Belongs to the DNA mismatch repair MutL/HexB family.
Component of the post-replicative DNA mismatch repair system (MMR). Involved in B cell growth by positively regulating B cell proliferation and controlling replication efficiency. Controls cell cycle to prevent re-replication and defects in DNA damage-induced G2 checkpoint. Doesn't seem to counteract or control the immunoglobulin gene conversion (Ig GC) and to contribute to guanine/uracil mismatch repair. Possesses an ATPase activity, but in the absence of gross structural changes, ATP hydrolysis may not be necessary for proficient mismatch repair (By similarity).
Seems to be a major component of sperm tail outer dense fibers (ODF). ODFs 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 (By similarity).
Self-associates. Associates with microtubules and forms a fibrillar structure partially linked to the microtubule network (By similarity).
Probable component of a centromeric complex involved in assembly of kinetochore proteins, mitotic progression and chromosome segregation. May play 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.
Lacks conserved residue(s) required for the propagation of feature annotation.
Belongs to the TPT transporter family. SLC35C subfamily.
Belongs to the STXBP/unc-18/SEC1 family.
Esterifies acyl-group from acyl-ACP to the sn-1 position of glycerol-3-phosphate, an essential step in glycerolipids biosynthesis such as triglycerides, phosphatidic acids and lysophosphatidic acids.
Belongs to the cytidylyltransferase family.
Catalyzes the key rate-limiting step in the CDP-choline pathway for phosphatidylcholine biosynthesis.
The avian keratins (F-ker, S-ker, C-ker and B-ker) are a complex mixture of very similar polypeptides.
Essential component of the TORC2 complex, which plays a critical role in AKT1 'Ser-473' phosphorylation, and may modulate the phosphorylation of PKCA and regulate actin cytoskeleton organization. May interact with a MAP kinase. May act on Ras-regulated pathways (By similarity).
Part of the target of rapamycin 2 complex (TORC2).
Belongs to the ubiquitin-conjugating enzyme family.
Interacts with glycogen, PPP1CC catalytic subunit of PP1 and PYGL. Associates with glycogen particles. Forms complexes with debranching enzyme, glycogen phosphorylase, glycogen synthase and phosphorylase kinase which is necessary for its regulation of PP1 activity.
Belongs to the fatty acid desaturase type 1 family. DEGS subfamily.
Expressed in retina and retinal pigment epithelium by Mueller cells (at protein level).
Has sphingolipid-delta-4-desaturase activity. Converts D-erythro-sphinganine to D-erythro-sphingosine (E-sphing-4-enine) (By similarity). Catalyzes the equilibrium isomerization of retinols (PubMed:23143414).
Interacts with RLBP1; the interaction increases synthesis of chromophore-precursors by DEGS1.
Belongs to the SIX/Sine oculis homeobox family.
Belongs to the complexin/synaphin family.
Belongs to the actin family. ARP6 subfamily.
Expressed abundantly in the early developmental stages.
Required for formation and/or maintenance of the proper nucleolar structure and function (By similarity). Plays a dual role in the regulation of ribosomal DNA (rDNA) transcription (PubMed:26164235). In the presence of high glucose, it maintains active rDNA transcription through H2A.Z deposition and under glucose starvation, is required for the repression of rDNA transcription, and this function may be independent of H2A.Z (PubMed:26164235).
Belongs to the intermediate filament family.
Heterotetramer of two type I and two type II keratins.
The nonhelical tail domain is involved in promoting KRT5-KRT14 filaments to self-organize into large bundles and enhances the mechanical properties involved in resilience of keratin intermediate filaments in vitro.
There are two types of cytoskeletal and microfibrillar keratin: I (acidic; 40-55 kDa) and II (neutral to basic; 56-70 kDa).
Although related to the Ser/Thr protein kinase family, has no protein kinase activity and acts as a mannose kinase instead.
Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. STKL subfamily.
Protein O-mannose kinase that specifically mediates phosphorylation at the 6-position of an O-mannose of the trisaccharide (N-acetylgalactosamine (GalNAc)-beta-1,3-N-acetylglucosamine (GlcNAc)-beta-1,4-mannose) to generate phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-beta-1,3-N-acetylglucosamine-beta-1,4-(phosphate-6-)mannose). Phosphorylated O-mannosyl trisaccharide is a carbohydrate structure present in alpha-dystroglycan (DAG1), which is required for binding laminin G-like domain-containing extracellular proteins with high affinity. Only shows kinase activity when the GalNAc-beta-3-GlcNAc-beta-terminus is linked to the 4-position of O-mannose, suggesting that this disaccharide serves as the substrate recognition motif (By similarity).
May interact with target proteins during translocation into the lumen of the endoplasmic reticulum. May protect unfolded target proteins against degradation and facilitate correct glycosylation.
Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. AIG1/Toc34/Toc159-like paraseptin GTPase family. IAN subfamily.
Belongs to the helicase family. RecQ subfamily.
Belongs to the DEAD box helicase family. DEAH subfamily. DDX15/PRP43 sub-subfamily.
Belongs to the nuclear hormone receptor family. NR2 subfamily.
Expressed exclusively in the neuroepithelium of the embryonic brain.
Orphan receptor that binds DNA as a monomer to hormone response elements (HRE) containing an extended core motif half-site sequence 5'-AAGGTCA-3' in which the 5' flanking nucleotides participate in determining receptor specificity. May be required to pattern anterior brain differentiation (By similarity). Involved in the regulation of retinal development.
Belongs to the G-alpha family. G(i/o/t/z) subfamily.
G proteins are composed of 3 units; alpha, beta and gamma. The alpha chain contains the guanine nucleotide binding site.
Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(i) proteins are involved in hormonal regulation of adenylate cyclase: they inhibit the cyclase in response to beta-adrenergic stimuli. May play a role in cell division (By similarity).
Belongs to the gastrin/cholecystokinin family.
By dietary protein, amino acids and medium-chain triacylglycerol.
In the small intestine, the major production site is around the vitelline diverticulum.
The precursor is cleaved by proteases to produce a number of active cholecystokinins.
This peptide hormone induces gall bladder contraction and the release of pancreatic enzymes in the gut. Its function in the brain is not clear (By similarity). It also decreases food intake and regulates gastrointestinal physiological processes.
Belongs to the calycin superfamily. Fatty-acid binding protein (FABP) family.
Skeletal muscle troponin C binds four calcium ions.
Troponin is the central regulatory protein of striated muscle contraction. Tn consists of three components: Tn-I which is the inhibitor of actomyosin ATPase, Tn-T which contains the binding site for tropomyosin and Tn-C. The binding of calcium to Tn-C abolishes the inhibitory action of Tn on actin filaments.
Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family.
May be signaling molecules that resemble neuropeptides.
Belongs to the transferase hexapeptide repeat family.
Belongs to the WD repeat PRL1/PRL2 family.
Belongs to the intercrine alpha (chemokine CxC) family.
By serum. Expressed constitutively in Rous sarcoma virus (RSV) infected cells.
May be an autocrine factor that promotes the growth of fibroblasts and is involved in the neoplastic transformation of fibroblasts by v-Src. Chemotactic for peripheral blood mononuclear cells as well as for heterophils.
Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily.
Does not seem to be a disulfide isomerase. Plays an important role in the processing of secretory proteins within the endoplasmic reticulum (ER), possibly by participating in the folding of proteins in the ER.
Belongs to the tumor necrosis factor family.
Expressed during the redifferentiation of pigmented epithelial cells (PEC).
Might be required for polymerization of melanin onto the core structure of melanosomes with enzymatic function of tyrosinase.
Mutations in PMEL cause the Dominant white, Dun and Smoky plumage phenotypes in chicken. Both Dominant white and Dun inhibit the expression of black eumelanin giving rise to white plumage while Smoky gives a gray phenotype. The Dominant white phenotype is a breed characteristic of the White leghorn strain.
Specific to pigmented epithelial cells and melanocytes. Not expressed in lens, neural retina, brain, heart, gizzard or liver.
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.
Belongs to the complex I NDUFS4 subunit family.
Adds the first glucose residue to the lipid-linked oligosaccharide precursor for N-linked glycosylation. Transfers glucose from dolichyl phosphate glucose (Dol-P-Glc) onto the lipid-linked oligosaccharide Man(9)GlcNAc(2)-PP-Dol (By similarity).
Adds the first glucose residue to the lipid-linked oligosaccharide precursor for N-linked glycosylation. Transfers glucose from dolichyl phosphate glucose (Dol-P-Glc) onto the lipid-linked oligosaccharide Man(9)GlcNAc(2)-PP-Dol.
Belongs to the ALG6/ALG8 glucosyltransferase family.
Belongs to the eukaryotic diacylglycerol kinase family.
Belongs to the aldehyde dehydrogenase family.
Converts retinaldehyde to retinoic acid. Recognizes as substrates free retinal and cellular retinol-binding protein-bound retinal. Can metabolize octanal and decanal, but has only very low activity with benzaldehyde, acetaldehyde and propanal. Displays complete lack of activity with citral.
Belongs to the histone deacetylase family. HD Type 1 subfamily.
Belongs to the glycosyl hydrolase 33 family.
Interacts with CENPH-CENPI complex at the kinetochore.
Probable component of a centromeric complex involved in assembly of kinetochore proteins, mitotic progression and chromosome segregation. Required for maintenance of sister chromatid adhesion during mitotic checkpoint activation.
Belongs to the chondroitin N-acetylgalactosaminyltransferase family.
Heterodimer; heterodimerizes with METTL3 to form an antiparallel heterodimer that constitutes an active methyltransferase. Component of the WMM complex, a N6-methyltransferase complex composed of a catalytic subcomplex, named MAC, and of an associated subcomplex, named MACOM. The MAC subcomplex is composed of METTL3 and METTL14.
The METTL3-METTL14 heterodimer forms a N6-methyltransferase complex that methylates adenosine residues at the N(6) position of some mRNAs and regulates the circadian clock, differentiation of embryonic stem cells and cortical neurogenesis. In the heterodimer formed with METTL3, METTL14 constitutes the RNA-binding scaffold that recognizes the substrate rather than the catalytic core. N6-methyladenosine (m6A), which takes place at the 5'-[AG]GAC-3' consensus sites of some mRNAs, plays a role in mRNA stability and processing.
Plays a role in primary cilia formation. May act as a downstream effector of HOXC8 during development. May be involved in cartilage and bone development. May play a role in the differentiation of cranial neural crest cells.
Acetylated. Acetylation promotes interaction with BRD9, and subsequently with RAD54, which is essential for homologous recombination (HR).
Belongs to the SNF2/RAD54 helicase family.
Highly expressed in bursa, thymus, testis, and ovary. Low level of expression seen in all other organs tested.
Homohexamer (By similarity). Interacts (via N-terminus) with RAD51 (By similarity). Interacts with NAP1L1 (By similarity). Interacts with BRD9; this interaction orchestrates RAD51-RAD54 complex formation (By similarity).
Phosphorylated. Phosphorylation at Ser-561 by NEK1 specifically in G2 phase allows efficient removal of RAD51 filaments from DNA.
Plays an essential role in homologous recombination (HR) which is a major pathway for repairing DNA double-strand breaks (DSBs), single-stranded DNA (ssDNA) gaps, and stalled or collapsed replication forks. Acts as a molecular motor during the homology search and guides RAD51 ssDNA along a donor dsDNA thereby changing the homology search from the diffusion-based mechanism to a motor-guided mechanism. Plays also an essential role in RAD51-mediated synaptic complex formation which consists of three strands encased in a protein filament formed once homology is recognized. Once DNA strand exchange occured, dissociates RAD51 from nucleoprotein filaments formed on dsDNA.
Belongs to the TRAFAC class dynamin-like GTPase superfamily. Dynamin/Fzo/YdjA family.
Dynamin-related GTPase that is essential for normal mitochondrial morphology by regulating the equilibrium between mitochondrial fusion and mitochondrial fission. Binds lipid membranes enriched in negatively charged phospholipids, such as cardiolipin, and promotes membrane tubulation. The intrinsic GTPase activity is low, and is strongly increased by interaction with lipid membranes (By similarity). Plays a role in remodeling cristae and the release of cytochrome c during apoptosis (By similarity).
Inactive form produced by cleavage at S1 position by OMA1 following stress conditions that induce loss of mitochondrial membrane potential, leading to negative regulation of mitochondrial fusion.
Oligomeric complex consisting of membrane-bound and soluble forms of OPA1. Binds PARL (By similarity).
PARL-dependent proteolytic processing releases an antiapoptotic soluble form not required for mitochondrial fusion. Cleaved by OMA1 at position S1 following stress conditions.
Belongs to the mitochondrial carrier (TC 2.A.29) family.
Belongs to the clathrin light chain family.
Clathrin is the major protein of the polyhedral coat of coated pits and vesicles.
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.
Belongs to the 5'-AMP-activated protein kinase gamma subunit family.
Microtubule-binding protein that negatively regulates centriole duplication. Binds to and stabilizes microtubules.
Belongs to the eukaryotic ribosomal protein eL29 family.
Belongs to the iron/manganese superoxide dismutase family.
Destroys radicals which are normally produced within the cells and which are toxic to biological systems.
Destroys superoxide anion radicals which are normally produced within the cells and which are toxic to biological systems.
Belongs to the serpin family. Ov-serpin subfamily.
Down-regulated by dietary stress. Decreased expression at day 14 in the magnum of the oviduct in the corticosterone-fed laying hens.
Major protein of egg white (PubMed:25436390, PubMed:16428832). Expressed in the magnum of the oviduct (at protein level) (PubMed:25436390).
N-glycosylated on at least two Asn residues by ovomucoid type carbohydrate units.
Belongs to the glycosyltransferase 23 family.
Catalyzes the addition of fucose in alpha 1-6 linkage to the first GlcNAc residue, next to the peptide chains in N-glycans.
Homodimer; disulfide-linked. Seems to also exist as monomers.
Belongs to the protein kinase superfamily.
Belongs to the arylamine N-acetyltransferase family.
Belongs to the tetraspanin (TM4SF) family.
Has antibacterial activity against a variety of bacteria including S.aureus, P.aeruginosa and M.tuberculosis. Acts by inducing bacterial membrane breakage.
Induces production of reactive oxygen species (ROS) which are necessary for cell proliferation. May play a role in inducing oxidative DNA damage and replicative senescence. May play a role in the coordination of mitochondrial morphology and cell proliferation.
Belongs to the VPS10-related sortilin family. SORL1 subfamily.
Belongs to the glycosyltransferase 2 family.
Belongs to the sarcoglycan beta/delta/gamma/zeta family.
Component of the sarcoglycan complex, a subcomplex of the dystrophin-glycoprotein complex which forms a link between the F-actin cytoskeleton and the extracellular matrix.
Cross-link to form 2 major subcomplexes: one consisting of SGCB, SGCD and SGCG and the other consisting of SGCB and SGCD. The association between SGCB and SGCG is particularly strong while SGCA is loosely associated with the other sarcoglycans.
Belongs to the DHHC palmitoyltransferase family.
The DHHC domain is required for palmitoyltransferase activity.
Belongs to the small GTPase superfamily. Rab family.
Protein transport. Regulator of membrane traffic from the Golgi apparatus towards the endoplasmic reticulum (ER). Involved in COPI-independent retrograde transport from the Golgi to the ER.
Belongs to the bZIP family. ATF subfamily.
Binds DNA as a dimer and can form a homodimer in the absence of DNA. Can form a heterodimer with JUN. Heterodimerization is essential for its transcriptional activity (By similarity).
Transcriptional activator which regulates the transcription of various genes, including those involved in anti-apoptosis, cell growth, and DNA damage response. Dependent on its binding partner, binds to CRE (cAMP response element) consensus sequences (5'-TGACGTCA-3') or to AP-1 (activator protein 1) consensus sequences (5'-TGACTCA-3') (By similarity).
Binds 1 heme c group covalently per subunit.
Electron carrier protein. The oxidized form of the cytochrome c heme group can accept an electron from the heme group of the cytochrome c1 subunit of cytochrome reductase. Cytochrome c then transfers this electron to the cytochrome oxidase complex, the final protein carrier in the mitochondrial electron-transport chain.
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.
The RING-CH-type zinc finger domain is required for E3 ligase activity.
Actin-depolymerizing protein. Severs actin filaments (F-actin) and binds to actin monomers (G-actin). Acts in a pH-independent manner.
Belongs to the actin-binding proteins ADF family.
Mannosyltransferase involved in glycosylphosphatidylinositol-anchor biosynthesis.
Belongs to the myelin proteolipid protein family.
This protein is a cell adhesion molecule involved in neuron-neuron adhesion, neurite fasciculation, outgrowth of neurites, etc.
Belongs to the very long-chain fatty acids dehydratase HACD family.
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 to the production of VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators.
Neuronal cell surface protein that may be involved in cell recognition and cell adhesion (By similarity). Plays a role in angiogenesis.
Neuronal cell surface protein that may be involved in cell recognition and cell adhesion. May mediate intracellular signaling (By similarity).
Proccessed by alpha-secretase leading to the formation of an extracellular soluble protein as well as a C-terminal membrane-embedded fragment (CTF). Proteolysis of these CTFs by gamma-secretase releases intracellular domains (ICDs) and extracellular peptides (By similarity).
Produced by alternative splicing of isoform 1b.
Ligand for members of the frizzled family of seven transmembrane receptors.
Belongs to the PPP phosphatase family. PP-1 subfamily.
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. 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. May indirectly interact with SGOL1, most probably through regulatory B56 subunits (By similarity).
PP2A is the major phosphatase for microtubule-associated proteins (MAPs). PP2A can modulate the activity of phosphorylase B kinase casein kinase 2, mitogen-stimulated S6 kinase, and MAP-2 kinase.
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 (By similarity).
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 (By similarity).
Ubiquitin-like protein involved in autophagic vesicle formation.
Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IV subfamily.
Belongs to the xanthine dehydrogenase family.
Binds 1 Mo-molybdopterin (Mo-MPT) cofactor per subunit.
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. GPRK subfamily.
Efficient DNA binding requires dimerization with another bHLH protein.
The small GTPases Rab are key regulators in vesicle trafficking.
Belongs to the DNA polymerase type-B family.
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. RAC subfamily.
Belongs to the histidine acid phosphatase family. VIP1 subfamily.
