA and bacterial RNA (PubMed:23871209). In dendritic cells, required for induction of type I interferon production induced by cytoplasmic dsRNA via the activation of MAPK and NF-kappa-B signaling pathways (By similarity).
messages: Inflammasome
messages: Interacts with UBTF (PubMed:21930779). Interacts with DDX3X, EIF3G and EIF3H; the interaction is independent of RNA (PubMed:26100019). Interacts (via HA2 region and Helicase C-terminal domain) with the components of the large ribosomal subunit RPL3, RPL7, RPL26 and RPL27 (PubMed:26100019). Interacts (via DEAH box) with NLRP3 (via NACHT domain) (PubMed:23871209). Binds to mRNA (PubMed:26100019). Binds to double-stranded RNA (via the helicase C-terminal domain) (PubMed:23871209). Interacts (via the helicase C-terminal domain) with MAVS (By similarity).
messages: Nucleus
messages: Ubiquitinated, leading to its degradation by the proteasome. Deubiquitinated by USP36.
messages: nucleolus
messages: nucleoplasm

9606:STX8
gene id: 9606:STX8
uniprot id: Q9UNK0
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the syntaxin family.
messages: Forms a SNARE complex with STX7, VTI1B and VAMP8 which functions in the homotypic fusion of late endosomes. Part of the SNARE core complex containing STX7, VAMP8 and VTI1B. Interacts with VAMP8 (By similarity). Interacts with HECTD3 (By similarity). Interacts with TPC1 (By similarity).
messages: Highly expressed in heart. Also found in brain, kidney, liver, lung, placenta, skeletal muscle, spleen and pancreas.
messages: Membrane
messages: Ubiquitinated by HECTD3.
messages: Vesicle trafficking protein that functions in the early secretory pathway, possibly by mediating retrograde transport from cis-Golgi membranes to the ER.

9606:RBM24
gene id: 9606:RBM24
uniprot id: Q9BX46
names: Domain
names: Function
names: Induction
names: Sequence Caution
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts with HCV Serine protease/helicase NS3.
messages: (Microbial infection) Interacts with HCV mature core protein; this interaction, which enhances the interaction of Core with 5'-UTR may favor viral replication over translation.
messages: (Microbial infection) Promotes hepatitis C virus (HCV) replication over translation through the inhibition of viral protein expression. Decreases viral translation by linking viral 5'- and 3'-UTRs, blocking 80S ribosome assembly on the viral IRES and enhancing the interaction of the mature core protein and 5'-UTR.
messages: By p53/TP53 following DNA damage (at protein level) (PubMed:24356969). Up-regulated during embryonic stem cell (ESC) differentiation into cardiomyocytes (PubMed:19658189, PubMed:26990106).
messages: Cytoplasm
messages: Expressed in fetal and adult heart and skeletal muscles (PubMed:22345307, PubMed:25313962).
messages: Interacts with EIF4E; this interaction prevents EIF4E from binding to p53/TP53 mRNA and inhibits the assembly of translation initiation complex (PubMed:29358667).
messages: Multifunctional RNA-binding protein involved in the regulation of pre-mRNA splicing, mRNA stability and mRNA translation important for cell fate decision and differentiation (PubMed:20977548, PubMed:24375645, PubMed:29358667, PubMed:29104163). Plays a major role in pre-mRNA alternative splicing regulation (PubMed:26990106, PubMed:29104163). Mediates preferentially muscle-specific exon inclusion in numerous mRNAs important for striated cardiac and skeletal muscle cell differentiation (PubMed:29104163). Binds to intronic splicing enhancer (ISE) composed of stretches of GU-rich motifs localized in flanking intron of exon that will be included by alternative splicing (By similarity). Involved in embryonic stem cell (ESC) transition to cardiac cell differentiation by promoting pre-mRNA alternative splicing events of several pluripotency and/or differentiation genes (PubMed:26990106). Plays a role in the regulation of mRNA stability (PubMed:20977548, PubMed:24356969, PubMed:24375645, PubMed:29104163). Binds to 3'-untranslated region (UTR) AU-rich elements in target transcripts, such as CDKN1A and MYOG, leading to maintain their stabilities (PubMed:20977548, PubMed:24356969). Involved in myogenic differentiation by regulating MYOG levels (PubMed:20977548). Binds to multiple regions in the mRNA 3'-UTR of TP63 isoform 2, hence inducing its destabilization (PubMed:24375645). Promotes also the destabilization of the CHRM2 mRNA via its binding to a region in the coding sequence (PubMed:29104163). Plays a role in the regulation of mRNA translation (PubMed:29358667). Mediates repression of p53/TP53 mRNA translation through its binding to U-rich element in the 3'-UTR, hence preventing EIF4E from binding to p53/TP53 mRNA and translation initiation (PubMed:29358667). Binds to a huge amount of mRNAs (PubMed:29104163). Required for embryonic heart development, sarcomer and M-band formation in striated muscles (By similarity). Together with RBM20, promotes the expression of short isofo…
messages: Nucleus
messages: The RRM domain is necessary for mRNA stability and mRNA translation regulation (PubMed:24356969, PubMed:29358667).
messages: Unlikely isoform. Aberrant splice sites.

9606:NDUFA13
gene id: 9606:NDUFA13
uniprot id: Q9P0J0
names: Developmental Stage
names: Disease Annotation
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts with HHV-8 IRF1, in the nucleus, with HPV-16 E6 and SV40 LT (PubMed:12163600).
messages: Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis (PubMed:27626371). Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone (PubMed:27626371). Involved in the interferon/all-trans-retinoic acid (IFN/RA) induced cell death. This apoptotic activity is inhibited by interaction with viral IRF1. Prevents the transactivation of STAT3 target genes. May play a role in CARD15-mediated innate mucosal responses and serve to regulate intestinal epithelial cell responses to microbes (PubMed:15753091).
messages: Belongs to the complex I NDUFA13 subunit family.
messages: By IFNB1/IFN-beta combined with all-trans-retinoic acid (ATRA).
messages: Complex I is composed of 45 different subunits (PubMed:27626371). Interacts with CARD15, but not with CARD4 (PubMed:12611891, PubMed:15753091). Interacts with STAT3, but not with STAT1, STAT2 and STAT5A (PubMed:12628925, PubMed:12867595). Interacts with OLFM4 (PubMed:15059901).
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry.
messages: Expressed in numerous fetal tissues.
messages: Mitochondrion inner membrane
messages: Nucleus
messages: The disease may be caused by variants affecting the gene represented in this entry.
messages: Widely expressed, with highest expression in heart, skeletal muscle, liver, kidney and placenta. In intestinal mucosa, down-regulated in areas involved in Crohn disease and ulcerative colitis.

9606:CLVS2
gene id: 9606:CLVS2
uniprot id: Q5SYC1
names: Domain
names: Function
names: Miscellaneous
names: Subcellular Location Annotation
names: Subunit
messages: Binding to PtdIns(3,5)P2 is not required for localization.
messages: Early endosome membrane
messages: Forms a complex with clathrin heavy chain and gamma-adaptin.
messages: Required for normal morphology of late endosomes and/or lysosomes in neurons (By similarity). Binds phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2).
messages: The CRAL-TRIO domain is required for targeting to the membrane and for binding PtdIns(3,5)P2.
messages: clathrin-coated vesicle
messages: trans-Golgi network membrane

9606:PTS
gene id: 9606:PTS
uniprot id: Q03393
names: Cofactor
names: Disease Annotation
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subunit
messages: Belongs to the PTPS family.
messages: Binds 1 zinc ion per subunit.
messages: Homohexamer formed of two homotrimers in a head to head fashion.
messages: Involved in the biosynthesis of tetrahydrobiopterin, an essential cofactor of aromatic amino acid hydroxylases. Catalyzes the transformation of 7,8-dihydroneopterin triphosphate into 6-pyruvoyl tetrahydropterin.
messages: Phosphorylation of Ser-19 is required for maximal enzyme activity.
messages: The active site is at the interface between 2 subunits. The proton acceptor Cys is on one subunit, and the charge relay system is on the other subunit.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:THEM4
gene id: 9606:THEM4
uniprot id: Q5T1C6
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the THEM4/THEM5 thioesterase family.
messages: Cell membrane
messages: Cytoplasm
messages: Expressed predominantly in skeletal muscle, testis, uterus, brain and kidney. Down-regulated in glioblastoma or glioma compared to non-neoplastic brain due to promoter hypermethylation.
messages: Has acyl-CoA thioesterase activity towards medium and long-chain (C14 to C18) fatty acyl-CoA substrates, and probably plays a role in mitochondrial fatty acid metabolism. Plays a role in the apoptotic process, possibly via its regulation of AKT1 activity. According to PubMed:11598301, inhibits AKT1 phosphorylation and activity. According to PubMed:17615157, enhances AKT1 activity by favoring its phosphorylation and translocation to plasma membrane.
messages: Homodimer and homotetramer. Interacts with AKT1 in the cytosol.
messages: Mitochondrion
messages: Mitochondrion inner membrane
messages: Mitochondrion intermembrane space
messages: Phosphorylated.
messages: ruffle membrane

9606:ATXN10
gene id: 9606:ATXN10
uniprot id: Q9UBB4
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the ataxin-10 family.
messages: Defects in ATXN1 may be a cause of nephronophthisis a chronic tubulo-interstitial nephropathy that leads to anemia, polyuria, polydipsia, isosthenuria and death in uremia.
messages: Expressed in the central nervous system.
messages: Homooligomer (By similarity). Interacts with OGT (By similarity). Interacts with GNB2. Interacts with IQCB1.
messages: Necessary for the survival of cerebellar neurons. Induces neuritogenesis by activating the Ras-MAP kinase pathway. May play a role in the maintenance of a critical intracellular glycosylation level and homeostasis.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: perinuclear region

9606:CCDC13
gene id: 9606:CCDC13
uniprot id: Q8IYE1
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Interacts with PCM1, CEP290 and PCNT.
messages: Required for primary cilia formation and promotes the localization of the ciliopathy protein BBS4 to both centriolar satellites and cilia.
messages: centriolar satellite
messages: cilium basal body

9606:C6orf58
gene id: 9606:C6orf58
uniprot id: Q6P5S2
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the LEG1 family.
messages: Detected in saliva and in hypomineralized dental enamel (at protein level).
messages: May be involved in early liver development.
messages: Secreted

9606:EMC7
gene id: 9606:EMC7
uniprot id: Q9NPA0
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the EMC7 family.
messages: Component of the ER membrane protein complex (EMC).
messages: Endoplasmic reticulum membrane
messages: Part of the endoplasmic reticulum membrane protein complex (EMC) that enables the energy-independent insertion into endoplasmic reticulum membranes of newly synthesized membrane proteins (PubMed:30415835, PubMed:29809151, PubMed:29242231, PubMed:32459176, PubMed:32439656). Preferentially accommodates proteins with transmembrane domains that are weakly hydrophobic or contain destabilizing features such as charged and aromatic residues (PubMed:30415835, PubMed:29809151, PubMed:29242231). Involved in the cotranslational insertion of multi-pass membrane proteins in which stop-transfer membrane-anchor sequences become ER membrane spanning helices (PubMed:30415835, PubMed:29809151). It is also required for the post-translational insertion of tail-anchored/TA proteins in endoplasmic reticulum membranes (PubMed:29809151, PubMed:29242231). By mediating the proper cotranslational insertion of N-terminal transmembrane domains in an N-exo topology, with translocated N-terminus in the lumen of the ER, controls the topology of multi-pass membrane proteins like the G protein-coupled receptors (PubMed:30415835). By regulating the insertion of various proteins in membranes, it is indirectly involved in many cellular processes (Probable).

9606:CINP
gene id: 9606:CINP
uniprot id: Q9BW66
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the CINP family.
messages: Component of the DNA replication complex, which interacts with two kinases, CDK2 and CDC7, thereby providing a functional and physical link between CDK2 and CDC7 during firing of the origins of replication (PubMed:16082200, PubMed:19889979). Regulates ATR-mediated checkpoint signaling in response to DNA damage (PubMed:19889979). Also involved in the cytoplasmic maturation steps of pre-60S ribosomal particles by promoting the release of shuttling protein RSL24D1/RLP24 from the pre-ribosomal particles (PubMed:35354024). Promotes maturation of pre-60S ribosome together with AFG2A, AFG2B and AIRIM (PubMed:35354024).
messages: Homodimer (PubMed:16082200). Interacts with CDK2 and CDC7 (PubMed:16082200). Interacts with the components of the replication complex, MCM2, MCM3, MCM4, MCM5, MCM6, MCM7 and with ORC2-containing complexes (PubMed:16082200). Interacts with ATRIP (PubMed:19889979). Interacts with CEP152 (PubMed:21131973). Associates with pre-60S ribosomal particles (PubMed:35354024). Interacts with AIRIM (PubMed:35354024).
messages: Nucleus
messages: Phosphorylated by CDC7 but not by CDK2.

9606:TAAR2
gene id: 9606:TAAR2
uniprot id: Q9P1P5
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Not expressed in the pons, thalamus, hypothalamus, hippocampus, caudate, putamen, frontal cortex, basal forebrain, midbrain or liver.
messages: Orphan receptor.

9606:MPC1
gene id: 9606:MPC1
uniprot id: Q5TI65
uniprot id: Q9Y5U8
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the mitochondrial pyruvate carrier (MPC) (TC 2.A.105) family.
messages: Homodimer (PubMed:32403431). Forms heterodimer with MPC2. The heterodimer is the more stable and dominant form (PubMed:26253029, PubMed:32403431).
messages: Mediates the uptake of pyruvate into mitochondria.
messages: Membrane
messages: Mitochondrion inner membrane
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:CAPZB
gene id: 9606:CAPZB
uniprot id: A0A384MR50
uniprot id: B1AK85
uniprot id: B1AK88
uniprot id: B4DWA6
uniprot id: P47756
uniprot id: Q7L4N0
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the F-actin-capping protein beta subunit family.
messages: F-actin-capping proteins bind in a Ca(2+)-independent manner to the fast growing ends of actin filaments (barbed end) thereby blocking the exchange of subunits at these ends. Unlike other capping proteins (such as gelsolin and severin), these proteins do not sever actin filaments.
messages: F-actin-capping proteins bind in a Ca(2+)-independent manner to the fast growing ends of actin filaments (barbed end) thereby blocking the exchange of subunits at these ends. Unlike other capping proteins (such as gelsolin and severin), these proteins do not sever actin filaments. Plays a role in the regulation of cell morphology and cytoskeletal organization. Forms, with CAPZB, the barbed end of the fast growing ends of actin filaments in the dynactin complex and stabilizes dynactin structure. The dynactin multiprotein complex activates the molecular motor dynein for ultra-processive transport along microtubules (By similarity).
messages: Heterodimer of an alpha and a beta subunit.
messages: Heterodimer of an alpha and a beta subunit. Subunit of dynactin, a multiprotein complex part of a tripartite complex with dynein and a adapter, such as BICDL1, BICD2 or HOOK3. The dynactin complex is built around ACTR1A/ACTB filament and consists of an actin-related filament composed of a shoulder domain, a pointed end and a barbed end. Its length is defined by its flexible shoulder domain. The soulder is composed of 2 DCTN1 subunits, 4 DCTN2 and 2 DCTN3. The 4 DCNT2 (via N-terminus) bind the ACTR1A filament and act as molecular rulers to determine the length. The pointed end is important for binding dynein-dynactin cargo adapters. Consists of 4 subunits: ACTR10, DCNT4, DCTN5 and DCTN6. The barbed end is composed of a CAPZA1:CAPZB heterodimers, which binds ACTR1A/ACTB filament and dynactin and stabilizes dynactin (By similarity). Interacts with ARHGAP17 (PubMed:16678097). Interaction with RCSD1/CAPZIP (PubMed:15850461). Component of the WASH complex, composed of F-actin-capping protein subunit alpha (CAPZA1, CAPZA2 or CAPZA3), F-actin-capping protein subunit beta (CAPZB), WASH (WASHC1, WASH2P, WASH3P, WASH4P, WASH5P or WASH6P), WASHC2 (WASHC2A or WASHC2C), WASHC3, WASHC4 and WASHC5 (PubMed:19922875). Interacts with ACTG1 (PubMed:28493397). Directly interacts with CRACD; this interaction decreases binding to actin (PubMed:30361697).
messages: cytoskeleton
messages: sarcomere

9606:FOXN3
gene id: 9606:FOXN3
uniprot id: O00409
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Acts as a transcriptional repressor. May be involved in DNA damage-inducible cell cycle arrests (checkpoints).
messages: Interacts through its C-terminus with the C-terminus of SNW1/SKIP.
messages: Nucleus

9606:SKOR2
gene id: 9606:SKOR2
uniprot id: Q2VWA4
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the SKI family.
messages: Cytoplasm
messages: Exhibits transcriptional repressor activity (By similarity). Acts as a TGF-beta antagonist in the nervous system.
messages: Expressed in cerebellum, spinal cord and testis. Isoform 2 is present in cerebellum (at protein level).
messages: Interacts with SMAD2 and SMAD3.
messages: Nucleus

9606:PRMT5
gene id: 9606:PRMT5
uniprot id: B4DV00
uniprot id: O14744
names: Activity Regulation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Activity is increased by EGF, HGF, FGF1 or FGF2 treatments, and slightly decreased by NGF treatment.
messages: Arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and symmetrical dimethylarginine (sDMA), with a preference for the formation of MMA (PubMed:10531356, PubMed:11152681, PubMed:11747828, PubMed:12411503, PubMed:15737618, PubMed:17709427, PubMed:20159986, PubMed:20810653, PubMed:21258366, PubMed:21917714, PubMed:22269951, PubMed:21081503). Specifically mediates the symmetrical dimethylation of arginine residues in the small nuclear ribonucleoproteins Sm D1 (SNRPD1) and Sm D3 (SNRPD3); such methylation being required for the assembly and biogenesis of snRNP core particles (PubMed:12411503, PubMed:11747828, PubMed:17709427). Methylates SUPT5H and may regulate its transcriptional elongation properties (PubMed:12718890). May methylate the N-terminal region of MBD2 (PubMed:16428440). Mono- and dimethylates arginine residues of myelin basic protein (MBP) in vitro. May play a role in cytokine-activated transduction pathways. Negatively regulates cyclin E1 promoter activity and cellular proliferation. Methylates histone H2A and H4 'Arg-3' during germ cell development (By similarity). Methylates histone H3 'Arg-8', which may repress transcription (By similarity). Methylates the Piwi proteins (PIWIL1, PIWIL2 and PIWIL4), methylation of Piwi proteins being required for the interaction with Tudor domain-containing proteins and subsequent localization to the meiotic nuage (By similarity). Methylates RPS10. Attenuates EGF signaling through the MAPK1/MAPK3 pathway acting at 2 levels. First, monomethylates EGFR; this enhances EGFR 'Tyr-1197' phosphorylation and PTPN6 recruitment, eventually leading to reduced SOS1 phosphorylation (PubMed:21917714, PubMed:21258366). Second, methylates RAF1 and probably BRAF, hence destabilizing these 2 signaling proteins and reducing their catalytic activity (PubMed:21917714). Required for induction of E-selectin and VCAM-1, on the endothelial cells surface at sites of inflammation. Methylates HOXA9 (P…
messages: Arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and symmetrical dimethylarginine (sDMA).
messages: Belongs to the class I-like SAM-binding methyltransferase superfamily.
messages: Belongs to the class I-like SAM-binding methyltransferase superfamily. Protein arginine N-methyltransferase family.
messages: Chromosome
messages: Cytoplasm
messages: Forms, at least, homodimers and homotetramers (PubMed:11152681). Component of the methylosome complex, composed of PRMT5, WDR77 and CLNS1A (PubMed:21081503, PubMed:23071334, PubMed:33376131). Found in a complex composed of PRMT5, WDR77 and RIOK1 (PubMed:21081503). RIOK1 and CLNS1A associate with PRMT5 in a mutually exclusive fashion, which allows the recruitment of distinct methylation substrates, such as nucleolin/NCL and Sm proteins, respectively (PubMed:21081503). Interacts with PRDM1 (By similarity). Identified in a complex composed of methylosome and PRMT1 and ERH (PubMed:25284789). Interacts with EGFR; methylates EGFR and stimulates EGFR-mediated ERK activation. Interacts with HOXA9. Interacts with SRGAP2. Found in a complex with COPRS, RUNX1 and CBFB. Interacts with CHTOP; the interaction symmetrically methylates CHTOP, but seems to require the presence of PRMT1 (PubMed:25284789). Interacts with EPB41L3; this modulates methylation of target proteins. Component of a high molecular weight E2F-pocket protein complex, CERC (cyclin E1 repressor complex). Associates with SWI/SNF remodeling complexes containing SMARCA2 and SMARCA4. Interacts with JAK2, SSTR1, SUPT5H, BRAF and with active RAF1. Interacts with LSM11, PRMT7 and SNRPD3 (PubMed:17709427, PubMed:16087681). Interacts with COPRS; promoting its recruitment on histone H4. Interacts with CLNS1A/pICln (PubMed:21081503, PubMed:9556550). Identified in a complex with CLNS1A/pICln and Sm proteins. Interacts with RPS10 (PubMed:20159986). Interacts with WDR77. Interacts with IWS1. Interacts with CRY1. Interacts with POLR2A (PubMed:26700805). Interacts with SMN1/SMN2 (PubMed:26700805). Interacts with LYAR; this interaction is direct (PubMed:25092918). Interacts with TTC5/STRAP; this interaction is DNA damage-dependent and promotes PRMT5 interaction with p53/TP53 (PubMed:19011621). Interacts with p53/TP53 in response to DNA damage; the interaction is TTC5/STRAP dependent (PubMed:19011621). Interacts with FAM47E; the in…
messages: Golgi apparatus
messages: Nucleus
messages: Ubiquitous.

9606:NKX2-2
gene id: 9606:NKX2-2
uniprot id: O95096
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the NK-2 homeobox family.
messages: Interacts with OLIG2.
messages: Nucleus
messages: The homeodomain is essential for interaction with OLIG2.
messages: Transcriptional activator involved in the development of insulin-producting beta cells in the endocrine pancreas (By similarity). May also be involved in specifying diencephalic neuromeric boundaries, and in controlling the expression of genes that play a role in axonal guidance. Binds to elements within the NEUROD1 promoter (By similarity).

9606:EIF4EBP2
gene id: 9606:EIF4EBP2
uniprot id: Q13542
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the eIF4E-binding protein family.
messages: Cytoplasm
messages: Deamidated at Asn-99 and Asn-102 to aspartate (Asp) in brain. Deamidation promotes interaction with RPTOR, subsequent phosphorylation by mTORC1 and increased translation, leading to impair kinetics of excitatory synaptic transmission. Deamidation takes place during postnatal development, when the PI3K-Akt-mTOR signaling is reduced, suggesting it acts as a compensatory mechanism to promote translation despite attenuated PI3K-Akt-mTOR signaling in neuron development. Deamidation converts Asn residues into a mixture of Asp and isoaspartate; interactions with PCMT1 is required to prevent isoaspartate accumulation and convert isoaspartate to Asp.
messages: Hypophosphorylated EIF4EBP2 interacts with EIF4E; phosphorylation of EIF4EBP2 by mTORC1 causes dissociation of the complex allowing EIF4G1/EIF4G3 to bind and consequent initiation of translation (PubMed:7935836, PubMed:24207126, PubMed:21661078, PubMed:25533957). Interacts with RPTOR; promoting phosphorylation by mTORC1 (By similarity). Interacts with PCMT1; required to prevent isoaspartate accumulation and convert isoaspartate to Asp (By similarity).
messages: Intrinsically disordered protein that undergoes folding upon phosphorylation (PubMed:25533957). Hypophosphorylated form interacts strongly with EIF4E using (1) the YXXXXLPhi motif, that undergoes a disorder-to-helix transition upon binding and (2) the secondary EIF4E binding sites (residues 78-82) (PubMed:24207126, PubMed:25533957). Phosphorylation at Thr-37 and Thr-46 induces folding of region encompassing residues from Pro-18 to Arg-62 of into a four-stranded beta-domain that sequesters the helical YXXXXLPhi motif into a buried beta-strand, blocking accessibility to EIF4E. Protein phosphorylated at Thr-37 and Thr-46 is however unstable and subsequent phosphorylation at Ser-65, Thr-70 and Ser-83 is required to stabilize the fold, decreasing affinity for EIF4E by a factor of 4000 (PubMed:24207126, PubMed:25533957).
messages: Nucleus
messages: Phosphorylation at Thr-37, Thr-46, Ser-65, Thr-70 and Ser-83 is mediated by MTOR and corresponds to the hyperphosphorylated form: it abolishes binding to EIF4E by inducing folding of intrinsically disordered regions (PubMed:24207126, PubMed:25533957). First phosphorylated at Thr-37 and Thr-46 by MTOR, inducing folding of region encompassing residues from Pro-18 to Arg-62 of into a four-stranded beta-domain that sequesters the helical YXXXXLPhi motif into a partly buried beta-strand, blocking accessibility to EIF4E. Protein phosphorylated at Thr-37 and Thr-46 is however unstable and subsequent phosphorylation at Ser-65, Thr-70 and Ser-83 is required to stabilize the fold, decreasing affinity for EIF4E by a factor of 4000 (PubMed:24207126, PubMed:25533957). Phosphorylated in response to insulin, EGF and PDGF.
messages: Repressor of translation initiation involved in synaptic plasticity, learning and memory formation (PubMed:30765518). Regulates EIF4E activity by preventing its assembly into the eIF4F complex: hypophosphorylated form of EIF4EBP2 competes with EIF4G1/EIF4G3 and strongly binds to EIF4E, leading to repress translation. In contrast, hyperphosphorylated form dissociates from EIF4E, allowing interaction between EIF4G1/EIF4G3 and EIF4E, leading to initiation of translation (PubMed:30765518, PubMed:25533957). EIF4EBP2 is enriched in brain and acts as a regulator of synapse activity and neuronal stem cell renewal via its ability to repress translation initiation (By similarity). Mediates the regulation of protein translation by hormones, growth factors and other stimuli that signal through the MAP kinase and mTORC1 pathways (By similarity).
messages: The TOS motif mediates interaction with RPTOR, leading to promote phosphorylation by mTORC1 complex.

9606:UBE3B
gene id: 9606:UBE3B
uniprot id: Q7Z3V4
names: Disease Annotation
names: Function
names: Miscellaneous
names: Tissue Specificity
messages: E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates.
messages: Major isoform.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Widely expressed.

9606:FAM200A
gene id: 9606:FAM200A
uniprot id: Q8TCP9
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the FAM200 family.
messages: Membrane

9606:NKX2-3
gene id: 9606:NKX2-3
uniprot id: Q8TAU0
names: Function
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the NK-2 homeobox family.
messages: Nucleus
messages: The lack of 97 nucleotides within coding exon 2 produces a frameshift and results in a truncated protein.
messages: Transcription factor.

9606:MESP2
gene id: 9606:MESP2
uniprot id: Q0VG99
names: Disease Annotation
names: Function
names: PTM
names: Polymorphism
names: Subcellular Location Annotation
messages: Degraded by the proteasome.
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The number of GQ repeats at position 179 is polymorphic.
messages: Transcription factor with important role in somitogenesis. Defines the rostrocaudal patterning of the somite by participating in distinct Notch pathways. Regulates also the FGF signaling pathway. Specifies the rostral half of the somites. Generates rostro-caudal polarity of somites by down-regulating in the presumptive rostral domain DLL1, a Notch ligand. Participates in the segment border formation by activating in the anterior presomitic mesoderm LFNG, a negative regulator of DLL1-Notch signaling. Acts as a strong suppressor of Notch activity. Together with MESP1 is involved in the epithelialization of somitic mesoderm and in the development of cardiac mesoderm.

9606:ASS1
gene id: 9606:ASS1
uniprot id: P00966
names: Developmental Stage
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acetylated by CLOCK in a circadian manner which negatively regulates its enzyme activity. Deacetylated by histone deacetylases.
messages: Belongs to the argininosuccinate synthase family. Type 1 subfamily.
messages: Expressed in adult liver.
messages: Expressed in fetal liver and kidney.
messages: Homotetramer (PubMed:18323623). Interacts with NMRAL1 (PubMed:17496144). Interacts with CLOCK; in a circadian manner (PubMed:28985504). Forms tissue-specific complexes with ASL, SLC7A1, HSP90AA1 and nitric oxide synthase NOS1, NOS2 or NOS3; the complex regulates cell-autonomous L-arginine synthesis and citrulline recycling while channeling extracellular L-arginine to nitric oxide synthesis pathway.
messages: One of the enzymes of the urea cycle, the metabolic pathway transforming neurotoxic amonia produced by protein catabolism into inocuous urea in the liver of ureotelic animals. Catalyzes the formation of arginosuccinate from aspartate, citrulline and ATP and together with ASL it is responsible for the biosynthesis of arginine in most body tissues.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: cytosol

9606:AP2A1
gene id: 9606:AP2A1
uniprot id: O95782
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Adaptor protein complex 2 (AP-2) is a heterotetramer composed of two large adaptins (alpha-type subunit AP2A1 or AP2A2 and beta-type subunit AP2B1), a medium adaptin (mu-type subunit AP2M1) and a small adaptin (sigma-type subunit AP2S1). Interacts with SGIP1 (By similarity). Interacts with HIP1 and RAB11FIP2 (PubMed:11532990, PubMed:12364336). Interacts with SLC12A5 (By similarity). Interacts with clathrin (By similarity). Interacts with RFTN1 (PubMed:27022195). Interacts with KIAA1107 (PubMed:29262337). Interacts with PICALM (PubMed:16262731). Together with AP2B1 and AP2M1, it interacts with ADAM10; this interaction facilitates ADAM10 endocytosis from the plasma membrane during long-term potentiation in hippocampal neurons (PubMed:23676497). Interacts with ABCB11; this interaction regulates cell membrane expression of ABCB11 through its internalization in a clathrin-dependent manner and its subsequent degradation (PubMed:22262466).
messages: Belongs to the adaptor complexes large subunit family.
messages: Cell membrane
messages: Component of the adaptor protein complex 2 (AP-2). Adaptor protein complexes function in protein transport via transport vesicles in different membrane traffic pathways. Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation. AP-2 is involved in clathrin-dependent endocytosis in which cargo proteins are incorporated into vesicles surrounded by clathrin (clathrin-coated vesicles, CCVs) which are destined for fusion with the early endosome. The clathrin lattice serves as a mechanical scaffold but is itself unable to bind directly to membrane components. Clathrin-associated adaptor protein (AP) complexes which can bind directly to both the clathrin lattice and to the lipid and protein components of membranes are considered to be the major clathrin adaptors contributing the CCV formation. AP-2 also serves as a cargo receptor to selectively sort the membrane proteins involved in receptor-mediated endocytosis. AP-2 seems to play a role in the recycling of synaptic vesicle membranes from the presynaptic surface. AP-2 recognizes Y-X-X-[FILMV] (Y-X-X-Phi) and [ED]-X-X-X-L-[LI] endocytosis signal motifs within the cytosolic tails of transmembrane cargo molecules. AP-2 may also play a role in maintaining normal post-endocytic trafficking through the ARF6-regulated, non-clathrin pathway. During long-term potentiation in hippocampal neurons, AP-2 is responsible for the endocytosis of ADAM10 (PubMed:23676497). The AP-2 alpha subunit binds polyphosphoinositide-containing lipids, positioning AP-2 on the membrane. The AP-2 alpha subunit acts via its C-terminal appendage domain as a scaffolding platform for endocytic accessory proteins. The AP-2 alpha and AP-2 sigma subunits are thought to contribute to the recognition of the [ED]-X-X-X-L-[LI] motif (By similarity).
messages: Expressed in the brain (at protein level) (PubMed:23676497). Isoform A: Expressed in forebrain, skeletal muscle, spinal cord, cerebellum, salivary gland, heart and colon. Isoform B: Widely expressed in tissues and also in breast cancer and in prostate carcinoma cells.
messages: coated pit

9606:ENY2
gene id: 9606:ENY2
uniprot id: Q9NPA8
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the ENY2 family.
messages: Component of the nuclear pore complex (NPC)-associated TREX-2 complex (transcription and export complex 2), composed of at least ENY2, the isoform GANP of the MCM3AP gene, PCID2, SEM1, and either centrin CETN2 or CETN3. TREX-2 contains 2 ENY2 chains. The TREX-2 complex also associates with ALYREF/ALY and with the nucleoporin NUP153 (PubMed:23591820, PubMed:22307388). Component of some SAGA transcription coactivator-HAT complexes, at least composed of ATXN7, ATXN7L3, ENY2, GCN5L2, SUPT3H/SPT3, TAF10, TRRAP and USP22 (PubMed:18206972, PubMed:21746879, PubMed:23591820, PubMed:27601583). Within the SAGA complex, ENY2, ATXN7, ATXN7L3, and USP22 form an additional subcomplex of SAGA called the DUB module (deubiquitination module) (PubMed:18206972, PubMed:21746879, PubMed:27601583). Interacts with RNA polymerase II subunit POLR2A (PubMed:22307388). Interacts with ATXN7L3B (PubMed:27601583).
messages: Involved in mRNA export coupled transcription activation by association with both the TREX-2 and the SAGA complexes. The transcription regulatory histone acetylation (HAT) complex SAGA is a multiprotein complex that activates transcription by remodeling chromatin and mediating histone acetylation and deubiquitination. Within the SAGA complex, participates in a subcomplex that specifically deubiquitinates both histones H2A and H2B. The SAGA complex is recruited to specific gene promoters by activators such as MYC, where it is required for transcription. Required for nuclear receptor-mediated transactivation (PubMed:18206972, PubMed:21746879). As a component of the TREX-2 complex, involved in the export of mRNAs to the cytoplasm through the nuclear pores (PubMed:23591820).
messages: nucleoplasm

9606:CCNY
gene id: 9606:CCNY
uniprot id: B7Z8E4
uniprot id: Q8ND76
names: Developmental Stage
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the cyclin family. Cyclin Y subfamily.
messages: Cell membrane
messages: Enriched at G2/M.
messages: Found in a complex with CAPRIN2, LRP6 and CDK14 during G2/M stage; CAPRIN2 functions as a scaffold for the complex by binding to CCNY via its N terminus and to CDK14 via its C terminus (PubMed:27821587). Interacts with CDK14 (PubMed:19524571, PubMed:20059949). Interacts with CDK16 (PubMed:22184064). Interacts with LRP6 (PubMed:20059949).
messages: Heavily phosphorylated. Phosphorylation at Ser-71 and Ser-73 by CDK14 is enhanced during the G2 and M cell cycle phases, and creates a phosphodegron triggering SCF-dependent ubiquitination.
messages: Nucleus
messages: Positive regulatory subunit of the cyclin-dependent kinases CDK14/PFTK1 and CDK16. Acts as a cell-cycle regulator of Wnt signaling pathway during G2/M phase by recruiting CDK14/PFTK1 to the plasma membrane and promoting phosphorylation of LRP6, leading to the activation of the Wnt signaling pathway. Recruits CDK16 to the plasma membrane. Isoform 3 might play a role in the activation of MYC-mediated transcription.
messages: Ubiquitinated; leading to its degradation.
messages: Widely expressed.

9606:OR2T4
gene id: 9606:OR2T4
uniprot id: Q8NH00
names: Caution
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: It is uncertain whether Met-1 or Met-29 is the initiator.
messages: Odorant receptor.

9606:NMS
gene id: 9606:NMS
uniprot id: A0A250SI41
uniprot id: Q5H8A3
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the NmU family.
messages: Implicated in the regulation of circadian rhythms through autocrine and/or paracrine actions.
messages: Secreted

9606:ADCY3
gene id: 9606:ADCY3
uniprot id: A0A0A0MSC1
uniprot id: B7ZLX9
uniprot id: O60266
names: Activity Regulation
names: Cofactor
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Activated by forskolin. After forskolin treatment, activity is further increased by calcium/calmodulin. In the absence of forskolin, calcium/calmodulin has little effect on enzyme activity.
messages: Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.
messages: Binds 2 magnesium ions per subunit. Is also active with manganese (in vitro).
messages: Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling.
messages: Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling. Participates in signaling cascades triggered by odorant receptors via its function in cAMP biosynthesis. Required for the perception of odorants. Required for normal sperm motility and normal male fertility. Plays a role in regulating insulin levels and body fat accumulation in response to a high fat diet.
messages: Cell membrane
messages: Cytoplasm
messages: Detected in zona glomerulosa and zona fasciculata in the adrenal gland (at protein level) (PubMed:11549699). Expressed in brain, heart, kidney, liver, lung, pancreas islets, placenta, and skeletal muscle (PubMed:9920776). Detected in testis (PubMed:15705663).
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry.
messages: Genetic variations at the ADCY3 locus define the body mass index quantitative trait locus 19 (BMIQ19) [MIM:617885]. Variance in body mass index is a susceptibility factor for obesity.
messages: Golgi apparatus
messages: Membrane
messages: N-glycosylated.
messages: Rapidly phosphorylated after stimulation by odorants or forskolin. Phosphorylation by CaMK2 at Ser-1076 down-regulates enzyme activity.
messages: Sumoylated. Sumoylation is required for targeting ot olfactory cilia.
messages: The protein contains two modules with six transmembrane helices each; both are required for catalytic activity. Isolated N-terminal or C-terminal modules have no catalytic activity, but when they are brought together, enzyme activity is restored. The active site is at the interface of the two modules.
messages: cilium

9606:MYCBP2
gene id: 9606:MYCBP2
uniprot id: O75592
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Atypical E3 ubiquitin-protein ligase which specifically mediates ubiquitination of threonine and serine residues on target proteins, instead of ubiquitinating lysine residues (PubMed:29643511). Shows esterification activity towards both threonine and serine, with a preference for threonine, and acts via two essential catalytic cysteine residues that relay ubiquitin to its substrate via thioester intermediates (PubMed:29643511). Interacts with the E2 enzymes UBE2D1, UBE2D3, UBE2E1 and UBE2L3 (PubMed:18308511, PubMed:29643511). Plays a key role in neural development, probably by mediating ubiquitination of threonine residues on target proteins (Probable). Involved in different processes such as regulation of neurite outgrowth, synaptic growth, synaptogenesis and axon degeneration (By similarity). Required for the formation of major central nervous system axon tracts (By similarity). Required for proper axon growth by regulating axon navigation and axon branching: acts by regulating the subcellular location and stability of MAP3K12/DLK (By similarity). Required for proper localization of retinogeniculate projections but not for eye-specific segregation (By similarity). Regulates axon guidance in the olfactory system (By similarity). Involved in Wallerian axon degeneration, an evolutionarily conserved process that drives the loss of damaged axons: acts by promoting destabilization of NMNAT2, probably via ubiquitination of NMNAT2 (By similarity). Catalyzes ubiquitination of threonine and/or serine residues on NMNAT2, consequences of threonine and/or serine ubiquitination are however unknown (PubMed:29643511). Regulates the internalization of TRPV1 in peripheral sensory neurons (By similarity). Mediates ubiquitination and subsequent proteasomal degradation of TSC2/tuberin (PubMed:18308511, PubMed:27278822). Independently of the E3 ubiquitin-protein ligase activity, also acts as a guanosine exchange factor (GEF) for RAN in neurons of dorsal root ganglia (PubMed:26304119). …
messages: Autoubiquitinated.
messages: Belongs to the RING-Cys relay (RCR) family.
messages: Expressed in all tissues examined, expression is exceptionally abundant in brain and thymus. Colocalizes with TSC1 and TSC2 along the neurites and in the growth cones. Highly expressed in peripheral and central neurons. Colocalized with TSC1 in one of the filopodial extensions at the tip of a growth cone.
messages: Interacts with MYC (PubMed:9689053). Interacts with TSC2 (tuberin) when TSC2 is in complex with TSC1 (hamartin) (PubMed:14559897). Interacts with FBXO45 (PubMed:19398581). Interacts with RAE1 (PubMed:22357847). Interacts with CPNE1 (via VWFA domain) and CPNE4 (via VWFA domain) (By similarity). Interacts with (sumoylated) RANGAP1; interaction with sumoylated RANGAP1 inhibits E3 ubiquitin-protein ligase activity and promotes MYCBP2 translocation to the nucleus (PubMed:26304119). Interacts with RAN (PubMed:26304119).Interacts with ATP13A2; the interaction inhibits the ubiquitination of TSC2 by MYCBP2 (PubMed:27278822). Interacts with USP11 (PubMed:29293652).
messages: Nucleus
messages: The PHR domains are compact beta-sandwich folds composed of 11 antiparallel strands and decorated with conserved apical loops. They are likely to play a structural role and mediate interactions with substrates or partners (By similarity).
messages: The tandem cysteine domain region confers threonine specificity and contains the two essential catalytic cysteine residues that relay ubiquitin. It binds four zinc ions in a C5HC7HC2 configuration.
messages: axon
messages: cytoskeleton

9606:COL4A6
gene id: 9606:COL4A6
uniprot id: A0A087WZY5
uniprot id: A8MXH5
uniprot id: A8VPY0
uniprot id: B2RTX6
uniprot id: B7ZMM7
uniprot id: F5H3Q5
uniprot id: Q14031
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Alpha chains of type IV collagen have a non-collagenous domain (NC1) at their C-terminus, frequent interruptions of the G-X-Y repeats in the long central triple-helical domain (which may cause flexibility in the triple helix), and a short N-terminal triple-helical 7S domain.
messages: Belongs to the type IV collagen family.
messages: Deletions covering the N-terminal regions of COL4A5 and COL4A6, which are localized in a head-to-head manner, are found in the chromosome Xq22.3 centromeric deletion syndrome. This results in a phenotype with features of diffuse leiomyomatosis and Alport syndrome (DL-ATS).
messages: Membrane
messages: Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The trimeric structure of the NC1 domains is stabilized by covalent bonds between Lys and Met residues.
messages: There are six type IV collagen isoforms, alpha 1(IV)-alpha 6(IV), each of which can form a triple helix structure with 2 other chains to generate type IV collagen network.
messages: Type IV collagen is the major structural component of glomerular basement membranes (GBM), forming a 'chicken-wire' meshwork together with laminins, proteoglycans and entactin/nidogen.
messages: Type IV collagens contain numerous cysteine residues which are involved in inter- and intramolecular disulfide bonding. 12 of these, located in the NC1 domain, are conserved in all known type IV collagens.
messages: basement membrane

9606:CT55
gene id: 9606:CT55
uniprot id: Q8WUE5
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cytoplasm
messages: Interacts with GABARAP; this interaction may be important for GABARAP protein stability (PubMed:36481789). Isoform 1 interacts with LAMP2; this interaction may be important for LAMP2 protein stability (PubMed:36481789).
messages: Plays a role in spermatogenesis, possibly acting in the regulation of the autophagy pathway.
messages: Testis-specific (PubMed:15499386). Expressed in spermatozoa (at protein level) (PubMed:36481789).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: acrosome
messages: flagellum

9606:ZCCHC12
gene id: 9606:ZCCHC12
uniprot id: Q6PEW1
names: Function
names: Similarity
names: Subunit
messages: Belongs to the ZCCHC12 family.
messages: Interacts with SMAD1 and CREB-binding protein (CBP). Forms a protein-DNA complex through its association with SMAD1 (By similarity).
messages: Transcriptional coactivator in the bone morphogenetic protein (BMP)-signaling pathway. It positively modulates BMP signaling by interacting with SMAD1 and associating with CBP in the transcription complex. It contributes to the BMP-induced enhancement of cholinergic-neuron-specific gene expression (By similarity).

9606:STK33
gene id: 9606:STK33
uniprot id: B4DDH2
uniprot id: Q9BYT3
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Autophosphorylated.
messages: Belongs to the protein kinase superfamily.
messages: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily.
messages: Highly expressed in testis, fetal lung and heart, followed by pituitary gland, kidney, interventricular septum, pancreas, heart, trachea, thyroid gland and uterus. Weak hybridization signals were observed in the following tissues: amygdala, aorta, esophagus, colon ascending, colon transverse, skeletal muscle, spleen, peripheral blood leukocyte, lymph node, bone marrow, placenta, prostate, liver, salivary gland, mammary gland, some tumor cell lines, fetal brain, fetal liver, fetal spleen and fetal thymus. No signal at all was detectable in RNA from tissues of the nervous system.
messages: Interacts with VIME.
messages: Serine/threonine protein kinase which phosphorylates VIME. May play a specific role in the dynamic behavior of the intermediate filament cytoskeleton by phosphorylation of VIME (By similarity). Not essential for the survival of KRAS-dependent AML cell lines.
messages: perinuclear region

9606:CCN6
gene id: 9606:CCN6
uniprot id: A0A384NYW3
uniprot id: O95389
names: Caution
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the CCN family.
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: Mitochondrion
messages: Plays a role in mitochondrial electron transport and mitochondrial respiration (PubMed:27252383). Through its regulation of the mitochondrial function may play a role in normal postnatal skeletal growth and cartilage homeostasis (PubMed:27252383, PubMed:10471507).
messages: Predominant expression in adult kidney and testis and fetal kidney. Weaker expression found in placenta, ovary, prostate and small intestine (PubMed:9843955, PubMed:10471507). Also expressed in skeletally-derived cells such as synoviocytes and articular cartilage chondrocytes (PubMed:10471507).
messages: Secreted
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:TMEM52B
gene id: 9606:TMEM52B
uniprot id: Q4KMG9
names: Subcellular Location Annotation
messages: Membrane

9606:LRIF1
gene id: 9606:LRIF1
uniprot id: Q5T3J3
names: Disease Annotation
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the LRIF1 family.
messages: Chromosome
messages: Interacts with RARA (PubMed:17455211). Interacts with SMCHD1; leading to recruitment to inactivated chromosome X in females (PubMed:23542155). Interacts (via PxVxL motif) with HP1 (CBX1/HP1-beta, CBX3/HP1-gamma and CBX5/HP1-alpha) (PubMed:23542155).
messages: Nucleus matrix
messages: The Pro-Xaa-Val-Xaa-Leu (PxVxL) motif mediates interaction with HP1 (CBX1/HP1-beta, CBX3/HP1-gamma and CBX5/HP1-alpha).
messages: The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry. The disease is caused by a LRIF1 homozygous variant resulting in loss of isoform 1, in the presence of an haplotype on chromosome 4 permissive for chromatin relaxation of the D4Z4 macrosatellite and inappropriate DUX4 expression. Deregulated expression of DUX4 in skeletal muscle can lead to cell death.
messages: Together with SMCHD1, involved in chromosome X inactivation in females by promoting the compaction of heterochromatin (PubMed:23542155). Also able to repress the ligand-induced transcriptional activity of retinoic acid receptor alpha (RARA), possibly through direct recruitment of histone deacetylases (PubMed:17455211). Also required for silencing of the DUX4 locus in somatic cells (PubMed:32467133).
messages: Widely expressed, with the highest expression levels in heart, liver and placenta.

9606:HSFX3
gene id: 9606:HSFX3
uniprot id: A0A1B0GWH4
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the HSF family.
messages: Nucleus

9606:CDKN2AIP
gene id: 9606:CDKN2AIP
uniprot id: J3KNE1
uniprot id: Q9NXV6
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the CARF family.
messages: Interacts with CDKN2A/p14ARF, p53/TP53 and MDM2. Interacts with CHEK2 and MAPK3. Interacts with XRN2 (PubMed:24462208).
messages: May be ubiquitinated.
messages: Regulates DNA damage response in a dose-dependent manner through a number of signaling pathways involved in cell proliferation, apoptosis and senescence.
messages: Ubiquitously expressed.
messages: Up-regulated during replicative senescence, in response to DNA-damaging drugs, telomere unprotection and oncogenic Ras-induced stress. Induced by proteasomal inhibitor MG132. Up-regulated at G1 and G2 stages of cell cycle.
messages: nucleoplasm

9606:UPK1B
gene id: 9606:UPK1B
uniprot id: O75841
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the tetraspanin (TM4SF) family.
messages: Bladder epithelium.
messages: Component of the asymmetric unit membrane (AUM); a highly specialized biomembrane elaborated by terminally differentiated urothelial cells. May play an important role in normal bladder epithelial physiology, possibly in regulating membrane permeability of superficial umbrella cells or in stabilizing the apical membrane through AUM/cytoskeletal interactions (By similarity).
messages: Heterodimer with uroplakin-3A (UPK3A) or uroplakin-3B (UPK3B).
messages: Membrane
messages: N-glycosylated with high-mannose oligosaccharides.

9606:YWHAE
gene id: 9606:YWHAE
uniprot id: P62258
uniprot id: V9HW98
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Interacts with HCV core protein.
messages: Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner (By similarity). Positively regulates phosphorylated protein HSF1 nuclear export to the cytoplasm (PubMed:12917326).
messages: Belongs to the 14-3-3 family.
messages: Cytoplasm
messages: Homodimer (PubMed:17085597). Heterodimerizes with YWHAZ (PubMed:16376338). Interacts with PKA-phosphorylated AANAT (PubMed:11427721). Interacts with ABL1 (phosphorylated form); the interaction retains it in the cytoplasm (PubMed:15696159). Interacts with ARHGEF28 (By similarity). Interacts with BEX3 (By similarity). Weakly interacts with CDKN1B (PubMed:12042314). Interacts with the 'Thr-369' phosphorylated form of DAPK2 (PubMed:26047703). Interacts with DENND1A (PubMed:26055712). Interacts with GAB2 (PubMed:19172738). Interacts with phosphorylated GRB10 (PubMed:15722337). Interacts with KSR1 (PubMed:10409742). Interacts with NDEL1 (By similarity). Interacts with PI4KB, TBC1D22A and TBC1D22B (PubMed:23572552). Interacts with the phosphorylated (by AKT1) form of SRPK2 (PubMed:19592491). Interacts with TIAM2. Interacts with the 'Ser-1134' and 'Ser-1161' phosphorylated form of SOS1 (By similarity). Interacts with ZFP36 (via phosphorylated form) (By similarity). Interacts with SLITRK1 (PubMed:19640509). Interacts with HSF1 (via phosphorylated form); this interaction promotes HSF1 sequestration in the cytoplasm in a ERK-dependent manner (PubMed:12917326). Interacts with RIPOR2 isoform 2 (PubMed:25588844). Interacts with KLHL22; required for the nuclear localization of KLHL22 upon amino acid starvation (PubMed:29769719). Interacts with CRTC1 (PubMed:30611118). Interacts with CRTC2 (probably when phosphorylated at 'Ser-171') (PubMed:30611118). Interacts with CRTC3 (probably when phosphorylated at 'Ser-162' and/or 'Ser-273') (PubMed:30611118). Interacts with ATP2B1 and ATP2B3; this interaction inhibits calcium-transporting ATPase activity (PubMed:18029012). Interacts with MEFV (PubMed:27030597).
messages: Melanosome
messages: Nucleus
messages: Unable to dimerize with YWHAZ.

9606:TSPY2
gene id: 9606:TSPY2
uniprot id: A6NGT6
uniprot id: A6NKD2
names: Function
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the nucleosome assembly protein (NAP) family.
messages: Cytoplasm
messages: Maps to a tandemly repeated region on chromosome Yp11; additionally at least one copy is reported originating from Yq. The gene is thought to be present with an inter-individual variation in copy number and between 20 and 60 copies per Y chromosome are expected. PubMed:12815422 reports 35 tandemly repeated gene copies on Yp11 originating from one individual.
messages: May be involved in sperm differentiation and proliferation.
messages: Nucleus

9606:MAP7D3
gene id: 9606:MAP7D3
uniprot id: Q8IWC1
names: Function
names: Induction
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the MAP7 family.
messages: Contaminating sequence. Potential poly-A sequence.
messages: Expression is cell cycle dependent with the highest levels during G1, S, and M phases, and low level in G2 phase.
messages: Interacts (via N-terminus coiled coil domains) with tubulin and microtubules.
messages: Promotes the assembly and stability of microtubules.
messages: spindle

9606:COMMD3
gene id: 9606:COMMD3
uniprot id: Q9UBI1
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cytoplasm
messages: Interacts (via COMM domain) with COMMD1 (via COMM domain). Interacts with NFKB1/p105. Interacts with CCDC22, CCDC93, SCNN1B, CUL3, CUL4A, CUL4B, CUL5.
messages: May modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes (PubMed:21778237). May down-regulate activation of NF-kappa-B (PubMed:15799966). Modulates Na(+) transport in epithelial cells by regulation of apical cell surface expression of amiloride-sensitive sodium channel (ENaC) subunits (PubMed:23637203).
messages: Nucleus
messages: Widely expressed with highest expression in thymus.

9606:SLC35F6
gene id: 9606:SLC35F6
uniprot id: Q8N357
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the SLC35F solute transporter family.
messages: Expressed in pancreatic ductal adenocarcinoma (PDAC) (at protein level). Strongly expressed in prostate and thyroid. Weakly expressed in lung, heart, liver and kidney.
messages: Interacts with SLC25A5.
messages: Involved in the maintenance of mitochondrial membrane potential in pancreatic ductal adenocarcinoma (PDAC) cells. Promotes pancreatic ductal adenocarcinoma (PDAC) cell growth. May play a role as a nucleotide-sugar transporter.
messages: Lysosome membrane
messages: Mitochondrion

9606:CDKN2A
gene id: 9606:CDKN2A
uniprot id: P42771
uniprot id: Q8N726
names: Caution
names: Disease Annotation
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acts as a negative regulator of the proliferation of normal cells by interacting strongly with CDK4 and CDK6. This inhibits their ability to interact with cyclins D and to phosphorylate the retinoblastoma protein.
messages: Barely detectable in non-tumor cells.
messages: Belongs to the CDKN2 cyclin-dependent kinase inhibitor family.
messages: Capable of inducing cell cycle arrest in G1 and G2 phases. Acts as a tumor suppressor. Binds to MDM2 and blocks its nucleocytoplasmic shuttling by sequestering it in the nucleolus. This inhibits the oncogenic action of MDM2 by blocking MDM2-induced degradation of p53 and enhancing p53-dependent transactivation and apoptosis. Also induces G2 arrest and apoptosis in a p53-independent manner by preventing the activation of cyclin B1/CDC2 complexes. Binds to BCL6 and down-regulates BCL6-induced transcriptional repression. Binds to E2F1 and MYC and blocks their transcriptional activator activity but has no effect on MYC transcriptional repression. Binds to TOP1/TOPOI and stimulates its activity. This complex binds to rRNA gene promoters and may play a role in rRNA transcription and/or maturation. Interacts with NPM1/B23 and promotes its polyubiquitination and degradation, thus inhibiting rRNA processing. Plays a role in inhibiting ribosome biogenesis, perhaps by binding to the nucleolar localization sequence of transcription termination factor TTF1, and thereby preventing nucleolar localization of TTF1 (By similarity). Interacts with COMMD1 and promotes its 'Lys63'-linked polyubiquitination. Interacts with UBE2I/UBC9 and enhances sumoylation of a number of its binding partners including MDM2 and E2F1. Binds to HUWE1 and represses its ubiquitin ligase activity. May play a role in controlling cell proliferation and apoptosis during mammary gland development.
messages: Cytoplasm
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry.
messages: Does not interact with cyclins, CDK1, CDK2, CDK4, CDK5 or CDK6. Binds to BCL6, E2F1, HUWE1, MDM2, MYC, NPM1/B23, TOP1/TOPOI and UBE2I/UBC9. Interacts with TBRG1 and COMMD1. Interacts with CDKN2AIP and E4F1. Interacts with CDK5RAP3 and MDM2; form a ternary complex involved in regulation of p53/TP53 (PubMed:16173922). Interacts with NOP53; the interaction is direct and promotes ARF nucleoplasmic relocalization and ubiquitin-mediated proteasomal degradation (PubMed:27323397). Interacts with TTF1 (via the N-terminal region (NRD) and a C-terminal region); the interaction is direct and inhibits the nucleolar localization of TTF1 (By similarity).
messages: Heterodimer with CDK4 or CDK6. Predominant p16 complexes contained CDK6. Interacts with CDK4 (both 'T-172'-phosphorylated and non-phosphorylated forms); the interaction inhibits cyclin D-CDK4 kinase activity. Interacts with ISCO2.
messages: Interacts with C1QBP.
messages: May be involved in regulation of autophagy and caspase-independent cell death; the short-lived mitochondrial isoform is stabilized by C1QBP.
messages: Mitochondrion
messages: Nucleus
messages: Phosphorylation seems to increase interaction with CDK4.
messages: The association between cutaneous and uveal melanomas in some families suggests that mutations in CDKN2A may account for a proportion of uveal melanomas. However, CDKN2A mutations are rarely found in uveal melanoma patients.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The proteins described here are encoded by the gene CDKN2A, but are completely unrelated in terms of sequence and function to cyclin-dependent kinase inhibitor 2A (AC P42771) which is encoded by the same gene.
messages: The proteins described here are encoded by the gene CDKN2A, but are completely unrelated in terms of sequence and function to tumor suppressor ARF (AC Q8N726) which is encoded by the same gene.
messages: Ubiquitinated in normal cells by TRIP12 via the ubiquitin fusion degradation (UFD) pathway, a process that mediates ubiquitination at the N-terminus, regardless of the absence of lysine residues. Ubiquitination leads to its proteasomal degradation. In cancer cells, however, TRIP12 is located in a different cell compartment, preventing ubiquitination and degradation.
messages: Widely expressed but not detected in brain or skeletal muscle. Isoform 3 is pancreas-specific.
messages: nucleolus
messages: nucleoplasm

9606:MTX2
gene id: 9606:MTX2
uniprot id: O75431
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the metaxin family.
messages: Interacts with MTX1/metaxin-1. Associates with the mitochondrial contact site and cristae organizing system (MICOS) complex, composed of at least MICOS10/MIC10, CHCHD3/MIC19, CHCHD6/MIC25, APOOL/MIC27, IMMT/MIC60, APOO/MIC23/MIC26 and QIL1/MIC13. This complex was also known under the names MINOS or MitOS complex. The MICOS complex associates with mitochondrial outer membrane proteins SAMM50, MTX1 and MTX2 (together described as components of the mitochondrial outer membrane sorting assembly machinery (SAM) complex) and DNAJC11, mitochondrial inner membrane protein TMEM11 and with HSPA9. The MICOS and SAM complexes together with DNAJC11 are part of a large protein complex spanning both membranes termed the mitochondrial intermembrane space bridging (MIB) complex.
messages: Involved in transport of proteins into the mitochondrion.
messages: Mitochondrion
messages: Mitochondrion outer membrane
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:CEP120
gene id: 9606:CEP120
uniprot id: Q8N960
names: Disease Annotation
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the CEP120 family.
messages: Interacts with TACC2, TACC3, CCDC52, TALPID3.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Plays a role in the microtubule-dependent coupling of the nucleus and the centrosome. Involved in the processes that regulate centrosome-mediated interkinetic nuclear migration (INM) of neural progenitors and for proper positioning of neurons during brain development. Also implicated in the migration and selfrenewal of neural progenitors. Required for centriole duplication and maturation during mitosis and subsequent ciliogenesis (By similarity). Required for the recruitment of CEP295 to the proximal end of new-born centrioles at the centriolar microtubule wall during early S phase in a PLK4-dependent manner (PubMed:27185865).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: centrosome

9606:ZNF581
gene id: 9606:ZNF581
uniprot id: Q9P0T4
names: Function
names: Subcellular Location Annotation
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:ADIPOR1
gene id: 9606:ADIPOR1
uniprot id: Q96A54
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the ADIPOR family.
messages: Cell membrane
messages: May form homooligomers and heterooligomers with ADIPOR2 (PubMed:12802337). Interacts with APPL2 (via BAR domain); hinders the accessibility of APPL1 to ADIPOR1; negatively regulates adiponectin signaling; ADIPOQ dissociates this interaction and facilitates the recruitment of APPL1 to ADIPOR1. Interacts with APPL1; ADIPOQ enhances this interaction; inhibites adiponectin-stimulated binding of APPL2 to ADIPOR1 (By similarity).
messages: Receptor for ADIPOQ, an essential hormone secreted by adipocytes that regulates glucose and lipid metabolism (PubMed:25855295, PubMed:12802337). Required for normal glucose and fat homeostasis and for maintaining a normal body weight. ADIPOQ-binding activates a signaling cascade that leads to increased AMPK activity, and ultimately to increased fatty acid oxidation, increased glucose uptake and decreased gluconeogenesis. Has high affinity for globular adiponectin and low affinity for full-length adiponectin (By similarity).
messages: The N-terminus is cytoplasmic and the C-terminus is extracellular, contrary to what is observed for G-protein coupled receptors. Unlike G-protein coupled receptors, transmembrane helices are not kinked or tilted relative to the plane of the membrane.
messages: Widely expressed (PubMed:16044242). Highly expressed in heart and skeletal muscle (PubMed:12802337). Expressed at intermediate level in brain, spleen, kidney, liver, placenta, lung and peripheral blood leukocytes (PubMed:12802337). Weakly expressed in colon, thymus and small intestine (PubMed:12802337).

9606:PARP9
gene id: 9606:PARP9
uniprot id: Q59ER9
uniprot id: Q8IXQ6
names: Activity Regulation
names: Disease Annotation
names: Domain
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: ADP-ribosylated by PARP14.
messages: ADP-ribosyltransferase which, in association with E3 ligase DTX3L, plays a role in DNA damage repair and in immune responses including interferon-mediated antiviral defenses (PubMed:16809771, PubMed:23230272, PubMed:26479788, PubMed:27796300). Within the complex, enhances DTX3L E3 ligase activity which is further enhanced by PARP9 binding to poly(ADP-ribose) (PubMed:28525742). In association with DTX3L and in presence of E1 and E2 enzymes, mediates NAD(+)-dependent mono-ADP-ribosylation of ubiquitin which prevents ubiquitin conjugation to substrates such as histones (PubMed:28525742). During DNA repair, PARP1 recruits PARP9/BAL1-DTX3L complex to DNA damage sites via PARP9 binding to ribosylated PARP1 (PubMed:23230272). Subsequent PARP1-dependent PARP9/BAL1-DTX3L-mediated ubiquitination promotes the rapid and specific recruitment of 53BP1/TP53BP1, UIMC1/RAP80, and BRCA1 to DNA damage sites (PubMed:23230272, PubMed:28525742). In response to DNA damage, PARP9-DTX3L complex is required for efficient non-homologous end joining (NHEJ); the complex function is negatively modulated by PARP9 activity (PubMed:28525742). Dispensable for B-cell receptor (BCR) assembly through V(D)J recombination and class switch recombination (CSR) (By similarity). In macrophages, positively regulates pro-inflammatory cytokines production in response to IFNG stimulation by suppressing PARP14-mediated STAT1 ADP-ribosylation and thus promoting STAT1 phosphorylation (PubMed:27796300). Also suppresses PARP14-mediated STAT6 ADP-ribosylation (PubMed:27796300).
messages: Belongs to the ARTD/PARP family.
messages: Binding to poly(ADP-ribose) does not affect its activity.
messages: Expressed in lymphocyte-rich tissues, spleen, lymph nodes, peripheral blood lymphocytes and colonic mucosa (PubMed:11110709, PubMed:16809771). Expressed in macrophages (PubMed:27796300). Also expressed in nonhematopoietic tissues such as heart and skeletal muscle (PubMed:11110709, PubMed:16809771). Isoform 2 is the predominant form (PubMed:11110709). Most abundantly expressed in lymphomas with a brisk host inflammatory response (PubMed:11110709, PubMed:16809771). In diffuse large B-cell lymphomas tumors, expressed specifically by malignant B-cells (PubMed:11110709, PubMed:16809771).
messages: Forms a stable complex with E3 ligase DTX3L; the interaction is required for PARP9 mediated ADP-ribosylation of ubiquitin (PubMed:12670957, PubMed:28525742). Interacts (via PARP catalytic domain) with DTX3L (via N-terminus) (PubMed:26479788). Forms a complex with STAT1 and DTX3L independently of IFNB1 or IFNG-mediated STAT1 'Tyr-701' phosphorylation (PubMed:26479788). Forms a complex with STAT1, DTX3L and histone H2B H2BC9/H2BJ; the interaction is likely to induce H2BC9/H2BJ ubiquitination (PubMed:26479788). Interacts (via N-terminus) with STAT1 (PubMed:26479788). Interacts with PARP14 in IFNG-stimulated macrophages; the interaction prevents PARP14-mediated STAT1 and STAT6 ADP-riboslylation (PubMed:27796300). Interacts with PARP1 (when poly-ADP-ribosylated) (PubMed:23230272).
messages: Macro domains 1 and 2 may be involved in the binding to poly(ADP-ribose) (PubMed:28525742, PubMed:26479788). Macro domain 2 is required for recruitment to DNA damage sites (PubMed:23230272). Macro domains 1 and 2 are probably dispensable for the interaction with STAT1 and DTX3L and for STAT1 phosphorylation (PubMed:26479788).
messages: Nucleus
messages: Overexpressed at significantly higher levels in fatal high-risk diffuse large B-cell lymphomas (DLB-CL) compared to cured low-risk tumors. Overexpression in B-cell lymphoma transfectants may promote malignant B-cell migration. May therefore be involved in promoting B-cell migration and dissemination of high-risk DLB-CL tumors (PubMed:11110709).
messages: Up-regulated by IFNG in macrophages and in B-cell lymphoma cell lines (PubMed:16809771, PubMed:27796300, PubMed:26479788). Up-regulated by IFNB1 or viral infection (PubMed:26479788). Down-regulated by IL4 in macrophages (PubMed:27796300).
messages: cytosol

9606:GPR158
gene id: 9606:GPR158
uniprot id: Q5T848
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the G-protein coupled receptor 3 family.
messages: Cell membrane
messages: Homodimer (PubMed:31189666, PubMed:34815401, PubMed:34793198). Associates with the RGS7-GNB5 complex, promoting its localization to the cell membrane and regulating its GTPase activator activity (PubMed:31189666, PubMed:34815401, PubMed:34793198). Interacts (via VCPWE motifs) with GNAO1 (PubMed:31189666). Interacts with GPC4 (By similarity). Interacts with EGFLAM (By similarity).
messages: Metabotropic receptor for glycine that controls synapse formation and function in the brain (PubMed:36996198). Acts as an atypical G-protein coupled receptor that recruits and regulates the RGS7-GNB5 complex instead of activating G proteins (PubMed:31189666, PubMed:36996198). In absence of glycine ligand, promotes the GTPase activator activity of RGS7, increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form (PubMed:36996198). Glycine-binding changes the conformation of the intracellular surface, inhibiting the GTPase activator activity of the RGS7-GNB5 complex, promoting G protein alpha subunits into their active GTP-bound form and regulating cAMP levels (PubMed:36996198). Also able to bind taurine, a compound closely related to glycine, but with a two-fold lower affinity (PubMed:36996198). Glycine receptor-dependent regulation of cAMP controls key ion channels, kinases and neurotrophic factors involved in neuronal excitability and synaptic transmission (PubMed:36996198). Plays a pivotal role in regulating mood and cognition via its ability to regulate neuronal excitability in L2/L3 pyramidal neurons of the prefrontal cortex (By similarity). Also involved in spatial learning by regulating hippocampal CA1 neuronal excitability (By similarity). Acts as a synaptic organizer in the hippocampus, required for proper mossy fiber-CA3 neurocircuitry establishment, structure and function: induces presynaptic differentiation in contacting axons via its interaction with GPC4 (By similarity). In addition to glycine, may also act as a receptor for osteocalcin (BGLAP) hormone: osteocalcin-binding initiates a signaling response that prevents neuronal apoptosis in the hippocampus and regulates the synthesis of neurotransmitters (By similarity).
messages: Nucleus
messages: Postsynaptic cell membrane
messages: Presynaptic cell membrane
messages: The Cache-like region shares similarity with the Cache domain, a well-known receptor for amino acids (PubMed:34793198). It acts as a ligand-binding module that recognizes and binds glycine and taurine (PubMed:36996198).

9606:COL23A1
gene id: 9606:COL23A1
uniprot id: Q86Y22
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: Cell membrane
messages: Homotrimer.
messages: Undergoes proteolytic cleavage by furin protease to yield a 60 kDa soluble form that forms a homotrimer and exhibits a low affinity interaction with heparin.

9606:CPXM1
gene id: 9606:CPXM1
uniprot id: Q96SM3
names: Cofactor
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the peptidase M14 family.
messages: Binds 1 zinc ion per subunit.
messages: May be involved in cell-cell interactions. No carboxypeptidase activity was found yet (By similarity).
messages: Secreted

9606:CCDC159
gene id: 9606:CCDC159
uniprot id: P0C7I6
names: Sequence Caution
messages: Cloning artifact.
messages: Intron retention.

9606:PIANP
gene id: 9606:PIANP
uniprot id: Q8IYJ0
names: Function
names: PTM
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Acts as a ligand for PILRA in neural tissues, where it may be involved in immune regulation.
messages: Mainly expressed in adult brain and cerebellum. Weaker expression in fetal brain and virtually no expression in spleen, heart, kidney, liver and dorsal ganglion relative to brain.
messages: Membrane
messages: O-glycosylation at Thr-140 is essential for recognition by PILRA.

9606:GJA8
gene id: 9606:GJA8
uniprot id: P48165
uniprot id: X5D7G1
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: A connexon is composed of a hexamer of connexins.
messages: A hemichannel or connexon is composed of a hexamer of connexins. A functional gap junction is formed by the apposition of two hemichannels. Forms heteromeric channels with GJA3.
messages: Belongs to the connexin family. Alpha-type (group II) subfamily.
messages: Cell membrane
messages: Eye lens.
messages: Membrane
messages: One gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell.
messages: Structural component of eye lens gap junctions (PubMed:18006672, PubMed:19756179). Gap junctions are dodecameric channels that connect the cytoplasm of adjoining cells. They are formed by the docking of two hexameric hemichannels, one from each cell membrane (By similarity). Small molecules and ions diffuse from one cell to a neighboring cell via the central pore (PubMed:18006672, PubMed:19756179).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: gap junction

9606:CYREN
gene id: 9606:CYREN
uniprot id: Q9BWK5
names: Domain
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Cell-cycle-specific regulator of classical non-homologous end joining (NHEJ) of DNA double-strand break (DSB) repair, which can act both as an activator or inhibitor of NHEJ, depending on the cell cycle phase (PubMed:24610814, PubMed:28959974). Acts as a regulator of DNA repair pathway choice by specifically inhibiting classical NHEJ during the S and G2 phases, thereby promoting error-free repair by homologous recombination during cell cycle phases when sister chromatids are present (PubMed:28959974). Preferentially protects single-stranded overhangs at break sites by inhibiting classical NHEJ, thereby creating a local environment that favors homologous recombination (PubMed:28959974). Acts via interaction with XRCC5/Ku80 and XRCC6/Ku70 (PubMed:28959974). In contrast, acts as an activator of NHEJ during G1 phase of the cell cycle: promotes classical NHEJ in G1 phase cells via multivalent interactions that increase the affinity of DNA damage response proteins for DSB-associated chromatin. Also involved in immunoglobulin V(D)J recombination (By similarity). May also act as an indirect regulator of proteasome (By similarity).
messages: Chromosome
messages: Cytoplasm
messages: Does not interact with XRCC5/Ku80 and XRCC6/Ku70 heterodimer (PubMed:24610814).
messages: Interacts (via KBM motif) with XRCC5/Ku80 and XRCC6/Ku70 heterodimer (PubMed:24610814, PubMed:27063109, PubMed:28959974). Interacts (via XLF motif) with TRIM28/KAP1, ATM, MRE11, NBN and RAD50 (By similarity).
messages: Interacts (via KBM motif) with XRCC5/Ku80 and XRCC6/Ku70 heterodimer (PubMed:24610814, PubMed:28959974).
messages: Nucleus
messages: The KBM (Ku-binding motif) mediates interaction with XRCC5/Ku80 and XRCC6/Ku70 and recruitment to DNA damage sites.
messages: The XLM (XLF-like motif) mediates interaction with DNA damage response proteins TRIM28/KAP1, ATM and members of the MRN complex (MRE11, NBN and RAD50).

9606:MCCC2
gene id: 9606:MCCC2
uniprot id: A0A140VK29
uniprot id: Q9HCC0
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the AccD/PCCB family.
messages: Carboxyltransferase subunit of the 3-methylcrotonyl-CoA carboxylase, an enzyme that catalyzes the conversion of 3-methylcrotonyl-CoA to 3-methylglutaconyl-CoA, a critical step for leucine and isovaleric acid catabolism.
messages: Mitochondrion matrix
messages: Probably a dodecamer composed of six biotin-containing alpha subunits (MCCC1) and six beta (MCCC2) subunits.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:WAC
gene id: 9606:WAC
uniprot id: Q9BTA9
names: Disease Annotation
names: Function
names: Miscellaneous
names: PTM
names: Sequence Caution
names: Subcellular Location Annotation
names: Subunit
messages: Acts as a linker between gene transcription and histone H2B monoubiquitination at 'Lys-120' (H2BK120ub1) (PubMed:21329877). Interacts with the RNA polymerase II transcriptional machinery via its WW domain and with RNF20-RNF40 via its coiled coil region, thereby linking and regulating H2BK120ub1 and gene transcription (PubMed:21329877). Regulates the cell-cycle checkpoint activation in response to DNA damage (PubMed:21329877). Positive regulator of amino acid starvation-induced autophagy (PubMed:22354037). Also acts as a negative regulator of basal autophagy (PubMed:26812014). Positively regulates MTOR activity by promoting, in an energy-dependent manner, the assembly of the TTT complex composed of TELO2, TTI1 and TTI2 and the RUVBL complex composed of RUVBL1 and RUVBL2 into the TTT-RUVBL complex. This leads to the dimerization of the mTORC1 complex and its subsequent activation (PubMed:26812014). May negatively regulate the ubiquitin proteasome pathway (PubMed:21329877).
messages: Defects in WAC are the cause of a form of intellectual disability characterized by hypotonia, behavioral problems and distinctive facial dysmorphisms including a square-shaped face, deep set eyes, long palpebral fissures, and a broad mouth and chin.
messages: Interacts (via coiled coil domain) with RNF20, RNF40 and UBE2A (PubMed:21329877). Interacts (via WW domain) with RNA polymerase II (PubMed:21329877). Interacts with MTOR and other components of the MTOR pathway including RPTOR, RUVBL1, RUVBL2, TTI1 and TTI2 (PubMed:26812014).
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Nucleus
messages: Nucleus speckle
messages: Phosphorylated on tyrosine residues.
messages: Probable cloning artifact.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:CST9
gene id: 9606:CST9
uniprot id: Q5W186
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the cystatin family.
messages: Expressed in heart, placenta, lung, liver, skeletal muscle and pancreas (PubMed:12535658). Not expressed in brain (PubMed:12535658). Expressed in epididymis, kidney, testis, spinal cord, and thymus with a strong expression in epididymis and kidney and a weak expression in the spinal cord and thymus (PubMed:20565543).
messages: May be involved in testis development (By similarity). May play a role in hematopoietic differentiation or inflammation (PubMed:12535658). Has immunomodulatory and antimicrobial functions against Francisella tularensis, a Gram-negative bacteria (PubMed:23922243).
messages: Secreted
messages: Up-regulated by bacterial lipopolysaccharides (LPS), in some cancer cells such as promyelocytic leukemia cells (HL-60) or myelomonocytic leukemia cells (U-937).

9606:ZNF518A
gene id: 9606:ZNF518A
uniprot id: Q6AHZ1
names: Function
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: Contaminating sequence. Potential poly-A sequence.
messages: Nucleus
messages: Through its association with the EHMT1-EHMT2/G9A and PRC2/EED-EZH2 histone methyltransferase complexes may function in gene silencing, regulating repressive post-translational methylation of histone tails at promoters of target genes.

9606:ALPK1
gene id: 9606:ALPK1
uniprot id: Q96QP1
names: Activity Regulation
names: Caution
names: Disease Annotation
names: Function
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the protein kinase superfamily. Alpha-type protein kinase family. ALPK subfamily.
messages: D-glycero-beta-D-manno-heptose 1,7-bisphosphate (HBP) was initially thought to constitute the bacterial pathogen-associated molecular pattern metabolite (PAMP) triggering the ALPK1-TIFA innate immunune response (PubMed:28877472, PubMed:28222186). It was however shown that ADP-D-glycero-beta-D-manno-heptose (ADP-Heptose) constitutes the main PAMP that activates the kinase activity of ALPK1 (PubMed:30111836).
messages: Highly expressed in liver. Expressed in the optic nerve and retinal pigmented epithelium. Lower expression is observed in the macula and extramacular retina (PubMed:30967659).
messages: Intron retention.
messages: Serine/threonine-protein kinase activity is stimulated upon ADP-D-glycero-beta-D-manno-heptose (ADP-Heptose)-binding.
messages: Serine/threonine-protein kinase that detects bacterial pathogen-associated molecular pattern metabolites (PAMPs) and initiates an innate immune response, a critical step for pathogen elimination and engagement of adaptive immunity (PubMed:28877472, PubMed:28222186, PubMed:30111836). Specifically recognizes and binds ADP-D-glycero-beta-D-manno-heptose (ADP-Heptose), a potent PAMP present in all Gram-negative and some Gram-positive bacteria (PubMed:30111836). ADP-Heptose-binding stimulates its kinase activity to phosphorylate and activate TIFA, triggering pro-inflammatory NF-kappa-B signaling (PubMed:30111836). May be involved in monosodium urate monohydrate (MSU)-induced inflammation by mediating phosphorylation of unconventional myosin MYO9A (PubMed:27169898). May also play a role in apical protein transport by mediating phosphorylation of unconventional myosin MYO1A (PubMed:15883161). May play a role in ciliogenesis (PubMed:30967659).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: centrosome
messages: cilium
messages: cytosol
messages: spindle pole

9606:SLC43A3
gene id: 9606:SLC43A3
uniprot id: B0AZP8
uniprot id: Q8NBI5
names: Activity Regulation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: 6-mercaptopurine-transport is inhibited by 6-thioguanine, 6-methylmercaptopurine and decynium-22.
messages: Adenine transport is strongly inhibited by decynium-22.
messages: Basolateral cell membrane
messages: Belongs to the SLC43A transporter (TC 2.A.1.44) family.
messages: Membrane
messages: Sodium-independent purine-selective nucleobase transporter which mediates the equilibrative transport of extracellular purine nucleobase adenine (PubMed:30910793). Mediates the influx and efflux of the purine nucleobase analog drug 6-mercaptopurine across the membrane (PubMed:30910793).
messages: Sodium-independent purine-selective nucleobase transporter which mediates the equilibrative transport of extracellular purine nucleobases such as adenine, guanine and hypoxanthine (PubMed:26455426, PubMed:32339528). May regulate fatty acid (FA) transport in adipocytes, acting as a positive regulator of FA efflux and as a negative regulator of FA uptake (By similarity).
messages: Widely expressed with highest levels in the liver and lung, followed by the pancreas (PubMed:26455426). Highly expressed in macrophages (Ref.1).

9606:BPIFB3
gene id: 9606:BPIFB3
uniprot id: P59826
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the BPI/LBP/Plunc superfamily. BPI/LBP family.
messages: Cytoplasm
messages: Detected in nasal septal epithelium.
messages: May have the capacity to recognize and bind specific classes of odorants. May act as a carrier molecule, transporting odorants across the mucus layer to access receptor sites. May serve as a primary defense mechanism by recognizing and removing potentially harmful odorants or pathogenic microorganisms from the mucosa or clearing excess odorant from mucus to enable new odorant stimuli to be received (By similarity).
messages: Secreted

9606:DDX43
gene id: 9606:DDX43
uniprot id: Q9NXZ2
names: Similarity
names: Tissue Specificity
messages: Belongs to the DEAD box helicase family.
messages: Expressed in testis. Expressed in many tumors of various histological types at a level that is 100-fold higher than the level observed in normal tissues except testis.

9606:CPB1
gene id: 9606:CPB1
uniprot id: P15086
names: Cofactor
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the peptidase M14 family.
messages: Binds 1 zinc ion per subunit.
messages: Pancreas.
messages: Secreted
messages: Zymogen granule lumen

9606:EIF5AL1
gene id: 9606:EIF5AL1
uniprot id: Q6IS14
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the eIF-5A family.
messages: Cytoplasm
messages: Endoplasmic reticulum membrane
messages: Lys-50 undergoes hypusination, a unique post-translational modification that consists in the addition of a butylamino group from spermidine to lysine side chain, leading to the formation of the unusual amino acid hypusine. eIF-5As are the only known proteins to undergo this modification, which is essential for their function.
messages: Nucleus
messages: Translation factor that promotes translation elongation and termination, particularly upon ribosome stalling at specific amino acid sequence contexts (By similarity). Binds between the exit (E) and peptidyl (P) site of the ribosome and promotes rescue of stalled ribosome: specifically required for efficient translation of polyproline-containing peptides as well as other motifs that stall the ribosome. Acts as ribosome quality control (RQC) cofactor by joining the RQC complex to facilitate peptidyl transfer during CAT tailing step (By similarity). Also involved in actin dynamics and cell cycle progression, mRNA decay and probably in a pathway involved in stress response and maintenance of cell wall integrity (By similarity).

9606:UBXN4
gene id: 9606:UBXN4
uniprot id: Q92575
names: Domain
names: Function
names: Induction
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: By ER stress-inducing agents such as tunicamycin, thapsigargin, DTT and the calcium ionophore A23187 (at protein level).
messages: Directly interacts with VCP. Interacts with UBQLN1. Forms a complex with VCP and UBQLN1.
messages: Endoplasmic reticulum membrane
messages: Expressed in many tissues, including heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. Accumulates in Alzheimer disease-afflicted brains (at protein level).
messages: Involved in endoplasmic reticulum-associated protein degradation (ERAD). Acts as a platform to recruit both UBQLN1 and VCP to the ER during ERAD (PubMed:19822669).
messages: Nucleus envelope
messages: The UBX domain is required for interaction with VCP.
messages: The intramembrane domain also contains the signal for ER targeting.

9606:ILF2
gene id: 9606:ILF2
uniprot id: Q12905
names: Function
names: PTM
names: Sequence Caution
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Interacts with Japanese encephalitis virus protein NS3.
messages: (Microbial infection) Interacts with enterovirus 71 protein 2B; this interaction relocalizes ILF2 from the nucleus to the cytoplasm.
messages: (Microbial infection) Plays a positive role in HIV-1 virus production by binding to and thereby stabilizing HIV-1 RNA, together with ILF3.
messages: Chimeric cDNA.
messages: Chromatin-interacting protein that forms a stable heterodimer with interleukin enhancer-binding factor 3/ILF3 and plays a role in several biological processes including transcription, innate immunity or cell growth (PubMed:18458058, PubMed:31212927). Essential for the efficient reshuttling of ILF3 (isoform 1 and isoform 2) into the nucleus. Together with ILF3, forms an RNA-binding complex that is required for mitotic progression and cytokinesis by regulating the expression of a cluster of mitotic genes. Mechanistically, competes with STAU1/STAU2-mediated mRNA decay (PubMed:32433969). Also plays a role in the inhibition of various viruses including Japanese encephalitis virus or enterovirus 71.
messages: Cytoplasm
messages: Forms heterodimers with ILF3 (PubMed:18458058). ILF2-ILF3 heterodimers may also bind to PRKDC/XRCC7: this may stabilize the interaction of PRKDC/XRCC7 and the heterodimeric complex of G22P1/KU70 and XRCC5/KU80. Forms a complex with ILF3, YLPM1, KHDRBS1, RBMX, NCOA5 and PPP1CA. Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Interacts with IGF2BP1. Interacts with CRBN; this interaction promotes ubiquitination and subsequent degradation of ILF2 (PubMed:33009960).
messages: Nucleus
messages: Ubiquitinated at Lys-45 by CRBN with polyubiquitin chains by the CUL4-RING E3 ligase (CRL4-CRBN) and then degraded by the proteasome.
messages: nucleolus

9606:GOLGA6A
gene id: 9606:GOLGA6A
uniprot id: Q9NYA3
names: Caution
names: Similarity
names: Tissue Specificity
messages: Belongs to the GOLGA6 family.
messages: Highly expressed in seminiferous tubes in testis. Highly expressed in spermatids, barely detectable in late pachytene spermatocytes, and not detectable in spermatogonia. Detected at intermediate levels in pancreas and lymph nodes, and at much lower levels in spleen, peripheral blood leukocytes, skeletal muscle, liver, lung, placenta, brain and heart.
messages: Maps to a duplicated region on chromosome 15; the gene is present in at least 4 almost identical copies.