Bifunctional inositol kinase that acts in concert with the IP6K kinases 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, may regulate a variety of cellular processes, including apoptosis, vesicle trafficking, cytoskeletal dynamics, and exocytosis. Phosphorylates inositol hexakisphosphate (InsP6).
Component of the ubiquinol-cytochrome c oxidoreductase, a multisubunit transmembrane complex that is part of the mitochondrial electron transport chain which drives oxidative phosphorylation.
Belongs to the CND2 (condensin subunit 2) family.
Regulatory subunit of the condensin complex, a complex required for conversion of interphase chromatin into mitotic-like condense chromosomes.
Catalyzes the transfer of endogenously produced octanoic acid from octanoyl-acyl-carrier-protein onto the lipoyl domains of lipoate-dependent enzymes. Lipoyl-ACP can also act as a substrate although octanoyl-ACP is likely to be the physiological substrate.
Suppressor of specific microRNA (miRNA) biogenesis. Binds target primary miRNA transcripts and sequester them in the nucleolus, away from the microprocessor complex, hence preventing their processing into mature miRNA. The specific interaction with target pri-miRNAs occurs via an 5'-GGAG-3' motif in the pre-miRNA terminal loop.
Required for 60S pre-ribosomal subunits export to the cytoplasm.
Belongs to the G-protein coupled receptor 1 family.
3'-5' DNA helicase involved in repair of alkylated DNA. Promotes DNA unwinding to generate single-stranded substrate needed for ALKBH3, enabling ALKBH3 to process alkylated N3-methylcytosine (3mC) within double-stranded regions. Also involved in activation of the ribosome quality control (RQC) pathway, a pathway that degrades nascent peptide chains during problematic translation. Drives the splitting of stalled ribosomes.
Feedback inhibitor of fibroblast growth factor mediated Ras-MAPK signaling and ERK activation. May inhibit FGF-induced FGFR1 tyrosine phosphorylation (By similarity). Inhibits TGFB-induced epithelial-to-mesenchymal transition in lens epithelial cells (By similarity).
Belongs to the phosphoenolpyruvate carboxykinase [GTP] family.
In eukaryotes there are two isozymes: a cytoplasmic one and a mitochondrial one.
Phosphoenolpyruvate carboxykinase activity is regulated by glucose levels (By similarity). Phosphorylation at Ser-90 reduces the binding affinity to oxaloacetate and converts the enzyme into an atypical protein kinase using GTP as donor (By similarity).
Phosphorylation at Ser-90 reduces the binding affinity to oxaloacetate and promotes the protein kinase activity.
Regulates cataplerosis and anaplerosis, the processes that control the levels of metabolic intermediates in the citric acid cycle. At low glucose levels, it catalyzes the cataplerotic conversion of oxaloacetate (OAA) to phosphoenolpyruvate (PEP), the rate-limiting step in the metabolic pathway that produces glucose from lactate and other precursors derived from the citric acid cycle. At high glucose levels, it catalyzes the anaplerotic conversion of phosphoenolpyruvate to oxaloacetate. In addition to the phosphoenolpyruvate carboxykinase activity, also acts as a protein kinase when phosphorylated at Ser-90: phosphorylation at Ser-90 reduces the binding affinity to oxaloacetate and promotes an atypical serine protein kinase activity using GTP as donor.
Belongs to the UDP-glycosyltransferase family.
Activated when phosphorylated and inactivated when dephosphorylated.
Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. I-kappa-B kinase subfamily.
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. Phosphorylates 'Ser-10' of histone H3 at NF-kappa-B-regulated promoters during inflammatory responses triggered by cytokines.
Belongs to the class-III pyridoxal-phosphate-dependent aminotransferase family.
Belongs to the dicarboxylate/amino acid:cation symporter (DAACS) (TC 2.A.23) family.
Plays a role in axon and dendrite arborization during cranial nerve development. May also be important for neural crest migration and early development of other anterior structures including eye, brain and cranial cartilage.
Belongs to the phosphorylase b kinase regulatory chain family.
Phosphorylase b kinase catalyzes the phosphorylation of serine in certain substrates, including troponin I.
Belongs to the eukaryotic ribosomal protein P1/P2 family.
Heterodimer with RPLP1 at the lateral ribosomal stalk of the large ribosomal subunit.
Plays an important role in the elongation step of protein synthesis.
Belongs to the small GTPase superfamily. Arf family.
GTP-binding protein involved in protein trafficking; modulates vesicle budding and uncoating within the Golgi apparatus.
Belongs to the Golgi pH regulator (TC 1.A.38) family.
Voltage dependent anion channel required for acidification and functions of the Golgi apparatus that may function in counter-ion conductance (By similarity). Plays a role in lymphocyte development (By similarity).
Belongs to the methylenetetrahydrofolate reductase family.
Interacts with the cannabinoid receptor CNR1 (via C-terminus). Does not interact with cannabinoid receptor CNR2.
Suppresses cannabinoid receptor CNR1-mediated tonic inhibition of voltage-gated calcium channels.
Belongs to the adenosylhomocysteinase family.
2 molecules of GDNFR-alpha are thought to form a complex with the disulfide-linked GDNF dimer and with 2 molecules of RET.
Receptor for GDNF. Mediates the GDNF-induced autophosphorylation and activation of the RET receptor (By similarity).
Belongs to the SEC23/SEC24 family. SEC24 subfamily.
Cells lacking CHAF1A show delayed S-phase progression with retarded DNA synthesis and defects in a rapid nucleosome formation of newly replicated DNA.
Complex that is thought to mediate chromatin assembly in DNA replication and DNA repair. Assembles histone octamers onto replicating DNA in vitro. CAF-1 performs the first step of the nucleosome assembly process, bringing newly synthesized histones H3 and H4 to replicating DNA; histones H2A/H2B can bind to this chromatin precursor subsequent to DNA replication to complete the histone octamer.
Contains one Pro-Xaa-Val-Xaa-Leu (PxVxL) motif, which is required for interaction with chromoshadow domains.
Subunit of the CAF-1 complex that contains RBBP4, CHAF1B and CHAF1A. Interacts with CHAF1B, PCNA and RBBP4 (PubMed:17065558).
Belongs to the SMC family. SMC1 subfamily.
Belongs to the flavoprotein pyridine nucleotide cytochrome reductase family.
Belongs to the glycosyltransferase 43 family.
At stage 16, in the posterior trunk region, expressed in the neural crest and in neural crest cells migrating into the sclerotome. From stages 24 to 27, expressed in the liver and in elements of the developing peripheral nervous system derived from the neural crest, including dorsal root ganglia, cranial ganglia, enteric ganglia and peripheral nerve tracts.
Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.
Homodimer. Heterodimer; with a RAR molecule. Binds DNA preferentially as a RAR/RXR heterodimer.
Isoform 1 is highly expressed inliver. Isoform 2 is abundantly expressed in eye and dorsal root ganglia.
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) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5. The high affinity ligand for RXRs is 9-cis retinoic acid (By similarity).
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. The WAVE complex regulates actin filament reorganization via its interaction with the Arp2/3 complex.
Belongs to the pterin-4-alpha-carbinolamine dehydratase family.
Highest level found in the kidney, liver, heart and ovarian follicles.
Involved in tetrahydrobiopterin biosynthesis. Seems to both prevent the formation of 7-pterins and accelerate the formation of quinonoid-BH2 (By similarity).
Regulates the dimerization of homeodomain protein HNF-1-alpha and enhances its transcriptional activity.
Belongs to the G-protein coupled receptor Fz/Smo family.
Component of a complex, at least composed of TSPAN12, FZD4 and norrin (NDP).
Palmitoylated; required for interaction with ADAM10. The precise position of palmitoylated residues is unclear and occurs either on Cys-9, Cys-12 and/or Cys-83 (By similarity).
Regulator of cell surface receptor signal transduction. Plays a central role in retinal vascularization by regulating norrin (NDP) signal transduction. Acts in concert with norrin (NDP) to promote FZD4 multimerization and subsequent activation of FZD4, leading to promote accumulation of beta-catenin (CTNNB1) and stimulate LEF/TCF-mediated transcriptional programs. Suprisingly, it only activates the norrin (NDP)-dependent activation of FZD4, while it does not activate the Wnt-dependent activation of FZD4, suggesting the existence of a Wnt-independent signaling that also promote accumulation the beta-catenin (CTNNB1) (By similarity).
Cathepsin D is responsible for intraoocytic processing of vitellogenin.
Causes an allergic reaction in human (PubMed:26897338). Binds to IgE (PubMed:20509661, PubMed:26897338).
Phosvitin is believed to be of importance in sequestering calcium, iron and other cations for the developing embryo.
Phosvitin, an egg yolk storage protein, is one of the most highly phosphorylated (10%) proteins in nature.
Precursor of the egg-yolk proteins that are sources of nutrients during early development of oviparous organisms.
Produced by the liver, secreted into the blood and then sequestered by receptor mediated endocytosis into growing oocytes, where it is generally cleaved, giving rise to the respective yolk components.
Phosphatidylinositol 3,4,5-trisphosphate-dependent guanine nucleotide exchange factor (GEF) which, independently of RAS, transduces signals from tyrosine kinase receptors to RAC. It also mediates signaling of membrane ruffling. Regulates the actin cytoskeleton as an effector or adapter protein in response to agonist stimulated phosphatidylinositol (3,4)-bisphosphate production and cell protrusion (By similarity).
The PH domain is essential for phosphatidylinositol 3,4,5-trisphosphate binding.
The SWAP complex consists of NPM1, NCL, PARP1 and SWAP70.
Belongs to the poly(ADP-ribose) glycohydrolase family.
Belongs to the ATPase alpha/beta chains family.
Non-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. 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.
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.
Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.
Responds to activation by environmental stress and pro-inflammatory cytokines by phosphorylating a number of transcription factors, and thus regulates transcriptional activity.
Belongs to the teashirt C2H2-type zinc-finger protein family.
Component of the DCX(DTL) E3 ubiquitin ligase complex, at least composed of CUL4 (CUL4A or CUL4B), DDB1, DTL/CDT2 and RBX1.
Substrate-specific adapter of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex required for cell cycle control, DNA damage response and translesion DNA synthesis. The DCX(DTL) complex, also named CRL4(CDT2) complex, mediates the polyubiquitination and subsequent degradation of CDT1, CDKN1A/p21(CIP1), KMT5A and SDE2. CDT1 degradation in response to DNA damage is necessary to ensure proper cell cycle regulation of DNA replication. CDKN1A/p21(CIP1) degradation during S phase or following UV irradiation is essential to control replication licensing. KMT5A degradation is also important for a proper regulation of mechanisms such as TGF-beta signaling, cell cycle progression, DNA repair and cell migration. Most substrates require their interaction with PCNA for their polyubiquitination: substrates interact with PCNA via their PIP-box, and those containing the 'K+4' motif in the PIP box, recruit the DCX(DTL) complex, leading to their degradation. In undamaged proliferating cells, the DCX(DTL) complex also promotes the 'Lys-164' monoubiquitination of PCNA, thereby being involved in PCNA-dependent translesion DNA synthesis (By similarity). May play a role in the regulation of the circadian clock (By similarity).
Belongs to the histone deacetylase family. HD type 2 subfamily.
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 (By similarity).
Belongs to the XPG/RAD2 endonuclease family. XPG subfamily.
Belongs to the TFIIE alpha subunit family.
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.
Belongs to the sodium channel (TC 1.A.1.10) family.
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.
Could coordinate an aspect of bone turnover.
Belongs to the Mediator complex subunit 30 family.
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.
Adaptor protein complex 2 (AP-2) is a heterotetramer composed of two large adaptins (alpha-type subunit and beta-type subunit), a medium adaptin (mu-type subunit) and a small adaptin (sigma-type subunit).
Belongs to the adaptor complexes medium subunit family.
Component of the adaptor complexes which link clathrin to receptors in coated vesicles. Clathrin-associated protein complexes are believed to interact with the cytoplasmic tails of membrane proteins, leading to their selection and concentration. AP50 is a subunit of the plasma membrane adaptor. The complex binds polyphosphoinositide-containing lipids.
Belongs to the small GTPase superfamily. Ras family.
Probable GTP-binding protein that possesses GTPase activity. May play a role in endothelial cell polarity and endothelial barrier function (By similarity).
Component of the cap-binding complex (CBC), which binds co-transcriptionally to the 5' cap of pre-mRNAs and is involved in various processes such as pre-mRNA splicing, translation regulation, nonsense-mediated mRNA decay, RNA-mediated gene silencing (RNAi) by microRNAs (miRNAs) and mRNA export. The CBC complex is involved in mRNA export from the nucleus, leading to the recruitment of the mRNA export machinery to the 5' end of mRNA and to mRNA export in a 5' to 3' direction through the nuclear pore. The CBC complex is also involved in mediating U snRNA and intronless mRNAs export from the nucleus. The CBC complex is essential for a pioneer round of mRNA translation, before steady state translation when the CBC complex is replaced by cytoplasmic cap-binding protein eIF4E. The pioneer round of mRNA translation mediated by the CBC complex plays a central role in nonsense-mediated mRNA decay (NMD), NMD only taking place in mRNAs bound to the CBC complex, but not on eIF4E-bound mRNAs. The CBC complex enhances NMD in mRNAs containing at least one exon-junction complex (EJC), promoting the interaction between UPF1 and UPF2. The CBC complex is also involved in 'failsafe' NMD, which is independent of the EJC complex, while it does not participate in Staufen-mediated mRNA decay (SMD). During cell proliferation, the CBC complex is also involved in microRNAs (miRNAs) biogenesis via its interaction with SRRT/ARS2, thereby being required for miRNA-mediated RNA interference. The CBC complex also acts as a negative regulator of PARN, thereby acting as an inhibitor of mRNA deadenylation. In the CBC complex, NCBP2/CBP20 recognizes and binds capped RNAs (m7GpppG-capped RNA) but requires NCBP1/CBP80 to stabilize the movement of its N-terminal loop and lock the CBC into a high affinity cap-binding state with the cap structure. The conventional cap-binding complex with NCBP2 binds both small nuclear RNA (snRNA) and messenger (mRNA) and is involved in their export from the nucleus (By similarity).
Component of the nuclear cap-binding complex (CBC), a heterodimer composed of NCBP1/CBP80 and NCBP2/CBP20 that interacts with m7GpppG-capped RNA.
Belongs to the membrane magnesium transporter (TC 1.A.67) family.
Part of the endoplasmic reticulum membrane protein complex (EMC) that enables the energy-independent insertion into endoplasmic reticulum membranes of newly synthesized membrane proteins. May be involved in Mg(2+) transport.
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.
Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Alpha-5/CHRNA5 sub-subfamily.
Neuronal AChR seems to be composed of two different type of subunits: alpha and non-alpha (also called beta). A functional receptor seems to consist of two alpha-chains and three non-alpha chains.
Belongs to the TRAFAC class YlqF/YawG GTPase family. MTG1 subfamily.
Plays a role in the regulation of the mitochondrial ribosome assembly and of translational activity. Displays mitochondrial GTPase activity.
Monomer. Oligomerizes upon binding of cytochrome c and dATP.
Oligomeric Apaf-1 mediates the cytochrome c-dependent autocatalytic activation of pro-caspase-9 (Apaf-3), leading to the activation of caspase-3 and apoptosis. This activation requires ATP.
Belongs to the two pore domain potassium channel (TC 1.A.1.8) family.
Forms high-affinity heterodimers with RNASE1, ANG and RNASE2.
Ribonuclease inhibitor which inhibits RNASE1, RNASE2 and ANG. May play a role in redox homeostasis.
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.
Transcriptional repressor regulating the expression of a number of genes. Probably functions through recruitment of histone deacetylases involved in chromatin silencing (By similarity).
Belongs to the peptidase M28 family. M28B subfamily.
Cellular uptake of iron occurs via receptor-mediated endocytosis of ligand-occupied transferrin receptor into specialized endosomes (By similarity). Endosomal acidification leads to iron release. The apotransferrin-receptor complex is then recycled to the cell surface with a return to neutral pH and the concomitant loss of affinity of apotransferrin for its receptor. Transferrin receptor is necessary for development of erythrocytes and the nervous system (By similarity). Acts as a lipid sensor that regulates mitochondrial fusion by regulating activation of the JNK pathway (By similarity). When dietary levels of stearate (C18:0) are low, promotes activation of the JNK pathway, resulting in HUWE1-mediated ubiquitination and subsequent degradation of the mitofusin MFN2 and inhibition of mitochondrial fusion (By similarity). When dietary levels of stearate (C18:0) are high, TFRC stearoylation inhibits activation of the JNK pathway and thus degradation of the mitofusin MFN2 (By similarity).
Homodimer; disulfide-linked. Binds one transferrin molecule per subunit (By similarity).
N- and O-glycosylated, phosphorylated and palmitoylated.
Stearoylated (By similarity). Stearoylation does not affect iron uptake (By similarity).
Belongs to the nuclear hormone receptor family. NR3 subfamily.
Binds DNA as a homodimer. Can form a heterodimer with ER-alpha.
Binds estrogens with an affinity similar to that of ER-alpha, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent manner.
Binds specifically to collagen. Could be involved as a chaperone in the biosynthetic pathway of collagen.
Belongs to the NmrA-type oxidoreductase family.
Lacks the conserved Tyr residue in the active site triad of Ser-Tyr-Lys necessary for dehydrogenase activity, suggesting that it has no oxidoreductase activity.
Redox sensor protein. Undergoes restructuring and subcellular redistribution in response to changes in intracellular NADPH/NADP(+) levels (By similarity).
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.
Belongs to the dynein light intermediate chain family.
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).
Belongs to the complex I NDUFA1 subunit family.
Belongs to the heat shock protein 70 family.
Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation. This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones. The affinity for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. It goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release.
The N-terminal nucleotide binding domain (NBD) (also known as the ATPase domain) is responsible for binding and hydrolyzing ATP. The C-terminal substrate-binding domain (SBD) (also known as peptide-binding domain) binds to the client/substrate proteins. The two domains are allosterically coupled so that, when ATP is bound to the NBD, the SBD binds relatively weakly to clients. When ADP is bound in the NBD, a conformational change enhances the affinity of the SBD for client proteins.