9606:FGF7
gene id: 9606:FGF7
uniprot id: A0A7U3JVY2
uniprot id: P21781
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the heparin-binding growth factors family.
messages: Epithelial cell.
messages: Interacts with FGFBP1. Interacts with FGFR2. Affinity between fibroblast growth factors (FGFs) and their receptors is increased by heparan sulfate glycosaminoglycans that function as coreceptors.
messages: Plays an important role in the regulation of embryonic development, cell proliferation and cell differentiation. Required for normal branching morphogenesis. Growth factor active on keratinocytes. Possible major paracrine effector of normal epithelial cell proliferation.
messages: Secreted

9606:ADCY6
gene id: 9606:ADCY6
uniprot id: O43306
names: Activity Regulation
names: Cofactor
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Activated by forskolin (PubMed:17916776, PubMed:17110384). Inhibited by calcium ions, already at micromolar concentrations (By similarity). Inhibited by adenosine, AMP and their analogs (By similarity). Activated by GNAS (PubMed:17110384). Is further activated by the complex formed by GNB1 and GNG2 (PubMed:17110384). Phosphorylation by RAF1 results in its activation (By similarity).
messages: Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.
messages: Binds 2 magnesium ions per subunit. Is also active with manganese (in vitro).
messages: Catalyzes the formation of the signaling molecule cAMP downstream of G protein-coupled receptors (PubMed:17916776, PubMed:17110384). Functions in signaling cascades downstream of beta-adrenergic receptors in the heart and in vascular smooth muscle cells (PubMed:17916776). Functions in signaling cascades downstream of the vasopressin receptor in the kidney and has a role in renal water reabsorption. Functions in signaling cascades downstream of PTH1R and plays a role in regulating renal phosphate excretion. Functions in signaling cascades downstream of the VIP and SCT receptors in pancreas and contributes to the regulation of pancreatic amylase and fluid secretion (By similarity). Signaling mediates cAMP-dependent activation of protein kinase PKA. This promotes increased phosphorylation of various proteins, including AKT. Plays a role in regulating cardiac sarcoplasmic reticulum Ca(2+) uptake and storage, and is required for normal heart ventricular contractibility. May contribute to normal heart function (By similarity). Mediates vasodilatation after activation of beta-adrenergic receptors by isoproterenol (PubMed:17916776). Contributes to bone cell responses to mechanical stimuli (By similarity).
messages: Cell membrane
messages: Detected in peripheral blood mononuclear leukocytes (at protein level) (PubMed:17916776). Detected in thyroid (PubMed:10978539).
messages: Part of a complex containing AKAP5, ADCY5, PDE4C and PKD2 (By similarity). Interacts with RAF1 (PubMed:15385642). Interacts (via cytoplasmic N-terminus) with GNAS, GNB1 and GNG2 (PubMed:17110384).
messages: Phosphorylation by RAF1 increases enzyme activity. Phosphorylation by PKA at Ser-662 inhibits the GNAS-mediated increase in catalytic activity. Phosphorylation by PKC at Ser-556, Ser-662 and Thr-919 inhibits catalytic activity.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The protein contains two modules with six transmembrane helices each; both are required for catalytic activity. Isolated N-terminal or C-terminal guanylate cyclase domains have no catalytic activity, but when they are brought together, enzyme activity is restored. The active site is at the interface of the two domains. Both contribute substrate-binding residues, but the catalytic metal ions are bound exclusively via the N-terminal guanylate cyclase domain.
messages: cilium
messages: stereocilium

9606:LRR1
gene id: 9606:LRR1
uniprot id: Q96L50
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Component of the probable ECS(LRR1) E3 ubiquitin-protein ligase complex which contains CUL2, RBX1, Elongin BC complex and LRR1. Interacts with CUL2, RBX1, ELOB and ELOC.
messages: Nucleus
messages: Substrate recognition subunit of an ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:15601820). ECS(LRR1) ubiquitinates MCM7 and promotes CMG replisome disassembly by VCP and chromatin extraction during S-phase (By similarity). May negatively regulate the 4-1BB-mediated signaling cascades which result in the activation of NK-kappaB and JNK1 (PubMed:11804328).
messages: Ubiquitous. Maximal expression was seen in the heart and skeletal muscle and minimal expression seen in the kidney.

9606:IGIP
gene id: 9606:IGIP
uniprot id: A6NJ69
names: Caution
names: Function
names: Subcellular Location Annotation
messages: Enhances IgA secretion from B-cells stimulated via CD40.
messages: It is uncertain whether Met-1 or Met-7 is the initiator.
messages: Secreted

9606:ARF4
gene id: 9606:ARF4
uniprot id: P18085
names: Caution
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the small GTPase superfamily. Arf family.
messages: Forms a complex containing RAB11A, ASAP1, RAB3IP, RAP11FIP3 and ARF4; the complex promotes preciliary trafficking; the complex binds to RHO in photoreceptor cells and promotes RHO ciliary transport.
messages: GTP-binding protein that functions as an allosteric activator of the cholera toxin catalytic subunit, an ADP-ribosyltransferase. Involved in protein trafficking; may modulate vesicle budding and uncoating within the Golgi apparatus. Part of the ciliary targeting complex containing Rab11, ASAP1, Rabin8/RAB3IP, RAB11FIP3 and ARF4, which direct preciliary vesicle trafficking to mother centriole and ciliogenesis initiation (PubMed:25673879).
messages: Golgi apparatus
messages: Membrane
messages: Was originally thought to be ARF2.

9606:DMRT2
gene id: 9606:DMRT2
uniprot id: Q05C20
uniprot id: Q5HYK2
uniprot id: Q9Y5R5
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the DMRT family.
messages: Expressed in testis, kidney and skeletal muscle.
messages: Homodimer.
messages: Nucleus
messages: Produced by DMRT2 bicistronic transcripts (AF284223/AF284224) from non-overlapping reading frame, according to PubMed:10729224.
messages: Transcriptional activator that directly regulates early activation of the myogenic determination gene MYF5 by binding in a sequence-specific manner to the early epaxial enhancer element of it. Involved in somitogenesis during embryogenesis and somite development and differentiation into sclerotome and dermomyotome. Required for the initiation and/or maintenance of proper organization of the sclerotome, dermomyotome and myotome (By similarity).

9606:MYH8
gene id: 9606:MYH8
uniprot id: P13535
names: Disease Annotation
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.
messages: Limited proteolysis of myosin heavy chain produces 1 light meromyosin (LMM) and 1 heavy meromyosin (HMM). HMM can be further cleaved into 2 globular subfragments (S1) and 1 rod-shaped subfragment (S2).
messages: Muscle contraction.
messages: Muscle myosin is a hexameric protein that consists of 2 heavy chain subunits (MHC), 2 alkali light chain subunits (MLC) and 2 regulatory light chain subunits (MLC-2).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The rodlike tail sequence is highly repetitive, showing cycles of a 28-residue repeat pattern composed of 4 heptapeptides, characteristic for alpha-helical coiled coils.
messages: myofibril

9606:JAK1
gene id: 9606:JAK1
uniprot id: A0A8V8TPQ9
uniprot id: P23458
names: Cofactor
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Autophosphorylated (PubMed:7615558). Phosphorylated by TYK2 on tyrosine residues in response to type-I interferon signaling, leading to its activation (PubMed:8232552). Phosphorylated on tyrosine residues in response to interferon gamma signaling (PubMed:7615558). Dephosphorylation of Tyr-1034 and Tyr-1035 by PTPN2 negatively regulates cytokine-mediated signaling (PubMed:11909529).
messages: Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily.
messages: Endomembrane system
messages: Expressed at higher levels in primary colon tumors than in normal colon tissue. The expression level in metastatic colon tumors is comparable to the expression level in normal colon tissue.
messages: Interacts with IL31RA (PubMed:15194700). Interacts with IFNGR1 (PubMed:7615558). Interacts with JAKMIP1 (PubMed:15277531). Interacts with SHB (PubMed:12200137). Interacts (via N-terminus) with IL2RB and IL10RA (via its cytoplasmic domain) (PubMed:12133952). Interacts with FER (By similarity).
messages: Mn(2+) was used in the in vitro kinase assay but Mg(2+) is likely to be the in vivo cofactor.
messages: The FERM domain mediates interaction with JAKMIP1.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The protein kinase 1 domain is also called the pseudokinase domain and has a regulatory role through the transactivation of other JAK kinases associated with signaling receptors.
messages: The protein kinase 2 domain is the catalytically active domain.
messages: Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway (PubMed:8232552, PubMed:7615558, PubMed:28111307, PubMed:32750333, PubMed:16239216). Kinase partner for the interleukin (IL)-2 receptor (PubMed:11909529) as well as interleukin (IL)-10 receptor (PubMed:12133952). Kinase partner for the type I interferon receptor IFNAR2 (PubMed:8232552, PubMed:7615558, PubMed:28111307, PubMed:32750333, PubMed:16239216). In response to interferon-binding to IFNAR1-IFNAR2 heterodimer, phosphorylates and activates its binding partner IFNAR2, creating docking sites for STAT proteins (PubMed:7759950). Directly phosphorylates STAT proteins but also activates STAT signaling through the transactivation of other JAK kinases associated with signaling receptors (PubMed:8232552, PubMed:16239216, PubMed:32750333).
messages: Ubiquitinated by RNF125; leading to its degradation by the proteasome.

9606:ARHGDIA
gene id: 9606:ARHGDIA
uniprot id: J3QQX2
uniprot id: P52565
uniprot id: V9HWE8
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the Rho GDI family.
messages: Controls Rho proteins homeostasis. Regulates the GDP/GTP exchange reaction of the Rho proteins by inhibiting the dissociation of GDP from them, and the subsequent binding of GTP to them. Retains Rho proteins such as CDC42, RAC1 and RHOA in an inactive cytosolic pool, regulating their stability and protecting them from degradation. Actively involved in the recycling and distribution of activated Rho GTPases in the cell, mediates extraction from membranes of both inactive and activated molecules due its exceptionally high affinity for prenylated forms. Through the modulation of Rho proteins, may play a role in cell motility regulation. In glioma cells, inhibits cell migration and invasion by mediating the signals of SEMA5A and PLXNB3 that lead to inactivation of RAC1.
messages: Cytoplasm
messages: Monomer (By similarity). Interacts with FER (PubMed:21122136). Interacts with PLXNB3 (By similarity). Forms a heterodimer with RAC1 (PubMed:23434736). Interacts with RHOA, the affinity is increased by three orders of magnitude when RHOA is prenylated (PubMed:20628200, PubMed:20400958, PubMed:26646181, PubMed:23434736). Interacts with PSMD10; the interaction increases ARHGDIA association with RHOA, leading to ARHGDIA-mediated inactivation of RHOA and ROCK and prolonged AKT activation (PubMed:20628200). Interacts with KANK2; the interaction is direct and may regulate the interaction of ARHGDIA with RHOA, RAC1 and CDC42 (PubMed:25961457). Interacts with RHOC (PubMed:20400958). Interacts with CDC42 (PubMed:23434736). Interacts with NGFR (via death domain); NGFR binding decreases the affinity for RHOA (PubMed:26646181).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:PARP3
gene id: 9606:PARP3
uniprot id: Q9Y6F1
names: Activity Regulation
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Auto-mono-ADP-ribosylated.
messages: Belongs to the ARTD/PARP family.
messages: Chromosome
messages: Interacts with PARP1; leading to activate PARP1 in absence of DNA (PubMed:16924674, PubMed:20064938). Interacts with PRKDC (PubMed:16924674). Interacts with XRCC5/Ku80; the interaction is dependent on nucleic acids (PubMed:16924674, PubMed:24598253). Interacts with XRCC6/Ku70; the interaction is dependent on nucleic acids (PubMed:16924674, PubMed:24598253). Interacts with EZH2, HDAC1, HDAC2, SUZ12, YY1, LRIG3 and LIG4 (PubMed:16924674).
messages: Mono-ADP-ribosyltransferase activity of PARP3 is selectively inhibited by ME0328 compound; ME0328 does not inhibit other ARTD/PARP enzymes, such as PARP1 (PubMed:23742272). Mono-ADP-ribosyltransferase is strongly inhibited by KU0058948 compound (PubMed:19354255).
messages: Mono-ADP-ribosyltransferase that mediates mono-ADP-ribosylation of target proteins and plays a key role in the response to DNA damage (PubMed:16924674, PubMed:20064938, PubMed:21211721, PubMed:21270334, PubMed:25043379, PubMed:24598253, PubMed:28447610, PubMed:19354255, PubMed:23742272). Mediates mono-ADP-ribosylation of glutamate, aspartate or lysine residues on target proteins (PubMed:20064938, PubMed:25043379). In contrast to PARP1 and PARP2, it is not able to mediate poly-ADP-ribosylation (PubMed:25043379). Involved in DNA repair by mediating mono-ADP-ribosylation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism, such as histone H2B, XRCC5 and XRCC6 (PubMed:16924674, PubMed:24598253). ADP-ribosylation follows DNA damage and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks (PubMed:16924674, PubMed:21211721, PubMed:21270334). Involved in single-strand break repair by catalyzing mono-ADP-ribosylation of histone H2B on 'Glu-2' (H2BE2ADPr) of nucleosomes containing nicked DNA (PubMed:27530147). Cooperates with the XRCC5-XRCC6 (Ku80-Ku70) heterodimer to limit end-resection thereby promoting accurate NHEJ (PubMed:24598253). Suppresses G-quadruplex (G4) structures in response to DNA damage (PubMed:28447610). Associates with a number of DNA repair factors and is involved in the response to exogenous and endogenous DNA strand breaks (PubMed:16924674, PubMed:21211721, PubMed:21270334). Together with APLF, promotes the retention of the LIG4-XRCC4 complex on chromatin and accelerate DNA ligation during non-homologous end-joining (NHEJ) (PubMed:21211721). May link the DNA damage surveillance network to the mitotic fidelity checkpoint (PubMed:16924674). Acts as a negative regulator of immunoglobulin class switch recombination, probably by controlling the level of AICDA /AID on the chromatin (By similarity). In addition to proteins, also able to ADP-ribosylate DNA: medi…
messages: Most abundant isoform.
messages: Nucleus
messages: Widely expressed; the highest levels are in the kidney, skeletal muscle, liver, heart and spleen; also detected in pancreas, lung, placenta, brain, leukocytes, colon, small intestine, ovary, testis, prostate and thymus.
messages: centriole
messages: centrosome

9606:PTK7
gene id: 9606:PTK7
uniprot id: Q13308
names: Domain
names: Function
names: Induction
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.
messages: Cell junction
messages: Higher expression in cell lines established from normal non-tumorigenic tissues compared to cell lines established from highly metastatic invasive carcinomas (at protein level).
messages: Highly expressed in lung, liver, pancreas, kidney, placenta and melanocytes. Weakly expressed in thyroid gland, ovary, brain, heart and skeletal muscle. Also expressed in erythroleukemia cells. But not expressed in colon.
messages: Inactive tyrosine kinase involved in Wnt signaling pathway. Component of both the non-canonical (also known as the Wnt/planar cell polarity signaling) and the canonical Wnt signaling pathway. Functions in cell adhesion, cell migration, cell polarity, proliferation, actin cytoskeleton reorganization and apoptosis. Has a role in embryogenesis, epithelial tissue organization and angiogenesis.
messages: Interacts with CTNNB1.
messages: MMP14 cleaves PTK7 between Pro-621 and Leu-622 generating an N-terminal soluble (70 kDa) fragment and a membrane C-terminal (50 kDa) fragment. Proteolysis by MMP14 regulates PTK7 function in non-canonical Wnt signaling pathway.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Membrane
messages: The protein kinase domain is predicted to be catalytically inactive.

9606:CACHD1
gene id: 9606:CACHD1
uniprot id: A0A0A0MQY7
uniprot id: Q5VU97
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the calcium channel subunit alpha-2/delta family.
messages: May regulate voltage-dependent calcium channels.
messages: Membrane

9606:BCAT2
gene id: 9606:BCAT2
uniprot id: B3KSI3
uniprot id: O15382
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the class-IV pyridoxal-phosphate-dependent aminotransferase family.
messages: Catalyzes the first reaction in the catabolism of the essential branched chain amino acids leucine, isoleucine, and valine (PubMed:8702755, PubMed:25653144, PubMed:17050531). May also function as a transporter of branched chain alpha-keto acids (By similarity).
messages: Homodimer.
messages: Mitochondrion
messages: The disease is caused by variants affecting the gene represented in this entry. A patient with hypervalinemia and hyperleucine-isoleucinemia was identified as compound heterozygote for Gln-170 (inherited from his father) and Lys-264 (inherited from his mother), both variants reduced the catalytic activity of the enzyme. After treatment with vitamin B6, a precursor of pyridoxal 5'-phosphate, a BCAT2 cofactor, the blood levels of branched chain amino acids, especially valine, were decreased and brain lesions were improved.
messages: Ubiquitous.

9606:ST6GAL2
gene id: 9606:ST6GAL2
uniprot id: Q96JF0
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the glycosyltransferase 29 family.
messages: By IL6/interleukin-6 and IL8//interleukin-8.
messages: Golgi stack membrane
messages: O-glycosylated.
messages: Transfers sialic acid from the donor of substrate CMP-sialic acid to galactose containing acceptor substrates. Has alpha-2,6-sialyltransferase activity toward oligosaccharides that have the Gal-beta-1,4-GlcNAc sequence at the non-reducing end of their carbohydrate groups, but it has weak or no activities toward glycoproteins and glycolipids.
messages: Weakly expressed in some tissues, such as small intestine, colon and fetal brain.

9606:CCDC152
gene id: 9606:CCDC152
uniprot id: Q4G0S7
names: Tissue Specificity
messages: Detected in stomach.

9606:FGF13
gene id: 9606:FGF13
uniprot id: A8K1P5
uniprot id: Q92913
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the heparin-binding growth factors family.
messages: Cytoplasm
messages: Interacts with SCN8A; regulates SCN8A activity (PubMed:15282281, PubMed:21566136, PubMed:33245860). Interacts with SCN1A; may regulate SCN1A activity (PubMed:19406745, PubMed:21566136). Interacts with SCN5A; the interaction is direct and may regulate SNC5A density at membranes and function (PubMed:21817159). May also interact with SCN2A and SCN11A (PubMed:19406745, PubMed:21566136). Interacts with MAPK8IP2; may regulate the MAPK8IP2 scaffolding activity (PubMed:11378392).
messages: May be phosphorylated.
messages: Microtubule-binding protein which directly binds tubulin and is involved in both polymerization and stabilization of microtubules (By similarity). Through its action on microtubules, may participate in the refinement of axons by negatively regulating axonal and leading processes branching (By similarity). Plays a crucial role in neuron polarization and migration in the cerebral cortex and the hippocampus (By similarity). Regulates voltage-gated sodium channel transport and function (PubMed:15282281, PubMed:33245860, PubMed:36696443). May also play a role in MAPK signaling (By similarity). Required for the development of axonal initial segment-targeting inhibitory GABAergic synapses made by chandelier neurons (By similarity).
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitously expressed. Predominantly expressed in the nervous system.
messages: dendrite
messages: filopodium
messages: growth cone
messages: sarcolemma

9606:GABRR2
gene id: 9606:GABRR2
uniprot id: B4DER2
uniprot id: P28476
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the ligand-gated ion channel (TC 1.A.9) family.
messages: Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRR2 sub-subfamily.
messages: Cell membrane
messages: GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel. Rho-2 GABA receptor could play a role in retinal neurotransmission.
messages: Generally pentameric. There are five types of GABA(A) receptor chains: alpha, beta, gamma, delta, and rho. Interacts with SQSTM1 (By similarity).
messages: Isoform 2 could be translated from an upstream initiator ATG located in frame within the first coding exon. The probability of a signal peptide within this isoform is very low.
messages: Membrane
messages: Postsynaptic cell membrane
messages: Synaptic cell membrane

9606:UAP1
gene id: 9606:UAP1
uniprot id: Q16222
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the UDPGP type 1 family.
messages: Converts UTP and GlcNAc-1-P into UDP-GlcNAc, and UTP and GalNAc-1-P into UDP-GalNAc. Isoform AGX1 has 2 to 3 times higher activity towards GalNAc-1-P, while isoform AGX2 has 8 times more activity towards GlcNAc-1-P.
messages: Cytoplasm
messages: Monomer and homodimer. Isoform AGX1 is a homodimer. Isoform AGX2 is a monomer.
messages: Widely expressed. Isoform AGX1 is more abundant in testis than isoform AGX2, while isoform AGX2 is more abundant than isoform AGX1 in somatic tissue. Expressed at low level in placenta, muscle and liver.

9606:CDK5
gene id: 9606:CDK5
uniprot id: A0A090N7W4
uniprot id: Q00535
names: Activity Regulation
names: Disease Annotation
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the protein kinase superfamily.
messages: Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.
messages: Cell membrane
messages: Cytoplasm
messages: Dysregulation of CDK5 is associated with neurodegenerative disorders such as Alzheimer, Parkinson, and Niemann-Pick type C diseases, ischemia, and amyotrophic lateral sclerosis.
messages: Expressed in the testis, skeletal muscle, colon, bone marrow and ovary.
messages: Heterodimer composed of a catalytic subunit CDK5 and a regulatory subunit CDK5R1 (p25) and macromolecular complex composed of at least CDK5, CDK5R1 (p35) and CDK5RAP1 or CDK5RAP2 or CDK5RAP3. Only the heterodimer shows kinase activity. Under neurotoxic stress and neuronal injury conditions, p35 is cleaved by calpain to generate p25 that hyperactivates CDK5, that becomes functionally disabled and often toxic. Found in a trimolecular complex with CABLES1 and ABL1. Interacts with CABLES1 and CABLES2 (By similarity). Interacts with AATK and GSTP1. Binds to HDAC1 when in complex with p25. Interaction with myristoylation p35 promotes CDK5 association with membranes. Both isoforms 1 and 2 interacts with beta-catenin/CTNNB1. Interacts with delta-catenin/CTNND2 and APEX1. Interacts with P53/TP53 in neurons. Interacts with EPHA4; may mediate the activation of NGEF by EPHA4. Interacts with PTK2/FAK1 (By similarity). The complex p35/CDK5 interacts with CLOCK. Interacts with HTR6 (By similarity).
messages: Inhibited by 2-(1-ethyl-2-hydroxyethylamino)-6-benzylamino-9-isopropylpurine (roscovitine), 1-isopropyl-4-aminobenzyl-6-ether-linked benzimidazoles, resveratrol, AT-7519 and olomoucine. Activated by CDK5R1 (p35) and CDK5R2 (p39) during the development of the nervous system; degradation of CDK5R1 (p35) and CDK5R2 (p39) by proteasome result in down regulation of kinase activity, during this process, CDK5 phosphorylates p35 and induces its ubiquitination and subsequent degradation. Kinase activity is mainly determined by the amount of p35 available and subcellular location; reversible association to plasma membrane inhibits activity. Long-term inactivation as well as CDK5R1 (p25)-mediated hyperactivation of CDK5 triggers cell death. The pro-death activity of hyperactivated CDK5 is suppressed by membrane association of CDK5, via myristoylation of p35. Brain-derived neurotrophic factor, glial-derived neurotrophic factor, nerve growth factor (NGF), retinoic acid, laminin and neuregulin promote activity. Neurotoxicity enhances nuclear activity, thus leading to MEF2 phosphorylation and inhibition prior to apoptosis of cortical neurons. Repression by GSTP1 via p25/p35 translocation prevents neurodegeneration.
messages: Nucleus
messages: Perikaryon
messages: Phosphorylation at Ser-159 is essential for maximal catalytic activity.
messages: Phosphorylation on Tyr-15 by ABL1 and FYN, and on Ser-159 by casein kinase 1 promotes kinase activity. By contrast, phosphorylation at Thr-14 inhibits activity.
messages: Postsynaptic density
messages: Proline-directed serine/threonine-protein kinase essential for neuronal cell cycle arrest and differentiation and may be involved in apoptotic cell death in neuronal diseases by triggering abortive cell cycle re-entry. Interacts with D1 and D3-type G1 cyclins. Phosphorylates SRC, NOS3, VIM/vimentin, p35/CDK5R1, MEF2A, SIPA1L1, SH3GLB1, PXN, PAK1, MCAM/MUC18, SEPT5, SYN1, DNM1, AMPH, SYNJ1, CDK16, RAC1, RHOA, CDC42, TONEBP/NFAT5, MAPT/TAU, MAP1B, histone H1, p53/TP53, HDAC1, APEX1, PTK2/FAK1, huntingtin/HTT, ATM, MAP2, NEFH and NEFM. Regulates several neuronal development and physiological processes including neuronal survival, migration and differentiation, axonal and neurite growth, synaptogenesis, oligodendrocyte differentiation, synaptic plasticity and neurotransmission, by phosphorylating key proteins. Negatively regulates the CACNA1B/CAV2.2 -mediated Ca(2+) release probability at hippocampal neuronal soma and synaptic terminals (By similarity). Activated by interaction with CDK5R1 (p35) and CDK5R2 (p39), especially in postmitotic neurons, and promotes CDK5R1 (p35) expression in an autostimulation loop. Phosphorylates many downstream substrates such as Rho and Ras family small GTPases (e.g. PAK1, RAC1, RHOA, CDC42) or microtubule-binding proteins (e.g. MAPT/TAU, MAP2, MAP1B), and modulates actin dynamics to regulate neurite growth and/or spine morphogenesis. Phosphorylates also exocytosis associated proteins such as MCAM/MUC18, SEPT5, SYN1, and CDK16/PCTAIRE1 as well as endocytosis associated proteins such as DNM1, AMPH and SYNJ1 at synaptic terminals. In the mature central nervous system (CNS), regulates neurotransmitter movements by phosphorylating substrates associated with neurotransmitter release and synapse plasticity; synaptic vesicle exocytosis, vesicles fusion with the presynaptic membrane, and endocytosis. Promotes cell survival by activating anti-apoptotic proteins BCL2 and STAT3, and negatively regulating of JNK3/MAPK10 activity. Phosphorylation of p…
messages: Synapse
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitously expressed (PubMed:17009320, PubMed:19693690). Accumulates in cortical neurons (at protein level) (PubMed:17009320).
messages: growth cone
messages: lamellipodium

9606:POLE3
gene id: 9606:POLE3
uniprot id: Q9NRF9
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Accessory component of the DNA polymerase epsilon complex (PubMed:10801849). Participates in DNA repair and in chromosomal DNA replication (By similarity). Forms a complex with CHRAC1 and binds naked DNA, which is then incorporated into chromatin, aided by the nucleosome-remodeling activity of ISWI/SNF2H and ACF1 (PubMed:10801849). Does not enhance nucleosome sliding activity of the ACF-5 ISWI chromatin remodeling complex (PubMed:14759371).
messages: Component of the DNA polymerase epsilon complex consisting of four subunits: the catalytic subunit POLE and the accessory subunits POLE2, POLE3 and POLE4. Interaction with POLE4 is a prerequisite for further binding with POLE and POLE2. Heterodimer with CHRAC1; binds to DNA (PubMed:10880450). Component of the CHRAC ISWI chromatin remodeling complex at least composed of SMARCA5/SNF2H, BAZ1A/ACF1, CHRAC1 and POLE3; the complex preferentially binds DNA through the CHRAC1-POLE3 heterodimer and possesses ATP-dependent nucleosome-remodeling activity (PubMed:10880450). Within the complex, the heterodimer with CHRAC1 interacts with SMARCA5/SNF2H; the interaction is direct and enhances nucleosome sliding activity by the SMARCA5/SNF2H and BAZ1A/ACF1 interaction (PubMed:10880450, PubMed:14759371). Within the complex, the heterodimer with CHRAC1 interacts with BAZ1A/ACF1; the interactions are direct (PubMed:10880450, PubMed:12434153, PubMed:14759371).
messages: Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.
messages: Nucleus

9606:LYPD5
gene id: 9606:LYPD5
uniprot id: Q6UWN5
names: Subcellular Location Annotation
messages: Cell membrane

9606:FEM1A
gene id: 9606:FEM1A
uniprot id: Q9BSK4
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the fem-1 family.
messages: Component of a CRL2 E3 ubiquitin-protein ligase complex, also named ECS (Elongin BC-CUL2/5-SOCS-box protein) complex, composed of CUL2, Elongin BC (ELOB and ELOC), RBX1 and substrate-specific adapter FEM1A (PubMed:29779948). Interacts with PTGER4 (PubMed:16424369). Interacts with NFKB1; the interaction is direct (By similarity).
messages: Cytoplasm
messages: Frequently down-regulated in rhabdomyosarcoma.
messages: Mitochondrion
messages: Phosphorylated; highly phosphorylated in myoblasts and myotubes. Phosphorylation at Ser-108 promotes PGE2-EP4-mediated inhibition of inflammation. Dephosphorylated by protein phosphatase 2A (PP2A).
messages: Present in macrophages derived from peripheral blood monocytes. Also present in atheromata (at protein level).
messages: Substrate-recognition component of a Cul2-RING (CRL2) E3 ubiquitin-protein ligase complex of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation (PubMed:29779948, PubMed:33398168, PubMed:33398170). The C-degron recognized by the DesCEND pathway is usually a motif of less than ten residues and can be present in full-length proteins, truncated proteins or proteolytically cleaved forms (PubMed:29779948, PubMed:33398168, PubMed:33398170). The CRL2(FEM1A) complex specifically recognizes proteins with an arginine at the C-terminus: recognizes and binds proteins ending with -Lys/Arg-Xaa-Arg and -Lys/Arg-Xaa-Xaa-Arg C-degrons, such as SIL1 or OR51B2, leading to their ubiquitination and degradation (PubMed:33398168, PubMed:33398170). Promotes ubiquitination and degradation of SLBP (PubMed:28118078). Involved in PGE2-EP4-mediated inhibition of inflammation of macrophages via interaction with NFKB1 and PTGER4 (By similarity). Promotes inflammation in brain microglia through MAP2K4/MKK4-mediated signaling (By similarity).

9606:SHB
gene id: 9606:SHB
uniprot id: Q15464
names: Domain
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Adapter protein which regulates several signal transduction cascades by linking activated receptors to downstream signaling components. May play a role in angiogenesis by regulating FGFR1, VEGFR2 and PDGFR signaling. May also play a role in T-cell antigen receptor/TCR signaling, interleukin-2 signaling, apoptosis and neuronal cells differentiation by mediating basic-FGF and NGF-induced signaling cascades. May also regulate IRS1 and IRS2 signaling in insulin-producing cells.
messages: Cell membrane
messages: Cytoplasm
messages: Interacts with PTPN11 (By similarity). Interacts with phosphorylated 'Tyr-720' of the ligand-activated receptor PDGFRA via its SH2 domain. Interacts with the ligand-activated receptors PDGFRB, FGFR1, KDR/VEGFR2, IL2RB and IL2RG. Interacts with EPS8 and V-SRC. Interacts with GRB2 and GRAP. Interacts with CD3Z. Interacts with tyrosine-phosphorylated LAT upon T-cell antigen receptor activation. Interacts with PLCG1. Interacts with ZAP70, LCP2/SLP-76, VAV1 and GRAP2. Interacts with JAK1 and JAK3. Interacts with PTK2/FAK1. Interacts with CRK/CrKII. Interacts with IRS2.
messages: Phosphorylated upon PDGFRA, PDGFRB, TCR, IL2 receptor, FGFR1 or VEGFR2 activation.
messages: The SH2 domain preferentially binds phosphopeptides with the consensus sequence Y-[TVI]-X-L and mediates interaction with PDGFRA, PDGFRB, FGRFR1, IL2RB, IL2RG, CD3Z and CRK/CrKII.
messages: Widely expressed.

9606:DUSP6
gene id: 9606:DUSP6
uniprot id: Q16828
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily.
messages: Cytoplasm
messages: Expressed in keratinocytes (at protein level).
messages: Inactivates MAP kinases. Has a specificity for the ERK family (PubMed:9858808). Plays an important role in alleviating chronic postoperative pain. Necessary for the normal dephosphorylation of the long-lasting phosphorylated forms of spinal MAPK1/3 and MAP kinase p38 induced by peripheral surgery, which drives the resolution of acute postoperative allodynia (By similarity). Also important for dephosphorylation of MAPK1/3 in local wound tissue, which further contributes to resolution of acute pain (By similarity). Promotes cell differentiation by regulating MAPK1/MAPK3 activity and regulating the expression of AP1 transcription factors (PubMed:29043977).
messages: Interacts with MAPK1/ERK2.
messages: The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry. Some patients carrying mutations in DUSP6 also have a heterozygous mutation in another HH-associated gene including FGFR1 and SPRY4 (PubMed:23643382).

9606:POLR3K
gene id: 9606:POLR3K
uniprot id: Q9Y2Y1
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the archaeal RpoM/eukaryotic RPA12/RPB9/RPC11 RNA polymerase family.
messages: Component of the RNA polymerase III (Pol III) complex consisting of 17 subunits.
messages: DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates (PubMed:12391170). Component of RNA polymerase III which synthesizes small RNAs, such as 5S rRNA and tRNAs (PubMed:12391170, PubMed:30584594). Plays a key role in sensing and limiting infection by intracellular bacteria and DNA viruses (PubMed:19631370, PubMed:19609254). Acts as nuclear and cytosolic DNA sensor involved in innate immune response (PubMed:19631370, PubMed:19609254). Can sense non-self dsDNA that serves as template for transcription into dsRNA (PubMed:19631370, PubMed:19609254). The non-self RNA polymerase III transcripts, such as Epstein-Barr virus-encoded RNAs (EBERs) induce type I interferon and NF-kappa-B through the RIG-I pathway (PubMed:19631370, PubMed:19609254).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: nucleolus

9606:NPIPA7
gene id: 9606:NPIPA7
uniprot id: E9PJI5
uniprot id: P0DM63
names: Similarity
messages: Belongs to the NPIP family.

9606:SERPINA1
gene id: 9606:SERPINA1
uniprot id: E9KL23
uniprot id: P01009
names: Disease Annotation
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Proteolytically processed by Staphylococcus aureus seryl, cysteinyl, and metallo-proteases.
messages: Belongs to the serpin family.
messages: Endoplasmic reticulum
messages: Inhibitor of serine proteases. Its primary target is elastase, but it also has a moderate affinity for plasmin and thrombin. Irreversibly inhibits trypsin, chymotrypsin and plasminogen activator. The aberrant form inhibits insulin-induced NO synthesis in platelets, decreases coagulation time and has proteolytic activity against insulin and plasmin.
messages: Interacts with CELA2A (PubMed:31358993). Interacts with ERGIC3 and LMAN1/ERGIC53 (PubMed:31142615). Interacts with PRSS1/trypsin (PubMed:11057674). Interacts with PRSS1/Trypsin (PubMed:11057674). The variants S and Z interact with CANX and PDIA3 (PubMed:23826168).
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: N-glycosylated. Differential glycosylation produces a number of isoforms. N-linked glycan at Asn-107 is alternatively di-antennary, tri-antennary or tetra-antennary. The glycan at Asn-70 is di-antennary with trace amounts of tri-antennary. Glycan at Asn-271 is exclusively di-antennary. Structure of glycans at Asn-70 and Asn-271 is Hex5HexNAc4. The structure of the antennae is Neu5Ac(alpha1-6)Gal(beta1-4)GlcNAc attached to the core structure Man(alpha1-6)[Man(alpha1-3)]Man(beta1-4)GlcNAc(beta1-4)GlcNAc. Some antennae are fucosylated, which forms a Lewis-X determinant.
messages: Proteolytic processing may yield the truncated form that ranges from Asp-30 to Lys-418.
messages: Reversible chymotrypsin inhibitor. It also inhibits elastase, but not trypsin. Its major physiological function is the protection of the lower respiratory tract against proteolytic destruction by human leukocyte elastase (HLE).
messages: Secreted
messages: The aberrant form is found in the plasma of chronic smokers, and persists after smoking is ceased. It can still be found ten years after smoking has ceased.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The reactive center loop (RCL) extends out from the body of the protein and directs binding to the target protease. The protease cleaves the serpin at the reactive site within the RCL, establishing a covalent linkage between the carboxyl group of the serpin reactive site and the serine hydroxyl of the protease. The resulting inactive serpin-protease complex is highly stable.
messages: The sequence shown is that of the M1V allele which is the most common form of PI (44 to 49%). Other frequent alleles are: M1A 20 to 23%; M2 10 to 11%; M3 14 to 19%.
messages: Ubiquitous. Expressed in leukocytes and plasma.
messages: extracellular matrix

9606:DENND11
gene id: 9606:DENND11
uniprot id: A4D1U4
names: Function
names: Similarity
messages: Belongs to the DENND11 family.
messages: Probable guanine nucleotide exchange factor (GEF). May promote the exchange of GDP to GTP, converting inactive GDP-bound small GTPases into their active GTP-bound form (Probable). May play a role in neuritogenesis, as well as in neuronal recovery and/or restructuring in the hippocampus following transient cerebral ischemia (By similarity).

9606:SPACA7
gene id: 9606:SPACA7
uniprot id: Q96KW9
names: Function
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Expressed in spermatozoa (at protein level) (PubMed:22495889).
messages: Involved in fertilization. Seems not to play a direct role in sperm-egg binding or gamete fusion.
messages: Secreted
messages: acrosome
messages: acrosome lumen

9606:CSNK2A1
gene id: 9606:CSNK2A1
uniprot id: P68400
names: Activity Regulation
names: Disease Annotation
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. CK2 subfamily.
messages: Can use both ATP and GTP as phosphoryl donors. Phosphorylation by casein kinase 2 has been estimated to represent up to one quarter of the eukaryotic phosphoproteome. Casein kinase 2 has been found to be increased at protein level and up-regulated at the level of enzyme activity in the majority of cancers. However, elevated levels of casein kinase 2 are present in certain normal organs such as brain and testes.
messages: Catalytic subunit of a constitutively active serine/threonine-protein kinase complex that phosphorylates a large number of substrates containing acidic residues C-terminal to the phosphorylated serine or threonine (PubMed:11239457, PubMed:11704824, PubMed:16193064, PubMed:19188443, PubMed:20625391, PubMed:22406621, PubMed:24962073, PubMed:31439799). Regulates numerous cellular processes, such as cell cycle progression, apoptosis and transcription, as well as viral infection (PubMed:12631575, PubMed:19387552, PubMed:19387551). May act as a regulatory node which integrates and coordinates numerous signals leading to an appropriate cellular response (PubMed:12631575, PubMed:19387552, PubMed:19387551). During mitosis, functions as a component of the p53/TP53-dependent spindle assembly checkpoint (SAC) that maintains cyclin-B-CDK1 activity and G2 arrest in response to spindle damage (PubMed:11704824, PubMed:19188443). Also required for p53/TP53-mediated apoptosis, phosphorylating 'Ser-392' of p53/TP53 following UV irradiation. Can also negatively regulate apoptosis (PubMed:11239457). Phosphorylates the caspases CASP9 and CASP2 and the apoptotic regulator NOL3 (PubMed:16193064). Phosphorylation protects CASP9 from cleavage and activation by CASP8, and inhibits the dimerization of CASP2 and activation of CASP8 (PubMed:16193064). Phosphorylates YY1, protecting YY1 from cleavage by CASP7 during apoptosis (PubMed:22184066). Regulates transcription by direct phosphorylation of RNA polymerases I, II, III and IV (PubMed:19387550, PubMed:12631575, PubMed:19387552, PubMed:19387551, PubMed:23123191). Also phosphorylates and regulates numerous transcription factors including NF-kappa-B, STAT1, CREB1, IRF1, IRF2, ATF1, ATF4, SRF, MAX, JUN, FOS, MYC and MYB (PubMed:19387550, PubMed:12631575, PubMed:19387552, PubMed:19387551, PubMed:23123191). Phosphorylates Hsp90 and its co-chaperones FKBP4 and CDC37, which is essential for chaperone function (PubMed:19387550). Mediates sequential pho…
messages: Constitutively active protein kinase whose activity is not directly affected by phosphorylation. Seems to be regulated by level of expression and localization.
messages: Expressed in gastric carcinoma tissue and the expression gradually increases with the progression of the carcinoma (at protein level).
messages: Heterotetramer composed of two catalytic subunits (alpha chain and/or alpha' chain) and two regulatory subunits (beta chains). The tetramer can exist as a combination of 2 alpha/2 beta, 2 alpha'/2 beta or 1 alpha/1 alpha'/2 beta subunits. Also part of a CK2-SPT16-SSRP1 complex composed of SSRP1, SUPT16H, CSNK2A1, CSNK2A2 and CSNK2B, which forms following UV irradiation. Interacts with RNPS1. Interacts with SNAI1. Interacts with PML (isoform PML-12). Interacts with CCAR2.
messages: Nucleus
messages: Phosphorylated at Thr-344, Thr-360, Ser-362 and Ser-370 by CDK1 in prophase and metaphase and dephosphorylated during anaphase. Phosphorylation does not directly affect casein kinase 2 activity, but may contribute to its regulation by forming binding sites for interacting proteins and/or targeting it to different compartments.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:COMMD4
gene id: 9606:COMMD4
uniprot id: Q9H0A8
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cytoplasm
messages: Interacts (via COMM domain) with COMMD1 (via COMM domain). Interacts with RELA, RELB, NFKB1/p105. Interacts with CCDC22, CCDC93, SCNN1B, CUL2, CUL3, CUL4A, CUL5, CUL7.
messages: May modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes (PubMed:21778237). Down-regulates activation of NF-kappa-B.
messages: Nucleus
messages: Ubiquitous.

9606:FBXO2
gene id: 9606:FBXO2
uniprot id: Q9UK22
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Component of the SCF(FBXO2) complex consisting of CUL1, RBX1, SKP1 and FBXO2. Predominantly detected as heterodimer with SKP1; the heterodimer with SKP1 is not part of the SCF(FBXO2) complex (By similarity).
messages: Cytoplasm
messages: Microsome membrane
messages: Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Involved in the endoplasmic reticulum-associated degradation pathway (ERAD) for misfolded lumenal proteins by recognizing and binding sugar chains on unfolded glycoproteins that are retrotranslocated into the cytosol and promoting their ubiquitination and subsequent degradation. Prevents formation of cytosolic aggregates of unfolded glycoproteins that have been retrotranslocated into the cytosol. Able to recognize and bind denatured glycoproteins, preferentially those of the high-mannose type (By similarity).

9606:TSPAN11
gene id: 9606:TSPAN11
uniprot id: A1L157
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the tetraspanin (TM4SF) family.
messages: Membrane

9606:PHOSPHO1
gene id: 9606:PHOSPHO1
uniprot id: Q8TCT1
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the HAD-like hydrolase superfamily. PHOSPHO family.
messages: Expressed at sites of mineralization in bone and cartilage. Highly expressed in osteoblast cell line SaOS-2 which produces a mineralized matrix, but not in MG-63 cell line, which do not mineralize.
messages: Extracellular vesicle
messages: Phosphatase that has a high activity toward phosphoethanolamine (PEA) and phosphocholine (PCho) (PubMed:15175005). Involved in the generation of inorganic phosphate for bone mineralization (By similarity). Acts in a non-redundant manner with PHOSPHO1 in skeletal mineralization: while PHOSPHO1 mediates the initiation of hydroxyapatite crystallization in the matrix vesicles (MVs), ALPL/TNAP catalyzes the spread of hydroxyapatite crystallization in the extracellular matrix (By similarity).

9606:ACOT4
gene id: 9606:ACOT4
uniprot id: Q8N9L9
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the C/M/P thioester hydrolase family.
messages: Catalyzes the hydrolysis of acyl-CoAs into free fatty acids and coenzyme A (CoASH), regulating their respective intracellular levels (PubMed:16940157). Functions as a peroxisomal succinyl-coenzyme A thioesterase that can also hydrolyze glutaryl-CoA and long chain saturated acyl-CoAs (PubMed:16940157).
messages: Compared to mouse peroxisomal succinyl-coenzyme A thioesterase/ACOT4, the human enzyme has a broad substrate specificity overlapping the activity of three mouse acyl-coenzyme A thioesterases, providing an explanation for the unexpectedly low number of acyl-coenzyme A thioesterase genes in the human genome.
messages: Peroxisome
messages: Strongest expression in liver and kidney and weaker expression in placenta, heart, and muscle.

9606:TRAF5
gene id: 9606:TRAF5
uniprot id: O00463
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Adapter protein and signal transducer that links members of the tumor necrosis factor receptor family to different signaling pathways by association with the receptor cytoplasmic domain and kinases. Mediates activation of NF-kappa-B and probably JNK. Seems to be involved in apoptosis. Plays a role in mediating activation of NF-kappa-B by EIF2AK2/PKR.
messages: Belongs to the TNF receptor-associated factor family. A subfamily.
messages: Cytoplasm
messages: Expressed in spleen, thymus, prostate, testis, ovary, small intestine, colon, and peripheral blood.
messages: Homotrimer (Probable). Heteromer with TRAF3. Associates with TNFRSF5/CD40 through interaction with TRAF3. Associates with LTBR/TNFRSF3, TNFRSF4, TNFRSF8/CD30, TNFRSF11A/RANK, TNFRSF13B/TACI, TNFRSF14, TNFRSF17, TNFRSF19/TROY, RIPK2, MAP3K14, MAP3K5, and TRAF and TNF receptor associated protein TDP2. Interacts (via C-terminus) with EIF2AK2/PKR (via the kinase catalytic domain).
messages: The MATH/TRAF domain binds to receptor cytoplasmic domains.
messages: Ubiquitinated at Lys-318 by the SCF(FBXL2) complex, leading to its degradation by the proteasome.
messages: cytosol

9606:TENM2
gene id: 9606:TENM2
uniprot id: A0A8Q3SIA3
uniprot id: F8VNQ3
uniprot id: G3V106
uniprot id: Q9NT68
names: Caution
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acts as a ligand of the ADGRL1 receptor. Mediates axon guidance and heterophilic cell-cell adhesion.
messages: Belongs to the tenascin family. Teneurin subfamily.
messages: Cell membrane
messages: Cytoplasmic proline-rich regions could serve as docking domains for intracellular SH3-containing proteins.
messages: Derives from the membrane form by proteolytic processing.
messages: Derives from the plasma membrane form by proteolytic cleavage and translocates to the nucleus. Homophilic binding of the C-terminal extracellular domain stimulates its proteolytic cleavage and release in the cytoplasmic. Is subjected to rapid degradation by the proteasome pathway (By similarity).
messages: EGF-like domains 2 and 5 which have an odd number of cysteines might enable the formation of intermolecular disulfide bonds.
messages: Endoplasmic reticulum
messages: Golgi apparatus
messages: Highly expressed in heart, followed by brain, liver, kidney and fetal brain and weakly expressed in lung and testis. No expression was detected in skeletal muscle, pancreas, spleen, ovary and fetal liver.
messages: Homodimer; disulfide-linked (Probable). Heterodimer with either TENM1 or TENM3. May also form heterodimer with TENM4 (By similarity). Isoform 2 (C-terminal globular domain) interacts with ADGRL1 isoform 2.
messages: Induces gene transcription inhibition.
messages: Involved in neural development, regulating the establishment of proper connectivity within the nervous system. Promotes the formation of filopodia and enlarged growth cone in neuronal cells. Induces homophilic cell-cell adhesion (By similarity). May function as a cellular signal transducer.
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: Membrane
messages: PML body
messages: Postsynaptic cell membrane
messages: Synapse
messages: dendritic spine
messages: filopodium
messages: growth cone
messages: synaptosome

9606:MED4
gene id: 9606:MED4
uniprot id: Q9NPJ6
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the Mediator complex subunit 4 family.
messages: Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors.
messages: Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP.
messages: Nucleus

9606:GNG3
gene id: 9606:GNG3
uniprot id: P63215
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the G protein gamma family.
messages: Cell membrane
messages: G proteins are composed of 3 units, alpha, beta and gamma. Forms a complex with GNAO1 and GNB1 (PubMed:34685729). Interacts with SCN8A (PubMed:26900580).
messages: Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction.

9606:ZNF888
gene id: 9606:ZNF888
uniprot id: P0CJ79
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:TMEM242
gene id: 9606:TMEM242
uniprot id: Q9NWH2
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the TMEM242 family.
messages: Interacts with the core subunits NDUFAF1, ECSIT and ACAD9 of the MCIA complex (PubMed:33753518). Interacts with ATP5MC3, NDUFC2, TMEM70, MT-ND2 and MT-ND3 (PubMed:33753518).
messages: Mitochondrion inner membrane
messages: Scaffold protein that participates in the c-ring assembly of mitochondrial ATP synthase (F(1)F(0) ATP synthase or complex V) by facilitating the membrane insertion and oligomer formation of the subunit c/ATP5MC3 (PubMed:33753518). Participates in the incorporation of the c-ring into vestigial complexes (PubMed:33753518). Additionally influences the incorporation of subunits MT-ATP6, MT-ATP8, ATP5MJ, and ATP5MK in the ATP synthase (PubMed:33753518).

9606:SYCE1
gene id: 9606:SYCE1
uniprot id: A0A0B4J1R9
uniprot id: Q8N0S2
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the SYCE family.
messages: Chromosome
messages: Homodimer. Found in a complex with SYCP1 and SYCE2. Interacts with SYCP1, SYCE2 and SYCE3. Interacts with SIX6OS1.
messages: Major component of the transverse central element of synaptonemal complexes (SCS), formed between homologous chromosomes during meiotic prophase. Requires SYCP1 in order to be incorporated into the central element. May have a role in the synaptonemal complex assembly, stabilization and recombination.
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:ZNF625
gene id: 9606:ZNF625
uniprot id: Q96I27
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:PUM1
gene id: 9606:PUM1
uniprot id: Q14671
names: Disease Annotation
names: Domain
names: Function
names: Induction
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cytoplasm
messages: Cytoplasmic granule
messages: Expressed in brain, heart, kidney, muscle, intestine and stomach. Not expressed in cerebellum, corpus callosum, caudate nucleus, hippocampus, medulla oblongata and putamen. Expressed in all fetal tissues tested.
messages: P-body
messages: Phosphorylation at Ser-714 promotes RNA-binding activity. Following growth factor stimulation phosphorylated at Ser-714, promoting binding to the 3'-UTR of CDKN1B/p27 mRNA.
messages: Recruits the CCR4-POP2-NOT deadenylase leading to translational inhibition and mRNA degradation (PubMed:22955276). In case of viral infection, interacts with DHX58 (PubMed:25340845). Interacts with TRIM71 (via NHL repeats) in an RNA-dependent manner (PubMed:23125361).
messages: Sequence-specific RNA-binding protein that acts as a post-transcriptional repressor by binding the 3'-UTR of mRNA targets. Binds to an RNA consensus sequence, the Pumilio Response Element (PRE), 5'-UGUANAUA-3', that is related to the Nanos Response Element (NRE) (PubMed:21572425, PubMed:18328718, PubMed:21653694, PubMed:21397187). Mediates post-transcriptional repression of transcripts via different mechanisms: acts via direct recruitment of the CCR4-POP2-NOT deadenylase leading to translational inhibition and mRNA degradation (PubMed:22955276). Also mediates deadenylation-independent repression by promoting accessibility of miRNAs (PubMed:18776931, PubMed:20818387, PubMed:20860814, PubMed:22345517). Following growth factor stimulation, phosphorylated and binds to the 3'-UTR of CDKN1B/p27 mRNA, inducing a local conformational change that exposes miRNA-binding sites, promoting association of miR-221 and miR-222, efficient suppression of CDKN1B/p27 expression, and rapid entry to the cell cycle (PubMed:20818387). Acts as a post-transcriptional repressor of E2F3 mRNAs by binding to its 3'-UTR and facilitating miRNA regulation (PubMed:22345517, PubMed:29474920). Represses a program of genes necessary to maintain genomic stability such as key mitotic, DNA repair and DNA replication factors. Its ability to repress those target mRNAs is regulated by the lncRNA NORAD (non-coding RNA activated by DNA damage) which, due to its high abundance and multitude of PUMILIO binding sites, is able to sequester a significant fraction of PUM1 and PUM2 in the cytoplasm (PubMed:26724866). Involved in neuronal functions by regulating ATXN1 mRNA levels: acts by binding to the 3'-UTR of ATXN1 transcripts, leading to their down-regulation independently of the miRNA machinery (PubMed:25768905, PubMed:29474920). Plays a role in cytoplasmic sensing of viral infection (PubMed:25340845). In testis, acts as a post-transcriptional regulator of spermatogenesis by binding to the 3'-UTR of mRNAs coding …
messages: Strongly down-regulated in keratinocytes upon UVB irradiation.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The pumilio repeats mediate the association with RNA by packing together to form a right-handed superhelix that approximates a half donut. RNA-binding occurs on the concave side of the surface (PubMed:21397187). PUM1 is composed of 8 pumilio repeats of 36 residues; each repeat binds a single nucleotide in its RNA target. Residues at positions 12 and 16 of the pumilio repeat bind each RNA base via hydrogen bonding or van der Waals contacts with the Watson-Crick edge, while the amino acid at position 13 makes a stacking interaction. The recognition of RNA by pumilio repeats is base specific: cysteine and glutamine at position 12 and 16, respectively, bind adenine; asparagine and glutamine bind uracil; and serine and glutamate bind guanine (PubMed:21572425, PubMed:18328718, PubMed:21653694).

9606:IL6R
gene id: 9606:IL6R
uniprot id: A0A087WTB5
uniprot id: A0N0L5
uniprot id: P08887
names: Activity Regulation
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: A short soluble form is released from the membrane by proteolysis (PubMed:26876177). The sIL6R is formed mostly by limited proteolysis of membrane-bound receptors, a process referred to as ectodomain shedding, but is also directly secreted from the cells after alternative mRNA splicing (PubMed:26876177, PubMed:28060820). mIL6R is cleaved by the proteases ADAM10 and ADAM17 (PubMed:26876177, PubMed:28060820).
messages: Also interacts with SORL1; this interaction leads to soluble IL6R internalization. May form a trimeric complex with the soluble SORL1 ectodomain and circulating IL6 receptor; this interaction might stabilize circulating IL6, hence promote IL6 'trans-signaling,.
messages: Belongs to the type I cytokine receptor family. Type 3 subfamily.
messages: Cell membrane
messages: Classic and trans-signaling are both inhibited by tocilizumab, a humanized monoclonal antibody that blocks interleukin IL6R signaling.
messages: Component of a hexamer of two molecules each of IL6, IL6R and IL6ST; first binds to IL6 to associate with the signaling subunit IL6ST (PubMed:12829785, PubMed:28265003). Interacts (via N-terminal ectodomain) with SORL1; this interaction may affect IL6-binding to IL6R, hence decrease IL6 'classic-signaling' (PubMed:28265003).
messages: Expressed in peripheral blood mononuclear cells and weakly found in urine and serum. 1%-20% of the total sIL6R in plasma is generated by alternative splicing (PubMed:28060820).
messages: Genetic variations in IL6R define the IL6 serum level quantitative trait locus [MIM:614752].
messages: Genetic variations in IL6R determine soluble IL6R serum levels [MIM:614689].
messages: Glycosylated. Glycosylation is dispensable for transport, signaling, and cell-surface turnover. Glycosylation at Asn-55 is a protease-regulatory exosite. Glycosylation is required for ADAM17-mediated proteolysis.
messages: Membrane
messages: Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not transduce a signal (PubMed:28265003). Signal activation necessitate an association with IL6ST. Activation leads to the regulation of the immune response, acute-phase reactions and hematopoiesis (PubMed:30995492, PubMed:31235509). The interaction with membrane-bound IL6R and IL6ST stimulates 'classic signaling', the restricted expression of the IL6R limits classic IL6 signaling to only a few tissues such as the liver and some cells of the immune system. Whereas the binding of IL6 and soluble IL6R to IL6ST stimulates 'trans-signaling'. Alternatively, 'cluster signaling' occurs when membrane-bound IL6:IL6R complexes on transmitter cells activate IL6ST receptors on neighboring receiver cells (Probable).
messages: Secreted
messages: Signaling via the membrane-bound IL6R is mostly regenerative and anti-inflammatory (Probable). Drives naive CD4(+) T cells to the Th17 lineage, through 'cluster signaling' by dendritic cells (By similarity).
messages: Soluble form of IL6 receptor (sIL6R) that acts as an agonist of IL6 activity (PubMed:21990364). The IL6:sIL6R complex (hyper-IL6) binds to IL6ST/gp130 on cell surfaces and induces signaling also on cells that do not express membrane-bound IL6R in a process called IL6 'trans-signaling'. sIL6R is causative for the pro-inflammatory properties of IL6 and an important player in the development of chronic inflammatory diseases (PubMed:21990364). In complex with IL6, is required for induction of VEGF production (PubMed:12794819). Plays a protective role during liver injury, being required for maintenance of tissue regeneration (By similarity). 'Trans-signaling' in central nervous system regulates energy and glucose homeostasis (By similarity).
messages: The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The two fibronectin type-III-like domains, contained in the N-terminal part, form together a cytokine-binding domain.

9606:OR2M2
gene id: 9606:OR2M2
uniprot id: A0A126GWI7
uniprot id: Q96R28
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Membrane
messages: Odorant receptor.

9606:FLOT2
gene id: 9606:FLOT2
uniprot id: J3QLD9
uniprot id: Q14254
uniprot id: Q6FG43
uniprot id: Q9BTI6
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the band 7/mec-2 family. Flotillin subfamily.
messages: Cell membrane
messages: Endosome
messages: Heterooligomeric complex of flotillin-1 and flotillin-2 and caveolin-1 and caveolin-2 (By similarity). Interacts with ECPAS.
messages: Heterooligomeric complex of flotillin-1 and flotillin-2 and caveolin-1 and caveolin-2. Interacts with ECPAS.
messages: Heterooligomeric complex.
messages: In skin, expressed in epidermis and epidermal appendages but not in dermis. Expressed in all layers of the epidermis except the basal layer. In hair follicles, expressed in the suprabasal layer but not the basal layer. Also expressed in melanoma and carcinoma cell lines, fibroblasts and foreskin melanocytes.
messages: May act as a scaffolding protein within caveolar membranes, functionally participating in formation of caveolae or caveolae-like vesicles.
messages: May act as a scaffolding protein within caveolar membranes, functionally participating in formation of caveolae or caveolae-like vesicles. May be involved in epidermal cell adhesion and epidermal structure and function.
messages: Membrane
messages: Membrane raft
messages: ZDHHC5-catalyzed palmitoylation predominantly occurs at Cys-4. ZDHHC5-catalyzed palmitoylation may be required for the formation of higher-order complexes and for neurite outgrowth in cultured neural stem cells.
messages: caveola

9606:CNTN2
gene id: 9606:CNTN2
uniprot id: A1L3A3
uniprot id: Q02246
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the immunoglobulin superfamily. Contactin family.
messages: Cell membrane
messages: In conjunction with another transmembrane protein, CNTNAP2, contributes to the organization of axonal domains at nodes of Ranvier by maintaining voltage-gated potassium channels at the juxtaparanodal region. May be involved in cell adhesion.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:CPNE9
gene id: 9606:CPNE9
uniprot id: Q8IYJ1
names: Function
names: Similarity
names: Tissue Specificity
messages: Belongs to the copine family.
messages: Expressed in melanocytes (PubMed:23999003).
messages: Probable calcium-dependent phospholipid-binding protein that may play a role in calcium-mediated intracellular processes (By similarity). Plays a role in dendrite formation by melanocytes (PubMed:23999003).

9606:PEPD
gene id: 9606:PEPD
uniprot id: A0A140VJR2
uniprot id: P12955
names: Activity Regulation
names: Cofactor
names: Disease Annotation
names: Function
names: Similarity
names: Subunit
messages: Belongs to the peptidase M24B family.
messages: Belongs to the peptidase M24B family. Eukaryotic-type prolidase subfamily.
messages: Binds 2 manganese ions per subunit.
messages: Dipeptidase that catalyzes the hydrolysis of dipeptides with a prolyl (Xaa-Pro) or hydroxyprolyl residue in the C-terminal position (PubMed:17081196, PubMed:35165443). The preferred dipeptide substrate is Gly-Pro, but other Xaa-Pro dipeptides, such as Ala-Pro, Met-Pro, Phe-Pro, Val-Pro and Leu-Pro, can be cleaved (PubMed:17081196). Plays an important role in collagen metabolism because the high level of iminoacids in collagen (PubMed:2925654).
messages: Homodimer.
messages: Specifically inhibited by the pseudodipeptide CQ31 (PubMed:35165443). Inhibition by CQ31 indirectly activates the CARD8 inflammasome: dipeptide accumulation following PEPD inactivation weaky inhibit dipeptidyl peptidases DDP8 and DPP9, relieving DPP8- and/or DPP9-mediated inhibition of CARD8 (PubMed:35165443).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:SMU1
gene id: 9606:SMU1
uniprot id: A0MNN4
uniprot id: Q2TAY7
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Identified in a complex with IK and influenza A virus RNA polymerase subunits PB1 and PB2; does not directly interact with the viral proteins by itself.
messages: (Microbial infection) Required, together with IK, for normal splicing of influenza A virus NS1 pre-mRNA, which is required for the production of the exportin NS2 and for the production of influenza A virus particles. Not required for the production of VSV virus particles.
messages: Belongs to the WD repeat SMU1 family.
messages: Component of the spliceosome B complex (PubMed:22365833, PubMed:28781166). Interacts with IK (PubMed:28781166, PubMed:24945353, PubMed:22365833).
messages: Cytoplasm
messages: Involved in pre-mRNA splicing as a component of the spliceosome (PubMed:28781166). Regulates alternative splicing of the HSPG2 pre-mRNA (By similarity). Required for normal accumulation of IK (PubMed:24945353). Required for normal mitotic spindle assembly and normal progress through mitosis (By similarity).
messages: Nucleus
messages: Nucleus speckle
messages: The WD repeats assemble into a seven-bladed WD propeller.

9606:DNAJC6
gene id: 9606:DNAJC6
uniprot id: O75061
names: Disease Annotation
names: Function
names: Subunit
names: Tissue Specificity
messages: Expressed in various brain regions, including cerebellum, corpus callosum, cortex, striatum, brainstem, pons, putamen, spinal cord and substantia nigra. Very low expression in non-neural tissues such as leukocytes, liver, adipose tissue, skeletal muscle and bone marrow.
messages: Interacts with HSPA8/HSC70. Interacts with CLTC. Interacts with AP2A2 (By similarity).
messages: Recruits HSPA8/HSC70 to clathrin-coated vesicles and promotes uncoating of clathrin-coated vesicles. Plays a role in clathrin-mediated endocytosis in neurons (By similarity).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:PLSCR2
gene id: 9606:PLSCR2
uniprot id: Q9NRY7
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the phospholipid scramblase family.
messages: Expression of isoform 1 seems restricted to testis.
messages: Isoform 1 has no prospholipid scramblase activity, due to the lack of a N-terminal proline-rich domain.
messages: May mediate accelerated ATP-independent bidirectional transbilayer migration of phospholipids upon binding calcium ions that results in a loss of phospholipid asymmetry in the plasma membrane. May play a central role in the initiation of fibrin clot formation, in the activation of mast cells and in the recognition of apoptotic and injured cells by the reticuloendothelial system.
messages: Membrane
messages: Nucleus
messages: The N-terminal proline-rich domain (PRD) is required for phospholipid scramblase activity.

9606:CHRNA10
gene id: 9606:CHRNA10
uniprot id: C4IXS7
uniprot id: Q9GZZ6
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the ligand-gated ion channel (TC 1.A.9) family.
messages: Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Alpha-10/CHRNA10 sub-subfamily.
messages: Cell membrane
messages: Expressed in inner-ear tissue, tonsil, immortalized B-cells, cultured T-cells and peripheral blood lymphocytes.
messages: Forms heterooligomeric channels in conjunction with CHRNA9. The native outer hair cell receptor may be composed of CHRNA9-CHRNA10 heterooligomers. Interacts with the conotoxin GeXXA (PubMed:26395518). Interacts with the alpha-conotoxin RgIA (By similarity).
messages: Ionotropic receptor with a probable role in the modulation of auditory stimuli. Agonist binding may induce an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. The channel is permeable to a range of divalent cations including calcium, the influx of which may activate a potassium current which hyperpolarizes the cell membrane. In the ear, this may lead to a reduction in basilar membrane motion, altering the activity of auditory nerve fibers and reducing the range of dynamic hearing. This may protect against acoustic trauma.
messages: Membrane
messages: Postsynaptic cell membrane
messages: Synaptic cell membrane
messages: The heterooligomeric receptor composed of CHRNA9 and CHRNA10 has an atypical pharmacological profile, binding several non-nicotinic ligands including strychnine (a glycine receptor antagonist) and atropine (a muscarinic acetylcholine receptor antagonist).

9606:GALNT2
gene id: 9606:GALNT2
uniprot id: A0A1L7NY50
uniprot id: B7Z6K2
uniprot id: Q10471
names: Disease Annotation
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the glycosyltransferase 2 family. GalNAc-T subfamily.
messages: Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor. Has a broad spectrum of substrates for peptides such as EA2, Muc5AC, Muc1a, Muc1b. Probably involved in O-linked glycosylation of the immunoglobulin A1 (IgA1) hinge region. Involved in O-linked glycosylation of APOC-III, ANGPTL3 and PLTP. It participates in the regulation of HDL-C metabolism (PubMed:27508872, PubMed:32293671).
messages: Golgi apparatus membrane
messages: Golgi stack membrane
messages: Membrane
messages: Secreted
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The ricin B-type lectin domain binds to GalNAc and contributes to the glycopeptide specificity.
messages: There are two conserved domains in the glycosyltransferase region: the N-terminal domain (domain A, also called GT1 motif), which is probably involved in manganese coordination and substrate binding and the C-terminal domain (domain B, also called Gal/GalNAc-T motif), which is probably involved in catalytic reaction and UDP-Gal binding.
messages: Widely expressed.

9606:ENTPD7
gene id: 9606:ENTPD7
uniprot id: Q9NQZ7
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the GDA1/CD39 NTPase family.
messages: Catalyzes the hydrolysis of nucleoside triphosphates and diphosphates in a calcium- or magnesium-dependent manner. Preferentially hydrolyzes nucleoside 5'-triphosphates, with substrate preference for UTP > GTP > CTP. Hydrolyzes ATP and nucleoside diphosphates only to a minor extent.
messages: Cytoplasmic vesicle membrane

9606:ATP5MC3
gene id: 9606:ATP5MC3
uniprot id: P48201
names: Disease Annotation
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the ATPase C chain family.
messages: F-type ATPases have 2 components, CF(1) - the catalytic core - and CF(0) - the membrane proton channel. CF(1) has five subunits: alpha(3), beta(3), gamma(1), delta(1), epsilon(1). CF(0) has three main subunits: a, b and c. Interacts with TMEM70 and TMEM242 (PubMed:33753518).
messages: Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Part of the complex F(0) domain. A homomeric c-ring of probably 10 subunits is part of the complex rotary element.
messages: Mitochondrion membrane
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: There are three genes which encode the mitochondrial ATP synthase proteolipid and they specify precursors with different import sequences but identical mature proteins. Is the major protein stored in the storage bodies of animals or humans affected with ceroid lipofuscinosis (Batten disease).
messages: Trimethylated by ATPSCKMT at Lys-110. Methylation is required for proper incorporation of the C subunit into the ATP synthase complex and mitochondrial respiration.

9606:CCDC7
gene id: 9606:CCDC7
uniprot id: Q96M83
names: Function
names: Miscellaneous
names: Tissue Specificity
messages: Expressed in epithelium of normal cervix and cervical cancer. Overexpressed in early and interim cervical cancer.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: May play a role in tumorigenesis.

9606:RIPPLY2
gene id: 9606:RIPPLY2
uniprot id: Q5TAB7
names: Disease Annotation
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the ripply family.
messages: Nucleus
messages: Plays a role in somitogenesis. Required for somite segregation and establishment of rostrocaudal polarity in somites (By similarity).
messages: The WRPW motif is required for binding to tle/groucho proteins.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The ripply homology domain is required for transcriptional repression.

9606:HHLA2
gene id: 9606:HHLA2
uniprot id: Q9UM44
names: Function
names: Induction
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Expressed at high levels in colon, kidney, testis, lung and pancreas, and at lower levels in small intestine, liver and skeletal muscle. In immune cells, highly expressed in B-cells, dendritic cells and macrophages. Not detected in T-cells.
messages: Interacts with TMIGD2.
messages: Membrane
messages: Through interaction with TMIGD2, costimulates T-cells in the context of TCR-mediated activation. Enhances T-cell proliferation and cytokine production via an AKT-dependent signaling cascade.
messages: Up-regulated in antigen-presenting cells in response to inflammation. Induced in dendritic cells in response to IFNG, poly(I:C) or heat-killed Listeria monocytogenes (at protein level).

9606:OTUD4
gene id: 9606:OTUD4
uniprot id: Q01804
names: Activity Regulation
names: Caution
names: Function
names: Induction
names: Miscellaneous
names: PTM
names: Sequence Caution
names: Subcellular Location Annotation
names: Subunit
messages: By HIV-1 insertion.
messages: Cytoplasm
messages: Deubiquitinase which hydrolyzes the isopeptide bond between the ubiquitin C-terminus and the lysine epsilon-amino group of the target protein (PubMed:23827681, PubMed:25944111, PubMed:29395066). May negatively regulate inflammatory and pathogen recognition signaling in innate immune response. Upon phosphorylation at Ser-202 and Ser-204 residues, via IL-1 receptor and Toll-like receptor signaling pathway, specifically deubiquitinates 'Lys-63'-polyubiquitinated MYD88 adapter protein triggering down-regulation of NF-kappa-B-dependent transcription of inflammatory mediators (PubMed:29395066). Independently of the catalytic activity, acts as a scaffold for alternative deubiquitinases to assemble specific deubiquitinase-substrate complexes. Associates with USP7 and USP9X deubiquitinases to stabilize alkylation repair enzyme ALKBH3, thereby promoting the repair of alkylated DNA lesions (PubMed:25944111).
messages: Interacts with MYD88; the interaction is direct (PubMed:29395066). Interacts with ALKBH3; the interaction is direct (PubMed:25944111). Interacts with USP7; the interaction is direct (PubMed:25944111). Interacts with USP9X; the interaction is direct (PubMed:25944111).
messages: Intron retention.
messages: Nucleus
messages: Phosphorylated on Ser-202 and Ser-204 likely by CSNK2A1-CSNK2A2 serine/threonine-protein kinase complex. Activates 'Lys-63'-specific deubiquitinase activity.
messages: Phosphorylation on Ser-202 and Ser-204 induces 'Lys-63'-specific deubiquitinase activity.
messages: Predicted from a chimeric transcript isolated from HIV-1-infected cells. The premature stop may be due to intron retention.
messages: Sequence of unknown origin in the N-terminal part.
messages: When expressed in bacteria, recombinant OTUD4 specifically hydrolyzes 'Lys-48'-linked diubiquitin. The physiological relevance of this activity remains unknown (PubMed:23827681, PubMed:25944111, PubMed:29395066). In vivo deubiquitinates 'Lys-63'-linked ubiquitin chains (PubMed:29395066).

9606:DRAM1
gene id: 9606:DRAM1
uniprot id: Q8N682
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the DRAM/TMEM150 family.
messages: By p53/TP53 and p73/TP73. Directly activated by p53/TP53. Significantly down-regulated in tumor cell lines by methylation-dependent transcriptional silencing.
messages: Lysosomal modulator of autophagy that plays a central role in p53/TP53-mediated apoptosis. Not involved in p73/TP73-mediated autophagy.
messages: Lysosome membrane

9606:MSRB1
gene id: 9606:MSRB1
uniprot id: Q9NZV6
names: Cofactor
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the MsrB Met sulfoxide reductase family.
messages: Binds 1 zinc ion per subunit.
messages: Cytoplasm
messages: Methionine-sulfoxide reductase that specifically reduces methionine (R)-sulfoxide back to methionine. While in many cases, methionine oxidation is the result of random oxidation following oxidative stress, methionine oxidation is also a post-translational modification that takes place on specific residue. Acts as a regulator of actin assembly by reducing methionine (R)-sulfoxide mediated by MICALs (MICAL1, MICAL2 or MICAL3) on actin, thereby promoting filament repolymerization. Plays a role in innate immunity by reducing oxidized actin, leading to actin repolymerization in macrophages.
messages: Nucleus
messages: Truncated MSRB1/SEPX1 proteins produced by failed UGA/Sec decoding are ubiquitinated by some Cul2-RING E3 ubiquitin-protein ligase complexes (containing either PRAME, PRAMF6, PRAMF9 or FEM1C as substrate-recognition component).
messages: cytoskeleton

9606:LOXL3
gene id: 9606:LOXL3
uniprot id: P58215
names: Cofactor
names: Disease Annotation
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the lysyl oxidase family.
messages: Contains 1 lysine tyrosylquinone.
messages: Cytoplasm
messages: Defects in LOXL3 are found in a family with an autosomal recessive form of Stickler syndrome, an inherited disorder that associates ocular signs with more or less complete forms of Pierre Robin sequence and sensorineural deafness (PubMed:25663169). Pierre Robin sequence includes an opening in the roof of the mouth (a cleft palate) (PubMed:25663169). The degree of hearing loss varies among affected individuals and may become more severe over time (PubMed:25663169). Syndrome expressivity is variable (PubMed:25663169). Ocular disorders include non-progressive myopia with associated chorioretinal degeneration (PubMed:25663169).
messages: Interacts with STAT3 (PubMed:28065600).
messages: Isoform 1: Predominantly detected in the heart, placenta, lung, and small intestine (PubMed:17018530). Isoform 2: Highly detected in the kidney, pancreas, spleen, and thymus, and is absent in lung (PubMed:17018530). In eye, present in all layers of corneas as well as in the limbus and conjunctiva (at protein level) (PubMed:26218558).
messages: Misses three SRCR domains.
messages: Nucleus
messages: Protein-lysine 6-oxidase that mediates the oxidation of peptidyl lysine residues to allysine in target proteins (PubMed:17018530, PubMed:28065600). Catalyzes the post-translational oxidative deamination of peptidyl lysine residues in precursors of elastin and different types of collagens, a prerequisite in the formation of cross-links between collagens and elastin (PubMed:17018530). Required for somite boundary formation by catalyzing oxidation of fibronectin (FN1), enhancing integrin signaling in myofibers and their adhesion to the myotendinous junction (MTJ) (By similarity). Acts as a regulator of inflammatory response by inhibiting differentiation of naive CD4(+) T-cells into T-helper Th17 or regulatory T-cells (Treg): acts by interacting with STAT3 in the nucleus and catalyzing both deacetylation and oxidation of lysine residues on STAT3, leading to disrupt STAT3 dimerization and inhibit STAT3 transcription activity (PubMed:28065600). Oxidation of lysine residues to allysine on STAT3 preferentially takes place on lysine residues that are acetylated (PubMed:28065600). Also able to catalyze deacetylation of lysine residues on STAT3 (PubMed:28065600).
messages: Shows protein-lysine 6-oxidase activity toward elastin and different types of collagens, with the highest activity toward collagen type IV (PubMed:17018530).
messages: Shows protein-lysine 6-oxidase activity toward elastin and different types of collagens, with the highest activity toward collagen type VIII (PubMed:17018530).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The lysine tyrosylquinone cross-link (LTQ) is generated by condensation of the epsilon-amino group of a lysine with a topaquinone produced by oxidation of tyrosine.
messages: extracellular space

9606:ZNF595
gene id: 9606:ZNF595
uniprot id: Q8IYB9
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:TMEM63B
gene id: 9606:TMEM63B
uniprot id: Q5T3F8
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Acts as an osmosensitive calcium-permeable cation channel (By similarity). Mechanosensitive ion channel that converts mechanical stimuli into a flow of ion (By similarity).
messages: Belongs to the CSC1 (TC 1.A.17) family.
messages: Cell membrane

9606:WDHD1
gene id: 9606:WDHD1
uniprot id: O75717
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Core replisome component that acts as a replication initiation factor. Binds directly to the CMG complex and functions as a hub to recruit additional proteins to the replication fork.
messages: Trimer (PubMed:32453425, PubMed:34694004). Interacts with the polymerase alpha catalytic subunit POLA1. Interacts with MCM10 (PubMed:17761813). Interacts with DNA2 (PubMed:22570476). Interacts with CDC45 and GINS2 subunit of GINS complex; these interactions associate WDHD1 with the CMG helicase complex (PubMed:32453425, PubMed:34694004).
messages: nucleoplasm

9606:TFAP2C
gene id: 9606:TFAP2C
uniprot id: Q92754
names: Domain
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the AP-2 family.
messages: Binds DNA as a dimer. Can form homodimers or heterodimers with other AP-2 family members (By similarity). Interacts with WWOX. Interacts with CITED4. Interacts with UBE2I. Interacts with KCTD1; this interaction represses transcription activation. Interacts with CITED2 (via C-terminus); the interaction stimulates TFAP2B-transcriptional activity. Interacts with MTA1.
messages: During retinoic acid-mediated differentiation.
messages: Nucleus
messages: Sequence-specific DNA-binding protein that interacts with inducible viral and cellular enhancer elements to regulate transcription of selected genes. AP-2 factors bind to the consensus sequence 5'-GCCNNNGGC-3' and activate genes involved in a large spectrum of important biological functions including proper eye, face, body wall, limb and neural tube development. They also suppress a number of genes including MCAM/MUC18, C/EBP alpha and MYC. Involved in the MTA1-mediated epigenetic regulation of ESR1 expression in breast cancer.
messages: Sumoylated on Lys-10; which inhibits transcriptional activity.
messages: The PPxY motif mediates interaction with WWOX.

9606:PRAMEF2
gene id: 9606:PRAMEF2
uniprot id: O60811
names: Similarity
messages: Belongs to the PRAME family.

9606:RRM1
gene id: 9606:RRM1
uniprot id: B4DXD1
uniprot id: B4E0I8
uniprot id: E9PL69
uniprot id: P23921
names: Activity Regulation
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the ribonucleoside diphosphate reductase large chain family.
messages: Cytoplasm
messages: Heterodimer of a large and a small subunit. Heterodimer with small subunit RRM2 or RRM2B. The heterodimer with RRM2 has higher catalytic activity than the heterodimer with RRM2B. Interacts with AHCYL1 which inhibits its activity.
messages: Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides.
messages: The level of the enzyme activity is closely correlated with the growth rate of a cell and appears to vary with the cell cycle.
messages: Two distinct regulatory sites have been defined: the specificity site, which controls substrate specificity, and the activity site which regulates overall catalytic activity. A substrate-binding catalytic site, located on M1, is formed only in the presence of the second subunit M2.
messages: Under complex allosteric control mediated by deoxynucleoside triphosphates and ATP binding to separate specificity and activation sites on the M1 subunit. The type of nucleotide bound at the specificity site determines substrate preference. It seems probable that ATP makes the enzyme reduce CDP and UDP, dGTP favors ADP reduction and dTTP favors GDP reduction. Stimulated by ATP and inhibited by dATP binding to the activity site, the dATP inhibition is mediated by AHCYL1 which stabilizes dATP in the site.

9606:CHAMP1
gene id: 9606:CHAMP1
uniprot id: Q96JM3
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: Chromosome
messages: Interacts with MAD2L2. Interacts with POGZ, CBX1, CBX3 and CBX5.
messages: Nucleus
messages: Phosphorylated by CDK1. Mitotic phosphorylation is required for the attachment of spindle microtubules to the kinetochore.
messages: Required for proper alignment of chromosomes at metaphase and their accurate segregation during mitosis. Involved in the maintenance of spindle microtubules attachment to the kinetochore during sister chromatid biorientation. May recruit CENPE and CENPF to the kinetochore.
messages: kinetochore
messages: spindle

9606:OR4K1
gene id: 9606:OR4K1
uniprot id: Q8NGD4
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Odorant receptor.

9606:ZNF124
gene id: 9606:ZNF124
uniprot id: Q15973
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:SOBP
gene id: 9606:SOBP
uniprot id: A7XYQ1
names: Disease Annotation
names: Function
names: Sequence Caution
names: Similarity
names: Subunit
messages: Belongs to the SOBP family.
messages: Implicated in development of the cochlea.
messages: Interacts (via SIM domains) with SUMO1 and SUMO2.
messages: Intron retention.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:ODF1
gene id: 9606:ODF1
uniprot id: Q14990
names: Domain
names: Function
names: Subunit
names: Tissue Specificity
messages: Component of the outer dense fibers (ODF) of spermatozoa. ODF are filamentous structures located on the outside of the axoneme in the midpiece and principal piece of the mammalian sperm tail and may help to maintain the passive elastic structures and elastic recoil of the sperm tail.
messages: Interacts (via leucine zipper motif) with TCP11 isoform 2 and isoform 3 (PubMed:21597245). Interacts with SPAG4 (By similarity). Interacts with KLC3 (By similarity).
messages: Testis.
messages: The C-terminal contains many C-X-P repeats.

9606:CMBL
gene id: 9606:CMBL
uniprot id: Q96DG6
names: Activity Regulation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the dienelactone hydrolase family.
messages: Cysteine hydrolase. Can convert the prodrug olmesartan medoxomil into its pharmacologically active metabolite olmerstatan, an angiotensin receptor blocker, in liver and intestine. May also activate beta-lactam antibiotics faropenem medoxomil and lenampicillin.
messages: Strongly inhibited by p-chloromercuribenzoate (PCMB). Partially inhibited by bis-p-nitrophenylphosphate (BNPP). Not inhibited by DFP, PMSF, eserine or EDTA.
messages: Widely expressed, with highest levels in liver, followed by kidney, small intestine and colon. Present in liver and intestine (at protein level).
messages: cytosol

9606:MAFB
gene id: 9606:MAFB
uniprot id: Q9Y5Q3
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acts as a transcriptional activator or repressor (PubMed:27181683). Plays a pivotal role in regulating lineage-specific hematopoiesis by repressing ETS1-mediated transcription of erythroid-specific genes in myeloid cells. Required for monocytic, macrophage, osteoclast, podocyte and islet beta cell differentiation. Involved in renal tubule survival and F4/80 maturation. Activates the insulin and glucagon promoters. Together with PAX6, transactivates weakly the glucagon gene promoter through the G1 element. SUMO modification controls its transcriptional activity and ability to specify macrophage fate. Binds element G1 on the glucagon promoter (By similarity). Involved either as an oncogene or as a tumor suppressor, depending on the cell context. Required for the transcriptional activation of HOXB3 in the rhombomere r5 in the hindbrain (By similarity).
messages: Belongs to the bZIP family. Maf subfamily.
messages: Homodimer or heterodimer with other bHLH-Zip transcription factors. Binds DNA as a homodimer or a heterodimer. Forms homodimers and heterodimers with FOS, FOSB and FOSL2, but not with JUN proteins (JUN, JUNB and JUND). Interacts with PAX6; the interaction is direct. Interacts with ETS1 and LRP1 (By similarity). Interacts with the intracellular cytoplasmic domain of LRP1 (LRPICD); the interaction results in a moderate reduction of MAFB transcriptional potential.
messages: Nucleus
messages: Phosphorylated by GSK3 and MAPK13 on serine and threonine residues.
messages: Sumoylated. Sumoylation on Lys-32 and Lys-297 stimulates its transcriptional repression activity and promotes macrophage differentiation from myeloid progenitors (By similarity).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The leucine-zipper domain is involved in the interaction with LRPICD.
messages: Ubiquitous.

9606:SSH3
gene id: 9606:SSH3
uniprot id: Q8TE77
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the protein-tyrosine phosphatase family.
messages: Does not bind to, or colocalize with, filamentous actin.
messages: Nucleus
messages: Protein phosphatase which may play a role in the regulation of actin filament dynamics. Can dephosphorylate and activate the actin binding/depolymerizing factor cofilin, which subsequently binds to actin filaments and stimulates their disassembly (By similarity).
messages: Tyrosine phosphatase activity has not been demonstrated for this protein to date.
messages: cytoskeleton

9606:APBB1
gene id: 9606:APBB1
uniprot id: O00213
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acetylation at Lys-204 and Lys-701 by KAT5 promotes its transcription activator activity.
messages: Cell membrane
messages: Component of a complex, at least composed of APBB1, RASD1/DEXRAS1 and APP (PubMed:18922798, PubMed:18833287, PubMed:18468999). Interacts (via PID domain 2) with APP (with the intracellular domain of the amyloid-beta precursor protein) (PubMed:18833287, PubMed:18468999). Interacts (via PID domain 2) with RASD1/DEXRAS1; impairs the transcription activation activity (PubMed:18922798). Interacts (via PID domain 1) with KAT5/TIP60 (PubMed:33938178). Interacts (via the WW domain) with the proline-rich region of APBB1IP (By similarity). Interacts with TSHZ1 and TSHZ2 (By similarity). Interacts (via the WW domain) with histone H2AX (when phosphorylated on 'Tyr-142') and the proline-rich region of ENAH (PubMed:17686488). Interacts with MAPK8 (PubMed:19234442). Interacts (via PID domain 1) with TSHZ3 (via homeobox domain) (PubMed:19343227). Interacts with SET (PubMed:19343227). Found in a trimeric complex with HDAC1 and TSHZ3; the interaction between HDAC1 and APBB1 is mediated by TSHZ3 (PubMed:19343227). Interacts (via WWW domain) with NEK6 (PubMed:17512906). Interacts (via WWW domain) with ABL1 (PubMed:15031292). Interacts with RNF157 (PubMed:25342469).
messages: Cytoplasm
messages: Expressed preferentially in the brain.
messages: Highly expressed in brain; strongly reduced in post-mortem elderly subjects with Alzheimer disease.
messages: Nucleus
messages: Nucleus speckle
messages: Phosphorylation at Ser-610 by SGK1 promotes its localization to the nucleus (By similarity). Phosphorylated following nuclear translocation (PubMed:15031292, PubMed:18922798). Phosphorylation at Tyr-547 by ABL1 enhances transcriptional activation activity and reduces the affinity for RASD1/DEXRAS1 (PubMed:15031292, PubMed:18922798).
messages: Polyubiquitination by RNF157 leads to degradation by the proteasome (PubMed:25342469).
messages: Transcription coregulator that can have both coactivator and corepressor functions (PubMed:15031292, PubMed:18468999, PubMed:18922798, PubMed:25342469, PubMed:33938178). Adapter protein that forms a transcriptionally active complex with the gamma-secretase-derived amyloid precursor protein (APP) intracellular domain (PubMed:15031292, PubMed:18468999, PubMed:18922798, PubMed:25342469). Plays a central role in the response to DNA damage by translocating to the nucleus and inducing apoptosis (PubMed:15031292, PubMed:18468999, PubMed:18922798, PubMed:25342469). May act by specifically recognizing and binding histone H2AX phosphorylated on 'Tyr-142' (H2AXY142ph) at double-strand breaks (DSBs), recruiting other pro-apoptosis factors such as MAPK8/JNK1 (PubMed:19234442). Required for histone H4 acetylation at double-strand breaks (DSBs) (PubMed:19234442). Its ability to specifically bind modified histones and chromatin modifying enzymes such as KAT5/TIP60, probably explains its transcription activation activity (PubMed:33938178). Functions in association with TSHZ3, SET and HDAC factors as a transcriptional repressor, that inhibits the expression of CASP4 (PubMed:19343227). Associates with chromatin in a region surrounding the CASP4 transcriptional start site(s) (PubMed:19343227). Involved in hippocampal neurite branching and neuromuscular junction formation, as a result plays a role in spatial memory functioning (By similarity). Plays a role in the maintenance of lens transparency (By similarity). May play a role in muscle cell strength (By similarity).
messages: growth cone

9606:COPRS
gene id: 9606:COPRS
uniprot id: Q9NQ92
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Histone-binding protein required for histone H4 methyltransferase activity of PRMT5. Specifically required for histone H4 'Arg-3' methylation mediated by PRMT5, but not histone H3 'Arg-8' methylation, suggesting that it modulates the substrate specificity of PRMT5. Specifically interacts with the N-terminus of histone H4 but not with histone H3, suggesting that it acts by promoting the association between histone H4 and PRMT5. Involved in CCNE1 promoter repression. Plays a role in muscle cell differentiation by modulating the recruitment of PRMT5 to the promoter of genes involved in the coordination between cell cycle exit and muscle differentiation (By similarity).
messages: Interacts with PRMT5. Interacts with histone H4; specifically interacts with the N-terminus of histone H4 but not with histone H3. Interacts with CBFB (By similarity). Found in a complex with PRMT5, RUNX1 and CBFB (By similarity).
messages: Nucleus

9606:SPA17
gene id: 9606:SPA17
uniprot id: A0A172Q397
uniprot id: Q15506
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Homodimer (By similarity). May interact with ROPN1.
messages: Membrane
messages: Sperm surface zona pellucida binding protein. Helps to bind spermatozoa to the zona pellucida with high affinity. Might function in binding zona pellucida and carbohydrates (By similarity).
messages: Sperm surface zona pellucida binding protein. Helps to bind spermatozoa to the zona pellucida with high affinity. Might function in binding zona pellucida and carbohydrates.
messages: Testis and sperm specific.

9606:LIPF
gene id: 9606:LIPF
uniprot id: P07098
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the AB hydrolase superfamily. Lipase family.
messages: Catalyzes the hydrolysis of triacylglycerols to yield free fatty acids, diacylglycerol, monoacylglycerol, and glycerol (PubMed:2243091, PubMed:10358049). Shows a preferential hydrolysis at the sn-3 position of triacylglycerol (PubMed:2243091).
messages: Secreted

9606:MAPK8IP2
gene id: 9606:MAPK8IP2
uniprot id: Q13387
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the JIP scaffold family.
messages: Cytoplasm
messages: Expressed mainly in the brain and pancreas, including insulin-secreting cells. In the nervous system, more abundantly expressed in the cerebellum, pituitary gland, occipital lobe and the amygdala. Also expressed in fetal brain. Very low levels found in uterus, ovary, prostate, colon, testis, adrenal gland, thyroid gland and salivary gland.
messages: Forms homo- or heterooligomeric complexes. Binds specific components of the JNK signaling pathway namely JNK1, JNK2, JNK3, MAP2K7, MAP3K10, MAP3K11, MAP3K12 and MAPK13. Also binds the proline-rich domain-containing splice variant of apolipoprotein E receptor 2 (ApoER2). Binds the cytoplasmic tails of LRP1 and LRP2 (Megalin). Binds the TPR motif-containing C-terminal of kinesin light chain, Klc1, pre-assembled MAPK8IP1 scaffolding complexes are then transported as a cargo of kinesin, to the required subcellular location (By similarity). Interacts with the cytoplasmic domain of APP (By similarity). Interacts with DCLK2. Interacts with TIAM1 and TIAM2 (By similarity). Interacts with FGF13; enables the interaction with MAPK13 and may regulate the MAPK8IP2 scaffolding activity. Interacts with SH3RF2 (By similarity).
messages: Might be artifactual as it is only predicted from a genomic sequence.
messages: The JNK-interacting protein (JIP) group of scaffold proteins selectively mediates JNK signaling by aggregating specific components of the MAPK cascade to form a functional JNK signaling module. JIP2 inhibits IL1 beta-induced apoptosis in insulin-secreting cells. May function as a regulator of vesicle transport, through interactions with the JNK-signaling components and motor proteins (By similarity).

9606:MYLIP
gene id: 9606:MYLIP
uniprot id: Q8WY64
names: Activity Regulation
names: Developmental Stage
names: Domain
names: Function
names: Induction
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Autoubiquitinated.
messages: Can bind 1 iron ion per dimer. Iron binding seems to decrease LDLR degradation activity.
messages: Cell membrane
messages: Cytoplasm
messages: E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of myosin regulatory light chain (MRLC), LDLR, VLDLR and LRP8. Activity depends on E2 enzymes of the UBE2D family. Proteasomal degradation of MRLC leads to inhibit neurite outgrowth in presence of NGF by counteracting the stabilization of MRLC by saposin-like protein (CNPY2/MSAP) and reducing CNPY2-stimulated neurite outgrowth. Acts as a sterol-dependent inhibitor of cellular cholesterol uptake by mediating ubiquitination and subsequent degradation of LDLR.
messages: Expressed in fetal tissues and higher levels were detected in placenta and fetal lung.
messages: Expression is directly activated by NR1H2 and NR1H3. Expression is not dependent of the sterol-response element-binding proteins (SREBPs). Expression is indirectly induced by LDL.
messages: Homodimer. Interacts with the E2 ubiquitin-conjugating enzyme, UBE2D1 (via RING-type zinc finger). Interacts with myosin regulatory light chain (MRLC) and TMEM4.
messages: The FERM domain binds phospholipids and mediates lipoprotein receptors recognition at the plasma membrane through their cytoplasmic tails.
messages: The RING domain mediates ubiquitination and the neurite outgrowth inhibitory activity.
messages: The RING-type zinc finger mediates the interaction with UBE2D E2 enzymes.
messages: Ubiquitously expressed.

9606:CDC42EP2
gene id: 9606:CDC42EP2
uniprot id: O14613
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the BORG/CEP family.
messages: Endomembrane system
messages: Highly expressed in the heart. Weakly expressed in the pancreas and liver.
messages: Interacts with RHOQ and CDC42 in a GTP-dependent manner, and with SEPT7.
messages: Probably involved in the organization of the actin cytoskeleton. May act downstream of CDC42 to induce actin filament assembly leading to cell shape changes. Induces pseudopodia formation in fibroblasts in a CDC42-dependent manner.
messages: The CRIB domain mediates interaction with CDC42.
messages: cytoskeleton

9606:HACD3
gene id: 9606:HACD3
uniprot id: Q9P035
names: Caution
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the very long-chain fatty acids dehydratase HACD family.
messages: By AKAP12 and histone deacetylase inhibitors such as sodium butyrate.
messages: Catalyzes the third of the four reactions of the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process, allows the addition of two carbons to the chain of long- and very long-chain fatty acids/VLCFAs per cycle. This enzyme catalyzes the dehydration of the 3-hydroxyacyl-CoA intermediate into trans-2,3-enoyl-CoA, within each cycle of fatty acid elongation. Thereby, it participates in the production of VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators. May be involved in Rac1-signaling pathways leading to the modulation of gene expression. Promotes insulin receptor/INSR autophosphorylation and is involved in INSR internalization (PubMed:25687571).
messages: Endoplasmic reticulum membrane
messages: Highly expressed in testis, kidney, brain, liver and weakly in skeletal muscle, spleen and heart. No expression detected in leukocytes.
messages: May interact with enzymes of the ELO family (including ELOVL1); with those enzymes that mediate condensation, the first of the four steps of the reaction cycle responsible for fatty acids elongation, may be part of a larger fatty acids elongase complex (PubMed:18554506). Interacts with RAC1 (PubMed:10747961). Associates with internalized insulin receptor/INSR complexes on Golgi/endosomal membranes; HACD3/PTPLAD1 together with ATIC and PRKAA2/AMPK2 is proposed to be part of a signaling network regulating INSR autophosphorylation and endocytosis (PubMed:25687571).
messages: Shares some similarity with tyrosine phosphatase proteins but it has probably no phosphatase activity.

9606:SH3BGRL
gene id: 9606:SH3BGRL
uniprot id: O75368
uniprot id: V9HW48
names: Disease Annotation
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Appears to function as an adapter protein that bridges proteins together or proteins with mRNAs (PubMed:34331014). May function as a ubiquitin ligase-substrate adapter (PubMed:34331014, PubMed:34870550). Additionally, associates with translating cytoplasmic ribosomes and may promote the expression of specific mRNAs (PubMed:34331014, PubMed:34870550).
messages: Belongs to the SH3BGR family.
messages: Cell membrane
messages: Monomer (PubMed:16511048). Interacts with PFN1/Profilin-1 (PubMed:34331014). Interacts with ERBB2 (PubMed:32381043). Interacts with ATG12 (PubMed:34870550). Interacts with BECN1 (PubMed:34870550). Interacts with translating ribosomes (PubMed:34331014, PubMed:34870550).
messages: Promotes breast cancer progression by enhancing the interaction between E3 ligase STUB1 and PFN1, thereby promoting proteasomal degradation of PFN1 and subsequent activation of downstream signaling pathways including PI3K/AKT, NF-kB and WNT (PubMed:34331014). Promotes autophagy presumably by stabilizing the ubuiquitin-like protein ATG12 (PubMed:34870550). Enhances mRNA translation of E3 ligase STUB1 and the autophagy-related protein PIK3C3 (PubMed:34331014, PubMed:34870550). Promotes activation and phosphorylation of ERBB2 at 'Tyr-877' and 'Tyr-1196', and prolongs localization of ERBB2 to the cell membrane (PubMed:32381043). Breast cancer patients with SH3BGRL overexpression usually experience frequent relapse and poor prognosis (PubMed:32381043, PubMed:34870550).
messages: The SH3-binding motif is buried in the tertiary structure, and it is therefore unclear whether it directly mediates protein-binding.
messages: Ubiquitous.
messages: cytosol

9606:P2RY10
gene id: 9606:P2RY10
uniprot id: O00398
names: Developmental Stage
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Putative receptor for purines coupled to G-proteins.
messages: Up-regulated during promyelocytic cell differentiation along the monocytic pathway, but not during granulocytic differentiation.
messages: Weakly expressed in blood leukocytes.

9606:SLC28A2
gene id: 9606:SLC28A2
uniprot id: O43868
uniprot id: Q2M2A7
uniprot id: Q53H72
names: Activity Regulation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Apicolateral cell membrane
messages: Belongs to the concentrative nucleoside transporter (CNT) (TC 2.A.41) family.
messages: Expressed in heart and skeletal muscle followed by liver, kidney, intestine, pancreas, placenta and brain (PubMed:9435697). Weak expression in lung (PubMed:9435697). In testis, primarily localized to the apicolateral membranes of Sertoli cells and vascular endothelial cells, and weakly expressed in Leydig cells, peritubular myoid cells and germ cells (PubMed:35307651).
messages: Inhibited by formycin B.
messages: Membrane
messages: Sodium-dependent and purine-selective transporter (PubMed:9435697, PubMed:10087507). Exhibits the transport characteristics of the nucleoside transport system cif or N1 subtype (N1/cif) (selective for purine nucleosides and uridine) (PubMed:9435697, PubMed:10087507, PubMed:21795683). Plays a critical role in specific uptake and salvage of purine nucleosides in kidney and other tissues (PubMed:9435697). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable).

9606:CFHR4
gene id: 9606:CFHR4
uniprot id: Q92496
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Expressed by the liver and secreted in plasma.
messages: Glycosylated.
messages: Homodimer.
messages: Involved in complement regulation. Can associate with lipoproteins and may play a role in lipid metabolism.
messages: Secreted

9606:VASP
gene id: 9606:VASP
uniprot id: A0A024R0V4
uniprot id: P50552
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the Ena/VASP family.
messages: Cytoplasm
messages: Ena/VASP proteins are actin-associated proteins involved in a range of processes dependent on cytoskeleton remodeling and cell polarity such as axon guidance, lamellipodial and filopodial dynamics, platelet activation and cell migration.
messages: Ena/VASP proteins are actin-associated proteins involved in a range of processes dependent on cytoskeleton remodeling and cell polarity such as axon guidance, lamellipodial and filopodial dynamics, platelet activation and cell migration. VASP promotes actin filament elongation. It protects the barbed end of growing actin filaments against capping and increases the rate of actin polymerization in the presence of capping protein. VASP stimulates actin filament elongation by promoting the transfer of profilin-bound actin monomers onto the barbed end of growing actin filaments. Plays a role in actin-based mobility of Listeria monocytogenes in host cells. Regulates actin dynamics in platelets and plays an important role in regulating platelet aggregation.
messages: Highly expressed in platelets.
messages: Homotetramer. Interacts with PFN1, PFN2, LPP, ACTN1 and ACTG1. Interacts, via the EVH1 domain, with the Pro-rich regions of ZYX. This interaction is important for targeting to focal adhesions and the formation of actin-rich structures at the apical surface of cells. Interacts, via the EVH1 domain, with the Pro-rich domain of Listeria monocytogenes actA. Interacts with APBB1IP. Interacts, via the Pro-rich domain, with the C-terminal SH3 domain of DNMBP (By similarity). Interacts weakly with MEFV.
messages: Major substrate for cAMP-dependent (PKA) and cGMP-dependent protein kinase (PKG) in platelets. The preferred site for PKA is Ser-157, the preferred site for PKG/PRKG1, Ser-239. In ADP-activated platelets, phosphorylation by PKA or PKG on Ser-157 leads to fibrinogen receptor inhibition. Phosphorylation on Thr-278 requires prior phosphorylation on Ser-157 and Ser-239. In response to phorbol ester (PMA) stimulation, phosphorylated by PKC/PRKCA. In response to thrombin, phosphorylated by both PKC and ROCK1. Phosphorylation at Thr-278 by AMPK does not require prior phosphorylation at Ser-157 or Ser-239. Phosphorylation at Ser-157 by PKA is required for localization to the tight junctions in epithelial cells. Phosphorylation modulates F-actin binding, actin filament elongation and platelet activation. Phosphorylation at Ser-322 by AMPK also alters actin filament binding. Carbon monoxide (CO) promotes phosphorylation at Ser-157, while nitric oxide (NO) promotes phosphorylation at Ser-157, but also at Ser-239. Response to NO and CO is blunted in platelets from diabetic patients, and VASP is not phosphorylated efficiently at Ser-157 and Ser-239.
messages: The EVH2 domain is comprised of 3 regions. Block A is a thymosin-like domain required for G-actin binding. The KLKR motif within this block is essential for the G-actin binding and for actin polymerization. Block B is required for F-actin binding and subcellular location, and Block C for tetramerization.
messages: The WH1 domain mediates interaction with XIRP1.
messages: VASP phosphorylation is used to monitor the effect of so-called antiplatelet drugs that reduce platelet reactivity and are used to prevent stent thrombosis, strokes and heart attacks in patients at risk for these problems.
messages: cytoskeleton
messages: filopodium membrane
messages: focal adhesion
messages: lamellipodium membrane
messages: tight junction

9606:SSB
gene id: 9606:SSB
uniprot id: P05455
names: Function
names: Miscellaneous
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: Binds to the 3' poly(U) terminus of nascent RNA polymerase III transcripts, protecting them from exonuclease digestion and facilitating their folding and maturation (PubMed:3192525, PubMed:2470590). In case of Coxsackievirus B3 infection, binds to the viral internal ribosome entry site (IRES) and stimulates the IRES-mediated translation (PubMed:12384597).
messages: Interacts with DDX15. May interact with RUFY1.
messages: Nucleus
messages: Phosphorylated. The phosphorylation sites are at the C-terminal part of the protein.
messages: Sera from patients with systemic lupus erythematosus (SLE) often contain antibodies that react with the normal cellular La protein as if this antigen was foreign.
messages: The N-terminus is blocked.

9606:C14orf39
gene id: 9606:C14orf39
uniprot id: Q8N1H7
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Chromosome
messages: Highest expression in retina, skeletal muscle, testis and colon.
messages: Interacts with SYCE1 (By similarity). Interacts with proteasome subunit PSMA8; to participate in meiosis progression during spermatogenesis (By similarity).
messages: Meiotic protein that localizes to the central element of the synaptonemal complex and is required for chromosome synapsis during meiotic recombination. Required for the appropriate processing of intermediate recombination nodules before crossover formation.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:PPP1CA
gene id: 9606:PPP1CA
uniprot id: A0A140VJS9
uniprot id: P62136
names: Activity Regulation
names: Caution
names: Cofactor
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Interacts with HHV-1 ICP34.5.
messages: (Microbial infection) Interacts with Venezuelan equine encephalitis virus (VEEV) capsid protein; this interaction dephosphorylates the capsid protein, which increases its ability to bind to the viral genome.
messages: (Microbial infection) Necessary for alphaviruses replication.
messages: Belongs to the PPP phosphatase family. PP-1 subfamily.
messages: Binds 1 Fe cation per subunit.
messages: Binds 2 manganese ions per subunit.
messages: Cytoplasm
messages: Nucleus
messages: PP1 comprises a catalytic subunit, PPP1CA, PPP1CB or PPP1CC, which is folded into its native form by inhibitor 2 and glycogen synthetase kinase 3, and then complexed to one or several targeting or regulatory subunits. PPP1R12A, PPP1R12B and PPP1R12C mediate binding to myosin. PPP1R3A (in skeletal muscle), PPP1R3B (in liver), PPP1R3C, PPP1R3D and PPP1R3F (in brain) mediate binding to glycogen. Interacts with PPP1R39 (By similarity). Interacts with BTBD10 (By similarity). Interacts with KCTD20 (By similarity). Interacts with PPP1R9A and PPP1R9B. Part of a complex containing PPP1R15B, PP1 and NCK1/2. Interacts with PHACTR4; which acts as an activator of PP1 activity (By similarity). Interacts with PPP1R15A and PPP1R15B; the interactions mediate binding to EIF2S1 (PubMed:26095357). Interacts with PPP1R7. Interacts with YLPM1. Forms a complex with ILF2, ILF3, YLPM1, KHDRBS1, RBMX and NCOA5. Interacts with NOM1 and PPP1R8. Interacts with PPP1R16B. Interacts with RPSA only in the presence of PPP1R16B. Component of the PTW/PP1 phosphatase complex, composed of PPP1R10/PNUTS, TOX4, WDR82, and PPP1CA or PPP1CB or PPP1CC. Interacts with PPP1R10/PNUTS and PPP1R8. Interacts with WDR82 in the presence of PPP1R10/PNUTS. Interacts with TRIM28; the interaction dephosphorylates TRIM28 on 'Ser-824' and forms a complex at the p21 promoter site. Interacts with isoform 1 and isoform 4 of NEK2. Interacts with FER; this promotes phosphorylation at Thr-320. Interacts with DAB2; the interaction is mutually exclusive with the AXIN1:PPP1CA interaction. Interacts with FOXP3 (PubMed:23396208). Interacts with CENPA (PubMed:25556658). Interacts with ATG16L1 (PubMed:26083323). Found in a complex with PPP1CA, PPP1CC, SHC1 and PEAK1 (PubMed:23846654). Interacts with tensin TNS1 (PubMed:19826001). Interacts with SAXO4, PPP1R21, PPP1R26, PPP1R27, PPP1R35, PPP1R36, PPP1R37, SH3RF2, ELFN1 and ELFN2 (PubMed:19389623).
messages: Phosphorylated. Dephosphorylated at Thr-320 in the presence of ionizing radiation.
messages: Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets. Protein phosphatase 1 (PP1) is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Involved in regulation of ionic conductances and long-term synaptic plasticity. May play an important role in dephosphorylating substrates such as the postsynaptic density-associated Ca(2+)/calmodulin dependent protein kinase II. Component of the PTW/PP1 phosphatase complex, which plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase. Regulates NEK2 function in terms of kinase activity and centrosome number and splitting, both in the presence and absence of radiation-induced DNA damage. Regulator of neural tube and optic fissure closure, and enteric neural crest cell (ENCCs) migration during development. In balance with CSNK1D and CSNK1E, determines the circadian period length, through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation. May dephosphorylate CSNK1D and CSNK1E. Dephosphorylates the 'Ser-418' residue of FOXP3 in regulatory T-cells (Treg) from patients with rheumatoid arthritis, thereby inactivating FOXP3 and rendering Treg cells functionally defective (PubMed:23396208). Dephosphorylates CENPA (PubMed:25556658). Dephosphorylates the 'Ser-139' residue of ATG16L1 causing dissociation of ATG12-ATG5-ATG16L1 complex, thereby inhibiting autophagy (PubMed:26083323).
messages: The phosphatase activity of the PPP1R15A-PP1 complex toward EIF2S1 is specifically inhibited by Salubrinal, a drug that protects cells from endoplasmic reticulum stress.
messages: Up-regulated in synovial fluid mononuclear cells and peripheral blood mononuclear cells from patients with rheumatoid arthritis.
messages: Was originally thought to be part of the MLL5-L complex, at least composed of KMT2E, STK38, PPP1CA, PPP1CB, PPP1CC, HCFC1, ACTB and OGT (PubMed:19377461). However, the corresponding article has been retracted (PubMed:24336203).
messages: nucleolus
messages: nucleoplasm

9606:ETNK1
gene id: 9606:ETNK1
uniprot id: Q9HBU6
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the choline/ethanolamine kinase family.
messages: Cytoplasm
messages: Expressed in kidney, liver, placenta, heart, leukocyte, ovary and testis.
messages: Highly specific for ethanolamine phosphorylation. May be a rate-controlling step in phosphatidylethanolamine biosynthesis.

9606:MADCAM1
gene id: 9606:MADCAM1
uniprot id: Q13477
names: Function
names: PTM
names: Polymorphism
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cell adhesion leukocyte receptor expressed by mucosal venules, helps to direct lymphocyte traffic into mucosal tissues including the Peyer patches and the intestinal lamina propria. It can bind both integrin alpha-4/beta-7 and L-selectin, regulating both the passage and retention of leukocytes. Isoform 2, lacking the mucin-like domain, may be specialized in supporting integrin alpha-4/beta-7-dependent adhesion strengthening, independent of L-selectin binding.
messages: Highly expressed on high endothelial venules (HEV) and lamina propia venules found in the small intestine, and to a lesser extent in the colon and spleen. Very low levels of expression found in pancreas and brain. Not expressed in the thymus, prostate, ovaries, testis, heart, placenta, lung, liver, skeletal muscle, kidney or peripheral blood leukocytes.
messages: Homodimer.
messages: Membrane
messages: The Ser/Thr-rich mucin-like domain may provide possible sites for O-glycosylation.
messages: The number of repeats in the mucin domain varies between 5 and 8 repeats.

9606:UXS1
gene id: 9606:UXS1
uniprot id: Q8NBZ7
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the NAD(P)-dependent epimerase/dehydratase family. UDP-glucuronic acid decarboxylase subfamily.
messages: Catalyzes the NAD-dependent decarboxylation of UDP-glucuronic acid to UDP-xylose (PubMed:23656592, PubMed:22810237, PubMed:25521717). Necessary for the biosynthesis of the core tetrasaccharide in glycosaminoglycan biosynthesis (PubMed:23656592, PubMed:22810237, PubMed:25521717).
messages: Golgi stack membrane
messages: Homodimer and homotetramer (PubMed:23656592). Interacts with AKT1 (By similarity).

9606:TUBB1
gene id: 9606:TUBB1
uniprot id: Q9H4B7
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the tubulin family.
messages: Dimer of alpha and beta chains. A typical microtubule is a hollow water-filled tube with an outer diameter of 25 nm and an inner diameter of 15 nM. Alpha-beta heterodimers associate head-to-tail to form protofilaments running lengthwise along the microtubule wall with the beta-tubulin subunit facing the microtubule plus end conferring a structural polarity. Microtubules usually have 13 protofilaments but different protofilament numbers can be found in some organisms and specialized cells. Interacts with RANBP10.
messages: Hematopoietic cell-specific. Major isotype in leukocytes, where it represents 50% of all beta-tubulins.
messages: Phosphorylated on Ser-172 by CDK1 during the cell cycle, from metaphase to telophase, but not in interphase. This phosphorylation inhibits tubulin incorporation into microtubules.
messages: Some glutamate residues at the C-terminus are monoglycylated but not polyglycylated due to the absence of functional TTLL10 in human. Monoglycylation is mainly limited to tubulin incorporated into cilia and flagella axonemes, which is required for their stability and maintenance. Flagella glycylation controls sperm motility. Both polyglutamylation and monoglycylation can coexist on the same protein on adjacent residues, and lowering glycylation levels increases polyglutamylation, and reciprocally.
messages: Some glutamate residues at the C-terminus are polyglutamylated, resulting in polyglutamate chains on the gamma-carboxyl group (PubMed:26875866). Polyglutamylation plays a key role in microtubule severing by spastin (SPAST). SPAST preferentially recognizes and acts on microtubules decorated with short polyglutamate tails: severing activity by SPAST increases as the number of glutamates per tubulin rises from one to eight, but decreases beyond this glutamylation threshold (PubMed:26875866). Glutamylation is also involved in cilia motility (By similarity).
messages: The MREI motif is common among all beta-tubulin isoforms and may be critical for tubulin autoregulation.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin.
messages: cytoskeleton

9606:VWC2L
gene id: 9606:VWC2L
uniprot id: B2RUY7
uniprot id: B7ZW27
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: May play a role in neurogenesis. May play a role in bone differentiation and matrix mineralization.
messages: Peripherally associated with AMPAR complex. AMPAR complex consists of an inner core made of 4 pore-forming GluA/GRIA proteins (GRIA1, GRIA2, GRIA3 and GRIA4) and 4 major auxiliary subunits arranged in a twofold symmetry. One of the two pairs of distinct binding sites is occupied either by CNIH2, CNIH3 or CACNG2, CACNG3. The other harbors CACNG2, CACNG3, CACNG4, CACNG8 or GSG1L. This inner core of AMPAR complex is complemented by outer core constituents binding directly to the GluA/GRIA proteins at sites distinct from the interaction sites of the inner core constituents. Outer core constituents include at least PRRT1, PRRT2, CKAMP44/SHISA9, FRRS1L and NRN1. The proteins of the inner and outer core serve as a platform for other, more peripherally associated AMPAR constituents, including VWC2L. Alone or in combination, these auxiliary subunits control the gating and pharmacology of the AMPAR complex and profoundly impact their biogenesis and protein processing (By similarity).
messages: Secreted
messages: Synapse

9606:PRRG2
gene id: 9606:PRRG2
uniprot id: O14669
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cell membrane
messages: Gamma-carboxyglutamate residues are formed by vitamin K dependent carboxylation. These residues are essential for the binding of calcium.
messages: Interacts with NEDD4 (By similarity). Interacts (via cytoplasmic domain) with transcriptional coactivator YAP1 (PubMed:17502622).
messages: Widely expressed with highest levels in kidney (PubMed:23873930). Also highly expressed in the thyroid (PubMed:9256434, PubMed:23873930).

9606:CACNG1
gene id: 9606:CACNG1
uniprot id: Q06432
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the PMP-22/EMP/MP20 family. CACNG subfamily.
messages: Component of a calcium channel complex consisting of a pore-forming alpha subunit (CACNA1S) and the ancillary subunits CACNB1 or CACNB2, CACNG1 and CACNA2D1. The channel complex contains alpha, beta, gamma and delta subunits in a 1:1:1:1 ratio, i.e. it contains either CACNB1 or CACNB2.
messages: N-glycosylated.
messages: Regulatory subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents in skeletal muscle. Regulates channel inactivation kinetics.
messages: Skeletal muscle.
messages: sarcolemma

9606:PRMT3
gene id: 9606:PRMT3
uniprot id: O60678
uniprot id: Q8WUV3
names: Activity Regulation
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the class I-like SAM-binding methyltransferase superfamily. Protein arginine N-methyltransferase family.
messages: Cytoplasm
messages: Inhibited by N-ethylmaleimide and high concentrations of zinc chloride.
messages: Monomer and homodimer (By similarity). Interacts with EPB41L3 (via FERM domain); the interaction is direct and inhibits the protein-arginine N-methyltransferase activity of PRMT3 (PubMed:15334060). Interacts with the 40S ribosomal protein RPS2 (PubMed:21059412, PubMed:30530495). Interacts with ALDH1A1; the interaction is direct, inhibits ALDH1A1 aldehyde dehydrogenase activity and is independent of the methyltransferase activity of PRMT3 (PubMed:33495566).
messages: Protein-arginine N-methyltransferase that catalyzes both the monomethylation and asymmetric dimethylation of the guanidino nitrogens of arginine residues in target proteins, and therefore falls into the group of type I methyltransferases (Probable). May regulate retinoic acid synthesis and signaling by inhibiting ALDH1A1 retinal dehydrogenase activity (PubMed:33495566).
messages: The C2H2-type zinc-finger is responsible for substrate specificity.

9606:TRIM59
gene id: 9606:TRIM59
uniprot id: Q8IWR1
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the TRIM/RBCC family.
messages: E3 ubiquitin ligase involved in different processes such as development and immune response (PubMed:22588174, PubMed:30231667). Serves as a negative regulator for innate immune signaling pathways by suppressing RLR-induced activation of IRF3/7 and NF-kappa-B via interaction with adapter ECSIT (PubMed:22588174). Regulates autophagy through modulating both the transcription and the ubiquitination of BECN1 (PubMed:30231667). On the one hand, regulates the transcription of BECN1 through negatively modulating the NF-kappa-B pathway. On the other hand, regulates TRAF6-mediated 'Lys-63'-linked ubiquitination of BECN1, thus affecting the formation of the BECN1-PIK3C3 complex. In addition, mediates 'Lys-48'-linked ubiquitination of TRAF6 and thereby promotes TRAF6 proteasomal degradation (PubMed:30231667). Acts also as a critical regulator for early embryo development from blastocyst stage to gastrula through modulating F-actin assembly and WASH1 'Lys-63'-linked ubiquitination (By similarity).
messages: Endoplasmic reticulum membrane
messages: Interacts with ECSIT (PubMed:22588174).

9606:ABCC1
gene id: 9606:ABCC1
uniprot id: P33527
names: Activity Regulation
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts with human cytomegalovirus protein UL138; this interaction mediates MRP1 degradation via the lysosome.
messages: Belongs to the ABC transporter superfamily. ABCC family. Conjugate transporter (TC 3.A.1.208) subfamily.
messages: Cell membrane
messages: Lung, testis and peripheral blood mononuclear cells.
messages: MK 571 inhibits sphingosine 1-phosphate and leukotriene C4 export.
messages: Mediates export of organic anions and drugs from the cytoplasm (PubMed:7961706, PubMed:16230346, PubMed:9281595, PubMed:10064732, PubMed:11114332). Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotrexate, antiviral drugs and other xenobiotics (PubMed:7961706, PubMed:16230346, PubMed:9281595, PubMed:10064732, PubMed:11114332). Confers resistance to anticancer drugs by decreasing accumulation of drug in cells, and by mediating ATP- and GSH-dependent drug export (PubMed:9281595). Hydrolyzes ATP with low efficiency (PubMed:16230346). Catalyzes the export of sphingosine 1-phosphate from mast cells independently of their degranulation (PubMed:17050692). Participates in inflammatory response by allowing export of leukotriene C4 from leukotriene C4-synthezing cells (By similarity). Mediates ATP-dependent, GSH-independent cyclic GMP-AMP (cGAMP) export (PubMed:36070769). Thus, by limiting intracellular cGAMP concentrations negatively regulates the cGAS-STING pathway (PubMed:36070769).
messages: The gene represented in this entry is involved in disease pathogenesis.

9606:PPM1A
gene id: 9606:PPM1A
uniprot id: B2R8E4
uniprot id: P35813
names: Cofactor
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the PP2C family.
messages: Binds 2 magnesium or manganese ions per subunit.
messages: Enzyme with a broad specificity. Negatively regulates TGF-beta signaling through dephosphorylating SMAD2 and SMAD3, resulting in their dissociation from SMAD4, nuclear export of the SMADs and termination of the TGF-beta-mediated signaling. Dephosphorylates PRKAA1 and PRKAA2. Plays an important role in the termination of TNF-alpha-mediated NF-kappa-B activation through dephosphorylating and inactivating IKBKB/IKKB.
messages: Membrane
messages: Monomer. Interacts with SMAD2; the interaction dephosphorylates SMAD2 in its C-terminal SXS motif resulting in disruption of the SMAD2/SMAD4 complex, SMAD2 nuclear export and termination of the TGF-beta-mediated signaling. Interacts with SMAD2; the interaction dephosphorylates SMAD2 in its C-terminal SXS motif resulting in disruption of the SMAD2/SMAD4 complex, SMAD2 nuclear export and termination of the TGF-beta-mediated signaling. Interacts with the phosphorylated form of IKBKB/IKKB.
messages: N-myristoylation is essential for the recognition of its substrates for dephosphorylation.
messages: Nucleus
messages: cytosol

9606:MECP2
gene id: 9606:MECP2
uniprot id: A0A140VKC4
uniprot id: D3YJ43
uniprot id: P51608
names: Disease Annotation
names: Function
names: Miscellaneous
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Chromosomal protein that binds to methylated DNA. It can bind specifically to a single methyl-CpG pair. It is not influenced by sequences flanking the methyl-CpGs. Binds both 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC)-containing DNA, with a preference for 5-methylcytosine (5mC).
messages: Chromosomal protein that binds to methylated DNA. It can bind specifically to a single methyl-CpG pair. It is not influenced by sequences flanking the methyl-CpGs. Mediates transcriptional repression through interaction with histone deacetylase and the corepressor SIN3A. Binds both 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC)-containing DNA, with a preference for 5-methylcytosine (5mC).
messages: Interacts with FNBP3 (By similarity). Interacts with CDKL5 (PubMed:15917271). Interacts with ATRX; MECP2 recruits ATRX to pericentric heterochromatin in neuronal cells (By similarity). Interacts with NCOR2 (By similarity). Interacts with TBL1XR1; bridges interaction between MECP2 and NCOR1 (PubMed:28348241). Interacts with TBL1X; recruits TBL1X to the heterochromatin foci (PubMed:28348241).
messages: Nucleus
messages: Phosphorylated on Ser-423 in brain upon synaptic activity, which attenuates its repressor activity and seems to regulate dendritic growth and spine maturation.
messages: Present in all adult somatic tissues tested.
messages: Ten times higher expression levels than isoform A in brain.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The disease is caused by variants affecting the gene represented in this entry. Increased dosage of MECP2 due to gene duplication appears to be responsible for the intellectual disability phenotype.
messages: The disease is caused by variants affecting the gene represented in this entry. The MECP2 gene is mutated in Rett syndrome, a severe neurodevelopmental disorder that almost always occurs in females. Although it was first thought that MECP2 mutations causing Rett syndrome were lethal in males, later reports identified a severe neonatal encephalopathy in surviving male sibs of patients with Rett syndrome. Additional reports have confirmed a severe phenotype in males with Rett syndrome-associated MECP2 mutations.
messages: The disease may be caused by variants affecting the gene represented in this entry.

9606:SH3BP5L
gene id: 9606:SH3BP5L
uniprot id: Q7L8J4
names: Function
names: Similarity
messages: Belongs to the SH3BP5 family.
messages: Functions as guanine nucleotide exchange factor (GEF) for RAB11A.

9606:TMEM244
gene id: 9606:TMEM244
uniprot id: Q5VVB8
names: Subcellular Location Annotation
messages: Membrane

9606:USH1C
gene id: 9606:USH1C
uniprot id: Q9Y6N9
names: Disease Annotation
names: Domain
names: Function
names: Miscellaneous
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Anchoring/scaffolding protein that is a part of the functional network formed by USH1C, USH1G, CDH23 and MYO7A that mediates mechanotransduction in cochlear hair cells. Required for normal development and maintenance of cochlear hair cell bundles (By similarity). As part of the intermicrovillar adhesion complex/IMAC plays a role in brush border differentiation, controlling microvilli organization and length. Probably plays a central regulatory role in the assembly of the complex, recruiting CDHR2, CDHR5 and MYO7B to the microvilli tips (PubMed:24725409, PubMed:26812018).
messages: Expressed in small intestine, colon, kidney, eye and weakly in pancreas. Expressed also in vestibule of the inner ear.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Part of the IMAC/intermicrovillar adhesion complex/intermicrovillar tip-link complex composed of ANKS4B, MYO7B, USH1C, CDHR2 and CDHR5 (Probable). Part of a complex composed of USH1C, USH1G and MYO7A (PubMed:21709241). Interacts with F-actin (By similarity). Interacts with USH2A (PubMed:16301216). Interacts with SLC4A7 (PubMed:16301216). Interacts (via PDZ1 domain) with the C-terminus of USHBP1 (PubMed:11311560). Interacts (via N-terminus and PDZ 2 domain) with CDH23 (PubMed:19297620). Interacts with USH1G (PubMed:12588794, PubMed:20142502). Interacts with MYO7B (PubMed:24725409, PubMed:26812017). Interacts with CDHR2 and CDHR5; may mediate their interaction with MYO7B at the microvilli tip (PubMed:24725409, PubMed:26812017). Interacts (via PDZ 1 domain) with ANKS4B (PubMed:26812018, PubMed:26812017). Interacts (via PDZ 1 domain) with DOCK4 (PubMed:16464467).
messages: The N-terminal region constitutes an independently folded domain that has structural similarity with the CCM2 C-terminus, despite very low sequence similarity.
messages: The PDZ 1 domain mediates interaction with ANKS4B, DOCK4, USHBP1, USH1G, SLC4A7.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: cytoskeleton
messages: cytosol
messages: microvillus

9606:GBP6
gene id: 9606:GBP6
uniprot id: B4DRX0
uniprot id: B4E1U2
uniprot id: Q6ZN66
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
messages: (Microbial infection) Ubiquitinated by S.flexneri IpaH9.8, leading to its degradation by the proteasome, thereby preventing its ability to promote host defense against bacterial infection.
messages: Belongs to the TRAFAC class dynamin-like GTPase superfamily. GB1/RHD3 GTPase family.
messages: Belongs to the TRAFAC class dynamin-like GTPase superfamily. GB1/RHD3 GTPase family. GB1 subfamily.
messages: Cytoplasmic vesicle
messages: Interferon (IFN)-inducible GTPase that plays important roles in innate immunity against a diverse range of bacterial, viral and protozoan pathogens, such as bacterial pathogens Listeria monocytogenes and Mycobacterium bovis BCG as well as the protozoan pathogen Toxoplasma gondii (By similarity). Confers protection to several pathogens, including the bacterial pathogens Listeria monocytogenes and Mycobacterium bovis BCG as well as the protozoan pathogen Toxoplasma gondii (By similarity).

9606:PIP5K1C
gene id: 9606:PIP5K1C
uniprot id: O60331
names: Disease Annotation
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acetylation at Lys-265 and Lys-268 seems to decrease lipid 1-phosphatidylinositol-4-phosphate 5-kinase activity. Deacetylation of these sites by SIRT1 positively regulates the exocytosis of TSH-containing granules from pituitary cells.
messages: Catalyzes the phosphorylation of phosphatidylinositol 4-phosphate (PtdIns(4)P/PI4P) to form phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2/PIP2), a lipid second messenger that regulates several cellular processes such as signal transduction, vesicle trafficking, actin cytoskeleton dynamics, cell adhesion, and cell motility (PubMed:12422219, PubMed:22942276). PtdIns(4,5)P2 can directly act as a second messenger or can be utilized as a precursor to generate other second messengers: inositol 1,4,5-trisphosphate (IP3), diacylglycerol (DAG) or phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3/PIP3) (Probable). PIP5K1A-mediated phosphorylation of PtdIns(4)P is the predominant pathway for PtdIns(4,5)P2 synthesis (By similarity). Together with PIP5K1A, is required for phagocytosis, both enzymes regulating different types of actin remodeling at sequential steps (By similarity). Promotes particle attachment by generating the pool of PtdIns(4,5)P2 that induces controlled actin depolymerization to facilitate Fc-gamma-R clustering. Mediates RAC1-dependent reorganization of actin filaments. Required for synaptic vesicle transport (By similarity). Controls the plasma membrane pool of PtdIns(4,5)P2 implicated in synaptic vesicle endocytosis and exocytosis (PubMed:12847086). Plays a role in endocytosis mediated by clathrin and AP-2 (adaptor protein complex 2) (PubMed:12847086). Required for clathrin-coated pits assembly at the synapse (PubMed:17261850). Participates in cell junction assembly (PubMed:17261850). Modulates adherens junctions formation by facilitating CDH1/cadherin trafficking (PubMed:17261850). Required for focal adhesion dynamics. Modulates the targeting of talins (TLN1 and TLN2) to the plasma membrane and their efficient assembly into focal adhesions (PubMed:12422219). Regulates the interaction between talins (TLN1 and TLN2) and beta-integrins (PubMed:12422219). Required for uropodium formation and retraction of the cell rear during directed migration (…
messages: Cell membrane
messages: Cytoplasm
messages: Endomembrane system
messages: Interacts with TLN1 (By similarity). Interacts with TLN2; interaction stimulates 1-phosphatidylinositol-4-phosphate 5-kinase activity (PubMed:12422219). May compete with beta-integrins for the same binding site on TLN1 and TLN2. Interacts with ARF6; interaction stimulates 1-phosphatidylinositol-4-phosphate 5-kinase activity. Interacts with AP2B1. Interacts with AP2M1; phosphorylation of PIP5K1C by CSK disrupts the interaction; clathrin competes with PIP5K1C (By similarity). Interacts with CDH1. Interacts with CSK (By similarity). Interacts with PLCG1; interaction is abolished upon EGF stimulation (By similarity). Interacts with LAPTM4B; promotes SNX5 association with LAPTM4B; kinase activity of PIP5K1C is required; interaction is regulated by phosphatidylinositol 4,5-bisphosphate generated by PIP5K1C (PubMed:25588945).
messages: Isoform 1 is strongly expressed in brain and also detected in heart and lung.
messages: Isoform 2 is strongly expressed in pancreas and liver and in lesser quantities in brain, heart, lung and kidney.
messages: Isoform 3 is detected in large amounts in heart and large intestine, is also present in lung, pancreas and thyroid, and to a lesser extent in brain, stomach and kidney.
messages: Nucleus
messages: Phosphorylation on Ser-650 negatively regulates binding to TLN2 and is strongly stimulated in mitosis. Phosphorylation on Tyr-649 is necessary for targeting to focal adhesions. Phosphorylation on Ser-650 and Tyr-649 are mutually exclusive. Phosphorylated by SYK and CSK (By similarity). Tyrosine phosphorylation is enhanced by PTK2 signaling. Phosphorylated at Tyr-639 upon EGF stimulation. Some studies suggest that phosphorylation on Tyr-649 enhances binding to tailins (TLN1 and TLN2). According to PubMed:15738269 phosphorylation at Tyr-649 does not directly enhance binding to tailins (TLN1 and TLN2) but may act indirectly by inhibiting phosphorylation at Ser-650.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: adherens junction
messages: focal adhesion
messages: phagocytic cup
messages: ruffle membrane
messages: uropodium

9606:IL17RB
gene id: 9606:IL17RB
uniprot id: Q9NRM6
names: Function
names: Miscellaneous
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cell membrane
messages: Expressed in several endocrine tissues, mostly in fetal and adult liver, kidney, pancreas, testis, colon, brain and small intestine; not detected in peripheral blood leukocytes, lymphoid organs, and most cell lines.
messages: Interacts with DAZAP2 (PubMed:22070932). Interacts with TRAF3IP2 (PubMed:24120361).
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Receptor for the pro-inflammatory cytokines IL17B and IL17E. May play a role in controlling the growth and/or differentiation of hematopoietic cells.
messages: Secreted

9606:CCL28
gene id: 9606:CCL28
uniprot id: A0N0Q3
uniprot id: D6RC73
uniprot id: Q9NRJ3
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the intercrine beta (chemokine CC) family.
messages: Chemotactic activity for resting CD4, CD8 T-cells and eosinophils. Binds to CCR3 and CCR10 and induces calcium mobilization in a dose-dependent manner.
messages: Preferentially expressed by epithelial cells of diverse tissues including normal and pathological colon, salivary gland, mammary gland, trachea and rectum. Also found in prostate, spleen, thyroid, psoriasis skin and in lower levels in peripheral blood leukocytes, small intestine, Peyer patches, stomach and normal skin.
messages: Secreted

9606:PYGO2
gene id: 9606:PYGO2
uniprot id: Q9BRQ0
names: Function
names: Sequence Caution
names: Subcellular Location Annotation
names: Subunit
messages: Binds to BCL9 via the PHD-type zinc finger motif, and thereby becomes part of the nuclear beta-catenin/TCF complex.
messages: Involved in signal transduction through the Wnt pathway.
messages: Nucleus
messages: Sequencing errors.

9606:OR7A17
gene id: 9606:OR7A17
uniprot id: A0A126GVR5
uniprot id: O14581
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Membrane
messages: Odorant receptor.

9606:ODAD4
gene id: 9606:ODAD4
uniprot id: Q96NG3
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Component of the outer dynein arm-docking complex (ODA-DC) that mediates outer dynein arms (ODA) binding onto the doublet microtubule. Plays an essential role for the assembly of ODA-DC and for the docking of ODA in ciliary axoneme.
messages: Component of the outer dynein arm-docking complex along with ODAD1, ODAD2 and ODAD3. Interacts with ODAD1; this interaction may facilitate the recruitment and/or attachment of outer dynein arm docking complex proteins, including ODAD1, ODAD3 and ODAD2, to ciliary axonemes (PubMed:27486780). Interacts with components of the IFT complex A, including IFT140, TTC21B/IFT139 and WDR19/IFT144, and the IFT complex B, including IFT46, IFT52 and IFT57 (PubMed:25860617).
messages: Expressed in the nasal mucosa (at protein level).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: cilium axoneme

9606:MYCN
gene id: 9606:MYCN
uniprot id: P04198
names: Developmental Stage
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Amplification of the N-MYC gene is associated with a variety of human tumors, most frequently neuroblastoma, where the level of amplification appears to increase as the tumor progresses.
messages: Efficient DNA binding requires dimerization with another bHLH protein. Binds DNA as a heterodimer with MAX. Interacts with KDM5A, KDM5B and HUWE1. Interacts with MYCNOS. Interacts with AURKA; interaction is phospho-independent and triggers AURKA activation; AURKA competes with FBXW7 for binding to unphosphorylated MYCN but not for binding to unphosphorylated MYCN (PubMed:27837025). Interacts with FBXW7; FBXW7 competes with AURKA for binding to unphosphorylated MYCN but not for binding to phosphorylated MYCN (PubMed:27837025).
messages: Expressed during fetal development.
messages: Expressed in the neuronal cells of the cerebrum, neuroblastomas and thyroid tumors (at protein level).
messages: Nucleus
messages: Phosphorylated by GSK3-beta which may promote its degradation (PubMed:24391509). Phosphorylated by AURKA (PubMed:27837025).
messages: Positively regulates the transcription of MYCNOS in neuroblastoma cells.
messages: The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:ARHGEF26
gene id: 9606:ARHGEF26
uniprot id: Q96DR7
names: Function
names: Induction
names: Sequence Caution
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Activates RhoG GTPase by promoting the exchange of GDP by GTP. Required for the formation of membrane ruffles during macropinocytosis. Required for the formation of cup-like structures during trans-endothelial migration of leukocytes. In case of Salmonella enterica infection, activated by SopB, which induces cytoskeleton rearrangements and promotes bacterial entry.
messages: Certain mRNA species appear to be up-regulated by androgens in prostate cancer cells.
messages: Interacts with ICAM1 and RHOG.
messages: Intron retention.
messages: Isoform 1 is broadly expressed, with highest levels in liver (at protein level). Certain mRNA species appear to be specifically expressed in prostate and liver.
messages: ruffle

9606:INO80
gene id: 9606:INO80
uniprot id: Q9ULG1
names: Activity Regulation
names: Domain
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts with Epstein Barr virus (EBV) lytic switch protein BZLF1; this interaction participates to the activation of early lytic viral genes by BZLF1.
messages: ATPase component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and DNA repair (PubMed:16230350, PubMed:16298340, PubMed:17721549, PubMed:20855601, PubMed:20237820). Binds DNA (PubMed:16298340, PubMed:21303910). As part of the INO80 complex, remodels chromatin by shifting nucleosomes (PubMed:16230350, PubMed:21303910). Regulates transcription upon recruitment by YY1 to YY1-activated genes, where it acts as an essential coactivator (PubMed:17721549). Involved in UV-damage excision DNA repair (PubMed:20855601). The contribution to DNA double-strand break repair appears to be largely indirect through transcriptional regulation (PubMed:20687897). Involved in DNA replication (PubMed:20237820). Required for microtubule assembly during mitosis thereby regulating chromosome segregation cycle (PubMed:20237820).
messages: According to PubMed:10574462, widely expressed. According to PubMed:16298340, specifically expressed in brain, liver and pancreas.
messages: Activated upon binding to double stranded DNA or nucleosomes.
messages: Although the ATP-dependent helicase activity displayed by the INO80 complex requires INO80 ATPase activity, it is likely that the helicase function is carried out by the other components of the complex, RUVBL1 and RUVBL2, and not by INO80 itself.
messages: Belongs to the SNF2/RAD54 helicase family.
messages: Chromosome
messages: Component of the chromatin remodeling INO80 complex; three different complex modules assemble on different domains of INO80 (PubMed:16230350, PubMed:18026119, PubMed:18922472, PubMed:21303910). Interacts with DDB1 (PubMed:20855601). Interacts with transcriptional repressor protein YY1; the interaction recruits the INO80 complex to YY1 target genes (PubMed:17721549, PubMed:18026119). Interacts with YY1AP1 (PubMed:27939641). Interacts with tubulin alpha (PubMed:20237820).
messages: Cytoplasm
messages: Nucleus
messages: The DBINO region is involved in binding to DNA.
messages: spindle

9606:MYL4
gene id: 9606:MYL4
uniprot id: P12829
names: Disease Annotation
names: Function
names: Subunit
messages: Myosin is a hexamer of 2 heavy chains and 4 light chains.
messages: Regulatory light chain of myosin. Does not bind calcium.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:CTNS
gene id: 9606:CTNS
uniprot id: A0A0S2Z3I9
uniprot id: A0A0S2Z3K3
uniprot id: I3L4A9
uniprot id: O60931
names: Disease Annotation
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the cystinosin family.
messages: Cell membrane
messages: Cystine/H(+) symporter that mediates export of cystine, the oxidized dimer of cysteine, from lysosomes (PubMed:11689434, PubMed:18337546, PubMed:22232659, PubMed:29467429, PubMed:33208952, PubMed:15128704). Plays an important role in melanin synthesis by catalyzing cystine export from melanosomes, possibly by inhibiting pheomelanin synthesis (PubMed:22649030). In addition to cystine export, also acts as a positive regulator of mTORC1 signaling in kidney proximal tubular cells, via interactions with components of the v-ATPase and Ragulator complexes (By similarity). Also involved in small GTPase-regulated vesicle trafficking and lysosomal localization of LAMP2A, independently of cystine transporter activity (By similarity).
messages: Interacts with components of the V-ATPase complex. Interacts with components of the Ragulator complex. Interacts with RRAGA/RagA and RRAGC/RagC (By similarity). Interacts with AP-3 complex subunit mu (AP3M1 or AP3M2) (PubMed:25753619).
messages: Lysosome membrane
messages: Melanosome membrane
messages: Membrane
messages: Represents 5-20 % of CTNS transcripts, with the exception of the testis that expresses both isoforms in equal proportions.
messages: Strongly expressed in pancreas, kidney (adult and fetal), skeletal muscle, melanocytes and keratinocytes (PubMed:22649030). Expressed at lower levels in placenta and heart. Weakly expressed in lung, liver and brain (adult and fetal) (PubMed:22649030).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The lysosomal targeting motif, together with the second PQ-loop mediate targeting to the lysosome.

9606:AGAP3
gene id: 9606:AGAP3
uniprot id: Q96P47
names: Activity Regulation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the centaurin gamma-like family.
messages: Cytoplasm
messages: GTPase activity is stimulated by oxidative stress.
messages: GTPase-activating protein for the ADP ribosylation factor family (Potential). GTPase which may be involved in the degradation of expanded polyglutamine proteins through the ubiquitin-proteasome pathway.
messages: Interacts with PML. Interacts with expanded polyglutamine proteins.
messages: Widely expressed.

9606:SLCO2B1
gene id: 9606:SLCO2B1
uniprot id: A0A024R5I4
uniprot id: A0A0A0MTF1
uniprot id: O94956
names: Activity Regulation
names: Caution
names: Domain
names: Function
names: Induction
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: A conserved histidine residue in the third transmembrane domain (His-136) might play an essential role in the pH sensitivity of SLCO2B1/OATP2B1-mediated substrate transport (PubMed:19129463). Transmembrane domain 1 (TM1) may be localized within the substrate binding pocket (PubMed:29871943).
messages: Apical cell membrane
messages: Basal cell membrane
messages: Basolateral cell membrane
messages: Belongs to the organo anion transporter (TC 2.A.60) family.
messages: Cell membrane
messages: E1S, DHEA-S and PregS transports are regulated by steroid hormones. In the case of testosterone, transport of E1S and DHEA-S was inhibited, whereas progesterone stimulated E1S, DHEA-S and PregS uptake (PubMed:16908597). Progesterone stimulates high-affinity uptake of E1S whereas it inhibits low-affinity uptake of E1S (Ref.24). Progesterone doesn't affect the uptake of PGE2 (Ref.24).
messages: Has estrone 3-sulfate (E1S) transport activity comparable with the full-length isoform 1.
messages: Highest expression in brain. Predominant isoform compared to isoform 3 in small intestine duodenum, kidney, placenta, and skeletal muscle.
messages: Its expression is regulated by HNF4A.
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: Mediates the Na(+)-independent transport of steroid sulfate conjugates and other specific organic anions (PubMed:10873595, PubMed:11159893, PubMed:11932330, PubMed:12724351, PubMed:14610227, PubMed:16908597, PubMed:18501590, PubMed:20507927, PubMed:22201122, PubMed:23531488, PubMed:25132355, PubMed:27576593, PubMed:26383540, PubMed:28408210, PubMed:29871943, PubMed:34628357). Responsible for the transport of estrone 3-sulfate (E1S) through the basal membrane of syncytiotrophoblast, highlighting a potential role in the placental absorption of fetal-derived sulfated steroids including the steroid hormone precursor dehydroepiandrosterone sulfate (DHEA-S) (PubMed:11932330, PubMed:12409283). Also facilitates the uptake of sulfated steroids at the basal/sinusoidal membrane of hepatocytes, therefore accounting for the major part of organic anions clearance of liver (PubMed:11159893). Mediates the intestinal uptake of sulfated steroids (PubMed:12724351, PubMed:28408210). Mediates the uptake of the neurosteroids DHEA-S and pregnenolone sulfate (PregS) into the endothelial cells of the blood-brain barrier as the first step to enter the brain (PubMed:16908597, PubMed:25132355). Also plays a role in the reuptake of neuropeptides such as substance P/TAC1 and vasoactive intestinal peptide/VIP released from retinal neurons (PubMed:25132355). May act as a heme transporter that promotes cellular iron availability via heme oxygenase/HMOX2 and independently of TFRC (PubMed:35714613). Also transports heme by-product coproporphyrin III (CPIII), and may be involved in their hepatic disposition (PubMed:26383540). Mediates the uptake of other substrates such as prostaglandins D2 (PGD2), E1 (PGE1) and E2 (PGE2), taurocholate, L-thyroxine, leukotriene C4 and thromboxane B2 (PubMed:10873595, PubMed:14610227, PubMed:19129463, Ref.24, PubMed:29871943). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable). Shows a pH-sensitive substra…
messages: Membrane
messages: Most likely contributes to the oral absorption and the disposition of a wide range of drugs in the intestine and the liver (PubMed:10873595, PubMed:11159893, PubMed:12724351, PubMed:14610227, PubMed:23531488, PubMed:26277985, Ref.24, PubMed:27576593).
messages: Predominant isoform compared to isoform 1 in liver. Also expressed in small intestine duodenum, kidney, brain, placenta, and skeletal muscle.
messages: Strongly expressed in the liver, at the sinusoidal membrane of the hepatocytes (PubMed:10873595, PubMed:11159893, PubMed:23531488). Expressed in the kidney (PubMed:11159893). Expressed in placental trophoblasts and syncytiotrophoblast (PubMed:11159893, PubMed:11932330, PubMed:12409283, PubMed:26277985). Expressed in the small intestine (PubMed:10873595, PubMed:11159893, PubMed:12724351, PubMed:23531488, PubMed:28408210). Expressed in the blood-brain barrier, in endothelial cells of brain capillaries (PubMed:11159893, PubMed:25132355). Expressed in the retina, in the inner nuclear layer and the inner plexiform layer (PubMed:25132355). Expressed in skelettal muscles (PubMed:23531488). In testis, primarily localized to the basal membrane of Sertoli cells and weakly expressed within the tubules (PubMed:10873595, PubMed:11159893, PubMed:35307651). Also expressed in pancreas, lung, heart, colon, ovary and spleen (PubMed:10873595, PubMed:11159893). Expressed in fetal brain, heart, kidney, liver, lung, skeletal muscle, spleen and pancreas (PubMed:10873595).
messages: While some reports have shown that E1S transport exhibited single-saturation kinetics (PubMed:11932330, PubMed:14610227), other studies demonstrated a biphasic saturation kinetics (PubMed:22201122, Ref.24, PubMed:11932330, PubMed:14610227). Despite a previous report that demonstrated a pH-dependent substrate uptake and a transport stimulation at low pH (PubMed:14610227), another study did not observe any pH-dependent E1S and taurocholate transport (PubMed:23531488, PubMed:14610227). Was shown to mediate bile acid taurocholate transport at low pH in some studies (PubMed:14610227, PubMed:29871943), but not others (PubMed:23531488, PubMed:11159893, PubMed:29871943). The enterocyte localization of SLCO2B1/OATP2B1 remains uncertain. While some authors found it in the apical membrane (PubMed:12724351), consistent with a function as uptake carrier contributing to the intestinal absorption of drugs, other studies demonstrated a basolateral membrane expression, supporting a physiological role in substrate uptake from the blood flow and intestinal clearance (PubMed:28408210, PubMed:12724351).

9606:CTU1
gene id: 9606:CTU1
uniprot id: Q7Z7A3
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the TtcA family. CTU1/NCS6/ATPBD3 subfamily.
messages: Component of a complex at least composed of URM1, CTU2/NCS2 and CTU1/ATPBD3. May form a heterodimer with CTU2/NCS2.
messages: Cytoplasm
messages: Plays a central role in 2-thiolation of mcm(5)S(2)U at tRNA wobble positions of tRNA(Lys), tRNA(Glu) and tRNA(Gln). Directly binds tRNAs and probably acts by catalyzing adenylation of tRNAs, an intermediate required for 2-thiolation. It is unclear whether it acts as a sulfurtransferase that transfers sulfur from thiocarboxylated URM1 onto the uridine of tRNAs at wobble position.

9606:DOK5
gene id: 9606:DOK5
uniprot id: Q9P104
names: Domain
names: Function
names: PTM
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Belongs to the DOK family. Type B subfamily.
messages: DOK proteins are enzymatically inert adaptor or scaffolding proteins. They provide a docking platform for the assembly of multimolecular signaling complexes. DOK5 functions in RET-mediated neurite outgrowth and plays a positive role in activation of the MAP kinase pathway. Putative link with downstream effectors of RET in neuronal differentiation.
messages: Highest expression in skeletal muscle, lower in brain, heart and kidney. Also detected in activated peripheral blood T-lymphocytes.
messages: Interacts with phosphorylated RET. In contrast to other DOK proteins, it does not interact with RASGAP (By similarity).
messages: PTB domain mediates receptor interaction.
messages: Phosphorylated on tyrosine residues in response to insulin, IGF1 and GDNF.

9606:STAR
gene id: 9606:STAR
uniprot id: P49675
uniprot id: Q6IBK0
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Expressed in gonads, adrenal cortex and kidney.
messages: May interact with TSPO.
messages: Mitochondrion
messages: Plays a key role in steroid hormone synthesis by enhancing the metabolism of cholesterol into pregnenolone. Mediates the transfer of cholesterol from the outer mitochondrial membrane to the inner mitochondrial membrane where it is cleaved to pregnenolone.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:APOD
gene id: 9606:APOD
uniprot id: P05090
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: APOD is primarily localized in HDL (60-65%), with most of the remainder in VHDL and only trace amounts in VLDL and LDL.
messages: APOD occurs in the macromolecular complex with lecithin-cholesterol acyltransferase. It is probably involved in the transport and binding of bilin. Appears to be able to transport a variety of ligands in a number of different contexts.
messages: Belongs to the calycin superfamily. Lipocalin family.
messages: Expressed in liver, intestine, pancreas, kidney, placenta, adrenal, spleen, fetal brain tissue and tears.
messages: Homodimer. In plasma, also exists as a disulfide-linked heterodimer with APOA2.
messages: N-glycosylatd. N-glycan heterogeneity at Asn-65: Hex5HexNAc4 (major) and Hex6HexNAc5 (minor); at Asn-98: Hex5HexNAc4 (minor), dHex1Hex5HexNAc4 (major), dHex1Hex6HexNAc5 (minor) and dHex1Hex7HexNAc6 (minor).
messages: Secreted

9606:OR2T11
gene id: 9606:OR2T11
uniprot id: Q8NH01
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Odorant receptor.

9606:RNASE12
gene id: 9606:RNASE12
uniprot id: Q5GAN4
uniprot id: W0UV30
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the pancreatic ribonuclease family.
messages: Does not exhibit any ribonuclease activity.
messages: Secreted

9606:ROPN1
gene id: 9606:ROPN1
uniprot id: A0A140VKB2
uniprot id: Q9HAT0
names: Developmental Stage
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: 'Ropporin' comes from the Japanese word 'oppo' which means 'tail'.
messages: Belongs to the ropporin family.
messages: Expressed in fetal liver.
messages: Homodimer. Interacts with AKAP3 and RHPN1 (By similarity). May interact with SPA17 (PubMed:17551920). Interacts with FSCB; the interaction increases upon spermatozoa capacitation conditions (By similarity).
messages: Important for male fertility. With ROPN1L, involved in fibrous sheath integrity and sperm motility, plays a role in PKA-dependent signaling processes required for spermatozoa capacitation.
messages: Sumoylated, sumoylation decreases upon spermatozoa capacitation conditions.
messages: Testis specific in adult. Overexpressed in hematologic tumor cells.
messages: The RIIa domain mediates interaction with AKAP3.
messages: flagellum

9606:AGPAT3
gene id: 9606:AGPAT3
uniprot id: Q9NRZ7
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the 1-acyl-sn-glycerol-3-phosphate acyltransferase family.
messages: Converts 1-acyl-sn-glycerol-3-phosphate (lysophosphatidic acid or LPA) into 1,2-diacyl-sn-glycerol-3-phosphate (phosphatidic acid or PA) by incorporating an acyl moiety at the sn-2 position of the glycerol backbone (PubMed:21173190). Acts on LPA containing saturated or unsaturated fatty acids C16:0-C20:4 at the sn-1 position using C18:1, C20:4 or C18:2-CoA as the acyl donor (PubMed:21173190). Also acts on lysophosphatidylcholine, lysophosphatidylinositol and lysophosphatidylserine using C18:1 or C20:4-CoA (PubMed:21173190). Has a preference for arachidonoyl-CoA as a donor (By similarity). Has also a modest lysophosphatidylinositol acyltransferase (LPIAT) activity, converts lysophosphatidylinositol (LPI) into phosphatidylinositol (By similarity).
messages: Endoplasmic reticulum membrane
messages: Nucleus envelope
messages: The HXXXXD motif is essential for acyltransferase activity and may constitute the binding site for the phosphate moiety of the glycerol-3-phosphate.
messages: Widely expressed with highest levels in testis, pancreas and kidney, followed by spleen, lung, adipose tissue and liver.

9606:ALS2
gene id: 9606:ALS2
uniprot id: Q96Q42
names: Disease Annotation
names: Function
names: Subunit
messages: Forms a heteromeric complex with ALS2CL. Interacts with ALS2CL.
messages: May act as a GTPase regulator. Controls survival and growth of spinal motoneurons (By similarity).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:B4GALT2
gene id: 9606:B4GALT2
uniprot id: O60909
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the glycosyltransferase 7 family.
messages: Golgi stack membrane
messages: Responsible for the synthesis of complex-type N-linked oligosaccharides in many glycoproteins as well as the carbohydrate moieties of glycolipids (PubMed:9405390). Can produce lactose (PubMed:9405390).
messages: Weakly expressed in various tissues. Highest expression in prostate, testis, ovary, intestine, muscle, and in fetal brain.

9606:SRGAP3
gene id: 9606:SRGAP3
uniprot id: O43295
names: Disease Annotation
names: Domain
names: Function
names: Subunit
names: Tissue Specificity
messages: A chromosomal aberration involving SRGAP3 is found in a patient with severe idiopathic intellectual disability (PubMed:12195014). Translocation t(X;3)(p11.2;p25) (PubMed:12195014).
messages: GTPase-activating protein for RAC1 and perhaps Cdc42, but not for RhoA small GTPase. May attenuate RAC1 signaling in neurons.
messages: Highly expressed in adult and fetal brain. Expressed at low levels in kidney. Isoform 3 is expressed in the kidney but is absent in the brain.
messages: Homodimer (Probable). Forms a heterooligomer with SRGAP1 and SRGAP2 through its F-BAR domain. Interacts with WASF1. Probably interacts with ROBO1. Interacts with FASLG.
messages: The F-BAR domain mediates oligomerization, binds membranes, and induces plasma membrane protrusions.

9606:B3GNT8
gene id: 9606:B3GNT8
uniprot id: Q7Z7M8
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the glycosyltransferase 31 family.
messages: Beta-1,3-N-acetylglucosaminyltransferase that plays a role in the elongation of specific branch structures of multiantennary N-glycans. Has strong activity towards tetraantennary N-glycans and 2,6 triantennary glycans.
messages: Golgi apparatus membrane
messages: Highly expressed in small intestine, pancreas, spleen, bone marrow, lung, throat, and ileum, and weakly in fetal brain, cerebellum, heart, liver, tongue, breast, uteri, and testis. Not detected in colon. Differentially expressed in human tumor cell lines.
messages: Interacts with B3GNT2; this interaction greatly increases B3GNT2 catalytic activity, independently of B3GNT8 enzymatic activity.
messages: Up-regulated in colon cancer.

9606:UNC13A
gene id: 9606:UNC13A
uniprot id: Q9UPW8
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the unc-13 family.
messages: Cell membrane
messages: Cytoplasm
messages: Expressed in pancreatic islet cells (PubMed:12871971). Expressed in melanocytes (PubMed:23999003).
messages: Interacts with the N-termini of STX1A and/or STX1B1 and DOC2A. Interacts with BSN. Interacts with RIMS1 which recruits UNC13A to the active zone. Forms homodimers via its first C2 domain. Also interacts via this domain with the zinc finger domain of RIMS2. Part of a complex consisting of ERC2, RIMS1 and UNC13A. Also part of a complex consisting of UNC13A, RIMS2 and RAB3A (By similarity). Interacts with FBXO45 (via SRY domain); leading to the degradation of UNC13A by the proteasome (By similarity).
messages: Plays a role in vesicle maturation during exocytosis as a target of the diacylglycerol second messenger pathway. Involved in neurotransmitter release by acting in synaptic vesicle priming prior to vesicle fusion and participates in the activity-dependent refilling of readily releasable vesicle pool (RRP). Essential for synaptic vesicle maturation in most excitatory/glutamatergic but not inhibitory/GABA-mediated synapses. Facilitates neuronal dense core vesicles fusion as well as controls the location and efficiency of their synaptic release (By similarity). Also involved in secretory granule priming in insulin secretion. Plays a role in dendrite formation by melanocytes (PubMed:23999003).
messages: Presynaptic active zone
messages: Presynaptic cell membrane
messages: The C-terminal region containing both MHD domains and the third C2 domain is required for synaptic vesicle priming activity.
messages: The C2 domains are not involved in calcium-dependent phospholipid binding.

9606:RBFOX1
gene id: 9606:RBFOX1
uniprot id: B7Z1U7
uniprot id: Q59HD3
uniprot id: Q9NWB1
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Binds to the C-terminus of ATXN2.
messages: Cytoplasm
messages: Nucleus
messages: Predominantly expressed in muscle and brain.
messages: RNA-binding protein that regulates alternative splicing events by binding to 5'-UGCAUGU-3' elements. Regulates alternative splicing of tissue-specific exons and of differentially spliced exons during erythropoiesis.
messages: RNA-binding protein that regulates alternative splicing events.

9606:PRRX1
gene id: 9606:PRRX1
uniprot id: P54821
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Acts as a transcriptional regulator of muscle creatine kinase (MCK) and so has a role in the establishment of diverse mesodermal muscle types. The protein binds to an A/T-rich element in the muscle creatine enhancer (By similarity).
messages: Belongs to the paired homeobox family.
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:MCEMP1
gene id: 9606:MCEMP1
uniprot id: Q8IX19
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Expressed specifically in mast cells. Found primarily in lung.
messages: Membrane

9606:WFDC5
gene id: 9606:WFDC5
uniprot id: Q8TCV5
names: Function
names: Induction
names: Subcellular Location Annotation
messages: By p53/TP53.
messages: Putative acid-stable proteinase inhibitor.
messages: Secreted

9606:NHLRC2
gene id: 9606:NHLRC2
uniprot id: Q8NBF2
names: Caution
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Contains a thioredoxin domain, but lacks thioredoxin activity.
messages: Monomer.
messages: Required for normal embryonic development.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitous. Detected in heart, kidney, muscle, brain, lung, liver and in skin fibroblasts (at protein level).
messages: cytosol

9606:CLCN1
gene id: 9606:CLCN1
uniprot id: P35523
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the chloride channel (TC 2.A.49) family. ClC-1/CLCN1 subfamily.
messages: Cell membrane
messages: Homodimer.
messages: Predominantly expressed in skeletal muscles.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Voltage-gated chloride channel (PubMed:8112288, PubMed:9122265, PubMed:12456816). Plays an important role in membrane repolarization in skeletal muscle cells after muscle contraction. The CLC channel family contains both chloride channels and proton-coupled anion transporters that exchange chloride or another anion for protons (Probable). The absence of conserved gating glutamate residues is typical for family members that function as channels (Probable).

9606:AMY1C
gene id: 9606:AMY1C
uniprot id: P0DTE7
uniprot id: P0DTE8
uniprot id: P0DUB6
names: Caution
names: Cofactor
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the glycosyl hydrolase 13 family.
messages: Binds 1 Ca(2+) ion per subunit.
messages: Binds 1 Cl(-) ion per subunit.
messages: Calcium-binding enzyme that initiates starch digestion in the oral cavity (PubMed:12527308). Catalyzes the hydrolysis of internal (1->4)-alpha-D-glucosidic bonds, yielding a mixture of maltose, isomaltose, small amounts of glucose as well as small linear and branched oligosaccharides called dextrins (PubMed:12527308).
messages: Monomer.
messages: Secreted
messages: Three distinct genes (AMY1A, AMY1B and AMY1C), located in a gene cluster on 1p21, encode proteins sharing the same peptidic sequence.

9606:CLRN2
gene id: 9606:CLRN2
uniprot id: A0PK11
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the clarin family.
messages: Plays a key role to hearing function. Required for normal organization and maintenance of the stereocilia bundle and for mechano-electrical transduction.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: stereocilium membrane

9606:SLC6A7
gene id: 9606:SLC6A7
uniprot id: Q99884
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A7 subfamily.
messages: Brain specific (at protein level) (PubMed:7651355). Highly expressed in hippocampus, corpus striatum and temporal cortex. Also expressed in frontal cortex, occipital cortex and, at lower levels, in cerebellum and parietal cortex (at protein level) (PubMed:7651355).
messages: Brain specific sodium (and chloride)-dependent proline transporter (PubMed:7651355). Terminates the action of proline by its high affinity sodium-dependent reuptake into presynaptic terminals (Probable).
messages: Synaptic cell membrane

9606:WIF1
gene id: 9606:WIF1
uniprot id: Q9Y5W5
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Binds to WNT proteins and inhibits their activities. May be involved in mesoderm segmentation.
messages: Interacts with MYOC.
messages: Secreted

9606:C9orf85
gene id: 9606:C9orf85
uniprot id: Q96MD7
names: Miscellaneous
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

9606:RGS9
gene id: 9606:RGS9
uniprot id: A8K1G1
uniprot id: O75916
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Heterodimer with GNB5. Interacts with RGS7BP, leading to regulate the subcellular location of the heterodimer formed with GNB5. Component of the RGS9-1-Gbeta5 complex composed of RGS9 (RGS9-1), Gbeta5 (GNB5) and RGS9BP. Interacts with PDE6G and GNAT1.
messages: Highly expressed in the caudate and putamen, lower levels found in the hypothalamus and nucleus accumbens and very low levels in cerebellum. Not expressed in globus pallidus or cingulate cortex. Isoform 2 is expressed predominantly in pineal gland and retina. Isoform 3 is expressed in retina (abundant in photoreceptors).
messages: In photoreceptor cells the DEP domain is essential for targeting RGS9 to the outer rod segments.
messages: Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form. Binds to GNAT1. Involved in phototransduction; key element in the recovery phase of visual transduction (By similarity).
messages: Membrane
messages: Retinal isoform 3 is light-dependent phosphorylated at 'Ser-478'. Phosphorylation is decreased by light exposition (By similarity).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:TOP3B
gene id: 9606:TOP3B
uniprot id: A8K4N2
uniprot id: O95985
names: Function
names: Similarity
names: Tissue Specificity
messages: Belongs to the type IA topoisomerase family.
messages: Introduces a single-strand break via transesterification at a target site in duplex DNA. Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(5'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 3'-OH DNA strand.
messages: Isoform 1 is found in testis, heart and skeletal muscle. A 4 kb transcript which probably represents isoform 2 is found in thymus, kidney and pancreas.
messages: Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(5'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 3'-OH DNA strand. The free DNA strand than undergoes passage around the unbroken strand thus removing DNA supercoils. Finally, in the religation step, the DNA 3'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone (By similarity). Possesses negatively supercoiled DNA relaxing activity.

9606:ACKR2
gene id: 9606:ACKR2
uniprot id: O00590
names: Domain
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Atypical chemokine receptor that controls chemokine levels and localization via high-affinity chemokine binding that is uncoupled from classic ligand-driven signal transduction cascades, resulting instead in chemokine sequestration, degradation, or transcytosis. Also known as interceptor (internalizing receptor) or chemokine-scavenging receptor or chemokine decoy receptor. Acts as a receptor for chemokines including CCL2, CCL3, CCL3L1, CCL4, CCL5, CCL7, CCL8, CCL11, CCL13, CCL17, CCL22, CCL23, CCL24, SCYA2/MCP-1, SCY3/MIP-1-alpha, SCYA5/RANTES and SCYA7/MCP-3. Upon active ligand stimulation, activates a beta-arrestin 1 (ARRB1)-dependent, G protein-independent signaling pathway that results in the phosphorylation of the actin-binding protein cofilin (CFL1) through a RAC1-PAK1-LIMK1 signaling pathway. Activation of this pathway results in up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation. By scavenging chemokines in tissues, on the surfaces of lymphatic vessels, and in placenta, plays an essential role in the resolution (termination) of the inflammatory response and in the regulation of adaptive immune responses. Plays a major role in the immune silencing of macrophages during the resolution of inflammation. Acts as a regulator of inflammatory leukocyte interactions with lymphatic endothelial cells (LECs) and is required for immature/mature dendritic cells discrimination by LECs.
messages: Belongs to the G-protein coupled receptor 1 family. Atypical chemokine receptor subfamily.
messages: By interleukin-6 and interferon-gamma.
messages: Cell membrane
messages: Early endosome
messages: Found in endothelial cells lining afferent lymphatics in dermis and lymph nodes. Also found in lymph nodes subcapsular and medullary sinuses, tonsillar lymphatic sinuses and lymphatics in mucosa and submucosa of small and large intestine and appendix. Also found in some malignant vascular tumors. Expressed at high levels in Kaposi sarcoma-related pathologies. Expressed on apoptotic neutrophils (at protein level). Expressed primarily in placenta and fetal liver, and found at very low levels in the lung and lymph node.
messages: Phosphorylated on serine residues in the C-terminal cytoplasmic tail.
messages: Recycling endosome
messages: The C-terminal cytoplasmic tail controls its phosphorylation, stability, intracellular trafficking itinerary, and chemokine scavenging properties.

9606:KIF24
gene id: 9606:KIF24
uniprot id: Q5T7B8
names: Developmental Stage
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family.
messages: Increases as cells progress through G1, peaks during S and G2 phases and decreases as cells enter mitosis during G2/M (at protein level).
messages: Interacts with CCP110, CEP97, TALPID3 (PubMed:21620453, PubMed:24421332). Interacts with MPHOSPH9 (PubMed:30375385).
messages: Microtubule-dependent motor protein that acts as a negative regulator of ciliogenesis by mediating recruitment of CCP110 to mother centriole in cycling cells, leading to restrict nucleation of cilia at centrioles. Mediates depolymerization of microtubules of centriolar origin, possibly to suppress aberrant cilia formation (PubMed:21620453). Following activation by NEK2 involved in disassembly of primary cilium during G2/M phase but does not disassemble fully formed ciliary axonemes. As cilium assembly and disassembly is proposed to coexist in a dynamic equilibrium may suppress nascent cilium assembly and, potentially, ciliar re-assembly in cells that have already disassembled their cilia ensuring the completion of cilium removal in the later stages of the cell cycle (PubMed:26290419). Plays an important role in recruiting MPHOSPH9, a negative regulator of cilia formation to the distal end of mother centriole (PubMed:30375385).
messages: centriole
messages: centrosome

9606:RFXAP
gene id: 9606:RFXAP
uniprot id: O00287
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Nucleus
messages: Part of the RFX complex that binds to the X-box of MHC II promoters.
messages: Phosphorylated.
messages: The C-terminal domain is necessary for the RFX complex formation.
messages: The RFX heterotetrameric complex consists of 2 molecules of RFX5 and one each of RFXAP and RFX-B/RFXANK; with each subunit representing a separate complementation group. RFX forms cooperative DNA binding complexes with X2BP and CBF/NF-Y. RFX associates with CIITA to form an active transcriptional complex.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitous.

9606:ZNF688
gene id: 9606:ZNF688
uniprot id: P0C7X2
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:RHOJ
gene id: 9606:RHOJ
uniprot id: Q9H4E5
names: Function
names: Induction
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the small GTPase superfamily. Rho family.
messages: Cell membrane
messages: Could be created by usage of an unusual splicing donor site.
messages: Expression is regulated by the transcription factor ERG.
messages: Interacts with the CRIB domains of proteins such as Pak1 and Was/Wasp (By similarity). Interacts with GLUL (PubMed:30158707).
messages: Palmitoylated; regulates localization to the plasma membrane and may be mediated by GLUL.
messages: Plasma membrane-associated small GTPase specifically involved in angiogenesis (PubMed:21628409, PubMed:24434213, PubMed:30158707). Required for endothelial cell migration during vascular development via its interaction with GLUL (PubMed:30158707). Elicits the formation of F-actin-rich structures, thereby regulating endothelial cell migration (PubMed:30158707).
messages: Specifically expressed in endothelial cells in different tissues, such as brain, heart, lung and liver.

9606:SPATA6L
gene id: 9606:SPATA6L
uniprot id: Q8N4H0
names: Miscellaneous
names: Similarity
messages: Belongs to the SPATA6 family.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

9606:PRPH
gene id: 9606:PRPH
uniprot id: B3KWQ6
uniprot id: P41219
names: Disease Annotation
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the intermediate filament family.
messages: Class-III neuronal intermediate filament protein (By similarity). May form an independent structural network without the involvement of other neurofilaments or may cooperate with the neuronal intermediate filament proteins NEFL, NEFH, NEFM and INA to form a filamentous network (PubMed:15446584, PubMed:15322088). Assembly of the neuronal intermediate filaments may be regulated by RAB7A (By similarity). Plays a role in the development of unmyelinated sensory neurons (By similarity). May be involved in axon elongation and axon regeneration after injury (By similarity). Inhibits neurite extension in type II spiral ganglion neurons in the cochlea (By similarity).
messages: Disease susceptibility may be associated with variants affecting the gene represented in this entry.
messages: Expressed in the neurons of the outer hair cells in the organ of Corti and to a lesser extent in type I spiral ganglion cells.
messages: Forms homodimers (in vitro) (By similarity). Homopolymerizes into a filamentous network (in vitro) (PubMed:15446584). Forms heterodimers with NEFL, NEFM or NEFH (in vitro) (By similarity). Interacts with DST (via C-terminus) (By similarity). Interacts with RAB7A; the interaction is direct (PubMed:23179371). Interacts with PRKCE (via phorbol-ester/DAG-type 2 domain) (PubMed:18408015).
messages: Gene prediction based on similarity to orthologs.
messages: Perikaryon
messages: Phosphorylated; phosphorylation increases after nerve injury in regenerating neurons.
messages: axon
messages: cytoskeleton

9606:ALKBH2
gene id: 9606:ALKBH2
uniprot id: Q6NS38
names: Activity Regulation
names: Cofactor
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Activated by ascorbate and magnesium ions.
messages: Belongs to the alkB family.
messages: Binds 1 Fe(2+) ion per subunit.
messages: Detected in colon, small intestine, ovary, testis, prostate, skeletal muscle, heart, liver and urinary bladder.
messages: Dioxygenase that repairs alkylated nucleic acid bases by direct reversal oxidative dealkylation. Can process both double-stranded (ds) and single-stranded (ss) DNA substrates, with a strong preference for dsDNA (PubMed:12486230, PubMed:12594517, PubMed:16174769, PubMed:20714506, PubMed:25797601, PubMed:23972994). Uses molecular oxygen, 2-oxoglutarate and iron as cofactors to oxidize the alkyl groups that are subsequently released as aldehydes, regenerating the undamaged bases. Probes the base pair stability, locates a weakened base pair and flips the damaged base to accommodate the lesion in its active site for efficient catalysis (PubMed:18432238, PubMed:22659876). Repairs monoalkylated bases, specifically N1-methyladenine and N3-methylcytosine, as well as higher order alkyl adducts such as bases modified with exocyclic bridged adducts known as etheno adducts including 1,N6-ethenoadenine, 3,N4-ethenocytosine and 1,N2-ethenoguanine (PubMed:12486230, PubMed:12594517, PubMed:16174769, PubMed:20714506, PubMed:25797601, PubMed:23972994, PubMed:26408825). Acts as a gatekeeper of genomic integrity under alkylation stress. Efficiently repairs alkylated lesions in ribosomal DNA (rDNA). These lesions can cause ss- and dsDNA strand breaks that severely impair rDNA transcription (PubMed:23972994). In a response mechanism to DNA damage, associates with PCNA at replication forks to repair alkylated adducts prior to replication (PubMed:19736315, PubMed:26408825).
messages: Interacts with PCNA homotrimer; this interaction is enhanced during the S-phase of the cell cycle (PubMed:19736315, PubMed:26408825, PubMed:23972994). Interacts with nucleolar proteins NCL, UBTF and NPM1 (PubMed:23972994). Interacts with XRCC5-XRCC6 heterodimer (PubMed:23972994).
messages: Nucleus
messages: The PCNA-binding motif (AlkB homolog 2 PCNA-interacting motif, APIM), mediates the colocalization of ALKBH2 with PCNA at the replication foci, coordinating the repair of alkylated DNA damage with DNA replication.
messages: nucleolus
messages: nucleoplasm

9606:MEI4
gene id: 9606:MEI4
uniprot id: A8MW99
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the MEI4L family.
messages: Chromosome
messages: Interacts with REC114 (PubMed:31704776). Part of the MCD recombinosome complex, at least composed of IHO1, REC114 and MEI4.
messages: Required for DNA double-strand breaks (DSBs) formation in unsynapsed regions during meiotic recombination. Probably acts by forming a complex with IHO1 and REC114, which activates DSBs formation in unsynapsed regions, an essential step to ensure completion of synapsis.

9606:CD79B
gene id: 9606:CD79B
uniprot id: P40259
names: Disease Annotation
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: B-cells.
messages: Cell membrane
messages: Heterodimer of alpha and beta chains; disulfide-linked. Part of the B-cell antigen receptor complex where the alpha/beta chain heterodimer is non-covalently associated with an antigen-specific membrane-bound surface immunoglobulin of two heavy chains and two light chains. Interacts with LYN (By similarity).
messages: Phosphorylated on tyrosine upon B-cell activation by SRC-type Tyr-kinases such as BLK, LYN and SYK.
messages: Required in cooperation with CD79A for initiation of the signal transduction cascade activated by the B-cell antigen receptor complex (BCR) which leads to internalization of the complex, trafficking to late endosomes and antigen presentation. Enhances phosphorylation of CD79A, possibly by recruiting kinases which phosphorylate CD79A or by recruiting proteins which bind to CD79A and protect it from dephosphorylation.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:NAF1
gene id: 9606:NAF1
uniprot id: Q96HR8
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the NAF1 family.
messages: Cytoplasm
messages: During assembly of the complex, component of the small nucleolar ribonucleoprotein particles containing H/ACA-type snoRNAs (H/ACA snoRNPs) which contains NOLA2/NHP2, NOLA3/NOP10, NAF1 and DKC1/NOLA4. Interacts directly with DKC1/NOLA4.
messages: Nucleus
messages: RNA-binding protein required for the maturation of box H/ACA snoRNPs complex and ribosome biogenesis. During assembly of the H/ACA snoRNPs complex, it associates with the complex and disappears during maturation of the complex and is replaced by NOLA1/GAR1 to yield mature H/ACA snoRNPs complex. Probably competes with NOLA1/GAR1 for binding with DKC1/NOLA4.

9606:CXCL9
gene id: 9606:CXCL9
uniprot id: Q07325
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the intercrine alpha (chemokine CxC) family.
messages: By IFNG/IFN-gamma. The induction is enhanced by TNF in dermal fibroblasts and vein endothelial cells.
messages: Cytokine that affects the growth, movement, or activation state of cells that participate in immune and inflammatory response. Chemotactic for activated T-cells. Binds to CXCR3.
messages: Secreted

9606:BARD1
gene id: 9606:BARD1
uniprot id: Q99728
names: Caution
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: E3 ubiquitin-protein ligase. The BRCA1-BARD1 heterodimer specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. Plays a central role in the control of the cell cycle in response to DNA damage. Acts by mediating ubiquitin E3 ligase activity that is required for its tumor suppressor function. Also forms a heterodimer with CSTF1/CSTF-50 to modulate mRNA processing and RNAP II stability by inhibiting pre-mRNA 3' cleavage.
messages: Homo- and heterodimer. Heterodimer (RING-type zinc finger) with BRCA1. Heterodimer (via ANK repeats and BRCT domains) with CSTF1/CSTF-50. Component of the BRCA1-A complex, at least composed of the BRCA1, BARD1, UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1. Interacts with UBXN1.
messages: It is uncertain whether Met-1 or Met-26 is the initiator.
messages: Nucleus
messages: Processed during apoptosis. The homodimer is more susceptible to proteolytic cleavage than the BARD1/BRCA1 heterodimer.