Acyltransferase which catalyzes the transfert of an acyl group from an acyl-CoA to a lysophospholipid leading to the production of a phospholipid and participates in the reacylation step of the phospholipid remodeling pathway also known as the Lands cycle. May catalyze preferentially the acylation of lysophosphatidylethanolamine (1-acyl-sn-glycero-3-phosphoethanolamine or LPE) and lysophosphatidic acid (LPA) and to a lesser extend lysophosphatidylcholine (LPC) and lysophosphatidylserine (LPS). Prefers oleoyl-CoA as the acyl donor.
Belongs to the membrane-bound acyltransferase family.
Belongs to the 1-acyl-sn-glycerol-3-phosphate acyltransferase family.
Belongs to the adenylate kinase family. AK3 subfamily.
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 binding. Assembling and dissambling the active center during each catalytic cycle provides an effective means to prevent GTP hydrolysis.
Involved in maintaining the homeostasis of cellular nucleotides by catalyzing the interconversion of nucleoside phosphates. Has GTP:AMP phosphotransferase and ITP:AMP phosphotransferase activities.
Belongs to the cyclin family. Cyclin D subfamily.
Interacts with the CDK4 and CDK6 protein kinases to form a serine/threonine kinase holoenzyme complex (By similarity). The cyclin subunit imparts substrate specificity to the complex (By similarity).
Phosphorylation at Thr-283 by MAP kinases is required for ubiquitination and degradation by the DCX(AMBRA1) complex.
Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals.
Ubiquitinated by the DCX(AMBRA1) complex during the transition from G1 to S cell phase, leading to its degradation. The DCX(AMBRA1) complex represents the major regulator of CCND1 stability during the G1/S transition.
Belongs to the AB hydrolase superfamily. AB hydrolase 4 family.
Belongs to the intercrine beta (chemokine CC) family.
Belongs to the group II decarboxylase family.
Multifunctional redox sensitive protein with various roles in different cellular compartments. 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. Can restructure the canonical nucleosome. Proposed to be an universal biosensor for nucleic acids. May promote inflammatory response to sterile and infectious signals and may be involved in the coordination and integration of innate and adaptive immune responses. In the cytoplasm may function as sensor and/or chaperone for immunogenic nucleic acids, and mediate autophagy. May act as danger associated molecular pattern (DAMP) molecule that amplifies immune responses during tissue injury.
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: 1- fully reduced HMGB1 (HMGB1C23hC45hC106h), 2- disulfide HMGB1 (HMGB1C23-C45C106h) and 3- sulfonyl HMGB1 (HMGB1C23soC45soC106so).
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; may involve Lys-3 and histone H3 'Lys-37' and 'Lys-38'.
In the C-terminal section; belongs to the phosphoglycerate mutase family.
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.
Belongs to the alpha-carbonic anhydrase family.
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).
Homodimer, and heterodimer with other family members.
Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.
Induces disassembly of actin filaments in conjunction with ADF/cofilin family proteins. Enhances cofilin-mediated actin severing (By similarity).
Cell autonomous antagonist of the canonical Wnt signaling pathway.
Heterohexamer; composed of 3 copies of TIMM9 and 3 copies of TIMM10/TIM10A, named soluble 70 kDa complex. The complex forms a 6-bladed alpha-propeller structure and associates with the TIMM22 component of the TIM22 complex. Interacts with multi-pass transmembrane proteins in transit (By similarity).
Mitochondrial intermembrane chaperone that participates in the import and insertion of multi-pass transmembrane proteins into the mitochondrial inner membrane. May also be 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 (By similarity).
The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of TIMM9 from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane (By similarity).
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.
Belongs to the class VI-like SAM-binding methyltransferase superfamily. PEMT/PEM2 methyltransferase family.
Catalyzes the three sequential steps of the methylation pathway for the biosynthesis of phosphatidylcholine, a critical and essential component for membrane structure. Uses S-adenosylmethionine (S-adenosyl-L-methionine, SAM or AdoMet) as the methyl group donor for the methylation of phosphatidylethanolamine (1,2-diacyl-sn-glycero-3-phosphoethanolamine, PE) to phosphatidylmonomethylethanolamine (1,2-diacyl-sn-glycero-3-phospho-N-methylethanolamine, PMME), PMME to phosphatidyldimethylethanolamine (1,2-diacyl-sn-glycero-3-phospho-N,N-dimethylethanolamine, PDME), and PDME to phosphatidylcholine (1,2-diacyl-sn-glycero-3-phosphocholine, PC), producing S-adenosyl-L-homocysteine in each step.
The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.
Transcriptional activator. May function as a switch in neuronal development. Keeps neural cells undifferentiated by counteracting the activity of proneural protein and suppresses neuronal differentiation.
Plays a role in transcriptional regulation. Involved in activated KRAS-mediated transcriptional activation of PRKD1. Binds to the PRKD1 promoter. Could play a role in the terminal differentiation of the intestine. Binds preferentially to methylated DNA.
Belongs to the Nudix hydrolase family. NudC subfamily.
Negatively regulates TGF-beta signaling.
Belongs to the class-II aminoacyl-tRNA synthetase family. Alax-L subfamily.
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.
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.
Monomer. Interacts with ANKRD16; the interaction is direct.
Plays a role in the process of neurogenesis.
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.
Tubulin-folding protein; involved in the early step of the tubulin folding pathway.
Belongs to the eukaryotic ribosomal protein eS7 family.
Belongs to the nuclear hormone receptor family. NR1 subfamily.
Homodimer in the absence of bound vitamin D3. Heterodimer with RXRA after vitamin D3 binding.
Nuclear receptor for calcitriol, the active form of vitamin D3 which mediates the action of this vitamin on cells. Enters the nucleus upon vitamin D3 binding where it forms heterodimers with the retinoid X receptor/RXR. The VDR-RXR heterodimers bind to specific response elements on DNA and activate the transcription of vitamin D3-responsive target genes. Recruited to promoters via its interaction with BAZ1B/WSTF which mediates the interaction with acetylated histones, an essential step for VDR-promoter association. Plays a central role in calcium homeostasis.
Belongs to the FARP (FMRFamide related peptide) family.
May be a centrosome-associated protein. Interacts with MYOC; affects its secretion and its aggregation.
ATPase activity is stimulated by microtubules, which promote homooligomerization. ATP-dependent microtubule severing is stimulated by interaction with KATNB1.
Belongs to the AAA ATPase family. Katanin p60 subunit A1 subfamily.
Can homooligomerize into hexameric rings, which may be promoted by interaction with microtubules. Interacts with KATNB1, which may serve as a targeting subunit.
Catalytic subunit of a complex which severs microtubules in an ATP-dependent manner. Microtubule severing may promote rapid reorganization of cellular microtubule arrays and the release of microtubules from the centrosome following nucleation.
Belongs to the major facilitator superfamily. Proton-dependent oligopeptide transporter (POT/PTR) (TC 2.A.17) family.
Produces ATP from ADP in the presence of a proton gradient across the membrane.
Important signaling molecule that activates signaling cascades downstream of NTRK2 (By similarity). During development, promotes the survival and differentiation of selected neuronal populations of the peripheral and central nervous systems. Participates in axonal growth, pathfinding and in the modulation of dendritic growth and morphology. Major regulator of synaptic transmission and plasticity at adult synapses in many regions of the CNS. The versatility of BDNF is emphasized by its contribution to a range of adaptive neuronal responses including long-term potentiation (LTP), long-term depression (LTD), certain forms of short-term synaptic plasticity, as well as homeostatic regulation of intrinsic neuronal excitability (By similarity).
Promotes the survival of neuronal populations that are all located either in the central nervous system or directly connected to it.
Forms a heterodimer with the catalytic subunit METTL1.
Required for the formation of N(7)-methylguanine at position 46 (m7G46) in tRNA. In the complex, it is required to stabilize and induce conformational changes of the catalytic subunit.
Belongs to the copper transporter (Ctr) (TC 1.A.56) family. SLC31A subfamily.
Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIA subfamily.
Ca(2+) and ATP binding cause major rearrangements of the cytoplasmic and transmembrane domains. According to the E1-E2 model, Ca(2+) binding to the cytosolic domain of the pump in the high-affinity E1 conformation is followed by the ATP-dependent phosphorylation of the active site Asp, giving rise to E1P. A conformational change of the phosphoenzyme gives rise to the low-affinity E2P state that exposes the Ca(2+) ions to the lumenal side and promotes Ca(2+) release. Dephosphorylation of the active site Asp mediates the subsequent return to the E1 conformation.
Catalyzes the hydrolysis of ATP coupled with the transport of calcium.
Interacts with sarcolipin (SLN) (By similarity). Interacts with phospholamban (PLN) (By similarity). Interacts with myoregulin (MRLN). Interacts with DWORF (By similarity). Interacts with TMX2.
Only isoform 2 is detected in heart, while both isoforms are expressed in brain, with isoform 2 being predominant.
PLN and SLN both have a single transmembrane helix; both occupy a similar binding site that is situated between the ATP2A2 transmembrane helices.
Reversibly inhibited by phospholamban (PLN) at low calcium concentrations (By similarity). Inhibited by sarcolipin (SLN) and myoregulin (MRLN) (By similarity). Enhanced by DWORF; DWORF increases activity by displacing sarcolipin (SLN), phospholamban (PLN) and myoregulin (MRLN) (By similarity).
This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen. Isoform SERCA2A is involved in the regulation of the contraction/relaxation cycle. May act as a regulator of TNFSF11-mediated Ca(2+) signaling during osteoclastogenesis.
Expressed in all developmental stages of erythroid cells but is additionally found in a limited subset of other tissues.
Transcriptional activator which probably serves as a general switch factor for cell-specific development. It binds to DNA sites with the consensus sequence 5'-[AT]GATA[AG]-3' within regulatory regions of genes.
Belongs to the distal-less homeobox family.
Belongs to the class I-like SAM-binding methyltransferase superfamily. RsmB/NOP family.
Belongs to the splicing factor SR family.
Catalyzes the conversion of phosphatidic acid (PA) to CDP-diacylglycerol (CDP-DAG), an essential intermediate in the synthesis of phosphatidylglycerol, cardiolipin and phosphatidylinositol.
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.
Belongs to the short-chain dehydrogenases/reductases (SDR) family.
Putative oxidoreductase. Acts as a tumor suppressor and plays a role in apoptosis. 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. Required for normal bone development. Inhibits Wnt signaling (By similarity).
Belongs to the glycosyltransferase 3 family.
Transfers the glycosyl residue from UDP-Glc to the non-reducing end of alpha-1,4-glucan.
Belongs to the eukaryotic ribosomal protein eL37 family.
Component of the large ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell.
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.
Belongs to the succinate/malate CoA ligase beta subunit family. ATP-specific subunit beta subfamily.
Heterodimer of an alpha and a beta subunit. The beta subunit determines specificity for ATP.
Actins are highly conserved proteins that are involved in various types of cell motility and are ubiquitously expressed in all eukaryotic cells.
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.
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.
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.
Belongs to the TRAFAC class dynamin-like GTPase superfamily. GB1/RHD3 GTPase family.
Belongs to the transient receptor (TC 1.A.4) family. STrpC subfamily. TRPC1 sub-subfamily.
Thought to form a receptor-activated non-selective calcium permeant cation channel. Probably is operated by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases or G-protein coupled receptors. Seems to be also activated by intracellular calcium store depletion.
Belongs to the small heat shock protein (HSP20) family.
Heteromer composed of three CRYAA and one CRYAB subunits. Aggregates with homologous proteins, including the small heat shock protein HSPB1, to form large heteromeric complexes. Inter-subunit bridging via zinc ions enhances stability, which is crucial as there is no protein turn over in the lens.
May contribute to the transparency and refractive index of the lens.
Belongs to the cyclic nucleotide-gated cation channel (TC 1.A.1.5) family.
Visual signal transduction is mediated by a G-protein coupled cascade using cGMP as second messenger. This protein can be activated by cyclic GMP which leads to an opening of the cation channel and thereby causing a depolarization of cone photoreceptors.
Belongs to the bacterial ribosomal protein bL9 family.
Bifunctional DNA N-glycosylase with associated apurinic/apyrimidinic (AP) lyase function that catalyzes the first step in base excision repair (BER), the primary repair pathway for the repair of oxidative DNA damage. The DNA N-glycosylase activity releases the damaged DNA base from DNA by cleaving the N-glycosidic bond, leaving an AP site. The AP lyase activity cleaves the phosphodiester bond 3' to the AP site by a beta-elimination. Primarily recognizes and repairs oxidative base damage of pyrimidines.
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.
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.
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.
Belongs to the eukaryotic initiation factor 4G family.
Belongs to the FPP/GGPP synthase family.
Exhibits acyl-CoA:lysocardiolipin acyltransferase (ALCAT) activity; catalyzes the reacylation of lyso-cardiolipin to cardiolipin (CL), a key step in CL remodeling (By similarity). Recognizes both monolysocardiolipin and dilysocardiolipin as substrates with a preference for linoleoyl-CoA and oleoyl-CoA as acyl donors (By similarity). Also exhibits 1-acyl-sn-glycerol-3-phosphate acyltransferase activity (AGPAT) activity; 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 (By similarity). Possesses both lysophosphatidylinositol acyltransferase (LPIAT) and lysophosphatidylglycerol acyltransferase (LPGAT) activities (By similarity). Required for establishment of the hematopoietic and endothelial lineages (By similarity).
The HXXXXD motif is essential for acyltransferase activity and may constitute the binding site for the phosphate moiety of the glycerol-3-phosphate.
In muscle, parvalbumin is thought to be involved in relaxation after contraction. It binds two calcium ions.
Belongs to the chloride channel (TC 2.A.49) family.
Belongs to the universal ribosomal protein uL14 family.
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily.
Belongs to the prefoldin subunit beta family.
Belongs to the monovalent cation:proton antiporter 1 (CPA1) transporter (TC 2.A.36) family.
Belongs to the trans-sulfuration enzymes family.
Belongs to the cytidine and deoxycytidylate deaminase family.
Belongs to the vitamin-B12 dependent methionine synthase family.
Catalyzes the transfer of a methyl group from methylcob(III)alamin (MeCbl) to homocysteine, yielding enzyme-bound cob(I)alamin and methionine in the cytosol. MeCbl is an active form of cobalamin (vitamin B12) used as a cofactor for methionine biosynthesis. Cob(I)alamin form is regenerated to MeCbl by a transfer of a methyl group from 5-methyltetrahydrofolate. The processing of cobalamin in the cytosol occurs in a multiprotein complex composed of at least MMACHC, MMADHC, MTRR (methionine synthase reductase) and MTR which may contribute to shuttle safely and efficiently cobalamin towards MTR in order to produce methionine.
Modular enzyme with four functionally distinct domains. The isolated Hcy-binding domain catalyzes methyl transfer from free methylcobalamin to homocysteine. The Hcy-binding domain in association with the pterin-binding domain catalyzes the methylation of cob(I)alamin by methyltetrahydrofolate and the methylation of homocysteine. The B12-binding domain binds the cofactor. The AdoMet activation domain binds S-adenosyl-L-methionine. Under aerobic conditions cob(I)alamin can be converted to inactive cob(II)alamin. Reductive methylation by S-adenosyl-L-methionine and flavodoxin regenerates methylcobalamin.
Cells that form rhombomere 4. Hensen node and the neural plate immediately anterior to it.
Ligand for members of the frizzled family of seven transmembrane receptors. Probable developmental protein. Is likely to signal over only few cell diameters. May be involved in the regulation of axis formation and in the rhombomere specification.
Palmitoleoylation is required for efficient binding to frizzled receptors (By similarity). Depalmitoleoylation leads to Wnt signaling pathway inhibition (By similarity).
Proteolytic processing by tiki1 and tiki2 promotes oxidation and formation of large disulfide-bond oligomers, leading to inactivation of wnt8c.
Belongs to the metallo-dependent hydrolases superfamily. TatD-type hydrolase family.
May regulate alternative splicing by interfering with constitutive 5'-splice site selection.
The RanBP2-type zinc fingers mediate binding to RNA.
May act as a component of a corepressor complex that represses transcription.
Putative regulator of protein phosphatase 1 (PP1) activity. May play a role in the endosomal sorting process or in endosome maturation pathway.
Detected in embryonic ocular vitreous fluid (at protein level) (PubMed:9442076). In the embryo present in retina, brain, cerebellum and spinal cord (PubMed:8670795). In adult, predominantly expressed in the brain (PubMed:8670795).
Serine protease inhibitor that inhibits plasminogen activators and plasmin but not thrombin (PubMed:9442076). May be involved in the formation or reorganization of synaptic connections as well as for synaptic plasticity in the adult nervous system. May protect neurons from cell damage by tissue-type plasminogen activator (Probable).
Belongs to the protein kinase superfamily. Tyr protein kinase family.
Belongs to the acetyltransferase family. AANAT subfamily.
Catalyzes the N-acetylation of serotonin into N-acetylserotonin.
Exhibits circadian rhythm pattern in the pineal gland with highest levels at ZT 24. Expression in the retinal photoreceptor cells oscillates in a circadian manner.
Expressed in follicular pineal cells and retinal photoreceptors with five times more expression in the pineal gland.
Monomer (By similarity). Interacts with YWHAZ; the interaction requires phosphorylation on Thr-29, and modulates the enzymatic activity of AANAT through preventing dephosphorylation and/or proteolysis and stabilizing substrate binding. Subsequently, a second molecule of AANAT can bind, via the phosphorylated Ser-203 site, the other ywhaz monomer with similar effect (By similarity).
Phosphorylated; cAMP-dependent phosphorylation on both N-terminal and C-terminal sites regulates AANAT activity through allowing interaction with 14-3-3 proteins and protecting the enzyme against proteasomal degradation.
Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. Septin GTPase family.
Belongs to the SLC35F solute transporter family.
Recognizes and binds the palindromic sequence 5'-TTGGCNNNNNGCCAA-3' present in viral and cellular promoters and in the origin of replication of adenovirus type 2. These proteins are individually capable of activating transcription and replication.
Involved in pre-mRNA splicing as a component of the spliceosome.
Calretinin is a calcium-binding protein which is abundant in auditory neurons.
Belongs to the beta/gamma-crystallin family.
Crystallins are the dominant structural components of the vertebrate eye lens.
Has a two-domain beta-structure, folded into four very similar Greek key motifs.
Homo/heterodimer, or complexes of higher-order. The structure of beta-crystallin oligomers seems to be stabilized through interactions between the N-terminal arms (By similarity).