9606:PRAMEF4
gene id: 9606:PRAMEF4
uniprot id: O60810
names: Similarity
messages: Belongs to the PRAME family.

9606:TNKS
gene id: 9606:TNKS
uniprot id: O95271
names: Activity Regulation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: ADP-ribosylated (-auto). Poly-ADP-ribosylated protein is recognized by RNF146, followed by ubiquitination.
messages: Belongs to the ARTD/PARP family.
messages: Cytoplasm
messages: Golgi apparatus membrane
messages: Oligomerizes and associates with TNKS2. Interacts with the cytoplasmic domain of LNPEP/Otase in SLC2A4/GLUT4-vesicles. Binds to the N-terminus of telomeric TERF1 via the ANK repeats. Found in a complex with POT1; TERF1 and TINF2 (PubMed:12768206). Interacts with AXIN1 (PubMed:19759537, PubMed:21478859, PubMed:21799911). Interacts with AXIN2 (PubMed:19759537, PubMed:21478859). Interacts with BLZF1 and CASC3 (PubMed:21478859). Interacts with NUMA1 (PubMed:12080061).
messages: Phosphorylated on serine residues by MAPK kinases upon insulin stimulation. Phosphorylated during mitosis.
messages: Poly-ADP-ribosyltransferase involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking (PubMed:10988299, PubMed:11739745, PubMed:16076287, PubMed:19759537, PubMed:21478859, PubMed:22864114, PubMed:23622245, PubMed:25043379). Acts as an activator of the Wnt signaling pathway by mediating poly-ADP-ribosylation (PARsylation) of AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex: poly-ADP-ribosylated target proteins are recognized by RNF146, which mediates their ubiquitination and subsequent degradation (PubMed:19759537, PubMed:21478859). Also mediates PARsylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination (PubMed:21478859). Mediates PARsylation of TERF1, thereby contributing to the regulation of telomere length (PubMed:11739745). Involved in centrosome maturation during prometaphase by mediating PARsylation of HEPACAM2/MIKI (PubMed:22864114). May also regulate vesicle trafficking and modulate the subcellular distribution of SLC2A4/GLUT4-vesicles (PubMed:10988299). May be involved in spindle pole assembly through PARsylation of NUMA1 (PubMed:16076287). Stimulates 26S proteasome activity (PubMed:23622245).
messages: Specifically inhibited by XAV939, a small molecule, leading to inhibit the Wnt signaling pathway by stabilizing AXIN1 and AXIN2 (PubMed:19759537). Inhibited by talazoparib (PubMed:33361107). Not inhibited by olaparib, niraparib and veliparib (PubMed:33361107).
messages: Ubiquitinated by RNF146 when auto-poly-ADP-ribosylated, leading to its degradation.
messages: Ubiquitous; highest levels in testis.
messages: centrosome
messages: nuclear pore complex
messages: spindle pole
messages: telomere

9606:SLC30A6
gene id: 9606:SLC30A6
uniprot id: B5MCR8
uniprot id: Q6NXT4
names: Caution
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the cation diffusion facilitator (CDF) transporter (TC 2.A.4) family. SLC30A subfamily.
messages: Expressed in brain; especially in cerebellum, hippocampus, parahippocampal gyrus, superior and middle temporal gyrus. Also expressed in B-cells, colon, eye, and lung. Lower expression was present in bone, brain, cervix, ear, heart, kidney, muscle, nerve, pancreas, prostate, skin, stomach, and testis.
messages: Has probably no intrinsic transporter activity but together with SLC30A5 forms a functional zinc ion:proton antiporter heterodimer, mediating zinc entry into the lumen of organelles along the secretory pathway (PubMed:15994300, PubMed:19366695, PubMed:19759014). As part of that zinc ion:proton antiporter, contributes to zinc ion homeostasis within the early secretory pathway and regulates the activation and folding of enzymes like alkaline phosphatases and enzymes involved in phosphatidylinositol glycan anchor biosynthesis (PubMed:15994300, PubMed:19759014, PubMed:35525268).
messages: Heterodimer with SLC30A5; form a functional zinc ion transmembrane transporter.
messages: Hydrophilic histidine residues that participate to zinc binding in transporters of the family are not conserved in SLC30A6.
messages: Membrane
messages: trans-Golgi network membrane

9606:UNC45A
gene id: 9606:UNC45A
uniprot id: Q9H3U1
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acts as co-chaperone for HSP90. Prevents the stimulation of HSP90AB1 ATPase activity by AHSA1. Positive factor in promoting PGR function in the cell. May be necessary for proper folding of myosin (Potential). Necessary for normal cell proliferation. Necessary for normal myotube formation and myosin accumulation during muscle cell development. May play a role in erythropoiesis in stroma cells in the spleen (By similarity).
messages: Cytoplasm
messages: Detected in peripheral blood leukocytes, bone marrow, adrenal gland, trachea, spinal cord, thyroid, lymph node and stomach.
messages: Interacts with PGR isoforms A and B as well as with NR3C1 in the absence of ligand, and with HSP90AB1. Binding to HSP90AB1 involves 2 UNC45A monomers per HSP90AB1 dimer.
messages: Nucleus
messages: The disease may be caused by variants affecting the gene represented in this entry.
messages: perinuclear region

9606:TOMM34
gene id: 9606:TOMM34
uniprot id: Q15785
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the Tom34 family.
messages: Cytoplasm
messages: Interacts with HSP90A, VCP, ATP6V1D, KIAA0665, AMPK, and DMAP1 through its TPR repeat.
messages: Mitochondrion outer membrane
messages: Plays a role in the import of cytosolically synthesized preproteins into mitochondria. Binds the mature portion of precursor proteins. Interacts with cellular components, and possesses weak ATPase activity. May be a chaperone-like protein that helps to keep newly synthesized precursors in an unfolded import compatible state.
messages: Ubiquitous.

9606:VWC2
gene id: 9606:VWC2
uniprot id: Q2TAL6
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: BMP antagonist which may play a role in neural development. Promotes cell adhesion (By similarity).
messages: Peripherally associated with AMPAR complex. AMPAR complex consists of an inner core made of 4 pore-forming GluA/GRIA proteins (GRIA1, GRIA2, GRIA3 and GRIA4) and 4 major auxiliary subunits arranged in a twofold symmetry. One of the two pairs of distinct binding sites is occupied either by CNIH2, CNIH3 or CACNG2, CACNG3. The other harbors CACNG2, CACNG3, CACNG4, CACNG8 or GSG1L. This inner core of AMPAR complex is complemented by outer core constituents binding directly to the GluA/GRIA proteins at sites distinct from the interaction sites of the inner core constituents. Outer core constituents include at least PRRT1, PRRT2, CKAMP44/SHISA9, FRRS1L and NRN1. The proteins of the inner and outer core serve as a platform for other, more peripherally associated AMPAR constituents, including VWC2. Alone or in combination, these auxiliary subunits control the gating and pharmacology of the AMPAR complex and profoundly impact their biogenesis and protein processing (By similarity).
messages: Synapse
messages: basement membrane

9606:KRT4
gene id: 9606:KRT4
uniprot id: P19013
names: Disease Annotation
names: Miscellaneous
names: Polymorphism
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Belongs to the intermediate filament family.
messages: Detected in the suprabasal layer of the stratified epithelium of the esophagus, exocervix, vagina, mouth and lingual mucosa, and in cells and cell clusters in the mucosa and serous gland ducts of the esophageal submucosa (at protein level). Expressed widely in the exocervix and esophageal epithelium, with lowest levels detected in the basal cell layer.
messages: Heterotetramer of two type I and two type II keratins. Keratin-4 is generally associated with keratin-13.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: There are two types of cytoskeletal and microfibrillar keratin: I (acidic; 40-55 kDa) and II (neutral to basic; 56-70 kDa).
messages: Three alleles of K4 are known: K4A1, K4A2 and K4B (displayed here).

9606:ANPEP
gene id: 9606:ANPEP
uniprot id: P15144
uniprot id: Q59E93
names: Cofactor
names: Function
names: Induction
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Acts as a receptor for human coronavirus 229E/HCoV-229E. In case of human coronavirus 229E (HCoV-229E) infection, serves as receptor for HCoV-229E spike glycoprotein.
messages: (Microbial infection) Interacts with the S1 domain of human coronavirus 229E/HCoV-229E spike protein.
messages: (Microbial infection) Mediates as well Human cytomegalovirus (HCMV) infection.
messages: Belongs to the peptidase M1 family.
messages: Binds 1 zinc ion per subunit.
messages: Broad specificity aminopeptidase which plays a role in the final digestion of peptides generated from hydrolysis of proteins by gastric and pancreatic proteases. Also involved in the processing of various peptides including peptide hormones, such as angiotensin III and IV, neuropeptides, and chemokines. May also be involved the cleavage of peptides bound to major histocompatibility complex class II molecules of antigen presenting cells. May have a role in angiogenesis and promote cholesterol crystallization. May have a role in amino acid transport by acting as binding partner of amino acid transporter SLC6A19 and regulating its activity (By similarity).
messages: Cell membrane
messages: Estradiol and IL8/interleukin-8 decrease enzymatic activity in vitro in endometrial stromal cells by 40% and 30%, respectively.
messages: Expressed in epithelial cells of the kidney, intestine, and respiratory tract; granulocytes, monocytes, fibroblasts, endothelial cells, cerebral pericytes at the blood-brain barrier, synaptic membranes of cells in the CNS. Also expressed in endometrial stromal cells, but not in the endometrial glandular cells. Found in the vasculature of tissues that undergo angiogenesis and in malignant gliomas and lymph node metastases from multiple tumor types but not in blood vessels of normal tissues. A soluble form has been found in plasma. It is found to be elevated in plasma and effusions of cancer patients.
messages: Found to serve as a receptor for tumor-homing peptides, more specifically NGR peptides. It could serve thus as a target for delivering drugs into tumors. Concentration in human hepatic bile, varies from 17.3 to 57.6 micrograms/ml.
messages: Homodimer. Interacts with SLC6A19 (By similarity).
messages: May undergo proteolysis and give rise to a soluble form.
messages: N- and O-glycosylated.
messages: Sulfated.

9606:DMP1
gene id: 9606:DMP1
uniprot id: Q13316
names: Disease Annotation
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cytoplasm
messages: Expressed in tooth particularly in odontoblast, ameloblast and cementoblast.
messages: Interacts with importin alpha.
messages: May have a dual function during osteoblast differentiation. In the nucleus of undifferentiated osteoblasts, unphosphorylated form acts as a transcriptional component for activation of osteoblast-specific genes like osteocalcin. During the osteoblast to osteocyte transition phase it is phosphorylated and exported into the extracellular matrix, where it regulates nucleation of hydroxyapatite.
messages: Nucleus
messages: Phosphorylated in the cytosol and extracellular matrix and unphosphorylated in the nucleus. Phosphorylation is necessary for nucleocytoplasmic transport and may be catalyzed by a nuclear isoform of CK2 and can be augmented by calcium. Phosphorylated (in vitro) by FAM20C in the extracellular medium at sites within the S-x-E/pS motif.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: extracellular matrix

9606:SLC22A3
gene id: 9606:SLC22A3
uniprot id: O75751
names: Domain
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Apical cell membrane
messages: Basolateral cell membrane
messages: Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family.
messages: Cell membrane
messages: Contains one proline-rich sequence (Pro-Glu-Ser-Pro-Arg) that is required for transport activity.
messages: Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:10196521, PubMed:10966924, PubMed:12538837, PubMed:17460754, PubMed:20858707). Cation cellular uptake or release is driven by the electrochemical potential, i.e. membrane potential and concentration gradient (PubMed:10966924). Functions as a Na(+)- and Cl(-)-independent, bidirectional uniporter (PubMed:12538837). Implicated in monoamine neurotransmitters uptake such as dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, histamine, serotonin and tyramine, thereby supporting a role in homeostatic regulation of aminergic neurotransmission in the brain (PubMed:10196521, PubMed:16581093, PubMed:20858707). Transports dopaminergic neuromodulators cyclo(his-pro) and salsolinol with low efficiency (PubMed:17460754). May be involved in the uptake and disposition of cationic compounds by renal clearance from the blood flow (PubMed:10966924). May contribute to regulate the transport of cationic compounds in testis across the blood-testis-barrier (Probable). Mediates the transport of polyamine spermidine and putrescine (By similarity). Mediates the bidirectional transport of polyamine agmatine (PubMed:12538837). Also transports guanidine (PubMed:10966924). May also mediate intracellular transport of organic cations, thereby playing a role in amine metabolism and intracellular signaling (By similarity).
messages: Endomembrane system
messages: Expressed in liver (PubMed:10196521, PubMed:9933568). Expressed in intestine (PubMed:16263091, PubMed:20858707). Expressed in kidney in proximal tubular cells (PubMed:10966924). Expressed in placenta (PubMed:9933568, PubMed:10966924). Expressed throughout the brain, including cerebral cortex, cerebrellum, substancia nigra, medulla oblongata, hippocampus, caudate nucleus, nucleus accumbens and pons with low levels of expression detected in nearly all brain regions (PubMed:10196521, PubMed:20858707). In testis, mostly localized to peritubular myoid cells and Leydig cells, and weakly expressed in developing germ cells (PubMed:35307651). Expressed in tracheal and bronchial epithelium of the respiratory tract, where it localizes to the apical membrane of ciliated cells, the entire membrane of basal cells and the basolateral membrane of intermediate cells (PubMed:15817714). Expressed in skeletal muscle, adrenal gland, heart, prostate, aorta, salivary gland, adrenal gland, uterus, lymph node, lung, trachea and spinal cord (PubMed:10196521, PubMed:9933568, PubMed:20858707). Expressed in fetal lung and liver (PubMed:9933568).
messages: Mediates the uptake of clinically used drugs including neurotoxin 1-methyl-4-phenylpyridinium (MPP(+)) and platinum-based drug oxaliplatin (PubMed:10196521, PubMed:10966924, PubMed:12538837, PubMed:15817714, PubMed:16263091, PubMed:16914559, PubMed:16581093, PubMed:20858707). Plays a role in the anticancer activity of oxaliplatin and may contribute to antitumor specificity (PubMed:16914559).
messages: Mitochondrion membrane
messages: Nucleus membrane
messages: Nucleus outer membrane

9606:AADAT
gene id: 9606:AADAT
uniprot id: Q8N5Z0
names: Activity Regulation
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the class-I pyridoxal-phosphate-dependent aminotransferase family.
messages: Higher expression in the liver. Also found in heart, brain, kidney, pancreas, prostate, testis and ovary.
messages: Homodimer.
messages: Kynurenine transaminase activity is competitively inhibited by aminoadipate, asparagine, glutamate, histidine, cysteine, lysine, 3-hydroxy-kynurenine and phenylalanine.
messages: May be due to a competing donor splice site.
messages: Mitochondrion
messages: Transaminase with broad substrate specificity. Has transaminase activity towards aminoadipate, kynurenine, methionine and glutamate. Shows activity also towards tryptophan, aspartate and hydroxykynurenine. Accepts a variety of oxo-acids as amino-group acceptors, with a preference for 2-oxoglutarate, 2-oxocaproic acid, phenylpyruvate and alpha-oxo-gamma-methiol butyric acid. Can also use glyoxylate as amino-group acceptor (in vitro).

9606:ALK
gene id: 9606:ALK
uniprot id: B6D4Y2
uniprot id: Q9UM73
names: Activity Regulation
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: A chromosomal aberration involving ALK has been identified in a subset of patients with non-small-cell lung carcinoma. This aberration leads to the production of a fusion protein between the N-terminus of EML4 et the C-terminus of ALK. It is unclear whether the fusion protein is caused by a simple inversion within 2p (inv(2)(p21p23)) or whether the chromosome translocation involving 2p is more complex. When tested in a heterologous system, the fusion protein EML4-ALK possesses transforming activity that is dependent on ALK catalytic activity, possibly due to spontaneous dimerization mediated by the EML4 moiety, leading to ALK kinase activation.
messages: A chromosomal aberration involving ALK is associated with anaplastic large-cell lymphoma (ALCL). Translocation t(2;17)(p23;q25) with ALO17.
messages: A chromosomal aberration involving ALK is associated with inflammatory myofibroblastic tumors (IMTs). Translocation t(2;11)(p23;p15) with CARS; translocation t(2;4)(p23;q21) with SEC31A.
messages: A chromosomal aberration involving ALK is found in a form of non-Hodgkin lymphoma. Translocation t(2;5)(p23;q35) with NPM1. The resulting chimeric NPM1-ALK protein homodimerize and the kinase becomes constitutively activated. The constitutively active fusion proteins are responsible for 5-10% of non-Hodgkin lymphomas.
messages: A chromosomal aberration involving ALK is found in one subject with colorectal cancer. Translocation t(2;2)(p23.1;p23.3). A 5 million base pair tandem duplication generates an in-frame WDCP-ALK gene fusion.
messages: Activated upon ALKAL2 ligand-binding (PubMed:34646012, PubMed:34819673). ALKAL2-driven activation is coupled with heparin-binding (PubMed:25605972, PubMed:34646012). Following ligand-binding, homodimerizes and autophosphorylates, activating its kinase activity (PubMed:16317043, PubMed:17681947, PubMed:34646012, PubMed:34819673). Inactivated through dephosphorylation by receptor protein tyrosine phosphatase beta and zeta complex (PTPRB/PTPRZ1) when there is no stimulation by a ligand (PubMed:17681947). Staurosporine, crizotinib and CH5424802 act as inhibitors of ALK kinase activity (PubMed:21575866).
messages: Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.
messages: Cell membrane
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry.
messages: Expressed in brain and CNS. Also expressed in the small intestine and testis, but not in normal lymphoid cells.
messages: Homodimer; homodimerizes following heparin- and ligand-binding (PubMed:16317043, PubMed:25605972, PubMed:34646012, PubMed:34819673). Interacts with CBL, IRS1, PIK3R1 and PLCG1 (PubMed:15226403). Interacts with FRS2 and SHC1 (PubMed:15226403, PubMed:16878150, PubMed:17274988). Interacts with PTN and MDK (PubMed:11278720, PubMed:12122009).
messages: N-glycosylated.
messages: Neuronal receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system (PubMed:11121404, PubMed:11387242, PubMed:16317043, PubMed:17274988, PubMed:30061385, PubMed:34646012, PubMed:34819673). Also acts as a key thinness protein involved in the resistance to weight gain: in hypothalamic neurons, controls energy expenditure acting as a negative regulator of white adipose tissue lipolysis and sympathetic tone to fine-tune energy homeostasis (By similarity). Following activation by ALKAL2 ligand at the cell surface, transduces an extracellular signal into an intracellular response (PubMed:30061385, PubMed:33411331, PubMed:34646012, PubMed:34819673). In contrast, ALKAL1 is not a potent physiological ligand for ALK (PubMed:34646012). Ligand-binding to the extracellular domain induces tyrosine kinase activation, leading to activation of the mitogen-activated protein kinase (MAPK) pathway (PubMed:34819673). Phosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-Y-Y motif (PubMed:15226403, PubMed:16878150). Induces tyrosine phosphorylation of CBL, FRS2, IRS1 and SHC1, as well as of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1 (PubMed:15226403, PubMed:16878150). ALK activation may also be regulated by pleiotrophin (PTN) and midkine (MDK) (PubMed:11278720, PubMed:11809760, PubMed:12107166, PubMed:12122009). PTN-binding induces MAPK pathway activation, which is important for the anti-apoptotic signaling of PTN and regulation of cell proliferation (PubMed:11278720, PubMed:11809760, PubMed:12107166). MDK-binding induces phosphorylation of the ALK target insulin receptor substrate (IRS1), activates mitogen-activated protein kinases (MAPKs) and PI3-kinase, resulting also in cell proliferation induction (PubMed:12122009). Drives NF-kappa-B activation, probably through IRS1 and the activation of the AKT serine/thr…
messages: Phosphorylated at tyrosine residues by autocatalysis, which activates kinase activity (PubMed:11121404, PubMed:15938644, PubMed:16878150, PubMed:34819673). In cells not stimulated by a ligand, receptor protein tyrosine phosphatase beta and zeta complex (PTPRB/PTPRZ1) dephosphorylates ALK at the sites in ALK that are undergoing autophosphorylation through autoactivation (PubMed:17681947). Phosphorylation at Tyr-1507 is critical for SHC1 association (PubMed:17274988).
messages: The ALK signaling pathway plays an important role in glioblastoma, the most common malignant brain tumor of adults and one of the most lethal cancers. It regulates both glioblastoma migration and growth.
messages: The EGF-like region drives the cytokine specificity for ALKAL2.
messages: The heparin-binding region binds heparin glycosaminoglycan (PubMed:25605972, PubMed:34646012). Heparin-binding is required for ALKAL2-driven activation (PubMed:34646012).

9606:TMED6
gene id: 9606:TMED6
uniprot id: Q8WW62
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the EMP24/GP25L family.
messages: Endoplasmic reticulum membrane

9606:OR6C3
gene id: 9606:OR6C3
uniprot id: A0A126GW44
uniprot id: Q9NZP0
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Membrane
messages: Odorant receptor.

9606:LRRC3C
gene id: 9606:LRRC3C
uniprot id: A6NJW4
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the LRRC3 family.
messages: Membrane

9606:SUGT1
gene id: 9606:SUGT1
uniprot id: A8K7W3
uniprot id: B4DYC6
uniprot id: Q9Y2Z0
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the SGT1 family.
messages: Cytoplasm
messages: May play a role in ubiquitination and subsequent proteasomal degradation of target proteins.
messages: Nucleus
messages: Phosphorylated at Ser-281 and Ser-331, dephosphorylation promotes nuclear translocation, most likely due to disruption of the SUGT1-HSP90 complex.
messages: Probably associates with SCF (SKP1-CUL1-F-box protein) complex through interaction with SKP1. Interacts with S100A6. Interacts with HSP90.
messages: The CS domain mediates interaction with HSP90.

9606:VIL1
gene id: 9606:VIL1
uniprot id: P09327
uniprot id: Q53F91
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the villin/gelsolin family.
messages: Biliary atresia is a chronic and progressive cholestatic liver disease of chilhood characterized by an abnormal villin gene expression and severe malformation of canalicular microvillus structure.
messages: Consists of a large core fragment in the N-terminal portion and a small headpiece (HP) in the C-terminal portion. The core fragment is necessary for both actin-nucleating and -severing activities, whereas the HP binds F-actin strongly in both the presence and absence of calcium and is necessary in actin-bundling activity. The Gelsolin-like 1 repeat is necessary for the actin-capping activity. The entire core fragment is necessary for the actin-severing activity. Two major calcium-sensitive sites are involved in conformational changes and determine separate functional properties: the first site (Glu-25, Asp-44 and Glu-74) regulates the actin-capping and actin-severing activities; while the second site (Asp-61, Asp-86 and Ala-93) regulates only the actin-severing activity.
messages: Epithelial cell-specific Ca(2+)-regulated actin-modifying protein that modulates the reorganization of microvillar actin filaments. Plays a role in the actin nucleation, actin filament bundle assembly, actin filament capping and severing. Binds phosphatidylinositol 4,5-bisphosphate (PIP2) and lysophosphatidic acid (LPA); binds LPA with higher affinity than PIP2. Binding to LPA increases its phosphorylation by SRC and inhibits all actin-modifying activities. Binding to PIP2 inhibits actin-capping and -severing activities but enhances actin-bundling activity. Regulates the intestinal epithelial cell morphology, cell invasion, cell migration and apoptosis. Protects against apoptosis induced by dextran sodium sulfate (DSS) in the gastrointestinal epithelium. Appears to regulate cell death by maintaining mitochondrial integrity. Enhances hepatocyte growth factor (HGF)-induced epithelial cell motility, chemotaxis and wound repair. Upon S.flexneri cell infection, its actin-severing activity enhances actin-based motility of the bacteria and plays a role during the dissemination.
messages: Monomer. Homodimer; homodimerization is necessary for actin-bundling. Associates with F-actin; phosphorylation at tyrosine residues decreases the association with F-actin. Interacts (phosphorylated at C-terminus tyrosine phosphorylation sites) with PLCG1 (via the SH2 domains). Interacts (phosphorylated form) with PLCG1; the interaction is enhanced by hepatocyte growth factor (HGF) (By similarity).
messages: Specifically expressed in epithelial cells. Major component of microvilli of intestinal epithelial cells and kidney proximal tubule cells. Expressed in canalicular microvilli of hepatocytes (at protein level).
messages: Tyrosine phosphorylation is induced by epidermal growth factor (EGF) and stimulates cell migration (By similarity). Phosphorylated on tyrosine residues by SRC. The unphosphorylated form increases the initial rate of actin-nucleating activity, whereas the tyrosine-phosphorylated form inhibits actin-nucleating activity, enhances actin-bundling activity and enhances actin-severing activity by reducing high Ca(2+) requirements. The tyrosine-phosphorylated form does not regulate actin-capping activity. Tyrosine phosphorylation is essential for cell migration: tyrosine phosphorylation sites in the N-terminus half regulate actin reorganization and cell morphology, whereas tyrosine phosphorylation sites in the C-terminus half regulate cell migration via interaction with PLCG1.
messages: cytoskeleton
messages: filopodium
messages: filopodium tip
messages: lamellipodium
messages: microvillus
messages: ruffle

9606:MLANA
gene id: 9606:MLANA
uniprot id: Q16655
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acylated.
messages: Endoplasmic reticulum membrane
messages: Expression is restricted to melanoma and melanocyte cell lines and retina.
messages: Golgi apparatus
messages: Interacts with PMEL. Interacts with GPR143.
messages: Involved in melanosome biogenesis by ensuring the stability of GPR143. Plays a vital role in the expression, stability, trafficking, and processing of melanocyte protein PMEL, which is critical to the formation of stage II melanosomes.
messages: Melanosome
messages: trans-Golgi network membrane

9606:SLC30A7
gene id: 9606:SLC30A7
uniprot id: Q8NEW0
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the cation diffusion facilitator (CDF) transporter (TC 2.A.4) family. SLC30A subfamily.
messages: Cytoplasmic vesicle
messages: Golgi apparatus membrane
messages: Homooligomer.
messages: Increased intracellular zinc level, resulting from extracellular zinc supplementation, do not induce any up- or down-regulation of gene expression. Up-regulated by zinc depletion.
messages: Mitochondrion
messages: Sarcoplasmic reticulum
messages: Zinc ion transporter mediating zinc entry from the cytosol into the lumen of organelles along the secretory pathway (PubMed:15525635, PubMed:15994300). By contributing to zinc ion homeostasis within the early secretory pathway, regulates the activation and folding of enzymes like alkaline phosphatases (PubMed:15525635, PubMed:15994300).
messages: trans-Golgi network

9606:LYN
gene id: 9606:LYN
uniprot id: A8K379
uniprot id: B4DQ79
uniprot id: P07948
uniprot id: Q6NUK7
names: Activity Regulation
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts with Epstein-Barr virus LMP2A.
messages: (Microbial infection) Interacts with Herpes virus saimiri tyrosine kinase interacting protein (Tip).
messages: Autophosphorylated (PubMed:7935444, PubMed:9171348, PubMed:9341198, PubMed:18056483, PubMed:18070987). Phosphorylated on tyrosine residues in response to KIT signaling (PubMed:9341198). Phosphorylation at Tyr-397 is required for optimal activity (PubMed:16920712). Phosphorylation at Tyr-508 inhibits kinase activity (PubMed:9171348). Phosphorylated at Tyr-508 by CSK (PubMed:7935444). Dephosphorylated by PTPRC/CD45 (By similarity). Becomes rapidly phosphorylated upon activation of the B-cell receptor and the immunoglobulin receptor FCGR1A (PubMed:8064233). Phosphorylated in response to ITGB1 in B-cells (PubMed:9020138).
messages: Belongs to the protein kinase superfamily. Tyr protein kinase family.
messages: Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily.
messages: Cell membrane
messages: Constitutively phosphorylated and activated in cells from a number of chronic myelogenous leukemia (CML) and acute myeloid leukemia (AML) patients. Mediates phosphorylation of the BCR-ABL fusion protein. Abnormally elevated expression levels or activation of LYN signaling may play a role in survival and proliferation of some types of cancer cells.
messages: Cytoplasm
messages: Detected in monocytes (at protein level). Detected in placenta, and in fetal brain, lung, liver and kidney. Widely expressed in a variety of organs, tissues, and cell types such as epidermoid, hematopoietic, and neuronal cells. Expressed in primary neuroblastoma tumors.
messages: Golgi apparatus
messages: Interacts with TEC. Interacts (via SH2 domain) with FLT3 (tyrosine phosphorylated). Interacts with LIME1 and with CD79A upon activation of the B-cell antigen receptor. Interacts with the B-cell receptor complex. Interacts with phosphorylated THEMIS2. Interacts with EPOR. Interacts with MS4A2/FCER1B. Interaction (via the SH2 and SH3 domains) with MUC1 is stimulated by IL7 and the subsequent phosphorylation increases the binding between MUC1 and CTNNB1/beta-catenin. Interacts with ADAM15. Interacts with NDFIP2 and more weakly with NDFIP1. Interacts with FASLG. Interacts with KIT. Interacts with HCLS1. Interacts with FCGR2B. Interacts with FCGR1A; the interaction may be indirect. Interacts with CD19, CD22, CD79A and CD79B. Interacts (via SH3 domain) with CBLC, PPP1R15A and PDE4A. Interacts with TGFB1I1. Interacts (via SH3 domain) with PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase; this interaction enhances phosphatidylinositol 3-kinase activity. Interacts with CSF2RB, the common subunit of the IL3, IL5 and CSF2 receptors. Interacts with PAG1; identified in a complex with PAG1 and STAT3. Interacts with ABL1. Interacts with PTPN6/SHP-1. Interacts (via SH3 domain) with SCIMP (via proline-rich region) (PubMed:21930792). This interaction facilitates the phosphorylation of SCIMP on 'Tyr-107', which enhances binding of SCIMP to TLR4, and consequently the phosphorylation of TLR4 in response to stimulation by lipopolysaccharide in macrophages (By similarity). Interacts with LPXN (via LD motif 3) and the interaction is induced upon B-cell antigen receptor (BCR) activation. Interacts (via SH3-domain) with ANKRD54 (via ankyrin repeat region) in an activation-independent status of LYN. Forms a multiprotein complex with ANKRD54 and HCLS1. Interacts (via SH2 and SH3 domains) with UNC119; leading to LYN activation. Interacts with CD36. Interacts with LYN (By similarity). Interacts with SKAP1 and FYB1; this interaction promotes the phosphorylation of CLNK (By similari…
messages: Membrane
messages: Non-receptor tyrosine-protein kinase that transmits signals from cell surface receptors and plays an important role in the regulation of innate and adaptive immune responses, hematopoiesis, responses to growth factors and cytokines, integrin signaling, but also responses to DNA damage and genotoxic agents. Functions primarily as negative regulator, but can also function as activator, depending on the context. Required for the initiation of the B-cell response, but also for its down-regulation and termination. Plays an important role in the regulation of B-cell differentiation, proliferation, survival and apoptosis, and is important for immune self-tolerance. Acts downstream of several immune receptors, including the B-cell receptor, CD79A, CD79B, CD5, CD19, CD22, FCER1, FCGR2, FCGR1A, TLR2 and TLR4. Plays a role in the inflammatory response to bacterial lipopolysaccharide. Mediates the responses to cytokines and growth factors in hematopoietic progenitors, platelets, erythrocytes, and in mature myeloid cells, such as dendritic cells, neutrophils and eosinophils. Acts downstream of EPOR, KIT, MPL, the chemokine receptor CXCR4, as well as the receptors for IL3, IL5 and CSF2. Plays an important role in integrin signaling. Regulates cell proliferation, survival, differentiation, migration, adhesion, degranulation, and cytokine release. Down-regulates signaling pathways by phosphorylation of immunoreceptor tyrosine-based inhibitory motifs (ITIM), that then serve as binding sites for phosphatases, such as PTPN6/SHP-1, PTPN11/SHP-2 and INPP5D/SHIP-1, that modulate signaling by dephosphorylation of kinases and their substrates. Phosphorylates LIME1 in response to CD22 activation. Phosphorylates BTK, CBL, CD5, CD19, CD72, CD79A, CD79B, CSF2RB, DOK1, HCLS1, LILRB3/PIR-B, MS4A2/FCER1B, SYK and TEC. Promotes phosphorylation of SIRPA, PTPN6/SHP-1, PTPN11/SHP-2 and INPP5D/SHIP-1. Mediates phosphorylation of the BCR-ABL fusion protein. Required for rapid phosphorylation of FER in …
messages: Nucleus
messages: Subject to autoinhibition, mediated by intramolecular interactions between the SH2 domain and the C-terminal phosphotyrosine. Phosphorylation at Tyr-397 is required for optimal activity. Phosphorylated by CSK at Tyr-508; phosphorylation at Tyr-508 inhibits kinase activity. Kinase activity is modulated by dephosphorylation by PTPRC/CD45. Inhibited by Dasatinib, PP2, and SU6656.
messages: The protein kinase domain plays an important role in its localization in the cell membrane.
messages: Ubiquitinated by CBL, leading to its degradation. Ubiquitination is SH3-dependent.
messages: perinuclear region

9606:ZNF799
gene id: 9606:ZNF799
uniprot id: Q96GE5
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:NR1D2
gene id: 9606:NR1D2
uniprot id: B4DXD3
uniprot id: F1D8P2
uniprot id: Q14995
names: Activity Regulation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the nuclear hormone receptor family.
messages: Belongs to the nuclear hormone receptor family. NR1 subfamily.
messages: Binds DNA as a monomer or a homodimer (PubMed:17870090). Interacts with NCOA5 coactivator, leading to a strong increase of transcription of target genes (PubMed:11113208). Interacts (via N-terminus) with KAT5 (PubMed:17996965). Interacts (via C-terminus) with HDAC1 (PubMed:17996965). Interacts with ZNHIT1 (PubMed:17892483). Interacts with SIAH2 (PubMed:26392558).
messages: Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.
messages: Cytoplasm
messages: Deacetylated by HDAC1. Acetylation and deacetylation regulate its transcriptional regulatory activity.
messages: Nucleus
messages: Phosphorylated by CSNK1E; phosphorylation enhances its cytoplasmic localization.
messages: The heme-bound form can bind gaseous signaling molecules such as CO and nitric oxide (NO) and NO can reverse its transcriptional repressor activity.
messages: Transcriptional repressor which coordinates circadian rhythm and metabolic pathways in a heme-dependent manner. Integral component of the complex transcription machinery that governs circadian rhythmicity and forms a critical negative limb of the circadian clock by directly repressing the expression of core clock components BMAL1 and CLOCK. Also regulates genes involved in metabolic functions, including lipid metabolism and the inflammatory response. Acts as a receptor for heme which stimulates its interaction with the NCOR1/HDAC3 corepressor complex, enhancing transcriptional repression. Recognizes two classes of DNA response elements within the promoter of its target genes and can bind to DNA as either monomers or homodimers, depending on the nature of the response element. Binds as a monomer to a response element composed of the consensus half-site motif 5'-[A/G]GGTCA-3' preceded by an A/T-rich 5' sequence (RevRE), or as a homodimer to a direct repeat of the core motif spaced by two nuclegotides (RevDR-2). Acts as a potent competitive repressor of ROR alpha (RORA) function and also negatively regulates the expression of NR1D1. Regulates lipid and energy homeostasis in the skeletal muscle via repression of genes involved in lipid metabolism and myogenesis including: CD36, FABP3, FABP4, UCP3, SCD1 and MSTN. Regulates hepatic lipid metabolism via the repression of APOC3. Represses gene expression at a distance in macrophages by inhibiting the transcription of enhancer-derived RNAs (eRNAs). In addition to its activity as a repressor, can also act as a transcriptional activator. Acts as a transcriptional activator of the sterol regulatory element-binding protein 1 (SREBF1) and the inflammatory mediator interleukin-6 (IL6) in the skeletal muscle (By similarity). Plays a role in the regulation of circadian sleep/wake cycle; essential for maintaining wakefulness during the dark phase or active period (By similarity). Key regulator of skeletal muscle mitochondrial functio…
messages: Ubiquitinated by SIAH2; leading to proteasomal degradation.
messages: Under more reducing intracellular redox conditions, Cys-384 is in its heme-bound state, which is optimal for recruitment of the NCOR1/HDAC3 corepressor complex and repression of target genes. When subjected to oxidative stress conditions, Cys-384 undergoes oxidation to form a disulfide bridge with Cys-374, also triggering a ligand switch that results in release of bound heme and derepression of target genes.
messages: Widely expressed. Expressed at high levels in the liver, adipose tissue, skeletal muscle and brain. Expression oscillates diurnally in the suprachiasmatic nucleus (SCN) of the hypothalamus as well as in peripheral tissues.

9606:TLCD5
gene id: 9606:TLCD5
uniprot id: A8K0W5
uniprot id: Q6ZRR5
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the TLCD5 family.
messages: Membrane

9606:TMEM106A
gene id: 9606:TMEM106A
uniprot id: B7Z779
uniprot id: Q96A25
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Activates macrophages and polarizes them into M1-like macrophages through the activation of the MAPK and NF-kappaB signaling pathway. Upon activation, up-regulates the expression of CD80, CD86, CD69 and MHC II on macrophages, and induces the release of pro-inflammatory cytokines such as TNF, IL1B, IL6, CCL2 and nitric oxide (By similarity). May play a role in inhibition of proliferation and migration (PubMed:30456879, PubMed:29131025).
messages: Belongs to the TMEM106 family.
messages: Cell membrane
messages: Expressed in renal cells (at protein level) (PubMed:29131025). Expressed in epithelial cells (PubMed:30456879).

9606:CTNNA1
gene id: 9606:CTNNA1
uniprot id: A0A384MDY0
uniprot id: B4DKT9
uniprot id: B4DU00
uniprot id: G3XAM7
uniprot id: P35221
names: Disease Annotation
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Associates with the cytoplasmic domain of a variety of cadherins. The association of catenins to cadherins produces a complex which is linked to the actin filament network, and which seems to be of primary importance for cadherins cell-adhesion properties. Can associate with both E- and N-cadherins. Originally believed to be a stable component of E-cadherin/catenin adhesion complexes and to mediate the linkage of cadherins to the actin cytoskeleton at adherens junctions. In contrast, cortical actin was found to be much more dynamic than E-cadherin/catenin complexes and CTNNA1 was shown not to bind to F-actin when assembled in the complex suggesting a different linkage between actin and adherens junctions components. The homodimeric form may regulate actin filament assembly and inhibit actin branching by competing with the Arp2/3 complex for binding to actin filaments. Involved in the regulation of WWTR1/TAZ, YAP1 and TGFB1-dependent SMAD2 and SMAD3 nuclear accumulation (By similarity). May play a crucial role in cell differentiation.
messages: Belongs to the vinculin/alpha-catenin family.
messages: Cell junction
messages: Cell membrane
messages: Expressed at high levels in the nervous system. Lacks the beta-catenin interaction domain.
messages: Expressed ubiquitously in normal tissues.
messages: Germline CTNNA1 truncating mutations have been detected in patients with hereditary diffuse gastric cancer (HDGC) and may play a role in disease susceptibility. Diffuse gastric cancer is a malignant disease characterized by poorly differentiated infiltrating lesions resulting in thickening of the stomach. Malignant tumors start in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body.
messages: Membrane
messages: Monomer and homodimer; the monomer preferentially binds to CTNNB1 and the homodimer to actin (By similarity). Component of an cadherin:catenin adhesion complex composed of at least of CDH26, beta-catenin/CTNNB1, alpha-catenin/CTNNA1 and p120 catenin/CTNND1 (PubMed:28051089). Possible component of an E-cadherin/ catenin adhesion complex together with E-cadherin/CDH1 and beta-catenin/CTNNB1 or gamma-catenin/JUP; the complex is located to adherens junctions (By similarity). The stable association of CTNNA1 is controversial as CTNNA1 was shown not to bind to F-actin when assembled in the complex (By similarity). Alternatively, the CTNNA1-containing complex may be linked to F-actin by other proteins such as LIMA1 (By similarity). Binds AFDN and F-actin (By similarity). Interacts with ARHGAP21 (PubMed:16184169). Interacts with AJUBA (PubMed:12417594). Interacts with LIMA1 (PubMed:18093941). Interacts with vinculin/VCL (PubMed:26691986). Interacts with TJP2/ZO2 (via N-terminus) (By similarity). Interacts with TJP1/ZO1 (via N-terminus) (By similarity).
messages: Phosphorylation seems to contribute to the strength of cell-cell adhesion rather than to the basic capacity for cell-cell adhesion.
messages: Sumoylated.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: adherens junction
messages: cytoskeleton

9606:COL6A5
gene id: 9606:COL6A5
uniprot id: A8TX70
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the type VI collagen family.
messages: Collagen VI acts as a cell-binding protein.
messages: Expressed in skin, followed by lung, small intestine, colon and testis. In skin, it is expressed in the epidermis with strongest staining in suprabasal viable layers. In ATOD patients, it is absent in the most differentiated upper spinous and granular layers (at protein level).
messages: Patients affected by atopic dermatitis display an abnormal distribution of COL29A1 mRNA and protein in skin suggesting that COL29A1 may be involved in the pathogenesis of the disease.
messages: Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.
messages: Trimers composed of three different chains: alpha-1(VI), alpha-2(VI), and alpha-3(VI) or alpha-5(VI) or alpha-6(VI).
messages: extracellular matrix

9606:TFAM
gene id: 9606:TFAM
uniprot id: Q00059
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: Binds DNA via its HMG boxes. When bound to the mitochondrial light strand promoter, bends DNA into a U-turn shape, each HMG box bending the DNA by 90 degrees.
messages: Binds to the mitochondrial light strand promoter and functions in mitochondrial transcription regulation (PubMed:29445193, PubMed:32183942). Component of the mitochondrial transcription initiation complex, composed at least of TFB2M, TFAM and POLRMT that is required for basal transcription of mitochondrial DNA (PubMed:29149603). In this complex, TFAM recruits POLRMT to a specific promoter whereas TFB2M induces structural changes in POLRMT to enable promoter opening and trapping of the DNA non-template strand (PubMed:20410300). Required for accurate and efficient promoter recognition by the mitochondrial RNA polymerase (PubMed:22037172). Promotes transcription initiation from the HSP1 and the light strand promoter by binding immediately upstream of transcriptional start sites (PubMed:22037172). Is able to unwind DNA (PubMed:22037172). Bends the mitochondrial light strand promoter DNA into a U-turn shape via its HMG boxes (PubMed:1737790). Required for maintenance of normal levels of mitochondrial DNA (PubMed:22841477, PubMed:19304746). May play a role in organizing and compacting mitochondrial DNA (PubMed:22037171).
messages: Mitochondrion
messages: Monomer; binds DNA as a monomer (PubMed:19304746, PubMed:22037171, PubMed:22037172). Homodimer (PubMed:29149603). Component of the mitochondrial transcription initiation complex, composed at least of TFB2M, TFAM and POLRMT (PubMed:29149603). In this complex TFAM recruits POLRMT to the promoter whereas TFB2M induces structural changes in POLRMT to enable promoter opening and trapping of the DNA non-template strand (PubMed:29149603). Upon metabolic stress, forms a complex composed of FOXO3, SIRT3, TFAM and POLRMT (PubMed:29445193, PubMed:12897151). Interacts with TFB1M and TFB2M (PubMed:12897151). Interacts with CLPX; this enhances DNA-binding (PubMed:22841477).
messages: Phosphorylation by PKA within the HMG box 1 impairs DNA binding and promotes degradation by the AAA+ Lon protease.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: mitochondrion nucleoid

9606:TRPC4
gene id: 9606:TRPC4
uniprot id: Q9UBN4
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the transient receptor (TC 1.A.4) family. STrpC subfamily. TRPC4 sub-subfamily.
messages: Cell membrane
messages: Forms a receptor-activated non-selective calcium permeant cation channel. Acts as a cell-cell contact-dependent endothelial calcium entry channel. Probably operated by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases or G-protein coupled receptors. Mediates cation entry, with an enhanced permeability to barium over calcium. May also be activated by intracellular calcium store depletion.
messages: Interacts with TRPC4AP (By similarity). Homotetramer and heterotetramer with TRPC1 and/or TRPC5 (PubMed:12032305). Isoform alpha but not isoform beta interacts with ITPR1, ITPR2 and ITPR3 (PubMed:11163362). Interacts with (via PDZ-binding domain) with NHERF1 (PubMed:12154080). Interacts with MX1 and RNF24 (PubMed:15757897, PubMed:17850865). Interacts (via CIRB domain) with SESTD1 (via spectrin 1 repeat) (PubMed:20164195). Interacts with CDH5 and CTNNB1 (PubMed:19996314). Interacts with SPTAN1 (via C-terminal spectrin repeats) and SPTBN5 (via C-terminus) (PubMed:18048348). Interacts (via protein 4.1-binding domain) with EPB41L2 (PubMed:16254212). Interacts with PLSCR1 (By similarity).
messages: Membrane
messages: Phosphorylation modulates TRPC channel function by regulating the level of TRPC4 at the cell surface and by increasing the association with NHERF1.
messages: Strongly expressed in placenta. Expressed at lower levels in heart, pancreas, kidney and brain. Expressed in endothelial cells. Isoform alpha was found to be the predominant isoform. Isoform beta was not found in pancreas and brain.
messages: The calmodulin- and inositol 1,4,5-trisphosphate receptor-binding (CIRB) domain (695-724) is sufficient for the interaction with SESTD1.
messages: The cell membrane presentation, the calcium entry function and the interaction with junctional proteins (CTNNB1 and CDH5) are controlled by endothelial cell-cell contacts.
messages: The interaction with spectrin is important in controlling the translocation of TRPC4 channels to the plasma membrane following EGF stimulation.
messages: The protein 4.1-binding domain (654-685) is required for binding to EPB41L2 and channel activation.
messages: The spectrin-binding domain (730-758) is required for binding to SPTAN1 and SPTBN5.

9606:GPR153
gene id: 9606:GPR153
uniprot id: Q6NV75
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Orphan receptor.

9606:SPR
gene id: 9606:SPR
uniprot id: P35270
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the sepiapterin reductase family.
messages: Catalyzes the final one or two reductions in tetra-hydrobiopterin biosynthesis to form 5,6,7,8-tetrahydrobiopterin.
messages: Cytoplasm
messages: Homodimer.
messages: In vitro phosphorylation of Ser-213 by CaMK2 does not change kinetic parameters.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:CENPL
gene id: 9606:CENPL
uniprot id: Q8N0S6
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the CENP-L/IML3 family.
messages: Component of the CENPA-CAD (nucleosome distal) complex, a complex recruited to centromeres which is involved in assembly of kinetochore proteins, mitotic progression and chromosome segregation. May be involved in incorporation of newly synthesized CENPA into centromeres via its interaction with the CENPA-NAC complex.
messages: Component of the CENPA-CAD complex, composed of CENPI, CENPK, CENPL, CENPO, CENPP, CENPQ, CENPR and CENPS. The CENPA-CAD complex interacts with the CENPA-NAC complex, at least composed of CENPA, CENPC, CENPH, CENPM, CENPN, CENPT and CENPU.
messages: Nucleus
messages: centromere

9606:NFX1
gene id: 9606:NFX1
uniprot id: Q12986
names: Domain
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Isoform 1 and isoform 3 interact with human papillomavirus (HPV) type-16 E6 oncoprotein.
messages: Belongs to the NFX1 family.
messages: Binds to the X-box motif of MHC class II genes and represses their expression. May play an important role in regulating the duration of an inflammatory response by limiting the period in which MHC class II molecules are induced by interferon-gamma. Isoform 3 binds to the X-box motif of TERT promoter and represses its expression. Together with PABPC1 or PABPC4, isoform 1 acts as a coactivator for TERT expression. Mediates E2-dependent ubiquitination.
messages: By IFNG/IFN-gamma.
messages: Isoform 1 interacts with PABPC1 and PABPC4.
messages: Isoform 3 is polyubiquitinated in the presence of HPV16 E6 protein; which leads to proteasomal degradation. Isoform 1 is not polyubiquitinated.
messages: Nucleus
messages: The RING-type zinc finger domain interacts with an ubiquitin-conjugating enzyme (E2) and facilitates ubiquitination.

9606:OR51B5
gene id: 9606:OR51B5
uniprot id: Q05CQ2
uniprot id: Q9H339
names: Caution
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: Membrane
messages: Odorant receptor.

9606:SLC39A1
gene id: 9606:SLC39A1
uniprot id: Q9NY26
names: Activity Regulation
names: Function
names: Induction
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the ZIP transporter (TC 2.A.5) family.
messages: Cell membrane
messages: Down-regulated in prostate cancer.
messages: Endoplasmic reticulum membrane
messages: Inhibited by Ni(2+) ions. Fe(2+) ions do not inhibit zinc uptake.
messages: Transporter for the divalent cation Zn(2+). Mediates the influx of Zn(2+) into cells from extracellular space (PubMed:11301334, PubMed:12888280, PubMed:16844077). Functions as the major importer of zinc from circulating blood plasma into prostate cells (PubMed:12888280).
messages: Ubiquitous (PubMed:10610721, PubMed:11301334). Expressed in most adult and fetal tissues including the epidermis.

9606:CHST14
gene id: 9606:CHST14
uniprot id: Q8NCH0
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the sulfotransferase 2 family.
messages: Catalyzes the transfer of sulfate to position 4 of the N-acetylgalactosamine (GalNAc) residue of dermatan sulfate. Plays a pivotal role in the formation of 4-0-sulfated IdoA blocks in dermatan sulfate. Transfers sulfate to the C-4 hydroxyl of beta1,4-linked GalNAc that is substituted with an alpha-linked iduronic acid (IdoUA) at the C-3 hydroxyl. Transfers sulfate more efficiently to GalNAc residues in -IdoUA-GalNAc-IdoUA- than in -GlcUA-GalNAc-GlcUA-sequences. Has preference for partially desulfated dermatan sulfate. Addition of sulfate to GalNAc may occur immediately after epimerization of GlcUA to IdoUA. Appears to have an important role in the formation of the cerebellar neural network during postnatal brain development.
messages: Golgi apparatus membrane
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Widely expressed. Expressed at high level in pituitary gland, placenta, uterus and thyroid.

9606:TNS2
gene id: 9606:TNS2
uniprot id: Q63HR2
names: Domain
names: Function
names: Induction
names: PTM
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the PTEN phosphatase protein family.
messages: By high glucose levels in differentiated podocytes (at protein level).
messages: Cell membrane
messages: Cytoplasm
messages: Detected in heart, kidney, brain, thymus, spleen, liver, placenta, lung, skeletal muscle and small intestine.
messages: Interacts with AXL (PubMed:12470648). Interacts with SYK; leading to its phosphorylation (PubMed:22019427). Interacts with SQSTM1 (via PB1 domain); the interaction leads to sequestration of TNS2 in cytoplasmic aggregates with SQSTM1 and promotes TNS2 ubiquitination and proteasomal degradation (PubMed:25101860).
messages: Intron retention.
messages: The SH3 domain mediates binding to phosphatidylinositol-3,4,5-triphosphate (PtdIns(3,4,5)P3) (PubMed:30092354). It is also required to ensure podocyte integrity while the phosphatase domain is dispensible for podocyte maintenance (By similarity).
messages: Tyrosine-protein phosphatase which regulates cell motility, proliferation and muscle-response to insulin (PubMed:15817639, PubMed:23401856). Phosphatase activity is mediated by binding to phosphatidylinositol-3,4,5-triphosphate (PtdIns(3,4,5)P3) via the SH2 domain (PubMed:30092354). In muscles and under catabolic conditions, dephosphorylates IRS1 leading to its degradation and muscle atrophy (PubMed:23401856, PubMed:30092354). Negatively regulates PI3K-AKT pathway activation (PubMed:15817639, PubMed:23401856, PubMed:30092354). Dephosphorylates nephrin NPHS1 in podocytes which regulates activity of the mTORC1 complex (PubMed:28955049). Under normal glucose conditions, NPHS1 outcompetes IRS1 for binding to phosphatidylinositol 3-kinase (PI3K) which balances mTORC1 activity but high glucose conditions lead to up-regulation of TNS2, increased NPHS1 dephosphorylation and activation of mTORC1, contributing to podocyte hypertrophy and proteinuria (PubMed:28955049). Required for correct podocyte morphology, podocyte-glomerular basement membrane interaction and integrity of the glomerular filtration barrier (By similarity). Enhances RHOA activation in the presence of DLC1 (PubMed:26427649). Plays a role in promoting DLC1-dependent remodeling of the extracellular matrix (PubMed:20069572).
messages: Ubiquitinated following sequestration in cytoplasmic aggregates with SQSTM1, leading to proteasomal degradation.
messages: focal adhesion

9606:BTBD18
gene id: 9606:BTBD18
uniprot id: B2RXH4
names: Function
names: Subcellular Location Annotation
messages: Nucleus
messages: Specifically required during spermatogenesis to promote expression of piRNA precursors. The piRNA metabolic process mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and governs the methylation and subsequent repression of transposons, which is essential for the germline integrity. Acts by facilitating transcription elongation at piRNA loci during pachytene.

9606:E2F3
gene id: 9606:E2F3
uniprot id: O00716
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the E2F/DP family.
messages: Component of the DRTF1/E2F transcription factor complex. Binds cooperatively with TFDP1/Dp-1 to E2F sites. Interacts with retinoblastoma protein RB1 and related proteins (such as RBL1) that inhibit the E2F transactivation domain. Binds EAPP.
messages: Nucleus
messages: Transcription activator that binds DNA cooperatively with DP proteins through the E2 recognition site, 5'-TTTC[CG]CGC-3' found in the promoter region of a number of genes whose products are involved in cell cycle regulation or in DNA replication. The DRTF1/E2F complex functions in the control of cell-cycle progression from G1 to S phase. E2F3 binds specifically to RB1 in a cell-cycle dependent manner. Inhibits adipogenesis, probably through the repression of CEBPA binding to its target gene promoters (By similarity).

9606:RPLP2
gene id: 9606:RPLP2
uniprot id: P05387
names: Function
names: Similarity
names: Subunit
messages: Belongs to the eukaryotic ribosomal protein P1/P2 family.
messages: Heterodimer with P1 at the lateral ribosomal stalk of the large ribosomal subunit.
messages: Plays an important role in the elongation step of protein synthesis.

9606:ARPIN
gene id: 9606:ARPIN
uniprot id: H0YMP5
uniprot id: Q7Z6K5
names: Domain
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Associates with the Arp2/3 complex. Interacts with ARPC2; enhanced by activated RAC1. Interacts with ARPC5; the interaction is dependent on RAC1.
messages: Based on a naturally occurring readthrough transcript which produces a C15orf38-AP3S2 fusion protein.
messages: Belongs to the Arpin family.
messages: Regulates actin polymerization by inhibiting the actin-nucleating activity of the Arp2/3 complex; the function is competitive with nucleation promoting factors. Participates in an incoherent feedforward loop at the lamellipodium tip where it inhibits the ARP2/2 complex in response to Rac signaling and where Rac also stimulates actin polymerization through the WAVE complex. Involved in steering cell migration by controlling its directional persistence.
messages: The acidic C-terminus is necessary and sufficient to inhibit ARP2/3 complex activity.
messages: lamellipodium

9606:EMC1
gene id: 9606:EMC1
uniprot id: Q8N766
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the EMC1 family.
messages: Component of the ER membrane protein complex (EMC).
messages: Endoplasmic reticulum membrane
messages: Part of the endoplasmic reticulum membrane protein complex (EMC) that enables the energy-independent insertion into endoplasmic reticulum membranes of newly synthesized membrane proteins (PubMed:30415835, PubMed:29809151, PubMed:29242231, PubMed:32459176, PubMed:32439656). Preferentially accommodates proteins with transmembrane domains that are weakly hydrophobic or contain destabilizing features such as charged and aromatic residues (PubMed:30415835, PubMed:29809151, PubMed:29242231). Involved in the cotranslational insertion of multi-pass membrane proteins in which stop-transfer membrane-anchor sequences become ER membrane spanning helices (PubMed:30415835, PubMed:29809151). It is also required for the post-translational insertion of tail-anchored/TA proteins in endoplasmic reticulum membranes (PubMed:29809151, PubMed:29242231). By mediating the proper cotranslational insertion of N-terminal transmembrane domains in an N-exo topology, with translocated N-terminus in the lumen of the ER, controls the topology of multi-pass membrane proteins like the G protein-coupled receptors (PubMed:30415835). By regulating the insertion of various proteins in membranes, it is indirectly involved in many cellular processes (Probable).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:NUDT4
gene id: 9606:NUDT4
uniprot id: A0A024RBG1
uniprot id: Q9NZJ9
names: Cofactor
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the Nudix hydrolase family. DIPP subfamily.
messages: Binds 3 Mg(2+) or Mn(2+) ions per subunit.
messages: Cleaves a beta-phosphate from the diphosphate groups in PP-InsP5 (diphosphoinositol pentakisphosphate), PP-InsP4 and [PP]2-InsP4 (bisdiphosphoinositol tetrakisphosphate), suggesting that it may play a role in signal transduction (PubMed:10777568, PubMed:12370170). Can also catalyze the hydrolysis of diadenosine 5',5'''-P1,P6-hexaphosphate (Ap6A) but not diadenosine 5',5'''-P1,P5-pentaphosphate (Ap5A) and the major reaction products are ADP and p4a from Ap6A (PubMed:12370170). Also able to hydrolyze 5-phosphoribose 1-diphosphate (PubMed:12370170). Does not play a role in U8 snoRNA decapping activity (By similarity). Binds U8 snoRNA (By similarity).
messages: Cleaves a beta-phosphate from the diphosphate groups in PP-InsP5 (diphosphoinositol pentakisphosphate), PP-InsP4 and [PP]2-InsP4 (bisdiphosphoinositol tetrakisphosphate), suggesting that it may play a role in signal transduction. Also able to catalyze the hydrolysis of dinucleoside oligophosphate Ap6A, but not Ap5A. The major reaction products are ADP and p4a from Ap6A. Also able to hydrolyze 5-phosphoribose 1-diphosphate. Does not play a role in U8 snoRNA decapping activity. Binds U8 snoRNA.
messages: Cytoplasm
messages: Expressed in heart and, at lower level in skeletal muscle, pancreas and kidney.

9606:ELK1
gene id: 9606:ELK1
uniprot id: P19419
uniprot id: Q86SR6
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the ETS family.
messages: Interacts in its sumoylated form with PIAS2/PIASX which enhances its transcriptional activator activity (PubMed:15920481). Interacts with MAD2L2; the interaction is direct and promotes phosphorylation by the kinases MAPK8 and/or MAPK9 (PubMed:17296730). Interacts with POU1F1 (PubMed:26612202).
messages: Lung and testis.
messages: Nucleus
messages: On mitogenic stimulation, phosphorylated on C-terminal serine and threonine residues by MAPK1. Ser-383 and Ser-389 are the preferred sites for MAPK1. In vitro, phosphorylation by MAPK1 potentiates ternary complex formation with the serum responses factors, SRE and SRF. Also phosphorylated on Ser-383 by MAPK8 and/or MAKP9. Phosphorylation leads to loss of sumoylation and restores transcriptional activator activity. Phosphorylated and activated by CAMK4, MAPK11, MAPK12 and MAPK14. Upon bFGF stimulus, phosphorylated by PAK1 (By similarity).
messages: Sumoylation represses transcriptional activator activity as it results in recruitment of HDAC2 to target gene promoters which leads to decreased histone acetylation and reduced transactivator activity. It also regulates nuclear retention.
messages: Transcription factor that binds to purine-rich DNA sequences. Forms a ternary complex with SRF and the ETS and SRF motifs of the serum response element (SRE) on the promoter region of immediate early genes such as FOS and IER2. Induces target gene transcription upon JNK-signaling pathway stimulation (By similarity).

9606:KRT36
gene id: 9606:KRT36
uniprot id: O76013
names: Miscellaneous
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Belongs to the intermediate filament family.
messages: Expressed in the hair follicles.
messages: Heterotetramer of two type I and two type II keratins.
messages: There are two types of hair/microfibrillar keratin, I (acidic) and II (neutral to basic).

9606:SLC25A30
gene id: 9606:SLC25A30
uniprot id: B3KSR0
uniprot id: B3KTE8
uniprot id: Q5SVS4
names: Activity Regulation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Antiporter that transports inorganic anions (sulfate, sulfite, thiosulfate and phosphate) and, to a lesser extent, a variety of dicarboxylates (e.g. malonate, malate and citramalate) and, even more so, aspartate (PubMed:31356773). The sulfate/sulfate exchange is much higher than the phosphate/phosphate and malate/malate exchanges (PubMed:31356773). The transport affinities is higher for sulfate and thiosulfate than for any other substrate (PubMed:31356773). May catalyze the export of sulfite and thiosulfate (the hydrogen sulfide degradation products) from the mitochondria, thereby modulating the level of the hydrogen sulfide (Probable). Also may mediate a very low unidirectional transport of sulfate, phosphate and (S)-malate (PubMed:31356773).
messages: Belongs to the mitochondrial carrier (TC 2.A.29) family.
messages: Increased activity at pH 6.0 (PubMed:31356773). sulfate/sulfate exchange activity is inhibited strongly by pyridoxal 5'-phosphate, bathophenanthroline and the organic mercurials mersalyl, p-chloromercuribenzoate and HgCl2 (PubMed:31356773).
messages: Interacts with VDAC1.
messages: Membrane
messages: Mitochondrion inner membrane

9606:NT5M
gene id: 9606:NT5M
uniprot id: Q9NPB1
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the 5'(3')-deoxyribonucleotidase family.
messages: Dephosphorylates specifically the 5' and 2'(3')-phosphates of uracil and thymine deoxyribonucleotides, and so protects mitochondrial DNA replication from excess dTTP. Has only marginal activity towards dIMP and dGMP.
messages: Highly expressed in heart, brain and skeletal muscle. Detected at very low levels in kidney and pancreas.
messages: Homodimer.
messages: Mitochondrion

9606:CMKLR2
gene id: 9606:CMKLR2
uniprot id: P46091
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: (Microbial infection) Coreceptor for HIV-1.
messages: Belongs to the chemokine-like receptor (CMKLR) family.
messages: Cell membrane
messages: Expressed in hippocampus.
messages: Receptor for chemoattractant adipokine chemerin/RARRES2 suggesting a role for this receptor in the regulation of inflammation and energy homesotasis (PubMed:18165312, PubMed:27716822). Signals mainly via beta-arrestin pathway. Binding of RARRES2 activates weakly G proteins, calcium mobilization and MAPK1/MAPK3 (ERK1/2) phosphorylation too (PubMed:27716822). Acts also as a receptor for TAFA1, mediates its effects on neuronal stem-cell proliferation and differentiation via the activation of ROCK/ERK and ROCK/STAT3 signaling pathway (By similarity).

9606:MDFI
gene id: 9606:MDFI
uniprot id: B1AKB6
uniprot id: Q99750
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the MDFI family.
messages: Cytoplasm
messages: Inhibits the transactivation activity of the Myod family of myogenic factors and represses myogenesis. Acts by associating with Myod family members and retaining them in the cytoplasm by masking their nuclear localization signals. Can also interfere with the DNA-binding activity of Myod family members. Plays an important role in trophoblast and chondrogenic differentiation. Regulates the transcriptional activity of TCF7L1/TCF3 by interacting directly with TCF7L1/TCF3 and preventing it from binding DNA. Binds to the axin complex, resulting in an increase in the level of free beta-catenin. Affects axin regulation of the WNT and JNK signaling pathways (By similarity).
messages: Nucleus
messages: The C-terminus interacts with AXIN1 and LEF1 (By similarity). Interacts with CCNT2 (PubMed:17289077).

9606:TRIM2
gene id: 9606:TRIM2
uniprot id: A0A0J9YW02
uniprot id: A0A6Q8PG16
uniprot id: Q9C040
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the TRIM/RBCC family.
messages: Cytoplasm
messages: Forms homooligomers (PubMed:36481767). Interacts with TRIM3; this interaction reduces TRIM2 activity (PubMed:36481767). Interacts with myosin V; myosin V may not be a substrate for ubiquitination (By similarity). Interacts with NEFL (By similarity). Interacts with phosphorylated BCL2L11. Interacts with SIRPA (By similarity).
messages: RING-type zinc finger-dependent and UBE2D1-dependent autoubiquitination.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The interaction with myosin V is dependent upon its NHL repeats, which form a beta-propeller (NHL) domain containing six blades.
messages: UBE2D1-dependent E3 ubiquitin-protein ligase that mediates the ubiquitination of NEFL and of phosphorylated BCL2L11. Plays a neuroprotective function. May play a role in neuronal rapid ischemic tolerance. Plays a role in antiviral immunity and limits New World arenavirus infection independently of its ubiquitin ligase activity (PubMed:24068738).

9606:TAS2R40
gene id: 9606:TAS2R40
uniprot id: P59535
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor T2R family.
messages: Expressed in subsets of taste receptor cells of the tongue and exclusively in gustducin-positive cells.
messages: Gustducin-coupled receptor implicated in the perception of bitter compounds in the oral cavity and the gastrointestinal tract. Signals through PLCB2 and the calcium-regulated cation channel TRPM5.
messages: Membrane
messages: Several bitter taste receptors are expressed in a single taste receptor cell.

9606:ELOA2
gene id: 9606:ELOA2
uniprot id: Q8IYF1
names: Domain
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Heterotrimer of an A (ELOA, ELOA2 or ELOA3P), ELOB and ELOC subunit.
messages: Nucleus
messages: SIII, also known as elongin, is a general transcription elongation factor that increases the RNA polymerase II transcription elongation past template-encoded arresting sites. Subunit A2 is transcriptionally active but its transcription activity is not enhanced by binding to the dimeric complex of the SIII regulatory subunits B and C (elongin BC complex).
messages: Specifically expressed in testis.
messages: The BC-box, which mediates binding to the elongin BC complex, has the consensus sequence [APST]-L-x(3)-C-x(3)-[AILV].

9606:MPO
gene id: 9606:MPO
uniprot id: P05164
names: Cofactor
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the peroxidase family. XPO subfamily.
messages: Binds 1 Ca(2+) ion per monomer.
messages: Binds 1 heme b (iron(II)-protoporphyrin IX) group covalently per monomer.
messages: Homodimer; disulfide-linked. Each monomer consists of a light and a heavy chain.
messages: Lysosome
messages: Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production of hypohalous acids, primarily hypochlorous acid in physiologic situations, and other toxic intermediates that greatly enhance PMN microbicidal activity (PubMed:9922160). Mediates the proteolytic cleavage of alpha-1-microglobulin to form t-alpha-1-microglobulin, which potently inhibits oxidation of low-density lipoprotein particles and limits vascular damage (PubMed:25698971).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:SUCLA2
gene id: 9606:SUCLA2
uniprot id: E5KS60
uniprot id: Q9P2R7
names: Cofactor
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: ATP-specific succinyl-CoA synthetase functions in the citric acid cycle (TCA), coupling the hydrolysis of succinyl-CoA to the synthesis of ATP and thus represents the only step of substrate-level phosphorylation in the TCA (PubMed:15877282). The beta subunit provides nucleotide specificity of the enzyme and binds the substrate succinate, while the binding sites for coenzyme A and phosphate are found in the alpha subunit (By similarity).
messages: ATP-specific succinyl-CoA synthetase functions in the citric acid cycle (TCA), coupling the hydrolysis of succinyl-CoA to the synthesis of ATP and thus represents the only step of substrate-level phosphorylation in the TCA. The beta subunit provides nucleotide specificity of the enzyme and binds the substrate succinate, while the binding sites for coenzyme A and phosphate are found in the alpha subunit.
messages: Belongs to the succinate/malate CoA ligase beta subunit family. ATP-specific subunit beta subfamily.
messages: Binds 1 Mg(2+) ion per subunit.
messages: Heterodimer of an alpha and a beta subunit. The beta subunit determines specificity for ATP (By similarity). Interacts with ALAS2 (PubMed:14643893).
messages: Heterodimer of an alpha and a beta subunit. The beta subunit determines specificity for ATP.
messages: Mitochondrion
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Widely expressed. Not expressed in liver and lung.

9606:ZYX
gene id: 9606:ZYX
uniprot id: Q15942
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Interacts with human papillomavirus type 6/HPV6 protein E6. Does not interact significantly with E6 proteins from HPV types 11, 16, or 18.
messages: Adhesion plaque protein. Binds alpha-actinin and the CRP protein. Important for targeting TES and ENA/VASP family members to focal adhesions and for the formation of actin-rich structures. May be a component of a signal transduction pathway that mediates adhesion-stimulated changes in gene expression (By similarity).
messages: Belongs to the zyxin/ajuba family.
messages: Cytoplasm
messages: Interacts with HPV type 6 protein E6. Does not interact significantly with E6 proteins from HPV types 11, 16, or 18. Interacts, via the Pro-rich regions, with the EVH1 domains of ENAH, EVL and VASP. Interacts with the first LIM domain of TES. Interacts with NEBL (isoform 2). Interacts with SYNPO2.
messages: Nucleus
messages: cytoskeleton
messages: focal adhesion

9606:STAG3
gene id: 9606:STAG3
uniprot id: D6W5U7
uniprot id: Q9UJ98
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the SCC3 family.
messages: Chromosome
messages: Component of cohesin complex, a complex required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate.
messages: Component of the meiosis-specific cohesin complex, which also contains the SMC1 (SMC1A or SMC1B) and SMC3 heterodimer. Such complex likely contains RAD21, or the meiosis-specific related protein REC8. Interacts with CCDC79/TERB1; recruiting cohesin to telomeres to develop structural rigidity (By similarity).
messages: Meiosis specific component of cohesin complex. The cohesin complex is required for the cohesion of sister chromatids after DNA replication. The cohesin complex apparently forms a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. The meiosis-specific cohesin complex probably replaces mitosis specific cohesin complex when it dissociates from chromatin during prophase I.
messages: Nucleus
messages: Part of the cohesin complex which is composed of a heterodimer between a SMC1 protein (SMC1A or SMC1B) and SMC3, which are attached via their hinge domain, and RAD21 which link them at their heads, and one STAG protein.
messages: Phosphorylated.
messages: Testis specific.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The disease is caused by variants affecting the gene represented in this entry. A homozygous deletion in STAG3 predicted to result in frameshift and premature truncation, has been shown to be the cause of premature ovarian failure in a large consanguineous family.
messages: centromere

9606:WASF1
gene id: 9606:WASF1
uniprot id: Q92558
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the SCAR/WAVE family.
messages: Binds the Arp2/3 complex through the C-terminal region and actin through verprolin homology (VPH) domain.
messages: Component of the WAVE1 complex composed of ABI2, CYFIP1 or CYFIP2, BRK1, NCKAP1 and WASF1/WAVE1. Within the complex, a heterodimer containing NCKAP1 and CYFIP1 interacts with a heterotrimer formed by WAVE1, ABI2 and BRK1. CYFIP2 binds to activated RAC1 which causes the complex to dissociate, releasing activated WASF1. The complex can also be activated by NCK1. Binds actin and the Arp2/3 complex. Interacts with BAIAP2. Interacts with SHANK3; the interaction mediates the association of SHANK3 with the WAVE1 complex. Interacts with ABI1 (via N-terminus). Interacts with SORBS2; this interaction greatly enhances phosphorylation by ABL1 and dephosphorylation by PTPN12 and might mediate partial to focal adhesion sites.
messages: Downstream effector molecule involved in the transmission of signals from tyrosine kinase receptors and small GTPases to the actin cytoskeleton. Promotes formation of actin filaments. Part of the WAVE complex that regulates lamellipodia formation (PubMed:29961568). The WAVE complex regulates actin filament reorganization via its interaction with the Arp2/3 complex (By similarity). As component of the WAVE1 complex, required for BDNF-NTRK2 endocytic trafficking and signaling from early endosomes (By similarity). Also involved in the regulation of mitochondrial dynamics (PubMed:29961568).
messages: Highly expressed in brain. Lowly expressed in testis, ovary, colon, kidney, pancreas, thymus, small intestine and peripheral blood.
messages: Phosphorylated on tyrosine residues by ABL1 and dephosphorylated by PTPN12.
messages: Synapse
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: cytoskeleton
messages: focal adhesion

9606:H2AC11
gene id: 9606:H2AC11
uniprot id: A4FTV9
uniprot id: B2R5B3
uniprot id: P0C0S8
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the histone H2A family.
messages: Chromosome
messages: Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
messages: Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.
messages: Deiminated on Arg-4 in granulocytes upon calcium entry.
messages: Glutamine methylation at Gln-105 (H2AQ104me) by FBL is specifically dedicated to polymerase I. It is present at 35S ribosomal DNA locus and impairs binding of the FACT complex (PubMed:24352239).
messages: Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.
messages: Monoubiquitination of Lys-120 (H2AK119Ub) by RING1, TRIM37 and RNF2/RING2 complex gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. It is involved in the initiation of both imprinted and random X inactivation. Ubiquitinated H2A is enriched in inactive X chromosome chromatin. Ubiquitination of H2A functions downstream of methylation of 'Lys-27' of histone H3 (H3K27me). H2AK119Ub by RNF2/RING2 can also be induced by ultraviolet and may be involved in DNA repair. Monoubiquitination of Lys-120 (H2AK119Ub) by TRIM37 may promote transformation of cells in a number of breast cancers (PubMed:25470042). Following DNA double-strand breaks (DSBs), it is ubiquitinated through 'Lys-63' linkage of ubiquitin moieties by the E2 ligase UBE2N and the E3 ligases RNF8 and RNF168, leading to the recruitment of repair proteins to sites of DNA damage. Ubiquitination at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) in response to DNA damage is initiated by RNF168 that mediates monoubiquitination at these 2 sites, and 'Lys-63'-linked ubiquitin are then conjugated to monoubiquitin; RNF8 is able to extend 'Lys-63'-linked ubiquitin chains in vitro. Deubiquitinated by USP51 at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) after damaged DNA is repaired (PubMed:27083998). H2AK119Ub and ionizing radiation-induced 'Lys-63'-linked ubiquitination (H2AK13Ub and H2AK15Ub) are distinct events.
messages: Nucleus
messages: Phosphorylation on Ser-2 (H2AS1ph) is enhanced during mitosis. Phosphorylation on Ser-2 by RPS6KA5/MSK1 directly represses transcription. Acetylation of H3 inhibits Ser-2 phosphorylation by RPS6KA5/MSK1. Phosphorylation at Thr-121 (H2AT120ph) by DCAF1 is present in the regulatory region of many tumor suppresor genes and down-regulates their transcription.
messages: Symmetric dimethylation on Arg-4 by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage.
messages: The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.

9606:DPY19L4
gene id: 9606:DPY19L4
uniprot id: Q7Z388
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the dpy-19 family.
messages: Membrane
messages: Probable C-mannosyltransferase that mediates C-mannosylation of tryptophan residues on target proteins.
messages: Widely expressed.

9606:MRO
gene id: 9606:MRO
uniprot id: Q9BYG7
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Ubiquitous.
messages: nucleolus

9606:ARMCX4
gene id: 9606:ARMCX4
uniprot id: Q5H9R4
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the eutherian X-chromosome-specific Armcx family.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Membrane

9606:RYK
gene id: 9606:RYK
uniprot id: P34925
names: Caution
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: According to some authors, has impaired kinase activity.
messages: Belongs to the protein kinase superfamily. Tyr protein kinase family.
messages: Cytoplasm
messages: Interacts with DVL1 (via PDZ domain).
messages: May be a coreceptor along with FZD8 of Wnt proteins, such as WNT1, WNT3, WNT3A and WNT5A. Involved in neuron differentiation, axon guidance, corpus callosum establishment and neurite outgrowth. In response to WNT3 stimulation, receptor C-terminal cleavage occurs in its transmembrane region and allows the C-terminal intracellular product to translocate from the cytoplasm to the nucleus where it plays a crucial role in neuronal development.
messages: Membrane
messages: Nucleus
messages: Observed in all the tissues examined.
messages: Proteolytically cleaved, in part by presenilin, in response to WNT3 stimulation. Cleavage occurs during neuronal differentiation.
messages: The extracellular WIF domain is responsible for Wnt binding.

9606:CCDC110
gene id: 9606:CCDC110
uniprot id: Q8TBZ0
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Expressed specifically in testis. Also expressed in tumors of different origins.
messages: Nucleus

9606:OTOA
gene id: 9606:OTOA
uniprot id: Q05BM7
uniprot id: Q7RTW8
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Apical cell membrane
messages: Belongs to the mesothelin family.
messages: Belongs to the stereocilin family.
messages: May act as an adhesion molecule.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: extracellular matrix

9606:SH2D1B
gene id: 9606:SH2D1B
uniprot id: O14796
names: Function
names: Subunit
messages: Binds to the phosphorylated receptors CD84, SLAMF1, LY9 and CD244. Does not bind to non-phosphorylated SLAMF1 (PubMed:11689425). Interacts with SLAMF7 (via ITSM phosphorylated on 'Tyr-304'). Interacts with Src kinases HCK, LYN, FYN, FGR and LCK (via kinase domains) (By similarity). Interacts (phosphorylated at Tyr-127) with PLCG1.
messages: Cytoplasmic adapter regulating receptors of the signaling lymphocytic activation molecule (SLAM) family such as CD84, SLAMF1, LY9 and CD244 (PubMed:11689425). In SLAM signaling seems to cooperate with SH2D1A/SAP. Plays a role in regulation of effector functions of natural killer (NK) cells by controlling signal transduction through CD244/2B4 without effecting its tyrosine phosphorylation; downstream signaling involves PLCG1 and ERK activation (PubMed:24687958). Activation of SLAMF7-mediated NK cell function does not effect receptor tyrosine phosphorylation but distal signaling (By similarity). In the context of NK cell-mediated cytotoxicity does not enhance conjugate formation with target cells but stimulates polarization of the microtubule-organizing center and cytotoxic granules toward the NK cell synapse (PubMed:24687958). Negatively regulates CD40-induced cytokine production in dendritic cells downstream of SLAM family receptors probably by inducing activation of the PI3K pathway to inhibit p38 MAPK and JNK activation (By similarity).

9606:CCL7
gene id: 9606:CCL7
uniprot id: P80098
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the intercrine beta (chemokine CC) family.
messages: Chemotactic factor that attracts monocytes and eosinophils, but not neutrophils. Augments monocyte anti-tumor activity. Also induces the release of gelatinase B. This protein can bind heparin. Binds to CCR1, CCR2 and CCR3.
messages: Monomer. Interacts with TNFAIP6 (via Link domain).
messages: O-glycosylated.
messages: Secreted

9606:RAB8B
gene id: 9606:RAB8B
uniprot id: Q92930
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Associated with actin, delta-catenin and alpha and beta tubulins (By similarity). Interacts with OTOF (By similarity). Interacts with PEX5R (By similarity). Interacts with RAB3IP (PubMed:12221131). Interacts with VIM (By similarity). Interacts with CDH1 (By similarity). Interacts with MICALL2 (By similarity). Interacts with GDI1, GDI2, CHML and CHM; phosphorylation at Thr-72 disrupts these interactions (PubMed:29125462). Interacts with MICAL1 (PubMed:32344433).
messages: Belongs to the small GTPase superfamily. Rab family.
messages: Cell membrane
messages: Endosome membrane
messages: Phosphorylation of Thr-72 in the switch II region by LRRK2 prevents the association of RAB regulatory proteins, including CHM, CHML and RAB GDP dissociation inhibitors GDI1 and GDI2.
messages: The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes. Rabs cycle between an inactive GDP-bound form and an active GTP-bound form that is able to recruit to membranes different sets of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. That Rab may be involved in polarized vesicular trafficking and neurotransmitter release. May participate in cell junction dynamics in Sertoli cells (By similarity). May participate in the export of a subset of neosynthesized proteins through a Rab8-Rab10-Rab11-dependent endososomal export route (PubMed:32344433).
messages: phagosome
messages: phagosome membrane

9606:UBQLNL
gene id: 9606:UBQLNL
uniprot id: Q8IYU4
names: Sequence Caution
messages: Chimeric cDNA.

9606:PMPCA
gene id: 9606:PMPCA
uniprot id: Q10713
uniprot id: Q5SXN9
names: Caution
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the peptidase M16 family.
messages: Does not seem to have protease activity as it lacks the zinc-binding site.
messages: Heterodimer of PMPCA (alpha) and PMPCB (beta) subunits, forming the mitochondrial processing protease (MPP) in which PMPCA is involved in substrate recognition and binding and PMPCB is the catalytic subunit.
messages: Mitochondrion inner membrane
messages: Mitochondrion matrix
messages: Substrate recognition and binding subunit of the essential mitochondrial processing protease (MPP), which cleaves the mitochondrial sequence off newly imported precursors proteins.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitously expressed with highest expression in fetal tissues and adult brain, cerebellum and cerebellar vermis.

9606:ZNF519
gene id: 9606:ZNF519
uniprot id: Q8TB69
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:LAMB4
gene id: 9606:LAMB4
uniprot id: A4D0S4
uniprot id: B4DTV7
uniprot id: B7ZMJ6
uniprot id: C9JMJ0
uniprot id: O95127
names: Caution
names: Domain
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components.
messages: Domains VI and IV are globular.
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: Laminin is a complex glycoprotein, consisting of three different polypeptide chains (alpha, beta, gamma), which are bound to each other by disulfide bonds into a cross-shaped molecule comprising one long and three short arms with globules at each end.
messages: Membrane
messages: The alpha-helical domains I and II are thought to interact with other laminin chains to form a coiled coil structure.
messages: basement membrane

9606:LYZL6
gene id: 9606:LYZL6
uniprot id: A0A080YUZ6
uniprot id: O75951
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the glycosyl hydrolase 22 family.
messages: Cell surface
messages: Expressed in testis, epididymis and spermatozoa (at protein level) (PubMed:16014814, PubMed:28182716). Expressed in late-stage spermatocytes and round spermatids (PubMed:28182716).
messages: May be involved sperm-egg plasma membrane adhesion and fusion during fertilization (PubMed:28182716). Exhibits bacteriolytic activity in vitro against Micrococcus luteus and Staphylococcus aureus (PubMed:28182716, PubMed:24013621). Shows weak bacteriolytic activity against Gram-positive bacteria at physiological pH (PubMed:28182716). Bacteriolytic activity is pH-dependent, with a maximum at around pH 5.6 (PubMed:28182716).
messages: Monomer.
messages: Secreted
messages: flagellum

9606:MAP4
gene id: 9606:MAP4
uniprot id: P27816
names: Function
names: Miscellaneous
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: Interacts with SEPTIN2; this interaction impedes tubulin-binding. Interacts with TRAF3IP1 (By similarity). Interacts with KNSTRN (PubMed:29180244).
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Non-neuronal microtubule-associated protein. Promotes microtubule assembly.
messages: Phosphorylated at serine residues in K-X-G-S motifs by MAP/microtubule affinity-regulating kinase (MARK1 or MARK2), causing detachment from microtubules, and their disassembly (By similarity). Phosphorylation on Ser-787 negatively regulates MAP4 activity to promote microtubule assembly. Isoform 3 is phosphorylated on Ser-337 and Ser-338.
messages: cytoskeleton
messages: microtubule organizing center

9606:ESR1
gene id: 9606:ESR1
uniprot id: A0A125SXW3
uniprot id: A8KAF4
uniprot id: G4XH65
uniprot id: H0Y4W6
uniprot id: P03372
names: Caution
names: Disease Annotation
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Polymorphism
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the nuclear hormone receptor family.
messages: Belongs to the nuclear hormone receptor family. NR3 subfamily.
messages: Binds DNA as a homodimer.
messages: Binds DNA as a homodimer. Can form a heterodimer with ESR2. Interacts with FOXC2, MAP1S, SLC30A9, UBE1C and NCOA3 coactivator (By similarity). Interacts with PELP1, the interaction is enhanced by 17-beta-estradiol, the interaction increases ESR1 transcriptional activity (PubMed:11481323, PubMed:14963108). Interacts with EP300; the interaction is estrogen-dependent and enhanced by CITED1. Interacts with CITED1; the interaction is estrogen-dependent. Interacts with NCOA5 and NCOA6 coactivators. Interacts with NCOA7; the interaction is a ligand-inducible. Interacts with PHB2, and UBE1C. Interacts with AKAP13. Interacts with CUEDC2. Interacts with KDM5A. Interacts with SMARD1. Interacts with HEXIM1. Interacts with PBXIP1. Interaction with MUC1 is stimulated by 7 beta-estradiol (E2) and enhances ESR1-mediated transcription. Interacts with DNTTIP2, FAM120B and UIMC1. Interacts with isoform 4 of TXNRD1. Interacts with KMT2D/MLL2. Interacts with ATAD2 and this interaction is enhanced by estradiol. Interacts with KIF18A and LDB1. Interacts with RLIM (via C-terminus). Interacts with MACROD1. Interacts with SH2D4A and PLCG. Interaction with SH2D4A blocks binding to PLCG and inhibits estrogen-induced cell proliferation. Interacts with DYNLL1. Interacts with CCDC62 in the presence of estradiol/E2; this interaction seems to enhance the transcription of target genes. Interacts with NR2C1; the interaction prevents homodimerization of ESR1 and suppresses its transcriptional activity and cell growth. Interacts with DNAAF4. Interacts with PRMT2. Interacts with RBFOX2. Interacts with STK3/MST2 only in the presence of SAV1 and vice-versa. Binds to CSNK1D. Interacts with NCOA2; NCOA2 can interact with ESR1 AF-1 and AF-2 domains simultaneously and mediate their transcriptional synergy. Interacts with DDX5 (PubMed:11682626). Interacts with NCOA1; the interaction seems to require a self-association of N-terminal and C-terminal regions. Interacts with ZNF366, DDX17, NFKB1, RELA, SP1 and SP3.…
messages: Cell membrane
messages: Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain. The modulating domain, also known as A/B or AF-1 domain has a ligand-independent transactivation function. The C-terminus contains a ligand-dependent transactivation domain, also known as E/F or AF-2 domain which overlaps with the ligand binding domain. AF-1 and AF-2 activate transcription independently and synergistically and act in a promoter- and cell-specific manner. AF-1 seems to provide the major transactivation function in differentiated cells.
messages: Cytoplasm
messages: Dimethylated by PRMT1 at Arg-260. The methylation may favor cytoplasmic localization (PubMed:18657504, PubMed:24498420). Demethylated by JMJD6 at Arg-260 (PubMed:24498420).
messages: Genetic variations in ESR1 are correlated with bone mineral density (BMD). Low BMD is a risk factor for osteoporotic fracture. Osteoporosis is characterized by reduced bone mineral density, disruption of bone microarchitecture, and the alteration of the amount and variety of non-collagenous proteins in bone. Osteoporotic bones are more at risk of fracture.
messages: Glycosylated; contains N-acetylglucosamine, probably O-linked.
messages: Golgi apparatus
messages: Involved in activation of NOS3 and endothelial nitric oxide production (PubMed:21937726). Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full-length receptor (PubMed:10970861). Binds to ERE and inhibits isoform 1 (PubMed:10970861).
messages: Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3 (PubMed:17922032).
messages: Nucleus
messages: Palmitoylated (isoform 3). Not biotinylated (isoform 3).
messages: Palmitoylated by ZDHHC7 and ZDHHC21. Palmitoylation is required for plasma membrane targeting and for rapid intracellular signaling via ERK and AKT kinases and cAMP generation, but not for signaling mediated by the nuclear hormone receptor.
messages: Phosphorylated by cyclin A/CDK2 and CK1. Phosphorylation probably enhances transcriptional activity. Self-association induces phosphorylation. Dephosphorylation at Ser-118 by PPP5C inhibits its transactivation activity. Phosphorylated by LMTK3 in vitro.
messages: Probably homodimerizes or heterodimerizes with isoform 1 and ESR2.
messages: Produced by alternative promoter usage.
messages: Produced by alternative splicing of isoform 3.
messages: Selective estrogen receptor modulators (SERMs), such as tamoxifen, raloxifene, toremifene, lasofoxifene, clomifene, femarelle and ormeloxifene, have tissue selective agonistic and antagonistic effects on the estrogen receptor (ER). They interfere with the ER association with coactivators or corepressors, mainly involving the AF-2 domain.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues.
messages: Ubiquitinated; regulated by LATS1 via DCAF1 it leads to ESR1 proteasomal degradation (PubMed:21602804, PubMed:28068668). Deubiquitinated by OTUB1 (PubMed:19383985).
messages: Was reported to be activated by DDX5. However, this study has been retracted due to concerns of image manipulation.
messages: Widely expressed (PubMed:10970861). Not expressed in the pituitary gland (PubMed:10970861).
messages: Widely expressed, however not expressed in the pituitary gland.
messages: contains an in-frame duplication of exons 6 and 7.

9606:PABPN1
gene id: 9606:PABPN1
uniprot id: Q86U42
names: Disease Annotation
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Polymorphism
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Arginine dimethylation is asymmetric and involves PRMT1 and PRMT3. It does not influence the RNA binding properties (By similarity).
messages: Cytoplasm
messages: Involved in the 3'-end formation of mRNA precursors (pre-mRNA) by the addition of a poly(A) tail of 200-250 nt to the upstream cleavage product (By similarity). Stimulates poly(A) polymerase (PAPOLA) conferring processivity on the poly(A) tail elongation reaction and controls also the poly(A) tail length (By similarity). Increases the affinity of poly(A) polymerase for RNA (By similarity). Is also present at various stages of mRNA metabolism including nucleocytoplasmic trafficking and nonsense-mediated decay (NMD) of mRNA. Cooperates with SKIP to synergistically activate E-box-mediated transcription through MYOD1 and may regulate the expression of muscle-specific genes (PubMed:11371506). Binds to poly(A) and to poly(G) with high affinity (By similarity). May protect the poly(A) tail from degradation (By similarity). Subunit of the trimeric poly(A) tail exosome targeting (PAXT) complex, a complex that directs a subset of long and polyadenylated poly(A) RNAs for exosomal degradation. The RNA exosome is fundamental for the degradation of RNA in eukaryotic nuclei. Substrate targeting is facilitated by its cofactor MTREX, which links to RNA-binding protein adapters (PubMed:27871484).
messages: May be due to a competing donor splice site.
messages: May interact with SETX (PubMed:21700224). Monomer and homooligomer. Binds RNA as a monomer and oligomerizes when bound to poly(A). Interacts with PAPOLA, but only in presence of oligo(A) RNA. Interacts with transportin. Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Association in a ternary complex with CPSF4 and influenza A virus NS1 blocks pre-mRNAs processing, thereby preventing nuclear export of host cell mRNAs. Associates in a single complex with SKIP and MYOD1 and interacts with SKIP in differentiated myocytes. Interacts with NUDT21/CPSF5. Interacts (via RRM domain and C-terminal arginine-rich region) with ZFP36 (via hypophosphorylated form); this interaction occurs in the nucleus in a RNA-independent manner, decreases in presence of single-stranded poly(A) RNA-oligomer and in a p38-dependent-manner and may down-regulated RNA poly(A) polymerase activity (By similarity). Component of the poly(A) tail exosome targeting (PAXT) complex made of accessory factors, such as PABPN1, ZFC3H1 and MTREX (PubMed:27871484). Interacts with ZFC3H1 in a RNase-insensitive manner (PubMed:27871484). Interacts with FRG1 (PubMed:17103222).
messages: Nucleus
messages: Nucleus speckle
messages: The RRM domain is essential for specific adenine bases recognition in the poly(A) tail but not sufficient for poly(A) binding.
messages: The association of the expanded polyalanine mutations together with the capability to oligomerize may induce intranuclear inclusions and cell death. Expanded polyalanine mutations may either result from unequal crossing over during germ cell homologous recombination or from DNA slippage. The pathogenic mechanisms mediated by polyalanine expansion mutations may be either a general disruption of cellular RNA metabolism due to the trapping by the inclusions of PABPN1, mRNAs and/or nuclear proteins, resulting in the induction of cell death; or may change the normal muscle cell differentiation.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The poly-Ala region of PABPN1 is polymorphic (6-7 repeats) in the population and is expanded to 8-13 repeats in OPMD patients. Compound heterozygotes for (GCG)9 mutation and a (GCG)7 allele result in earlier onset and more severe clinical manifestations of the disease.
messages: Ubiquitous.

9606:TXNDC15
gene id: 9606:TXNDC15
uniprot id: Q96J42
names: Caution
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
messages: Acts as a positive regulator of ciliary hedgehog signaling (By similarity). Involved in ciliogenesis (PubMed:27894351).
messages: It is uncertain whether Met-1 or Met-13 is the initiator.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: cilium membrane

9606:TNFAIP8L2
gene id: 9606:TNFAIP8L2
uniprot id: Q6P589
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acts as a negative regulator of innate and adaptive immunity by maintaining immune homeostasis (PubMed:27043859). Plays a regulatory role in the Toll-like signaling pathway by determining the strength of LPS-induced signaling and gene expression (PubMed:32188758). Inhibits TCR-mediated T-cell activation and negatively regulate T-cell function to prevent hyperresponsiveness (By similarity). Inhibits also autolysosome formation via negatively modulating MTOR activation by interacting with RAC1 and promoting the disassociation of the RAC1-MTOR complex (PubMed:32460619). Plays an essential role in NK-cell biology by acting as a checkpoint and displaying an expression pattern correlating with NK-cell maturation process and by negatively regulating NK-cell maturation and antitumor immunity (By similarity). Mechanistically, suppresses IL-15-triggered mTOR activity in NK-cells (By similarity).
messages: Belongs to the TNFAIP8 family. TNFAIP8L2 subfamily.
messages: Cytoplasm
messages: Expressed in T-cells, B-cells, macrophages, neurons in the brain and brainstem, and stratified squamous epithelia of the esophagus, cervix and skin.
messages: Lysosome
messages: May interact with CASP8; however, such result is unclear since PubMed:19079267 could not reproduce the interaction with CASP8. Interacts with RAC1 (PubMed:32460619).
messages: Nucleus
messages: Phosphorylated by TAK1/MAP3K7; this phosphorylation triggers association with BTRC and subsequent ubiquitination and degradation.
messages: The central region was initially thought to constitute a DED (death effector) domain. However, 3D-structure data reveal a previously uncharacterized fold that is different from the predicted fold of a DED (death effector) domain. It consists of a large, hydrophobic central cavity that is poised for cofactor binding.
messages: Ubiquitinated in a BTRC-depdent manner; leading to degradation mediated through the proteasome pathway.

9606:CTAGE4
gene id: 9606:CTAGE4
uniprot id: Q8IX94
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the cTAGE family.
messages: Expressed in testis, placenta and skin. Expressed at lower level in mammary gland and stomach.
messages: Membrane
messages: Tumor-associated antigen found in several cutaneous T-cell lymphoma (CTCL). Also found in colorectal and breast carcinomas, head and neck squamous cell carcinomas and melanoma.
messages: Tumor-associated antigen.

9606:CEP76
gene id: 9606:CEP76
uniprot id: Q8TAP6
names: Developmental Stage
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the CEP76 family.
messages: Centrosomal protein involved in regulation of centriole duplication. Required to limit centriole duplication to once per cell cycle by preventing centriole reduplication.
messages: Expressed at low level in G1 and is induced in S and G2 phase, during which point centrioles have already commenced duplication (at protein level).
messages: Interacts with CCP110 and CEP97.
messages: centriole
messages: centrosome

9606:TGFBI
gene id: 9606:TGFBI
uniprot id: A0A0S2Z4Q2
uniprot id: Q15582
names: Disease Annotation
names: Function
names: Induction
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Binds to type I, II, and IV collagens.
messages: By TGF-beta (PubMed:1388724, PubMed:8024701).
messages: Gamma-carboxylation is controversial. Gamma-carboxyglutamated; gamma-carboxyglutamate residues are formed by vitamin K dependent carboxylation; these residues may be required for binding to calcium (PubMed:18450759). According to a more recent report, does not contain vitamin K-dependent gamma-carboxyglutamate residues (PubMed:26273833).
messages: Highly expressed in the corneal epithelium (PubMed:27609313, PubMed:8077289). Expressed in heart, placenta, lung, liver, skeletal muscle, kidney and pancreas (PubMed:8077289).
messages: Plays a role in cell adhesion (PubMed:8024701). May play a role in cell-collagen interactions (By similarity).
messages: Secreted
messages: The EMI domain contains 2 expected intradomain disulfide bridges (Cys-49-Cys85 and Cys-84-Cys-97) and one unusual interdomain disulfide bridge to the second FAS1 domain (Cys-74-Cys-339). This arrangement violates the predicted disulfide bridge pattern of an EMI domain.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: extracellular matrix

9606:NEURL4
gene id: 9606:NEURL4
uniprot id: Q96JN8
names: Domain
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Interacts with CCP110; this interaction propmotes CCP110 ubiquitination and degradation via the proteasome pathway. Via its interaction with CCP110, may indirectly interact with CEP97. Interacts with the E3 ubiquitin-protein ligase HERC2 and UBE3A. May interact with MAPK6 and hence mediate MAPK6 interaction with UBE3A. Interaction with UBE3A may be indirect and mediated by HERC2.
messages: Promotes CCP110 ubiquitination and proteasome-dependent degradation. By counteracting accumulation of CP110, maintains normal centriolar homeostasis and preventing formation of ectopic microtubular organizing centers.
messages: The third NHR domain (NHR 3) is required for localization to both mother and daughter centrioles. NHR 1 restricts targeting to daughter centriole (PubMed:22441691). NHR 3 and 4 are required for CCP110/CEP97-binding, but not for HERC2-binding. NHR 5 and 6 are important for HERC2-binding and centrosomal localization (PubMed:22261722).
messages: Ubiquitinated; undergoes HERC2-dependent 'Lys-48' ubiquitination. This ubiquitination leads to proteasomal degradation.
messages: Widely expressed at high levels (including brain).
messages: centriole

9606:LHX2
gene id: 9606:LHX2
uniprot id: B3KNJ5
uniprot id: P50458
names: Domain
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Acts as a transcriptional activator. Stimulates the promoter of the alpha-glycoprotein gene. Transcriptional regulatory protein involved in the control of cell differentiation in developing lymphoid and neural cell types (By similarity).
messages: Interacts (via LIM domains) with CITED2. Interacts with POU4F2.
messages: LIM domains are necessary for transcription activation.
messages: Nucleus

9606:ONECUT3
gene id: 9606:ONECUT3
uniprot id: O60422
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the CUT homeobox family.
messages: Nucleus
messages: Transcriptional activator. Binds the consensus DNA sequence 5'-DHWATTGAYTWWD-3' on a variety of gene promoters such as those of HNF3B and TTR (By similarity).

9606:RCAN3
gene id: 9606:RCAN3
uniprot id: Q9UKA8
names: Function
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Belongs to the RCAN family.
messages: Highest expression in heart, skeletal muscle kidney, liver and peripheral blood leukocytes. Lower expression in all other tissues.
messages: Inhibits calcineurin-dependent transcriptional responses by binding to the catalytic domain of calcineurin A. Could play a role during central nervous system development (By similarity).
messages: Interacts with protein phosphatase PPP3CA/calcineurin A.

9606:LYNX1-SLURP2
gene id: 9606:LYNX1-SLURP2
uniprot id: P0DP58
names: Function
names: Miscellaneous
names: Subcellular Location Annotation
names: Subunit
messages: Acts in different tissues through interaction to nicotinic acetylcholine receptors (nAChRs) (PubMed:21252236). The proposed role as modulator of nAChR activity seems to be dependent on the nAChR subtype and stoichiometry, and to involve an effect on nAChR trafficking and its cell surface expression, and on single channel properties of the nAChR inserted in the plasma membrane. Modulates functional properties of nicotinic acetylcholine receptors (nAChRs) to prevent excessive excitation, and hence neurodegeneration. Enhances desensitization by increasing both the rate and extent of desensitization of alpha-4:beta-2-containing nAChRs and slowing recovery from desensitization. Promotes large amplitude ACh-evoked currents through alpha-4:beta-2 nAChRs. Is involved in regulation of the nAChR pentameric assembly in the endoplasmic reticulum. Shifts stoichiometry from high sensitivity alpha-4(2):beta-2(3) to low sensitivity alpha-4(3):beta-2(2) nAChR (By similarity). In vitro modulates alpha-3:beta-4-containing nAChRs. Reduces cell surface expression of (alpha-3:beta-4)(2):beta-4 and (alpha-3:beta-4)(2):alpha-5 nAChRs suggesting an interaction with nAChR alpha-3(-):(+)beta-4 subunit interfaces and an allosteric mode. Corresponding single channel effects characterized by decreased unitary conductance, altered burst proportions and enhanced desensitization/inactivation seem to depend on nAChR alpha:alpha subunit interfaces and are greater in (alpha-3:beta-2)(2):alpha-3 when compared to (alpha-3:beta-2)(2):alpha-5 nAChRs (PubMed:28100642). Prevents plasticity in the primary visual cortex late in life (By similarity).
messages: Based on a naturally occurring readthrough transcript which produces a LYNX1-SLURP2 fusion protein.
messages: Cell membrane
messages: Endoplasmic reticulum
messages: Interacts with nAChRs containing alpha-4:beta-2 (CHRNA4:CHRNB2) and alpha-7 (CHRNA7) subunits. Interacts with CHRNA4 probably in the endoplasmic reticulum prior to nAChR pentameric assembly (By similarity).
messages: Isoform 1 is considered to be an endogenous 'prototoxin', that shares a N-terminal three-finger structure with snake alpha-neurotoxins.
messages: dendrite

9606:SIGLEC14
gene id: 9606:SIGLEC14
uniprot id: Q08ET2
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the immunoglobulin superfamily. SIGLEC (sialic acid binding Ig-like lectin) family.
messages: Cell membrane
messages: Interacts with TYROBP.
messages: Mainly expressed in hematopoietic tissues including bone marrow, spleen and fetal liver. Also detected in lung and testis.
messages: Putative adhesion molecule. Sialic acid-binding paired receptor which may activate associated receptors.

9606:NUP62CL
gene id: 9606:NUP62CL
uniprot id: A0A0S2Z5E8
uniprot id: Q9H1M0
names: Similarity
messages: Belongs to the nucleoporin NSP1/NUP62 family.

9606:DSG4
gene id: 9606:DSG4
uniprot id: Q86SJ6
names: Disease Annotation
names: Domain
names: Function
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Autoantibodies against DSG4 are found in patients with pemphigus vulgaris. Pemphigus vulgaris is a potentially lethal skin disease in which epidermal blisters occur as the result of the loss of cell-cell adhesion.
messages: Cell membrane
messages: Component of intercellular desmosome junctions. Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion. Coordinates the transition from proliferation to differentiation in hair follicle keratinocytes (By similarity).
messages: Highly expressed in skin, testis and prostate; less in salivary gland. In scalp follicles, present in the inner root sheath (IRS) and all layers of the matrix and precortex.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain.
messages: desmosome

9606:UBXN1
gene id: 9606:UBXN1
uniprot id: A0A087WTZ5
uniprot id: Q04323
names: Domain
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Interacts (via C-terminal UBX domain) with nipah virus protein V.
messages: Cytoplasm
messages: Interacts with MAVS; this interaction prevents MAVS oligomerization and thus disrupts the RLR signaling pathway (PubMed:23545497). Interacts with CUL1; this interaction inhibits CUL1-mediated degradation of NF-kappa-B inhibitors (PubMed:28152074). Interacts with BIRC2/c-IAP1; this interaction prevents TNFalpha-stimulated RIP1 ubiquitination and subsequent NF-kappa-B activation (PubMed:25681446). Component of a complex required to couple retrotranslocation, ubiquitination and deglycosylation composed of NGLY1, SAKS1, AMFR, VCP and RAD23B. Interacts with HOMER2 (By similarity). Interacts directly with VCP. Interacts with BRCA1 and BARD1; interaction takes place when BRCA1 is not autoubiquitinated but is strongly enhanced in the presence of autoubiquitinated BRCA1.
messages: The UBA domain specifically recognizes and binds 'Lys-6'-linked polyubiquitin chains.
messages: Ubiquitin-binding protein that plays a role in the modulation of innate immune response. Blocks both the RIG-I-like receptors (RLR) and NF-kappa-B pathways. Following viral infection, UBXN1 is induced and recruited to the RLR component MAVS. In turn, interferes with MAVS oligomerization, and disrupts the MAVS/TRAF3/TRAF6 signalosome. This function probably serves as a brake to prevent excessive RLR signaling (PubMed:23545497). Interferes with the TNFalpha-triggered NF-kappa-B pathway by interacting with cellular inhibitors of apoptosis proteins (cIAPs) and thereby inhibiting their recruitment to TNFR1 (PubMed:25681446). Prevents also the activation of NF-kappa-B by associating with CUL1 and thus inhibiting NF-kappa-B inhibitor alpha/NFKBIA degradation that remains bound to NF-kappa-B (PubMed:28152074). Interacts with the BRCA1-BARD1 heterodimer and regulates its activity. Specifically binds 'Lys-6'-linked polyubiquitin chains. Interaction with autoubiquitinated BRCA1 leads to the inhibition of the E3 ubiquitin-protein ligase activity of the BRCA1-BARD1 heterodimer (PubMed:20351172). Component of a complex required to couple deglycosylation and proteasome-mediated degradation of misfolded proteins in the endoplasmic reticulum that are retrotranslocated in the cytosol.

9606:OAS1
gene id: 9606:OAS1
uniprot id: P00973
names: Activity Regulation
names: Caution
names: Disease Annotation
names: Function
names: Induction
names: PTM
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the 2-5A synthase family.
messages: By type I interferon (IFN) and viruses.
messages: Cytoplasm
messages: Endoplasmic reticulum
messages: Expressed in lungs.
messages: Interferon-induced, dsRNA-activated antiviral enzyme which plays a critical role in cellular innate antiviral response (PubMed:34581622). In addition, it may also play a role in other cellular processes such as apoptosis, cell growth, differentiation and gene regulation. Synthesizes higher oligomers of 2'-5'-oligoadenylates (2-5A) from ATP which then bind to the inactive monomeric form of ribonuclease L (RNase L) leading to its dimerization and subsequent activation. Activation of RNase L leads to degradation of cellular as well as viral RNA, resulting in the inhibition of protein synthesis, thus terminating viral replication (PubMed:34581622, PubMed:34145065). Can mediate the antiviral effect via the classical RNase L-dependent pathway or an alternative antiviral pathway independent of RNase L. The secreted form displays antiviral effect against vesicular stomatitis virus (VSV), herpes simplex virus type 2 (HSV-2), and encephalomyocarditis virus (EMCV) and stimulates the alternative antiviral pathway independent of RNase L.
messages: Microsome
messages: Mitochondrion
messages: Monomer (PubMed:9407111). Homotetramer (PubMed:9407111, PubMed:23319625).
messages: Not prenylated at C-terminal, is diffusely localized and unable to initiate a detectable block to SARS-CoV-2 replication.
messages: Not prenylated at C-terminal. The non-prenylated form is diffusely localized and unable to initiate a detectable block to SARS-CoV-2 replication.
messages: Nucleus
messages: Polymorphism dbSNP:rs10774671 is associated with protection against severe COVID-19 disease (PubMed:34581622, PubMed:33633408). In humans, the OAS1 protein is expressed as two major forms designated p46 and p42. The longer p46 isoform is generated by alternative splicing to an exon downstream of the terminal exon used by the p42 isoform. Although all human genotypes contain the exon that completes the transcript encoding p46, an intronic SNP (rs10774671) determines OAS1 exon usage. Alleles with a G at this SNP (G alleles) specify expression of the p46 isoform and some p42, whereas alleles with A at this position predominantly encode the p42 isoform and cannot express the p46 isoform (PubMed:34581622). The p42 isoform, which is the most common isoform in humans (~61% of alleles), has no detectable anti-SARS-CoV-2 activity. The p46 isoform has anti-SARS-CoV-2 activity (PubMed:34581622).
messages: Prenylated at C-terminal. C-terminal prenylation is necessary to initiate a block to SARS-CoV-2 and is associated with protection from severe COVID-1. The prenylated form is targeted to perinuclear structures rich in viral dsRNA, whereas the non-prenylated form is diffusely localized and unable to initiate a detectable block to SARS-CoV-2 replication (Probable). C-terminal prenylation is also necessary to initiate a block to cardiovirus EMCV (Probable).
messages: Produced as a latent enzyme which is activated by dsRNA generated during the course of viral infection. The dsRNA activator must be at least 15 nucleotides long, and no modification of the 2'-hydroxyl group is tolerated (PubMed:34581622). ssRNA or dsDNA do not act as activators.
messages: PubMed:1651324 sequence was originally thought to originate from mouse.
messages: Secreted
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: When prenylated at C-terminal, acts as a double-stranded RNA (dsRNA) sensor specifically targeted to membranous replicative organelles in SARS coronavirus-2/SARS-CoV-2 infected cells where it binds to dsRNA structures in the SARS-CoV-2 5'-UTR and initiates a potent block to SARS-CoV-2 replication. Recognizes short stretches of dsRNA and activates RNase L. The binding is remarkably specific, with two conserved stem loops in the SARS-CoV-2 5'- untranslated region (UTR) constituting the principal viral target (PubMed:34581622). The same mechanism is necessary to initiate a block to cardiovirus EMCV (PubMed:34581622).

9606:TRDMT1
gene id: 9606:TRDMT1
uniprot id: O14717
uniprot id: Q6ICS7
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the class I-like SAM-binding methyltransferase superfamily. C5-methyltransferase family.
messages: Cytoplasm
messages: Specifically methylates cytosine 38 in the anticodon loop of tRNA(Asp).
messages: Ubiquitous. Higher expression in testis, ovary and thymus and at much lower levels in spleen, prostate, colon, small intestine, and peripheral blood leukocytes.

9606:YIPF1
gene id: 9606:YIPF1
uniprot id: Q9Y548
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the YIP1 family.
messages: Interacts with YIPF6; this interaction may stabilize YIPF1. May also form a ternary complex with YIPF2 and YIPF6.
messages: Late endosome membrane
messages: cis-Golgi network membrane
messages: trans-Golgi network membrane

9606:NYX
gene id: 9606:NYX
uniprot id: Q9GZU5
names: Disease Annotation
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the small leucine-rich proteoglycan (SLRP) family. SLRP class IV subfamily.
messages: Expressed in kidney and retina. Also at low levels in brain, testis and muscle. Within the retina, expressed in the inner segment of photoreceptors, outer and inner nuclear layers and the ganglion cell layer.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: extracellular matrix

9606:SULT1C3
gene id: 9606:SULT1C3
uniprot id: Q6IMI6
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the sulfotransferase 1 family.
messages: Cytoplasm
messages: Exhibits weak sulphating activity and only toward chloro phenols (pentachlorophenol and 3,3',5,5'-tetrachloro-4,4'-biphenyldiol).
messages: Expressed in the small intestine.
messages: Not detectable in any of the tissues tested.
messages: SULT1C3 gene appears to be present only in humans and other primates.
messages: Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor. Has sulfotransferase activity towards various substrates, such as bile acids, thyroid hormones and toward xenobiotic compounds such as chloro phenols and hydroxypyrenes. Lithocholic acid appears to be the best substrate among the endogenous compounds tested and 3,3',5,5'-tetrachloro-4,4'-biphenyldiol shows the highest specific activity among the xenobiotic compounds.

9606:UGT2A1
gene id: 9606:UGT2A1
uniprot id: A0A140T9Z0
uniprot id: D6RFW5
uniprot id: P0DTE4
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the UDP-glycosyltransferase family.
messages: Endoplasmic reticulum membrane
messages: Membrane
messages: Olfactory epithelium, brain and fetal lung (PubMed:10359671). Not present in liver (PubMed:10359671).
messages: UDP-glucuronosyltransferase (UGT) that catalyzes phase II biotransformation reactions in which lipophilic substrates are conjugated with glucuronic acid to increase the metabolite's water solubility, thereby facilitating excretion into either the urine or bile (PubMed:10359671, PubMed:19858781, PubMed:18719240, PubMed:19022937, PubMed:23756265, PubMed:23288867). Essential for the elimination and detoxification of drugs, xenobiotics and endogenous compounds (PubMed:10359671, PubMed:19858781, PubMed:23756265). Catalyzes the glucuronidation of endogenous steroid hormones such as androgens (testosterone and epitestosterone) and estrogens (estradiol and epiestriol) (PubMed:18719240, PubMed:19858781, PubMed:19022937, PubMed:23288867). Contributes to bile acid (BA) detoxification by catalyzing the glucuronidation of BA substrates, which are natural detergents for dietary lipids absorption (PubMed:23756265). Shows a high affinity to aliphatic odorants such as citronellol as well as olfactory tissue specificity, and therefore may be involved in olfaction (PubMed:10359671). Shows a potential role in detoxification of toxic waste compounds in the amniotic fluid before birth, and air-born chemical after birth (PubMed:19858781).
messages: UGT2A1 isoform is part of the UGT2A complex locus which displays alternative use of promoters and exons. The locus is defined by 2 alternative promoters giving rise to 2 fonctionally active polypeptides UGT2A1 and UGT2A2. Alternative splicing of exons results in additional isoforms for each protein class.

9606:PCDHB11
gene id: 9606:PCDHB11
uniprot id: Q9Y5F2
names: Function
names: Subcellular Location Annotation
messages: Cell membrane
messages: Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain.

9606:GNPNAT1
gene id: 9606:GNPNAT1
uniprot id: Q96EK6
names: Disease Annotation
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the acetyltransferase family. GNA1 subfamily.
messages: Endosome membrane
messages: Golgi apparatus membrane
messages: Homodimer.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:NOTCH4
gene id: 9606:NOTCH4
uniprot id: A0A1U9X983
uniprot id: Q99466
names: Caution
names: Function
names: PTM
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts with Epstein-Barr virus (EBV) RK-BARF0.
messages: Belongs to the NOTCH family.
messages: Cell membrane
messages: Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects the implementation of differentiation, proliferation and apoptotic programs. May regulate branching morphogenesis in the developing vascular system (By similarity).
messages: Heterodimer of a C-terminal fragment N(TM) and a N-terminal fragment N(EC) which are probably linked by disulfide bonds (By similarity). Interacts with MAML1, MAML2 and MAML3 which act as transcriptional coactivators for NOTCH4.
messages: Highly expressed in the heart, moderately in the lung and placenta and at low levels in the liver, skeletal muscle, kidney, pancreas, spleen, lymph node, thymus, bone marrow and fetal liver. No expression was seen in adult brain or peripheral blood leukocytes.
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: Membrane
messages: Nucleus
messages: Phosphorylated.
messages: Synthesized in the endoplasmic reticulum as an inactive form which is proteolytically cleaved by a furin-like convertase in the trans-Golgi network before it reaches the plasma membrane to yield an active, ligand-accessible form. Cleavage results in a C-terminal fragment N(TM) and a N-terminal fragment N(EC). Following ligand binding, it is cleaved by TNF-alpha converting enzyme (TACE) to yield a membrane-associated intermediate fragment called notch extracellular truncation (NEXT). This fragment is then cleaved by presenilin dependent gamma-secretase to release a notch-derived peptide containing the intracellular domain (NICD) from the membrane (By similarity).
messages: The poly-Leu region of NOTCH4 (in the signal peptide) is polymorphic and the number of Leu varies in the population (from 6 to 12).

9606:EXOSC2
gene id: 9606:EXOSC2
uniprot id: Q13868
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the RRP4 family.
messages: Component of the RNA exosome complex (PubMed:29906447). Specifically part of the catalytically inactive RNA exosome core (Exo-9) complex which is believed to associate with catalytic subunits EXOSC10, and DIS3 or DIS3L in cytoplasmic- and nuclear-specific RNA exosome complex forms (PubMed:11719186, PubMed:20531389, PubMed:26166824). Exo-9 is formed by a hexameric ring of RNase PH domain-containing subunits specifically containing the heterodimers EXOSC4-EXOSC9, EXOSC5-EXOSC8 and EXOSC6-EXOSC7, and peripheral S1 domain-containing components EXOSC1, EXOSC2 and EXOSC3 located on the top of the ring structure (PubMed:11719186, PubMed:20531389). Interacts with DIS3 (PubMed:20531389). Interacts with GTPBP1 (PubMed:21515746). Interacts with ZFP36L1 (via N-terminus) (PubMed:15687258).
messages: Cytoplasm
messages: Non-catalytic component of the RNA exosome complex which has 3'->5' exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events. In the nucleus, the RNA exosome complex is involved in proper maturation of stable RNA species such as rRNA, snRNA and snoRNA, in the elimination of RNA processing by-products and non-coding 'pervasive' transcripts, such as antisense RNA species and promoter-upstream transcripts (PROMPTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. The RNA exosome may be involved in Ig class switch recombination (CSR) and/or Ig variable region somatic hypermutation (SHM) by targeting AICDA deamination activity to transcribed dsDNA substrates. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and specifically degrades inherently unstable mRNAs containing AU-rich elements (AREs) within their 3' untranslated regions, and in RNA surveillance pathways, preventing translation of aberrant mRNAs. It seems to be involved in degradation of histone mRNA. The catalytic inactive RNA exosome core complex of 9 subunits (Exo-9) is proposed to play a pivotal role in the binding and presentation of RNA for ribonucleolysis, and to serve as a scaffold for the association with catalytic subunits and accessory proteins or complexes. EXOSC2 as peripheral part of the Exo-9 complex stabilizes the hexameric ring of RNase PH-domain subunits through contacts with EXOSC4 and EXOSC7.
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: nucleolus

9606:RNASEL
gene id: 9606:RNASEL
uniprot id: Q05823
names: Activity Regulation
names: Cofactor
names: Disease Annotation
names: Domain
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: After binding to 2-5A (5'-phosphorylated 2',5'-linked oligoadenylates) the homodimerization and subsequent activation occurs. Inhibited by RNASEL inhibitor ABCE1/RLI, a cytoplasmic member of the ATP-binding cassette (ABC) transporter family.
messages: Belongs to the protein kinase superfamily.
messages: By interferons. Virus replication in higher vertebrates is restrained by IFNs that cause cells to transcribe genes encoding antiviral proteins, such as 2'-5' oligoadenylate synthetases (OASs). oligoadenylate synthetase is stimulated by dsRNA to produce 5'-phosphorylated, 2'-5'-linked oligoadenylates (2-5A), whose function is to activate RNASEL.
messages: Cytoplasm
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry.
messages: Endoribonuclease that functions in the interferon (IFN) antiviral response. In INF treated and virus infected cells, RNASEL probably mediates its antiviral effects through a combination of direct cleavage of single-stranded viral RNAs, inhibition of protein synthesis through the degradation of rRNA, induction of apoptosis, and induction of other antiviral genes. RNASEL mediated apoptosis is the result of a JNK-dependent stress-response pathway leading to cytochrome c release from mitochondria and caspase-dependent apoptosis. Therefore, activation of RNASEL could lead to elimination of virus infected cells under some circumstances. In the crosstalk between autophagy and apoptosis proposed to induce autophagy as an early stress response to small double-stranded RNA and at later stages of prolonged stress to activate caspase-dependent proteolytic cleavage of BECN1 to terminate autophagy and promote apoptosis (PubMed:26263979). Might play a central role in the regulation of mRNA turnover (PubMed:11585831). Cleaves 3' of UpNp dimers, with preference for UU and UA sequences, to sets of discrete products ranging from between 4 and 22 nucleotides in length.
messages: Highly expressed in spleen and thymus followed by prostate, testis, uterus, small intestine, colon and peripheral blood leukocytes.
messages: Manganese or magnesium. Required for optimal RNA cleavage rates.
messages: Mitochondrion
messages: Monomer (inactive form) or homodimer. Interacts with ABCE1; this interaction inhibits the RNASEL.
messages: The nine ankyrin repeats also called 2-5A sensor constitute the N-terminus 2-5A binding domain.
messages: The protein kinase domain is predicted to be catalytically inactive. It allows the homodimerization.
messages: The ribonuclease domain is located in the C-terminus. A single active nuclease domain in a dimer is sufficient for ribonuclease activity (By similarity).

9606:MT1X
gene id: 9606:MT1X
uniprot id: A0A140VJP8
uniprot id: P80297
names: Domain
names: Function
names: Similarity
names: Subunit
messages: Belongs to the metallothionein superfamily. Type 1 family.
messages: Class I metallothioneins contain 2 metal-binding domains: four divalent ions are chelated within cluster A of the alpha domain and are coordinated via cysteinyl thiolate bridges to 11 cysteine ligands. Cluster B, the corresponding region within the beta domain, can ligate three divalent ions to 9 cysteines.
messages: Metallothioneins have a high content of cysteine residues that bind various heavy metals.
messages: Metallothioneins have a high content of cysteine residues that bind various heavy metals; these proteins are transcriptionally regulated by both heavy metals and glucocorticoids. May be involved in FAM168A anti-apoptotic signaling (PubMed:23251525).
messages: Monomer. Interacts with FAM168A (PubMed:23251525).

9606:ARHGEF10L
gene id: 9606:ARHGEF10L
uniprot id: Q9HCE6
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acts as guanine nucleotide exchange factor (GEF) for RHOA, RHOB and RHOC.
messages: Cytoplasm
messages: Detected in heart, liver, skeletal muscle, kidney and pancreas.
messages: Interacts with RHOA, RHOB and RHOC.

9606:ADCY4
gene id: 9606:ADCY4
uniprot id: Q86TZ7
uniprot id: Q8NFM4
names: Activity Regulation
names: Cofactor
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Activated by forskolin. Insensitive to calcium/calmodulin. Stimulated by GNAS and by the G-protein beta and gamma subunit complex.
messages: Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.
messages: Binds 2 magnesium ions per subunit. Is also active with manganese (in vitro).
messages: Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling.
messages: Cell membrane
messages: Cytoplasm
messages: Detected in the zona glomerulosa and the zona fasciculata in the adrenal gland (at protein level).
messages: Membrane
messages: The protein contains two modules with six transmembrane helices each; both are required for catalytic activity. Isolated N-terminal or C-terminal modules have no catalytic activity, but when they are brought together, enzyme activity is restored. The active site is at the interface of the two modules.

9606:MECR
gene id: 9606:MECR
uniprot id: Q9BV79
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the zinc-containing alcohol dehydrogenase family. Quinone oxidoreductase subfamily.
messages: Catalyzes the NADPH-dependent reduction of trans-2-enoyl thioesters in mitochondrial fatty acid synthesis (fatty acid synthesis type II). Fatty acid chain elongation in mitochondria uses acyl carrier protein (ACP) as an acyl group carrier, but the enzyme accepts both ACP and CoA thioesters as substrates in vitro. Displays a preference for medium-chain over short- and long-chain substrates (PubMed:18479707, PubMed:12654921, PubMed:27817865). May provide the octanoyl chain used for lipoic acid biosynthesis, regulating protein lipoylation and mitochondrial respiratory activity particularly in Purkinje cells (By similarity).
messages: Cytoplasm
messages: Highly expressed in skeletal and heart muscle. Expressed at lower level in placenta, liver, kidney and pancreas. Weakly or not expressed in lung.
messages: Homodimer (PubMed:12654921, PubMed:18479707). Isoform 2 interacts with PPARA in the nucleus and increases its activity (By similarity).
messages: Mitochondrion
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:DOK7
gene id: 9606:DOK7
uniprot id: Q18PE1
names: Disease Annotation
names: Domain
names: Function
names: Sequence Caution
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cell membrane
messages: Contains a poly-A tail in the 5'region.
messages: Homodimer (By similarity). Forms a heterotetramer composed of 2 DOK7 and 2 MUSK molecules which facilitates MUSK trans-autophosphorylation on tyrosine residue and activation (By similarity). Interacts (via IRS-type PTB domain) with MUSK (via cytoplasmic part); requires MUSK phosphorylation.
messages: Preferentially expressed in skeletal muscle and heart. Present in thigh muscle, diaphragm and heart but not in the liver or spleen (at protein level).
messages: Probable muscle-intrinsic activator of MUSK that plays an essential role in neuromuscular synaptogenesis. Acts in aneural activation of MUSK and subsequent acetylcholine receptor (AchR) clustering in myotubes. Induces autophosphorylation of MUSK.
messages: Synapse
messages: The PH domain mediated binding to phospholipids with phosphoinositol headgroups. Affinity is highest for phosphatidyl 3,4,5-trisphosphate, followed by phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 4,5-bisphosphate (By similarity).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:SPIN4
gene id: 9606:SPIN4
uniprot id: Q56A73
names: Function
names: Similarity
names: Subunit
messages: Belongs to the SPIN/STSY family.
messages: Exhibits H3K4me3-binding activity.
messages: Interacts with C11orf84/SPINDOC (PubMed:29061846).

9606:PAQR9
gene id: 9606:PAQR9
uniprot id: Q6ZVX9
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the ADIPOR family.
messages: Cell membrane
messages: Expression levels vary widely in a range of tissues (PubMed:16044242). Expressed in the brain, at high level in the pituitary gland and also in hypothalamus, limbic system, caudate nucleus accumens, pons and olfactory bulb (PubMed:23161870).
messages: Homodimer.
messages: Non-classical progesterone receptors involved in extranuclear signaling are classified in 2 groups: the class II progestin and adipoQ receptor (PAQR) family (also called mPRs) (PAQR5, PAQR6, PAQR7, PAQR8 and PAQR9) and the b5-like heme/steroid-binding protein family (also called MAPRs) (PGRMC1, PGRMC2, NENF and CYB5D2).
messages: Plasma membrane progesterone (P4) receptor coupled to G proteins (PubMed:23763432, PubMed:23161870). Seems to act through a G(s) mediated pathway (PubMed:23161870). May be involved in regulating rapid P4 signaling in the nervous system (PubMed:23763432). Also binds dehydroepiandrosterone (DHEA), pregnanolone, pregnenolone and allopregnanolone (PubMed:23161870).

9606:POLR1E
gene id: 9606:POLR1E
uniprot id: B4E005
uniprot id: Q9GZS1
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Acetylated at Lys-373 by CREBBP/CBP, leading to decreased RNA polymerase I transcription (PubMed:24207024). In normal conditions, deacetylated by SIRT7, promoting the association of RNA polymerase I with the rDNA promoter region and coding region (PubMed:24207024). In response to stress, SIRT7 is released from nucleoli leading to hyperacetylation of POLR1E/PAF53 and decreased association of RNA polymerase I with the rDNA promoter region (PubMed:24207024).
messages: Belongs to the eukaryotic RPA49/POLR1E RNA polymerase subunit family.
messages: Component of the RNA polymerase I (Pol I) complex consisting of at least 13 subunits (PubMed:16809778, PubMed:29065309). Interacts with POLR1G (By similarity). Also binds UBTF/UBF (By similarity). Interacts with PWP1 (PubMed:29065309).
messages: DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase I which synthesizes ribosomal RNA precursors (PubMed:24207024). Appears to be involved in the formation of the initiation complex at the promoter by mediating the interaction between Pol I and UBTF/UBF (PubMed:24207024).
messages: Dubious isoform produced through intron retention.
messages: nucleolus

9606:LGI4
gene id: 9606:LGI4
uniprot id: Q8N135
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Can bind to ADAM11, ADAM22 and ADAM23.
messages: Component of Schwann cell signaling pathway(s) that controls axon segregation and myelin formation (By similarity).
messages: Secreted
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Widely expressed, with highest expression in brain.

9606:ZFP36
gene id: 9606:ZFP36
uniprot id: M0QY76
uniprot id: P26651
names: Domain
names: Function
names: Induction
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts (via C-terminus) with HTLV-1 TAX (via C-terminus); this interaction inhibits HTLV-1 TAX to transactivate viral long terminal repeat (LTR) promoter (PubMed:14679154).
messages: (Microbial infection) Negatively regulates HTLV-1 TAX-dependent transactivation of viral long terminal repeat (LTR) promoter.
messages: Associates with cytoplasmic CCR4-NOT and PAN2-PAN3 deadenylase complexes to trigger ARE-containing mRNA deadenylation and decay processes (By similarity). Part of a mRNA decay activation complex at least composed of poly(A)-specific exoribonucleases CNOT6, EXOSC2 and XRN1 and mRNA-decapping enzymes DCP1A and DCP2 (PubMed:15687258). Associates with the RNA exosome complex (PubMed:11719186). Interacts (via phosphorylated form) with 14-3-3 proteins; these interactions promote exclusion of ZFP36 from cytoplasmic stress granules in response to arsenite treatment in a MAPKAPK2-dependent manner and does not prevent CCR4-NOT deadenylase complex recruitment or ZFP36-induced ARE-containing mRNA deadenylation and decay processes (By similarity). Interacts with 14-3-3 proteins; these interactions occur in response to rapamycin in an Akt-dependent manner (PubMed:16702957). Interacts with AGO2 and AGO4 (PubMed:15766526). Interacts (via C-terminus) with CNOT1; this interaction occurs in a RNA-independent manner and induces mRNA deadenylation (PubMed:23644599). Interacts (via N-terminus) with CNOT6 (PubMed:15687258). Interacts with CNOT6L (By similarity). Interacts (via C-terminus) with CNOT7; this interaction occurs in a RNA-independent manner, induces mRNA deadenylation and is inhibited in a phosphorylation MAPKAPK2-dependent manner (PubMed:25106868). Interacts (via unphosphorylated form) with CNOT8; this interaction occurs in a RNA-independent manner and is inhibited in a phosphorylation MAPKAPK2-dependent manner (By similarity). Interacts with DCP1A (PubMed:15687258). Interacts (via N-terminus) with DCP2 (PubMed:15687258, PubMed:16364915). Interacts with EDC3 (PubMed:16364915). Interacts (via N-terminus) with EXOSC2 (PubMed:15687258). Interacts with heat shock 70 kDa proteins (PubMed:20221403). Interacts with KHSRP; this interaction increases upon cytokine-induced treatment (PubMed:16126846). Interacts with MAP3K4; this interaction enhances the association with SH3KBP1/CIN85 (P…
messages: Associates with the cytoplasmic CCR4-NOT deadenylase complex to trigger ARE-containing mRNA deadenylation and decay processes.
messages: Cytoplasm
messages: Cytoplasmic granule
messages: Expressed in both basal and suprabasal epidermal layers (PubMed:27182009). Expressed in epidermal keratinocytes (PubMed:27182009). Expressed strongly in mature dendritic cells (PubMed:18367721). Expressed in immature dendritic cells (at protein level) (PubMed:18367721).
messages: Nucleus
messages: P-body
messages: Phosphorylated. Phosphorylation at serine and/or threonine residues occurs in a p38 MAPK- and MAPKAPK2-dependent manner (PubMed:16702957). Phosphorylated by MAPKAPK2 at Ser-60 and Ser-186; phosphorylation increases its stability and cytoplasmic localization, promotes binding to 14-3-3 adapter proteins and inhibits the recruitment of cytoplasmic CCR4-NOT and PAN2-PAN3 deadenylase complexes to the mRNA decay machinery, thereby inhibiting ZFP36-induced ARE-containing mRNA deadenylation and decay processes. Phosphorylation by MAPKAPK2 does not impair ARE-containing RNA-binding. Phosphorylated in a MAPKAPK2- and p38 MAPK-dependent manner upon skeletal muscle satellite cell activation; this phosphorylation inhibits ZFP36-mediated mRNA decay activity, and hence stabilizes MYOD1 mRNA (By similarity). Phosphorylated by MAPK1 upon mitogen stimulation (By similarity). Phosphorylated at Ser-66 and Ser-93; these phosphorylations increase in a SH3KBP1-dependent manner (PubMed:20221403). Phosphorylated at serine and threonine residues in a pyruvate kinase PKM- and p38 MAPK-dependent manner (PubMed:26926077). Phosphorylation at Ser-60 may participate in the PKM-mediated degradation of ZFP36 in a p38 MAPK-dependent manner (PubMed:26926077). Dephosphorylated by serine/threonine phosphatase 2A at Ser-186 (By similarity).
messages: The C3H1-type zinc finger domains are necessary for ARE-binding activity (PubMed:10330172).
messages: Ubiquitinated; pyruvate kinase (PKM)-dependent ubiquitination leads to proteasomal degradation through a p38 MAPK signaling pathway (PubMed:26926077).
messages: Up-regulated by T cell activation (PubMed:15634918). Up-regulated in keratinocytes in response to wounding (PubMed:27182009). Up-regulated by lipopolysaccharide (LPS) in a p38 MAPK- and ERK-dependent manner (at protein level) (PubMed:15187101, PubMed:16508015). Up-regulated strongly during epidermal repair after wounding in keratinocytes (PubMed:20166898). Up-regulated strongly by epidermal growth factor (EGF) and tumor necrosis factor (TNF-alpha) in keratinocytes (PubMed:20166898). Up-regulated moderately by granulocyte macrophage colony-stimulating factor (GM-CSF) and fibroblast growth factor (FGF1) in keratinocytes (PubMed:20166898). Up-regulated also by glucocorticoid dexamethasone in keratinocytes (PubMed:20166898). Up-regulated in keratinocytes in response to wounding (PubMed:27182009). Up-regulated by LPS in a p38 MAPK-dependent manner (PubMed:14766228, PubMed:15187101).
messages: Zinc-finger RNA-binding protein that destabilizes several cytoplasmic AU-rich element (ARE)-containing mRNA transcripts by promoting their poly(A) tail removal or deadenylation, and hence provide a mechanism for attenuating protein synthesis (PubMed:9703499, PubMed:10330172, PubMed:10751406, PubMed:11279239, PubMed:12115244, PubMed:12748283, PubMed:15187101, PubMed:15634918, PubMed:17030620, PubMed:16702957, PubMed:20702587, PubMed:20221403, PubMed:21775632, PubMed:27193233, PubMed:23644599, PubMed:25815583, PubMed:31439631). Acts as an 3'-untranslated region (UTR) ARE mRNA-binding adapter protein to communicate signaling events to the mRNA decay machinery (PubMed:15687258, PubMed:23644599). Recruits deadenylase CNOT7 (and probably the CCR4-NOT complex) via association with CNOT1, and hence promotes ARE-mediated mRNA deadenylation (PubMed:23644599). Functions also by recruiting components of the cytoplasmic RNA decay machinery to the bound ARE-containing mRNAs (PubMed:11719186, PubMed:12748283, PubMed:15687258, PubMed:16364915). Self regulates by destabilizing its own mRNA (PubMed:15187101). Binds to 3'-UTR ARE of numerous mRNAs and of its own mRNA (PubMed:10330172, PubMed:10751406, PubMed:12115244, PubMed:15187101, PubMed:15634918, PubMed:17030620, PubMed:16702957, PubMed:19188452, PubMed:20702587, PubMed:20221403, PubMed:21775632, PubMed:25815583). Plays a role in anti-inflammatory responses; suppresses tumor necrosis factor (TNF)-alpha production by stimulating ARE-mediated TNF-alpha mRNA decay and several other inflammatory ARE-containing mRNAs in interferon (IFN)- and/or lipopolysaccharide (LPS)-induced macrophages (By similarity). Also plays a role in the regulation of dendritic cell maturation at the post-transcriptional level, and hence operates as part of a negative feedback loop to limit the inflammatory response (PubMed:18367721). Promotes ARE-mediated mRNA decay of hypoxia-inducible factor HIF1A mRNA during the response of endothelial cells to hypoxia (P…
messages: Zinc-finger RNA-binding protein that destabilizes several cytoplasmic AU-rich element (ARE)-containing mRNA transcripts by promoting their poly(A) tail removal or deadenylation, and hence provide a mechanism for attenuating protein synthesis. Acts as a 3'-untranslated region (UTR) ARE mRNA-binding adapter protein to communicate signaling events to the mRNA decay machinery. Functions by recruiting the CCR4-NOT deadenylase complex and probably other components of the cytoplasmic RNA decay machinery to the bound ARE-containing mRNAs, and hence promotes ARE-mediated mRNA deadenylation and decay processes. Binds to 3'-UTR ARE of numerous mRNAs.

9606:LRSAM1
gene id: 9606:LRSAM1
uniprot id: Q6UWE0
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cytoplasm
messages: E3 ubiquitin-protein ligase that mediates monoubiquitination of TSG101 at multiple sites, leading to inactivate the ability of TSG101 to sort endocytic (EGF receptors) and exocytic (HIV-1 viral proteins) cargos (PubMed:15256501). Bacterial recognition protein that defends the cytoplasm from invasive pathogens (PubMed:23245322). Localizes to several intracellular bacterial pathogens and generates the bacteria-associated ubiquitin signal leading to autophagy-mediated intracellular bacteria degradation (xenophagy) (PubMed:23245322, PubMed:25484098).
messages: Highly expressed in adult spinal cord motoneurons as well as in fetal spinal cord and muscle tissue.
messages: Interacts with TSG101 (PubMed:17556548). Interacts with PHF23 (PubMed:25484098). Interacts with FUS (PubMed:27615052).
messages: The LRR domain is necessary and sufficient for localization to bacterial targets.
messages: The PTAP motifs mediate the binding to UEV domains.
messages: The RING domain is required for ubiquitination.
messages: The coiled coil domains interact with the SB domain of TSG101.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitination promoted by PHF23 leads to proteasomal degradation.

9606:MRS2
gene id: 9606:MRS2
uniprot id: A0A0A0MQX2
uniprot id: B4DSN2
uniprot id: Q9HD23
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the CorA metal ion transporter (MIT) (TC 1.A.35) family.
messages: Has the ability to complement a deletion of MRS2 in S.cerevisiae and partly restore mitochondrial magnesium concentrations.
messages: Magnesium transporter that mediates the influx of magnesium into the mitochondrial matrix (PubMed:11401429, PubMed:18384665). Required for normal expression of the mitochondrial respiratory complex I subunits (PubMed:18384665).
messages: Mitochondrion inner membrane

9606:CRABP2
gene id: 9606:CRABP2
uniprot id: P29373
names: Domain
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the calycin superfamily. Fatty-acid binding protein (FABP) family.
messages: By retinoic acid.
messages: Cytoplasm
messages: Endoplasmic reticulum
messages: Forms a beta-barrel structure that accommodates hydrophobic ligands in its interior.
messages: Interacts with RXR and RARA (By similarity). Interacts with importin alpha.
messages: Nucleus
messages: Sumoylated in response to retinoic acid binding, sumoylation is critical for dissociation from ER and subsequent nuclear translocation.
messages: Transports retinoic acid to the nucleus. Regulates the access of retinoic acid to the nuclear retinoic acid receptors.

9606:CTCFL
gene id: 9606:CTCFL
uniprot id: Q8NI51
names: Developmental Stage
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the CTCF zinc-finger protein family.
messages: Cytoplasm
messages: Interacts with histones, PRMT7 and SETD1A. Interacts (via N-terminus) with BAG6/BAT3.
messages: Is up-regulated in primary spermatocytes (expression overlapping with the genome-wide erasure of methylation) to become silenced on activation of CTCF in post-meiotic germline cells (expression corresponding to DNA remethylation).
messages: Nucleus
messages: Testis specific. Specifically expressed in primary spermatocytes.
messages: Testis-specific DNA binding protein responsible for insulator function, nuclear architecture and transcriptional control, which probably acts by recruiting epigenetic chromatin modifiers. Plays a key role in gene imprinting in male germline, by participating in the establishment of differential methylation at the IGF2/H19 imprinted control region (ICR). Directly binds the unmethylated H19 ICR and recruits the PRMT7 methyltransferase, leading to methylate histone H4 'Arg-3' to form H4R3sme2. This probably leads to recruit de novo DNA methyltransferases at these sites (By similarity). Seems to act as tumor suppressor. In association with DNMT1 and DNMT3B, involved in activation of BAG1 gene expression by binding to its promoter. Required for dimethylation of H3 lysine 4 (H3K4me2) of MYC and BRCA1 promoters.

9606:GPR137B
gene id: 9606:GPR137B
uniprot id: O60478
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acts also as a negative regulator of osteoclast activity (By similarity). Involved in interleukin-4-induced M2 macrophage polarization (By similarity).
messages: Belongs to the GPR137 family.
messages: Expressed in kidney, heart, brain and placenta.
messages: Interaction with RRAGA; increases RRAGA recruitment to lysosomes (PubMed:31036939). Interacts with MTOR; this interaction is amino acid sensitive (PubMed:31036939).
messages: Lysosomal integral membrane protein that regulates the localization and activity of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids (PubMed:31036939). Interacts with Rag GTPases and increases the lysosomial localization and activity of Rag GTPases and thereby regulates mTORC1 translocation and activity in lysosome (PubMed:31036939). Involved in the regulation of lysosomal morphology and autophagy (PubMed:31036939).
messages: Lysosome membrane

9606:DGKD
gene id: 9606:DGKD
uniprot id: Q16760
names: Domain
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the eukaryotic diacylglycerol kinase family.
messages: Cell membrane
messages: Cytoplasm
messages: Diacylglycerol kinase that converts diacylglycerol/DAG into phosphatidic acid/phosphatidate/PA and regulates the respective levels of these two bioactive lipids (PubMed:12200442, PubMed:23949095). Thereby, acts as a central switch between the signaling pathways activated by these second messengers with different cellular targets and opposite effects in numerous biological processes (Probable). By controlling the levels of diacylglycerol, regulates for instance the PKC and EGF receptor signaling pathways and plays a crucial role during development (By similarity). May also regulate clathrin-dependent endocytosis (PubMed:17880279).
messages: Down-regulated by phorbol esters.
messages: Homooligomer (PubMed:12200442, PubMed:12084710). Monomer (PubMed:12084710). Interacts with AP2A2; regulates clathrin-dependent endocytosis (PubMed:17880279).
messages: Only detected in ovary, and to a lesser extent in spleen.
messages: Phosphorylated (PubMed:12084710). Phosphorylation by PKC induced by phorbol esters prevents homooligomerization and promotes association with membranes (PubMed:12084710).
messages: The PH domain mediates association with membranes.
messages: The SAM domain mediates homooligomerization.
messages: Up-regulated by phorbol esters and EGF.
messages: Widely expressed.
messages: clathrin-coated pit

9606:TOM1L1
gene id: 9606:TOM1L1
uniprot id: O75674
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the TOM1 family.
messages: Cytoplasm
messages: Endosome membrane
messages: Golgi stack
messages: Interacts with FYN, GRB2 and PIK3R1 when phosphorylated. Interacts with LYN.
messages: Membrane
messages: Phosphorylated on tyrosines by FYN and LYN.
messages: Probable adapter protein involved in signaling pathways. Interacts with the SH2 and SH3 domains of various signaling proteins when it is phosphorylated. May promote FYN activation, possibly by disrupting intramolecular SH3-dependent interactions (By similarity).

9606:TADA2A
gene id: 9606:TADA2A
uniprot id: A0A024R0Y4
uniprot id: A0A087WWR4
uniprot id: B3KU13
uniprot id: O75478
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Chromosome
messages: Component of the ATAC complex, a complex with histone acetyltransferase activity on histones H3 and H4. Required for the function of some acidic activation domains, which activate transcription from a distant site (By similarity). Binds double-stranded DNA. Binds dinucleosomes, probably at the linker region between neighboring nucleosomes. Plays a role in chromatin remodeling. May promote TP53/p53 'Lys-321' acetylation, leading to reduced TP53 stability and transcriptional activity (PubMed:22644376). May also promote XRCC6 acetylation thus facilitating cell apoptosis in response to DNA damage (PubMed:22644376).
messages: Expressed in all tissues, but most abundantly in testis.
messages: Interacts with GCN5 and NR3C1. Associated with the P/CAF protein in the PCAF complex. Component of the PCAF complex, at least composed of TADA2L/ADA2, TADA3L/ADA3, TAF5L/PAF65-beta, TAF6L/PAF65-alpha, TAF10/TAFII30, TAF12/TAFII20, TAF9/TAFII31 and TRRAP. Component of the ADA2A-containing complex (ATAC), composed of KAT14, KAT2A, TADA2L, TADA3L, ZZ3, MBIP, WDR5, YEATS2, CCDC101 and DR1. Interacts with CCDC134 (PubMed:22644376).
messages: Nucleus

9606:UIMC1
gene id: 9606:UIMC1
uniprot id: Q96RL1
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the RAP80 family.
messages: Component of the ARISC complex, at least composed of UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1 (PubMed:24075985). Component of the BRCA1-A complex, at least composed of the BRCA1, BARD1, UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1 (PubMed:17525341, PubMed:17525342, PubMed:19261746, PubMed:19261749). In the BRCA1-A complex, interacts directly with ABRAXAS1 (PubMed:17643121, PubMed:17643122, PubMed:19261749, PubMed:19261748, PubMed:18077395). Interacts with UBE2I (PubMed:17698038). Interacts with NR6A1 (PubMed:12080054). Interacts with ESR1 (PubMed:17311814). Interacts with TSP57 (By similarity). Interacts with TRAIP (PubMed:26781088).
messages: Expressed in testis, ovary, thymus and heart. Expressed in germ cells of the testis.
messages: Nucleus
messages: Phosphorylated upon DNA damage by ATM or ATR.
messages: Sumoylated.
messages: The Abraxas-interacting region (AIR) mediates the interaction with ABRAXAS1.
messages: The tandem UIM domains form a continuous 60 Angstrom-long alpha-helix and mediate binding to 'Lys-63'-linked ubiquitins. UIM1 and UIM2 bind to the proximal and distal ubiquitin moieties and recognize an 'Ile-44'-centered hydrophobic patch. Since UIMs don't interact with the 'Lys-63' isopeptide bond the UIM-linker region between the 2 UIM domains determines the selectivity for 'Lys-63'-linkage, and its length is very important for specificity.
messages: Ubiquitin-binding protein (PubMed:24627472). Specifically recognizes and binds 'Lys-63'-linked ubiquitin (PubMed:19328070, Ref.38). Plays a central role in the BRCA1-A complex by specifically binding 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). The BRCA1-A complex also possesses deubiquitinase activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX. Also weakly binds monoubiquitin but with much less affinity than 'Lys-63'-linked ubiquitin. May interact with monoubiquitinated histones H2A and H2B; the relevance of such results is however unclear in vivo. Does not bind Lys-48'-linked ubiquitin. May indirectly act as a transcriptional repressor by inhibiting the interaction of NR6A1 with the corepressor NCOR1.

9606:SLC25A34
gene id: 9606:SLC25A34
uniprot id: Q6PIV7
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the mitochondrial carrier (TC 2.A.29) family.
messages: Mitochondrion inner membrane
messages: Putative antiporter that exchanges dicarboxylates and sulfur oxoanions across the inner membrane of mitochondria.

9606:SLC48A1
gene id: 9606:SLC48A1
uniprot id: Q6P1K1
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the HRG family.
messages: Endosome membrane
messages: Heme transporter that regulates intracellular heme availability through the endosomal or lysosomal compartment (PubMed:18418376). In macrophages of the reticuloendothelial system, is the heme transporter for heme-iron recycling. Essential for macrophage iron homeostasis, transports heme from the phagolysosome to the cytoplasm during erythrophagocytosis (EP) (PubMed:23395172).
messages: Highly expressed in the brain, kidney, heart and skeletal muscle. Moderately expressed in the liver, lung, placenta and small intestine. Strongly expressed in macrophages of the reticuloendothelial system (PubMed:23395172).
messages: Induced by iron via heme and non-iron metalloporphyrins in macrophages as well as by erythrophagocytosis (at protein level). Also induced by hemolysis.
messages: Lysosome membrane
messages: phagosome membrane

9606:TGFBR3
gene id: 9606:TGFBR3
uniprot id: Q03167
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: Binds to TGF-beta. Could be involved in capturing and retaining TGF-beta for presentation to the signaling receptors (By similarity). In gonadotrope cells, acts as an inhibin A coreceptor and regulates follicle-stimulating hormone (FSH) levels and female fertility (PubMed:34910520).
messages: Cell membrane
messages: Extensively modified by glycosaminoglycan groups (GAG).
messages: Interacts with DYNLT4.
messages: Secreted
messages: extracellular matrix

9606:TAMALIN
gene id: 9606:TAMALIN
uniprot id: Q7Z6J2
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Cell membrane
messages: Heteromer. Composed of TAMALIN, CYTH2 and at least one GRM1. Also interacts with CYTH3, GRM2, GRM3 and GRM5 (By similarity).
messages: Plays a role in intracellular trafficking and contributes to the macromolecular organization of group 1 metabotropic glutamate receptors (mGluRs) at synapses.
messages: Postsynaptic cell membrane
messages: perinuclear region

9606:FLNC
gene id: 9606:FLNC
uniprot id: Q14315
uniprot id: Q59H94
names: Developmental Stage
names: Disease Annotation
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the filamin family.
messages: Cytoplasm
messages: Expressed in both differentiating and adult muscles.
messages: Highly expressed in striated muscles. Weakly expressed in thyroid, fetal brain, fetal lung, retina, spinal cord and bone marrow. Not expressed in testis, pancreas, adrenal gland, placenta, liver and kidney.
messages: Homodimer; the filamin repeat 24 and the second hinge domain are important for dimer formation. Interacts with FLNB, INPPL1, ITGB1A, KCND2, MYOT, MYOZ1 and MYOZ3. Interacts with sarcoglycans SGCD and SGCG. Interacts (via filament repeats 17-18, 20-21 and 24) with USP25 (isoform USP25m only). Interacts with FBLIM1. Interacts with XIRP1; this interaction is mediated by filamin 20 repeat. Interacts with KY. Interacts with IGFN1 (By similarity). Interacts with MICALL2 (By similarity). Interacts with ANK3. Interacts with SYNPO2.
messages: Membrane
messages: Muscle-specific filamin, which plays a central role in sarcomere assembly and organization (PubMed:34405687). Critical for normal myogenesis, it probably functions as a large actin-cross-linking protein with structural functions at the Z lines in muscle cells. May be involved in reorganizing the actin cytoskeleton in response to signaling events (By similarity).
messages: Silenced in MKN28 and MKN74 gastric cancer cell lines due to aberrant methylation of the gene.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitinated by FBXL22, leading to proteasomal degradation.
messages: Z line
messages: cytoskeleton

9606:LRRIQ1
gene id: 9606:LRRIQ1
uniprot id: Q96JM4
names: Sequence Caution
messages: Contaminating sequence. Potential poly-A sequence.
messages: Probable cloning artifact.

9606:OR1L6
gene id: 9606:OR1L6
uniprot id: A0A0C4DFP2
uniprot id: Q8NGR2
names: Caution
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: It is uncertain whether Met-1 or Met-37 is the initiator.
messages: Membrane
messages: Odorant receptor.

9606:RPS15
gene id: 9606:RPS15
uniprot id: K7ELC2
uniprot id: P62841
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the universal ribosomal protein uS19 family.
messages: Component of the small ribosomal subunit (PubMed:23636399). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399).
messages: Component of the small ribosomal subunit.
messages: Cytoplasm

9606:ST8SIA4
gene id: 9606:ST8SIA4
uniprot id: Q92187
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the glycosyltransferase 29 family.
messages: Catalyzes the polycondensation of alpha-2,8-linked sialic acid required for the synthesis of polysialic acid (PSA), which is present on the embryonic neural cell adhesion molecule (N-CAM), necessary for plasticity of neural cells.
messages: Golgi apparatus membrane
messages: Highly expressed in fetal brain, lung and kidney and in adult heart, spleen and thymus. Present to a lesser extent in adult brain, placenta, lung, large and small intestine and peripheral blood leukocytes.

9606:UBASH3A
gene id: 9606:UBASH3A
uniprot id: P57075
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cytoplasm
messages: Highest expression of UBASH3A in tissues belonging to the immune system, including spleen, peripheral blood leukocytes, thymus and bone marrow.
messages: Homodimer or homooligomer. Interacts with CBL. Part of a complex containing CBL and activated EGFR. Interacts with ubiquitin and with mono-ubiquitinated proteins. Interacts with dynamin.
messages: Interferes with CBL-mediated down-regulation and degradation of receptor-type tyrosine kinases. Promotes accumulation of activated target receptors, such as T-cell receptors, EGFR and PDGFRB, on the cell surface. Exhibits negligigle protein tyrosine phosphatase activity at neutral pH. May act as a dominant-negative regulator of UBASH3B-dependent dephosphorylation. May inhibit dynamin-dependent endocytic pathways by functionally sequestering dynamin via its SH3 domain.
messages: Nucleus

9606:EPO
gene id: 9606:EPO
uniprot id: G9JKG7
uniprot id: P01588
names: Disease Annotation
names: Function
names: Pharmaceutical
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the EPO/TPO family.
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry.
messages: Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation thereby activating specific downstream effectors, including STAT1 and STAT3.
messages: Produced by kidney or liver of adult mammals and by liver of fetal or neonatal mammals.
messages: Secreted
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Used for the treatment of anemia. Available under the names Epogen (Amgen), Epogin (Chugai), Epomax (Elanex), Eprex (Janssen-Cilag), NeoRecormon or Recormon (Roche), Dynepo (Shire Pharmaceuticals) and Procrit (Ortho Biotech). Variations in the glycosylation pattern of EPO distinguishes these products. Epogen, Epogin, Eprex and Procrit are generically known as epoetin alfa, NeoRecormon and Recormon as epoetin beta, Dynepo as epoetin delta and Epomax as epoetin omega. Epoetin zeta is the name used for some 'biosimilars' forms of epoetin alfa and is available under the names Silapo (Stada) and Retacrit (Hospira). Darbepoetin alfa is a form created by 5 substitutions (Asn-57, Thr-59, Val-114, Asn-115 and Thr-117) that create 2 new N-glycosylation sites. It has a longer circulating half-life in vivo. It is available under the name Aranesp (Amgen). EPO is being much misused as a performance-enhancing drug in endurance athletes.

9606:LYZL2
gene id: 9606:LYZL2
uniprot id: A0A080YUZ9
uniprot id: Q7Z4W2
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the glycosyl hydrolase 22 family.
messages: Expressed in testis, epididymis and placenta.
messages: Monomer.
messages: Secreted

9606:YWHAB
gene id: 9606:YWHAB
uniprot id: P31946
uniprot id: V9HWD6
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Interacts with herpes simplex virus 1 protein UL46.
messages: (Microbial infection) Probably interacts with Chlamydia trachomatis protein IncG.
messages: Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner. Negative regulator of osteogenesis. Blocks the nuclear translocation of the phosphorylated form (by AKT1) of SRPK2 and antagonizes its stimulatory effect on cyclin D1 expression resulting in blockage of neuronal apoptosis elicited by SRPK2. Negative regulator of signaling cascades that mediate activation of MAP kinases via AKAP13.
messages: Belongs to the 14-3-3 family.
messages: Cytoplasm
messages: Homodimer (PubMed:17717073). Interacts with SAMSN1 and PRKCE (By similarity). Interacts with AKAP13 (PubMed:21224381). Interacts with SSH1 and TORC2/CRTC2 (PubMed:15454081, PubMed:15159416). Interacts with ABL1; the interaction results in cytoplasmic location of ABL1 and inhibition of cABL-mediated apoptosis (PubMed:15696159). Interacts with ROR2 (dimer); the interaction results in phosphorylation of YWHAB on tyrosine residues (PubMed:17717073). Interacts with GAB2 (PubMed:19172738). Interacts with YAP1 (phosphorylated form) (PubMed:17974916). Interacts with the phosphorylated (by AKT1) form of SRPK2 (PubMed:19592491). Interacts with PKA-phosphorylated AANAT (PubMed:11427721). Interacts with MYO1C (PubMed:24636949). Interacts with SIRT2 (PubMed:18249187). Interacts with the 'Thr-369' phosphorylated form of DAPK2 (PubMed:26047703). Interacts with PI4KB, TBC1D22A and TBC1D22B (PubMed:23572552). Interacts with the 'Ser-1134' and 'Ser-1161' phosphorylated form of SOS1 (PubMed:22827337). Interacts (via phosphorylated form) with YWHAB; this interaction occurs in a protein kinase AKT1-dependent manner (PubMed:15538381). Interacts with SLITRK1 (PubMed:19640509). Interacts with SYNPO2 (phosphorylated form); YWHAB competes with ACTN2 for interaction with SYNPO2 (By similarity). Interacts with RIPOR2 (via phosphorylated form) isoform 2; this interaction occurs in a chemokine-dependent manner and does not compete for binding of RIPOR2 with RHOA nor blocks inhibition of RIPOR2-mediated RHOA activity (PubMed:25588844). Interacts with MARK2 and MARK3 (PubMed:16959763). Interacts with TESK1; the interaction is dependent on the phosphorylation of TESK1 'Ser-437' and inhibits TESK1 kinase activity (PubMed:11555644). Interacts with MEFV (PubMed:27030597). Interacts with HDAC4 (PubMed:33537682). Interacts with ADAM22 (via C-terminus) (PubMed:15882968).
messages: Melanosome
messages: The alpha, brain-specific form differs from the beta form in being phosphorylated. Phosphorylated on Ser-60 by protein kinase C delta type catalytic subunit in a sphingosine-dependent fashion.
messages: Vacuole membrane

9606:SELENOK
gene id: 9606:SELENOK
uniprot id: Q9Y6D0
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the selenoprotein K family.
messages: By ER stress (at protein level). Displays a slow increase with a lag phase of 6 hours but exhibits a dramatic increase after incubation with ER stress agents for more than 12 hours with maximum induction at 24 hours. Also induced by accumulation of misfolded proteins in the ER.
messages: Cell membrane
messages: Cleaved by CAPN2/m-calpain in resting macrophages but not in activated macrophages. Macrophage activation up-regulates expression of the calpain inhibitor CAST/calpastatin, resulting in inhibition of CAPN2 activity (By similarity).
messages: Endoplasmic reticulum membrane
messages: Highly expressed in heart.
messages: Interacts with DERL1, DERL2, DERL3 and SELENOS (PubMed:22016385). The SELENOK-SELENOS complex interacts with VCP (PubMed:22016385). Interacts with ZDHHC6 (PubMed:25368151).
messages: Required for Ca(2+) flux in immune cells and plays a role in T-cell proliferation and in T-cell and neutrophil migration (By similarity). Involved in endoplasmic reticulum-associated degradation (ERAD) of soluble glycosylated proteins (PubMed:22016385). Required for palmitoylation and cell surface expression of CD36 and involved in macrophage uptake of low-density lipoprotein and in foam cell formation (By similarity). Together with ZDHHC6, required for palmitoylation of ITPR1 in immune cells, leading to regulate ITPR1 stability and function (PubMed:25368151). Plays a role in protection of cells from ER stress-induced apoptosis (PubMed:20692228). Protects cells from oxidative stress when overexpressed in cardiomyocytes (PubMed:16962588).
messages: Truncated SELENOK proteins produced by failed UGA/Sec decoding are ubiquitinated by the CRL2(KLHDC2) complex, which recognizes the diglycine (Gly-Gly) at the C-terminus of truncated SELENOK proteins.

9606:N4BP1
gene id: 9606:N4BP1
uniprot id: O75113
names: Activity Regulation
names: Domain
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the N4BP1 family.
messages: Detected in heart, lung, brain, liver, skeletal muscle, pancreas, kidney, spleen, testis and ovary.
messages: Interacts with NEDD4. Interacts with ITCH (via WW domain 2).
messages: Mono- and polyubiquitinated on the CoCUN region (PubMed:31319543). Monoubiquitinated by NEDD4 (By similarity). Polyubiquitinated, leading to its degradation by the proteasome (By similarity). Sumoylated with SUMO1, abrogating polyubiquitination and subsequent degradation (By similarity). Desumoylated by SENP1, leading to accumulation in PML nuclear bodies (By similarity).
messages: Nucleus
messages: PML body
messages: Potent suppressor of cytokine production that acts as a regulator of innate immune signaling and inflammation. Acts as a key negative regulator of select cytokine and chemokine responses elicited by TRIF-independent Toll-like receptors (TLRs), thereby limiting inflammatory cytokine responses to minor insults. In response to more threatening pathogens, cleaved by CASP8 downstream of TLR3 or TLR4, leading to its inactivation, thereby allowing production of inflammatory cytokines (By similarity). Acts as a restriction factor against some viruses, such as HIV-1: restricts HIV-1 replication by binding to HIV-1 mRNAs and mediating their degradation via its ribonuclease activity (PubMed:31133753). Also acts as an inhibitor of the E3 ubiquitin-protein ligase ITCH: acts by interacting with the second WW domain of ITCH, leading to compete with ITCH's substrates and impairing ubiquitination of substrates (By similarity).
messages: Proteolytic cleavage by CASP8 or MALT1 leads to its inactivation.
messages: Proteolytically cleaved by CASP8 downstream of TLR3 or TLR4, leading to its inactivation. Mainly cleaved at Asp-490 by CASP8 (By similarity). Cleaved by caspase-like protein MALT1 in T-cells following TCR-mediated activation, leading to its inactivation and subsequent viral reactivation during HIV-1 infection (PubMed:31133753).
messages: The CoCUN region mediates binding to ubiquitin (PubMed:31319543). Does not interact with NEDD8 (PubMed:31319543).
messages: Up-regulated in response to interferon alpha (IFN-alpha) stimulation (at protein level).
messages: cytosol
messages: nucleolus

9606:SEC14L2
gene id: 9606:SEC14L2
uniprot id: O76054
names: Developmental Stage
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Carrier protein. Binds to some hydrophobic molecules and promotes their transfer between the different cellular sites. Binds with high affinity to alpha-tocopherol. Also binds with a weaker affinity to other tocopherols and to tocotrienols. May have a transcriptional activatory activity via its association with alpha-tocopherol. Probably recognizes and binds some squalene structure, suggesting that it may regulate cholesterol biosynthesis by increasing the transfer of squalene to a metabolic active pool in the cell.
messages: Cytoplasm
messages: Low expression in fetal tissues.
messages: Monomer.
messages: Nucleus
messages: Widely expressed. Strong expression in liver, brain and prostate.

9606:TSPY10
gene id: 9606:TSPY10
uniprot id: F2Z2I4
uniprot id: P0CV98
uniprot id: P0CW01
uniprot id: Q01534
names: Developmental Stage
names: Disease Annotation
names: Function
names: Induction
names: PTM
names: Polymorphism
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the nucleosome assembly protein (NAP) family.
messages: Cytoplasm
messages: Detected in 22-week old testis.
messages: Maps to a tandemly repeated region on chromosome Yp11; additionally at least one copy is reported originating from Yq. The gene is thought to be present with an inter-individual variation in copy number and between 20 and 60 copies per Y chromosome are expected. 35 tandemly repeated gene copies on Yp11 originating from one individual have been reported (PubMed:12815422).
messages: Maps to a tandemly repeated region on chromosome Yp11; additionally at least one copy is reported originating from Yq. The gene is thought to be present with an inter-individual variation in copy number and between 20 and 60 copies per Y chromosome are expected. PubMed:12815422 reports 35 tandemly repeated gene copies on Yp11 originating from one individual.
messages: May be involved in sperm differentiation and proliferation.
messages: Nucleus
messages: Phosphorylated.
messages: Probable unspliced transcript.
messages: Sequence of unknown origin inserted in the coding sequence.
messages: Specifically expressed in testicular tissues. Isoform 1 and isoform 2 are expressed in spermatogonia and spermatocytes. Found in early testicular carcinoma in situ, spermatogonial cells in testicular tissues of 46,X,Y female and in prostate cancer cell lines.
messages: TSPY is located in the gonadoblastoma critical region and is preferentially expressed in tumor germ cells of gonadoblastoma specimens. Expression also correlates with testicular seminoma and tumorigenesis of the prostate gland.
messages: Up-regulated by androgen in a prostate cancer cell line.
messages: Variants Val-Glu-Val-Val-Ala-Glu-79 Ins and Arg-195 are shown to be present in a number of TSPY1 copies of the Yp11 loci. Variant Arg-195 is shown to be present at least in one TSPY1 copy of the Yq locus.

9606:NUDT12
gene id: 9606:NUDT12
uniprot id: Q9BQG2
names: Cofactor
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the Nudix hydrolase family. NudC subfamily.
messages: Binds 1 zinc ion per subunit.
messages: Binds 3 Mg(2+) ions per subunit.
messages: Cytoplasm
messages: Cytoplasmic granule
messages: Homodimer (PubMed:31875550). Homodimerization is essential for its catalytic activity and protein stability (PubMed:31875550). Interacts (via ANK repeats) with BLMH (PubMed:31875550).
messages: Peroxisome
messages: mRNA decapping enzyme that specifically removes the nicotinamide adenine dinucleotide (NAD) cap from a subset of mRNAs by hydrolyzing the diphosphate linkage to produce nicotinamide mononucleotide (NMN) and 5' monophosphate mRNA (PubMed:31101919, PubMed:31875550). The NAD-cap is present at the 5'-end of some RNAs; in contrast to the canonical N7 methylguanosine (m7G) cap, the NAD cap promotes mRNA decay (PubMed:31101919). Preferentially acts on NAD-capped transcripts in response to nutrient stress (PubMed:31101919). Also acts on free nicotinamide adenine dinucleotide molecules: hydrolyzes NAD(H) into NMN(H) and AMP, and NADPH into NMNH and 2',5'-ADP (PubMed:12790796). May act to regulate the concentration of peroxisomal nicotinamide nucleotide cofactors required for oxidative metabolism in this organelle (PubMed:12790796). Regulates the levels of circadian clock components PER1, PER2, PER3 and CRY2 in the liver (By similarity).

9606:LGALS9C
gene id: 9606:LGALS9C
uniprot id: Q6DKI2
names: Function
names: Miscellaneous
messages: Binds galactosides.
messages: The LGALS9-like proteins are encoded by a duplicated regions on chromosome 17; there are at least 3 genes coding for galectin-9-like proteins.

9606:RNFT2
gene id: 9606:RNFT2
uniprot id: Q96EX2
names: Function
names: Subcellular Location Annotation
messages: E3 ubiquitin-protein ligase that negatively regulates IL3-dependent cellular responses through IL3RA ubiquitination and degradation by the proteasome, having an anti-inflammatory effect.
messages: Membrane

9606:RTN1
gene id: 9606:RTN1
uniprot id: A8K3B9
uniprot id: Q16799
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Endoplasmic reticulum membrane
messages: Expressed in neural and neuroendocrine tissues and cell cultures derived therefrom. Expression of isoform RTN1-C is strongly correlated with neuronal differentiation.
messages: Golgi apparatus membrane
messages: Inhibits amyloid precursor protein processing, probably by blocking BACE1 activity.
messages: Interacts with NDRG1 (PubMed:15922294). Interacts with BACE1 (PubMed:15286784).
messages: Interacts with TMEM33 (PubMed:25612671).
messages: Interacts with UGCG; regulates the ceramide glucosyltransferase activity of UGCG (PubMed:12873973).
messages: Isoforms RTN1-A and RTN1-B are phosphorylated.
messages: Membrane

9606:KRI1
gene id: 9606:KRI1
uniprot id: A0A494C108
uniprot id: Q8N9T8
names: Sequence Caution
names: Similarity
messages: Belongs to the KRI1 family.
messages: Probable cloning artifact.

9606:MAP4K1
gene id: 9606:MAP4K1
uniprot id: Q92918
names: Function
names: PTM
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Autophosphorylates: phosphorylation promotes ubiquitination by the Cul7-RING(FBXW8) ubiquitin-protein ligase complex, leading to its degradation by the proteasome.
messages: Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.
messages: Expressed primarily in hematopoietic organs, including bone marrow, spleen and thymus. Also expressed at very low levels in lung, kidney, mammary glands and small intestine.
messages: Interacts with MAP3K1 (PubMed:8824585). Interacts with FBXW8 (PubMed:24362026). Interacts with CLNK (via its SH2 domain) (By similarity).
messages: Serine/threonine-protein kinase, which may play a role in the response to environmental stress (PubMed:24362026). Appears to act upstream of the JUN N-terminal pathway (PubMed:8824585). May play a role in hematopoietic lineage decisions and growth regulation (PubMed:8824585, PubMed:24362026). Able to autophosphorylate (PubMed:8824585). Together with CLNK, it enhances CD3-triggered activation of T-cells and subsequent IL2 production (By similarity).
messages: Tyrosine-phosphorylated after activation of hemopoietic cells.
messages: Ubiquitinated by the Cul7-RING(FBXW8) ubiquitin-protein ligase complex following autophosphorylation, leading to its degradation by the proteasome.

9606:ALPK3
gene id: 9606:ALPK3
uniprot id: Q96L96
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the protein kinase superfamily. Alpha-type protein kinase family. ALPK subfamily.
messages: Involved in cardiomyocyte differentiation.
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:KLRC3
gene id: 9606:KLRC3
uniprot id: Q07444
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Can form disulfide-bonded heterodimer with CD94.
messages: Membrane
messages: Natural killer cells.
messages: Plays a role as a receptor for the recognition of MHC class I HLA-E molecules by NK cells and some cytotoxic T-cells.

9606:PGLS
gene id: 9606:PGLS
uniprot id: A0A0K0K1K7
uniprot id: O95336
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the glucosamine/galactosamine-6-phosphate isomerase family. 6-phosphogluconolactonase subfamily.
messages: Cytoplasm
messages: Hydrolysis of 6-phosphogluconolactone to 6-phosphogluconate.

9606:ACSBG1
gene id: 9606:ACSBG1
uniprot id: Q96GR2
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the ATP-dependent AMP-binding enzyme family. Bubblegum subfamily.
messages: Catalyzes the conversion of fatty acids such as long-chain and very long-chain fatty acids to their active form acyl-CoAs for both synthesis of cellular lipids, and degradation via beta-oxidation (PubMed:12975357, PubMed:24269233, PubMed:10954726). Can activate diverse saturated, monosaturated and polyunsaturated fatty acids (PubMed:10954726).
messages: Cell membrane
messages: Cytoplasm
messages: Cytoplasmic vesicle
messages: Endoplasmic reticulum
messages: Expressed primarily in brain. Expressed at lower level in testis and adrenal gland. Present in all regions of brain except pituitary.
messages: Microsome

9606:BCAP29
gene id: 9606:BCAP29
uniprot id: E9PAJ1
uniprot id: Q9UHQ4
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the BCAP29/BCAP31 family.
messages: Endoplasmic reticulum membrane
messages: Homodimer (PubMed:25327138). Heterodimer with BCAP31. Binds CASP8 (isoform 9) as a complex containing BCAP31, BCAP29, BCL2 and/or BCL2L1. Interacts with VAMP3, VAMP1 and membrane IgD immunoglobulins. May interact with ACTG1 and non-muscle myosin II (By similarity).
messages: May play a role in anterograde transport of membrane proteins from the endoplasmic reticulum to the Golgi. May be involved in CASP8-mediated apoptosis (By similarity).
messages: Membrane
messages: Plays a role in the export of secreted proteins in the ER.

9606:PICK1
gene id: 9606:PICK1
uniprot id: Q9NRD5
names: Domain
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Membrane
messages: Monomer and homodimer. Interacts with CXADR. Interacts presynaptically with the glutamate receptors GRIA2, GRIA3, GRIK3, isoform 3 of GRIA4, isoform A of GRM4, GRM7 and GRM8; with NAPA and NAPB; and with BTG2. The interaction with NAPA and NAPB disrupts the interaction with GRIA2, conducting to the internalization of GRIA2. Interacts with PRKCA; with the amine transporters SLC6A2 and SLC6A3; with the channels ASIC1 and ASIC2; with the GTP-binding proteins ARF1 and ARF3; with the ephrin receptor tyrosine kinases EPHA7, EPHB1 and EPHB2; with ERBB2 and through its PDZ domain with the C-terminal tail of PRLHR. Interacts with UNC5A. Interacts (via AH domain) with NCS1/FREQ; in a calcium-dependent manner. Interacts with F-actin and associates with the ARP2/3 complex. Interacts (via PDZ domain) with ARF1 (activated); the interaction blocks Arp2/3 complex inhibition.
messages: Palmitoylation on Cys-413 is essential for long-term synaptic depression (LTD).
messages: Phosphorylation at Thr-82 appears to inhibit the interaction with AMPA receptors.
messages: Postsynaptic density
messages: Probable adapter protein that bind to and organize the subcellular localization of a variety of membrane proteins containing some PDZ recognition sequence. Involved in the clustering of various receptors, possibly by acting at the receptor internalization level. Plays a role in synaptic plasticity by regulating the trafficking and internalization of AMPA receptors. May be regulated upon PRKCA activation. May regulate ASIC1/ASIC3 channel. Regulates actin polymerization by inhibiting the actin-nucleating activity of the Arp2/3 complex; the function is competitive with nucleation promoting factors and is linked to neuronal morphology regulation and AMPA receptor (AMPAR) endocytosis. Via interaction with the Arp2/3 complex involved in regulation of synaptic plasicity of excitatory synapses and required for spine shrinkage during long-term depression (LTD). Involved in regulation of astrocyte morphology, antagonistic to Arp2/3 complex activator WASL/N-WASP function.
messages: The AH domain mediates binding to F-actin.
messages: The unoccupied PDZ domain is probably involved in allosteric modulation by forming an intramolecular bridge with the AH domain leading to a 'closed' formation. Binding of a PDZ ligand, such as GRIA2, allows enhanced interactions with F-actin and the Arp2/3 complex thus enhanced inhibition of actin polymerization (By similarity).
messages: Ubiquitous.
messages: cytoskeleton
messages: perinuclear region
messages: synaptosome

9606:KLHL29
gene id: 9606:KLHL29
uniprot id: Q96CT2
names: Caution
names: Sequence Caution
messages: Although the complete sequence is not known with certainty, sequence shown here appears to be the most probable in accordance with the mouse sequence ortholog.
messages: Intron retention.