Belongs to the phosphoglycerate mutase family. BPG-dependent PGAM subfamily.
Catalyzes the interconversion of 2-phosphoglycerate and 3-phosphoglyceratea crucial step in glycolysis, by using 2,3-bisphosphoglycerate. Also catalyzes the interconversion of (2R)-2,3-bisphosphoglycerate and (2R)-3-phospho-glyceroyl phosphate.
Acts as a GTPase-activating protein (GAP) for tubulin in concert with tubulin-specific chaperone C, but does not enhance tubulin heterodimerization. Acts as a GTPase-activating protein. May act as guanine nucleotide dissociation inhibitor towards ADP-ribosylation factor-like proteins (By similarity).
Myristoylated on Gly-2; which may be required for membrane targeting.
Palmitoylated on Cys-3; which may be required for plasma membrane targeting.
Belongs to the glycosyltransferase 2 family. GalNAc-T subfamily.
Belongs to the MIP/aquaporin (TC 1.A.8) family.
Interacts with FLNA (via filamin repeat 21); increases PKA-mediated phosphorylation of FLNA.
This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium.
Cellular myosin that appears to play a role in cytokinesis, cell shape, and specialized functions such as secretion and capping.
Expressed in fibroblasts, brain, lung, kidney, spleen, and skeletal, cardiac and smooth muscles.
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).
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.
Belongs to the nucleotide-sugar transporter family. SLC35B subfamily.
Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family.
Single-stranded DNA-dependent ATP-dependent helicase.
Belongs to the G-alpha family. G(12) subfamily.
Belongs to the integrin beta chain family.
Belongs to the gamma-glutamyltransferase family.
Cleaves the gamma-glutamyl peptide bond of glutathione and glutathione conjugates.
Involved in trafficking and recycling of synaptic vesicles.
Belongs to the X(+)/potassium ATPases subunit beta family.
The sodium/potassium-transporting ATPase is composed of a catalytic alpha subunit, an auxiliary non-catalytic beta subunit and an additional regulatory subunit.
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-3 subunit is not known.
Was originally thought to be the beta-2 subunit.
Belongs to the ferroportin (FP) (TC 2.A.100) family. SLC40A subfamily.
May be involved in iron transport and iron homeostasis.
Ribosome biogenesis factor. Involved in nucleolar processing of pre-18S ribosomal RNA. Required for optimal pre-ribosomal RNA transcription by RNA polymerase I.
Homodimeric cytokine expressed predominantly by T-lymphocytes and NK cells that plays an important role in the survival, differentiation, and chemotaxis of eosinophils. Acts also on activated and resting B-cells to induce immunoglobulin production, growth, and differentiation. Mechanistically, exerts its biological effects through a receptor composed of IL5RA subunit and the cytokine receptor common subunit beta/CSF2RB. 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.
Belongs to the protein-tyrosine phosphatase family. Non-receptor class CDC14 subfamily.
May play a role in the integrity of hemidesmosome and the attachment of basal keratinocytes to the underlying basement membrane.
Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.
The 120 kDa linear IgA disease antigen homolog is an anchoring filament component involved in dermal-epidermal cohesion.
The ectodomain is shedded from the surface of keratinocytes resulting in a 120-kDa soluble form, also named as 120 kDa linear IgA disease antigen homolog. The shedding is mediated by membrane-bound metalloproteases (By similarity).
The intracellular/endo domain is disulfide-linked.
Essential transcriptional regulator necessary for development and differentiation of erythroid and megakaryocytic lineages. Alters histone methylation by recruiting histone methyltransferase to target genes promoters. Plays a role in heterochromatin formation.
Expressed in erythroid cells of primitive and definitive lineage and bone marrow cells.
The zinc finger domain is essential for erythroid expansion and acts as an activation domain whereas non finger domain serves as repression domain.
Belongs to the krueppel C2H2-type zinc-finger protein family.
Transcription factor that binds specifically to the RAS-responsive elements (RRE) of gene promoters.
May be involved in vesicle transport between the ER and the Golgi complex.
Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family.
Belongs to the protein disulfide isomerase family.
Belongs to the glycosyltransferase 65 family.
Belongs to the ATP-dependent AMP-binding enzyme family.
Component of 2 distinct SNARE complexes.
Endoplasmic reticulum-Golgi intermediate compartment membrane
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.
EGF stimulates the growth of various epidermal and epithelial tissues in vivo and in vitro and of some fibroblasts in cell culture. Magnesiotropic hormone that stimulates magnesium reabsorption in the renal distal convoluted tubule via engagement of EGFR and activation of the magnesium channel TRPM6.
Interacts with EGFR and promotes EGFR dimerization.
Regulates ADAM17 protease, a sheddase of the epidermal growth factor (EGF) receptor ligands and TNF, thereby plays a role in sleep, cell survival, proliferation, migration and inflammation. Does not exhibit any protease activity on its own.
Belongs to the DNA mismatch repair MutS family.
Component of the post-replicative DNA mismatch repair system (MMR).
Belongs to the major facilitator superfamily. Sugar transporter (TC 2.A.1.1) family. Glucose transporter subfamily.
Deoxyglucose transport is inhibit by D-glucose, D-galactose and maltose. Galactose transport is inhibited by D-glucose and maltose.
Facilitative glucose transporter that can also mediate the uptake of various other monosaccharides across the cell membrane. Mediates the uptake of glucose, 2-deoxyglucose, galactose, mannose, xylose and fucose, and probably also dehydroascorbate. Does not mediate fructose transport.
Transport is mediated via a series of conformation changes, switching between a conformation where the substrate-binding cavity is accessible from the outside, and a another conformation where it is accessible from the cytoplasm.
DNA polymerase II participates in chromosomal DNA replication.
Belongs to the class I-like SAM-binding methyltransferase superfamily. Trm1 family.
May play a role in motor coordination and exploratory behavior.
Belongs to the eukaryotic RPC34/RPC39 RNA polymerase subunit family.
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.
Belongs to the SLC29A/ENT transporter (TC 2.A.57) family.
Somewhat implicated in the biogenesis of peroxisomes.
Belongs to the TRAPP small subunits family. Sedlin subfamily.
Endoplasmic reticulum-Golgi intermediate compartment
May play a role in vesicular transport from endoplasmic reticulum to Golgi.
Part of the multisubunit TRAPP (transport protein particle) complex.
Belongs to the zinc-containing alcohol dehydrogenase family. Quinone oxidoreductase subfamily.
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.
Receptor for NPAF (A-18-F-amide) and NPFF (F-8-F-amide) neuropeptides, also known as morphine-modulating peptides. Can also be activated by a variety of naturally occurring or synthetic FMRF-amide like ligands. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system.
Acetylated; mainly by myristic acid but also by a small amount of palmitic acid.
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.
Belongs to the vinculin/alpha-catenin family.
Exhibits self-association properties. Interacts with APBB1IP, NRAP and 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.
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.
Isoform Metavinculin is muscle-specific.
Phosphorylated; on serines, threonines and tyrosines. Phosphorylation on Tyr-1134 in activated platelets affects head-tail interactions and cell spreading but has no effect on actin binding nor on localization to focal adhesion plaques.
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. 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.
Structural component of the gap junctions and the hemichannels.
Belongs to the enhancer of polycomb family.
Putative Rab GTPase-activating protein which plays a role in vesicular trafficking. Involved in endosome-to-Golgi trafficking. Acts as a bridging protein by binding simultaneously to golgins, located at the trans-Golgi, and to the WASH complex, located on endosome-derived vesicles (By similarity). Plays a role in brain development (By similarity). May act as a general inhibitor of innate immunity signaling (By similarity).
Although its dehydrogenase activity is NAD-specific, it can also utilize NADP at a reduced efficiency.
Belongs to the tetrahydrofolate dehydrogenase/cyclohydrolase family.
Belongs to the class I-like SAM-binding methyltransferase superfamily. TRM5/TYW2 family.
Specifically methylates the N1 position of guanosine-37 in various cytoplasmic and mitochondrial tRNAs. Methylation is not dependent on the nature of the nucleoside 5' of the target nucleoside. This is the first step in the biosynthesis of wybutosine (yW), a modified base adjacent to the anticodon of tRNAs and required for accurate decoding.
May be involved in the intracellular transport of sterols or other lipids. May bind cholesterol or other sterols.
Plays a role in neurogenesis and neuronal migration. Necessary for correct formation of mitotic spindles and chromosome separation during mitosis. Necessary for cytokinesis and cell proliferation (By similarity).
Reversibly phosphorylated on serine residues during the M phase of the cell cycle. Phosphorylation is necessary for correct formation of mitotic spindles and chromosome separation during mitosis (By similarity).
This is a copper-containing oxidase that functions in the formation of pigments such as melanins and other polyphenolic compounds (By similarity). Catalyzes the initial and rate limiting step in the cascade of reactions leading to melanin production from tyrosine (By similarity). In addition to hydroxylating tyrosine to DOPA (3,4-dihydroxyphenylalanine), also catalyzes the oxidation of DOPA to DOPA-quinone, and possibly the oxidation of DHI (5,6-dihydroxyindole) to indole-5,6 quinone (By similarity).
Belongs to the class I-like SAM-binding methyltransferase superfamily. TPMT family.
Component of the transcription factor SL1/TIF-IB complex, composed of TBP and at least TAF1A, TAF1B, TAF1C and TAF1D. Interacts with UBTF.
Component of the transcription factor SL1/TIF-IB complex, which is involved in the assembly of the PIC (preinitiation complex) during RNA polymerase I-dependent transcription. The rate of PIC formation probably is primarily dependent on the rate of association of SL1/TIF-IB with the rDNA promoter. SL1/TIF-IB is involved in stabilization of nucleolar transcription factor 1/UBTF on rDNA. Formation of SL1/TIF-IB excludes the association of TBP with TFIID subunits.
Histone chaperone that stabilizes pre-existing histone tetramers and regulates replication-independent histone exchange on chromatin. Required for normal chromatin refolding in the coding region of transcribed genes, and for the suppression of spurious transcription. Binds DNA and histones and promotes nucleosome assembly (in vitro) (By similarity). Modulates RNA polymerase 1-mediated transcription (PubMed:23378026). Required for optimal growth in the presence of the DNA damaging agents actinomycin D or mitomycin C (in vitro) (PubMed:23378026). Facilitates formation of tetrameric histone complexes containing histone H3 and H4 (By similarity). Modulates RNA polymerase 1-mediated transcription (By similarity). Binds DNA, with a preference for branched DNA species, such as Y-form DNA and Holliday junction DNA (By similarity).
Interacts with POLR1A (Probable) (PubMed:23378026). Interacts with histones (PubMed:23378026). Interacts with a heterotetrameric complex formed by histone H3 and H4, especially when the histone tetramer is not bound to DNA (By similarity).
The acidic C-terminal domain mediates interaction with histone H3/H4 complexes.
Belongs to the LanC-like protein family.
Binds 1 divalent metal cation per subunit.
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.
Catalyzes the cleavage of L-kynurenine (L-Kyn) and L-3-hydroxykynurenine (L-3OHKyn) into anthranilic acid (AA) and 3-hydroxyanthranilic acid (3-OHAA), respectively.
Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation upon binding with glial cell derived neurotrophic factor family ligands.
Heterooligomeric complex of about 850 to 900 kDa that forms two stacked rings, 12 to 16 nm in diameter.
Molecular chaperone; assists the folding of proteins upon ATP hydrolysis. Known to play a role, in vitro, in the folding of actin and tubulin.
Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.
Serine/threonine-protein kinase that acts as a regulator of the p38/MAPK14 stress-activated MAPK cascade and of the MAPK8/JNK cascade. Acts as an activator of the p38/MAPK14 stress-activated MAPK cascade. In response to DNA damage, involved in the G2/M transition DNA damage checkpoint by activating the p38/MAPK14 stress-activated MAPK cascade, probably by mediating phosphorylation of upstream MAP kinase kinases. Inhibits basal activity of MAPK8/JNK cascade (By similarity).
May be involved in the trafficking of signaling proteins to the cilia.
Belongs to the succinate/malate CoA ligase beta subunit family. GTP-specific subunit beta subfamily.
GTP-specific succinyl-CoA synthetase functions in the citric acid cycle (TCA), coupling the hydrolysis of succinyl-CoA to the synthesis of GTP 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.
Heterodimer of an alpha and a beta subunit. The beta subunit determines specificity for GTP.
Belongs to the WD repeat G protein beta family.
Belongs to the enoyl-CoA hydratase/isomerase family.
In the N-terminal section; belongs to the enoyl-CoA hydratase/isomerase family.
Belongs to the Integrator subunit 7 family.
Belongs to the multiprotein complex Integrator.
Component of the Integrator complex, a complex involved in the small nuclear RNAs (snRNA) U1 and U2 transcription and in their 3'-box-dependent processing. May play a role in DNA damage response (DDR) signaling during the S phase.
Belongs to the MICOS complex subunit Mic60 family.
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.
Component of the mitochondrial contact site and cristae organizing system (MICOS) complex.
Belongs to the cytochrome c oxidase VIIa family.
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.
Interacts with the GATOR1 complex; interaction is disrupted when BMT2/SAMTOR binds S-adenosyl-L-methionine. Interacts with the KICSTOR complex; interaction is disrupted when BMT2/SAMTOR binds S-adenosyl-L-methionine.
S-adenosyl-L-methionine-binding protein that acts as an inhibitor of mTORC1 signaling via interaction with the GATOR1 and KICSTOR complexes. Acts as a sensor of S-adenosyl-L-methionine to signal methionine sufficiency to mTORC1: in presence of methionine, binds S-adenosyl-L-methionine, leading to disrupt interaction with the GATOR1 and KICSTOR complexes and promote mTORC1 signaling. Upon methionine starvation, S-adenosyl-L-methionine levels are reduced, thereby promoting the association with GATOR1 and KICSTOR, leading to inhibit mTORC1 signaling. Probably also acts as a S-adenosyl-L-methionine-dependent methyltransferase.
Belongs to the type II pantothenate kinase family.
In the N-terminal section; belongs to the type II pantothenate kinase family.
Belongs to the ribonucleoside diphosphate reductase small chain family.
Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.
Binds 2 magnesium ions per subunit. Is also active with manganese (in vitro).
Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling.
Binds calmodulin. Interacts with NDUFAF3.
Belongs to the G-protein coupled receptor 2 family.
Belongs to the major facilitator superfamily. Sugar transporter (TC 2.A.1.1) family.
Belongs to the ammonium transporter (TC 2.A.49) family. Rh subfamily.
Belongs to the PDGF/VEGF growth factor family.
Component of the nexin-dynein regulatory complex (N-DRC).
Accessory component of the DNA polymerase epsilon complex (By similarity). Participates in DNA repair and in chromosomal DNA replication (By similarity).
Belongs to the DNA polymerase epsilon subunit B family.
Component of the DNA polymerase epsilon complex consisting of four subunits: the catalytic subunit POLE and the accessory subunits POLE2, POLE3 and POLE4.
In eukaryotes there are five DNA polymerases: alpha, beta, gamma, delta, and epsilon which are responsible for different reactions of DNA synthesis.
Belongs to the protease inhibitor I35 (TIMP) family.
Complexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to their catalytic zinc cofactor.
The activity of TIMP2 is dependent on the presence of disulfide bonds.
Belongs to the eukaryotic RPC9 RNA polymerase subunit family.
Belongs to the acyl-CoA dehydrogenase family.
Belongs to the universal ribosomal protein uS14 family.
Belongs to the inward rectifier-type potassium channel family.
Inward rectifying potassium channel that is activated by phosphatidylinositol 4,5-bisphosphate and that probably participates in controlling the resting membrane potential in electrically excitable cells. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. The inward rectification is probably due to the blockage of outward current by cytoplasmic polyamines and/or magnesium ions.
Phosphatidylinositol 4,5-bisphosphate binding to the cytoplasmic side of the channel triggers a conformation change leading to channel opening.
Belongs to the thiolase-like superfamily. HMG-CoA synthase family.
Catalyzes the condensation of acetyl-CoA with acetoacetyl-CoA to form HMG-CoA, which is converted by HMG-CoA reductase (HMGCR) into mevalonate, a precursor for cholesterol synthesis.
Catalyzes the condensation of acetyl-CoA with acetoacetyl-CoA to form HMG-CoA.
Expressed in the otic placode beginning at stage 10 and exhibits a dynamic expression pattern during formation and further differentiation of the otic vesicle.
Transcription factor involved in specification of neuronal cell types and which is required for inner ear and hypothalamus development. Binds to the 5'-CAAGTG-3' core sequence (By similarity).
Belongs to the G-protein coupled receptor 3 family.
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.
Its physiological role is not yet clear.
Mediates the nuclear export of proteins (cargos) with broad substrate specificity.
Substrate-binding subunit of tRNA (adenine-N1-)-methyltransferase, which catalyzes the formation of N1-methyladenine at position 58 (m1A58) in initiator methionyl-tRNA.
Proposed core component of the chromatin remodeling Ino80 complex which exhibits DNA- and nucleosome-activated ATPase activity and catalyzes ATP-dependent nucleosome sliding.
Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.
Promotes the growth of epithelial cells.
Belongs to the TALE/IRO homeobox family.
Down-regulated by dietary stress. Significantly decreased expression between days 0 to 5 in egg whites of eggs laid by corticosterone-fed hens (at protein level). Decreased expression at day 14 in the magnum of the oviduct in the corticosterone-fed laying hens.
Expressed in developing retina and brain, but not in heart, liver or kidney. In brain, located in a narrow strip in the boundary between the ventricular zone (consisting of proliferating cells) and the intermediate zone (consisting of postmitotic, differentiating cells). Expressed in all major regions of the developing brain, including the myelencephalon, the mesencephalon, the telencephalon and the diencephalon. In the developing retina, expression is scattered across the retinal neural epithelium (PubMed:9514522). Expressed in egg white (at protein level). Expressed in the magnum of the oviduct (at protein level) (PubMed:25436390).
In brain, not abundant during the early stages of neurogenesis. Expression increases during cytogenesis followed by a rapid decrease towards the end of cytogenesis. Undetectable at 16 dpc. In retina, expression is detected at 4 dpc and 6 dpc, and becomes scarce by 8 dpc. Not detected in the mature retina.