9606:HBD
gene id: 9606:HBD
uniprot id: A0N071
uniprot id: P02042
names: Function
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Belongs to the globin family.
messages: Heterotetramer of two alpha chains and two delta chains in adult hemoglobin A2 (HbA2). HbA2 represents less than 3.5% of adult hemoglobin.
messages: Involved in oxygen transport from the lung to the various peripheral tissues.
messages: Red blood cells.

9606:HIGD1B
gene id: 9606:HIGD1B
uniprot id: Q9P298
names: Subcellular Location Annotation
messages: Membrane

9606:LGI1
gene id: 9606:LGI1
uniprot id: A0A0S2Z4S7
uniprot id: A0A0S2Z4X3
uniprot id: A0A0S2Z5G1
uniprot id: A0A1B0GUD3
uniprot id: O95970
names: Disease Annotation
names: Function
names: Induction
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Abundantly expressed in the occipital cortex and weakly expressed in the hippocampus (at protein level).
messages: Cytoplasm
messages: Down-regulated in neuroblastoma cells.
messages: Endoplasmic reticulum
messages: Expressed in the occipital cortex and hippocampus; higher amounts are observed in the parietal and frontal cortices, putamen, and, particularly, in the temporal neocortex, where it is between 3 and 5 times more abundant than in the hippocampus (at protein level) (PubMed:16787412). Expression is absent in the cerebellum (PubMed:16787412).
messages: Glycosylated.
messages: Golgi apparatus
messages: Oligomer. Interacts with KCNA1 within a complex containing KCNA1, KCNA4 and KCNAB1. Part of a complex containing ADAM22, DLG4/PSD95 and CACNG2/Stargazin (PubMed:27066583). Can bind to ADAM11 and ADAM23.
messages: Predominantly expressed in neural tissues, especially in brain. Expression is reduced in low-grade brain tumors and significantly reduced or absent in malignant gliomas.
messages: Regulates voltage-gated potassium channels assembled from KCNA1, KCNA4 and KCNAB1. It slows down channel inactivation by precluding channel closure mediated by the KCNAB1 subunit. Ligand for ADAM22 that positively regulates synaptic transmission mediated by AMPA-type glutamate receptors (By similarity). Plays a role in suppressing the production of MMP1/3 through the phosphatidylinositol 3-kinase/ERK pathway. May play a role in the control of neuroblastoma cell survival.
messages: Secreted
messages: Synapse
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:PSG1
gene id: 9606:PSG1
uniprot id: P11464
names: Developmental Stage
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the immunoglobulin superfamily. CEA family.
messages: PSBG are produced in high quantity during pregnancy.
messages: Secreted

9606:GPR37
gene id: 9606:GPR37
uniprot id: O15354
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Endoplasmic reticulum membrane
messages: Expressed in brain and spinal cord, and at lower levels in testis, placenta and liver, but no detectable expression observed in any other tissue. When overexpressed in cells, tends to become insoluble and unfolded. Accumulation of the unfolded protein may lead to dopaminergic neuronal death in juvenile Parkinson disease (PDJ).
messages: Forms a complex with PRKN, STUB1 and HSP70. The amount of STUB1 in the complex increases during ER stress. STUB1 promotes the dissociation of HSP70 from PRKN, thus facilitating PRKN-mediated GPR37 ubiquitination. Interacts with PACRG.
messages: Receptor for the neuroprotective and glioprotective factor prosaposin. Ligand binding induces endocytosis, followed by an ERK phosphorylation cascade.
messages: Ubiquitinated by PRKN in the presence of UBE2E1 and UBE2L3 in the endoplasmic reticulum. The unfolded form is specifically ubiquitinated by SYVN1, which promotes its proteasomal degradation and prevents neuronal cell death.

9606:SNRPA
gene id: 9606:SNRPA
uniprot id: P09012
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the RRM U1 A/B'' family.
messages: Component of the spliceosomal U1 snRNP, which is essential for recognition of the pre-mRNA 5' splice-site and the subsequent assembly of the spliceosome. U1 snRNP is the first snRNP to interact with pre-mRNA. This interaction is required for the subsequent binding of U2 snRNP and the U4/U6/U5 tri-snRNP. SNRPA binds stem loop II of U1 snRNA. In a snRNP-free form (SF-A) may be involved in coupled pre-mRNA splicing and polyadenylation process. May bind preferentially to the 5'-UGCAC-3' motif on RNAs.
messages: Nucleus
messages: U1 snRNP is composed of the 7 core Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP, and at least three U1 snRNP-specific proteins SNRNP70/U1-70K, SNRPA/U1-A and SNRPC/U1-C. Interacts with SFPQ; component of a snRNP-free complex with SFPQ.

9606:CTSF
gene id: 9606:CTSF
uniprot id: Q9UBX1
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the peptidase C1 family.
messages: High expression levels in heart, skeletal muscle, brain, testis and ovary; moderate levels in prostate, placenta, liver and colon; and no detectable expression in peripheral leukocytes and thymus.
messages: Lysosome
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Thiol protease which is believed to participate in intracellular degradation and turnover of proteins. Has also been implicated in tumor invasion and metastasis.

9606:PCYT1A
gene id: 9606:PCYT1A
uniprot id: B4E322
uniprot id: P49585
names: Activity Regulation
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the cytidylyltransferase family.
messages: Brain, placenta, liver, fetal and adult lung.
messages: By phosphorylation (By similarity). Activated by anionic lipid vesicles and by oleic acid or diacylglycerol-containing phosphatidylcholine vesicles (PubMed:7918629, PubMed:8155650).
messages: Catalyzes the key rate-limiting step in the CDP-choline pathway for phosphatidylcholine biosynthesis.
messages: Endoplasmic reticulum
messages: Homodimer.
messages: Membrane
messages: Monoubiquitinated by the SCF(FBXL2) complex, leading to proteasomal degradation.
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The serine residues of the C-terminus are phosphorylated. The inactive soluble form is stabilized by phosphorylation, the active membrane bound form is promoted by anionic lipids or diacylglycerol, and is stabilized by dephosphorylation (By similarity).
messages: cytosol

9606:FASTKD2
gene id: 9606:FASTKD2
uniprot id: Q9NYY8
names: Caution
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the FAST kinase family.
messages: Expression detected in spleen, thymus, testis, ovary, colon, heart, smooth muscle, kidney, brain, lung, liver and white adipose tissue with highest expression in heart, smooth muscle and thyroid.
messages: It is uncertain whether Met-1 or Met-17 is the initiator.
messages: Mitochondrion matrix
messages: Monomer. Found in a complex with GRSF1, DDX28, DHX30 and FASTKD5. Associates with the 16S mitochondrial rRNA (16S mt-rRNA) (PubMed:25683715). Forms a regulatory protein-RNA complex, consisting of RCC1L, NGRN, RPUSD3, RPUSD4, TRUB2, FASTKD2 and 16S mt-rRNA (PubMed:27667664).
messages: Plays an important role in assembly of the mitochondrial large ribosomal subunit (PubMed:25683715). As a component of a functional protein-RNA module, consisting of RCC1L, NGRN, RPUSD3, RPUSD4, TRUB2, FASTKD2 and 16S mitochondrial ribosomal RNA (16S mt-rRNA), controls 16S mt-rRNA abundance and is required for intra-mitochondrial translation (PubMed:27667664, PubMed:25683715, PubMed:26370583). May play a role in mitochondrial apoptosis.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: mitochondrion nucleoid

9606:CTDNEP1
gene id: 9606:CTDNEP1
uniprot id: O95476
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the dullard family.
messages: Endoplasmic reticulum membrane
messages: Interacts with CNEP1R1; the complex dephosphorylates LPIN1 and LPIN2.
messages: Muscle specific with lower expression in other metabolic tissues.
messages: Nucleus membrane
messages: Serine/threonine protein phosphatase forming with CNEP1R1 an active phosphatase complex that dephosphorylates and may activate LPIN1 and LPIN2. LPIN1 and LPIN2 are phosphatidate phosphatases that catalyze the conversion of phosphatidic acid to diacylglycerol and control the metabolism of fatty acids at different levels. May indirectly modulate the lipid composition of nuclear and/or endoplasmic reticulum membranes and be required for proper nuclear membrane morphology and/or dynamics. May also indirectly regulate the production of lipid droplets and triacylglycerol. May antagonize BMP signaling.

9606:CDR2
gene id: 9606:CDR2
uniprot id: Q01850
names: Similarity
messages: Belongs to the CDR2 family.

9606:SYCE3
gene id: 9606:SYCE3
uniprot id: A1L190
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Chromosome
messages: Homodimer. Interacts with SYCE1. Interacts with SYCE2. Interacts with proteasome subunit PSMA8; to participate in meiosis progression during spermatogenesis (By similarity). Interacts with SPO16 (By similarity).
messages: Major component of the transverse central element of synaptonemal complexes (SCS), formed between homologous chromosomes during meiotic prophase. Required for chromosome loading of the central element-specific SCS proteins, and for initiating synapsis between homologous chromosomes. Chromosome loading appears to require SYCP1. Required for fertility.
messages: Nucleus

9606:AKR1D1
gene id: 9606:AKR1D1
uniprot id: P51857
names: Activity Regulation
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the aldo/keto reductase family.
messages: Catalyzes the stereospecific NADPH-dependent reduction of the C4-C5 double bond of bile acid intermediates and steroid hormones carrying a delta(4)-3-one structure to yield an A/B cis-ring junction. This cis-configuration is crucial for bile acid biosynthesis and plays important roles in steroid metabolism. Capable of reducing a broad range of delta-(4)-3-ketosteroids from C18 (such as, 17beta-hydroxyestr-4-en-3-one) to C27 (such as, 7alpha-hydroxycholest-4-en-3-one).
messages: Cytoplasm
messages: Highly expressed in liver. Expressed in testis and weakly in colon.
messages: Subject to inhibition by high substrate concentrations. Inhibited by testosterone concentrations above 10 uM (PubMed:18407998). Inhibited by the primary and secondary bile acids chenodeoxycholic acid and ursodeoxycholic acid (PubMed:21255593).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:LAT2
gene id: 9606:LAT2
uniprot id: Q9GZY6
names: Disease Annotation
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cell membrane
messages: Highly expressed in spleen, peripheral blood lymphocytes, and germinal centers of lymph nodes. Also expressed in placenta, lung, pancreas and small intestine. Present in B-cells, NK cells and monocytes. Absent from T-cells (at protein level).
messages: Involved in FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. May also be involved in BCR (B-cell antigen receptor)-mediated signaling in B-cells and FCGR1 (high affinity immunoglobulin gamma Fc receptor I)-mediated signaling in myeloid cells. Couples activation of these receptors and their associated kinases with distal intracellular events through the recruitment of GRB2.
messages: LAT2 is located in the Williams-Beuren syndrome (WBS) critical region. WBS results from a hemizygous deletion of several genes on chromosome 7q11.23, thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region. Haploinsufficiency of LAT2 may be the cause of certain cardiovascular and musculo-skeletal abnormalities observed in the disease.
messages: May be polyubiquitinated.
messages: Phosphorylated on tyrosines following cross-linking of BCR in B-cells, FCGR1 in myeloid cells, or FCER1 in mast cells; which induces the recruitment of GRB2.
messages: When phosphorylated, interacts with GRB2. May also interact with SOS1, GAB1 and CBL.

9606:PSMB4
gene id: 9606:PSMB4
uniprot id: A0A140VK46
uniprot id: P28070
names: Caution
names: Disease Annotation
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Interacts with HIV-1 Nef and Tat proteins.
messages: (Microbial infection) Interacts with HTLV-1 Tax protein.
messages: A report observed N-glycosylation at Asn-83 (PubMed:19139490). However, as the protein does not localize in an extracellular compartment of the cell, additional evidence is required to confirm this result.
messages: Belongs to the peptidase T1B family.
messages: Cytoplasm
messages: Non-catalytic component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex). SMAD1/OAZ1/PSMB4 complex mediates the degradation of the CREBBP/EP300 repressor SNIP1.
messages: Non-catalytic component of the proteasome.
messages: Nucleus
messages: The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits (PubMed:25599644, PubMed:26133119, PubMed:27342858, PubMed:27428775, PubMed:27493187, PubMed:9344905, PubMed:34711951). The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings (PubMed:25599644, PubMed:26133119, PubMed:27342858, PubMed:27428775, PubMed:27493187, PubMed:9344905, PubMed:34711951). The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits (PubMed:25599644, PubMed:26133119, PubMed:27342858, PubMed:27428775, PubMed:27493187, PubMed:9344905, PubMed:34711951). The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7 (PubMed:25599644, PubMed:26133119, PubMed:27342858, PubMed:27428775, PubMed:27493187, PubMed:9344905, PubMed:34711951). Forms a ternary complex with SMAD1 and OAZ1 before PSMB4 is incorporated into the 20S proteasome (PubMed:11571290, PubMed:12097147). Interacts with PRPF19 (PubMed:15660529).
messages: The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry.
messages: Up-regulated in fibrolamellar carcinomas.

9606:SCRG1
gene id: 9606:SCRG1
uniprot id: O75711
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the SCRG1 family.
messages: Expressed abundantly in the central nervous system of adult, but not at all in fetal brain. High levels of SCRG1 transcripts are also observed in testis and aorta.
messages: Secreted

9606:SPATA31A3
gene id: 9606:SPATA31A3
uniprot id: Q5VYP0
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the SPATA31 family.
messages: May play a role in spermatogenesis.
messages: Membrane

9606:OR52A1
gene id: 9606:OR52A1
uniprot id: Q9UKL2
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Odorant receptor.

9606:CPO
gene id: 9606:CPO
uniprot id: Q8IVL8
names: Activity Regulation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Apical cell membrane
messages: Belongs to the peptidase M14 family.
messages: Carboxypeptidase which preferentially cleaves C-terminal acidic residues from peptides and proteins. Can also cleave C-terminal hydrophobic amino acids, with a preference for small residues over large residues.
messages: Detected in enterocytes of the ileum.
messages: N-glycosylated.
messages: Strongly inhibited by potato carboxypeptidase inhibitor, and the chelating agents EDTA and 1,10-phenanthroline. Also inhibited by compounds with multiple carboxylic acid groups such as citrate and succinate, and to a lesser exent the amino acids aspartate and glutamate. Not significantly inhibited by benzylsuccinic acid.

9606:C1R
gene id: 9606:C1R
uniprot id: P00736
names: Disease Annotation
names: Function
names: PTM
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the peptidase S1 family.
messages: C1 is a calcium-dependent trimolecular complex of C1q, C1r and C1s in the molar ration of 1:2:2. C1r is a dimer of identical chains, each of which is activated by cleavage into two chains, A and B, connected by disulfide bonds.
messages: C1r B chain is a serine protease that combines with C1q and C1s to form C1, the first component of the classical pathway of the complement system.
messages: Complement component C1r deficiency [MIM:216950] leads to the failure of the classical complement system activation pathway (C1 deficiency). Individuals with C1 deficiency are highly susceptible to infections by microorganisms and have greater risk in developing autoimmune diseases such as systemic lupus erythematosus (SLE).
messages: Secreted
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains.

9606:SCAMP3
gene id: 9606:SCAMP3
uniprot id: O14828
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the SCAMP family.
messages: Functions in post-Golgi recycling pathways. Acts as a recycling carrier to the cell surface.
messages: Interacts with NEDD4, NEDD4L and TSG101. Interacts with RNF126.
messages: Membrane
messages: Monoubiquitinated.
messages: Widely expressed, with highest expression in heart and skeletal muscle.

9606:EFNB2
gene id: 9606:EFNB2
uniprot id: P52799
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Acts as a receptor for Hendra virus and Nipah virus.
messages: (Microbial infection) Interacts with Hendra virus and Nipah virus G protein (PubMed:16007075, PubMed:16477309, PubMed:17376907, PubMed:15998730).
messages: Belongs to the ephrin family.
messages: Cell membrane
messages: Cell surface transmembrane ligand for Eph receptors, a family of receptor tyrosine kinases which are crucial for migration, repulsion and adhesion during neuronal, vascular and epithelial development. Binds promiscuously Eph receptors residing on adjacent cells, leading to contact-dependent bidirectional signaling into neighboring cells. The signaling pathway downstream of the receptor is referred to as forward signaling while the signaling pathway downstream of the ephrin ligand is referred to as reverse signaling. Binds to receptor tyrosine kinase including EPHA4, EPHA3 and EPHB4. Together with EPHB4 plays a central role in heart morphogenesis and angiogenesis through regulation of cell adhesion and cell migration. EPHB4-mediated forward signaling controls cellular repulsion and segregation from EFNB2-expressing cells. May play a role in constraining the orientation of longitudinally projecting axons.
messages: Inducible phosphorylation of tyrosine residues in the cytoplasmic domain.
messages: Interacts with PDZRN3 (By similarity). Binds to the receptor tyrosine kinases EPHA4, EPHB4 and EPHA3.
messages: Lung and kidney.
messages: adherens junction

9606:TPTE2
gene id: 9606:TPTE2
uniprot id: Q6XPS3
names: Function
names: Miscellaneous
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Acts as a lipid phosphatase, removing the phosphate in the D3 position of the inositol ring from phosphatidylinositol 3,4,5-trisphosphate.
messages: Cytoplasm
messages: Endoplasmic reticulum membrane
messages: Expressed in testis, strongly inhibits cell growth in HeLa cells.
messages: Golgi apparatus membrane
messages: Isoform 3 is expressed in testis, brain and stomach while isoform 4 seems to be testis-specific.
messages: Shows no phosphoinositide phosphatase activity.

9606:ENSA
gene id: 9606:ENSA
uniprot id: O43768
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the endosulfine family.
messages: Cytoplasm
messages: Interacts (when phosphorylated at Ser-67) with PPP2R2D (By similarity). Interacts with ABCC8. Interacts with SNCA; interaction is disrupted when phosphorylated at Ser-109.
messages: Phosphorylation at Ser-67 by GWL during mitosis is essential for interaction with PPP2R2D (PR55-delta) and subsequent inactivation of PP2A (By similarity). Phosphorylated by PKA.
messages: Protein phosphatase inhibitor that specifically inhibits protein phosphatase 2A (PP2A) during mitosis. When phosphorylated at Ser-67 during mitosis, specifically interacts with PPP2R2D (PR55-delta) and inhibits its activity, leading to inactivation of PP2A, an essential condition to keep cyclin-B1-CDK1 activity high during M phase (By similarity). Also acts as a stimulator of insulin secretion by interacting with sulfonylurea receptor (ABCC8), thereby preventing sulfonylurea from binding to its receptor and reducing K(ATP) channel currents.
messages: Widely expressed with high levels in skeletal muscle and brain and lower levels in the pancreas.

9606:SPEF2
gene id: 9606:SPEF2
uniprot id: Q9C093
names: Disease Annotation
names: Function
names: Miscellaneous
names: Subcellular Location Annotation
names: Subunit
messages: Cytoplasm
messages: Golgi apparatus
messages: Interacts (via C-terminus) with IFT20 (PubMed:19889948). Interacts with DYNC1I2 (By similarity).
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Required for correct axoneme development in spermatozoa. Important for normal development of the manchette and sperm head morphology. Essential for male fertility. Plays a role in localization of the intraflagellar transport protein IFT20 to the manchette, suggesting function as an adapter for dynein-mediated protein transport during spermatogenesis (PubMed:31278745, PubMed:31151990, PubMed:31048344). Also plays a role in bone growth where it seems to be required for normal osteoblast differentiation (By similarity).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: flagellum

9606:POU2AF3
gene id: 9606:POU2AF3
uniprot id: A8K830
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the POU2AF family.
messages: Cytoplasm
messages: Expressed in many cell types of epithelial, mesenchymal and hematopoietic origins (PubMed:24154973). Expressed in tufs cells (PubMed:35576971).
messages: In the N-terminus possesses a conserved OCA domain for bivalent binding to class II POU domain-containing transcription factors and to an octamer DNA motif (5'-ATGAAAT-3').
messages: Interacts with POU2F3 in a DNA-dependent manner; this interaction increases POU2F3 transactivation activity.
messages: Nucleus
messages: Transcriptional coactivator that specifically associates with POU2F3 (PubMed:35576971). This complex drives the development of tuft cells, a rare a rare chemosensory cells that coordinate immune and neural functions within mucosal epithelial tissues (PubMed:35576971).

9606:RPS10
gene id: 9606:RPS10
uniprot id: P46783
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the eukaryotic ribosomal protein eS10 family.
messages: Component of the 40S ribosomal subunit (PubMed:23636399). The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell (PubMed:23636399).
messages: Component of the small ribosomal subunit (PubMed:23636399). The methylated form interacts with NPM1 (PubMed:20159986).
messages: Cytoplasm
messages: Methylated by PRMT5. Methylation is necessary for its interaction with NPS1, its localization in the granular component (GC) region of the nucleolus, for the proper assembly of ribosomes, protein synthesis and optimal cell proliferation.
messages: Monoubiquitinated by ZNF598 when a ribosome has stalled during translation of poly(A) sequences, leading to preclude synthesis of a long poly-lysine tail and initiate the ribosome quality control (RQC) pathway to degrade the potentially detrimental aberrant nascent polypeptide (PubMed:28065601, PubMed:28132843, PubMed:28685749, PubMed:32011234, PubMed:36302773). Deubiquitinated by OTUD3 and USP21, antagonizing ZNF598 activity (PubMed:32011234). Deubiquitinated by OTUD1, antagonizing ZNF598 activity and stimulating formation of polysomes: deubiquitination by OTUD1 promotes stability and translation of a subset mRNAs with a high abundance of rare codons can limit the translation rate (PubMed:36445135). Deubiquitinated by USP10 (PubMed:31981475).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: nucleolus

9606:GBP2
gene id: 9606:GBP2
uniprot id: P32456
uniprot id: Q8TCE5
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Ubiquitinated by S.flexneri IpaH9.8, leading to its degradation by the proteasome, thereby preventing its ability to promote host defense against bacterial infection.
messages: Belongs to the TRAFAC class dynamin-like GTPase superfamily. GB1/RHD3 GTPase family.
messages: Belongs to the TRAFAC class dynamin-like GTPase superfamily. GB1/RHD3 GTPase family. GB1 subfamily.
messages: By IFNG/IFN-gamma during macrophage activation, and by TNF and IL1B.
messages: Cytoplasm
messages: Cytoplasmic vesicle membrane
messages: Golgi apparatus membrane
messages: Homodimer; homodimerization occurs upon GTP-binding and is required for the association with membranous structures (PubMed:21151871). Heterodimer with other family members, including GBP1, GBP3, GBP4 and GBP5 (PubMed:21151871).
messages: Interferon (IFN)-inducible GTPase that plays important roles in innate immunity against a diverse range of bacterial, viral and protozoan pathogens (PubMed:31091448). Hydrolyzes GTP to GMP in 2 consecutive cleavage reactions, but the major reaction product is GDP (PubMed:8706832). Following infection, recruited to the pathogen-containing vacuoles or vacuole-escaped bacteria and acts as a positive regulator of inflammasome assembly by promoting the release of inflammasome ligands from bacteria (By similarity). Acts by promoting lysis of pathogen-containing vacuoles, releasing pathogens into the cytosol (By similarity). Following pathogen release in the cytosol, promotes recruitment of proteins that mediate bacterial cytolysis: this liberates ligands that are detected by inflammasomes, such as lipopolysaccharide (LPS) that activates the non-canonical CASP4/CASP11 inflammasome or double-stranded DNA (dsDNA) that activates the AIM2 inflammasome (By similarity). Confers protection to the protozoan pathogen Toxoplasma gondii (By similarity). Independently of its GTPase activity, acts as an inhibitor of various viruses infectivity, such as HIV-1, Zika and influenza A viruses, by inhibiting FURIN-mediated maturation of viral envelope proteins (PubMed:31091448).
messages: Isoprenylation is required for proper subcellular location.
messages: perinuclear region

9606:OR2T33
gene id: 9606:OR2T33
uniprot id: Q8NG76
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Odorant receptor.

9606:GATM
gene id: 9606:GATM
uniprot id: A0A140VK19
uniprot id: P50440
names: Disease Annotation
names: Domain
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the amidinotransferase family.
messages: Cytoplasm
messages: Expressed in brain, heart, kidney, liver, lung, salivary gland and skeletal muscle tissue, with the highest expression in kidney. Biallelically expressed in placenta and fetal tissues.
messages: Expression is elevated in the myocardium during heart failure, and decreased in inter-uterine growth restriction (IUGR)-associated placenta.
messages: Homodimer.
messages: Homodimer. There is an equilibrium between the monomeric and dimeric forms, shifted towards the side of the monomer.
messages: Mitochondrion inner membrane
messages: One chain folds into a compact single domain composed of repeating units, five beta-beta-alpha-beta modules, which surround the central active site.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Transamidinase that catalyzes the transfer of the amidino group of L-arginine onto the amino moiety of acceptor metabolites such as glycine, beta-alanine, gamma-aminobutyric acid (GABA) and taurine yielding the corresponding guanidine derivatives (PubMed:3800397, PubMed:16820567, PubMed:36543883, PubMed:27233232). Catalyzes the rate-limiting step of creatine biosynthesis, namely the transfer of the amidino group from L-arginine to glycine to generate guanidinoacetate, which is then methylated by GAMT to form creatine. Provides creatine as a source for ATP generation in tissues with high energy demands, in particular skeletal muscle, heart and brain (PubMed:3800397, PubMed:36543883, PubMed:9266688, PubMed:27233232) (Probable).
messages: Transamidinase that catalyzes the transfer of the amidino group of L-arginine onto the amino moiety of acceptor metabolites such as glycine, beta-alanine, gamma-aminobutyric acid (GABA) and taurine yielding the corresponding guanidine derivatives. Catalyzes the rate-limiting step of creatine biosynthesis, namely the transfer of the amidino group from L-arginine to glycine to generate guanidinoacetate, which is then methylated by GAMT to form creatine. Provides creatine as a source for ATP generation in tissues with high energy demands, in particular skeletal muscle, heart and brain.

9606:MMP28
gene id: 9606:MMP28
uniprot id: B3KV06
uniprot id: C0H5X0
uniprot id: Q9H239
names: Cofactor
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the peptidase M10A family.
messages: Binds 1 zinc ion per subunit.
messages: Binds 2 Zn(2+) ions per subunit.
messages: Can bind about 5 Ca(2+) ions per subunit.
messages: Can degrade casein. Could play a role in tissues homeostasis and repair.
messages: Expressed at high levels in testes and lung. Low levels are detected in kidney, pancreas and skin. Also expressed in fetal lung, brain, skeletal muscle and kidney. Expressed selectively in keratinocytes. Widely expressed in several carcinomas as well. Is up-regulated in response to injury in the skin.
messages: The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.
messages: The precursor is cleaved by a furin endopeptidase.
messages: extracellular matrix

9606:EYA2
gene id: 9606:EYA2
uniprot id: E7ETN2
uniprot id: O00167
names: Cofactor
names: Developmental Stage
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: At the begin of fourth week of development detected in cytoplasm of somite cells. Between the sixth and eighth week of development detected in cytoplasm of limb bud cells.
messages: Belongs to the HAD-like hydrolase superfamily. EYA family.
messages: Binds 1 Mg(2+) ion per subunit.
messages: Cytoplasm
messages: Functions both as protein phosphatase and as transcriptional coactivator for SIX1, and probably also for SIX2, SIX4 and SIX5 (PubMed:12500905, PubMed:23435380). Tyrosine phosphatase that dephosphorylates 'Tyr-142' of histone H2AX (H2AXY142ph) and promotes efficient DNA repair via the recruitment of DNA repair complexes containing MDC1. 'Tyr-142' phosphorylation of histone H2AX plays a central role in DNA repair and acts as a mark that distinguishes between apoptotic and repair responses to genotoxic stress (PubMed:19351884). Its function as histone phosphatase may contribute to its function in transcription regulation during organogenesis. Plays an important role in hypaxial muscle development together with SIX1 and DACH2; in this it is functionally redundant with EYA1 (PubMed:12500905).
messages: Highest expression in muscle with lower levels in kidney, placenta, pancreas, brain and heart.
messages: Interacts with DACH2 and SIX1, and probably with SIX2, SIX4 and SIX5. Interacts with CAPN8 (By similarity). Interacts with GNAZ and GNAI2; this precludes interaction with SIX1.
messages: Nucleus

9606:ABHD12
gene id: 9606:ABHD12
uniprot id: Q8N2K0
names: Activity Regulation
names: Caution
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
messages: A family suffering from Polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract (PHARC) was initially clinically diagnosed with Usher syndrome type 3 (PubMed:22938382). Reexamination of one affected member of this family revealed ataxia but not polyneuropathy, demonstrating the phenotypic heterogeneity in PHARC and the need for careful neurological assessments to distinguish this disease from other neuropathic disorders (PubMed:22938382).
messages: Belongs to the serine esterase family.
messages: Endoplasmic reticulum membrane
messages: Glycosylated; glycosylation is required for optimal activity.
messages: Lysophosphatidylserine (LPS) lipase that mediates the hydrolysis of lysophosphatidylserine, a class of signaling lipids that regulates immunological and neurological processes (PubMed:25290914, PubMed:30237167, PubMed:30420694, PubMed:30720278, PubMed:30643283). Represents a major lysophosphatidylserine lipase in the brain, thereby playing a key role in the central nervous system (By similarity). Also able to hydrolyze oxidized phosphatidylserine; oxidized phosphatidylserine is produced in response to severe inflammatory stress and constitutes a proapoptotic 'eat me' signal (PubMed:30643283). Also has monoacylglycerol (MAG) lipase activity: hydrolyzes 2-arachidonoylglycerol (2-AG), thereby acting as a regulator of endocannabinoid signaling pathways (PubMed:22969151, PubMed:24027063). Has a strong preference for very-long-chain lipid substrates; substrate specificity is likely due to improved catalysis and not improved substrate binding (PubMed:30237167).
messages: Selectively inhibited by DO264 (N-3-pyridyl-N'-(1-[3-chloro-4-{2-chloro-4-(trifluoromethoxy)phenoxy}pyridine-2-yl]piperidin-4-yl)thiourea) (PubMed:30420694, PubMed:30720278). Reversibly inhibited by triterpenoids, but with rather low potency (PubMed:24879289).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:RPH3A
gene id: 9606:RPH3A
uniprot id: Q9Y2J0
names: Domain
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: Binds calcium via the C2 domains. The calcium-bound C2 domains mediate interactions with phospholipid bilayers (By similarity).
messages: Interacts with RAB3B, RAB3C, RAB3D, RAB8A, RAB27A and RAB27B (By similarity). Interacts with RAB3A; this interaction recruits RPH3A to synaptic vesicules (PubMed:15207266). Interacts (via C2B domain) with SNAP25 (By similarity). Interacts with deubiquitinating enzyme CAND1; this interaction results in the deubiquitination of RPH3A (By similarity). Interacts with GRIN2A and DLG4; this ternary complex regulates NMDA receptor composition at postsynaptic membranes (By similarity). Interacts with SNCA (PubMed:15207266).
messages: Membrane
messages: Plays an essential role in docking and fusion steps of regulated exocytosis (By similarity). At the presynaptic level, RPH3A is recruited by RAB3A to the synaptic vesicle membrane in a GTP-dependent manner where it modulates synaptic vesicle trafficking and calcium-triggered neurotransmitter release (By similarity). In the post-synaptic compartment, forms a ternary complex with GRIN2A and DLG4 and regulates NMDA receptor stability. Also plays a role in the exocytosis of arginine vasopressin hormone (By similarity).
messages: Postsynaptic cell membrane
messages: Ubiquitinated. Deubiquitinated by CAND1 to prevent its degradation.
messages: dendritic spine
messages: synaptic vesicle membrane

9606:RNASE3
gene id: 9606:RNASE3
uniprot id: P12724
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the pancreatic ribonuclease family.
messages: Cytotoxin and helminthotoxin with low-efficiency ribonuclease activity. Possesses a wide variety of biological activities. Exhibits antibacterial activity, including cytoplasmic membrane depolarization of preferentially Gram-negative, but also Gram-positive strains. Promotes E.coli outer membrane detachment, alteration of the overall cell shape and partial loss of cell content.
messages: Interacts with bacterial lipopolysaccharide (LPS) and lipoteichoic acid (LTA). In vitro interacts with and insert into lipid bilayers composed of dioleoyl phosphatidylcholine and dioleoyl phosphatidylglycerol. In vitro, tends to form amyloid-like aggregates at pH 3, but not at pH 5, nor 7.
messages: Secreted

9606:ECE1
gene id: 9606:ECE1
uniprot id: P42892
names: Activity Regulation
names: Cofactor
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: All isoforms are expressed in umbilical vein endothelial cells, polynuclear neutrophils, fibroblasts, atrium cardiomyocytes and ventricles. Isoforms A, B and C are also expressed in placenta, lung, heart, adrenal gland and phaeochromocytoma; isoforms A and C in liver, testis and small intestine; isoform B, C and D in endothelial cells and umbilical vein smooth muscle cells; isoforms C and D in saphenous vein cells, and isoform C in kidney.
messages: Belongs to the peptidase M13 family.
messages: Binds 1 zinc ion per subunit.
messages: Cell membrane
messages: Converts big endothelin-1 to endothelin-1.
messages: Homodimer; disulfide-linked (PubMed:18992253). Interacts with PPP1R16B (By similarity).
messages: Inhibited by phosphoramidon (PubMed:18992253). Activated by K49-P1-20, a twenty-residue synthetic peptide shortened from the snake B.asper myotoxin II (PubMed:26931059).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:PSMD8
gene id: 9606:PSMD8
uniprot id: P48556
uniprot id: V9HW09
names: Caution
names: Function
names: Similarity
names: Subunit
messages: Belongs to the proteasome subunit S14 family.
messages: Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits including PSMD8, a base containing 6 ATPases and few additional components. Interacts with DDI2 (PubMed:29290612). Interacts with TASOR (By similarity).
messages: Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair.
messages: It is uncertain whether Met-1 or Met-64 is the initiator.

9606:REM1
gene id: 9606:REM1
uniprot id: O75628
names: Function
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Belongs to the small GTPase superfamily. RGK family.
messages: In vitro, interacts with calmodulin in a calcium-dependent manner.
messages: Most highly expressed in the endothelial lining of the blood vessels in uterus and heart. Lower levels found in spleen, lymph node, kidney and testis. Also found in cells with secretory function such as the islets of Langerhans, lobule/duct epithelium in the breast, bile duct epithelium in the liver, surface epithelium in the endometrial glands of the uterus, colon mucosa and acinar cells in the pancreas and the prostate.
messages: Promotes endothelial cell sprouting and actin cytoskeletal reorganization. May be involved in angiogenesis. May function in Ca(2+) signaling.

9606:MYOD1
gene id: 9606:MYOD1
uniprot id: P15172
names: Disease Annotation
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: Acetylated by a complex containing EP300 and PCAF. The acetylation is essential to activate target genes. Conversely, its deacetylation by SIRT1 inhibits its function (By similarity).
messages: Acts as a transcriptional activator that promotes transcription of muscle-specific target genes and plays a role in muscle differentiation. Together with MYF5 and MYOG, co-occupies muscle-specific gene promoter core region during myogenesis. Induces fibroblasts to differentiate into myoblasts. Interacts with and is inhibited by the twist protein. This interaction probably involves the basic domains of both proteins (By similarity).
messages: Efficient DNA binding requires dimerization with another bHLH protein. Seems to form active heterodimers with ITF-2. Interacts with SUV39H1. Interacts with DDX5. Interacts with CHD2. Interacts with TSC22D3 (By similarity). Interacts with SETD3 (By similarity). Interacts with P-TEFB complex; promotes the transcriptional activity of MYOD1 through its CDK9-mediated phosphorylation (By similarity) (PubMed:12037670). Interacts with CSRP3. Interacts with NUPR1 (By similarity).
messages: Methylation at Lys-104 by EHMT2/G9a inhibits myogenic activity.
messages: Nucleus
messages: Phosphorylated by CDK9. This phosphorylation promotes its function in muscle differentiation.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitinated on the N-terminus; which is required for proteasomal degradation.

9606:IRGC
gene id: 9606:IRGC
uniprot id: J7NNX4
uniprot id: Q6NXR0
names: Similarity
messages: Belongs to the TRAFAC class dynamin-like GTPase superfamily. IRG family.

9606:SPAG5
gene id: 9606:SPAG5
uniprot id: Q96R06
names: Function
names: Induction
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cytoplasm
messages: Cytoplasmic granule
messages: Essential component of the mitotic spindle required for normal chromosome segregation and progression into anaphase (PubMed:11724960, PubMed:12356910, PubMed:27462074). Required for chromosome alignment, normal timing of sister chromatid segregation, and maintenance of spindle pole architecture (PubMed:17664331, PubMed:27462074). In complex with SKAP, promotes stable microtubule-kinetochore attachments. May contribute to the regulation of separase activity. May regulate AURKA localization to mitotic spindle, but not to centrosomes and CCNB1 localization to both mitotic spindle and centrosomes (PubMed:18361916, PubMed:21402792). Involved in centriole duplication. Required for CDK5RAP2, CEP152, WDR62 and CEP63 centrosomal localization and promotes the centrosomal localization of CDK2 (PubMed:26297806). In non-mitotic cells, upon stress induction, inhibits mammalian target of rapamycin complex 1 (mTORC1) association and recruits the mTORC1 component RPTOR to stress granules (SGs), thereby preventing mTORC1 hyperactivation-induced apoptosis (PubMed:23953116). May enhance GSK3B-mediated phosphorylation of other substrates, such as MAPT/TAU (PubMed:18055457).
messages: Expression is cell cycle-regulated, with an increase from prophase to cytokinesis and return to basal levels at the next G1 phase.
messages: Highly expressed in testis. Detected at low levels in placenta, liver, pancreas, thymus and colon.
messages: Homodimer, with a globular head domain and a long stalk. Homooligomer; the globular head domains associate, resulting in aster-like structures. Binds to microtubules in the mitotic spindle (PubMed:27462074). Interacts with DCLRE1B/Apollo. Part of an astrin (SPAG5)-kinastrin (SKAP) complex containing KNSTRN, SPAG5, PLK1, DYNLL1 and SGO2. Interacts with KNSTRN. Interacts with RPTOR; this interaction competes with RPTOR binding to MTOR, resulting in decreased mTORC1 formation. Interacts with G3BP1. The complex formed with G3BP1 AND RPTOR is increased by oxidative stress. Interacts with OSBPL8, PCM1 and CDK5RAP2 (PubMed:24424245, PubMed:26297806). Interacts (via C-terminus) with NUMA1 (via C-terminus); this interaction promotes the recruitment of SPAG5 to the microtubules at spindle poles in a dynein-dynactin-dependent manner (PubMed:27462074). Interacts with DYNLL1 (PubMed:22965910).
messages: Midbody
messages: Phosphorylated by AURKA.
messages: centriolar satellite
messages: centrosome
messages: cytoskeleton
messages: kinetochore
messages: spindle
messages: spindle pole

9606:OR5H2
gene id: 9606:OR5H2
uniprot id: Q8NGV7
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Odorant receptor.

9606:RHOV
gene id: 9606:RHOV
uniprot id: Q96L33
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the small GTPase superfamily. Rho family.
messages: Cell membrane
messages: Endosome membrane
messages: Highly expressed in pancreas, placenta, and fetal brain.
messages: Interacts with PAK2.
messages: Plays a role in the control of the actin cytoskeleton via activation of the JNK pathway.

9606:DEFB127
gene id: 9606:DEFB127
uniprot id: Q9H1M4
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the beta-defensin family.
messages: Has antibacterial activity.
messages: Secreted

9606:MEAK7
gene id: 9606:MEAK7
uniprot id: Q6P9B6
names: Function
names: Induction
names: Subcellular Location Annotation
names: Subunit
messages: Activates an alternative mTOR signaling through RPS6KB2 activation and EIF4EBP1 repression to regulate cell proliferation and migration (PubMed:29750193). Recruits MTOR at the lysosome, essential for MTOR signaling at the lysosome (PubMed:29750193).
messages: Addition of nutrients and insulin induces its expression (at protein level).
messages: Cytoplasm
messages: Interacts (via C-terminal domain) with MTOR and MLST8; the interaction with MTOR increases upon nutrient stimulation.
messages: Lysosome
messages: Membrane

9606:YAE1
gene id: 9606:YAE1
uniprot id: Q9NRH1
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Cytoplasm
messages: Forms a complex with LTO1.
messages: Nucleus
messages: The complex LTO1:YAE1 functions as a target specific adapter that probably recruits apo-ABCE1 to the cytosolic iron-sulfur protein assembly (CIA) complex machinery (PubMed:26182403). May be required for biogenesis of the large ribosomal subunit and initiation of translation (PubMed:26182403).

9606:THSD1
gene id: 9606:THSD1
uniprot id: Q9NS62
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Endosome membrane
messages: Is a positive regulator of nascent focal adhesion assembly, involved in the modulation of endothelial cell attachment to the extracellular matrix.
messages: Membrane
messages: Part of a complex composed of THSD1, PTK2/FAK1, TLN1 and VCL (PubMed:29069646). Interacts with TLN1 (PubMed:27895300, PubMed:29069646).
messages: Secreted
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: focal adhesion

9606:HDAC9
gene id: 9606:HDAC9
uniprot id: A0A7P0T8F4
uniprot id: A0A7P0TAB5
uniprot id: A0A9L9PXL9
uniprot id: B7Z3P7
uniprot id: Q9UKV0
names: Activity Regulation
names: Disease Annotation
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: A chromosomal aberration involving HDAC9 is found in a family with Peters anomaly. Translocation t(1;7)(q41;p21) with TGFB2 resulting in lack of HDAC9 protein.
messages: Belongs to the histone deacetylase family. HD type 2 subfamily.
messages: Broadly expressed, with highest levels in brain, heart, muscle and testis. Isoform 3 is present in human bladder carcinoma cells (at protein level).
messages: Excluded from the nucleus. Does not interact with ETV6.
messages: Homodimer. Interacts with CTBP1. The phosphorylated form interacts with 14-3-3 (By similarity). Interacts with HDAC1 and HDAC3, and probably with HDAC4 and HDAC5. Interacts with MEF2, MAPK10, ETV6, NCOR1 and BCL6. Interacts with FOXP3 in the absence of T-cell stimulation.
messages: Inhibited by Trichostatin A (TSA) and suberoylanilide hydroxamic acid.
messages: Isoform 3 lacks active site residues and therefore is catalytically inactive. Represses MEF2-dependent transcription by recruiting HDAC1 and/or HDAC3. Seems to inhibit skeletal myogenesis and to be involved in heart development. Protects neurons from apoptosis, both by inhibiting JUN phosphorylation by MAPK10 and by repressing JUN transcription via HDAC1 recruitment to JUN promoter.
messages: Major form in most tissues. Inactive due to lack of active site residues.
messages: Nucleus
messages: Phosphorylated on Ser-220 and Ser-450; which promotes 14-3-3-binding, impairs interaction with MEF2, and antagonizes antimyogenic activity. Phosphorylated on Ser-240; which impairs nuclear accumulation (By similarity). Isoform 7 is phosphorylated on Tyr-1010. Phosphorylated by the PKC kinases PKN1 and PKN2, impairing nuclear import.
messages: Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Represses MEF2-dependent transcription.
messages: Sumoylated.

9606:AGMO
gene id: 9606:AGMO
uniprot id: Q6ZNB7
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the sterol desaturase family. TMEM195 subfamily.
messages: Endoplasmic reticulum membrane
messages: Glyceryl-ether monooxygenase that cleaves the O-alkyl bond of ether lipids. Ether lipids are essential components of brain membranes.

9606:UBE2N
gene id: 9606:UBE2N
uniprot id: P61088
uniprot id: V9HW41
names: Activity Regulation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Activity is inhibited by binding to OTUB1, which prevents 'Lys-63'-linked polyubiquitination (PubMed:20725033, PubMed:22325355, PubMed:22367539). Activity is inhibited by GPS2, leading to prevent 'Lys-63'-linked polyubiquitination (By similarity).
messages: Belongs to the ubiquitin-conjugating enzyme family.
messages: Conjugation to ISG15 impairs formation of the thioester bond with ubiquitin but not interaction with UBE2V2.
messages: Cytoplasm
messages: Heterodimer with UBE2V2 (PubMed:10089880, PubMed:11473255, PubMed:14562038, PubMed:16307917, PubMed:16307917). Interacts (UBE2V2-UBE2N heterodimer) with the E3 ligase STUB1 (via the U-box domain); the complex has a specific 'Lys-63'-linked polyubiquitination activity (PubMed:16307917). Interacts with RNF8 and RNF168 (PubMed:16215985, PubMed:19203578). Interacts with RNF11 (PubMed:18615712). Interacts with the E3 ligases, HLTF and SHPRH; the interactions promote the 'Lys-63'-linked polyubiquitination of PCNA upon genotoxic stress and lead to DNA repair (PubMed:17108083, PubMed:17130289, PubMed:18316726, PubMed:18719106). Interacts with ARIH2 (via RING-type 2) (PubMed:19340006). Interacts with OTUB1; leading to inhibit E2-conjugating activity (PubMed:20725033, PubMed:22325355, PubMed:22367539). Interacts with GPS2; leading to inhibit E2-conjugating activity (By similarity). Interacts with RIGI and RNF135; involved in RIGI ubiquitination and activation (PubMed:28469175). Interacts with ZNRF1 (PubMed:29626159).
messages: Nucleus
messages: The UBE2V1-UBE2N and UBE2V2-UBE2N heterodimers catalyze the synthesis of non-canonical 'Lys-63'-linked polyubiquitin chains. This type of polyubiquitination does not lead to protein degradation by the proteasome. Mediates transcriptional activation of target genes. Plays a role in the control of progress through the cell cycle and differentiation. Plays a role in the error-free DNA repair pathway and contributes to the survival of cells after DNA damage. Acts together with the E3 ligases, HLTF and SHPRH, in the 'Lys-63'-linked poly-ubiquitination of PCNA upon genotoxic stress, which is required for DNA repair. Appears to act together with E3 ligase RNF5 in the 'Lys-63'-linked polyubiquitination of JKAMP thereby regulating JKAMP function by decreasing its association with components of the proteasome and ERAD. Promotes TRIM5 capsid-specific restriction activity and the UBE2V1-UBE2N heterodimer acts in concert with TRIM5 to generate 'Lys-63'-linked polyubiquitin chains which activate the MAP3K7/TAK1 complex which in turn results in the induction and expression of NF-kappa-B and MAPK-responsive inflammatory genes. Together with RNF135 and UB2V1, catalyzes the viral RNA-dependent 'Lys-63'-linked polyubiquitination of RIGI to activate the downstream signaling pathway that leads to interferon beta production (PubMed:28469175, PubMed:31006531). UBE2V1-UBE2N together with TRAF3IP2 E3 ubiquitin ligase mediate 'Lys-63'-linked polyubiquitination of TRAF6, a component of IL17A-mediated signaling pathway.

9606:KCNG4
gene id: 9606:KCNG4
uniprot id: Q32MC1
uniprot id: Q547S7
uniprot id: Q8TDN1
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the potassium channel family. G (TC 1.A.1.2) subfamily. Kv6.4/KCNG4 sub-subfamily.
messages: Cell membrane
messages: Heterotetramer with KCNB1 (PubMed:19074135).
messages: Highly expressed in brain, and at lower levels in liver, small intestine and colon.
messages: Membrane
messages: Potassium channel subunit that does not form functional channels by itself. Can form functional heterotetrameric channels with KCNB1; modulates the delayed rectifier voltage-gated potassium channel activation and deactivation rates of KCNB1 (PubMed:19074135).
messages: The transmembrane segment S4 functions as voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Channel opening and closing is effected by a conformation change that affects the position and orientation of the voltage-sensor paddle formed by S3 and S4 within the membrane. A transmembrane electric field that is positive inside would push the positively charged S4 segment outwards, thereby opening the pore, while a field that is negative inside would pull the S4 segment inwards and close the pore. Changes in the position and orientation of S4 are then transmitted to the activation gate formed by the inner helix bundle via the S4-S5 linker region.

9606:SLC35B1
gene id: 9606:SLC35B1
uniprot id: P78383
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: ATP:ADP antiporter that catalyzes the exchange of ATP and ADP across the endoplasmic reticulum (ER) membrane. Imports ATP from the cytosol to the ER lumen and exports ADP in the opposite direction (PubMed:30154480, PubMed:35041824). Regulates ER energy metabolism and protein biogenesis. Appears to be part of a calcium-dependent ER to cytosol low energy response axis, where calcium efflux from ER to the cytosol triggers ATP import into the ER lumen to maintain sufficient ATP supply. Provides ATP to ER chaperone HSPA5 that drives protein folding and trafficking in the ER (PubMed:30154480, PubMed:35041824). Can transport dATP, UTP or UDP in exchange for ATP, but the physiological relevance of this process remains to be established (PubMed:30154480, PubMed:35041824).
messages: ATP:ADP antiporter.
messages: Belongs to the nucleotide-sugar transporter family. SLC35B subfamily.
messages: Endoplasmic reticulum membrane
messages: The di-lysine motif confers endoplasmic reticulum localization for type I membrane proteins.

9606:RSRC1
gene id: 9606:RSRC1
uniprot id: Q96IZ7
names: Disease Annotation
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cytoplasm
messages: Has a role in alternative splicing and transcription regulation (PubMed:29522154). Involved in both constitutive and alternative pre-mRNA splicing. May have a role in the recognition of the 3' splice site during the second step of splicing.
messages: Interacts (via Arg/Ser-rich domain) with LUC7L3, RBM39 and RSF1.
messages: Nucleus
messages: Nucleus speckle
messages: Phosphorylated.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Widely expressed. Expressed in brain, spinal cord, cerebellum.

9606:OR52E4
gene id: 9606:OR52E4
uniprot id: Q8NGH9
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Odorant receptor.

9606:MRGPRG
gene id: 9606:MRGPRG
uniprot id: Q86SM5
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family. Mas subfamily.
messages: Cell membrane
messages: Orphan receptor. May regulate nociceptor function and/or development, including the sensation or modulation of pain (By similarity).

9606:TSC1
gene id: 9606:TSC1
uniprot id: Q92574
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Component of the TSC-TBC complex (also named Rhebulator complex), composed of 2 molecules of TSC1, 2 molecules of TSC2 and 1 molecule of TBC1D7 (PubMed:9809973, PubMed:9580671, PubMed:10585443, PubMed:12172553, PubMed:12906785, PubMed:16464865, PubMed:17658474, PubMed:28215400, PubMed:15963462, PubMed:22795129, PubMed:24529379, PubMed:26893383, PubMed:33436626). Probably forms a complex composed of chaperones HSP90 and HSP70, co-chaperones STIP1/HOP, CDC37, PPP5C, PTGES3/p23, TSC1 and client protein TSC2 (PubMed:29127155). Forms a complex composed of chaperones HSP90 and HSP70, co-chaperones CDC37, PPP5C, TSC1 and client protein TSC2, CDK4, AKT, RAF1 and NR3C1; this complex does not contain co-chaperones STIP1/HOP and PTGES3/p23 (PubMed:29127155). Forms a complex containing HSP90AA1, TSC1 and TSC2; TSC1 is required to recruit TCS2 to the complex (PubMed:29127155). Interacts (via C-terminus) with the closed form of HSP90AA1 (via the middle domain and TPR repeat-binding motif) (PubMed:29127155). Interacts with DOCK7 (PubMed:15963462). Interacts with FBXW5 (PubMed:18381890). Interacts with WDR45B (PubMed:28561066). Interacts with RPAP3 and URI1 (PubMed:28561026).
messages: Highly expressed in skeletal muscle, followed by heart, brain, placenta, pancreas, lung, liver and kidney (PubMed:9242607). Also expressed in embryonic kidney cells (PubMed:9242607).
messages: Lysosome membrane
messages: Non-catalytic component of the TSC-TBC complex, a multiprotein complex that acts as a negative regulator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolecule biosynthesis to promote cellular biomass generation and growth (PubMed:12172553, PubMed:12906785, PubMed:12271141, PubMed:28215400, PubMed:15340059, PubMed:24529379). The TSC-TBC complex acts as a GTPase-activating protein (GAP) for the small GTPase RHEB, a direct activator of the protein kinase activity of mTORC1 (PubMed:12906785, PubMed:15340059, PubMed:24529379). In absence of nutrients, the TSC-TBC complex inhibits mTORC1, thereby preventing phosphorylation of ribosomal protein S6 kinase (RPS6KB1 and RPS6KB2) and EIF4EBP1 (4E-BP1) by the mTORC1 signaling (PubMed:12271141, PubMed:24529379, PubMed:28215400). The TSC-TBC complex is inactivated in response to nutrients, relieving inhibition of mTORC1 (PubMed:12172553, PubMed:24529379). Within the TSC-TBC complex, TSC1 stabilizes TSC2 and prevents TSC2 self-aggregation (PubMed:10585443, PubMed:28215400). Acts as a tumor suppressor (PubMed:9242607). Involved in microtubule-mediated protein transport via its ability to regulate mTORC1 signaling (By similarity). Also acts as a co-chaperone for HSP90AA1 facilitating HSP90AA1 chaperoning of protein clients such as kinases, TSC2 and glucocorticoid receptor NR3C1 (PubMed:29127155). Increases ATP binding to HSP90AA1 and inhibits HSP90AA1 ATPase activity (PubMed:29127155). Competes with the activating co-chaperone AHSA1 for binding to HSP90AA1, thereby providing a reciprocal regulatory mechanism for chaperoning of client proteins (PubMed:29127155). Recruits TSC2 to HSP90AA1 and stabilizes TSC2 by preventing the interaction between TSC2 and ubiquitin ligase HERC1 (PubMed:16464865, PubMed:29127155).
messages: Phosphorylation at Ser-505 does not affect interaction with TSC2.
messages: The C-terminal putative coiled-coil domain is necessary for interaction with TSC2.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: cytosol

9606:RANBP17
gene id: 9606:RANBP17
uniprot id: Q546R4
uniprot id: Q8IVM9
uniprot id: Q9H2T7
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the exportin family.
messages: Binds to nucleoporins and the GTP-bound form of Ran.
messages: Cytoplasm
messages: Highly expressed in testis, moderately in pancreas and weakly in other tissues studied.
messages: May function as a nuclear transport receptor.
messages: Nucleus
messages: nuclear pore complex

9606:CHD6
gene id: 9606:CHD6
uniprot id: Q8TD26
names: Disease Annotation
names: Function
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Acts as a transcriptional repressor of different viruses including influenza virus or papillomavirus. During influenza virus infection, the viral polymerase complex localizes CHD6 to inactive chromatin where it gets degraded in a proteasome independent-manner.
messages: (Microbial infection) Interacts (via N-terminus) with human papillomavirus protein E8^E2C (via C-terminus); this interaction induces transcriptional repression of the viral genome.
messages: (Microbial infection) Interacts with the influenza A polymerase complex composed fo PB1, PB2 and PA.
messages: A chromosomal aberration disrupting CHD6 has been found in a patient with mild to moderate intellectual disability and minor facial anomalies. Translocation t(18;20)(q21.1;q11.2) with TCF4 producing a CHD6-TCF4 fusion transcript (PubMed:18627065).
messages: Belongs to the SNF2/RAD54 helicase family.
messages: DNA-dependent ATPase that plays a role in chromatin remodeling. Regulates transcription by disrupting nucleosomes in a largely non-sliding manner which strongly increases the accessibility of chromatin (PubMed:28533432). Activates transcription of specific genes in response to oxidative stress through interaction with NFE2L2.
messages: Interacts with NFE2L2; involved in activation of the transcription.
messages: The sequence differs from position 1528 onward for unknown reasons.
messages: Widely expressed.
messages: nucleoplasm

9606:MED22
gene id: 9606:MED22
uniprot id: Q15528
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the Mediator complex subunit 22 family.
messages: Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors.
messages: Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP.
messages: Nucleus

9606:HAMP
gene id: 9606:HAMP
uniprot id: P81172
names: Disease Annotation
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the hepcidin family.
messages: Expression in hepatocytes is induced by LPS stimulus and the induction is mediated by IL6 (PubMed:15124018). Expression is inhibited in presence of TNF (PubMed:15124018).
messages: Has strong antimicrobial activity against E.coli ML35P N.cinerea and weaker against S.epidermidis, S.aureus and group b streptococcus bacteria. Active against the fungus C.albicans. No activity against P.aeruginosa (PubMed:11113131, PubMed:11034317).
messages: Highest expression in liver and to a lesser extent in heart and brain. Low levels in lung, tonsils, salivary gland, trachea, prostate gland, adrenal gland and thyroid gland. Secreted into the urine and blood (PubMed:11034317). Expressed by hepatocytes (PubMed:15124018).
messages: Interacts with SLC40A1; this interaction promotes SLC40A1 rapid ubiquitination.
messages: Liver-produced hormone that constitutes the main circulating regulator of iron absorption and distribution across tissues. Acts by promoting endocytosis and degradation of ferroportin/SLC40A1, leading to the retention of iron in iron-exporting cells and decreased flow of iron into plasma (PubMed:22682227, PubMed:29237594, PubMed:32814342). Controls the major flows of iron into plasma: absorption of dietary iron in the intestine, recycling of iron by macrophages, which phagocytose old erythrocytes and other cells, and mobilization of stored iron from hepatocytes (PubMed:22306005).
messages: Secreted
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:GUCY1A2
gene id: 9606:GUCY1A2
uniprot id: P33402
names: Activity Regulation
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Activated by nitric oxide in the presence of magnesium or manganese ions.
messages: Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.
messages: Cytoplasm
messages: Has guanylyl cyclase on binding to the beta-1 subunit.
messages: Heterodimer of an alpha and a beta chain.
messages: Isoform 1 is expressed in fetal brain, liver, colon, endothelium and testis. Isoform 2 is expressed only in liver, colon and endothelium.
messages: Isoform 2 acts as a negative regulator of guanylyl cyclase activity as it forms non-functional heterodimers with the beta subunits.
messages: There are two types of guanylate cyclases: soluble forms and membrane-associated receptor forms.

9606:MAGEA1
gene id: 9606:MAGEA1
uniprot id: P43355
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cytoplasm
messages: Expressed in many tumors of several types, such as melanoma, head and neck squamous cell carcinoma, lung carcinoma and breast carcinoma, but not in normal tissues except for testes. Never expressed in kidney tumors, leukemias and lymphomas.
messages: Interacts with SNW1 and HDCA1.
messages: May be involved in transcriptional regulation through interaction with SNW1 and recruiting histone deactelyase HDAC1. May inhibit notch intracellular domain (NICD) transactivation. May play a role in embryonal development and tumor transformation or aspects of tumor progression. Antigen recognized on a melanoma by autologous cytolytic T-lymphocytes.
messages: Nucleus

9606:NR1I2
gene id: 9606:NR1I2
uniprot id: F1D8P9
uniprot id: O75469
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the nuclear hormone receptor family.
messages: Belongs to the nuclear hormone receptor family. NR1 subfamily.
messages: Expressed in liver, colon and small intestine.
messages: Heterodimer with RXR. Interacts with NCOA1. Interacts (via domain NR LBD) with CRY1 and CRY2 in a ligand-dependent manner (By similarity).
messages: Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes.
messages: Nucleus

9606:CR1L
gene id: 9606:CR1L
uniprot id: Q2VPA4
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the receptors of complement activation (RCA) family.
messages: Cytoplasm
messages: Expressed in fetal liver and to a lesser extent in fetal spleen and thymus. Expression appears to be limited to hematopoietic and fetal lymphoid tissue.
messages: Interacts with iC4 (methylamine-treated C4) but not for iC3 (methylamine-treated C3).
messages: Membrane
messages: Secreted

9606:TTC39C
gene id: 9606:TTC39C
uniprot id: B7Z3X0
uniprot id: G3V1P2
uniprot id: Q8N584
names: Similarity
messages: Belongs to the TTC39 family.

9606:HYDIN
gene id: 9606:HYDIN
uniprot id: Q4G0P3
names: Disease Annotation
names: Function
names: Miscellaneous
names: Subcellular Location Annotation
names: Subunit
messages: Interacts with KIF9.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Required for ciliary motility.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: cilium
messages: cilium axoneme

9606:KCNQ1
gene id: 9606:KCNQ1
uniprot id: P51787
uniprot id: Q96AI9
names: Disease Annotation
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Abundantly expressed in heart, pancreas, prostate, kidney, small intestine and peripheral blood leukocytes. Less abundant in placenta, lung, spleen, colon, thymus, testis and ovaries.
messages: Apical cell membrane
messages: Basolateral cell membrane
messages: Belongs to the potassium channel family. KQT (TC 1.A.1.15) subfamily. Kv7.1/KCNQ1 sub-subfamily.
messages: Cell membrane
messages: Contaminating sequence. Sequence of unknown origin in the N-terminal part.
messages: Cytoplasmic vesicle membrane
messages: Deubiquitinated by USP2; counteracts the NEDD4L-specific down-regulation of I(Ks) and restores the membrane localization.
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry.
messages: Early endosome
messages: Endoplasmic reticulum
messages: Membrane
messages: Membrane raft
messages: Mutagenesis experiments were carried out by expressing in Xenopus oocytes or COS-7 cells KCNQ1 mutants either individually (homomultimers) or in combination with both wild-type KCNQ1 (mut/wt homomultimers) and minK (heteromultimers).
messages: Non-functional alone but modulatory when coexpressed with the full-length isoform 1.
messages: Phosphorylation at Ser-27 by PKA; increases delayed rectifier potassium channel activity of the KCNQ1-KCNE1 complex through a macromolecular complex that includes PKA, PP1, and the targeting protein AKAP9.
messages: Potassium channel that plays an important role in a number of tissues, including heart, inner ear, stomach and colon (PubMed:10646604, PubMed:25441029). Associates with KCNE beta subunits that modulates current kinetics (PubMed:9312006, PubMed:9108097, PubMed:8900283, PubMed:10646604, PubMed:11101505, PubMed:19687231). Induces a voltage-dependent current by rapidly activating and slowly deactivating potassium-selective outward current (PubMed:9312006, PubMed:9108097, PubMed:8900283, PubMed:10646604, PubMed:11101505, PubMed:25441029). Promotes also a delayed voltage activated potassium current showing outward rectification characteristic (By similarity). During beta-adrenergic receptor stimulation participates in cardiac repolarization by associating with KCNE1 to form the I(Ks) cardiac potassium current that increases the amplitude and slows down the activation kinetics of outward potassium current I(Ks) (By similarity) (PubMed:9312006, PubMed:9108097, PubMed:8900283, PubMed:10646604, PubMed:11101505). Muscarinic agonist oxotremorine-M strongly suppresses KCNQ1/KCNE1 current (PubMed:10713961). When associated with KCNE3, forms the potassium channel that is important for cyclic AMP-stimulated intestinal secretion of chloride ions (PubMed:10646604). This interaction with KCNE3 is reduced by 17beta-estradiol, resulting in the reduction of currents (By similarity). During conditions of increased substrate load, maintains the driving force for proximal tubular and intestinal sodium ions absorption, gastric acid secretion, and cAMP-induced jejunal chloride ions secretion (By similarity). Allows the provision of potassium ions to the luminal membrane of the secretory canaliculus in the resting state as well as during stimulated acid secretion (By similarity). When associated with KCNE2, forms a heterooligomer complex leading to currents with an apparently instantaneous activation, a rapid deactivation process and a linear current-voltage relationship and decreases the ampl…
messages: Tetramer (PubMed:18165683, PubMed:19693805, PubMed:25441029). Heterotetramer with KCNE1; targets to the membrane raft (PubMed:25037568, PubMed:19693805, PubMed:20533308). Interacts (via C-terminus) with CALM; forms a heterooctameric structure (with 4:4 KCNQ1:CALM stoichiometry) in a calcium-independent manner (PubMed:18165683, PubMed:25441029). Interacts with AKAP9; targets protein kinase A (PKA) catalytic and regulatory subunits and protein phosphatase 1 (PP1) to the KCNQ1-KCNE1 complex, allowing PKA-mediated phosphorylation and increase of delayed rectifier potassium channel activity (PubMed:11799244, PubMed:25037568). Interacts with KCNE2; forms a heterooligomer complex that targets to the membrane raft and leading to currents with an apparently instantaneous activation, a rapid deactivation process and a linear current-voltage relationship and decreases the amplitude of the outward current (PubMed:11101505, PubMed:20533308). Interacts with AP2M1; mediates estrogen-induced internalization via clathrin-coated vesicles (PubMed:23529131). Interacts with NEDD4L; promotes internalization and decreases I(Ks) currents (PubMed:23529131, PubMed:22024150). Interacts with USP2; counteracts the NEDD4L-specific down-regulation of I(Ks) and restore plasma membrane localization (PubMed:22024150). Heterotetramer with KCNQ5; has a voltage-gated potassium channel activity (PubMed:24855057). Interacts with KCNE3; alters membrane raft localization (PubMed:20533308). Interacts with KCNE4; impairs KCNQ1 localization in lipid rafts and inhibits voltage-gated potassium channel activity (PubMed:19687231, PubMed:20533308). Interacts with KCNE5; impairs KCNQ1 localization in lipid rafts and only conducts current upon strong and continued depolarization (PubMed:20533308, PubMed:12324418). Interacts with SLC5A3; forms coregulatory channel-transporter complexes that modulate Na(+)-coupled myo-inositol influx through the transporter.
messages: The C-terminal assembly domain promotes self-interactiona; allows functional channel.
messages: The C-terminal coiled-coil domain interacts with a single CALM molecule via the first two membrane-proximal helical regions, with CALM forming a clamp-like structure. Binding of CALM C-terminus to the first helical region is calcium-independent but is essential for assembly of the structure. Binding of CALM N-terminus to the second helical region is calcium-dependent and regulates electrophysiological activity of the channel.
messages: The coiled-coil domain mediates tetramerization.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.
messages: The segment S6 is involved in the inhibition of voltage-gated potassium channel activity by KCNE4.
messages: Ubiquitinated by NEDD4L; promotes internalization (PubMed:22024150). The ubiquitinylated form is internalized through a clathrin-mediated endocytosis by interacting with AP2M1 and is recycled back to the cell membrane via RAB4A and RAB11A (PubMed:23529131).

9606:ST6GALNAC5
gene id: 9606:ST6GALNAC5
uniprot id: Q9BVH7
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the glycosyltransferase 29 family.
messages: Golgi apparatus membrane
messages: Predominantly catalyzes the biosynthesis of ganglioside GD1alpha from GM1b in the brain, by transferring the sialyl group (N-acetyl-alpha-neuraminyl or NeuAc) from CMP-NeuAc to the GalNAc residue on the NeuAc-alpha-2,3-Gal-beta-1,3-GalNAc sequence of GM1b (PubMed:12668675). GD1alpha is a critical molecule in the communication and interaction between neuronal cells and their supportive cells, particularly in brain tissues, and functions as an adhesion molecule in the process of metastasis (By similarity). Also shows activity towards sialyl Lc4Cer (N-acetyl-alpha-neuraminosyl-(2->3)-beta-D-galactosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->3)-beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1<->1')-N-acyl-sphing-4-enine) generating disialyl Lc4Cer, which can lead to the synthesis of disialyl Lewis a (Le(a)), suggested to be a cancer-associated antigen (PubMed:12668675).

9606:CRHBP
gene id: 9606:CRHBP
uniprot id: P24387
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the CRF-binding protein family.
messages: Binds CRF and inactivates it. May prevent inappropriate pituitary-adrenal stimulation in pregnancy.
messages: Secreted

9606:ETFRF1
gene id: 9606:ETFRF1
uniprot id: Q6IPR1
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Acts as a regulator of the electron transfer flavoprotein by promoting the removal of flavin from the ETF holoenzyme (composed of ETFA and ETFB).
messages: Belongs to the complex I LYR family.
messages: Mitochondrion
messages: homotetramer (Probable). Interacts with NDUFAB1 (PubMed:27499296). Interacts with ETFA (PubMed:27499296). Interacts with ETFB (PubMed:27499296).

9606:AJUBA
gene id: 9606:AJUBA
uniprot id: Q96IF1
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: 'Ajuba' means 'curiosity' in Urdu, an Indian dialect.
messages: Adapter or scaffold protein which participates in the assembly of numerous protein complexes and is involved in several cellular processes such as cell fate determination, cytoskeletal organization, repression of gene transcription, mitosis, cell-cell adhesion, cell differentiation, proliferation and migration. Contributes to the linking and/or strengthening of epithelia cell-cell junctions in part by linking adhesive receptors to the actin cytoskeleton. May be involved in signal transduction from cell adhesion sites to the nucleus. Plays an important role in regulation of the kinase activity of AURKA for mitotic commitment. Also a component of the IL-1 signaling pathway modulating IL-1-induced NFKB1 activation by influencing the assembly and activity of the PRKCZ-SQSTM1-TRAF6 multiprotein signaling complex. Functions as an HDAC-dependent corepressor for a subset of GFI1 target genes. Acts as a transcriptional corepressor for SNAI1 and SNAI2/SLUG-dependent repression of E-cadherin transcription. Acts as a hypoxic regulator by bridging an association between the prolyl hydroxylases and VHL enabling efficient degradation of HIF1A. Positively regulates microRNA (miRNA)-mediated gene silencing. Negatively regulates the Hippo signaling pathway and antagonizes phosphorylation of YAP1.
messages: Belongs to the zyxin/ajuba family.
messages: Cell junction
messages: Cell membrane
messages: Interacts with GRB2, PIP5K1B and SLC1A2 (By similarity). Interacts with AURKA; the interaction occurs during mitosis and both proteins are phosphorylated as they form a complex. Interacts with CTNNA1 and with F-actin. Interacts with LATS2; the interaction occurs during mitosis and the complex regulates organization of the spindle apparatus through recruitment of TUBG to the centrosome. Forms a complex with SQSTM1, PRKCZ and TRAF6. Component of the GFI1-AJUBA-HDAC1 repressor complex. Interacts directly (via the LIM domains) with GFI1; the interaction results in the HDAC-dependent corepression of a subset of GFI1 target genes, and is independent of the GFI1 SNAG domain. Interacts with HDAC1, HDAC2 and HDAC3. Interacts with SNAI2/SLUG (via SNAG domain) and SCRT1 (via SNAG domain) (By similarity). Interacts with EIF4E, AGO1, AGO2, DCP2, DDX6, LATS1, LATS2, SAV1, EGLN2/PHD1 and EGLN3/PHD3. Interacts (via LIM domains) with isoform 1 and isoform 3 of VHL. Interacts (via LIM domains) with SNAI1 (via SNAG domain).
messages: LIM region interacts with CTNNA1. The preLIM region binds directly actin filaments.
messages: LIM-2 and LIM-3 domains mediate the interaction with the N-terminal region of AURKA. The association between LATS2 and AJUBA required the second LIM domain of AJUBA.
messages: Nucleus
messages: P-body
messages: Phosphorylated by LATS2 during mitosis. Phosphorylated by AURKA.
messages: centrosome
messages: cytoskeleton

9606:NAT8L
gene id: 9606:NAT8L
uniprot id: Q8N9F0
names: Activity Regulation
names: Disease Annotation
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Aminooxyacetic acid (AOAA) blocks its activity in both cytoplasm and mitochondria.
messages: Belongs to the camello family.
messages: By methamphetamine in brain, via dopamine receptor activation (at protein level).
messages: Catalyzes the synthesis of N-acetylaspartate acid (NAA) from L-aspartate and acetyl-CoA (PubMed:19524112, PubMed:19807691, PubMed:20385109). Promotes dopamine uptake by regulating TNF-alpha expression (By similarity). Attenuates methamphetamine-induced inhibition of dopamine uptake (PubMed:20385109).
messages: Cytoplasm
messages: Endoplasmic reticulum membrane
messages: Expressed in brain.
messages: Microsome membrane
messages: Mitochondrion membrane
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:TSPAN4
gene id: 9606:TSPAN4
uniprot id: A8MVV6
uniprot id: O14817
names: Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the tetraspanin (TM4SF) family.
messages: Expressed in multiple tissues but is absent in brain, lymphoid cells, and platelets.
messages: Forms a complex with integrins.
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: Membrane

9606:ZNF526
gene id: 9606:ZNF526
uniprot id: Q8TF50
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: May be involved in transcriptional regulation.
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Widely expressed.

9606:STRBP
gene id: 9606:STRBP
uniprot id: Q96SI9
names: Function
names: Sequence Caution
names: Subcellular Location Annotation
names: Subunit
messages: Contaminating sequence. Potential poly-A sequence.
messages: Cytoplasm
messages: Interacts with EIF2AK2. Associates with microtubules; it is unsure whether such interaction is direct or indirect.
messages: Involved in spermatogenesis and sperm function. Plays a role in regulation of cell growth. Binds to double-stranded DNA and RNA. Binds most efficiently to poly(I:C) RNA than to poly(dI:dC) DNA. Binds also to single-stranded poly(G) RNA. Binds non-specifically to the mRNA PRM1 3'-UTR and adenovirus VA RNA (By similarity).

9606:SLA2
gene id: 9606:SLA2
uniprot id: Q9H6Q3
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Adapter protein, which negatively regulates T-cell receptor (TCR) signaling. Inhibits T-cell antigen-receptor induced activation of nuclear factor of activated T-cells. May act by linking signaling proteins such as ZAP70 with CBL, leading to a CBL dependent degradation of signaling proteins.
messages: Cell membrane
messages: Cytoplasm
messages: Cytoplasmic vesicle
messages: Interacts (via SH2 domain) with ZAP70 (phosphorylated) and CD3Z (phosphorylated). Interacts (via SH2 domain) with CSF1R (phosphorylated) (By similarity). Interacts (via its C-terminal domain) with CBL (phosphorylated).
messages: Phosphorylated by CSF1R.
messages: Predominantly expressed in immune system, with highest levels in peripheral blood leukocytes. Expressed in spleen, thymus and lymph nodes. Expressed in T-cells as well as in monocytes, and at low level in B-cells. Also detected in placenta, prostate, skin, retina and colon.
messages: Produced by alternative initiation at Met-28 of isoform 1.
messages: Produced by alternative initiation at Met-28 of isoform 2.
messages: The loss of the C-terminal domain partially abolishes the inhibitory function, but can be partially compensated by higher level of protein expression.

9606:SCG5
gene id: 9606:SCG5
uniprot id: P05408
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Acts as a molecular chaperone for PCSK2/PC2, preventing its premature activation in the regulated secretory pathway. Binds to inactive PCSK2 in the endoplasmic reticulum and facilitates its transport from there to later compartments of the secretory pathway where it is proteolytically matured and activated. Also required for cleavage of PCSK2 but does not appear to be involved in its folding. Plays a role in regulating pituitary hormone secretion. The C-terminal peptide inhibits PCSK2 in vitro.
messages: Belongs to the 7B2 family.
messages: Interacts with PCSK2/PC2 early in the secretory pathway. Dissociation occurs at later stages.
messages: Proteolytically cleaved in the Golgi by a furin-like convertase to generate bioactive peptides.
messages: Secreted
messages: Sulfated on tyrosine residues.

9606:NMNAT1
gene id: 9606:NMNAT1
uniprot id: Q9HAN9
names: Activity Regulation
names: Cofactor
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Activity is strongly inhibited by galotannin. Inhibited by P1-(adenosine-5')-P4-(nicotinic-acid-riboside-5')-tetraphosphate (Nap4AD).
messages: Belongs to the eukaryotic NMN adenylyltransferase family.
messages: Catalyzes the formation of NAD(+) from nicotinamide mononucleotide (NMN) and ATP (PubMed:17402747). Can also use the deamidated form; nicotinic acid mononucleotide (NaMN) as substrate with the same efficiency (PubMed:17402747). Can use triazofurin monophosphate (TrMP) as substrate (PubMed:17402747). Also catalyzes the reverse reaction, i.e. the pyrophosphorolytic cleavage of NAD(+) (PubMed:17402747). For the pyrophosphorolytic activity, prefers NAD(+) and NaAD as substrates and degrades NADH, nicotinic acid adenine dinucleotide phosphate (NHD) and nicotinamide guanine dinucleotide (NGD) less effectively (PubMed:17402747). Involved in the synthesis of ATP in the nucleus, together with PARP1, PARG and NUDT5 (PubMed:27257257). Nuclear ATP generation is required for extensive chromatin remodeling events that are energy-consuming (PubMed:27257257). Also acts as a cofactor for glutamate and aspartate ADP-ribosylation by directing PARP1 catalytic activity to glutamate and aspartate residues on histones (By similarity). Fails to cleave phosphorylated dinucleotides NADP(+), NADPH and NaADP(+) (PubMed:17402747). Protects against axonal degeneration following mechanical or toxic insults (By similarity).
messages: Divalent metal cations. Zn(2+) confers higher activity as compared to Mg(2+).
messages: Homohexamer (PubMed:11751893). Interacts with ADPRT/PARP1 (PubMed:11248244).
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Widely expressed with highest levels in skeletal muscle, heart and kidney. Also expressed in the liver pancreas and placenta. Widely expressed throughout the brain.

9606:GPR18
gene id: 9606:GPR18
uniprot id: H9NIM1
uniprot id: Q14330
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Cytoplasmic vesicle membrane
messages: Expressed in midpiece of spermatozoon (at protein level) (PubMed:27572937). Most abundant in testis and spleen (PubMed:16844083). Highly expressed in CD4 and CD8-positive T-cells as well as CD19-positive B-cells (PubMed:16844083).
messages: Receptor for endocannabinoid N-arachidonyl glycine (NAGly) (PubMed:16844083, PubMed:24762058, PubMed:27572937). However, conflicting results about the role of NAGly as an agonist are reported (PubMed:27018161). Can also be activated by plant-derived and synthetic cannabinoid agonists (PubMed:24762058). The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase (PubMed:16844083). May contribute to regulation of the immune system. Is required for normal homeostasis of CD8+ subsets of intraepithelial lymphocytes (IELs) (CD8alphaalpha and CD8alphabeta IELs)in small intstine by supporting preferential migration of CD8alphaalpha T-cells to intraepithelial compartment over lamina propria compartment, and by mediating their reconstitution into small intestine after bone marrow transplant (By similarity). Plays a role in hypotensive responses, mediating reduction in intraocular and blood pressure (By similarity). Mediates NAGly-induced process of reorganization of actin filaments and induction of acrosomal exocytosis (PubMed:27572937).

9606:MS4A5
gene id: 9606:MS4A5
uniprot id: Q9H3V2
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the MS4A family.
messages: Expressed at high level in the testis. Detected also in the pancreas, heart and in the brain.
messages: May be involved in signal transduction as a component of a multimeric receptor complex.
messages: Membrane

9606:ZBTB14
gene id: 9606:ZBTB14
uniprot id: O43829
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: Interacts with ZBTB21.
messages: Nucleus
messages: The BTB/POZ domain seems to direct the protein to discrete regions in the nucleus.
messages: Transcriptional activator of the dopamine transporter (DAT), binding it's promoter at the consensus sequence 5'-CCTGCACAGTTCACGGA-3'. Binds to 5'-d(GCC)(n)-3' trinucleotide repeats in promoter regions and acts as a repressor of the FMR1 gene. Transcriptional repressor of MYC and thymidine kinase promoters.

9606:VAPB
gene id: 9606:VAPB
uniprot id: O95292
uniprot id: Q53XM7
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts (via MSP domain) with hepatitis C virus (HCV) non-structural protein 5A (via disordered domain D3) (PubMed:16227268, PubMed:22720086). Interacts with HCV RNA-directed RNA polymerase (PubMed:16227268).
messages: Belongs to the VAMP-associated protein (VAP) (TC 9.B.17) family.
messages: Endoplasmic reticulum membrane
messages: Endoplasmic reticulum-anchored protein that mediates the formation of contact sites between the endoplasmic (ER) and late endosomes via interaction with STARD3 in a FFAT motif phosphorylation dependent manner (PubMed:33124732). Participates in the endoplasmic reticulum unfolded protein response (UPR) by inducing ERN1/IRE1 activity (PubMed:16891305, PubMed:20940299). Involved in cellular calcium homeostasis regulation (PubMed:22131369).
messages: Homodimer, and heterodimer with VAPA (PubMed:20940299). Interacts with VAMP1 and VAMP2 (PubMed:9920726, PubMed:20940299). Interacts (via MSP domain) with ZFYVE27 (PubMed:21976701, PubMed:19289470). Interacts with RMDN3 (PubMed:22131369). Interacts with KIF5A in a ZFYVE27-dependent manner (PubMed:21976701). Interacts (via MSP domain) with STARD3 (via phospho-FFAT motif) (PubMed:24105263, PubMed:33124732). Interacts with STARD3NL (via FFAT motif) (PubMed:24105263). Interacts with CERT1 (PubMed:16895911). Interacts with PLEKHA3 and SACM1L to form a ternary complex (PubMed:30659099). Interacts with VPS13A (via FFAT motif) (PubMed:30741634). Interacts with RB1CC1 (via phosphorylated FFAT motif), MIGA2 (via phosphorylated FFAT motif), RMDN3 (via phosphorylated FFAT motif), OSBPL1A (via FFAT motif), KCNB1 (via phosphorylated FFAT motif) and KCNB2 (via phosphorylated FFAT motif) (PubMed:33124732).
messages: Membrane
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitous. Isoform 1 predominates.

9606:KCNF1
gene id: 9606:KCNF1
uniprot id: Q9H3M0
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the potassium channel family. F (TC 1.A.1.2) subfamily. Kv5.1/KCNF1 sub-subfamily.
messages: Detected in heart, brain, liver, skeletal muscle, kidney and pancreas.
messages: Heteromultimer with KCNG3, KCNG4 and KCNV2. Interacts with DLG1.
messages: Membrane
messages: Putative voltage-gated potassium channel.
messages: The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.

9606:SHLD2
gene id: 9606:SHLD2
uniprot id: Q86V20
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the SHLD2 family.
messages: Chromosome
messages: Component of the shieldin complex, consisting of SHLD1, SHLD2, SHLD3 and MAD2L2/REV7 (PubMed:29656893, PubMed:29789392). Within the complex, SHLD2 forms a scaffold which interacts with a SHLD3-MAD2L2 subcomplex via its N-terminus, and with SHLD1 via its C-terminus (PubMed:29656893). Interacts with TP53BP1 (PubMed:29789392). Interacts with RIF1 (PubMed:29789392).
messages: Component of the shieldin complex, which plays an important role in repair of DNA double-stranded breaks (DSBs) (PubMed:29656893, PubMed:29789392). During G1 and S phase of the cell cycle, the complex functions downstream of TP53BP1 to promote non-homologous end joining (NHEJ) and suppress DNA end resection (PubMed:29656893, PubMed:29789392). Mediates various NHEJ-dependent processes including immunoglobulin class-switch recombination, and fusion of unprotected telomeres (PubMed:29656893).
messages: In BRCA1-deficient cells, function of the shieldin complex is necessary for sensitivity to camptothecin and the PARP inhibitor olaparib.
messages: Nucleus

9606:SNRPB
gene id: 9606:SNRPB
uniprot id: P14678
uniprot id: Q66K91
names: Disease Annotation
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the snRNP SmB/SmN family.
messages: Core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome (PubMed:11991638, PubMed:10025403, PubMed:19325628, PubMed:21516107, PubMed:25555158, PubMed:26912367, PubMed:28502770, PubMed:28781166, PubMed:28076346). Most spliceosomal snRNPs contain a common set of Sm proteins, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP (PubMed:10025403, PubMed:19325628, PubMed:21516107, PubMed:25555158, PubMed:26912367, PubMed:28502770, PubMed:28781166, PubMed:28076346). Component of the U1 snRNP (PubMed:19325628, PubMed:25555158). The U1 snRNP is composed of the U1 snRNA and the 7 core Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG, and at least three U1 snRNP-specific proteins SNRNP70/U1-70K, SNRPA/U1-A and SNRPC/U1-C (PubMed:19325628, PubMed:25555158). Component of the U4/U6-U5 tri-snRNP complex composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39, plus LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8 (PubMed:26912367). Component of the U7 snRNP complex, or U7 Sm protein core complex, that is composed of the U7 snRNA and at least LSM10, LSM11, SNRPB, SNRPD3, SNRPE, SNRPF and SNRPG; the complex does not contain SNRPD1 and SNRPD2 (PubMed:11574479, PubMed:12975319). Component of the minor spliceosome, which splices U12-type introns (PubMed:15146077, PubMed:33509932). Part of the SMN-Sm complex that contains SMN1, GEMIN2/SIP1, DDX20/GEMIN3, GEMIN4, GEMIN5, GEMIN6, GEMIN7, GEMIN8, STRAP/UNRIP and the Sm proteins SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF and SNRPG; catalyzes core snRNPs assembly (PubMed:12095920, PubMed:18984161, PubMed:16314521). Forms a 6S pICln-Sm complex composed of CLNS1A/pICln, SNRPD1, SNRPD2, SNRPE…
messages: Methylated by PRMT5 (By similarity). Arg-108 and Arg-112 are dimethylated, probably to asymmetric dimethylarginine (PubMed:16087681, Ref.10).
messages: Nucleus
messages: Patients with the autoimmune disease systemic lupus erythematosus (SLE) have autoantibodies directed against some of the individual snRNP polypeptides. The most common autoantigen is called Sm. B/b' bear Sm epitopes.
messages: Plays a role in pre-mRNA splicing as a core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome (PubMed:11991638, PubMed:18984161, PubMed:19325628, PubMed:25555158, PubMed:26912367, PubMed:28502770, PubMed:28781166, PubMed:28076346). Component of both the pre-catalytic spliceosome B complex and activated spliceosome C complexes (PubMed:11991638, PubMed:28502770, PubMed:28781166, PubMed:28076346). As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (PubMed:15146077). As part of the U7 snRNP it is involved in histone pre-mRNA 3'-end processing (PubMed:12975319).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: cytosol

9606:KRTAP3-1
gene id: 9606:KRTAP3-1
uniprot id: Q9BYR8
names: Function
names: Similarity
names: Subunit
messages: Belongs to the KRTAP type 3 family.
messages: In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.
messages: Interacts with hair keratins.

9606:DKK4
gene id: 9606:DKK4
uniprot id: Q9UBT3
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Antagonizes canonical Wnt signaling by inhibiting LRP5/6 interaction with Wnt and by forming a ternary complex with the transmembrane protein KREMEN that promotes internalization of LRP5/6. DKKs play an important role in vertebrate development, where they locally inhibit Wnt regulated processes such as antero-posterior axial patterning, limb development, somitogenesis and eye formation. In the adult, Dkks are implicated in bone formation and bone disease, cancer and Alzheimer disease (By similarity).
messages: Appears to be not glycosylated.
messages: Belongs to the dickkopf family.
messages: Can be proteolytically processed by a furin-like protease.
messages: Expressed in cerebellum, T-cells, esophagus and lung.
messages: Interacts with LRP5 and LRP6.
messages: Secreted
messages: The C-terminal cysteine-rich domain mediates interaction with LRP5 and LRP6.

9606:KPNA2
gene id: 9606:KPNA2
uniprot id: P52292
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts with Epstein-Barr virus EBNA1; this interaction allows the nuclear import of EBNA1.
messages: (Microbial infection) Interacts with HIV-1 Vpr.
messages: (Microbial infection) Interacts with SARS-COV virus ORF6 protein; this interaction blocks the receptor-mediated transport through the nuclear pore.
messages: (Microbial infection) Interacts with SARS-CoV-2 ORF6 protein; this interaction may inhibit IFN-beta production by blocking IRF3 nuclear translocation.
messages: (Microbial infection) Interacts with Zika virus RNA-directed RNA polymerase NS5.
messages: (Microbial infection) Part of a tetrameric complex composed of CRM1, importin alpha/beta dimer and the Venezuelan equine encephalitis virus (VEEV) capsid; this complex blocks the receptor-mediated transport through the nuclear pore.
messages: Belongs to the importin alpha family.
messages: Consists of an N-terminal hydrophilic region, a hydrophobic central region composed of 10 repeats, and a short hydrophilic C-terminus. The N-terminal hydrophilic region contains the importin beta binding domain (IBB domain), which is sufficient for binding importin beta and essential for nuclear protein import.
messages: Cytoplasm
messages: Endoplasmic reticulum membrane
messages: Expressed ubiquitously.
messages: Functions in nuclear protein import as an adapter protein for nuclear receptor KPNB1. Binds specifically and directly to substrates containing either a simple or bipartite NLS motif. Docking of the importin/substrate complex to the nuclear pore complex (NPC) is mediated by KPNB1 through binding to nucleoporin FxFG repeats and the complex is subsequently translocated through the pore by an energy requiring, Ran-dependent mechanism. At the nucleoplasmic side of the NPC, Ran binds to importin-beta and the three components separate and importin-alpha and -beta are re-exported from the nucleus to the cytoplasm where GTP hydrolysis releases Ran from importin. The directionality of nuclear import is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus.
messages: Golgi apparatus membrane
messages: Heterodimer; with KPNB1 (PubMed:17596301). Interacts with ANP32E (By similarity). Component of a complex containing CSE1L, RAN and KPNA2. Interacts directly with CSE1L. Interacts with PLAG1. Interacts with APEX1 (via N-terminus). Interacts with FRG1 (via N-terminus). Interacts with ARL4A, CTNNBL1 and NBN. Interacts with SNAI1 (via zinc fingers) and SNAI2 (via zinc fingers). Interacts with BAG6 (PubMed:29042515). Interacts with AIFM2; this interaction likely mediates the translocation of AIFM2 into the nucleus upon oxidative stress. Interacts with RSL1D1 (PubMed:36647821).
messages: Nucleus
messages: The IBB domain is thought to act as an intrasteric autoregulatory sequence by interacting with the internal autoinhibitory NLS. Binding of KPNB1 probably overlaps the internal NLS and contributes to a high affinity for cytoplasmic NLS-containing cargo substrates. After dissociation of the importin/substrate complex in the nucleus the internal autohibitory NLS contributes to a low affinity for nuclear NLS-containing proteins (By similarity).
messages: The major and minor NLS binding sites are mainly involved in recognition of simple or bipartite NLS motifs. Structurally located within in a helical surface groove they contain several conserved Trp and Asn residues of the corresponding third helices (H3) of ARM repeats which mainly contribute to binding (By similarity).

9606:PDE1B
gene id: 9606:PDE1B
uniprot id: B4DK72
uniprot id: Q01064
names: Activity Regulation
names: Cofactor
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the cyclic nucleotide phosphodiesterase family. PDE1 subfamily.
messages: Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions.
messages: Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions.
messages: Binds 2 divalent metal cations per subunit. Site 2 has a preference for magnesium ions.
messages: Cyclic nucleotide phosphodiesterase with a dual specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes (PubMed:8855339, PubMed:9419816, PubMed:15260978). Has a preference for cGMP as a substrate (PubMed:9419816).
messages: Homodimer.
messages: Type I PDE are activated by the binding of calmodulin in the presence of Ca(2+).
messages: cytosol

9606:BTRC
gene id: 9606:BTRC
uniprot id: Q9Y297
names: Domain
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Interacts with HIV-1 Vpu.
messages: (Microbial infection) Interacts with vaccinia virus A49; this interaction inhibits NF-kappa-B activation.
messages: Cytoplasm
messages: Expressed in epididymis (at protein level).
messages: Homodimer. Self-associates. Component of the SCF(BTRC) complex formed of CUL1, SKP1, RBX1 and a BTRC dimer (PubMed:10066435, PubMed:9990852, PubMed:22017875, PubMed:22017876, PubMed:22017877, PubMed:36608670). Direct interaction with SKP1 occurs via the F-box domain. Interacts with phosphorylated ubiquitination substrates SMAD3 and SMAD4. Interacts with phosphorylated ubiquitination substrates CTNNB1, NFKBIA, NFKBIB, NFKBIE, NFKB1/nuclear factor NF-kappa-B p105 subunit, ATF4, CDC25A, DLG1, FBXO5 and SNAI1; the interaction requires the phosphorylation of the 2 serine residues in the substrate destruction motif D-S-G-X(2,3,4)-S. Binds UBQLN1. Interacts with CDC34 and UBE2R2. Interacts with FBXW11. Interacts with CUL4A and DDB1. Part of a SCF(BTRC)-like complex lacking CUL1, which is associated with phosphorylated NKBIA and RELA; RELA interacts directly with NFKBIA. Interacts with the phosphorylated form of GLI3. Interacts with CLU. Interacts with PER1 (phosphorylated), PER2 (phosphorylated) and PER3. Interacts with phosphorylated ubiquitination substrate CEP68 (PubMed:25704143, PubMed:25503564). Interacts with ZC3H12A; this interaction occurs when ZC3H12A is phosphorylated in a IKBKB/IKKB-dependent manner (By similarity). Interacts with HSF1; this interaction occurs during mitosis and induces HSF1 ubiquitin-dependent degradation, a process inhibited by CDC20 (PubMed:18794143). Interacts with NFE2L1 (By similarity). Interacts with INAVA (PubMed:29420262). Interacts with IL10RA; this interaction leads to IL10RA ubiquitination and subsequent degradation (PubMed:22087322). Interacts with REST (PubMed:18354482). Interacts with KLF4; this interaction leads to KLF4 ubiquitination and subsequent degradation (By similarity).
messages: Nucleus
messages: Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:10066435, PubMed:10497169, PubMed:9990852, PubMed:10644755, PubMed:10835356, PubMed:11238952, PubMed:11359933, PubMed:11158290, PubMed:11994270, PubMed:12791267, PubMed:12902344, PubMed:14603323, PubMed:14681206, PubMed:14988407, PubMed:15448698, PubMed:15917222, PubMed:16371461, PubMed:25503564, PubMed:25704143, PubMed:9859996, PubMed:22017875, PubMed:22017876, PubMed:22017877, PubMed:22087322, PubMed:36608670). Recognizes and binds to phosphorylated target proteins (PubMed:10066435, PubMed:10497169, PubMed:9990852, PubMed:10644755, PubMed:10835356, PubMed:11238952, PubMed:11359933, PubMed:11158290, PubMed:11994270, PubMed:12791267, PubMed:12902344, PubMed:14603323, PubMed:14681206, PubMed:14988407, PubMed:15448698, PubMed:15917222, PubMed:16371461, PubMed:25503564, PubMed:25704143, PubMed:9859996, PubMed:22017875, PubMed:22017876, PubMed:22017877, PubMed:22087322, PubMed:36608670). SCF(BTRC) mediates the ubiquitination of CTNNB1 and participates in Wnt signaling (PubMed:12077367, PubMed:12820959). SCF(BTRC) mediates the ubiquitination of phosphorylated NFKB1, ATF4, CDC25A, DLG1, FBXO5, PER1, SMAD3, SMAD4, SNAI1 and probably NFKB2 (PubMed:10835356, PubMed:11238952, PubMed:14681206, PubMed:14603323). SCF(BTRC) mediates the ubiquitination of NFKBIA, NFKBIB and NFKBIE; the degradation frees the associated NFKB1 to translocate into the nucleus and to activate transcription (PubMed:9859996, PubMed:10066435, PubMed:10497169, PubMed:10644755). Ubiquitination of NFKBIA occurs at 'Lys-21' and 'Lys-22' (PubMed:10066435). The SCF(FBXW11) complex also regulates NF-kappa-B by mediating ubiquitination of phosphorylated NFKB1: specifically ubiquitinates the p105 form of NFKB1, leading to its degradation (PubMed:10835356, PubMed:11158290, PubMed:14673179). SCF(BTRC) mediates the ub…
messages: The N-terminal D domain mediates homodimerization.
messages: Ubiquitinated (PubMed:33110214). Deubiquitinated by OTUD5, promoting its stability (PubMed:33110214).

9606:IQCF1
gene id: 9606:IQCF1
uniprot id: Q8N6M8
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Interacts with calmodulin.
messages: Involved in sperm capacitation and acrosome reaction.
messages: acrosome

9606:NIBAN2
gene id: 9606:NIBAN2
uniprot id: Q96TA1
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
messages: As apoptosis proceeds, degraded via an proteasome-independent pathway, probably by caspases.
messages: Belongs to the Niban family.
messages: May play a role in apoptosis suppression. May promote melanoma cell invasion in vitro.
messages: Membrane
messages: Phosphorylated at Ser-641, Ser-646, Ser-692 and Ser-696 by the BRAF/MKK/ERK signaling cascade. In melanoma cells, the C-terminal phosphorylation may prevent targeting to the plasma membrane.
messages: adherens junction
messages: cytosol

9606:LMBR1
gene id: 9606:LMBR1
uniprot id: Q8WVP7
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the LIMR family.
messages: Membrane
messages: Putative membrane receptor.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The disease is caused by variants affecting the gene represented in this entry. Disease-causing mutations are located in intron 5 of LMBR1. The mutations do not alter normal LMBR1 expression and function, but disrupt a long-range, cis-regulatory element of SHH expression contained in LMBR1 intron 5, known as ZPA regulatory sequence (ZRS).
messages: The disease is caused by variants affecting the gene represented in this entry. Disease-causing mutations are located in intron 5 of LMBR1. The mutations do not alter normal LMBR1 expression and function, but disrupt a long-range, cis-regulatory element of SHH expression contained in LMBR1 intron 5.
messages: The disease is caused by variants affecting the gene represented in this entry. Disease-causing mutations consists of duplications (16-75 kb) involving the ZPA regulatory sequence (ZRS), a SHH long-range cis-regulatory element, located in LMBR1 intron 5. The mutations do not alter normal LMBR1 expression and function, but affect SHH limb expression.
messages: The disease is caused by variants affecting the gene represented in this entry. Disease-causing mutations consists of duplications (89-589 kb) involving the ZPA regulatory sequence (ZRS), a SHH long-range cis-regulatory element, located in LMBR1 intron 5. The mutations do not alter normal LMBR1 expression and function, but affect SHH limb expression.
messages: The gene represented in this entry is involved in disease pathogenesis. Mutations located in intron 5 of LMBR1 disrupt a long-range, cis-regulatory element of SHH expression.
messages: Widely expressed with strongest expression in heart and pancreas.

9606:ZFHX3
gene id: 9606:ZFHX3
uniprot id: Q15911
names: Function
names: PTM
names: Polymorphism
names: Sequence Caution
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Adult brain-derived ZFHX3 is sensitive, but embryonic brain-derived ZFHX3 is resistant to calpain 1-mediated proteolysis.
messages: Cytoplasm
messages: Genetic variations in ZFHX3 are associated with atrial fibrillation and ischemic stroke in individuals of European ancestry.
messages: Interacts with FNBP3 (By similarity). Interacts with ALKBH4 and PIAS3. Interacts with ESR1. Interacts with RUNX3. Interacts with TRIM25. Interacts with SMAD2 and SMAD3.
messages: Not found in normal gastric mucosa but found in gastric carcinoma cells (at protein level). Expression is higher in ER-positive breast tumors than ER-negative breast tumors (at protein level).
messages: Nuclear localization is essential for its sumoylation.
messages: Nucleus
messages: Phosphorylation decreases its sensitivity to calpain-mediated proteolysis.
messages: The sequence differs from that shown due translation of the 5'-UTR region.
messages: Transcriptional regulator which can act as an activator or a repressor. Inhibits the enhancer element of the AFP gene by binding to its AT-rich core sequence. In concert with SMAD-dependent TGF-beta signaling can repress the transcription of AFP via its interaction with SMAD2/3 (PubMed:25105025). Regulates the circadian locomotor rhythms via transcriptional activation of neuropeptidergic genes which are essential for intercellular synchrony and rhythm amplitude in the suprachiasmatic nucleus (SCN) of the brain (By similarity). Regulator of myoblasts differentiation through the binding to the AT-rich sequence of MYF6 promoter and promoter repression (PubMed:11312261). Down-regulates the MUC5AC promoter in gastric cancer (PubMed:17330845). In association with RUNX3, up-regulates CDKN1A promoter activity following TGF-beta stimulation (PubMed:20599712). Inhibits estrogen receptor (ESR1) function by selectively competing with coactivator NCOA3 for binding to ESR1 in ESR1-positive breast cancer cells (PubMed:20720010).
messages: Ubiquitinated, leading to its proteasomal degradation.

9606:MCOLN1
gene id: 9606:MCOLN1
uniprot id: Q9GZU1
names: Activity Regulation
names: Caution
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the transient receptor (TC 1.A.4) family. Polycystin subfamily. MCOLN1 sub-subfamily.
messages: Cell membrane
messages: Channel activity is controlled by multiple regulatory mechanisms in different subcellular compartments. Channel function is transiently modulated by changes in Ca(2+), and inhibited by a reduction of pH; pH changes modify the aggregation state of unitary channels; a negative cooperativity between extracellular/lumenal Ca(2+) and H(+) is suggested (PubMed:12459486, PubMed:28112729). Regulated by phosphoinositides in a compartment-specific manner: in lysosomes activated by PtdIns(3,5)P2 (Phosphatidylinositol 3,5-bisphosphate) and at the plasma membrane inhibited by PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) (PubMed:22733759, PubMed:29019983).
messages: Cytoplasmic vesicle membrane
messages: Homotetramer (PubMed:28112729, PubMed:29019983). Homooligomer (PubMed:14749347). Can heterooligomerize with MCOLN2 or MCOLN3; heteromeric assemblies have different channel properties as compared to the respective homooligomers and may be tissue-specific (PubMed:19885840). Interacts with PDCD6 (PubMed:19864416). Interacts with TMEM163 (PubMed:25130899). Interacts with LAPTM4B (PubMed:21224396).
messages: Late endosome membrane
messages: Lysosome membrane
messages: May contribute to cellular lipase activity within the late endosomal pathway or at the cell surface which may be involved in processes of membrane reshaping and vesiculation, especially the growth of tubular structures. However, it is not known, whether it conveys the enzymatic activity directly, or merely facilitates the activity of an associated phospholipase.
messages: Nonselective cation channel probably playing a role in the regulation of membrane trafficking events and of metal homeostasis (PubMed:11013137, PubMed:12459486, PubMed:15336987, PubMed:14749347, PubMed:29019983, PubMed:27623384). Proposed to play a major role in Ca(2+) release from late endosome and lysosome vesicles to the cytoplasm, which is important for many lysosome-dependent cellular events, including the fusion and trafficking of these organelles, exocytosis and autophagy (PubMed:11013137, PubMed:12459486, PubMed:15336987, PubMed:14749347, PubMed:25720963, PubMed:29019983, PubMed:27623384). Required for efficient uptake of large particles in macrophages in which Ca(2+) release from the lysosomes triggers lysosomal exocytosis. May also play a role in phagosome-lysosome fusion (By similarity). Involved in lactosylceramide trafficking indicative for a role in the regulation of late endocytic membrane fusion/fission events (PubMed:16978393). By mediating lysosomal Ca(2+) release is involved in regulation of mTORC1 signaling and in mTOR/TFEB-dependent lysosomal adaptation to environmental cues such as nutrient levels (PubMed:25720963, PubMed:25733853, PubMed:27787197). Seems to act as lysosomal active oxygen species (ROS) sensor involved in ROS-induced TFEB activation and autophagy (PubMed:27357649). Functions as a Fe(2+) permeable channel in late endosomes and lysosomes (PubMed:18794901). Proposed to play a role in zinc homeostasis probably implicating its association with TMEM163 (PubMed:25130899) In adaptive immunity, TRPML2 and TRPML1 may play redundant roles in the function of the specialized lysosomes of B cells (By similarity).
messages: Palmitoylated; involved in association with membranes.
messages: Phosphorylation by PKA inhibits channel activity. Dephosphorylation increases activity.
messages: Probable cloning artifact.
messages: Proteolytically cleaved probably involving multiple lysosomal proteases including cathepsin B; inhibits lysosomal channel activity (PubMed:16257972).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The most N-terminal extracellular/lumenal domain (referred to as I-II linker or polycystin-mucolipin domain) contributes to a structure with a four-fold rotational symmetry in a tetrameric assembly; the structure contains a central highly electronegative pore with a 14 A diameter. The pore is critical for Ca(2+) and pH regulation. The protruding structure formed by the I-II linkers may contain all the interaction sites with lipids and proteins in the endolysosomal lumen.
messages: There are conflicting results relative to ion selectivity and permeation. Initially outward rectification has been reported which makes the proposed activity as lysosymal Ca(2+) release channel unlikely. Inward rectification has been decribed in later studies supporting the Ca(2+) release activity.
messages: Widely expressed in adult and fetal tissues.
messages: phagocytic cup
messages: phagosome membrane

9606:MNDA
gene id: 9606:MNDA
uniprot id: P41218
names: Domain
names: Function
names: Induction
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cytoplasm
messages: Expressed constitutively in cells of the myeloid lineage. Found in promyelocyte stage cells as well as in all other stage cells including peripheral blood monocytes and granulocytes. Also appears in myeloblast cells in some cases of acute myeloid Leukemia.
messages: Its N-terminal half (200 amino acids) is sufficient for maximum enhancement of YY1 DNA binding and a portion of this sequence is responsible for binding YY1.
messages: May act as a transcriptional activator/repressor in the myeloid lineage. Plays a role in the granulocyte/monocyte cell-specific response to interferon. Stimulates the DNA binding of the transcriptional repressor protein YY1.
messages: Nucleus
messages: Participates in a ternary complex with YY1 and the YY1 target DNA element. Binds nucleolin and nucleophosmin/NPM/B23.
messages: Strongly induced by alpha interferon which selectively affects expression in late stage cells in the monocytic but not the granulocytic lineage. Induced in vitro by dimethylsulfoxide and 1,25 dihydroxyvitamin D3.

9606:WDR25
gene id: 9606:WDR25
uniprot id: Q64LD2
names: Tissue Specificity
messages: Expressed in heart, muscle, testis, ovary, uterus and prostate.

9606:KIF1C
gene id: 9606:KIF1C
uniprot id: O43896
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. Unc-104 subfamily.
messages: Expressed in all tissues examined, with most abundant expression in heart and skeletal muscle.
messages: Monomer. Interacts with BICD2.
messages: Motor required for the retrograde transport of Golgi vesicles to the endoplasmic reticulum. Has a microtubule plus end-directed motility.
messages: Phosphorylated on tyrosine residues.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: cytoskeleton

9606:CCDC172
gene id: 9606:CCDC172
uniprot id: P0C7W6
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the CCDC172 family.
messages: Cytoplasm
messages: May interact with TEKT2.
messages: cilium

9606:SIX2
gene id: 9606:SIX2
uniprot id: Q8TBA2
uniprot id: Q9NPC8
names: Developmental Stage
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the SIX/Sine oculis homeobox family.
messages: Found at 48 dpc in the anterior cranial base with detection concentrated in the sphenoid precursor. Expression is also detected in the pituitary gland.
messages: Interacts with TCF7L2; in a canonical Wnt signaling independent manner; prevents transcription of differentiation genes in cap mesenchyme. Interacts with OSR1; form a strong repressor complex with TCF7L2, TLE2 and TLE3 to prevent the activation of Wnt/beta-catenin target genes in the cap mesenchyme. Interacts with HOXA11, EYA1 and EYA3.
messages: Nucleus
messages: Strongly expressed in skeletal muscle. Expressed in Wilms' tumor and in the cap mesenchyme of fetal kidney (at protein level).
messages: Transcription factor that plays an important role in the development of several organs, including kidney, skull and stomach. During kidney development, maintains cap mesenchyme multipotent nephron progenitor cells in an undifferentiated state by opposing the inductive signals emanating from the ureteric bud and cooperates with WNT9B to promote renewing progenitor cells proliferation. Acts through its interaction with TCF7L2 and OSR1 in a canonical Wnt signaling independent manner preventing transcription of differentiation genes in cap mesenchyme such as WNT4. Also acts independently of OSR1 to activate expression of many cap mesenchyme genes, including itself, GDNF and OSR1. During craniofacial development plays a role in growth and elongation of the cranial base through regulation of chondrocyte differentiation. During stomach organogenesis, controls pyloric sphincter formation and mucosal growth through regulation of a gene network including NKX2-5, BMPR1B, BMP4, SOX9 and GREM1. During branchial arch development, acts to mediate HOXA2 control over the insulin-like growth factor pathway. May also be involved in limb tendon and ligament development (By similarity). Plays a role in cell proliferation and migration.

9606:ILKAP
gene id: 9606:ILKAP
uniprot id: Q9H0C8
names: Activity Regulation
names: Cofactor
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the PP2C family.
messages: Binds 2 magnesium or manganese ions per subunit.
messages: Cytoplasm
messages: Inhibited rather than stimulated by magnesium.
messages: Interacts with ILK. Specific association with ILK is independent of the catalytic activity of either partner.
messages: Protein phosphatase that may play a role in regulation of cell cycle progression via dephosphorylation of its substrates whose appropriate phosphorylation states might be crucial for cell proliferation. Selectively associates with integrin linked kinase (ILK), to modulate cell adhesion and growth factor signaling. Inhibits the ILK-GSK3B signaling axis and may play an important role in inhibiting oncogenic transformation.
messages: Widely expressed. Highest levels expressed in striated muscle. Much lower levels evident in various smooth muscle tissues.

9606:ARHGAP24
gene id: 9606:ARHGAP24
uniprot id: Q8N264
names: Domain
names: Function
names: Induction
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cell projection
messages: Interacts with FLNA.
messages: Isoform 1 is widely expressed with a higher level in kidney. Isoform 2 is mainly expressed in endothelial cells.
messages: Phosphorylated by ROCK, leading to activate the RacGAP activity.
messages: Rho GTPase-activating protein involved in cell polarity, cell morphology and cytoskeletal organization. Acts as a GTPase activator for the Rac-type GTPase by converting it to an inactive GDP-bound state. Controls actin remodeling by inactivating Rac downstream of Rho leading to suppress leading edge protrusion and promotes cell retraction to achieve cellular polarity. Able to suppress RAC1 and CDC42 activity in vitro. Overexpression induces cell rounding with partial or complete disruption of actin stress fibers and formation of membrane ruffles, lamellipodia, and filopodia. Isoform 2 is a vascular cell-specific GAP involved in modulation of angiogenesis.
messages: The coiled coil domain mediates the interaction with FLNA leading to its recruitment to lamellae.
messages: Up-regulated during capillary tube formation in umbilical vein endothelial cells.
messages: adherens junction
messages: cytoskeleton
messages: focal adhesion

9606:IRF2BPL
gene id: 9606:IRF2BPL
uniprot id: Q9H1B7
names: Disease Annotation
names: Function
names: Polymorphism
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Aberrant splicing.
messages: Belongs to the IRF2BP family.
messages: Highly expressed in the heart, moderately in skeletal muscle and pancreas, and weakly in brain, kidney, liver, testis, thyroid gland and lymphocytes.
messages: Interacts with CTNNB1.
messages: Nucleus
messages: Probable E3 ubiquitin protein ligase involved in the proteasome-mediated ubiquitin-dependent degradation of target proteins (PubMed:29374064). Through the degradation of CTNNB1, functions downstream of FOXF2 to negatively regulate the Wnt signaling pathway (PubMed:29374064). Probably plays a role in the development of the central nervous system and in neuronal maintenance (Probable). Also acts as a transcriptional regulator of genes controlling female reproductive function. May play a role in gene transcription by transactivating GNRH1 promoter and repressing PENK promoter (By similarity).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The poly-Gln region is polymorphic; the most frequent allele contained 24 Gln. Stretches of 20-31 Gln are observed in healthy individuals.

9606:GTF2H4
gene id: 9606:GTF2H4
uniprot id: A0A1U9X7S4
uniprot id: Q92759
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the TFB2 family.
messages: Component of the 7-subunit TFIIH core complex composed of XPB/ERCC3, XPD/ERCC2, GTF2H1, GTF2H2, GTF2H3, GTF2H4 and GTF2H5, which is active in NER. The core complex associates with the 3-subunit CDK-activating kinase (CAK) module composed of CCNH/cyclin H, CDK7 and MNAT1 to form the 10-subunit holoenzyme (holo-TFIIH) active in transcription.
messages: Component of the general transcription and DNA repair factor IIH (TFIIH) core complex which is involved in general and transcription-coupled nucleotide excision repair (NER) of damaged DNA.
messages: Component of the general transcription and DNA repair factor IIH (TFIIH) core complex, which is involved in general and transcription-coupled nucleotide excision repair (NER) of damaged DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II. In NER, TFIIH acts by opening DNA around the lesion to allow the excision of the damaged oligonucleotide and its replacement by a new DNA fragment. In transcription, TFIIH has an essential role in transcription initiation. When the pre-initiation complex (PIC) has been established, TFIIH is required for promoter opening and promoter escape. Phosphorylation of the C-terminal tail (CTD) of the largest subunit of RNA polymerase II by the kinase module CAK controls the initiation of transcription.
messages: Nucleus

9606:KRT74
gene id: 9606:KRT74
uniprot id: Q7RTS7
names: Disease Annotation
names: Function
names: Miscellaneous
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Belongs to the intermediate filament family.
messages: Has a role in hair formation. Specific component of keratin intermediate filaments in the inner root sheath (IRS) of the hair follicle (Probable).
messages: Heterotetramer of two type I and two type II keratins.
messages: Highly expressed in hair follicles from scalp. In hair, it is specifically present in the inner root sheath (IRS) of the hair follicle. Present in the IRS Huxley layer, but not in Henle layer or cuticle of the IRS. In the IRS Huxley layer, it is expressed in specialized Huxley cells, termed 'Fluegelzellen, along the area of differentiated Henle cells (at protein level).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: There are two types of cytoskeletal and microfibrillar keratin, I (acidic) and II (neutral to basic) (40-55 and 56-70 kDa, respectively).

9606:SPIDR
gene id: 9606:SPIDR
uniprot id: Q14159
names: Disease Annotation
names: Function
names: Induction
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Up-regulated upon SARS-CoV infection.
messages: Found in a complex, at least composed of BLM, RAD51 and SPIDR; the complex formation is mediated by SPIDR. Interacts (via C-terminal region) with BLM; the interaction is direct. Interacts with RAD51; the interaction is direct. Interacts (via the C-terminal region) with FIGNL1 (via N-terminal one-half region); the interaction is direct.
messages: Nucleus
messages: Plays a role in DNA double-strand break (DBS) repair via homologous recombination (HR). Serves as a scaffolding protein that helps to promote the recruitment of DNA-processing enzymes like the helicase BLM and recombinase RAD51 to site of DNA damage, and hence contributes to maintain genomic integrity.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Up-regulated in vascular endothelial cells treated with IL4.

9606:OXT
gene id: 9606:OXT
uniprot id: P01178
uniprot id: X5D7M6
names: Function
names: Pharmaceutical
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the vasopressin/oxytocin family.
messages: Interacts with oxytocin receptor (Ki=1.5 nM) (PubMed:18174156). Interacts with vasopressin V1aR/AVPR1A (Ki=37 nM), V1bR/AVPR1B (Ki=222 nM) and V2R/AVPR2 receptors (Ki=823 nM) (PubMed:18174156).
messages: Neurophysin 1 specifically binds oxytocin.
messages: Oxytocin causes contraction of the smooth muscle of the uterus and of the mammary gland. Acts by binding to oxytocin receptor (OXTR) (PubMed:18174156).
messages: Oxytocin is available under the names Pitocin (Parke-Davis) and Syntocinon (Sandoz). Used to artificially speed or induce labor.
messages: Secreted

9606:MCM3
gene id: 9606:MCM3
uniprot id: A0A0S2Z4T1
uniprot id: A0A499FHX9
uniprot id: B4DUQ9
uniprot id: P25205
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Acetylated by MCM3AP.
messages: Acts as component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built (PubMed:32453425, PubMed:34694004, PubMed:34700328, PubMed:35585232). The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity (PubMed:32453425). Required for the entry in S phase and for cell division (Probable).
messages: Acts as component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity.
messages: Belongs to the MCM family.
messages: Chromosome
messages: Component of the MCM2-7 complex (PubMed:16899510, PubMed:17296731). The complex forms a toroidal hexameric ring with the proposed subunit order MCM2-MCM6-MCM4-MCM7-MCM3-MCM5 (PubMed:16899510, PubMed:17296731, PubMed:34700328, PubMed:34694004, PubMed:32453425). Component of the CMG helicase complex, a hexameric ring of related MCM2-7 subunits stabilized by CDC45 and the tetrameric GINS complex (PubMed:34700328, PubMed:34694004, PubMed:32453425). Associated with the replication-specific DNA polymerase alpha (By similarity). Interacts with MCMBP (PubMed:17296731). Interacts with ANKRD17 (PubMed:23711367). Interacts with MCM3AP isoform MCM3AP; this interaction leads to MCM3 acetylation (PubMed:9712829, PubMed:11258703, PubMed:12226073).
messages: Component of the MCM2-7 complex.
messages: Early fractionation of eukaryotic MCM proteins yielded a variety of dimeric, trimeric and tetrameric complexes with unclear biological significance. The MCM2-7 hexamer is the proposed physiological active complex.
messages: Nucleus
messages: O-glycosylated (O-GlcNAcylated), in a cell cycle-dependent manner.

9606:SPATA31F1
gene id: 9606:SPATA31F1
uniprot id: B4DY95
uniprot id: Q6ZU69
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the SPATA31 family.
messages: Membrane

9606:JSRP1
gene id: 9606:JSRP1
uniprot id: Q96MG2
names: Caution
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Endoplasmic reticulum membrane
messages: Interacts with CACNA1S, CACNB1 and calsequestrin.
messages: Involved in skeletal muscle excitation/contraction coupling (EC), probably acting as a regulator of the voltage-sensitive calcium channel CACNA1S. EC is a physiological process whereby an electrical signal (depolarization of the plasma membrane) is converted into a chemical signal, a calcium gradient, by the opening of ryanodine receptor calcium release channels. May regulate CACNA1S membrane targeting and activity.
messages: It is uncertain whether Met-1 or Met-3 is the initiator.
messages: Sarcoplasmic reticulum membrane

9606:USP34
gene id: 9606:USP34
uniprot id: Q70CQ2
names: Function
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Belongs to the peptidase C19 family.
messages: Expressed in brain at low level.
messages: Interacts with AXIN1 and AXIN2.
messages: Ubiquitin hydrolase that can remove conjugated ubiquitin from AXIN1 and AXIN2, thereby acting as a regulator of Wnt signaling pathway. Acts as an activator of the Wnt signaling pathway downstream of the beta-catenin destruction complex by deubiquitinating and stabilizing AXIN1 and AXIN2, leading to promote nuclear accumulation of AXIN1 and AXIN2 and positively regulate beta-catenin (CTNBB1)-mediated transcription. Recognizes and hydrolyzes the peptide bond at the C-terminal Gly of ubiquitin. Involved in the processing of poly-ubiquitin precursors as well as that of ubiquitinated proteins.

9606:PCDHGC3
gene id: 9606:PCDHGC3
uniprot id: Q9UN70
names: Function
names: Sequence Caution
names: Subcellular Location Annotation
messages: Cell membrane
messages: Contaminating sequence. The C-terminus matches chromosome 8 region.
messages: Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain.

9606:C15orf61
gene id: 9606:C15orf61
uniprot id: A6NNL5
names: Subcellular Location Annotation
messages: Secreted

9606:ORMDL3
gene id: 9606:ORMDL3
uniprot id: Q8N138
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the ORM family.
messages: Ceramide-sensitive subunit of the serine palmitoyltransferase (SPT) complex, which is also composed of SPTLC1, SPTLC2/3 and SPTSSA/B.
messages: Ceramides bind to ORMDL3 N-terminus and stabilize it in a conformation that physically restricts the accessibility of the substrates to their binding sites in the serine palmitoyltransferase (SPT) complex, hence inhibiting SPT catalytic activity. In the absence of ceramides, the N-terminus is flexible and permits substrate binding, thus liberating SPT from inhibition.
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry. SNPs on 17q21 locus that are associated with childhood asthma also show a consistent and strong association with transcript levels of ORMDL3, indicating that genetic variants regulating ORMDL3 expression are determinants of susceptibility to childhood asthma.
messages: Endoplasmic reticulum membrane
messages: Plays an essential role in the homeostatic regulation of sphingolipid de novo biosynthesis by modulating the activity of the serine palmitoyltransferase (SPT) in response to ceramide levels (PubMed:20182505, PubMed:30700557, PubMed:37308477). When complexed to SPT, the binding of ceramides to its N-terminus stabilizes a conformation that block SPT substrate entry, hence preventing SPT catalytic activity. Through this mechanism, maintains ceramide levels at sufficient concentrations for the production of complex sphingolipids, but which prevents the accumulation of ceramides to levels that trigger apoptosis (PubMed:37308477).
messages: When hydroxylated at Pro-137, ubiquitinated via 'Lys-48'-linkage, leading to proteasomal degradation. In endothelial cells, ORMDL3 proteasomal degradation is controlled by the sphingosine 1-phosphate receptor signaling pathway.
messages: Widely expressed. Expressed in adult and fetal heart, brain, lung, liver, skeletal muscle and kidney. Expressed in adult pancreas and placenta and in fetal spleen and thymus.

9606:ZIC2
gene id: 9606:ZIC2
uniprot id: O95409
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Acts as a transcriptional activator or repressor. Plays important roles in the early stage of organogenesis of the CNS. Activates the transcription of the serotonin transporter SERT in uncrossed ipsilateral retinal ganglion cells (iRGCs) to refine eye-specific projections in primary visual targets. Its transcriptional activity is repressed by MDFIC. Involved in the formation of the ipsilateral retinal projection at the optic chiasm midline. Drives the expression of EPHB1 on ipsilaterally projecting growth cones. Binds to the minimal GLI-consensus sequence 5'-TGGGTGGTC-3'. Associates to the basal SERT promoter region from ventrotemporal retinal segments of retinal embryos.
messages: Belongs to the GLI C2H2-type zinc-finger protein family.
messages: Cytoplasm
messages: Interacts with RNF180. Interacts (via the C2H2-type domains 3, 4 and 5) with MDFIC (via the C2H2-type domains 3, 4 and 5); the interaction reduces its transcriptional activity. Interacts with GLI1 and GLI2 (By similarity). Interacts (via C2H2-type domain 3) with DHX9 (PubMed:17251188).
messages: Nucleus
messages: Phosphorylated.
messages: The C2H2-type 3, 4 and 5 zinc finger domains are necessary for transcription activation.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The poly-His region between amino acids 231-239 of ZIC2 is polymorphic and the number of His can vary from 8 to 12.
messages: Ubiquitinated by RNF180, leading to its degradation.

9606:USP8
gene id: 9606:USP8
uniprot id: P40818
names: Disease Annotation
names: Domain
names: Function
names: Induction
names: PTM
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Interacts with Zika virus non-structural protein 1.
messages: Belongs to the peptidase C19 family.
messages: Cell membrane
messages: Contaminating sequence. Potential poly-A sequence.
messages: Cytoplasm
messages: Endosome membrane
messages: Forms a ternary complex with RNF128 and OTUB1. Interacts (via C-terminal UCH catalytic domain) with OTUB1 isoform 1. Interacts with STAM2 (via SH3 domain). Interacts with DNAJB3, EGFR, EPS15, RASGRF1, RNF41, YWHAE, YWHAG and YWHAZ (By similarity). Interacts with NBR1, RASGRF1, RNF41 and IST1. Associates with the ESCRT-0 complex and with microtubules (By similarity). Interacts with BIRC6/bruce and KIF23/MKLP1.
messages: Hydrolase that can remove conjugated ubiquitin from proteins and therefore plays an important regulatory role at the level of protein turnover by preventing degradation. Converts both 'Lys-48' an 'Lys-63'-linked ubiquitin chains. Catalytic activity is enhanced in the M phase. Involved in cell proliferation. Required to enter into S phase in response to serum stimulation. May regulate T-cell anergy mediated by RNF128 via the formation of a complex containing RNF128 and OTUB1. Probably regulates the stability of STAM2 and RASGRF1. Regulates endosomal ubiquitin dynamics, cargo sorting, membrane traffic at early endosomes, and maintenance of ESCRT-0 stability. The level of protein ubiquitination on endosomes is essential for maintaining the morphology of the organelle. Deubiquitinates EPS15 and controls tyrosine kinase stability. Removes conjugated ubiquitin from EGFR thus regulating EGFR degradation and downstream MAPK signaling. Involved in acrosome biogenesis through interaction with the spermatid ESCRT-0 complex and microtubules. Deubiquitinates BIRC6/bruce and KIF23/MKLP1. Deubiquitinates BACE1 which inhibits BACE1 lysosomal degradation and modulates BACE-mediated APP cleavage and amyloid-beta formation (PubMed:27302062).
messages: Nucleus
messages: Phosphorylation of Ser-718 is essential for interaction with YWHAE and for cytosol localization. Undergoes dephosphorylation at Ser-718 in the M phase. Tyrosine-phosphorylated in its N-terminal half in an EGFR-dependent manner.
messages: The MIT domain is required for endosomal localization, CHMP1B-binding, maintenance of ESCRT-0 stability and EGFR degradation.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The rhodanese domain is sufficient for RNF41-binding.
messages: Ubiquitinated. Inactive form is mostly monoubiquitinated, but polyubiquitination happens too. Ubiquitination is increased in EGF-stimulated cells. Ubiquitination of active form is undetectable, suggesting a possibility that USP8 deubiquitinates itself, thereby regulating its own function (By similarity).
messages: Upon growth stimulation in starved human fibroblasts. Decreases in response to growth arrest induced by cell-cell contact.

9606:PARVG
gene id: 9606:PARVG
uniprot id: Q9HBI0
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the parvin family.
messages: Cell membrane
messages: Expressed predominantly in lymphoid organs, including spleen, thymus, lymph node, bone marrow and peripheral blood leukocytes and moderately in the digestive tract, including stomach, duodenum, jejunum, ileum, ileocecum and appendix, as well as in lung and liver. Also expressed in tumors, but at a lower level than in the corresponding normal tissues.
messages: Interacts with integrin-linked protein kinase and actin.
messages: Probably plays a role in the regulation of cell adhesion and cytoskeleton organization.
messages: cytoskeleton
messages: focal adhesion

9606:NUMBL
gene id: 9606:NUMBL
uniprot id: A0A0C4DGH3
uniprot id: A8K033
uniprot id: B7Z5W0
uniprot id: Q9Y6R0
names: Domain
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Cytoplasm
messages: Interacts (via PTB domain) with MAP3K7IP2 (via C-terminal). Interacts (via C-terminal) with TRAF6 (via TRAF domains). Associates with EPS15 and NOTCH1.
messages: Plays a role in the process of neurogenesis.
messages: Plays a role in the process of neurogenesis. Required throughout embryonic neurogenesis to maintain neural progenitor cells, also called radial glial cells (RGCs), by allowing their daughter cells to choose progenitor over neuronal cell fate. Not required for the proliferation of neural progenitor cells before the onset of embryonic neurogenesis. Also required postnatally in the subventricular zone (SVZ) neurogenesis by regulating SVZ neuroblasts survival and ependymal wall integrity. Negative regulator of NF-kappa-B signaling pathway. The inhibition of NF-kappa-B activation is mediated at least in part, by preventing MAP3K7IP2 to interact with polyubiquitin chains of TRAF6 and RIPK1 and by stimulating the 'Lys-48'-linked polyubiquitination and degradation of TRAF6 in cortical neurons.
messages: The PTB domain is necessary for the inhibition of MAP3K7IP2-mediated activation of NF-kappa-B.

9606:SLC39A14
gene id: 9606:SLC39A14
uniprot id: A0A0S2Z534
uniprot id: Q15043
names: Disease Annotation
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Apical cell membrane
messages: Basolateral cell membrane
messages: Belongs to the ZIP transporter (TC 2.A.5) family.
messages: Cell membrane
messages: Early endosome membrane
messages: Electroneutral transporter of the plasma membrane mediating the cellular uptake of the divalent metal cations zinc, manganese and iron that are important for tissue homeostasis, metabolism, development and immunity (PubMed:15642354, PubMed:27231142, PubMed:29621230). Functions as an energy-dependent symporter, transporting through the membranes an electroneutral complex composed of a divalent metal cation and two bicarbonate anions (By similarity). Beside these endogenous cellular substrates, can also import cadmium a non-essential metal which is cytotoxic and carcinogenic (By similarity). Controls the cellular uptake by the intestinal epithelium of systemic zinc, which is in turn required to maintain tight junctions and the intestinal permeability (By similarity). Modifies the activity of zinc-dependent phosphodiesterases, thereby indirectly regulating G protein-coupled receptor signaling pathways important for gluconeogenesis and chondrocyte differentiation (By similarity). Regulates insulin receptor signaling, glucose uptake, glycogen synthesis and gluconeogenesis in hepatocytes through the zinc-dependent intracellular catabolism of insulin (PubMed:27703010). Through zinc cellular uptake also plays a role in the adaptation of cells to endoplasmic reticulum stress (By similarity). Major manganese transporter of the basolateral membrane of intestinal epithelial cells, it plays a central role in manganese systemic homeostasis through intestinal manganese uptake (PubMed:31028174). Also involved in manganese extracellular uptake by cells of the blood-brain barrier (PubMed:31699897). May also play a role in manganese and zinc homeostasis participating in their elimination from the blood through the hepatobiliary excretion (By similarity). Also functions in the extracellular uptake of free iron. May also function intracellularly and mediate the transport from endosomes to cytosol of iron endocytosed by transferrin (PubMed:20682781). Plays a role in innate immunity by re…
messages: Homotrimer.
messages: Late endosome membrane
messages: Lysosome membrane
messages: Membrane
messages: N-glycosylated. N-glycosylation at Asn-102 is required for iron-regulated extraction of the transporter from membranes and subsequent proteasomal degradation.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The disease is caused by variants affecting the gene represented in this entry. Conditional knockin mice overexpressing Arg-438 variant, which is the mouse equivalent of human variant Leu-441, in osteoblasts have a severe skeletal phenotype marked by a drastic increase in cortical thickness due to an enhanced endosteal bone formation, resembling the underlying pathology in HCI patients.
messages: Ubiquitinated. Ubiquitination occurs upon iron depletion. The ubiquitinated form undergoes proteasomal degradation.
messages: Ubiquitously expressed, with higher expression in liver, pancreas, fetal liver, thyroid gland, left and right ventricle, right atrium and fetal heart (PubMed:7584044, PubMed:15642354, PubMed:20682781). Weakly expressed in spleen, thymus, and peripheral blood leukocytes (PubMed:7584044). Expressed in liver and in brain by large neurons in the globus pallidus, the insular cortex and the dentate nucleus and to a lower extent in the putamen and the caudate nucleus (at protein level) (PubMed:27231142). Expressed in osteoblasts and giant osteoclast-like cells, but not in osteocytes found osteoblastoma and giant cell tumors (at protein level) (PubMed:29621230). Expressed by microvascular capillary endothelial cells that constitute the blood-brain barrier (at protein level) (PubMed:31699897). Expressed by macrophages (PubMed:23052185).
messages: Up-regulated by iron (at protein level) (PubMed:24927598). Down-regulation upon iron depletion occurs through proteasomal degradation of the intracellular pool (PubMed:24927598). Up-regulated by tunicamycin, a drug inducing endoplasmic reticulum stress (at protein level) (PubMed:28673968). Up-regulated by lipopolysaccharide/LPS (PubMed:23052185).
messages: Widely expressed but not detected in brain, heart, skeletal muscle, placenta and fetal skin.

9606:LMTK2
gene id: 9606:LMTK2
uniprot id: Q8IWU2
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Autophosphorylated. Phosphorylated (By similarity).
messages: Belongs to the protein kinase superfamily. Tyr protein kinase family.
messages: Interacts with PPP1C and inhibitor-2.
messages: Mainly expressed in skeletal muscle, and weakly in brain and pancreas.
messages: Membrane
messages: Phosphorylates PPP1C, phosphorylase b and CFTR.

9606:GRIP1
gene id: 9606:GRIP1
uniprot id: Q9Y3R0
names: Disease Annotation
names: Domain
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Cytoplasm
messages: Cytoplasmic vesicle
messages: Endomembrane system
messages: Endoplasmic reticulum membrane
messages: Interacts with EPHA7, EPHB2, KIF5A, KIF5B, KIF5C, GRIA2, GRIA3, GRIPAP1/GRASP1, PPFIA1, PPFIA4, FRAS1, PLCD4, PTPRF and liprins-alpha. Can form homomultimers or heteromultimers with GRIP2. Forms a ternary complex with GRIA2 and CSPG4 (By similarity). Interacts with ATAD1 in an ATP-dependent manner. ATAD1-catalyzed ATP hydrolysis disrupts binding to ATAD1 and to GRIA2 and leads to AMPAR complex disassembly (By similarity). Interacts with EFNB1, EFNB3 and the C-terminal tail of PRLHR. Interacts with SLC30A9 (By similarity). Interacts with BUD23. Forms a complex with NSG1, GRIA2 and STX12; controls the intracellular fate of AMPAR and the endosomal sorting of the GRIA2 subunit toward recycling and membrane targeting. Interacts with NSG1 (By similarity).
messages: May play a role as a localized scaffold for the assembly of a multiprotein signaling complex and as mediator of the trafficking of its binding partners at specific subcellular location in neurons (PubMed:10197531). Through complex formation with NSG1, GRIA2 and STX12 controls the intracellular fate of AMPAR and the endosomal sorting of the GRIA2 subunit toward recycling and membrane targeting (By similarity).
messages: PDZ 6 mediates interaction with the PDZ recognition motif of EFNB1 and EPHB2 and with the C-terminus of PPFIA1 and PPFIA4. PDZ 4 and PDZ 5 mediate interaction with the C-terminus of GRIA2 and GRIA3. PDZ 4, PDZ 5 and PDZ 6 mediate homomultimers. PDZ 7 mediates interaction with PDZ domain of GRASP1. PDZ 7 domain binds CSPG4. PDZ 6 mediates interaction with the C-terminus of liprins-alpha. PDZ 1, PDZ 2 and PDZ 3 mediate interaction with the PDZ-binding motif of FRAS1 (By similarity). PDZ 4 and PDZ 5 mediate interaction with PRLHR.
messages: Perikaryon
messages: Postsynaptic cell membrane
messages: Postsynaptic density
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: dendrite

9606:TRMT11
gene id: 9606:TRMT11
uniprot id: Q7Z4G4
names: Function
names: Similarity
names: Subunit
messages: Belongs to the class I-like SAM-binding methyltransferase superfamily. TRM11 methyltransferase family.
messages: Catalytic subunit of an S-adenosyl-L-methionine-dependent tRNA methyltransferase complex that mediates the methylation of the guanosine nucleotide at position 10 (m2G10) in tRNAs.
messages: Interacts with TRMT112.

9606:BGLAP
gene id: 9606:BGLAP
uniprot id: P02818
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the osteocalcin/matrix Gla protein family.
messages: Bone protein that constitutes 1-2% of the total bone protein, and which acts as a negative regulator of bone formation (PubMed:3019668, PubMed:6967872). Functions to limit bone formation without impairing bone resorption or mineralization (By similarity). It binds strongly to apatite and calcium (PubMed:6967872).
messages: Gamma-carboxyglutamate residues are formed by vitamin K dependent carboxylation by GGCX. These residues are essential for the binding of calcium (By similarity) (PubMed:6967872). Decarboxylation promotes the hormone activity (By similarity).
messages: Secreted
messages: The uncarboxylated form acts as a hormone secreted by osteoblasts, which regulates different cellular processes, such as energy metabolism, male fertility and brain development. Regulates of energy metabolism by acting as a hormone favoring pancreatic beta-cell proliferation, insulin secretion and sensitivity and energy expenditure. Uncarboxylated osteocalcin hormone also promotes testosterone production in the testes: acts as a ligand for G protein-coupled receptor GPRC6A at the surface of Leydig cells, initiating a signaling response that promotes the expression of enzymes required for testosterone synthesis in a CREB-dependent manner. Also acts as a regulator of brain development: osteocalcin hormone crosses the blood-brain barrier and acts as a ligand for GPR158 on neurons, initiating a signaling response that prevents neuronal apoptosis in the hippocampus, favors the synthesis of all monoamine neurotransmitters and inhibits that of gamma-aminobutyric acid (GABA). Osteocalcin also crosses the placenta during pregnancy and maternal osteocalcin is required for fetal brain development.

9606:KLHL3
gene id: 9606:KLHL3
uniprot id: Q9UH77
names: Caution
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the KLHL3 family.
messages: Homodimer (PubMed:28052936). Component of the BCR(KLHL3) E3 ubiquitin ligase complex, at least composed of CUL3 and KLHL3 and RBX1 (PubMed:14528312, PubMed:23387299, PubMed:23453970, PubMed:23576762, PubMed:23573258). Interacts with CLDN8 (By similarity).
messages: Phosphorylation at Ser-433 by PKA or PKC decreases the interaction with WNK1 and WNK4, leading to inhibit their degradation by the BCR(KLHL3) complex (PubMed:26435498, PubMed:27727489, PubMed:25313067, PubMed:30718414). Phosphorylated at Ser-433 by PKC in response to angiotensin II signaling, decreasing ability to promote degradation of WNK1 and WNK4, leading to activation of Na-Cl cotransporter SLC12A3/NCC (PubMed:25313067). Phosphorylation at Ser-433 is increased by insulin (PubMed:26435498). Dephosphorylated at Ser-433 by calcineurin PPP3CA, promoting degradation of WNK1 and WNK4 (PubMed:30718414).
messages: Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a regulator of ion transport in the distal nephron (PubMed:14528312, PubMed:22406640, PubMed:23387299, PubMed:23453970, PubMed:23576762, PubMed:23665031, PubMed:25313067, PubMed:35093948). The BCR(KLHL3) complex acts by mediating ubiquitination and degradation of WNK1 and WNK4, two activators of Na-Cl cotransporter SLC12A3/NCC in distal convoluted tubule cells of kidney, thereby regulating NaCl reabsorption (PubMed:23387299, PubMed:23453970, PubMed:23576762, PubMed:23665031, PubMed:25313067, PubMed:35093948). The BCR(KLHL3) complex also mediates ubiquitination and degradation of WNK3 (PubMed:35179207). The BCR(KLHL3) complex also mediates ubiquitination of CLDN8, a tight-junction protein required for paracellular chloride transport in the kidney, leading to its degradation (By similarity).
messages: The BCR(KLHL3) complex was initially thought to act by mediating ubiquitination of SLC12A3/NCC (PubMed:22406640). However, it was later shown that effects on SLC12A3/NCC are indirect and caused by impaired ubiquitination of WNK4 (PubMed:23387299).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Widely expressed.
messages: cytoskeleton
messages: cytosol

9606:OR6C74
gene id: 9606:OR6C74
uniprot id: A0A126GW13
uniprot id: A6NCV1
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the G-protein coupled receptor 1 family.
messages: Cell membrane
messages: Membrane
messages: Odorant receptor.

9606:FOXD4
gene id: 9606:FOXD4
uniprot id: Q12950
names: Subcellular Location Annotation
messages: Nucleus

9606:PRAMEF15
gene id: 9606:PRAMEF15
uniprot id: P0DUQ1
uniprot id: P0DUQ2
names: Function
names: Similarity
names: Subunit
messages: Belongs to the PRAME family.
messages: Component of a CRL2 E3 ubiquitin-protein ligase complex, also named ECS (Elongin BC-CUL2/5-SOCS-box protein) complex, composed of CUL2, Elongin BC (ELOB and ELOC), RBX1 and substrate-specific adapter PRAMEF9.
messages: Substrate-recognition component of a Cul2-RING (CRL2) E3 ubiquitin-protein ligase complex, which mediates ubiquitination of target proteins, leading to their degradation (PubMed:26138980). The CRL2(PRAMEF9) complex mediates ubiquitination and degradation of truncated MSRB1/SEPX1 selenoproteins produced by failed UGA/Sec decoding (PubMed:26138980).

9606:PAX5
gene id: 9606:PAX5
uniprot id: E7EQT0
uniprot id: E7ERW5
uniprot id: Q02548
names: Developmental Stage
names: Disease Annotation
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Interacts (via N-terminus) with Epstein-Barr virus protein BZLF1 (via C-terminus); this interaction inhibits BZLF1-mediated lytic viral reactivation (PubMed:23678172). Interacts also with EBNA1; this interaction promotes EBNA1-dependent transcription (PubMed:31941781).
messages: (Microbial infection) Plays an essential role in the maintenance of Epstein-Barr virus genome copy number within the host cell by promoting EBNA1/oriP-dependent binding and transcription (PubMed:31941781). Participates also in the inhibition of lytic EBV reactivation by modulating viral BZLF1 activity (PubMed:23678172).
messages: A chromosomal aberration involving PAX5 is a cause of acute lymphoblastic leukemia. Translocation t(9;18)(p13;q11.2) with ZNF521. Translocation t(9;3)(p13;p14.1) with FOXP1. Translocation t(9;12)(p13;p13) with ETV6.
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry.
messages: Expressed at early B-cell differentiation, in the developing CNS and in adult testis.
messages: Interacts with ETS1; this interaction alters PAX5 DNA-binding properties (PubMed:11779502). Binds DNA as a monomer (PubMed:11779502). Interacts with TBP; this interaction allows PAX5 to interact with the basal transcription machinery (PubMed:10197586). Interacts with RB1 (PubMed:10197586). Interacts with TLE4 (PubMed:10811620). Interacts with DAXX (By similarity).
messages: Nucleus
messages: O-glycosylated.
messages: Phosphorylated by SYK. This phosphorylation plays an important role in the abolition of BLIMP1 repression by PAX5 in order to trigger plasma cell differentiation.
messages: Transcription factor that plays an essential role in commitment of lymphoid progenitors to the B-lymphocyte lineage (PubMed:10811620, PubMed:27181361). Fulfills a dual role by repressing B-lineage inappropriate genes and simultaneously activating B-lineage-specific genes (PubMed:10811620, PubMed:27181361). In turn, regulates cell adhesion and migration, induces V(H)-to-D(H)J(H) recombination, facilitates pre-B-cell receptor signaling and promotes development to the mature B-cell stage (PubMed:32612238). Repression of the cohesin-release factor WAPL causes global changes of the chromosomal architecture in pro-B cells to facilitate the generation of a diverse antibody repertoire (PubMed:32612238).

9606:CEP55
gene id: 9606:CEP55
uniprot id: Q53EZ4
names: Disease Annotation
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cleavage furrow
messages: Cytoplasm
messages: Expressed in embryonic brain (PubMed:28264986). Expressed in fetal brain ganglionic eminence, kidney tubules and multinucleate neurons in the temporal cortex (PubMed:28264986). Expressed in adult brain, cerebellum, kidney tubules, intestine and muscles (at protein level) (PubMed:28295209, PubMed:28264986). Widely expressed, mostly in proliferative tissues. Highly expressed in testis. Intermediate levels in adult and fetal thymus, as well as in various cancer cell lines. Low levels in different parts of the digestive tract, bone marrow, lymph nodes, placenta, fetal heart and fetal spleen. Hardly detected in brain.
messages: Homodimer (PubMed:16406728). Interacts (phosphorylated on Ser-425 and Ser-428) with PLK1 (PubMed:16198290). Interacts with AKAP9/CG-NAP; the interaction occurs in interphase and is lost upon mitotic entry (PubMed:16198290). Interacts with PCNT/Kendrin; the interaction occurs in interphase and is lost upon mitotic entry (PubMed:16198290). Directly interacts with PDCD6IP; this interaction is required for PDCD6IP targeting to the midbody; CEP55 binds PDCD6IP in a 2:1 stoichiometry; PDCD6IP competes with TSG101 for the same binding site (PubMed:17853893, PubMed:17556548, PubMed:18641129, PubMed:18948538). Interacts with TSG101; TSG101 competes with PDCD6IP for the same binding site; interaction is required for cytokinesis but not for viral budding (PubMed:17853893, PubMed:17556548, PubMed:18948538). Interacts with MVB12A, VPS37B, VPS37C and VPS28 (PubMed:17853893).
messages: Midbody ring
messages: Plays a role in mitotic exit and cytokinesis (PubMed:16198290, PubMed:17853893). Recruits PDCD6IP and TSG101 to midbody during cytokinesis. Required for successful completion of cytokinesis (PubMed:17853893). Not required for microtubule nucleation (PubMed:16198290). Plays a role in the development of the brain and kidney (PubMed:28264986).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: There is a hierachy of phosphorylation, where both Ser-425 and Ser-428 are phosphorylated at the onset of mitosis, prior to Ser-436. Phosphorylation at Ser-425 and Ser-428 is required for dissociation from the centrosome at the G2/M boundary. Phosphorylation at the 3 sites, Ser-425, Ser-428 and Ser-436, is required for protein function at the final stages of cell division to complete cytokinesis successfully.
messages: centriole
messages: centrosome

9606:CRIP1
gene id: 9606:CRIP1
uniprot id: P50238
names: Function
messages: Seems to have a role in zinc absorption and may function as an intracellular zinc transport protein.

9606:MAGEA10
gene id: 9606:MAGEA10
uniprot id: P43363
names: Function
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Expressed in many tumors of several types, such as melanoma, head and neck squamous cell carcinoma, lung carcinoma and breast carcinoma, but not in normal tissues except for spermatogonia, spermatocytes and placenta.
messages: Not known, though may play a role in embryonal development and tumor transformation or aspects of tumor progression.
messages: Nucleus

9606:DAPK3
gene id: 9606:DAPK3
uniprot id: B3KNJ3
uniprot id: O43293
names: Activity Regulation
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: A sequential activation is proposed: autophosphorylation at consensus sites is leading to dimerization of the catalytic domain stabilized by phosphorylation at Ser-50 and activation segment exchange (producing an active confirmation of both kinase modules in trans) followed by phosphorylation at Thr-180 in the activation segment and at other regulatory sites (Probable). Phosphorylation at Thr-180, Thr-225 and Thr-265 is essential for activity. Oligomerization is required for full enzymatic activity. Inhibited by pyridone-6 (K00225), a potent, ATP-competitive inhibitor.
messages: Belongs to the protein kinase superfamily.
messages: Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. DAP kinase subfamily.
messages: Cytoplasm
messages: Homooligomer in its kinase-active form (homotrimers and homodimers are reported); monomeric in its kinase-inactive form. Homodimerization is required for activation segment autophosphorylation (Probable). Isoform 1 and isoform 2 interact with myosin and PPP1R12A; interaction of isoform 1 with PPP1R12A is inhibited by RhoA dominant negative form. Interacts with NLK, DAXX, STAT3, RHOD (GTP-bound form) and TCP10L. Interacts with PAWR; the interaction is reported conflictingly: according to PubMed:17953487 does not interact with PAWR. Interacts with ULK1; may be a substrate of ULK1.
messages: Nucleus
messages: Serine/threonine kinase which is involved in the regulation of apoptosis, autophagy, transcription, translation and actin cytoskeleton reorganization. Involved in the regulation of smooth muscle contraction. Regulates both type I (caspase-dependent) apoptotic and type II (caspase-independent) autophagic cell deaths signal, depending on the cellular setting. Involved in regulation of starvation-induced autophagy. Regulates myosin phosphorylation in both smooth muscle and non-muscle cells. In smooth muscle, regulates myosin either directly by phosphorylating MYL12B and MYL9 or through inhibition of smooth muscle myosin phosphatase (SMPP1M) via phosphorylation of PPP1R12A; the inhibition of SMPP1M functions to enhance muscle responsiveness to Ca(2+) and promote a contractile state. Phosphorylates MYL12B in non-muscle cells leading to reorganization of actin cytoskeleton. Isoform 2 can phosphorylate myosin, PPP1R12A and MYL12B. Overexpression leads to condensation of actin stress fibers into thick bundles. Involved in actin filament focal adhesion dynamics. The function in both reorganization of actin cytoskeleton and focal adhesion dissolution is modulated by RhoD. Positively regulates canonical Wnt/beta-catenin signaling through interaction with NLK and TCF7L2. Phosphorylates RPL13A on 'Ser-77' upon interferon-gamma activation which is causing RPL13A release from the ribosome, RPL13A association with the GAIT complex and its subsequent involvement in transcript-selective translation inhibition. Enhances transcription from AR-responsive promoters in a hormone- and kinase-dependent manner. Involved in regulation of cell cycle progression and cell proliferation. May be a tumor suppressor.
messages: The internal splice site between exon 8 and the 3' UTR, which yields this truncated isoform, is non-canonical.
messages: The phosphorylation status is critical for kinase activity, oligomerization and intracellular localization. Phosphorylation at Thr-180, Thr-225 and Thr-265 is essential for activity. The phosphorylated form is localized in the cytoplasm promoted by phosphorylation at Thr-299; nuclear translocation or retention is maximal when it is not phosphorylated. Phosphorylation increases the trimeric form, and its dephosphorylation favors a kinase-inactive monomeric form. Both isoform 1 and isoform 2 can undergo autophosphorylation.
messages: Widely expressed. Isoform 1 and isoform 2 are expressed in the bladder smooth muscle.

9606:KMT2D
gene id: 9606:KMT2D
uniprot id: O14686
uniprot id: Q59FG6
uniprot id: Q6PIA1
names: Caution
names: Disease Annotation
names: Domain
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Another protein KMT2B/MLL4, located on chromosome 19, was first named MLL2 (see AC Q9UMN6). Thus, KMT2B/MLL4 is often referred to as MLL2 and vice versa in the literature.
messages: Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. TRX/MLL subfamily.
messages: Component of the MLL2 complex (also named ASCOM complex), at least composed of catalytic subunit KMT2D/MLL2, ASH2L, RBBP5, WDR5, NCOA6, DPY30, KDM6A, PAXIP1/PTIP, PAGR1 and alpha- and beta-tubulin (PubMed:23508102, PubMed:17500065, PubMed:12482968, PubMed:16603732, PubMed:17021013, PubMed:17761849, PubMed:17851529). Forms a core complex with the evolutionary conserved subcomplex WRAD composed of WDR5, RBBP5, ASH2L/ASH2 and DPY30 subunits; WRAD differentially stimulates the methyltransferase activity (PubMed:25561738). Interacts with ESR1; interaction is direct (PubMed:16603732). Interacts (via WIN motif) with WDR5 (PubMed:22665483, PubMed:22266653).
messages: Expressed in most adult tissues, including a variety of hematoipoietic cells, with the exception of the liver.
messages: Histone methyltransferase that catalyzes methyl group transfer from S-adenosyl-L-methionine to the epsilon-amino group of 'Lys-4' of histone H3 (H3K4) (PubMed:25561738). Part of chromatin remodeling machinery predominantly forms H3K4me1 methylation marks at active chromatin sites where transcription and DNA repair take place (PubMed:25561738, PubMed:17500065). Acts as a coactivator for estrogen receptor by being recruited by ESR1, thereby activating transcription (PubMed:16603732).
messages: LXXLL motifs 5 and 6 are essential for the association with ESR1 nuclear receptor.
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: This gene mapped to a chromosomal region involved in duplications and translocations associated with cancer.

9606:MAP3K13
gene id: 9606:MAP3K13
uniprot id: O43283
names: Activity Regulation
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Activated by autophosphorylation and homodimerization.
messages: Activates the JUN N-terminal pathway through activation of the MAP kinase kinase MAP2K7. Acts synergistically with PRDX3 to regulate the activation of NF-kappa-B in the cytosol. This activation is kinase-dependent and involves activating the IKK complex, the IKBKB-containing complex that phosphorylates inhibitors of NF-kappa-B.
messages: Autophosphorylated on serine and threonine residues.
messages: Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.
messages: Cytoplasm
messages: Expressed in the adult brain, liver, placenta and pancreas, with expression strongest in the pancreas.
messages: Homodimer; forms dimers through the leucine-zipper motif. Interacts with the C-terminus of MAPK8IP1 through the kinase catalytic domain. Binds PRDX3. Associates with the IKK complex through the kinase domain.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Membrane

9606:FAM170B
gene id: 9606:FAM170B
uniprot id: A6NMN3
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the FAM170 family.
messages: Exclusively expressed in adult testis.
messages: Interacts with GOPC.
messages: Plays a role in fertilization through the acrosome reaction.
messages: acrosome
messages: acrosome outer membrane

9606:POLG2
gene id: 9606:POLG2
uniprot id: E5KS15
uniprot id: Q9UHN1
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Heterotrimer composed of a catalytic subunit and a homodimer of accessory subunits.
messages: Mitochondrial polymerase processivity subunit. It regulates the polymerase and exonuclease activities promoting processive DNA synthesis. Binds to ss-DNA.
messages: Mitochondrion
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The disease may be caused by variants affecting the gene represented in this entry.

9606:LRIT3
gene id: 9606:LRIT3
uniprot id: Q3SXY7
names: Disease Annotation
names: Function
names: PTM
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Detected in the outer plexiform layer (OPL) of the retina where it localizes to ON-bipolar cells (at protein level).
messages: Endoplasmic reticulum membrane
messages: Glycosylated.
messages: Perikaryon
messages: Plays a role in the synapse formation and synaptic transmission between cone photoreceptor cells and retinal bipolar cells (By similarity). Required for normal transmission of a light-evoked stimulus from the cone photoreceptor cells to the ON-bipolar cells and ON-ganglion cells in the inner retina (PubMed:28334377). Required in retinal ON-bipolar cells for normal localization of the cation channel TRPM1 at dendrite tips (By similarity). Seems to play a specific role in synaptic contacts made by ON-bipolar cells with cone photoreceptor pedicles (By similarity). May also have a role in cone synapse formation (By similarity). Might facilitate FGFR1 exit from the endoplasmic reticulum to the Golgi (PubMed:22673519). Could be a regulator of the FGFRs (PubMed:22673519).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: dendrite

9606:ND6
gene id: 9606:ND6
uniprot id: P03923
uniprot id: U5Z977
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the complex I subunit 6 family.
messages: Core subunit of respiratory chain NADH dehydrogenase (Complex I) which is composed of 45 different subunits.
messages: Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor (PubMed:8644732, PubMed:14595656). Essential for the catalytic activity and assembly of complex I (PubMed:8644732, PubMed:14595656).
messages: Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor. Essential for the catalytic activity and assembly of complex I.
messages: Mitochondrion inner membrane
messages: Mitochondrion membrane
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:ITLN2
gene id: 9606:ITLN2
uniprot id: Q8WWU7
names: Function
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Expressed only in the small intestine.
messages: May play a role in the defense system against pathogens.
messages: Secreted

9606:NUTM2D
gene id: 9606:NUTM2D
uniprot id: A0A075B6P9
uniprot id: Q8IVF1
names: Similarity
messages: Belongs to the NUT family.

9606:PDZD2
gene id: 9606:PDZD2
uniprot id: O15018
names: Miscellaneous
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: A secreted form is produced by caspase-mediated proteolytic cleavage.
messages: Cytoplasm
messages: Endoplasmic reticulum
messages: Interacts with SCN10A, CTNND2 and PKP4.
messages: Isoform 2 is expressed (at protein level) in prostate and many prostate tumors.
messages: May be due to aberrant splicing.
messages: Nucleus
messages: Secreted

9606:TUBA1C
gene id: 9606:TUBA1C
uniprot id: B7Z1K5
uniprot id: F5H5D3
uniprot id: Q9BQE3
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Acetylation of alpha chains at Lys-40 is located inside the microtubule lumen. This modification has been correlated with increased microtubule stability, intracellular transport and ciliary assembly.
messages: Belongs to the tubulin family.
messages: Detyrosination is involved in metaphase plate congression by guiding chromosomes during mitosis: detyrosination promotes interaction with CENPE, promoting pole-proximal transport of chromosomes toward the equator (PubMed:25908662). Detyrosination increases microtubules-dependent mechanotransduction in dystrophic cardiac and skeletal muscle. In cardiomyocytes, detyrosinated microtubules are required to resist to contractile compression during contraction: detyrosination promotes association with desmin (DES) at force-generating sarcomeres, leading to buckled microtubules and mechanical resistance to contraction (By similarity).
messages: Dimer of alpha and beta chains. A typical microtubule is a hollow water-filled tube with an outer diameter of 25 nm and an inner diameter of 15 nM. Alpha-beta heterodimers associate head-to-tail to form protofilaments running lengthwise along the microtubule wall with the beta-tubulin subunit facing the microtubule plus end conferring a structural polarity. Microtubules usually have 13 protofilaments but different protofilament numbers can be found in some organisms and specialized cells.
messages: Methylation of alpha chains at Lys-40 is found in mitotic microtubules and is required for normal mitosis and cytokinesis contributing to genomic stability.
messages: Nitration of Tyr-449 is irreversible and interferes with normal dynein intracellular distribution.
messages: Some glutamate residues at the C-terminus are monoglycylated but not polyglycylated due to the absence of functional TTLL10 in human. Monoglycylation is mainly limited to tubulin incorporated into cilia and flagella axonemes, which is required for their stability and maintenance. Flagella glycylation controls sperm motility. Both polyglutamylation and monoglycylation can coexist on the same protein on adjacent residues, and lowering glycylation levels increases polyglutamylation, and reciprocally.
messages: Some glutamate residues at the C-terminus are polyglutamylated, resulting in polyglutamate chains on the gamma-carboxyl group (PubMed:26875866). Polyglutamylation plays a key role in microtubule severing by spastin (SPAST). SPAST preferentially recognizes and acts on microtubules decorated with short polyglutamate tails: severing activity by SPAST increases as the number of glutamates per tubulin rises from one to eight, but decreases beyond this glutamylation threshold (PubMed:26875866). Glutamylation is also involved in cilia motility (By similarity).
messages: The MREC motif may be critical for tubulin autoregulation.
messages: Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin.
messages: Tyrosination promotes microtubule interaction with CAP-Gly domain-containing proteins such as CLIP1, CLIP2 and DCTN1 (By similarity). Tyrosination regulates the initiation of dynein-dynactin motility via interaction with DCTN1, which brings the dynein-dynactin complex into contact with microtubules (PubMed:26972003). In neurons, tyrosinated tubulins mediate the initiation of retrograde vesicle transport (By similarity).
messages: Undergoes a tyrosination/detyrosination cycle, the cyclic removal and re-addition of a C-terminal tyrosine residue by the enzymes tubulin tyrosine carboxypeptidase (KIAA0895L/MATCAP, VASH1 or VASH2) and tubulin tyrosine ligase (TTL), respectively.
messages: cytoskeleton

9606:ZNF570
gene id: 9606:ZNF570
uniprot id: Q96NI8
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:NINJ1
gene id: 9606:NINJ1
uniprot id: Q92982
names: Activity Regulation
names: Domain
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the ninjurin family.
messages: By nerve injury both in dorsal root ganglion neurons and in Schwann cells.
messages: Cell membrane
messages: Cleaved by MMP9 protease to generate the Secreted ninjurin-1 form.
messages: Composed of 4 alpha helices: 2 hydrophobic transmembrane regions (alpha3 and alpha4) and 2 alpha helices (alpha1 and alpha2) (PubMed:37198476). Alpha1 and alpha2 feature one hydrophobic side and a hydrophilic side (PubMed:37198476). In normal conditions, NINJ1 is inactivated and alpha1 and alpha2 helices are not inserted into the membrane (PubMed:37198476). Following NINJ1 activation, alpha1 and alpha2 helices insert into the membrane and drive NINJ1 oligomerization via interactions between alpha3 and alpha4 and the hydrophobic face of alpha1 from an adjacent subunit (PubMed:37198476). Such structures disrupt membrane integrity and form a lesion through the introduction of the hydrophilic faces of alpha1 and alpha2 into the hydrophobic membrane (PubMed:37198476).
messages: Effector of necroptotic and pyroptotic programmed cell death that mediates plasma membrane rupture (cytolysis) (PubMed:33472215, PubMed:36468682, PubMed:37196676, PubMed:37198476). Acts downstream of Gasdermin (GSDMA, GSDMB, GSDMC, GSDMD, or GSDME) or MLKL during pyroptosis or necroptosis, respectively: oligomerizes in response to death stimuli and promotes plasma membrane rupture by introducing hydrophilic faces of 2 alpha helices into the hydrophobic membrane, leading to release intracellular molecules named damage-associated molecular patterns (DAMPs) that propagate the inflammatory response (PubMed:33472215, PubMed:36468682, PubMed:37196676, PubMed:37198476). Acts as a regulator of Toll-like receptor 4 (TLR4) signaling triggered by lipopolysaccharide (LPS) during systemic inflammation; directly binds LPS (PubMed:26677008). Involved in leukocyte migration during inflammation by promoting transendothelial migration of macrophages via homotypic binding (By similarity). Promotes the migration of monocytes across the brain endothelium to central nervous system inflammatory lesions (PubMed:22162058). Also acts as a homophilic transmembrane adhesion molecule involved in various processes such as axonal growth, cell chemotaxis and angiogenesis (PubMed:8780658, PubMed:9261151, PubMed:33028854). Promotes cell adhesion by mediating homophilic interactions via its extracellular N-terminal adhesion motif (N-NAM) (PubMed:33028854). Involved in the progression of the inflammatory stress by promoting cell-to-cell interactions between immune cells and endothelial cells (PubMed:22162058, PubMed:26677008, PubMed:32147432). Plays a role in nerve regeneration by promoting maturation of Schwann cells (PubMed:8780658, PubMed:9261151). Acts as a regulator of angiogenesis (PubMed:33028854). Promotes the formation of new vessels by mediating the interaction between capillary pericyte cells and endothelial cells (By similarity). Promotes osteoclasts development by enhancing the survival o…
messages: Homooligomer; in response to death stimuli, homooligomerizes into long, highly branched filaments and large, ring-shaped structures in the membrane.
messages: In normal conditions, NINJ1 is inactivated (PubMed:37198476). In response to death stimuli, homooligomerizes and disrupts membrane integrity by introducing the hydrophilic faces of alpha1 and alpha2 helices into the hydrophobic membrane (PubMed:37198476). Homooligomerization and ability to mediate plasma membrane rupture is inhibited by glycine; it is unclear whether glycine directly or indirectly inhibits homooligomerization (PubMed:36468682).
messages: N-linked glycosylation is required for homooligomerization.
messages: Secreted
messages: Secreted form generated by cleavage, which has chemotactic activity (By similarity). Acts as an anti-inflammatory mediator by promoting monocyte recruitment, thereby ameliorating atherosclerosis (PubMed:32883094).
messages: Synaptic cell membrane
messages: Widely expressed in both adult and embryonic tissues, primarily those of epithelial origin.

9606:CFAP61
gene id: 9606:CFAP61
uniprot id: Q8NHU2
names: Function
names: Miscellaneous
names: Subcellular Location Annotation
messages: Created from a fragment entry and may await further characterization.
messages: May regulate cilium motility through its role in the assembly of the axonemal radial spokes.
messages: cilium axoneme

9606:RANBP2
gene id: 9606:RANBP2
uniprot id: P49792
names: Caution
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Interacts with HIV-1 Vpu protein; this interaction allows Vpu to down-regulate BLM sumoylation.
messages: A chromosomal aberration involving RANBP2 is a cause of chromosome 8p11 myeloproliferative syndrome. Translocation t(2;8)(q12;p11) with FGFR1. Chromosome 8p11 myeloproliferative syndrome is characterized by myeloid hyperplasia, eosinophilia and T-cell or B-cell lymphoblastic lymphoma. In general it progresses to acute myeloid leukemia.
messages: Belongs to the RanBP2 E3 ligase family.
messages: Contains FG repeats. FG repeats are interaction sites for karyopherins (importins, exportins) and form probably an affinity gradient, guiding the transport proteins unidirectionally with their cargo through the NPC. FG repeat regions are highly flexible and lack ordered secondary structure. The overall conservation of FG repeats regarding exact sequence, spacing, and repeat unit length is limited.
messages: Despite the presence of a PPIase cyclophilin-type domain, it has probably no peptidyl-prolyl cis-trans isomerase activity.
messages: E3 SUMO-protein ligase which facilitates SUMO1 and SUMO2 conjugation by UBE2I (PubMed:11792325, PubMed:12032081, PubMed:15378033, PubMed:22194619, PubMed:15931224). Involved in transport factor (Ran-GTP, karyopherin)-mediated protein import via the F-G repeat-containing domain which acts as a docking site for substrates (PubMed:7775481). Binds single-stranded RNA (in vitro) (PubMed:7775481). May bind DNA (PubMed:7775481). Component of the nuclear export pathway (PubMed:10078529). Specific docking site for the nuclear export factor exportin-1 (PubMed:10078529). Inhibits EIF4E-dependent mRNA export (PubMed:22902403). Sumoylates PML at 'Lys-490' which is essential for the proper assembly of PML-NB (PubMed:22155184). Recruits BICD2 to the nuclear envelope and cytoplasmic stacks of nuclear pore complex known as annulate lamellae during G2 phase of cell cycle (PubMed:20386726). Probable inactive PPIase with no peptidyl-prolyl cis-trans isomerase activity (PubMed:20676357, PubMed:23353830).
messages: Nucleus
messages: Nucleus envelope
messages: Nucleus membrane
messages: Part of the nuclear pore complex (PubMed:11839768, PubMed:20386726, PubMed:23353830, PubMed:7603572). Forms a complex with NXT1, NXF1 and RANGAP1 (PubMed:14729961). Forms a tight complex with RANBP1 and UBE2I (PubMed:15388847, PubMed:10078529, PubMed:15826666). Interacts with SUMO1 but not SUMO2 (PubMed:15388847, PubMed:10078529, PubMed:15826666). Interacts with PRKN (PubMed:16332688). Interacts with sumoylated RANGAP1 (PubMed:15378033, PubMed:10078529, PubMed:15826666). Interacts with CDCA8 (PubMed:19413330). Interacts with PML (isoform PML-4) (PubMed:22155184). Interacts with BICD2 (PubMed:20386726). Interacts with MCM3AP isoform GANP (PubMed:20005110). Interacts with COX11 (PubMed:34400285).
messages: Polyubiquitinated by PRKN, which leads to proteasomal degradation.
messages: The PPIase cyclophilin-type domain has high structural similarity with PPIA, but has extremely low and barely detectable proline isomerase activity (in vitro) (PubMed:23353830). Only about half of the residues that surround the PPIA active site cleft are conserved.
messages: The disease is caused by variants affecting the gene represented in this entry. Mutations in the RANBP2 gene predispose to IIAE3, but by themselves are insufficient to make the phenotype fully penetrant; additional genetic and environmental factors are required (PubMed:19118815).
messages: The inner channel of the NPC has a different redox environment from the cytoplasm and allows the formation of interchain disulfide bonds between some nucleoporins, the significant increase of these linkages upon oxidative stress reduces the permeability of the NPC.
messages: nuclear pore complex

9606:TTC1
gene id: 9606:TTC1
uniprot id: Q99614
names: Subunit
messages: Interacts with the GAP domain of NF1 (PubMed:8836031). Interacts (via TPR repeats) with HSP90AA1 and HSPA8 (PubMed:15708368).

9606:IFIH1
gene id: 9606:IFIH1
uniprot id: Q9BYX4
names: Disease Annotation
names: Function
names: Induction
names: Miscellaneous
names: PTM
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Cleaved and inactivated by the protease 2A of coxsackievirus B3, poliovirus and enterovirus 71 allowing the virus to disrupt the host type I interferon production.
messages: (Microbial infection) Interacts with Encephalomyocarditis virus protein 2C; this interaction inhibits the induction of the IFN-beta signal pathway.
messages: (Microbial infection) Interacts with SARS-COV-2 virus protein NSP3; the interaction antagonizes ISG15-dependent IFIH1 activation via active de-ISGylation.
messages: (Microbial infection) Interacts with V protein of paramyxoviruses; these interactions prevent IFN-beta induction, and subsequent establishment of an antiviral state.
messages: (Microbial infection) Interacts with herpes simplex virus 1 protein US11; this interaction prevents the interaction of MAVS/IPS1 to IFIH1.
messages: (Microbial infection) Interacts with protease 3C of coxsackievirus A16; this interaction inhibits IFIH1 thereby attenuating type-I IFN production.
messages: Belongs to the helicase family. RLR subfamily.
messages: By interferon (IFN) and TNF.
messages: Contaminating sequence. Potential poly-A sequence.
messages: Cytoplasm
messages: Disease susceptibility may be associated with variants affecting the gene represented in this entry.
messages: During apoptosis, processed into 3 cleavage products. The helicase-containing fragment, once liberated from the CARD domains, translocate from the cytoplasm to the nucleus. The processed protein significantly sensitizes cells to DNA degradation.
messages: IFIH1 is the CADM-140 autoantigen, involved in clinically amyopathic dermatomyositis (CADM). This is a chronic inflammatory disorder that shows typical skin manifestations of dermatomyositis but has no or little evidence of clinical myositis. Anti-CADM-140 antibodies appear to be specific to dermatomyositis, especially CADM. Patients with anti-CADM-140 antibodies frequently develop life-threatening acute progressive interstitial lung disease (ILD).
messages: ISGylated by ISG15. ISGylation increases upon infection with dengue (DENV) or Zika (ZIKV) viruses. ISGylation at Lys-23 and Lys-43 is dependent of dephosphorylation at Ser-88, regulates mitochondrial translocation and oligomerization. Essential for IFIH1/MDA5-mediated cytokine responses and restriction of virus replication.
messages: In HIV-1 infected HeLa-CD4 cells, overexpression of IFIH1 results in a great increase in the level of secreted viral p24 protein.
messages: Innate immune receptor which acts as a cytoplasmic sensor of viral nucleic acids and plays a major role in sensing viral infection and in the activation of a cascade of antiviral responses including the induction of type I interferons and pro-inflammatory cytokines (PubMed:32169843, PubMed:33727702, PubMed:28594402). Its ligands include mRNA lacking 2'-O-methylation at their 5' cap and long-dsRNA (>1 kb in length) (PubMed:22160685). Upon ligand binding it associates with mitochondria antiviral signaling protein (MAVS/IPS1) which activates the IKK-related kinases: TBK1 and IKBKE which phosphorylate interferon regulatory factors: IRF3 and IRF7 which in turn activate transcription of antiviral immunological genes, including interferons (IFNs); IFN-alpha and IFN-beta. Responsible for detecting the Picornaviridae family members such as encephalomyocarditis virus (EMCV), mengo encephalomyocarditis virus (ENMG), and rhinovirus (PubMed:28606988). Detects coronavirus SARS-CoV-2 (PubMed:33440148, PubMed:33514628). Can also detect other viruses such as dengue virus (DENV), west Nile virus (WNV), and reovirus. Also involved in antiviral signaling in response to viruses containing a dsDNA genome, such as vaccinia virus. Plays an important role in amplifying innate immune signaling through recognition of RNA metabolites that are produced during virus infection by ribonuclease L (RNase L). May play an important role in enhancing natural killer cell function and may be involved in growth inhibition and apoptosis in several tumor cell lines.
messages: Mitochondrion
messages: Monomer in the absence of ligands and homodimerizes in the presence of dsRNA ligands. Can assemble into helical or linear polymeric filaments on long dsRNA (PubMed:33727702). Interacts with MAVS/IPS1. Interacts (via the CARD domains) with TKFC, the interaction is inhibited by viral infection (PubMed:17600090). Interacts with PCBP2. Interacts with NLRC5. Interacts with PIAS2-beta. Interacts with DDX60. Interacts with ANKRD17. Interacts with IKBKE (PubMed:17600090). Interacts with ATG5 and ATG12, either as ATG5 and ATG12 monomers or as ATG12-ATG5 conjugates (PubMed:17709747). Interacts with ZCCHC3; leading to activate IFIH1/MDA5 (PubMed:30193849). Interacts with RNF123 (PubMed:27312109). Interacts with DDX3X (PubMed:20127681). Interacts with NOD1; this interaction promotes transcription of antiviral genes and inhibition of viral replication (PubMed:32169843). Interacts with ECSIT; this interaction bridges IFIH1 to the MAVS complex at the mitochondrion (PubMed:25228397).
messages: Nucleus
messages: Phosphorylated at Ser-88. Dephosphorylated by phsophatases PP1; dephosphorylation precedes and is required for ISGylation.
messages: Sumoylated. Sumoylation positively regulates its role in type I interferon induction and is enhanced by PIAS2-beta.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitinated by RNF125, leading to its degradation by the proteasome (PubMed:17460044). USP17/UPS17L2-dependent deubiquitination positively regulates the receptor (PubMed:20368735). Ubiquitinated by TRIM25 via 'Lys-63'-linked ubiquitination, promoting activation of IFIH1/MDA5 (PubMed:30193849). Ubiquitinated by TRIM40 via 'Lys-48'-linked ubiquitination; leading to proteasomal degradation (PubMed:29117565). Ubiquitinated by TRIM65 via 'Lys-63'-linked ubiquitination, promoting activation of IFIH1/MDA5 (PubMed:28594402).
messages: Widely expressed, at a low level. Expression is detected at slightly highest levels in placenta, pancreas and spleen and at barely levels in detectable brain, testis and lung.