May play a role in the developmental transition from cell proliferation to cell differentiation during neurogenesis.
Atypical homeodomain protein which does not bind DNA and is required to modulate cardiac growth and development. May act via an interaction with SRF, leading to modulate the expression of SRF-dependent cardiac-specific genes and cardiac development. May act as a co-chaperone for HSPA1A and HSPA1B chaperone proteins and assist in chaperone-mediated protein refolding.
Belongs to the ADP-ribosylglycohydrolase family.
Belongs to the GST superfamily. Mu family.
Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles (By similarity) (PubMed:10903867). Participates in the formation of novel hepoxilin regioisomers (By similarity).
Belongs to the cyclin family. Cyclin AB subfamily.
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 kinase holoenzyme complexes with the cyclin-dependent protein kinases CDK1 and CDK2. The cyclin subunit confers the substrate specificity of these complexes and differentially interacts with and activates CDK1 and CDK2 throughout the cell cycle.
Interacts with the CDK1 and CDK2 protein kinases to form serine/threonine kinase holoenzyme complexes.
Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. SETD6 subfamily.
Belongs to the complex I 30 kDa subunit family.
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.
The FYVE domain is important for binding to the endosomal membrane.
Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO), such as platelet dense granules and melanosomes. In concert with the AP-3 complex, the BLOC-1 complex is required to target membrane protein cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals. The BLOC-1 complex, in association with SNARE proteins, is also proposed to be involved in neurite extension. Plays a role in intracellular vesicle trafficking and synaptic vesicle recycling.
Belongs to the multisubunit FA complex composed of FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL/PHF9 and FANCM. This complex may also include HSP70.
DNA repair protein that may operate in a postreplication repair or a cell cycle checkpoint function. May be implicated in interstrand DNA cross-link repair and in the maintenance of normal chromosome stability. Upon IFNG induction, may facilitate STAT1 activation by recruiting STAT1 to IFNGR1.
Belongs to the transthyretin family. 5-hydroxyisourate hydrolase subfamily.
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 (By similarity).
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) (By similarity).
Belongs to the syndecan proteoglycan family.
Belongs to the cation diffusion facilitator (CDF) transporter (TC 2.A.4) family. SLC30A subfamily.
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 (Probable). 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 (By similarity).
Heterodimer with SLC30A5; form a functional zinc ion transmembrane transporter.
Hydrophilic histidine residues that participate to zinc binding in transporters of the family are not conserved in SLC30A6.
Cadherins are calcium-dependent cell adhesion proteins.
Appears first at 3 hours post-infection, increases to give the strongest signal at about 9 hours and gradually wanes to almost nothing at 24 hours.
Belongs to the alpha/beta interferon family.
Receptor for ghrelin, coupled to G-alpha-11 proteins. Stimulates growth hormone secretion. Binds also other growth hormone releasing peptides (GHRP) (e.g. Met-enkephalin and GHRP-6) as well as non-peptide, low molecular weight secretagogues (e.g. L-692,429, MK-0677, adenosine).
Belongs to the universal ribosomal protein uL2 family.
F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein (By similarity).
Ubiquitinated by FBXL22, leading to proteasomal degradation.
VIP causes vasodilation, lowers arterial blood pressure, stimulates myocardial contractility, increases glycogenolysis and relaxes the smooth muscle of trachea, stomach and gall bladder.
Belongs to the G-protein coupled receptor T2R family.
Bitter taste receptor (PubMed:25796330). Binds quinine, dextromethorphan, diphenhydramine, diphenidol, chlorpheniramine, diphenidol, chloramphenicol, chloroquine and coumarin, this latter being a weak agonist, as well as epiquinidine, ethylhydrocupreine and quinidine (PubMed:28811548).
Expressed in the oral cavity, as well as in the gastrointestinal tract, including in the upper palate, tongue, proventriculus, ventriculus, duodenum, jejunum, ileum, cecum and colon.
Belongs to the protein sulfotransferase family.
Catalyzes the O-sulfation of tyrosine residues within acidic motifs of polypeptides, using 3'-phosphoadenylyl sulfate (PAPS) as cosubstrate.
Substrate peptides must be flexible in order to adopt an L-shaped conformation in the deep binding cleft.
Belongs to the immunoglobulin superfamily. Contactin family.
Contactins mediate cell surface interactions during nervous system development. May contribute to the formation of somatotopic maps of cerebellar afferents during the development of the nervous system.
Expressed by subpopulations of Purkinje cells in the cerebellum. Also expressed by one type of Purkinje cell afferents, the climbing fibers.
Interacts with INgCAM/L1 and the tenascin-R TNP protein. Does not interacts with NrCAM.
May be involved in transcriptional regulation.
Belongs to the triosephosphate isomerase family.
It is also responsible for the non-negligible production of methylglyoxal a reactive cytotoxic side-product that modifies and can alter proteins, DNA and lipids.
Triosephosphate isomerase is an extremely efficient metabolic enzyme that catalyzes the interconversion between dihydroxyacetone phosphate (DHAP) and D-glyceraldehyde-3-phosphate (G3P) in glycolysis and gluconeogenesis.
Acts as an adapter for the XPO1/CRM1-mediated export of the 60S ribosomal subunit.
Has bactericidal activity. Potent activity against C.jejuni, C.perfringens, S.aureus, C.albicans and S.cerevisiae. Less potent against S.typhimurium and E.coli.
Strong expression in the testis, liver, gall bladder, kidney, esophagus and crop. Also expressed in the glandular stomach, ovary and male and female reproductive tracts. Low expression in the intestinal tract. Expressed in the ovarian stroma, but not in the ovarian follicles.
Interacts with TP53BP1 (when phosphorylated by ATM).
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:23333306). In response to DNA damage, interacts with ATM-phosphorylated TP53BP1, allowing recruitment to DNA DSBs (By similarity). 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 DSBs resection via homologous recombination (HR) during G1 phase (By similarity).
Belongs to the formin homology family. Diaphanous subfamily.
Belongs to the sulfotransferase 1 family.
5'->3' double-stranded DNA exonuclease which may also possess a cryptic 3'->5' double-stranded DNA exonuclease activity. Functions in DNA mismatch repair.
Belongs to the XPG/RAD2 endonuclease family. EXO1 subfamily.
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.
Heterodimer with MMACHC. Forms a multiprotein complex with MMACHC, MTR and MTRR.
Involved in cobalamin metabolism and trafficking. Plays a role in regulating the biosynthesis and the proportion of two coenzymes, methylcob(III)alamin (MeCbl) and 5'-deoxyadenosylcobalamin (AdoCbl). Promotes oxidation of cob(II)alamin bound to MMACHC. The processing of cobalamin in the cytosol occurs in a multiprotein complex composed of at least MMACHC, MMADHC, MTRR (methionine synthase reductase) and MTR (methionine synthase) which may contribute to shuttle safely and efficiently cobalamin towards MTR in order to produce methionine.
Belongs to the universal ribosomal protein uL24 family.
Efficient DNA binding requires dimerization with another bHLH protein. Binds DNA as a heterodimer with MAX.
Transcription factor that binds DNA in a non-specific manner, yet also specifically recognizes the core sequence 5'-CAC[GA]TG-3'. Activates the transcription of growth-related genes.
Involved in the tethering of the SIN3 complex to core histone proteins.
Collapsin-1, -2, -3, and -5 bind to overlapping but distinct axon tracts.
Plays an important role in signaling via the cell surface receptor PLXND1. Mediates reorganization of the actin cytoskeleton, leading to the retraction of cell projections. Promotes focal adhesion disassembly and inhibits adhesion of endothelial cells to the extracellular matrix. Regulates angiogenesis. Can down-regulate sprouting angiogenesis. Required for normal vascular patterning during embryogenesis. Induces the collapse and paralysis of neuronal growth cones. Plays an important role in ensuring the specificity of synapse formation (By similarity).
Strong binding to neuropilin is mediated by the carboxy third of the protein.
Belongs to the small leucine-rich proteoglycan (SLRP) family. SLRP class III subfamily.
May have a role in bone formation and also in establishing the ordered structure of cartilage through matrix organization.
Preferentially expressed in flattened chondrocytes of developing chick limb cartilage. Also found in the cartilage peripheral zone bordering with bone marrow cavity.
The O-linked glycosaminoglycan chain(s) are dermatan sulfate.
Belongs to the Mrp/NBP35 ATP-binding proteins family. NUBP1/NBP35 subfamily.
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.
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.
Heterotetramer of 2 NUBP1 and 2 NUBP2 chains.
Required for normal embryonic development.
Part of the Ragulator complex composed of LAMTOR1, LAMTOR2, LAMTOR3, LAMTOR4 and LAMTOR5. The Ragulator complex interacts with SLC38A9; the probable amino acid sensor. Component of the lysosomal folliculin complex (LFC).
Regulator of the TOR pathway, a signaling cascade that promotes cell growth in response to growth factors, energy levels, and amino acids. As part of the Ragulator complex, may activate the TOR signaling cascade in response to amino acids. Adapter protein that may regulate the MAP kinase cascade.
Alternates between an inactive form bound to GDP and an active form bound to GTP. Activated by a guanine nucleotide-exchange factor (GEF) and inactivated by a GTPase-activating protein (GAP).
Palmitoylated by the ZDHHC9-GOLGA7 complex. Depalmitoylated by ABHD17A, ABHD17B and ABHD17C. A continuous cycle of de- and re-palmitoylation regulates rapid exchange between plasma membrane and Golgi.
Ras proteins bind GDP/GTP and possess intrinsic GTPase activity.
Essential for Golgi structural integrity.
DNA binding protein that function as transcriptional activator. May play a role in the determination and function of cell types in the brain.
Belongs to the TFIID complex together with the TBP-associated factors (TAFs). Binds DNA as monomer.
General transcription factor that functions at the core of the DNA-binding multiprotein factor TFIID. Binding of TFIID to the TATA box is the initial transcriptional step of the pre-initiation complex (PIC), playing a role in the activation of eukaryotic genes transcribed by RNA polymerase II.
E3 ubiquitin-protein ligase that mediates ubiquitination of Delta receptors, which act as ligands of Notch proteins. Positively regulates the Delta-mediated Notch signaling by ubiquitinating the intracellular domain of Delta, leading to endocytosis of Delta receptors.
Belongs to the LAPTM4/LAPTM5 transporter family.
Belongs to the TNF receptor-associated factor family.
IGF-binding proteins prolong the half-life of the IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs on cell culture. They alter the interaction of IGFs with their cell surface receptors. Promotes cell migration.
Belongs to the universal ribosomal protein uL15 family.
Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins.
Auxillary component of the N-terminal acetyltransferase C (NatC) complex which catalyzes acetylation of N-terminal methionine residues.
Belongs to the snRNP Sm proteins family.
Component of the N-terminal acetyltransferase C (NatC) complex, which is composed of NAA35, NAA38 and NAA30.
Belongs to the glycosyl hydrolase 38 family.
Belongs to the adrenodoxin/putidaredoxin family.
Essential for the synthesis of various steroid hormones. Participates in the reduction of mitochondrial cytochrome P450 for steroidogenesis. Transfers electrons from adrenodoxin reductase to CYP11A1, a cytochrome P450 that catalyzes cholesterol side-chain cleavage. Does not form a ternary complex with adrenodoxin reductase and CYP11A1 but shuttles between the two enzymes to transfer electrons.
Belongs to the peptidase C19 family. USP10 subfamily.
Hydrolase that can remove conjugated ubiquitin from target proteins such as p53/TP53. Acts as an essential regulator of p53/TP53 stability: in unstressed cells, specifically deubiquitinates p53/TP53 in the cytoplasm, leading to counteracts MDM2 action and stabilize p53/TP53. Following DNA damage, translocates to the nucleus and deubiquitinates p53/TP53, leading to regulate the p53/TP53-dependent DNA damage response. Component of a regulatory loop that controls autophagy and p53/TP53 levels (By similarity).
Belongs to the Arg-specific ADP-ribosyltransferase family.
Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRA2 sub-subfamily.
Component of intercellular desmosome junctions. Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion.
Belongs to the class I-like SAM-binding methyltransferase superfamily. HNMT family.
N-methyltransferase that mediates the formation of anserine (beta-alanyl-N(Pi)-methyl-L-histidine) from carnosine. Anserine, a methylated derivative of carnosine (beta-alanyl-L-histidine), is an abundant constituent of vertebrate skeletal muscles.
Two different proteins belonging to two different protein families are able to mediate carnosine N-methyltransferase activity in chicken. This protein, which is not conserved in mammals, and another protein (AC F1N9S8), which is conserved from human to yeast.
Transfers N-acetylgalactosamine (GalNAc) from UDP-GalNAc to N-acetylglucosamine-beta-benzyl with a beta-1,4-linkage to form N,N'-diacetyllactosediamine, GalNAc-beta-1,4-GlcNAc structures in N-linked glycans and probably O-linked glycans.
Belongs to the adaptor complexes medium subunit family. Delta-COP subfamily.
Oligomeric complex that consists of at least the alpha, beta, beta', gamma, delta, epsilon and zeta subunits.
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 (By similarity).
Belongs to the small GTPase superfamily. SAR1 family.
Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WEE1 subfamily.
Cooperates with ASF1A to promote replication-independent chromatin assembly (By similarity). May regulate the transcription of a variety of genes controlling cell growth.
Expressed from gastrulation onwards with predominant expression in the neuroepithelium during neurulation. Expressed in regions of the embryo containing migrating neural crest cells, particularly those emanating from rhombomeres 4 and 6. Expressed throughout the rostral mesenchyme with higher levels of expression in regions containing neural crest cells. At later stages strong expression is seen in the neural crest derived regions of the head, the branchial arches and the pharyngeal pouches. Expression at the rhombomere boundaries increases around stage 16.
Interacts with ASF1, HDAC1, HDAC2 and RBBP4.
Required for replication-independent chromatin assembly and for the periodic repression of histone gene transcription during the cell cycle.
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.
Belongs to the protein kinase superfamily. Tyr protein kinase family. ROR subfamily.
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. Phosphotyrosine residues provide docking sites for interacting proteins and so are crucial for FGFR1 function and its regulation (By similarity).
Belongs to the protein kinase superfamily. Tyr protein kinase family. Fibroblast growth factor receptor subfamily.
Monomer. Homodimer after ligand binding (By similarity).
N-glycosylated in the endoplasmic reticulum. The N-glycan chains undergo further maturation to an Endo H-resistant form in the Golgi apparatus (By similarity).
Present in an inactive conformation in the absence of bound ligand. Ligand binding leads to dimerization and activation by sequential autophosphorylation on tyrosine residues (By similarity).
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 (By similarity).
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 normal skeletogenesis. 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 ubiquitination, internalization and degradation (By similarity).
Ubiquitinated. FGFR1 is rapidly ubiquitinated after autophosphorylation, leading to internalization and degradation (By similarity).
Component of the endosomal sorting complex required for transport II (ESCRT-II), which is required for multivesicular body (MVB) formation and sorting of endosomal cargo proteins into MVBs.
Component of the endosomal sorting complex required for transport II (ESCRT-II).
Calcium-dependent cell adhesion protein; preferentially mediates homotypic cell-cell adhesion (PubMed:2831236). Cadherins may thus contribute to the sorting of heterogeneous cell types, and thereby play an important role during embryonic development (By similarity).
Detected in embryonic brain and heart (at protein level) (PubMed:1638632). Detected in embryonic brain and heart (PubMed:2831236).
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 CTNNA2 (PubMed:1638632).
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.
Component of the signal recognition particle (SRP) complex, a ribonucleoprotein complex that mediates the cotranslational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER). SRP9 together with SRP14 and the Alu portion of the SRP RNA, constitutes the elongation arrest domain of SRP. The complex of SRP9 and SRP14 is required for SRP RNA binding.
Belongs to the amino acid-polyamine-organocation (APC) superfamily. L-type amino acid transporter (LAT) (TC 2.A.3.8) family.
Transcription repressor involved in the exit of embryonic stem cells (ESCs) from self-renewal.
Belongs to the TRAPP small subunits family. BET3 subfamily.
Belongs to the heat shock protein 90 family.
In contrast to other HSP90 heat shock proteins, this one is not induced by heat shock or mitogenic stimuli but is strictly constitutive.
In the resting state, through the dimerization of its C-terminal domain, HSP90 forms a homodimer which is defined as the open conformation. Upon ATP-binding, the N-terminal domain undergoes significant conformational changes and comes in contact to form an active closed conformation. 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.
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 linked to its ATPase 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. 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. 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.
The TPR repeat-binding motif mediates interaction with TPR repeat-containing proteins.
Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain.
Catalyzes the synthesis of dihydrouridine, a modified base found in the D-loop of most tRNAs.
Belongs to the immunoglobulin superfamily. DCC family.
Belongs to the inositol phosphokinase (IPK) family.
Component of the SMC5-SMC6 complex, that promotes sister chromatid alignment after DNA damage and facilitates double-stranded DNA breaks (DSBs) repair via homologous recombination between sister chromatids.
Belongs to the universal ribosomal protein uS9 family.
Belongs to the G-protein coupled receptor 1 family. Opsin subfamily.
Binds calmodulin with a greater affinity in the absence of Ca(2+) than in its presence.
First expressed in the body and head at embryonic stage 3 dpc (PubMed:2153895). Expressed in the mid-thoracic region of embryos and also in the spinal cord, dorsal root and sympathetic ganglia at embryonic stage 10 dpc (PubMed:2153895). Highly expressed in the brain at embryonic stage 13 dpc (PubMed:2153895). Expressed at low levels in the gut at embryonic stage 16 dpc (PubMed:2153895). Not expressed in heart, skeletal muscle or liver at embryonic stage 16 dpc (PubMed:2153895).
Palmitoylated (PubMed:9813098). Palmitoylation is essential for plasma membrane association (PubMed:9813098).
This protein is associated with nerve growth. It is a major component of the motile 'growth cones' that form the tips of elongating axons. Plays a role in axonal and dendritic filopodia induction (By similarity).
Belongs to the glycosyltransferase 54 family.
Glycosyltransferase that catalyzes the transfer of GlcNAc to the Manalpha1-6 arm to form GlcNAcBeta1-4Manalpha1-6 linkage (also named 'GnT-VI' activity). May also participate in the transfer of N-acetylglucosamine (GlcNAc) to the core mannose residues of N-linked glycans by catalyzing the formation of the GlcNAcbeta1-4 branch on the GlcNAcbeta1-2Manalpha1-3 arm of the core structure of N-linked glycans.