9606:ZNF12
gene id: 9606:ZNF12
uniprot id: P17014
names: Developmental Stage
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: Nucleus
messages: Shows a relatively higher expression level in the fetal brain and a lower level in adult. The expression level in liver is highest at 16 weeks of development and declines from 16 to 24 weeks and is lower in adult. Expressed strongly in fetal heart on 18 and 24 weeks, but relatively weakly on the other development stage of embryo, and then reaches a higher level in adult (isoform 3).
messages: Transcriptional repressor which suppresses activation protein 1 (AP-1)- and serum response element (SRE)-mediated transcriptional activity.
messages: Widely expressed in various adult tissues and embryonic developmental stages (isoform 3).

9606:ZNF740
gene id: 9606:ZNF740
uniprot id: Q8NDX6
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:ORC5
gene id: 9606:ORC5
uniprot id: A4D0P7
uniprot id: O43913
uniprot id: Q53FC8
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Abundant in spleen, ovary, prostate, testis, and colon mucosa.
messages: Belongs to the ORC5 family.
messages: Chromosome
messages: Component of ORC, a complex composed of at least 6 subunits: ORC1, ORC2, ORC3, ORC4, ORC5 and ORC6. ORC is regulated in a cell-cycle dependent manner. It is sequentially assembled at the exit from anaphase of mitosis and disassembled as cells enter S phase.
messages: Component of the origin recognition complex (ORC) that binds origins of replication. DNA-binding is ATP-dependent. The specific DNA sequences that define origins of replication have not been identified yet. ORC is required to assemble the pre-replication complex necessary to initiate DNA replication.
messages: Does not interact with ORC2.
messages: Multi-mono-ubiquitinated by OBI1; ubiquitination is important for efficient DNA replication origin site activation. Ubiquitination levels are low in mitotic and early G1-phAse cells and are induced in late G1-/early S-phase, peaking in S-phase and decrease toward the end of the cell cycle.
messages: Nucleus

9606:HBG1
gene id: 9606:HBG1
uniprot id: D9YZU8
uniprot id: P69891
names: Caution
names: Developmental Stage
names: Function
names: Induction
names: PTM
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Acetylation of Gly-2 converts Hb F to the minor Hb F1.
messages: Belongs to the globin family.
messages: By 5-azacytidine.
messages: Expressed until four or five weeks after birth. Detected at very low levels in adults, where it constitutes about 1% of the total hemoglobin. In contrast, the levels of fetal hemoglobin F (two alpha chains and two gamma chains) are increased in children and adults with beta-thalassemia or sickle-cell disease. In cases of homozygous alpha-thalassemia, homotetrameric hemoglobin Bart's is highly expressed and is the predominant form of hemoglobin after 10 weeks of gestation. Its levels increase steadily after 10 weeks of gestation and until birth (at protein level).
messages: Gamma chains make up the fetal hemoglobin F, in combination with alpha chains.
messages: Heterotetramer of two alpha chains and two gamma chains in fetal hemoglobin (Hb F). In the case of deletions affecting one or more of the alpha chains, the excess gamma chains form homotetramers that exhibit neither Bohr effect nor heme-heme cooperativity (hemoglobin Bart's).
messages: Red blood cells.
messages: The modification form of Leu-142 is subject of controversy and could be the artifactual result of sample handling.

9606:PRM3
gene id: 9606:PRM3
uniprot id: Q9NNZ6
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the protamine P3 family.
messages: Chromosome
messages: Nucleus
messages: Protamines substitute for histones in the chromatin of sperm during the haploid phase of spermatogenesis. They compact sperm DNA into a highly condensed, stable and inactive complex (By similarity).

9606:NME6
gene id: 9606:NME6
uniprot id: A0A0C4DG91
uniprot id: A0A2R8Y7V2
uniprot id: C9JQB1
uniprot id: O75414
names: Function
names: Similarity
names: Tissue Specificity
messages: Belongs to the NDK family.
messages: Expressed at a moderately low level in many tissues. Most abundant in kidney, prostate, ovary, intestine, and spleen.
messages: Major role in the synthesis of nucleoside triphosphates other than ATP. The ATP gamma phosphate is transferred to the NDP beta phosphate via a ping-pong mechanism, using a phosphorylated active-site intermediate. Inhibitor of p53-induced apoptosis.

9606:SPESP1
gene id: 9606:SPESP1
uniprot id: Q6UW49
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the SPESP1 family.
messages: Glycosylated. In testis there are two predominant forms of 77- and 67-kDa and a form of 47-kDa, whereas in epididymal sperm from caput, corpus, and cauda there are two forms of 47- and 43-kDa. Testis forms contain complex carbohydrate residues. Epididymal sperm forms are N-glycosylated. Then undergoes significant glycosylation in the testis and that the majority of these glycoconjugates are removed by the time sperm reach the caput epididymis.
messages: Highly expressed in testis, where it is localized in the acrosome of postmeiotic stages of spermiogenesis (round and elongating spermatids and in ejaculated spermatozoa) (at protein level). Poorly expressed in placenta and fetal lung.
messages: Involved in fertilization ability of sperm.
messages: acrosome

9606:HRCT1
gene id: 9606:HRCT1
uniprot id: Q6UXD1
names: Subcellular Location Annotation
messages: Membrane

9606:UBE2J1
gene id: 9606:UBE2J1
uniprot id: Q9Y385
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Promotes Dengue virus RNA replication by negatively regulating IFN-beta signaling and mediating 'Lys-48'-linked ubiquitination on IRF3 (PubMed:30157886).
messages: Belongs to the ubiquitin-conjugating enzyme family.
messages: By Dengue virus infection.
messages: Catalyzes the covalent attachment of ubiquitin to other proteins. Functions in the selective degradation of misfolded membrane proteins from the endoplasmic reticulum (ERAD) and is essential for cells to recover from ER stress (PubMed:28321712). Plays a role in MAPKAPK2-dependent translational control of TNF-alpha synthesis (PubMed:24020373). Acts also as a platform for perinuclear positioning of the endosomal system by mediating ubiquitination of SQSTM1 through interaction with the E3 ubiquitin-protein ligase RNF26 (PubMed:33472082).
messages: Component of the HRD1 complex, which comprises at least SYNV1/HRD1, DERL1/2, FAM8A1, HERPUD1/HERP, OS9, SEL1L and UBE2J1 (PubMed:28827405). Interacts with E3 ligase RNF26 (PubMed:33472082).
messages: Endoplasmic reticulum membrane
messages: Phosphorylated UBE2J1 is rapidly ubiquitinated and subsequently degraded by the proteasome.
messages: Phosphorylated at Ser-184 in a cytosolic stress-dependent manner by MAP kinase p38 MAPKAPK2.

9606:NEK9
gene id: 9606:NEK9
uniprot id: A0A7I2V454
uniprot id: A0A7I2V5R1
uniprot id: Q8TD19
names: Activity Regulation
names: Developmental Stage
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Activated during mitosis by intramolecular autophosphorylation (PubMed:11864968). Activity and autophosphorylation is activated by manganese >> magnesium ions (PubMed:11864968). Sensitive to increasing concentration of detergents (PubMed:11864968). It is not cell-cycle regulated but activity is higher in G0-arrested cells (PubMed:11864968).
messages: Autophosphorylated on serine and threonine residues (PubMed:27153399). When complexed with FACT, exhibits markedly elevated phosphorylation on Thr-210. During mitosis, not phosphorylated on Thr-210. Phosphorylated by CDK1 in vitro (PubMed:14660563).
messages: Belongs to the protein kinase superfamily. NEK Ser/Thr protein kinase family. NIMA subfamily.
messages: Cytoplasm
messages: Dimerizes through its coiled-coil domain.
messages: Expression varied mildly across the cell cycle, with highest expression observed in G1 and stationary-phase cells.
messages: Homodimer; homodimerization is required to activate NEK7 (PubMed:26522158, PubMed:23482567). Binds to Ran GTPase (PubMed:12101123). Has a greater affinity for Ran-GDP over Ran-GTP (PubMed:12101123). Interacts with SSRP1 and SUPT16H, the 2 subunits of the FACT complex (PubMed:14660563). Interacts with DYNLL1; phosphorylation at Ser-944 strongly reduces DYNLL1 binding (PubMed:23482567).
messages: Most abundant in heart, liver, kidney and testis. Also expressed in smooth muscle cells and fibroblasts.
messages: Nucleus
messages: Pleiotropic regulator of mitotic progression, participating in the control of spindle dynamics and chromosome separation (PubMed:12101123, PubMed:12840024, PubMed:14660563, PubMed:19941817). Phosphorylates different histones, myelin basic protein, beta-casein, and BICD2 (PubMed:11864968). Phosphorylates histone H3 on serine and threonine residues and beta-casein on serine residues (PubMed:11864968). Important for G1/S transition and S phase progression (PubMed:12840024, PubMed:14660563, PubMed:19941817). Phosphorylates NEK6 and NEK7 and stimulates their activity by releasing the autoinhibitory functions of Tyr-108 and Tyr-97 respectively (PubMed:12840024, PubMed:14660563, PubMed:19941817, PubMed:26522158).
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:DPEP2
gene id: 9606:DPEP2
uniprot id: Q9H4A9
names: Activity Regulation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the metallo-dependent hydrolases superfamily. Peptidase M19 family.
messages: Dipeptidase that hydrolyzes leukotriene D4 (LTD4) into leukotriene E4 (LTE4) (PubMed:32325220). Hydrolyzes cystinyl-bis-glycine (PubMed:32325220).
messages: Homodimer; disulfide-linked.
messages: Independently of its dipeptidase activity can also modulate macrophage inflammatory response by acting as a regulator of NF-kappaB inflammatory signaling pathway.
messages: Inhibited by L-penicillamine.
messages: Membrane

9606:SDR42E1
gene id: 9606:SDR42E1
uniprot id: Q8WUS8
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the 3-beta-HSD family.
messages: Membrane

9606:EHD2
gene id: 9606:EHD2
uniprot id: Q9NZN4
names: Activity Regulation
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: ATP- and membrane-binding protein that controls membrane reorganization/tubulation upon ATP hydrolysis (By similarity). Plays a role in membrane trafficking between the plasma membrane and endosomes (PubMed:17233914). Important for the internalization of GLUT4. Required for fusion of myoblasts to skeletal muscle myotubes. Required for normal translocation of FER1L5 to the plasma membrane (By similarity). Regulates the equilibrium between cell surface-associated and cell surface-dissociated caveolae by constraining caveolae at the cell membrane (PubMed:25588833).
messages: Belongs to the TRAFAC class dynamin-like GTPase superfamily. Dynamin/Fzo/YdjA family. EHD subfamily.
messages: Cell membrane
messages: Endosome membrane
messages: Highly expressed in heart and moderately expressed in placenta, lung, and skeletal muscle.
messages: Homodimer and homooligomer. Interacts with EHD1. May also interact with EHD3 and EHD4 (PubMed:17233914). Interacts with MYOF (PubMed:18502764). Interacts with EHBP1. Interacts with FER1L5 (via second C2 domain) (By similarity). Interacts with CAV1 in a cholesterol-dependent manner (PubMed:25588833). Interacts (via EH domain) with PACSIN2 (via NPF motifs); this interaction probably stabilizes the caveolae (PubMed:22323287).
messages: The EH domain interacts with Asn-Pro-Phe (NPF) motifs of target proteins.
messages: The very low intrinsic ATPase activity is increased upon interaction with liposomes.
messages: caveola
messages: cytosol

9606:MAP4K3
gene id: 9606:MAP4K3
uniprot id: A8K602
uniprot id: Q8IVH8
names: Function
names: Similarity
names: Subunit
names: Tissue Specificity
messages: Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.
messages: Interacts with SH3GL2. Interaction appears to regulate MAP4K3-mediated JNK activation (By similarity).
messages: May play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway.
messages: Ubiquitously expressed in all tissues examined, with high levels in heart, brain, placenta, skeletal muscle, kidney and pancreas and lower levels in lung and liver.

9606:HAS1
gene id: 9606:HAS1
uniprot id: Q92839
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the NodC/HAS family.
messages: Catalyzes the addition of GlcNAc or GlcUA monosaccharides to the nascent hyaluronan polymer. Therefore, it is essential to hyaluronan synthesis a major component of most extracellular matrices that has a structural role in tissues architectures and regulates cell adhesion, migration and differentiation. This is one of the isozymes catalyzing that reaction. Also able to catalyze the synthesis of chito-oligosaccharide depending on the substrate (By similarity).
messages: Membrane
messages: Widely expressed. Highly expressed in ovary followed by spleen, thymus, prostate, testes and large intestine. Weakly expressed in small intestine.

9606:LGALS9B
gene id: 9606:LGALS9B
uniprot id: Q3B8N2
names: Function
names: Miscellaneous
messages: Binds galactosides.
messages: The LGALS9-like proteins are encoded by a duplicated regions on chromosome 17; there are at least 3 genes coding for galectin-9-like proteins.

9606:ATP11A
gene id: 9606:ATP11A
uniprot id: E9PEJ6
uniprot id: P98196
uniprot id: Q659C3
uniprot id: Q6PJ25
names: Activity Regulation
names: Caution
names: Disease Annotation
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IV subfamily.
messages: Catalytic component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids, phosphatidylserines (PS) and phosphatidylethanolamines (PE), from the outer to the inner leaflet of the plasma membrane (PubMed:25315773, PubMed:25947375, PubMed:26567335, PubMed:29799007, PubMed:30018401). Does not show flippase activity toward phosphatidylcholine (PC) (PubMed:34403372). Contributes to the maintenance of membrane lipid asymmetry with a specific role in morphogenesis of muscle cells. In myoblasts, mediates PS enrichment at the inner leaflet of plasma membrane, triggering PIEZO1-dependent Ca2+ influx and Rho GTPases signal transduction, subsequently leading to the assembly of cortical actomyosin fibers and myotube formation (PubMed:29799007). May be involved in the uptake of farnesyltransferase inhibitor drugs, such as lonafarnib.
messages: Cell membrane
messages: Component of a P4-ATPase flippase complex which consists of a catalytic alpha subunit ATP11A and an accessory beta subunit TMEM30A.
messages: Early endosome
messages: Endoplasmic reticulum membrane
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: Membrane
messages: Overexpression of ATP11A confers resistance to lonafarnib.
messages: Proteolytically cleaved by CASP3.
messages: Recycling endosome
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The flippase activity is inactivated by caspase-mediated cleavage in apoptotic cells, allowing for PS exposure on the cell surface and engulfment of apoptotic cells by macrophages. The ATPase activity is up-regulated by aminophospholipids PS and PE and down-regulated by increasing intracellular Ca2+ levels.
messages: Widely expressed (PubMed:26567335). Expressed in myoblasts (PubMed:29799007).

9606:CCAR2
gene id: 9606:CCAR2
uniprot id: Q8N163
names: Function
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: ATM/ATR-mediated phosphorylation at Thr-454 upon DNA damage promotes binding to SIRT1. Phosphorylation at Thr-454 promotes its sumoylation by switching the binding partner of CCAR2 from SENP1 to PIAS3.
messages: Acetylation at Lys-112 and Lys-215 by KAT8 prevents inhibitory binding to SIRT1 and increases its deacetylase activity.
messages: Component of the DBIRD complex (PubMed:22446626). Interacts with ZNF326/ZIRD; the interaction is direct (PubMed:22446626). Interacts (via N-terminus) with SIRT1, which inhibits the deacetylation of substrates (PubMed:18235501, PubMed:18235502, PubMed:21030595, PubMed:22735644, PubMed:23352644, PubMed:24126058, PubMed:25406032). Interacts (via N-terminus) with SUV39H1; this interaction abolishes the interaction with SIRT1 (PubMed:19218236). Component of a nuclear receptor-mediated transcription complex composed of at least ZNF335, CCAR2 and EMSY; the complex stimulates the transcription of nuclear receptor target genes such as SOX9 and HOXA1 (PubMed:19131338). Within the complex interacts with EMSY and interacts with ZNF335 (via C-terminus) (PubMed:19131338). Components of this complex may associate with components of a histone methylation complex to form a complex at least composed of ZNF335, HCFC1, CCAR2, EMSY, MKI67, RBBP5, ASH2L and WDR5 (PubMed:19131338). Within this complex, interacts with ASH2L (PubMed:19131338). Interacts with NR1D1 (PubMed:23398316). Interacts (via N-terminus) with ESR1 and ESR2 (PubMed:20074560). Interacts (via N-terminus) with HDAC3 (via C-terminus) (PubMed:21030595). Interacts with HDAC1 and MED2F (PubMed:21030595). Interacts with MCC (PubMed:24824780). Interacts (via N-terminus) with NR1H2 and NR1H3 in a ligand-independent manner (PubMed:25661920). Interacts with CSNK2A1 (PubMed:24962073). Interacts (via N-terminus) with p53/TP53 (PubMed:25732823). Interacts (via N-terminus) with BRCA1 (via the BRCT domains) (PubMed:20160719). Interacts (via N-terminus) with CHEK2 (via protein kinase domain) (PubMed:25361978). Interacts with PSEM3 (PubMed:25361978). Interacts (via N-terminus) with PSIA3 and SENP1 (PubMed:25406032). The sumoylated form shows a preferential interaction with SIRT1 as compared to its unmodified form (PubMed:25406032).
messages: Core component of the DBIRD complex, a multiprotein complex that acts at the interface between core mRNP particles and RNA polymerase II (RNAPII) and integrates transcript elongation with the regulation of alternative splicing: the DBIRD complex affects local transcript elongation rates and alternative splicing of a large set of exons embedded in (A + T)-rich DNA regions (PubMed:22446626). Inhibits SIRT1 deacetylase activity leading to increasing levels of p53/TP53 acetylation and p53-mediated apoptosis (PubMed:18235501, PubMed:18235502, PubMed:23352644). Inhibits SUV39H1 methyltransferase activity (PubMed:19218236). Mediates ligand-dependent transcriptional activation by nuclear hormone receptors (PubMed:19131338). Plays a critical role in maintaining genomic stability and cellular integrity following UV-induced genotoxic stress (PubMed:23398316). Regulates the circadian expression of the core clock components NR1D1 and BMAL1 (PubMed:23398316). Enhances the transcriptional repressor activity of NR1D1 through stabilization of NR1D1 protein levels by preventing its ubiquitination and subsequent degradation (PubMed:23398316). Represses the ligand-dependent transcriptional activation function of ESR2 (PubMed:20074560). Acts as a regulator of PCK1 expression and gluconeogenesis by a mechanism that involves, at least in part, both NR1D1 and SIRT1 (PubMed:24415752). Negatively regulates the deacetylase activity of HDAC3 and can alter its subcellular localization (PubMed:21030595). Positively regulates the beta-catenin pathway (canonical Wnt signaling pathway) and is required for MCC-mediated repression of the beta-catenin pathway (PubMed:24824780). Represses ligand-dependent transcriptional activation function of NR1H2 and NR1H3 and inhibits the interaction of SIRT1 with NR1H3 (PubMed:25661920). Plays an important role in tumor suppression through p53/TP53 regulation; stabilizes p53/TP53 by affecting its interaction with ubiquitin ligase MDM2 (PubMed:25732823). Represses …
messages: Cytoplasm
messages: Expressed in gastric carcinoma tissue and the expression gradually increases with the progression of the carcinoma (at protein level). Expressed ubiquitously in normal tissues. Expressed in 84 to 100% of neoplastic breast, lung, and colon tissues.
messages: Genotoxic stress induces its sumoylation and sumoylation promotes the SIRT1-CCAR2 interaction which in turn inhibits SIRT1-mediated deacetylation of p53/TP53. Sumoylation leads to transcriptional activation of p53/TP53 by sequestering SIRT1 from p53/TP53. Desumoylated by SENP1.
messages: Nucleus
messages: spindle

9606:QRICH1
gene id: 9606:QRICH1
uniprot id: Q2TAL8
names: Disease Annotation
names: Domain
names: Function
names: Induction
names: Subcellular Location Annotation
messages: Cell membrane
messages: Cytoplasm
messages: Nucleus
messages: Regulated at the translational level via an alternative ribosome re-initiation mechanism in response to various stress such as endoplasmic reticulum stress or oxidative stress (PubMed:33384352). In the absence of stress, ribosomes re-initiate translation at an inhibitory upstream open reading frames (uORFs) of the QRICH1 transcript, which preclude QRICH1 translation. In response to stress and subsequent EIF2S1/eIF-2-alpha phosphorylation, ribosomes bypass the inhibitory uORFs and re-initiate translation at the QRICH1 coding sequence (PubMed:33384352). Positive autoregulation at the transcriptional level (PubMed:33384352).
messages: The CARD domain may be involved in the regulation of caspase activity in the context of programmed cell death.
messages: The disease may be caused by variants affecting the gene represented in this entry.
messages: Transcriptional regulator that acts as a mediator of the integrated stress response (ISR) through transcriptional control of protein homeostasis under conditions of ER stress (PubMed:33384352). Controls the outcome of the unfolded protein response (UPR) which is an ER-stress response pathway (PubMed:33384352). ER stress induces QRICH1 translation by a ribosome translation re-initiation mechanism in response to EIF2S1/eIF-2-alpha phosphorylation, and stress-induced QRICH1 regulates a transcriptional program associated with protein translation, protein secretion-mediated proteotoxicity and cell death during the terminal UPR (PubMed:33384352). May cooperate with ATF4 transcription factor signaling to regulate ER homeostasis which is critical for cell viability (PubMed:33384352). Up-regulates CASP3/caspase-3 activity in epithelial cells under ER stress. Central regulator of proteotoxicity associated with ER stress-mediated inflammatory diseases in the intestines and liver (PubMed:33384352). Involved in chondrocyte hypertrophy, a process required for normal longitudinal bone growth (PubMed:30281152).

9606:CLSPN
gene id: 9606:CLSPN
uniprot id: Q9HAW4
names: Domain
names: Function
names: Induction
names: PTM
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the claspin family.
messages: Contaminating sequence. Potential poly-A sequence.
messages: Expression peaks at S/G2 phases of the cell cycle.
messages: Interacts (phosphorylation-dependent) with CHEK1; regulates CLSPN function in checkpoint for DNA damage and replication (PubMed:12766152, PubMed:15707391, PubMed:16963448). Interacts with ATR and RAD9A and these interactions are slightly reduced during checkpoint activation (PubMed:12766152). Interacts with BRCA1 and this interaction increases during checkpoint activation (PubMed:15096610). Interacts with TIMELESS; the interaction is required for leading-strand replication (PubMed:17141802, PubMed:35585232, PubMed:34700328, PubMed:34694004). Associates with the MCM2-7 complex and other replisome factors (PubMed:34700328, PubMed:34694004, PubMed:27401717). Interacts (via the acidic patch) with CDC7; the interaction is required for phosphorylation of MCM proteins and CLASPIN by CDC7 (PubMed:27401717). Interacts with PCNA (PubMed:27401717). Interacts with FZR1 (PubMed:18662541).
messages: Nucleus
messages: Phosphorylated. Undergoes ATR-dependent phosphorylation by CHEK1 during activation of DNA replication or damage checkpoints. Phosphorylation by CSNK1G1/CK1 promotes CHEK1 binding (PubMed:12766152, PubMed:15096610, PubMed:16963448, PubMed:21680713). Phosphorylated by CDC7 during DNA replication, phosphorylation inhibits interaction between the acidic patch and N-terminal segments leading to increased binding to DNA and PCNA (PubMed:27401717).
messages: Proteolytically cleaved by caspase-7 (CASP7) in response to apoptosis, leading to its inactivation.
messages: Required for checkpoint mediated cell cycle arrest in response to inhibition of DNA replication or to DNA damage induced by both ionizing and UV irradiation (PubMed:12766152, PubMed:15190204, PubMed:15707391, PubMed:16123041). Adapter protein which binds to BRCA1 and the checkpoint kinase CHEK1 and facilitates the ATR-dependent phosphorylation of both proteins (PubMed:12766152, PubMed:15707391, PubMed:15096610, PubMed:16123041). Also required to maintain normal rates of replication fork progression during unperturbed DNA replication. Binds directly to DNA, with particular affinity for branched or forked molecules and interacts with multiple protein components of the replisome such as the MCM2-7 complex and TIMELESS (PubMed:15226314, PubMed:35585232, PubMed:34694004). Important for initiation of DNA replication, recruits kinase CDC7 to phosphorylate MCM2-7 components (PubMed:27401717).
messages: The C-terminus of the protein contains 3 potential CHEK1-binding motifs (CKB motifs). Potential phosphorylation sites within CKB motif 1 and CKB motif 2 are required for interaction with CHEK1.
messages: The acidic patch region is required for normal DNA replication. Interacts with the N-terminal segments and inhibits binding to DNA and PCNA. Mediates the interaction with the kinase CDC7 as well as some replisome factors and DNA polymerases.
messages: Ubiquitinated by the anaphase promoting complex/cyclosome (APC/C) during G1 phase, leading to its degradation by the proteasome. Ubiquitination is mediated via its interaction with FZR1/CDH1. Following DNA damage, it is deubiquitinated by USP28 in G2 phase, preventing its degradation.

9606:TMEM63A
gene id: 9606:TMEM63A
uniprot id: O94886
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Acts as an osmosensitive calcium-permeable cation channel (PubMed:30382938, PubMed:31587869). Mechanosensitive ion channel that converts mechanical stimuli into a flow of ion (PubMed:30382938, PubMed:31587869).
messages: Belongs to the CSC1 (TC 1.A.17) family.
messages: Cell membrane
messages: Lysosome membrane
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:CNIH2
gene id: 9606:CNIH2
uniprot id: Q6PI25
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acts as an auxiliary subunit for AMPA-selective glutamate receptors (AMPARs). Found in a complex with GRIA1, GRIA2, GRIA3, GRIA4, CNIH3, CACNG2, CACNG3, CACNG4, CACNG5, CACNG7 and CACNG8 (By similarity). Interacts with CACGN8 (By similarity). Interacts with GRIA1.
messages: Belongs to the cornichon family.
messages: Endoplasmic reticulum membrane
messages: Expression is up-regulated in dorsolateral prefrontal cortex of patients with schizophrenia (postmortem brain study).
messages: Postsynaptic cell membrane
messages: Postsynaptic density
messages: Regulates the trafficking and gating properties of AMPA-selective glutamate receptors (AMPARs). Promotes their targeting to the cell membrane and synapses and modulates their gating properties by regulating their rates of activation, deactivation and desensitization. Blocks CACNG8-mediated resensitization of AMPA receptors.
messages: dendrite
messages: dendritic spine

9606:ZSCAN32
gene id: 9606:ZSCAN32
uniprot id: Q9NX65
names: Function
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: Contaminating sequence. Potential poly-A sequence starting in position 426.
messages: May be involved in transcriptional regulation.
messages: Nucleus
messages: The cDNA sequence has been translated in the reverse direction.

9606:SLC38A6
gene id: 9606:SLC38A6
uniprot id: Q8IZM9
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Amino acid transporter with an apparent selectivity for L-glutamine and L-glutamate. May facilitate glutamine uptake in excitatory neurons. The transport mechanism remains to be elucidated.
messages: Belongs to the amino acid/polyamine transporter 2 family.
messages: Cell membrane
messages: Synapse

9606:FCGR1A
gene id: 9606:FCGR1A
uniprot id: P12314
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the immunoglobulin superfamily. FCGR1 family.
messages: Cell membrane
messages: High affinity receptor for the Fc region of immunoglobulins gamma. Functions in both innate and adaptive immune responses. Mediates IgG effector functions on monocytes triggering antibody-dependent cellular cytotoxicity (ADCC) of virus-infected cells.
messages: Interacts with IGHG1 (PubMed:11711607). Interacts with FCERG1; forms a functional signaling complex. Interacts with FLNA; prevents FCGR1A degradation. Interacts with EPB41L2, LAT and PPL. Interacts with HCK and LYN.
messages: Monocyte/macrophage specific.
messages: Phosphorylated on serine residues.

9606:DPPA2
gene id: 9606:DPPA2
uniprot id: Q7Z7J5
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Binds to target gene promoters, including NKX2-5 and SYCE1, but not GATA4, and may be involved in the maintenance of the active epigenetic status of these genes.
messages: Expressed in embryonic stem cells. No expression is seen in 5 months embryo, mesenchymal stem cells, embryonic fibrocytes and adult tissues.
messages: Interacts with DPPA4.
messages: Nucleus

9606:MPP4
gene id: 9606:MPP4
uniprot id: A0A087WUS1
uniprot id: Q96JB8
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the MAGUK family.
messages: Cytoplasm
messages: Expressed in the retina (at protein level). Highly expressed in the retina. Lower amounts are detected in brain, testis, ARPE-19, RPE/choroid and fetal eye. Isoform 5 is retina-specific.
messages: Interacts with MPDZ. May interact with GRIA2 (By similarity). Forms a complex with CRB1 and PALS1. Interacts with FASLG.
messages: May play a role in retinal photoreceptors development.

9606:ZNF280C
gene id: 9606:ZNF280C
uniprot id: Q8ND82
names: Function
names: Sequence Caution
names: Subcellular Location Annotation
messages: Contaminating sequence. Potential poly-A sequence.
messages: May function as a transcription factor.
messages: Nucleus

9606:PSMB11
gene id: 9606:PSMB11
uniprot id: A5LHX3
uniprot id: B3KVC3
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the peptidase T1B family.
messages: Component of the proteasome complex.
messages: Component of the proteasome, a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity.
messages: Cytoplasm
messages: Nucleus
messages: The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is composed of 28 subunits that are arranged in four stacked rings, resulting in a barrel-shaped structure. The two end rings are each formed by seven alpha subunits, and the two central rings are each formed by seven beta subunits. The catalytic chamber with the active sites is on the inside of the barrel. Incorporated instead of PSMB5 and PSMB8.
messages: The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. Incorporated instead of PSMB5 or PSMB8, this unit reduces the chymotrypsin-like activity of the proteasome (By similarity). Plays a pivotal role in development of CD8-positive T cells (By similarity).

9606:CEP135
gene id: 9606:CEP135
uniprot id: Q66GS9
names: Disease Annotation
names: Function
names: Sequence Caution
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the CEP135/TSGA10 family.
messages: Centrosomal protein involved in centriole biogenesis. Acts as a scaffolding protein during early centriole biogenesis. Required for the targeting of centriole satellite proteins to centrosomes such as of PCM1, SSX2IP and CEP290 and recruitment of WRAP73 to centrioles. Also required for centriole-centriole cohesion during interphase by acting as a platform protein for CEP250 at the centriole. Required for the recruitment of CEP295 to the proximal end of new-born centrioles at the centriolar microtubule wall during early S phase in a PLK4-dependent manner (PubMed:27185865).
messages: Contaminating sequence. Potential poly-A sequence.
messages: Interacts with DCTN2 (By similarity). Interacts with CEP250 (PubMed:18851962).
messages: Intron retention.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: centriole

9606:ZNF75D
gene id: 9606:ZNF75D
uniprot id: P51815
uniprot id: Q86TD5
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the krueppel C2H2-type zinc-finger protein family.
messages: May be involved in transcriptional regulation.
messages: Nucleus

9606:DPY19L1
gene id: 9606:DPY19L1
uniprot id: Q2PZI1
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the dpy-19 family.
messages: It has been suggested that DPY19L1 has a related pseudogene DPY19L1P1.
messages: Membrane
messages: Probable C-mannosyltransferase that mediates C-mannosylation of tryptophan residues on target proteins.
messages: Widely expressed.

9606:HMGB1
gene id: 9606:HMGB1
uniprot id: P09429
names: Caution
names: Domain
names: Function
names: Induction
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) Associates with the influenza A viral protein NP in the nucleus of infected cells, promoting viral growth and enhancing the activity of the viral polymerase.
messages: (Microbial infection) Critical for entry of human coronaviruses SARS-CoV and SARS-CoV-2, as well as human coronavirus NL63/HCoV-NL63 (PubMed:33147444). Regulates the expression of the pro-viral genes ACE2 and CTSL through chromatin modulation (PubMed:33147444). Required for SARS-CoV-2 ORF3A-induced reticulophagy which induces endoplasmic reticulum stress and inflammatory responses and facilitates viral infection (PubMed:35239449).
messages: (Microbial infection) Facilitates dengue virus propagation via interaction with the untranslated regions of viral genome. In turn, this interaction with viral RNA may regulate secondary structure of dengue RNA thus facilitating its recognition by the replication complex.
messages: (Microbial infection) Interacts with SARS-CoV-2 ORF3A protein; the interaction promotes association of HMGB1 with BECN1, promoting reticulophagy which induces endoplasmic reticulum stress and inflammatory responses and facilitates viral infection.
messages: (Microbial infection) Interacts with adenovirus protein pVII; this interaction immobilizes HMGB1 on chromatin, thus preventing its release from cell and subsequent inflammation activation.
messages: (Microbial infection) Interacts with influenza A virus protein NP; this interaction promotes viral replication.
messages: (Microbial infection) Promotes Epstein-Barr virus (EBV) latent-to-lytic switch by sustaining the expression of the viral transcription factor BZLF1 that acts as a molecular switch to induce the transition from the latent to the lytic or productive phase of the virus cycle. Mechanistically, participates in EBV reactivation through the NLRP3 inflammasome.
messages: (Microbial infection) Protein levels increase upon infection by human coronavirus SARS-CoV-2.
messages: Acetylated on multiple sites upon stimulation with LPS (PubMed:22801494). Acetylation on lysine residues in the nuclear localization signals (NLS 1 and NLS 2) leads to cytoplasmic localization and subsequent secretion (By similarity). Acetylation on Lys-3 results in preferential binding to DNA ends and impairs DNA bending activity (By similarity).
messages: Belongs to the HMGB family.
messages: Cell membrane
messages: Chromosome
messages: Cytoplasm
messages: Endoplasmic reticulum
messages: Endoplasmic reticulum-Golgi intermediate compartment
messages: Endosome
messages: Forms covalent cross-links mediated by transglutaminase TGM2, between a glutamine and the epsilon-amino group of a lysine residue, forming homopolymers and heteropolymers.
messages: HMG box 2 mediates pro-inflammatory cytokine-stimulating activity and binding to TLR4 (PubMed:12765338, PubMed:20547845). However, not involved in mediating immunogenic activity in the context of apoptosis-induced immune tolerance (PubMed:24474694).
messages: In the cytoplasm proposed to dissociate the BECN1:BCL2 complex via competitive interaction with BECN1 leading to autophagy activation (PubMed:20819940). Involved in oxidative stress-mediated autophagy (PubMed:21395369). Can protect BECN1 and ATG5 from calpain-mediated cleavage and thus proposed to control their proautophagic and proapoptotic functions and to regulate the extent and severity of inflammation-associated cellular injury (By similarity). In myeloid cells has a protective role against endotoxemia and bacterial infection by promoting autophagy (By similarity). Involved in endosomal translocation and activation of TLR9 in response to CpG-DNA in macrophages (By similarity).
messages: In the extracellular compartment (following either active secretion or passive release) involved in regulation of the inflammatory response. Fully reduced HGMB1 (which subsequently gets oxidized after release) in association with CXCL12 mediates the recruitment of inflammatory cells during the initial phase of tissue injury; the CXCL12:HMGB1 complex triggers CXCR4 homodimerization (PubMed:22370717). Induces the migration of monocyte-derived immature dendritic cells and seems to regulate adhesive and migratory functions of neutrophils implicating AGER/RAGE and ITGAM (By similarity). Can bind to various types of DNA and RNA including microbial unmethylated CpG-DNA to enhance the innate immune response to nucleic acids. Proposed to act in promiscuous DNA/RNA sensing which cooperates with subsequent discriminative sensing by specific pattern recognition receptors (By similarity). Promotes extracellular DNA-induced AIM2 inflammasome activation implicating AGER/RAGE (PubMed:24971542). Disulfide HMGB1 binds to transmembrane receptors, such as AGER/RAGE, TLR2, TLR4 and probably TREM1, thus activating their signal transduction pathways. Mediates the release of cytokines/chemokines such as TNF, IL-1, IL-6, IL-8, CCL2, CCL3, CCL4 and CXCL10 (PubMed:12765338, PubMed:18354232, PubMed:19264983, PubMed:20547845, PubMed:24474694). Promotes secretion of interferon-gamma by macrophage-stimulated natural killer (NK) cells in concert with other cytokines like IL-2 or IL-12 (PubMed:15607795). TLR4 is proposed to be the primary receptor promoting macrophage activation and signaling through TLR4 seems to implicate LY96/MD-2 (PubMed:20547845). In bacterial LPS- or LTA-mediated inflammatory responses binds to the endotoxins and transfers them to CD14 for signaling to the respective TLR4:LY96 and TLR2 complexes (PubMed:18354232, PubMed:21660935, PubMed:25660311). Contributes to tumor proliferation by association with ACER/RAGE (By similarity). Can bind to IL1-beta and signals through the IL1…
messages: In vitro cleavage by CASP1 is liberating a HMG box 1-containing peptide which may mediate immunogenic activity; the peptide antagonizes apoptosis-induced immune tolerance (PubMed:24474694). Can be proteolytically cleaved by a thrombin:thrombomodulin complex; reduces binding to heparin and pro-inflammatory activities (By similarity).
messages: Inconsistent experimental results may reflect the use of inconsistently defined redox forms. A recombinant fully reduced form has been used in a number of experiments. However, the redox states of HMGB1 administered in vivo, may interconvert among each other. Purified HMGB1 by itself has only weak pro-inflammatory activity.
messages: Interacts (fully reduced HMGB1) with CXCL12; probably in a 1:2 ratio involving two molecules of CXCL12, each interacting with one HMG box of HMGB1; inhibited by glycyrrhizin (PubMed:22370717). Associates with the TLR4:LY96 receptor complex (PubMed:20547845). Component of the RAG complex composed of core components RAG1 and RAG2, and associated component HMGB1 or HMGB2 (By similarity). Interacts (in cytoplasm upon starvation) with BECN1; inhibits the interaction of BECN1 and BCL2 leading to promotion of autophagy (PubMed:20819940). Interacts with KPNA1; involved in nuclear import (PubMed:17114460). Interacts with SREBF1, TLR2, TLR4, TLR9, PTPRZ1, APEX1, FEN1, POLB, TERT (By similarity). Interacts with IL1B, AGER, MSH2, XPA, XPC, HNF1A, TP53 (PubMed:15014079, PubMed:18250463, PubMed:18160415, PubMed:19446504, PubMed:24474694, PubMed:23063560). Interacts with CD24; the probable CD24:SIGLEC10 complex is proposed to inhibit HGMB1-mediated tissue damage immune response (PubMed:19264983). Interacts with THBD; prevents HGMB1 interaction with ACER/RAGE and inhibits HGMB1 pro-inflammatory activity (PubMed:15841214). Interacts with HAVCR2; impairs HMGB1 binding to B-DNA and likely HMGB1-mediated innate immune response (By similarity). Interacts with XPO1; mediating nuclear export (By similarity). Interacts with HTT (wild-type and mutant HTT with expanded polyglutamine repeat) (PubMed:23303669). Interacts with receptor RAGE/AGER (PubMed:34743181).
messages: Multifunctional redox sensitive protein with various roles in different cellular compartments. In the nucleus is one of the major chromatin-associated non-histone proteins and acts as a DNA chaperone involved in replication, transcription, chromatin remodeling, V(D)J recombination, DNA repair and genome stability (PubMed:33147444). Proposed to be an universal biosensor for nucleic acids. Promotes host inflammatory response to sterile and infectious signals and is involved in the coordination and integration of innate and adaptive immune responses. In the cytoplasm functions as sensor and/or chaperone for immunogenic nucleic acids implicating the activation of TLR9-mediated immune responses, and mediates autophagy. Acts as danger associated molecular pattern (DAMP) molecule that amplifies immune responses during tissue injury (PubMed:27362237). Released to the extracellular environment can bind DNA, nucleosomes, IL-1 beta, CXCL12, AGER isoform 2/sRAGE, lipopolysaccharide (LPS) and lipoteichoic acid (LTA), and activates cells through engagement of multiple surface receptors (PubMed:34743181). In the extracellular compartment fully reduced HMGB1 (released by necrosis) acts as a chemokine, disulfide HMGB1 (actively secreted) as a cytokine, and sulfonyl HMGB1 (released from apoptotic cells) promotes immunological tolerance (PubMed:23519706, PubMed:23446148, PubMed:23994764, PubMed:25048472). Has proangiogdenic activity (By similarity). May be involved in platelet activation (By similarity). Binds to phosphatidylserine and phosphatidylethanolamide (By similarity). Bound to RAGE mediates signaling for neuronal outgrowth (By similarity). May play a role in accumulation of expanded polyglutamine (polyQ) proteins such as huntingtin (HTT) or TBP (PubMed:23303669, PubMed:25549101).
messages: Nuclear functions are attributed to fully reduced HGMB1. Associates with chromatin and binds DNA with a preference to non-canonical DNA structures such as single-stranded DNA, DNA-containing cruciforms or bent structures, supercoiled DNA and ZDNA. Can bent DNA and enhance DNA flexibility by looping thus providing a mechanism to promote activities on various gene promoters by enhancing transcription factor binding and/or bringing distant regulatory sequences into close proximity (PubMed:20123072). May have an enhancing role in nucleotide excision repair (NER) (By similarity). However, effects in NER using in vitro systems have been reported conflictingly (PubMed:19446504, PubMed:19360789). May be involved in mismatch repair (MMR) and base excision repair (BER) pathways (PubMed:15014079, PubMed:16143102, PubMed:17803946). May be involved in double strand break repair such as non-homologous end joining (NHEJ) (By similarity). Involved in V(D)J recombination by acting as a cofactor of the RAG complex: acts by stimulating cleavage and RAG protein binding at the 23 bp spacer of conserved recombination signal sequences (RSS) (By similarity). In vitro can displace histone H1 from highly bent DNA (By similarity). Can restructure the canonical nucleosome leading to relaxation of structural constraints for transcription factor-binding (By similarity). Enhances binding of sterol regulatory element-binding proteins (SREBPs) such as SREBF1 to their cognate DNA sequences and increases their transcriptional activities (By similarity). Facilitates binding of TP53 to DNA (PubMed:23063560). Proposed to be involved in mitochondrial quality control and autophagy in a transcription-dependent fashion implicating HSPB1; however, this function has been questioned (By similarity). Can modulate the activity of the telomerase complex and may be involved in telomere maintenance (By similarity).
messages: Nucleus
messages: Phosphorylated at serine residues. Phosphorylation in both NLS regions is required for cytoplasmic translocation followed by secretion (PubMed:17114460).
messages: Poly-ADP-ribosylated by PARP1 when secreted following stimulation with LPS (By similarity).
messages: Proposed to contribute to the pathogenesis of various chronic inflammatory and autoimmune diseases, and cancer. High serum levels are found in several inflammatory events including sepsis, rheumatoid arthritis, artherosclerosis chronic kidney disease, systemic lupus erythematosus (SLE). Seems to be implicated in other diseases characterized by cell death and damage, including diabetes and Alzheimer's disease. Its nucleosome-associated release during secondary necrosis may play a role in SLE (PubMed:19064698). During chemotherapy can mediate regrowth and metastasis of remaining cells in a AGER/RAGE-dependent manner (PubMed:23040637). Purified HMG box 1 acts as a specific antagonist to HGMB1 pro-inflammatory activities (PubMed:14695889).
messages: Reduction/oxidation of cysteine residues Cys-23, Cys-45 and Cys-106 and a possible intramolecular disulfide bond involving Cys-23 and Cys-45 give rise to different redox forms with specific functional activities in various cellular compartments: 1- fully reduced HMGB1 (HMGB1C23hC45hC106h), 2- disulfide HMGB1 (HMGB1C23-C45C106h) and 3- sulfonyl HMGB1 (HMGB1C23soC45soC106so).
messages: Secreted
messages: The acidic C-terminal domain forms a flexible structure which can reversibly interact intramolecularily with the HMG boxes and modulate binding to DNA and other proteins (PubMed:23063560).
messages: Ubiquitous. Expressed in platelets (PubMed:11154118).

9606:ITGAE
gene id: 9606:ITGAE
uniprot id: P38570
names: Domain
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the integrin alpha chain family.
messages: Expressed on a subclass of T-lymphocytes known as intra-epithelial lymphocytes which are located between mucosal epithelial cells.
messages: Heterodimer of an alpha and a beta subunit. The alpha subunit is composed of a heavy and a light chains linked by a disulfide bond. Alpha-E associates with beta-7.
messages: Integrin alpha-E/beta-7 is a receptor for E-cadherin. It mediates adhesion of intra-epithelial T-lymphocytes to epithelial cell monolayers.
messages: Integrin alpha-E/beta-7 is induced by TGFB1.
messages: Membrane
messages: The integrin I-domain (insert) is a VWFA domain. Integrins with I-domains do not undergo protease cleavage.

9606:PLBD1
gene id: 9606:PLBD1
uniprot id: Q6P4A8
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the phospholipase B-like family.
messages: Expressed in neutrophils and monocytes.
messages: In view of the small size of the putative binding pocket, it has been proposed that it may act as an amidase or a peptidase (By similarity). Exhibits a weak phospholipase activity, acting on various phospholipids, including phosphatidylcholine, phosphatidylinositol, phosphatidylethanolamine and lysophospholipids.
messages: Lysosome
messages: May form a homodimer, each monomer is composed of a chain A and a chain B.
messages: The maturation cleavages that produces chains A and B are required to open the putative substrate binding pocket. Both chains A and B remain associated in the mature protein.

9606:ESYT2
gene id: 9606:ESYT2
uniprot id: A0FGR8
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Anchored to the endoplasmic reticulum membrane by a transmembrane hairpin structure; both N-terminus and C-terminus are cytoplasmic.
messages: Belongs to the extended synaptotagmin family.
messages: Cell membrane
messages: Endoplasmic reticulum membrane
messages: Homodimer. Interacts with ESYT1 and ESYT3. Interacts with FGFR1 that has been activated by FGF1 binding. Interacts with the AP-2 complex; identified in a complex with the AP-2 complex and FGFR1.
messages: Tethers the endoplasmic reticulum to the cell membrane and promotes the formation of appositions between the endoplasmic reticulum and the cell membrane. Binds glycerophospholipids in a barrel-like domain and may play a role in cellular lipid transport. Plays a role in FGF signaling via its role in the rapid internalization of FGFR1 that has been activated by FGF1 binding; this occurs most likely via the AP-2 complex. Promotes the localization of SACM1L at endoplasmic reticulum-plasma membrane contact sites (EPCS) (PubMed:27044890).
messages: The C2 domains mediate lipid and calcium binding. The N-terminal C2 domain binds calcium ions and is important for calcium-dependent lipid binding and interaction with membranes. Two calcium ions are bound at a high-affinity site and a third calcium ion is bound with lower affinity. May bind up to four calcium ions. In contrast, the second C2 domain apparently does not bind calcium (PubMed:24373768). The third C2 domain mediates interaction with membranes enriched in phosphatidylinositol 4,5-bisphosphate and is required for location at the cell membrane (PubMed:23791178).
messages: The SMP-LTD domain is a barrel-like domain that binds glycerophospholipids in its interior; can bind two lipid molecules simultaneously. Binds a variety of lipids, including phosphatidylethanolamine, phosphatidylcholine and phosphatidylinositol (PubMed:24847877).
messages: Widely expressed with high level in cerebellum.

9606:UHMK1
gene id: 9606:UHMK1
uniprot id: Q8TAS1
names: Developmental Stage
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.
messages: Interacts with stathmin and CDKN1B/p27Kip1 (By similarity). Interacts with PAM.
messages: Nucleus
messages: Regulated in a cell-cycle dependent manner, with lowest levels during S phase and highest at G1 phase (at protein level).
messages: Upon serum stimulation, phosphorylates CDKN1B/p27Kip1, thus controlling CDKN1B subcellular location and cell cycle progression in G1 phase. May be involved in trafficking and/or processing of RNA (By similarity).
messages: Widely expressed, with highest levels in skeletal muscle, kidney, placenta and peripheral blood leukocytes.

9606:DNAJC5
gene id: 9606:DNAJC5
uniprot id: Q9H3Z4
names: Disease Annotation
names: Function
names: Miscellaneous
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acts as a general chaperone in regulated exocytosis (By similarity). Acts as a co-chaperone for the SNARE protein SNAP-25 (By similarity). Involved in the calcium-mediated control of a late stage of exocytosis (By similarity). May have an important role in presynaptic function. May be involved in calcium-dependent neurotransmitter release at nerve endings (By similarity).
messages: Cell membrane
messages: Expressed in pancreas, kidney, skeletal muscle, liver, lung, placenta, brain and heart.
messages: Melanosome
messages: Membrane
messages: Oligomers (PubMed:27452402). Homodimer (By similarity). Interacts with the chaperone complex consisting of HSC70 and SGTA (By similarity). Interacts with ZDHHC13 (via ANK repeats) (By similarity). Interacts with ZDHHC17 (via ANK repeats) (PubMed:28882895). Interacts with SYT1, SYT5 and SYT7, and with SYT9, forming a complex with SNAP25 (By similarity).
messages: Palmitoylated. Could be palmitoylated by DHHC3, DHHC7, DHHC15 and DHHC17. Palmitoylation occurs probably in the cysteine-rich domain and regulates DNAJC5 membrane attachment.
messages: Ser-10 phosphorylation induces an order-to-disorder transition triggering the interaction with Lys-58 (PubMed:27452402). This conformational switch modulates DNAJC5's cellular functions by reducing binding to syntaxin and synaptogamin without altering HSC70 interactions (PubMed:27452402).
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Upon phosphorylation, Ser-10 interacts with Lys-58, a highly conserved residue in DnaJ proteins that is also a ubiquitination site in DNAJC5.
messages: chromaffin granule membrane
messages: cytosol

9606:RAI1
gene id: 9606:RAI1
uniprot id: Q7Z5J4
names: Disease Annotation
names: Function
names: Polymorphism
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Cytoplasm
messages: Expressed in all tissues examined with higher expression in the heart and brain. No expression was seen in the corpus callosum of the brain.
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The poly-Gln tract is polymorphic and the number of Gln varies from 12 to 14 (PubMed:11404004). The size of the poly-Gln region may influence the age at onset of spinocerebellar ataxia type 2 (SCA2) (PubMed:10915763).
messages: Transcriptional regulator of the circadian clock components: CLOCK, BMAL1, BMAL2, PER1/3, CRY1/2, NR1D1/2 and RORA/C. Positively regulates the transcriptional activity of CLOCK a core component of the circadian clock. Regulates transcription through chromatin remodeling by interacting with other proteins in chromatin as well as proteins in the basic transcriptional machinery. May be important for embryonic and postnatal development. May be involved in neuronal differentiation.

9606:DEGS1
gene id: 9606:DEGS1
uniprot id: O15121
names: Disease Annotation
names: Function
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the fatty acid desaturase type 1 family. DEGS subfamily.
messages: Endoplasmic reticulum membrane
messages: Has sphingolipid-delta-4-desaturase activity. Converts D-erythro-sphinganine to D-erythro-sphingosine (E-sphing-4-enine) (PubMed:11937514, PubMed:30620337, PubMed:30620338). Catalyzes the equilibrium isomerization of retinols (By similarity).
messages: Interacts with RLBP1; the interaction increases synthesis of chromophore-precursors by DEGS1.
messages: Mitochondrion membrane
messages: Myristoylation can target the enzyme to the mitochondria leading to an increase in ceramide levels.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitous.

9606:ZFAT
gene id: 9606:ZFAT
uniprot id: Q9P243
names: Function
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Isoform 1 is strongly expressed in placenta, spleen, kidney, testis and peripheral blood leukocytes. Expressed in CD4+ and CD8+ T-cells, CD19+ B-cells and CB14+ monocytes. Isoform 3 is strongly expressed in placenta, ovary, tonsil, CD19+ B-cells and CD14+ monocytes.
messages: May be involved in transcriptional regulation. Overexpression causes down-regulation of a number of genes involved in the immune response. Some genes are also up-regulated (By similarity).
messages: Nucleus
messages: cytosol

9606:PRAMEF5
gene id: 9606:PRAMEF5
uniprot id: Q5TYX0
names: Similarity
messages: Belongs to the PRAME family.

9606:SAG
gene id: 9606:SAG
uniprot id: P10523
names: Disease Annotation
names: Domain
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the arrestin family.
messages: Binds to photoactivated, phosphorylated RHO and terminates RHO signaling via G-proteins by competing with G-proteins for the same binding site on RHO (By similarity). May play a role in preventing light-dependent degeneration of retinal photoreceptor cells (PubMed:9565049).
messages: Detected in retina, in the proximal portion of the outer segment of rod photoreceptor cells (at protein level).
messages: Membrane
messages: Monomer. Homodimer. Homotetramer (PubMed:21288033). Interacts with RHO (via the phosphorylated C-terminus) (PubMed:26200343, PubMed:28753425).
messages: The C-terminus interferes with binding to non-phosphorylated RHO. Interaction with phosphorylated RHO triggers displacement of the C-terminus and leads to a conformation change that mediates high-affinity RHO binding.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: photoreceptor outer segment

9606:CARD6
gene id: 9606:CARD6
uniprot id: Q9BX69
names: Function
messages: May be involved in apoptosis.

9606:WDR19
gene id: 9606:WDR19
uniprot id: Q8NEZ3
names: Developmental Stage
names: Disease Annotation
names: Function
names: Induction
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: As component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs), it is involved in cilia function and/or assembly (PubMed:20889716). Essential for functional IFT-A assembly and ciliary entry of GPCRs (PubMed:20889716). Associates with the BBSome complex to mediate ciliary transport (By similarity).
messages: By androgenic hormones. Expression increased 3-fold in an androgen-stimulated androgen-sensitive prostate adenocarcinoma cell line compared with androgen-deprived cells.
messages: Component of the IFT complex A (IFT-A) complex (PubMed:20889716, PubMed:27932497). IFT-A complex is divided into a core subcomplex composed of IFT122:IFT140:WDR19 which is associated with TULP3 and a peripheral subcomplex composed of IFT43:WDR35:TTC21B (PubMed:27932497, PubMed:29220510). Interacts (via C-terminal region) with IFT122 (via C-terminal region) (PubMed:29220510). Interacts with BBS1 (By similarity). Interacts with TTC25 (PubMed:25860617).
messages: Expressed in fetal lung.
messages: Some isoforms are tissue-specific. Highly expressed in the prostate. Lower expression in the cerebellum, pituitary gland, fetal lung, and pancreas. In normal prostate, expressed in both basal and luminal epithelial cells. No expression detected in fibromuscular stromal cells, endothelial cells, or infiltrating lymphocytes. Uniformed expression in prostate adenocarcinoma cells.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The disease may be caused by variants affecting the gene represented in this entry.
messages: cilium
messages: cilium basal body
messages: flagellum
messages: photoreceptor outer segment

9606:TMEM132C
gene id: 9606:TMEM132C
uniprot id: Q8N3T6
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the TMEM132 family.
messages: Membrane

9606:MRPS10
gene id: 9606:MRPS10
uniprot id: B4DP77
uniprot id: P82664
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the universal ribosomal protein uS10 family.
messages: Component of the mitochondrial small ribosomal subunit (mt-SSU). Mature mammalian 55S mitochondrial ribosomes consist of a small (28S) and a large (39S) subunit. The 28S small subunit contains a 12S ribosomal RNA (12S mt-rRNA) and 30 different proteins. The 39S large subunit contains a 16S rRNA (16S mt-rRNA), a copy of mitochondrial valine transfer RNA (mt-tRNA(Val)), which plays an integral structural role, and 52 different proteins.
messages: Mitochondrion

9606:PGK1
gene id: 9606:PGK1
uniprot id: P00558
uniprot id: V9HWF4
names: Activity Regulation
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the phosphoglycerate kinase family.
messages: Catalyzes one of the two ATP producing reactions in the glycolytic pathway via the reversible conversion of 1,3-diphosphoglycerate to 3-phosphoglycerate (PubMed:30323285, PubMed:7391028). In addition to its role as a glycolytic enzyme, it seems that PGK-1 acts as a polymerase alpha cofactor protein (primer recognition protein) (PubMed:2324090). May play a role in sperm motility (PubMed:26677959).
messages: Cytoplasm
messages: Mainly expressed in spermatogonia. Localized on the principle piece in the sperm (at protein level). Expression significantly decreased in the testis of elderly men.
messages: Monomer.
messages: Specifically inhibited by heterocyclic compound CBR-470-0.
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:DAZAP2
gene id: 9606:DAZAP2
uniprot id: Q15038
names: Function
names: Induction
names: PTM
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Cytoplasm
messages: Following DNA damage, phosphorylated by HIPK2 which promotes DAZAP2 localization to the nucleus, reduces interaction of DAZAP2 with HIPK2 and SIAH1, and prevents DAZAP2-dependent ubiquitination of HIPK2 by E3 ubiquitin-protein ligase SIAH1 and subsequent HIPK2 proteasomal degradation.
messages: In unstressed cells, promotes SIAH1-mediated polyubiquitination and degradation of the serine/threonine-protein kinase HIPK2, probably by acting as a loading factor that potentiates complex formation between HIPK2 and ubiquitin ligase SIAH1 (PubMed:33591310). In response to DNA damage, localizes to the nucleus following phosphorylation by HIPK2 and modulates the expression of a subset of TP53/p53 target genes by binding to TP53 at target gene promoters (PubMed:33591310). This limits the expression of a number of cell death-mediating TP53 target genes, reducing DNA damage-induced cell death (PubMed:33591310). Enhances the binding of transcription factor TCF7L2/TCF4, a Wnt signaling pathway effector, to the promoters of target genes (By similarity). Plays a role in stress granule formation (PubMed:17984221).
messages: Induced by cellular stress.
messages: Interacts with SOX6 (By similarity). Interacts with DAZ1 and DAZL (PubMed:10857750). Interacts with IL17RB (PubMed:22070932). May interact with FAM168B (PubMed:22771904). Interacts with INCA1 (PubMed:21750715). Interacts with EIF4G1 and EIF4G2 (PubMed:17984221). Interacts (via PPAY motif) with NEDD4 (via WW domains) (PubMed:11342538). Interacts with transcription factor TCF7L2/TCF4; the interaction results in localization of DAZAP2 to the nucleus (PubMed:19304756). Interacts with transcription factors TCF7 and TCF7L1 (PubMed:19304756). Interacts with transcription factor LEF1 (PubMed:19304756). Interacts with serine/threonine-protein kinase HIPK2; the interaction results in phosphorylation of DAZAP2 which causes localization of DAZAP2 to the nucleus, reduces interaction of DAZAP2 with HIPK2 and prevents DAZAP2-dependent degradation of HIPK2 (PubMed:33591310). Interacts with ubiquitin ligase SIAH1; the interaction is decreased following phosphorylation of DAZAP2 by HIPK2 (PubMed:33591310). Interacts with TP53 at TP53 target gene promoters; the interaction is triggered by DNA damage (PubMed:33591310).
messages: Nucleus
messages: Nucleus speckle
messages: Stress granule
messages: Ubiquitinated (PubMed:11342538, PubMed:21274613, PubMed:22070932). Ubiquitinated by SMURF2, leading to proteasomal degradation (PubMed:22070932). Ubiquitinated by NEDD4, leading to proteasomal degradation (PubMed:11342538).
messages: Widely expressed. Expressed in spleen, thymus, prostate, testis, ovary, small intestine, colon and leukocytes. Down-regulated in multiple myeloma.
messages: nuclear body

9606:POLR2D
gene id: 9606:POLR2D
uniprot id: O15514
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the eukaryotic RPB4 RNA polymerase subunit family.
messages: Component of the RNA polymerase II (Pol II) complex consisting of 12 subunits. RPB4 and RPB7 form a subcomplex that protrudes from the 10-subunit Pol II core complex.
messages: DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB4 is part of a subcomplex with RPB7 that binds to a pocket formed by RPB1, RPB2 and RPB6 at the base of the clamp element. The RPB4-RPB7 subcomplex seems to lock the clamp via RPB7 in the closed conformation thus preventing double-stranded DNA to enter the active site cleft. The RPB4-RPB7 subcomplex binds single-stranded DNA and RNA (By similarity).
messages: Nucleus

9606:NADK
gene id: 9606:NADK
uniprot id: A0A0A0MR98
uniprot id: O95544
names: Similarity
names: Tissue Specificity
messages: Belongs to the NAD kinase family.
messages: Widely expressed but not detected in skeletal muscle.

9606:MAN1B1
gene id: 9606:MAN1B1
uniprot id: H0YG20
uniprot id: Q9UKM7
names: Activity Regulation
names: Caution
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the glycosyl hydrolase 47 family.
messages: Endoplasmic reticulum membrane
messages: Inhibited by both 1-deoxymannojirimycin (dMNJ) and kifunensine.
messages: Involved in glycoprotein quality control targeting of misfolded glycoproteins for degradation. It primarily trims a single alpha-1,2-linked mannose residue from Man(9)GlcNAc(2) to produce Man(8)GlcNAc(2), but at high enzyme concentrations, as found in the ER quality control compartment (ERQC), it further trims the carbohydrates to Man(5-6)GlcNAc(2).
messages: It is uncertain whether Met-1 or Met-37 is the initiator.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Widely expressed.

9606:CARNS1
gene id: 9606:CARNS1
uniprot id: A5YM72
names: Cofactor
names: Function
names: Subunit
messages: Binds 2 magnesium or manganese ions per subunit.
messages: Catalyzes the synthesis of carnosine and homocarnosine. Carnosine is synthesized more efficiently than homocarnosine.
messages: Homotetramer.

9606:M1AP
gene id: 9606:M1AP
uniprot id: Q8TC57
names: Disease Annotation
names: Function
names: Subcellular Location Annotation
messages: Cytoplasm
messages: Required for meiosis I progression during spermatogenesis.
messages: The disease may be caused by variants affecting the gene represented in this entry.

9606:GON4L
gene id: 9606:GON4L
uniprot id: A4PB67
uniprot id: Q3T8J9
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Found in a complex with YY1, SIN3A and HDAC1.
messages: Has transcriptional repressor activity, probably as part of a complex with YY1, SIN3A and HDAC1. Required for B cell lymphopoiesis.
messages: Nucleus

9606:OTUD7A
gene id: 9606:OTUD7A
uniprot id: Q8TE49
names: Function
names: Similarity
names: Subcellular Location Annotation
messages: Belongs to the peptidase C64 family.
messages: Cytoplasm
messages: Has deubiquitinating activity towards 'Lys-11'-linked polyubiquitin chains.
messages: Nucleus

9606:DNTTIP1
gene id: 9606:DNTTIP1
uniprot id: Q9H147
names: Domain
names: Function
names: Subcellular Location Annotation
names: Subunit
messages: Increases DNTT terminal deoxynucleotidyltransferase activity (in vitro) (PubMed:11473582). Also acts as a transcriptional regulator, binding to the consensus sequence 5'-GNTGCATG-3' following an AT-tract. Associates with RAB20 promoter and positively regulates its transcription. Binds DNA and nucleosomes; may recruit HDAC1 complexes to nucleosomes or naked DNA.
messages: Monomer and homodimer (PubMed:11473582, PubMed:25653165). A minor proportion may form homotrimers (PubMed:11473582). Interacts with ZNF541 (PubMed:21573134). Interacts with the terminal deoxynucleotidyltransferase DNTT (PubMed:11473582, PubMed:16371131). Interacts with TRERF1 (PubMed:16371131, PubMed:21573134). Identified in a histone deacetylase complex that contains DNTTIP1, HDAC1 and MIDEAS; this complex assembles into a tetramer that contains four copies of each protein chain (PubMed:25653165). Component of a histone deacetylase complex containing DNTTIP1, ZNF541, HDAC1 and HDAC2 (PubMed:21573134). Identified in a complex with KCTD19, HDAC1, HDAC2 and ZNF541 (By similarity).
messages: Nucleus
messages: The C-terminal domain mediates interaction with DNA and nucleosomes (PubMed:11473582, PubMed:25653165). It contains a HTH motif that mediates recognition of the consensus sequence (PubMed:23874396).
messages: The N-terminal domain mediates dimerization.

9606:RARRES1
gene id: 9606:RARRES1
uniprot id: P49788
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the protease inhibitor I47 (latexin) family.
messages: By tazarotene and by all the retinoic acid receptors tested.
messages: Detected in urine (at protein level).
messages: Inhibitor of the cytoplasmic carboxypeptidase AGBL2, may regulate the alpha-tubulin tyrosination cycle.
messages: Interacts with AGBL2, KIF11 and MAPRE1.
messages: Membrane
messages: Not N-glycosylated (PubMed:21303978). O-glycosylated; contains chondroitin sulfate (PubMed:27399812, PubMed:36213313).
messages: Secreted

9606:AP4M1
gene id: 9606:AP4M1
uniprot id: C9JC87
uniprot id: O00189
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Adaptor protein complex 4 (AP-4) is a heterotetramer composed of two large adaptins (epsilon-type subunit AP4E1 and beta-type subunit AP4B1), a medium adaptin (mu-type subunit AP4M1) and a small adaptin (sigma-type AP4S1) (PubMed:10436028, PubMed:10066790, PubMed:11802162). Interacts with tyrosine-based sorting signals on the cytoplasmic tail of cargo proteins such as APP, ATG9A, LAMP2 and NAGPA (PubMed:11139587, PubMed:26544806, PubMed:29180427, PubMed:20230749). Interacts with the C-terminal domain of GRID2 (By similarity). Interacts with GRIA1 and GRIA2; the interaction is indirect via CACNG3 (By similarity). Interacts with CACNG3; CACNG3 associates GRIA1 and GRIA2 with the adaptor protein complex 4 (AP-4) to target them to the somatodendritic compartment of neurons (By similarity). Interacts with HOOK1 and HOOK2; the interactions are direct, mediate the interaction between FTS-Hook-FHIP (FHF) complex and AP-4 and the perinuclear distribution of AP-4 (PubMed:32073997).
messages: Belongs to the adaptor complexes medium subunit family.
messages: Component of the adaptor protein complex 4 (AP-4). Adaptor protein complexes are vesicle coat components involved both in vesicle formation and cargo selection. They control the vesicular transport of proteins in different trafficking pathways (PubMed:10436028, PubMed:11139587, PubMed:10066790, PubMed:11802162, PubMed:20230749). AP-4 forms a non clathrin-associated coat on vesicles departing the trans-Golgi network (TGN) and may be involved in the targeting of proteins from the trans-Golgi network (TGN) to the endosomal-lysosomal system (PubMed:11139587, PubMed:20230749). It is also involved in protein sorting to the basolateral membrane in epithelial cells and the proper asymmetric localization of somatodendritic proteins in neurons (By similarity). Within AP-4, the mu-type subunit AP4M1 is directly involved in the recognition and binding of tyrosine-based sorting signals found in the cytoplasmic part of cargos (PubMed:10436028, PubMed:11139587, PubMed:26544806, PubMed:20230749). The adaptor protein complex 4 (AP-4) may also recognize other types of sorting signal (By similarity).
messages: Component of the adaptor protein complex 4 (AP-4). Adaptor protein complexes are vesicle coat components involved both in vesicle formation and cargo selection. They control the vesicular transport of proteins in different trafficking pathways. AP-4 forms a non clathrin-associated coat on vesicles departing the trans-Golgi network (TGN) and may be involved in the targeting of proteins from the trans-Golgi network (TGN) to the endosomal-lysosomal system. It is also involved in protein sorting to the basolateral membrane in epithelial cells and the proper asymmetric localization of somatodendritic proteins in neurons. Within AP-4, the mu-type subunit AP4M1 is directly involved in the recognition and binding of tyrosine-based sorting signals found in the cytoplasmic part of cargos. The adaptor protein complex 4 (AP-4) may also recognize other types of sorting signal.
messages: Early endosome
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Ubiquitous. Highly expressed in testis and lowly expressed in brain and lung.
messages: trans-Golgi network membrane

9606:ACRV1
gene id: 9606:ACRV1
uniprot id: P26436
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Testis.
messages: acrosome

9606:GPRC5B
gene id: 9606:GPRC5B
uniprot id: B7Z831
uniprot id: Q9NZH0
names: Caution
names: Function
names: Induction
names: Similarity
names: Subcellular Location Annotation
names: Tissue Specificity
messages: Belongs to the G-protein coupled receptor 3 family.
messages: By all-trans retinoic acid (ATRA).
messages: Cell membrane
messages: Cytoplasmic vesicle membrane
messages: Expression is high in kidney, pancreas, and testis, medium in brain, heart, prostate, small intestine, and spleen, low in liver, placenta, skeletal muscle, colon, ovary, and thymus, and not detectable in lung and peripheral leukocyte. According to PubMed:10945465, highly expressed in most brain areas examined, with the highest levels observed in corpus callosum, caudate nucleus, putamen, substantia nigra, thalamus, hippocampus, and spinal cord as well as in dorsal root ganglia (DRG). In the periphery, expression levels are relatively low, compared to the CNS, with the strongest expression detected in pancreas, testis, uterus, and stomach.
messages: It is uncertain whether Met-1 or Met-9 is the initiator.
messages: Membrane
messages: Unknown. This retinoic acid-inducible G-protein coupled receptor provide evidence for a possible interaction between retinoid and G-protein signaling pathways.

9606:CTC1
gene id: 9606:CTC1
uniprot id: Q2NKJ3
names: Disease Annotation
names: Function
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the CTC1 family.
messages: Component of the CST complex proposed to act as a specialized replication factor promoting DNA replication under conditions of replication stress or natural replication barriers such as the telomere duplex. The CST complex binds single-stranded DNA with high affinity in a sequence-independent manner, while isolated subunits bind DNA with low affinity by themselves. Initially the CST complex has been proposed to protect telomeres from DNA degradation (PubMed:19854130). However, the CST complex has been shown to be involved in several aspects of telomere replication. The CST complex inhibits telomerase and is involved in telomere length homeostasis; it is proposed to bind to newly telomerase-synthesized 3' overhangs and to terminate telomerase action implicating the association with the ACD:POT1 complex thus interfering with its telomerase stimulation activity. The CST complex is also proposed to be involved in fill-in synthesis of the telomeric C-strand probably implicating recruitment and activation of DNA polymerase alpha (PubMed:22763445). The CST complex facilitates recovery from many forms of exogenous DNA damage; seems to be involved in the re-initiation of DNA replication at repaired forks and/or dormant origins (PubMed:25483097). Involved in telomere maintenance (PubMed:19854131, PubMed:22863775). Involved in genome stability (PubMed:22863775). May be in involved in telomeric C-strand fill-in during late S/G2 phase (By similarity).
messages: Component of the CST complex, composed of TEN1/C17orf106, CTC1/C17orf68 and STN1; in the complex interacts directly with STN1. Interacts with ACD and POT1.
messages: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
messages: Nucleus
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: telomere

9606:TLR2
gene id: 9606:TLR2
uniprot id: A0A0S2Z4S4
uniprot id: B3KWR9
uniprot id: O60603
names: Caution
names: Domain
names: Function
names: Induction
names: PTM
names: Polymorphism
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: (Microbial infection) In macrophages, induced by SARS-CoV-2 infection.
messages: (Microbial infection) Interacts with M.bovis MPB83.
messages: (Microbial infection) Interacts with M.tuberculosis EsxA.
messages: (Microbial infection) Interacts with Staphylococcus aureus protein SSL5.
messages: Belongs to the Toll-like receptor family.
messages: Cooperates with LY96 to mediate the innate immune response to bacterial lipoproteins and other microbial cell wall components. Cooperates with TLR1 or TLR6 to mediate the innate immune response to bacterial lipoproteins or lipopeptides (PubMed:21078852, PubMed:17889651). Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. May also activate immune cells and promote apoptosis in response to the lipid moiety of lipoproteins (PubMed:10426995, PubMed:10426996). Recognizes mycoplasmal macrophage-activating lipopeptide-2kD (MALP-2), soluble tuberculosis factor (STF), phenol-soluble modulin (PSM) and B.burgdorferi outer surface protein A lipoprotein (OspA-L) cooperatively with TLR6 (PubMed:11441107). Stimulation of monocytes in vitro with M.tuberculosis PstS1 induces p38 MAPK and ERK1/2 activation primarily via this receptor, but also partially via TLR4 (PubMed:16622205). MAPK activation in response to bacterial peptidoglycan also occurs via this receptor (PubMed:16622205). Acts as a receptor for M.tuberculosis lipoproteins LprA, LprG, LpqH and PstS1, some lipoproteins are dependent on other coreceptors (TLR1, CD14 and/or CD36); the lipoproteins act as agonists to modulate antigen presenting cell functions in response to the pathogen (PubMed:19362712). M.tuberculosis HSP70 (dnaK) but not HSP65 (groEL-2) acts via this protein to stimulate NF-kappa-B expression (PubMed:15809303). Recognizes M.tuberculosis major T-antigen EsxA (ESAT-6) which inhibits downstream MYD88-dependent signaling (shown in mouse) (By similarity). Forms activation clusters composed of several receptors depending on the ligand, these clusters trigger signaling from the cell surface and subsequently are targeted to the Golgi in a lipid-raft dependent pathway. Forms the cluster TLR2:TLR6:CD14:CD36 in response to diacylated lipopeptides and TLR2:TLR1:CD14 in response to triacylated lipopeptides (PubMed:16880211). Required for normal uptake of M.tuberc…
messages: Cooperates with LY96 to mediate the innate immune response to bacterial lipoproteins and other microbial cell wall components. Cooperates with TLR1 or TLR6 to mediate the innate immune response to bacterial lipoproteins or lipopeptides. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response.
messages: Ester-bound lipid substrates are bound through a crevice formed between the LRR 11 and LRR 12.
messages: Genetic variations in TLR2 are associated with susceptibility to leprosy [MIM:246300]. Leprosy is a chronic disease associated with depressed cellular (but not humoral) immunity, the bacterium requires a lower temperature than 37 degrees Celsius and thrives particularly in peripheral Schwann cells and macrophages. The Trp-677 polymorphism in the intracellular domain of TLR2 has a role in susceptibility to lepromatous leprosy. Wild-type TLR2 mediates CD14-enhanced Mycobacterium leprae-dependent activation of NFKB1, but TLR2 containing the Trp-677 polymorphism did not. The impaired function of the Trp-677 polymorphism provides a molecular mechanism for the poor cellular immune response associated with lepromatous leprosy.
messages: Glycosylation of Asn-442 is critical for secretion of the N-terminal ectodomain of TLR2.
messages: Highly expressed in peripheral blood leukocytes, in particular in monocytes, in bone marrow, lymph node and in spleen. Also detected in lung and in fetal liver. Levels are low in other tissues.
messages: In some plant proteins and in human SARM1, the TIR domain has NAD(+) hydrolase (NADase) activity (By similarity). However, despite the presence of the catalytic Asp residue, the isolated TIR domain of human TLR4 lacks NADase activity (By similarity). Based on this, it is unlikely that Toll-like receptors have NADase activity.
messages: Interacts with LY96, TLR1 and TLR6 (via extracellular domain) (PubMed:17889651). TLR2 seems to exist in heterodimers with either TLR1 or TLR6 before stimulation by the ligand. The heterodimers form bigger oligomers in response to their corresponding ligands as well as further heterotypic associations with other receptors such as CD14 and/or CD36 (PubMed:16880211). Binds MYD88 (via TIR domain). Interacts with TICAM1 (PubMed:12471095). Interacts with CNPY3 (By similarity). Interacts with ATG16L1 (PubMed:23376921). Interacts with PPP1R11 (By similarity). Interacts with TICAM2 (PubMed:25385819). Interacts with TIRAP (PubMed:17322885).
messages: Membrane
messages: Membrane raft
messages: The ATG16L1-binding motif mediates interaction with ATG16L1.
messages: Ubiquitinated at Lys-754 by PPP1R11, leading to its degradation (PubMed:27805901). Deubiquitinated by USP2 (By similarity).
messages: phagosome membrane

9606:SP7
gene id: 9606:SP7
uniprot id: Q8TDD2
names: Disease Annotation
names: Domain
names: Function
names: Miscellaneous
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the Sp1 C2H2-type zinc-finger protein family.
messages: Generally expressed at much higher level than isoform 1.
messages: Interacts with RIOX1; the interaction is direct and inhibits transcription activator activity.
messages: Nucleus
messages: Propionylated. Depropionylation at Lys-371 by SIRT7 activates transcription factor activity and positively regulates bone formation by osteoblasts.
messages: Restricted to bone-derived cell.
messages: The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Transcriptional activator essential for osteoblast differentiation (PubMed:23457570). Binds to SP1 and EKLF consensus sequences and to other G/C-rich sequences (By similarity).
messages: Ubiquitination at leads to proteasomal degradation. SP7 is a short-live protein with an endogenous half-life of approximately 12 hours.

9606:PRCP
gene id: 9606:PRCP
uniprot id: B7Z7Q6
uniprot id: P42785
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the peptidase S28 family.
messages: Cleaves C-terminal amino acids linked to proline in peptides such as angiotensin II, III and des-Arg9-bradykinin. This cleavage occurs at acidic pH, but enzymatic activity is retained with some substrates at neutral pH.
messages: Highest levels in placenta, lung and liver. Also present in heart, brain, pancreas and kidney.
messages: Homodimer.
messages: Lysosome

9606:ATP6V0B
gene id: 9606:ATP6V0B
uniprot id: E9PNL3
uniprot id: Q99437
names: Caution
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the V-ATPase proteolipid subunit family.
messages: Lacks conserved residue(s) required for the propagation of feature annotation.
messages: Membrane
messages: Proton-conducting pore forming of the V0 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons. V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment.
messages: Proton-conducting pore forming subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons (PubMed:33065002). V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment (By similarity).
messages: Ubiquitous.
messages: V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex (PubMed:33065002). The V1 complex consists of three catalytic AB heterodimers that form a heterohexamer, three peripheral stalks each consisting of EG heterodimers, one central rotor including subunits D and F, and the regulatory subunits C and H (PubMed:33065002). The proton translocation complex V0 consists of the proton transport subunit a, a ring of proteolipid subunits c9c'', rotary subunit d, subunits e and f, and the accessory subunits ATP6AP1/Ac45 and ATP6AP2/PRR (PubMed:33065002). Interacts with IFITM3 (By similarity).
messages: V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex. The V1 complex consists of three catalytic AB heterodimers that form a heterohexamer, three peripheral stalks each consisting of EG heterodimers, one central rotor including subunits D and F, and the regulatory subunits C and H. The proton translocation complex V0 consists of the proton transport subunit a, a ring of proteolipid subunits c9c'', rotary subunit d, subunits e and f, and the accessory subunits.
messages: clathrin-coated vesicle membrane

9606:MSMB
gene id: 9606:MSMB
uniprot id: P08118
names: Caution
names: Disease Annotation
names: Miscellaneous
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the beta-microseminoprotein family.
messages: Disease susceptibility is associated with variants affecting the gene represented in this entry.
messages: Homodimer; Interacts with PI16.
messages: Secreted
messages: Specific receptors for this protein are found on spermatozoa and in the prostate.
messages: Strongly expressed in prostate, liver, kidney, breast and penis. Also expressed in pancreas, esophagus, stomach, deodenum, colon, trachea, lung, salivary glands and fallopian tube. PSP94 is expressed in lung and breast, whereas PSP57 is found in kidney and bladder.
messages: Was originally thought to inhibit the secretion of FSH by pituitary cells.

9606:PSMC2
gene id: 9606:PSMC2
uniprot id: A0A140VK70
uniprot id: P35998
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: (Microbial infection) Interacts with HIV-1 Tat.
messages: Belongs to the AAA ATPase family.
messages: Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP) (PubMed:27428775, PubMed:27342858). The regulatory particle is made of a lid composed of 9 subunits, a base containing 6 ATPases including PSMC2 and few additional components (PubMed:27428775, PubMed:27342858). Interacts with NDC80/HEC; this interaction is detected only during M phase (PubMed:9295362, PubMed:10409732). Interacts and SQSTM1 (PubMed:15340068). Interacts with PAAF1 (PubMed:15831487). Directly interacts with TRIM5 (PubMed:22078707).
messages: Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. PSMC2 belongs to the heterohexameric ring of AAA (ATPases associated with diverse cellular activities) proteins that unfolds ubiquitinated target proteins that are concurrently translocated into a proteolytic chamber and degraded into peptides.
messages: Cytoplasm
messages: Expression is not cell cycle-dependent and occurs throughout the cell cycle.
messages: Monoubiquitinated by RNF181.
messages: Phosphorylated (PubMed:28539385). Dephosphorylated by UBLCP1 which impairs PSMC2 ATPase activity and disrupts 26S proteasome assembly (PubMed:28539385).

9606:ND1
gene id: 9606:ND1
uniprot id: P03886
uniprot id: U5Z754
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the complex I subunit 1 family.
messages: Core subunit of respiratory chain NADH dehydrogenase (Complex I) which is composed of 45 different subunits.
messages: Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor (PubMed:1959619). Essential for the catalytic activity and assembly of complex I (PubMed:26929434, PubMed:1959619).
messages: Disease susceptibility may be associated with variants affecting the gene represented in this entry.
messages: Membrane
messages: Mitochondrion inner membrane
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: The gene represented in this entry may be involved in disease pathogenesis.

9606:ATCAY
gene id: 9606:ATCAY
uniprot id: Q86WG3
names: Disease Annotation
names: Domain
names: Function
names: PTM
names: Sequence Caution
names: Subcellular Location Annotation
names: Subunit
messages: Cleaved by CASP3 and CASP7. The potential C-terminal product released by CASP3 cleavage may inhibit the ERK signaling pathway through MAP2K2.
messages: Cytoplasm
messages: Functions in the development of neural tissues, particularly the postnatal maturation of the cerebellar cortex. May play a role in neurotransmission through regulation of glutaminase/GLS, an enzyme responsible for the production in neurons of the glutamate neurotransmitter. Alternatively, may regulate the localization of mitochondria within axons and dendrites.
messages: Interacts with KLC1; may link mitochondria to KLC1 and regulate mitochondria localization into neuron projections (By similarity). Interacts with GLS; the interaction is direct and may control GLS localization, negatively regulating its activity. Interacts with PIN1 (via WW domain); upon NGF stimulation. The interaction with PIN1 and GLS is competitive. May interact with MAP2K2.
messages: May be ubiquitinated by STUB1.
messages: Mitochondrion
messages: Presynapse
messages: The CRAL-TRIO domain is known to bind small hydrophobic molecules.
messages: The disease is caused by variants affecting the gene represented in this entry.
messages: Unlikely isoform. Aberrant splice sites.
messages: axon
messages: dendrite
messages: growth cone

9606:PIGS
gene id: 9606:PIGS
uniprot id: Q8NBL9
uniprot id: Q96IR5
uniprot id: Q96S52
names: Disease Annotation
names: Function
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the PIGS family.
messages: Component of the GPI transamidase complex. Essential for transfer of GPI to proteins, particularly for formation of carbonyl intermediates.
messages: Endoplasmic reticulum membrane
messages: Forms a complex with PIGK/GPI8, PIGT, PIGU and GAA1.
messages: Membrane
messages: The disease is caused by variants affecting the gene represented in this entry.

9606:AOC2
gene id: 9606:AOC2
uniprot id: O75106
names: Cofactor
names: Function
names: Induction
names: PTM
names: Similarity
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Belongs to the copper/topaquinone oxidase family.
messages: Binds 1 copper ion per subunit.
messages: Binds 2 calcium ions per subunit.
messages: Cell membrane
messages: Contains 1 topaquinone per subunit.
messages: Cytoplasm
messages: Expressed in many tissues with much higher expression in retina. Isoform 1 and isoform 2 are expressed in adipose tissue, whereas isoform 1 only seems to be present in thymus, and isoform 2 only in testis.
messages: Has a monoamine oxidase activity with substrate specificity for 2-phenylethylamine and tryptamine. May play a role in adipogenesis. May be a critical modulator of signal transmission in retina.
messages: Homodimer; disulfide-linked (By similarity). Forms a heterodimer with AOC3, in vitro.
messages: Topaquinone (TPQ) is generated by copper-dependent autoxidation of a specific tyrosyl residue.
messages: Up-regulated during in vitro adipocyte differentiation.

9606:AMY2B
gene id: 9606:AMY2B
uniprot id: P19961
names: Cofactor
names: Similarity
names: Subcellular Location Annotation
names: Subunit
messages: Belongs to the glycosyl hydrolase 13 family.
messages: Binds 1 Ca(2+) ion per subunit.
messages: Binds 1 Cl(-) ion per subunit.
messages: Monomer.
messages: Secreted

9606:STAB1
gene id: 9606:STAB1
uniprot id: Q9NY15
names: Function
names: Subcellular Location Annotation
names: Subunit
names: Tissue Specificity
messages: Acts as a scavenger receptor for acetylated low density lipoprotein. Binds to both Gram-positive and Gram-negative bacteria and may play a role in defense against bacterial infection. When inhibited in endothelial tube formation assays, there is a marked decrease in cell-cell interactions, suggesting a role in angiogenesis. Involved in the delivery of newly synthesized CHID1/SI-CLP from the biosynthetic compartment to the endosomal/lysosomal system.
messages: High levels found in spleen, lymph node, liver and placenta. Also expressed in endothelial cells.
messages: Interacts with CHID1.
messages: Membrane