Highly expressed in oviduct, spleen, lung and colon.
Myosin is a hexamer of 2 heavy chains and 4 light chains.
Myosin regulatory subunit that plays an important role in regulation of both smooth muscle and nonmuscle cell contractile activity. Implicated in cytokinesis, receptor capping, and cell locomotion (By similarity).
Phosphorylation increases the actin-activated myosin ATPase activity and thereby regulates the contractile activity.
Guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades. The alpha chain contains the guanine nucleotide binding site and alternates between an active, GTP-bound state and an inactive, GDP-bound state. Signaling by an activated GPCR promotes GDP release and GTP binding. The alpha subunit has a low GTPase activity that converts bound GTP to GDP, thereby terminating the signal. Both GDP release and GTP hydrolysis are modulated by numerous regulatory proteins (By similarity). Signaling is mediated via effector proteins, such as adenylate cyclase. Inhibits adenylate cyclase activity, leading to decreased intracellular cAMP levels (By similarity). Required for cortical dynein-dynactin complex recruitment during metaphase (By similarity).
Heterotrimeric G proteins are composed of 3 units; alpha, beta and gamma. The alpha chain contains the guanine nucleotide binding site. Part of a spindle orientation complex. Identified in complex with the beta subunit GNB1 and the gamma subunit GNG1. Identified in complex with the beta subunit GNB1 and the gamma subunit GNG2. GTP binding causes dissociation of the heterotrimer, liberating the individual subunits so that they can interact with downstream effector proteins (By similarity).
Myristoylation at Gly-2 is required for membrane anchoring before palmitoylation.
Palmitoylation at Cys-3 varies with membrane lipid composition.
Belongs to the protein-tyrosine phosphatase family. Non-receptor class myotubularin subfamily.
Phosphatase that acts on lipids with a phosphoinositol headgroup. Has phosphatase activity towards phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate (By similarity).
Does not show activity against influenza virus, VSV, Thogoto virus or Sendai virus.
Belongs to the carnitine/choline acetyltransferase family.
Lectin that binds to various sugars: galactose > mannose = fucose > N-acetylglucosamine > N-acetylgalactosamine. Acts as a chemoattractant, probably involved in the regulation of cell migration.
Widely expressed. Highly expressed in lung. Weakly expressed in larynx, syrinx and cranial air sac. Expressed throughout the lower gastrointestinal tract in increasing levels starting from a faint signal in duodenum and ending with relatively high signals in proctodeum, coprodeum and urodeum. In the upper part of the gastrointestinal tract, expressed in tongue, crop, and mucosa of the crop.
Belongs to the glycosyl hydrolase 47 family.
Belongs to the transglutaminase-like superfamily. PNGase family.
Specifically deglycosylates the denatured form of N-linked glycoproteins in the cytoplasm and assists their proteasome-mediated degradation. Cleaves the beta-aspartyl-glucosamine (GlcNAc) of the glycan and the amide side chain of Asn, converting Asn to Asp. Prefers proteins containing high-mannose over those bearing complex type oligosaccharides. Can recognize misfolded proteins in the endoplasmic reticulum that are exported to the cytosol to be destroyed and deglycosylate them, while it has no activity toward native proteins. Deglycosylation is a prerequisite for subsequent proteasome-mediated degradation of some, but not all, misfolded glycoproteins (By similarity).
Component of the signal peptidase complex.
Belongs to the beta-2-microglobulin family.
Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system.
Heterodimer of an alpha chain and a beta chain. Beta-2-microglobulin is the beta-chain of major histocompatibility complex class I molecules.
Belongs to the DEAD box helicase family. DDX59 subfamily.
May negatively regulate RAC1 signaling and RAC1-driven cytoskeletal remodeling. May regulate chemotaxis, cell migration and epithelial polarization by controlling the polarity, plasticity, duration and extent of protrusions.
As part of the MCIA complex, involved in the assembly of the mitochondrial complex I.
Belongs to the isocitrate and isopropylmalate dehydrogenases family.
Binds 1 Mg(2+) or Mn(2+) ion per subunit.
Component of the MRE11-RAD50-NBN (MRN complex) which plays a critical role in the cellular response to DNA damage and the maintenance of chromosome integrity (PubMed:12422221). The complex is involved in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity, cell cycle checkpoint control and meiosis (PubMed:12422221). The complex possesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity, which are provided by MRE11 (By similarity). RAD50 may be required to bind DNA ends and hold them in close proximity (By similarity). NBN modulate the DNA damage signal sensing by recruiting PI3/PI4-kinase family members ATM, ATR, and probably DNA-PKcs to the DNA damage sites and activating their functions (By similarity). It can also recruit MRE11 and RAD50 to the proximity of DSBs by an interaction with the histone H2AX (By similarity). NBN also functions in telomere length maintenance by generating the 3' overhang which serves as a primer for telomerase dependent telomere elongation (By similarity). NBN is a major player in the control of intra-S-phase checkpoint and there is some evidence that NBN is involved in G1 and G2 checkpoints (By similarity). The roles of NBS1/MRN encompass DNA damage sensor, signal transducer, and effector, which enable cells to maintain DNA integrity and genomic stability (By similarity). Forms a complex with RBBP8 to link DNA double-strand break sensing to resection (By similarity).
Component of the MRN complex composed of two heterodimers RAD50/MRE11 associated with a single NBN. Interacts with RBBP8; the interaction links the role of the MRN complex in DNA double-strand break sensing to resection.
Phosphorylated by ATM in response of ionizing radiation, and such phosphorylation is responsible intra-S phase checkpoint control and telomere maintenance.
The C-terminal domain contains a MRE11-binding site, and this interaction is required for the nuclear localization of the MRN complex.
The EEXXXDDL motif at the C-terminus is required for the interaction with ATM and its recruitment to sites of DNA damage and promote the phosphorylation of ATM substrates, leading to the events of DNA damage response.
The FHA and BRCT domains are likely to have a crucial role for both binding to histone H2AX and for relocalization of MRE11/RAD50 complex to the vicinity of DNA damage.
Actin- and myosin-binding protein implicated in the regulation of actomyosin interactions in smooth muscle and nonmuscle cells (could act as a bridge between myosin and actin filaments). Stimulates actin binding of tropomyosin which increases the stabilization of actin filament structure. In muscle tissues, inhibits the actomyosin ATPase by binding to F-actin. This inhibition is attenuated by calcium-calmodulin and is potentiated by tropomyosin. Interacts with actin, myosin, two molecules of tropomyosin and with calmodulin. Also plays an essential role during cellular mitosis and receptor capping.
High-molecular-weight caldesmon (h-caldesmon) is predominantly expressed in smooth muscles, whereas low-molecular-weight caldesmon (l-caldesmon) is widely distributed in non-muscle tissues and cells. Not expressed in skeletal muscle or heart.
Phosphorylated in non-muscle cells. Phosphorylation by CDK1 during mitosis causes caldesmon to dissociate from microfilaments. Phosphorylation reduces caldesmon binding to actin, myosin, and calmodulin as well as its inhibition of actomyosin ATPase activity. Phosphorylation also occurs in both quiescent and dividing smooth muscle cells with similar effects on the interaction with actin and calmodulin and on microfilaments reorganization (By similarity).
The N-terminal part seems to be a myosin/calmodulin-binding domain, and the C-terminal a tropomyosin/actin/calmodulin-binding domain. These two domains are separated by a central helical region in the muscle forms.
Transcriptional regulator that acts as a repressor or an activator. Binds DNA (By similarity).
Promotes degradation of target mRNA species. Plays a role in the regulation of circadian mRNA stability. Binds GTP and has GTPase activity.
Belongs to the dynein intermediate chain family.
S-nitrosylation inhibits channel currents and ATP release.
Down-regulated by thyroid hormone T3 in retinal ganglion layers during the embryonic development (PubMed:19179482).
Expressed in retina, hippocampus and cerebellum (PubMed:19179482). Expressed in the ganglion and bipolar cells of the inner and outer nuclear layers of the retina and in Purkinje cells (at protein level) (PubMed:19179482). Expressed strongly in brain and retina, weakly in testis and bone marrow (PubMed:19179482).
Plays a role in neuronal proliferation and differentiation (By similarity). Plays a role in the accumulation of cellular cholesterol (PubMed:19179482). Involved in intracellular lipid droplet formation (PubMed:19179482). May contribute to cholesterol homeostasis in neuronal cells (PubMed:19179482).
The SSD (sterol-sensing) domain is necessary for the increase in cellular cholesterol uptake (PubMed:19179482).
Belongs to the eIF-2B gamma/epsilon subunits family.
Activated by threonine and tyrosine phosphorylation.
Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. MAP kinase subfamily.
Interacts via its C2 domain with PtdIns(3)P and, to a lesser extent, PtdIns(5)P in vitro.
The EF-hand and C2 domains are essential for triggering Ca(2+) oscillating activity and the regulation of PLCZ1 enzyme activity.
The X-Y linker region between PI-PLC X-box and Y-box domains may be a target for proteolysis and may play an important regulatory role during fertilization.
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. In vitro, hydrolyzes PtdIns(4,5)P2 in a Ca(2+)-dependent manner. Triggers intracellular Ca(2+) oscillations in oocytes solely during M phase and is involved in inducing oocyte activation and initiating embryonic development up to the blastocyst stage. Is therefore a strong candidate for the egg-activating soluble sperm factor that is transferred from the sperm into the egg cytoplasm following gamete membrane fusion. May exert an inhibitory effect on phospholipase-C-coupled processes that depend on calcium ions and protein kinase C, including CFTR trafficking and function.
Probable core 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 (By similarity).
Probable core 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 (By similarity).
Belongs to the type IA topoisomerase family.
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.
Component of the tRNA-splicing ligase complex.
Belongs to the universal ribosomal protein uS17 family.
Belongs to the protein-tyrosine phosphatase family. Non-receptor class 1 subfamily.
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 (By similarity).
Phosphorylated on serine and threonine residues near the N-terminus by casein kinase II (CK2).
Belongs to the ABC transporter superfamily. ABCD family. Peroxisomal fatty acyl CoA transporter (TC 3.A.1.203) subfamily.
Belongs to the PNP/UDP phosphorylase family.
Catalyzes the reversible phosphorylytic cleavage of uridine and deoxyuridine to uracil and ribose- or deoxyribose-1-phosphate. The produced molecules are then utilized as carbon and energy sources or in the rescue of pyrimidine bases for nucleotide synthesis.
Belongs to the multicopper oxidase family.
Protein phosphatase 6 (PP6) holoenzyme is proposed to be a heterotrimeric complex formed by the catalytic subunit, a SAPS domain-containing subunit (PP6R) and an ankyrin repeat-domain containing regulatory subunit (ARS).
Regulatory subunit of protein phosphatase 6 (PP6). May function as a scaffolding PP6 subunit (By similarity).
An adhesive role by integrating collagen bundles. It is probably associated with the surface of interstitial collagen fibrils via COL1. The COL2 domain may then serve as a rigid arm which sticks out from the fibril and protrudes the large N-terminal globular domain into the extracellular space, where it might interact with other matrix molecules or cell surface receptors.
Belongs to the fibril-associated collagens with interrupted helices (FACIT) family.
Lysines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in all cases and bind carbohydrates.
May contain numerous cysteine residues involved in inter- and intramolecular disulfide bonding.
Wide tissue distribution; high presence in dense connective tissue in skeletal muscle.
Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. CDC5/Polo subfamily.
Belongs to the integrin alpha chain family.
Component of the ARISC complex, at least composed of UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1. Component of the BRCA1-A complex, at least composed of BRCA1, BARD1, UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1. In the BRCA1-A complex, interacts directly with ABRAXAS1, BRCC3/BRCC36 and BABAM1/NBA1. Binds polyubiquitin. Component of the BRISC complex, at least composed of ABRAXAS2, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1. Identified in a complex with SHMT2 and the other subunits of the BRISC complex. Component of the BRCA1/BRCA2 containing complex (BRCC), which also contains BRCA1, BRCA2, BARD1, BRCC3/BRCC36 and RAD51. BRCC is a ubiquitin E3 ligase complex that enhances cellular survival following DNA damage. May interact with FAS and TNFRSF1A.
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 acts as an adapter that bridges the interaction between BABAM1/NBA1 and the rest of the complex, thereby being required for the complex integrity and modulating the E3 ubiquitin ligase activity of the BRCA1-BARD1 heterodimer. Component of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys-63'-linked ubiquitin in various substrates. Within the BRISC complex, acts as an adapter that bridges the interaction between BABAM1/NBA1 and the rest of the complex, thereby being required for the complex integrity. The BRISC complex is required for normal mitotic spindle assembly and microtubule attachment to kinetochores via its role in deubiquitinating NUMA1. The BRISC complex 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. Down-regulates the response to bacterial lipopolysaccharide (LPS) via its role in IFNAR1 deubiquitination. May play a role in homeostasis or cellular differentiation in cells of neural, epithelial and germline origins. May also act as a death receptor-associated anti-apoptotic protein, which inhibits the mitochondrial apoptotic pathway. May regulate TNF-alpha signaling through its interactions with TNFRSF1A; however these effects may be indirect.
Contains 2 ubiquitin-conjugating enzyme family-like (UEV-like) regions. These regions lack the critical Cys residues required for ubiquitination but retain the ability to bind ubiquitin.
Belongs to the PNRC family. PNRC2 subfamily.
Involved in nonsense-mediated mRNA decay (NMD) by acting as a bridge between the mRNA decapping complex and the NMD machinery. May act by targeting the NMD machinery to the P-body and recruiting the decapping machinery to aberrant mRNAs. Required for UPF1/RENT1 localization to the P-body. Also acts as a nuclear receptor coactivator (By similarity).
Belongs to the class-V pyridoxal-phosphate-dependent aminotransferase family. NifS/IscS subfamily.
Belongs to the metallo-dependent hydrolases superfamily. Hydantoinase/dihydropyrimidinase family.
Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton. Plays a role in axon guidance, neuronal growth cone collapse and cell migration.
Belongs to the acetyltransferase family. GNAT subfamily.
Belongs to the complex I NDUFA10 subunit family.
Complex I is composed of 45 different subunits. This a component of the hydrophobic protein fraction.
Phosphorylates Ins(1,3,4,5,6)P5 at position 2 to form Ins(1,2,3,4,5,6)P6 (InsP6 or phytate).
The EXKPK motif is conserved in inositol-pentakisphosphate 2-kinases of both family 1 and 2.
Belongs to the ribonucleoside diphosphate reductase large chain family.
Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides.
Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily.
Belongs to the fatty acid desaturase type 1 family.
Belongs to the G-protein coupled receptor 1 family. Muscarinic acetylcholine receptor subfamily.
Belongs to the G-protein coupled receptor 1 family. Muscarinic acetylcholine receptor subfamily. CHRM4 sub-subfamily.
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins.
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is inhibition of adenylate cyclase. May couple to multiple functional responses in cell lines.
Involved in the synthesis of the GDP-mannose and dolichol-phosphate-mannose required for a number of critical mannosyl transfer reactions.
Belongs to the kynurenine formamidase family.
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.
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.
Belongs to the apolipoprotein C3 family.
Belongs to the universal ribosomal protein uL18 family.
Component of the large ribosomal subunit (LSU). Part of a LSU subcomplex, the 5S RNP which is composed of the 5S RNA, RPL5 and RPL11.
Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. The small ribosomal subunit (SSU) binds messenger RNAs (mRNAs) and translates the encoded message by selecting cognate aminoacyl-transfer RNA (tRNA) molecules. The large subunit (LSU) contains the ribosomal catalytic site termed the peptidyl transferase center (PTC), which catalyzes the formation of peptide bonds, thereby polymerizing the amino acids delivered by tRNAs into a polypeptide chain. The nascent polypeptides leave the ribosome through a tunnel in the LSU and interact with protein factors that function in enzymatic processing, targeting, and the membrane insertion of nascent chains at the exit of the ribosomal tunnel. As part of the 5S RNP/5S ribonucleoprotein particle it is an essential component of the LSU, required for its formation and the maturation of rRNAs. It also couples ribosome biogenesis to p53/TP53 activation. As part of the 5S RNP it accumulates in the nucleoplasm and inhibits MDM2, when ribosome biogenesis is perturbed, mediating the stabilization and the activation of TP53.
Belongs to the reduced folate carrier (RFC) transporter (TC 2.A.48) family.
Belongs to the TALE/PBX homeobox family.
Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair.
Belongs to the bacterial ribosomal protein bL20 family.
Belongs to the carbon-nitrogen hydrolase superfamily. NIT1/NIT2 family.
Belongs to the ATPase delta chain family.
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.
Belongs to the vasopressin/oxytocin family.
Seven disulfide bonds are present in neurophysin.
Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily.
Cyclins are positive regulatory subunits of the cyclin-dependent kinases (CDKs), and thereby play an essential role in the control of the cell cycle, notably via their destruction during cell division. Could be involved at the G2/M (mitosis or meiosis) transition. G2/M cyclins accumulate steadily during G2 and are abruptly destroyed at mitosis.
Interacts with the CDK1 and CDK2 protein kinases.
The N-terminal destruction box (D-box) probably acts as a recognition signal for degradation via the ubiquitin-proteasome pathway.
Ubiquitinated, leading to its degradation.
Highest expression is found in E1-E3 embryos with a significant decrease after 3.5 dpc.
In the embryo, expressed in early mesodermal cells, the neuroepithelial layer of the brain and the trunk neural tube, the neural layer of the retina and in the epithelial somite and dermomyotome. From mid-gastrulation to early somite stages, restricted to the posterior embryonic region but this posterior restriction is progressively lost during somitogenesis. As development proceeds, further restricted to the dorsal parts of the spinal cord and somites. In parallel, expression progresses caudally during axis elongation.
May play a role in anteroposterior axis elongation.
Belongs to the ELO family. ELOVL5 subfamily.
Catalyzes the first and rate-limiting reaction of the four reactions that constitute the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process allows the addition of 2 carbons to the chain of long- and very long-chain fatty acids (VLCFAs) per cycle. Condensing enzyme that acts specifically toward polyunsaturated acyl-CoA with the higher activity toward C18:3(n-6) acyl-CoA. May participate to the production of monounsaturated and of polyunsaturated VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators.
Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. Era GTPase family.
Probable GTPase that plays a role in the mitochondrial ribosomal small subunit assembly. Specifically binds the 12S mitochondrial rRNA (12S mt-rRNA) to a 33 nucleotide section delineating the 3' terminal stem-loop region. May act as a chaperone that protects the 12S mt-rRNA on the 28S mitoribosomal subunit during ribosomal small subunit assembly (By similarity).
Autophosphorylated on tyrosine residues upon ligand binding.
Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily.
Interacts with VEGFA, VEGFB and PGF. Monomer in the absence of bound VEGFA, VEGFB or PGF. Homodimer in the presence of bound VEGFA, VEGFB and PGF (By similarity).
Present in an inactive conformation in the absence of bound ligand. Binding of VEGFA, VEGFB or PGF leads to dimerization and activation by autophosphorylation on tyrosine residues (By similarity).
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the regulation of angiogenesis, cell survival, cell migration, macrophage function, and chemotaxis. Acts as a positive regulator of postnatal retinal hyaloid vessel regression (By similarity). Has very high affinity for VEGFA and relatively low protein kinase activity; may function as a negative regulator of VEGFA signaling by limiting the amount of free VEGFA and preventing its binding to KDR. 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 and the activation of protein kinase C. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leading to activation of phosphatidylinositol kinase and the downstream signaling pathway. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Phosphorylates PLCG1. Promotes phosphorylation of AKT1 and CBL (By similarity).
Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.
Lymphotoxin beta-activated kinase which seems to be exclusively involved in the activation of NF-kappa-B and its transcriptional activity.
Binds to the catalytic subunit of the cyclin dependent kinases and is essential for their biological function.
Forms a homohexamer that can probably bind six kinase subunits.
Core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome.
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. Component of both the pre-catalytic spliceosome B complex and activated spliceosome C complexes. Is also a component of the minor U12 spliceosome. As part of the U7 snRNP it is involved in histone 3'-end processing.
Detected in the theca and granulosa layers of the ovarian follicle in the white follicle (WF), F1, F3, F5, and postovulatory follicle stages.
Induced in the theca layer of the F3 stage ovarian follicle by intravenous injection of LPS. Expression in the kidney and liver is not affected by intravenous injection of LPS.
Strong expression in the bone marrow and testis. Expressed in the ovarian stroma and the theca layer of the ovarian follicles. Not expressed in the granulosa layer of the ovarian follicles.
Forms a homodimer or heterodimer with other members of the family.
The insulin-like growth factors, isolated from plasma, are structurally and functionally related to insulin but have a much higher growth-promoting activity. Acts as a ligand for IGF1R. Binds to the alpha subunit of IGF1R, leading to the activation of the intrinsic tyrosine kinase activity which autophosphorylates tyrosine residues in the beta subunit thus initiatiating a cascade of down-stream signaling events leading to activation of the PI3K-AKT/PKB and the Ras-MAPK pathways. Binds to integrins. Its binding to integrins and subsequent ternary complex formation with integrins and IGFR1 are essential for IGF1 signaling.
Belongs to the universal ribosomal protein uS7 family.
Component of the mitochondrial ribosome small subunit (28S) which comprises a 12S rRNA and about 30 distinct proteins.
Belongs to the GTP-binding SRP family. SRP54 subfamily.
Component of a signal recognition particle (SRP) complex that consists of a 7SL RNA molecule of 300 nucleotides and six protein subunits: SRP72, SRP68, SRP54, SRP19, SRP14 and SRP9.
Component of the signal recognition particle (SRP) complex, a ribonucleoprotein complex that mediates the cotranslational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER). Binds to the signal sequence of presecretory proteins when they emerge from the ribosomes.
Has a two domain structure: the G-domain binds GTP; the M-domain binds the 7S RNA in presence of SRP19 and also binds the signal sequence.
Signal recognition particle consists of a 7S RNA molecule and at least six protein subunits.
Belongs to the methyltransferase superfamily. METTL16/RlmF family.
Methyltransferase activity is autoinhibited by the K-loop region that blocks S-adenosyl-L-methionine-binding. Upon activation, K-loop changes conformation, allowing S-adenosyl-L-methionine-binding and subsequent methyltransferase activity. mRNA N6-adenosine-methyltransferase activity is inhibited by zinc.
RNA N6-methyltransferase that methylates adenosine residues at the N(6) position of a subset of RNAs and is involved in S-adenosyl-L-methionine homeostasis by regulating expression of MAT2A transcripts. Able to N6-methylate a subset of mRNAs and U6 small nuclear RNAs (U6 snRNAs). In contrast to the METTL3-METTL14 heterodimer, only able to methylate a limited number of RNAs: requires both a 5'UACAGAGAA-3' nonamer sequence and a specific RNA structure. Plays a key role in S-adenosyl-L-methionine homeostasis by mediating N6-methylation of MAT2A mRNAs, altering splicing of MAT2A transcripts: in presence of S-adenosyl-L-methionine, binds the 3'-UTR region of MAT2A mRNA and specifically N6-methylates the first hairpin of MAT2A mRNA, impairing MAT2A splicing and protein expression. In S-adenosyl-L-methionine-limiting conditions, binds the 3'-UTR region of MAT2A mRNA but stalls due to the lack of a methyl donor, preventing N6-methylation and promoting expression of MAT2A. In addition to mRNAs, also able to mediate N6-methylation of U6 small nuclear RNA (U6 snRNA): specifically N6-methylates adenine in position 43 of U6 snRNAs.
The K-loop region occludes the S-adenosyl-L-methionine-binding pocket. Upon activation, conformation of the K-loop changes, allowing S-adenosyl-L-methionine-binding.
The VCR (vertebrate conserved) regions bind the first hairpin of MAT2A mRNAs. The VCR regions interact with the internal stem-loop within U6 snRNAs, inducing the conformational rearrangement of the A43-containing region of U6 snRNA, thereby modifying the RNA structure to become suitable for productive catalysis by the methyltransferase region.
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. In contrast, Ca(2+) acts as a cofactor by inducing conformational change to the active open form. In absence of Ca(2+), Mg(2+) may bind Ca(2+)-binding sites, promoting GTP-binding and subsequent inhibition of the acyltransferase activity.
Belongs to the transglutaminase superfamily. Transglutaminase family.
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. Involved in many biological processes, such as bone development, angiogenesis, wound healing, cellular differentiation, chromatin modification and apoptosis. Acts as a protein-glutamine gamma-glutamyltransferase by mediating the cross-linking of proteins: under physiological conditions, the protein cross-linking activity is inhibited by GTP; inhibition is relieved by Ca(2+) in response to various stresses. When secreted, catalyzes cross-linking of proteins of the extracellular matrix, resulting in the formation of scaffolds. 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. 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 (By similarity). Mediates protein serotonylation of small GTPases during activation and aggregation of platelets, leading to constitutive activation of these GTPases (By similarity). Plays a key role in chromatin organization by mediating serotonylation and dopaminylation of histone H3. Catalyzes serotonylation of 'Gln-5' of histone H3 (H3Q5ser) during serotonergic neuron differentiation, thereby facilitating transcription. Acts as a mediator of neurotransmission-independent role of nuclear dopamine in ventral tegmental area (VTA) neurons: catalyzes dopaminylation of 'Gln-5' of histone H3 (H3Q5dop), thereby regulating relapse-related transcriptional plasticity in the reward system (By similarity). Also acts as a protein deamidase by mediating the side chain deamidation of specific glutamine residues of proteins to glutamate. May also act as an isopeptidase cleaving the previously formed cross-links. Also able to participate in signaling pathways independently of its acyltransferase activity: acts as a signal transducer in alpha-1 adrenergic receptor-mediated stimulation of phospholipase C-delta (PLCD) activity and is required for coupling alpha-1 adrenergic agonists to the stimulation of phosphoinositide lipid metabolism (By similarity).
Predominates in mature erythrocytes. Also found in kidney and cardiac muscle.
Divalent metal cations. Mn(2+) or Co(2+).
Metalloprotease that acts as a negative regulator of the Wnt signaling pathway by mediating the cleavage of the N-terminal residues of a subset of Wnt proteins. Following cleavage, Wnt proteins become oxidized and form large disulfide-bond oligomers, leading to their inactivation.
Transporter that mediates the import of reduced folates.
CNTF is a survival factor for various neuronal cell types. Seems to prevent the degeneration of motor axons after axotomy.
Catalyzes the transfer of one adenosine molecule from an ATP to an mRNA poly(A) tail bearing a 3'-OH terminal group and enhances mRNA stability and gene expression.
Belongs to the 5'-AMP-activated protein kinase beta subunit family.
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).
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.
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).
Monoubiquitination of Lys-120 (H2AK119Ub) gives a specific tag for epigenetic transcriptional repression. Following DNA double-strand breaks (DSBs), it is ubiquitinated through 'Lys-63' linkage of ubiquitin moieties, leading to the recruitment of repair proteins to sites of DNA damage. H2AK119Ub and ionizing radiation-induced 'Lys-63'-linked ubiquitination are distinct events (By similarity).
Phosphorylation on Ser-2 is enhanced during mitosis. Phosphorylation on Ser-2 directly represses transcription (By similarity).
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.
Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family.
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.
Cell surface proteoglycan that bears heparan sulfate.
Nuclear hormone receptor that can act as a repressor or activator of transcription. High affinity receptor for thyroid hormones, including triiodothyronine and thyroxine.
Potential NADPH-dependent oxidoreductase. May be involved in the regulation of neuronal survival, differentiation and axonal outgrowth (By similarity).
Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.
Belongs to the apolipoprotein A1/A4/E family.
Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. EF-G/EF-2 subfamily.
Component of the U5 snRNP and the U4/U6-U5 tri-snRNP complex, a building block of the spliceosome (By similarity). Component of the pre-catalytic, catalytic and post-catalytic spliceosome complexes (By similarity).
Required for pre-mRNA splicing as component of the spliceosome, including pre-catalytic, catalytic and post-catalytic spliceosomal complexes (By similarity). Component of the U5 snRNP and the U4/U6-U5 tri-snRNP complex, a building block of the spliceosome (By similarity).
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.
Butyrylation of histones marks active promoters and competes with histone acetylation.
Citrullination at Arg-4 (H4R3ci) by PADI4 impairs methylation.
Glutarylation at Lys-92 (H4K91glu) destabilizes nucleosomes by promoting dissociation of the H2A-H2B dimers from nucleosomes.
Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.
Monomethylated, dimethylated or trimethylated at Lys-21 (H4K20me1, H4K20me2, H4K20me3). Monomethylation is performed by KMT5A/SET8. Trimethylation is performed by KMT5B and KMT5C and induces gene silencing. Monomethylated at Lys-13 (H4K12me1) by N6AMT1; H4K12me1 modification is present at the promoters of numerous genes encoding cell cycle regulators.
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 (By similarity).
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 (By similarity).
Sumoylated, which is associated with transcriptional repression.
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) (By similarity).
Ufmylated; monofmylated by UFL1 at Lys-32 (H4K31Ufm1) in response to DNA damage.
Gamma-tubulin complex is necessary for microtubule nucleation at the centrosome.
Belongs to the somatotropin/prolactin family.
Belongs to the helicase family. RLR subfamily.
Belongs to the immunoglobulin superfamily. IgLON family.
Expressed in embryonic retina, telencephalon, tectum, cerebellum and diencephalon (at protein level).
May be involved in cell-adhesion. May participate in the regulation of neurite outgrowth in the developing brain.
Belongs to the glycosyl hydrolase 99 family.
Major helicase player in mitochondrial RNA metabolism. Component of the mitochondrial degradosome (mtEXO) complex, that degrades 3' overhang double-stranded RNA with a 3'-to-5' directionality in an ATP-dependent manner. ATPase and ATP-dependent multisubstrate helicase, able to unwind double-stranded (ds) DNA and RNA, and RNA/DNA heteroduplexes in the 5'-to-3' direction. Plays a role in the RNA surveillance system in mitochondria; regulates the stability of mature mRNAs, the removal of aberrantly formed mRNAs and the rapid degradation of non coding processing intermediates. Also implicated in recombination and chromatin maintenance pathways. May protect cells from apoptosis. Associates with mitochondrial DNA (By similarity).
Expressed in bone marrow, testis, ovary, lung and trachea. Expressed in the ovarian stroma, but not in the ovarian follicles.
Has bactericidal activity. Potent activity against S.typhimurium and S.entiriditis.
Adds a myristoyl group to the N-terminal glycine residue of certain cellular proteins.
Protein transport. Probably involved in vesicular traffic.
Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP.
Expressed at embryonic stage 20 in the notchcord and weakly in the foor plate and persist until stage 29. Expressed in the motor neuron pool at stage 23. At stage 26 and 29 highly expressed in the ventrolateral neural tube and also in the roof plate.
May play a role in CNS development by interacting with growth factors implicated in motor neuron differentiation and survival.
Belongs to the ubiquitin conjugation factor E4 family.
Belongs to the glycosyltransferase 29 family.
Binds two Mg(2+) per subunit. Required for catalysis and for stabilizing the dimer.
Calmodulin acts as part of a calcium signal transduction pathway by mediating the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. Calcium-binding is required for the activation of calmodulin. Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases, such as myosin light-chain kinases and calmodulin-dependent protein kinase type II (CaMK2), and phosphatases.
This protein has four functional calcium-binding sites.
Interacts with AP5Z1, AP5B1, AP5S1 and SPG11. Interacts with TTC19 and KIF13A.
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.
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. In the PRC1-like complex, regulates the E3 ubiquitin-protein ligase activity of RNF2/RING2.
During early nervous system development, robust expression was observed in the open neural plate and later in the dorsal neural tube and much of the brain. Also present in the developing heart primordia and the sensory placodes.
Belongs to the GMC oxidoreductase family.
Belongs to the calycin superfamily. Lipocalin family.
Interacts with TTR. Interaction with TTR prevents its loss by filtration through the kidney glomeruli. Interacts with STRA6.
Retinol-binding protein that mediates retinol transport in blood plasma. Delivers retinol from the liver stores to the peripheral tissues. Transfers the bound all-trans retinol to STRA6, that then facilitates retinol transport across the cell membrane.
Belongs to the DEAD box helicase family. DDX10/DBP4 subfamily.
The Q motif is unique to and characteristic of the DEAD box family of RNA helicases and controls ATP binding and hydrolysis.
RNA-binding protein that specifically bind the 3'-UTR of some transcripts, leading to maintain their stability. Also acts as a mRNA splicing factor. May play a role in myogenic differentiation (By similarity).
Belongs to the UPL family. K-HECT subfamily.
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.
Belongs to the protein kinase superfamily. ADCK protein kinase family.
Belongs to the dynein light chain family.
Functions in lipid transport from the endoplasmic reticulum and is involved in a wide array of cellular functions probably through regulation of the biogenesis of lipid microdomains at the plasma membrane. Regulates calcium efflux at the endoplasmic reticulum.
May function in lipid transport from the endoplasmic reticulum and be involved in a wide array of cellular functions probably through regulation of the biogenesis of lipid microdomains at the plasma membrane. May regulate calcium efflux at the endoplasmic reticulum (By similarity).
Sigma receptors are classified into two subtypes (Sigma-1 and Sigma-2) based on their different pharmacological profile.
The C-terminal helices form a flat, hydrophobic surface that is probably tightly associated with the cytosolic surface of the endoplasmic reticulum membrane.
Belongs to the prickle / espinas / testin family.
Belongs to the class-II aminoacyl-tRNA synthetase family. Type-1 seryl-tRNA synthetase subfamily.
Belongs to the WD repeat coronin family.
Association with CENPA-containing complexes may be indirect and due to the proximity of centromeric nucleosomes containing histone H3 with those containing CENPA.
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 (By similarity). The CENPA-NAC complex recruits the CENPA-CAD (nucleosome distal) complex and may be involved in incorporation of newly synthesized CENPA into centromeres (By similarity). Part of a nucleosome-associated complex that binds specifically to histone H3-containing nucleosomes at the centromere, as opposed to nucleosomes containing CENPA. Component of the heterotetrameric CENP-T-W-S-X complex that binds and supercoils DNA, and plays an important role in kinetochore assembly. CENPW has a fundamental role in kinetochore assembly and function. It is one of the inner kinetochore proteins, with most further proteins binding downstream. Required for normal chromosome organization and normal progress through mitosis.
Heterodimer with CENPT; this dimer coassembles with CENPS-CENPX heterodimers at centromeres to form the tetrameric CENP-T-W-S-X complex, which is a subcomplex of the large constitutive centromere-associated network (CCAN, also known as the interphase centromere complex or ICEN) (PubMed:19070575, PubMed:21464230, PubMed:22304917). Interacts with NPM1 (By similarity).
Can induce apoptosis in a caspase-dependent manner and plays a role in p53/TP53-dependent apoptosis.
The proline-rich region is required for endoplasmic reticulum localization.
Binds strongly to viral nucleic acids and promote their aggregation. Also destabilizes the nucleic acids duplexes via highly structured zinc-binding motifs.
Capsid protein p27: Self-associates to form the irregular polyhedron core composed of hexamers and pentamers, that encapsulates the genomic RNA-nucleocapsid complex. Assembles as a tube in vitro.
The products of the Gag polyproteins of infectious retroviruses perform highly complex orchestrated tasks during the assembly, budding, maturation, and infection stages of the viral replication cycle. During viral assembly, the proteins form membrane associations and self-associations that ultimately result in budding of an immature virion from the infected cell. Gag precursors also function during viral assembly to selectively bind and package two plus strands of genomic RNA. Endogenous Gag proteins may have kept, lost or modified their original function during evolution.
May be involved in normal spermatogenesis and sperm function. Binds to double-stranded DNA and RNA (By similarity).
Acts as a negative regulator of transcription.
Highly expressed in developing brain and spinal cord.
Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.
Binds to linear ubiquitin chains. Interacts with LC3 family members (By similarity).
Expressed in erythrocytes, skeletal muscle, heart, spleen and brain. Weakly expressed in lung and liver (at protein level).
Probably part of the TNF-alpha signaling pathway that can shift the equilibrium toward induction of cell death. May act by regulating membrane trafficking and cellular morphogenesis. May act as autophagy receptor that interacts directly with both the cargo to become degraded and an autophagy modifier of the MAP1 LC3 family.
The LIR (LC3-interacting region) motif mediates the interaction with ATG8 family proteins.
Ubiquitin-binding motif (UBAN) is essential for its inhibitory function, subcellular localization and interaction with TBK1.
Belongs to the nucleotide-sugar transporter family. SLC35A subfamily.
Confers resistance to the antitumor agent cisplatin. Binds preferentially to sites of DNA modified by cisplatin in vitro. Binds to double-stranded DNA in a cooperative manner resulting in the formation of filament-like structures. Binds to single-stranded DNA with no cooperativity. Binds to RNA.
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. Is not required for association of CNOT7 to the CCR4-NOT complex (By similarity).
Component of the CCR4-NOT complex. CNOT10 and CNOT11 form a subcomplex docked to the CNOT1 scaffold (By similarity).
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 cell growth and differentiation.
Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity.
A cytochrome P450 monooxygenase involved in the metabolism of all-trans retinoic acid (atRA), a signaling molecule that binds to retinoic acid receptors and regulates gene transcription (PubMed:10588879). 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 the hydroxylation of carbon hydrogen bonds of atRA primarily at C-4 (PubMed:10588879). Has no activity toward 9-cis and 13-cis retinoic acid stereoisomers. May play a role in the oxidative metabolism of xenobiotics such as tazarotenic acid (By similarity).
Expressed at stage 4 in the ectoderm, stage 5-7 in the nascent notochord and at stage 7 its expression decreases in the anterior part of the embryo. From stage 7-10 its expression is restricted to the dorsal folds of the neural tube and to rhombomere 2. At stage 10, it is expressed in the lateral plate endoderm and in the tail bud and by stage 11/12 it disappears in the neural tube, followed by a confined expression at stage 12 to dorsal neural tube and at stage 15 an increasing expression in the ectoderm.
Belongs to the glucose-6-phosphatase family.
Involved in cytoskeletal rearrangements required for phagocytosis of apoptotic cells and cell motility. Acts in association with DOCK1 and CRK. Was initially proposed to be required in complex with DOCK1 to activate Rac Rho small GTPases. May enhance the guanine nucleotide exchange factor (GEF) activity of DOCK1.
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PDPK1 subfamily.
Belongs to the bile acid:sodium symporter (BASS) (TC 2.A.28) family.
Receptor for neuropeptide Y and peptide YY. The activity of this receptor is mediated by G proteins that inhibit adenylate cyclase activity. Seems to be associated with food intake. Could be involved in feeding disorders.
Belongs to the universal ribosomal protein uS3 family.
Reversible hydration of carbon dioxide. Its role in saliva is unknown.
Belongs to the zinc-containing alcohol dehydrogenase family.
Mitochondrial NAD(+) kinase that phosphorylates NAD(+) to yield NADP(+). Can use both ATP or inorganic polyphosphate as the phosphoryl donor.
Belongs to the peroxiredoxin family. Prx6 subfamily.
Homodimer (By similarity). Interacts with GSTP1; mediates PRDX6 glutathionylation and regeneration (By similarity).
Irreversibly inactivated by overoxidation of Cys-46 to sulfinic acid (Cys-SO(2)H) and sulfonic acid (Cys-SO(3)H) forms upon oxidative stress.
Phosphorylation at Thr-176 by MAP kinases increases the phospholipase activity of the enzyme (By similarity). The phosphorylated form exhibits a greater lysophosphatidylcholine acyltransferase activity compared to the non-phosphorylated form (By similarity).
The active site is a conserved redox-active cysteine residue, the peroxidatic cysteine (C(P)), which makes the nucleophilic attack on the peroxide substrate. The peroxide oxidizes the C(P)-SH to cysteine sulfenic acid (C(P)-SOH), which then reacts with another cysteine residue, the resolving cysteine (C(R)), to form a disulfide bridge. The disulfide is subsequently reduced by an appropriate electron donor to complete the catalytic cycle. In this 1-Cys peroxiredoxin, no C(R) is present and C(P) instead forms a disulfide with a cysteine from another protein or with a small thiol molecule. C(P) is reactivated by glutathionylation mediated by glutathione S-transferase Pi, followed by spontaneous reduction of the enzyme with glutathione.
Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively (By similarity). Can reduce H(2)O(2) and short chain organic, fatty acid, and phospholipid hydroperoxides (By similarity). Also has phospholipase activity, and can therefore either reduce the oxidized sn-2 fatty acyl group of phospholipids (peroxidase activity) or hydrolyze the sn-2 ester bond of phospholipids (phospholipase activity) (By similarity). These activities are dependent on binding to phospholipids at acidic pH and to oxidized phospholipds at cytosolic pH (By similarity). Plays a role in cell protection against oxidative stress by detoxifying peroxides and in phospholipid homeostasis (By similarity). Exhibits acyl-CoA-dependent lysophospholipid acyltransferase which mediates the conversion of lysophosphatidylcholine (1-acyl-sn-glycero-3-phosphocholine or LPC) into phosphatidylcholine (1,2-diacyl-sn-glycero-3-phosphocholine or PC) (By similarity). Shows a clear preference for LPC as the lysophospholipid and for palmitoyl CoA as the fatty acyl substrate (By similarity).
Required during ciliogenesis for tubulin glutamylation in cilium. Probably acts by participating in the transport of tubulin polyglutamylases between the basal body and the cilium (By similarity).
Belongs to the SLC26A/SulP transporter (TC 2.A.53) family.
Lysophosphatidylserine (LPS) lipase that mediates the hydrolysis of lysophosphatidylserine, a class of signaling lipids that regulates immunological and neurological processes (By similarity). 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. Also has monoacylglycerol (MAG) lipase activity: hydrolyzes 2-arachidonoylglycerol (2-AG), thereby acting as a regulator of endocannabinoid signaling pathways. Has a strong preference for very-long-chain lipid substrates; substrate specificity is likely due to improved catalysis and not improved substrate binding (By similarity).
Belongs to the prostaglandin G/H synthase family.
Binds 1 heme b (iron(II)-protoporphyrin IX) group per subunit.
Conversion of arachidonate to prostaglandin H2 is mediated by 2 different isozymes: the constitutive PTGS1 and the inducible PTGS2. PTGS1 is expressed constitutively and generally produces prostanoids acutely in response to hormonal stimuli to fine-tune physiological processes requiring instantaneous, continuous regulation (e.g. hemostasis). PTGS2 is inducible and typically produces prostanoids that mediate responses to physiological stresses such as infection and inflammation.
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and brain, and in pathological conditions, such as in cancer. PTGS2 is responsible for production of inflammatory prostaglandins. Up-regulation of PTGS2 is also associated with increased cell adhesion, phenotypic changes, resistance to apoptosis and tumor angiogenesis. In cancer cells, PTGS2 is a key step in the production of prostaglandin E2 (PGE2), which plays important roles in modulating motility, proliferation and resistance to apoptosis.
PTGS1 and PTGS2 are the targets of nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin and ibuprofen. Aspirin is able to produce an irreversible inactivation of the enzyme through a serine acetylation. Inhibition of the PGHSs with NSAIDs acutely reduces inflammation, pain, and fever, and long-term use of these drugs reduces fatal thrombotic events, as well as the development of colon cancer and Alzheimer's disease. PTGS2 is the principal isozyme responsible for production of inflammatory prostaglandins. New generation PTGSs inhibitors strive to be selective for PTGS2, to avoid side effects such as gastrointestinal complications and ulceration.
The conversion of arachidonate to prostaglandin H2 is a 2 step reaction: a cyclooxygenase (COX) reaction which converts arachidonate to prostaglandin G2 (PGG2) and a peroxidase reaction in which PGG2 is reduced to prostaglandin H2 (PGH2). The cyclooxygenase reaction occurs in a hydrophobic channel in the core of the enzyme. The peroxidase reaction occurs at a heme-containing active site located near the protein surface. The nonsteroidal anti-inflammatory drugs (NSAIDs) binding site corresponds to the cyclooxygenase active site.
Binds to the inner side of the nucleosomal DNA thus altering the interaction between the DNA and the histone octamer. May be involved in the process which maintains transcribable genes in a unique chromatin conformation.
There are two HMG-14 proteins in chicken: HMG-14A the major component, and HMG-14B the minor component.
Hexadecamer of 4 heterotetramers, each composed of alpha, beta, gamma, and delta subunits. Alpha (PHKA1 or PHKA2) and beta (PHKB) are regulatory subunits, gamma (PHKG1 or PHKG2) is the catalytic subunit, and delta is calmodulin.
Belongs to the FAD-binding oxidoreductase/transferase type 4 family.
Catalyzes the exchange of an acyl for a long-chain alkyl group and the formation of the ether bond in the biosynthesis of ether phospholipids.
Ciliary ganglion neurons. Levels are higher in the choroid than the iris.
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.
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.
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. Induces somatostatin in the ciliary ganglion neurons and may play a role in regulating neurotransmitter phenotype.
Levels increase in the iris from embryonic day 9 (9 dpc) to 16 dpc and in the choroid, levels are high from 9 dpc to 14 dpc but drop at 16 dpc.
Belongs to the activator 1 small subunits family.
Belongs to the selenium-binding protein family.
Catalyzes the oxidation of methanethiol, an organosulfur compound known to be produced in substantial amounts by gut bacteria. Selenium-binding protein which may be involved in the sensing of reactive xenobiotics in the cytoplasm. May be involved in intra-Golgi protein transport.
Belongs to the ABC transporter superfamily. ABCG family. Eye pigment precursor importer (TC 3.A.1.204) subfamily.
Belongs to the class-II aminoacyl-tRNA synthetase family.
Binds DNA as a homodimer. Can form a heterodimer with ER-beta.
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 (By similarity).
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.
The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues.
Belongs to the type I cytokine receptor family. Type 2 subfamily.
Belongs to the class V-like SAM-binding methyltransferase superfamily.
Involved in the positive regulation of histone H3-K9 dimethylation.
Belongs to the cysteine synthase/cystathionine beta-synthase family.
Belongs to the replication factor A protein 3 family.
Belongs to the transcription factor STAT family.
Belongs to the DNA glycosylase MPG family.
Hydrolysis of the deoxyribose N-glycosidic bond to excise 3-methyladenine, and 7-methylguanine from the damaged DNA polymer formed by alkylation lesions.
Belongs to the glycosyl hydrolase 35 family.
Belongs to the dienelactone hydrolase family.
Chaperone protein which plays an important role in mitochondrial iron-sulfur cluster (ISC) biogenesis. Interacts with and stabilizes ISC cluster assembly proteins FXN, NFU1, NFS1 and ISCU. Regulates erythropoiesis via stabilization of ISC assembly. May play a role in the control of cell proliferation and cellular aging.
Interacts strongly with the intermediate form of FXN and weakly with its mature form. Associates with the mitochondrial contact site and cristae organizing system (MICOS) complex (also known as MINOS or MitOS complex).
Belongs to the DNA polymerase type-X family.
Can also utilize other divalent cations, such as Mn(2+) and Co(2+) (in vitro).
Template-independent DNA polymerase which catalyzes the random addition of deoxynucleoside 5'-triphosphate to the 3'-end of a DNA initiator. One of the in vivo functions of this enzyme is the addition of nucleotides at the junction (N region) of rearranged Ig heavy chain and T-cell receptor gene segments during the maturation of B- and T-cells.
Belongs to the natriuretic peptide family.
Cleaved by CORIN upon secretion to produce the functional hormone.
Hormone playing a key role in cardiovascular homeostasis through regulation of natriuresis, diuresis, and vasodilation. Specifically binds and stimulates the cGMP production of the NPR1 receptor. Binds the clearance receptor NPR3 (By similarity).
Belongs to the Mrp/NBP35 ATP-binding proteins family. NUBP2/CFD1 subfamily.
Belongs to the sulfotransferase 2 family.
Catalyzes the transfer of sulfate to position 3 of terminal glucuronic acid of both protein- and lipid-linked oligosaccharides. Participates in biosynthesis of HNK-1 carbohydrate structure, a sulfated glucuronyl-lactosaminyl residue carried by many neural recognition molecules, which is involved in cell interactions during ontogenetic development and in synaptic plasticity in the adult (By similarity).
Predominantly expressed in hypertrophic, prehypertrophic and proliferative chondrocytes at E12 but is down-regulated in epiphyseal chondrocytes.
Belongs to the nucleoporin NSP1/NUP62 family.
Belongs to the universal ribosomal protein uL6 family.
Homodimer. Interacts with GCSH. The glycine cleavage system is composed of four proteins: P (GLDC), T (GCST), L (DLD) and H (GCSH).
Stimulated by lipoic acid. Inhibited in presence of methylamine.
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).
Component of the ribosomal small subunit (SSU) processome.
Involved in nucleolar processing of pre-18S ribosomal RNA.
Core 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. MAEA and RMND5A are both required for catalytic activity of the CTLH E3 ubiquitin-protein ligase complex. MAEA is required for normal cell proliferation. The CTLH E3 ubiquitin-protein ligase complex is not required for the degradation of enzymes involved in gluconeogenesis, such as FBP1 (By similarity). Plays a role in erythroblast maturation and in the development of mature macrophages (By similarity). Mediates the attachment of erythroid cell to mature macrophages; this MAEA-mediated contact inhibits erythroid cell apoptosis (By similarity). Participates in erythroblastic island formation, which is the functional unit of definitive erythropoiesis. Associates with F-actin to regulate actin distribution in erythroblasts and macrophages (By similarity). May contribute to nuclear architecture and cells division events (By similarity).
Identified in the CTLH complex that contains at least MAEA, RMND5A, GID8, WDR26, and RANBP9 and/or RANBP10 as the catalytic core. Interacts with F-actin.
The expected RING-type zinc finger domain is highly divergent and most of the expected Cys residues are not conserved. Still, the protein is required for CTLH complex E3 ubiquitin-protein transferase activity. In addition, the conserved Cys-314 in this highly divergent region is required for ubiquitination by the yeast GID complex, suggesting a direct role in catalyzing ubiquitination.
Belongs to the pseudouridine synthase TruB family.
Belongs to the eukaryotic ribosomal protein eL8 family.
Component of the large ribosomal subunit.
Belongs to the quiescin-sulfhydryl oxidase (QSOX) family.
Catalyzes the oxidation of sulfhydryl groups in peptide and protein thiols to disulfides with the reduction of oxygen to hydrogen peroxide. Plays a role in disulfide bond formation in a variety of extracellular proteins. In fibroblasts, required for normal incorporation of laminin into the extracellular matrix, and thereby for normal cell-cell adhesion and cell migration.
N-glycosylated. O-glycosylated on Thr and Ser residues.
Required for MAP kinase p38 (MAPK11, MAPK12, MAPK13 and/or MAPK14) activation during gastrulation.
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.
Acts as component of the GARP complex that is involved in retrograde transport from early and late endosomes to the trans-Golgi network (TGN). Acts as component of the EARP complex that is involved in endocytic recycling.
Component of the Golgi-associated retrograde protein (GARP) complex. Component of the endosome-associated retrograde protein (EARP) complex.
Belongs to the eukaryotic ribosomal protein eL38 family.
Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family. CACNA1B subfamily.
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. This alpha-1B subunit gives rise to N-type calcium currents. N-type calcium channels belong to the 'high-voltage activated' (HVA) group. They are involved in pain signaling. Calcium channels containing alpha-1B subunit may play a role in directed migration of immature neurons.
Belongs to the cyclin family. Cyclin G subfamily.
May play a role in growth regulation. Is associated with G2/M phase arrest in response to DNA damage. May be an intermediate by which p53 mediates its role as an inhibitor of cellular proliferation.
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family.
Involved in the maintenance of the Golgi structure.
Belongs to the pICln (TC 1.A.47) family.
ATP binding enhances channel sensitivity to agonists. Ca(2+)-calmodulin prevents the ATP-mediated increased sensitivity to agonists.
Belongs to the transient receptor (TC 1.A.4) family. TrpV subfamily. TRPV4 sub-subfamily.
Homotetramer (By similarity). Interacts with Ca(2+)-calmodulin (PubMed:19864432).
Non-selective calcium permeant cation channel involved in osmotic sensitivity and mechanosensitivity (PubMed:11081638). Activation by exposure to hypotonicity within the physiological range exhibits an outward rectification (PubMed:11081638). Also activated by phorbol esters (PubMed:19864432). Channel activity seems to be regulated by a calmodulin-dependent mechanism (By similarity).
The ANK repeat region mediates interaction with Ca(2+)-calmodulin and ATP binding (PubMed:19864432). The ANK repeat region mediates interaction with phosphatidylinositol-4,5-bisphosphate and related phosphatidylinositides (PubMed:25256292).
Belongs to the potassium channel KCNE family.
Although strongly related to RNA-specific endonuclease proteins, it lacks the HXHXDH motif that binds zinc and participates in the catalytic center. Its function as endonuclease is therefore unsure.
Belongs to the metallo-beta-lactamase superfamily. RNA-metabolizing metallo-beta-lactamase-like family. INTS9 subfamily.
Component of the Integrator complex, a complex involved in the small nuclear RNAs (snRNA) U1 and U2 transcription and in their 3'-box-dependent processing.
Belongs to the GTP-binding elongation factor family. EF-G/EF-2 subfamily.
Mitochondrial GTPase that catalyzes the GTP-dependent ribosomal translocation step during translation elongation. During this step, the ribosome changes from the pre-translocational (PRE) to the post-translocational (POST) state as the newly formed A-site-bound peptidyl-tRNA and P-site-bound deacylated tRNA move to the P and E sites, respectively. Catalyzes the coordinated movement of the two tRNA molecules, the mRNA and conformational changes in the ribosome. Does not mediate the disassembly of ribosomes from messenger RNA at the termination of mitochondrial protein biosynthesis.
Belongs to the heparin-binding growth factors family.
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.
May play a role in an as yet undefined retina-specific signal transduction. Could bind to photoactivated-phosphorylated red/green opsins.
Belongs to the GST superfamily. Theta family.
Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.
Belongs to the HIBADH-related family. 3-hydroxyisobutyrate dehydrogenase subfamily.
Belongs to the D-glutamate cyclase family.
Belongs to the TALE/MEIS homeobox family.
Belongs to the methyltransferase superfamily.
Belongs to the sphingomyelin synthase family.
Sphingomyelin synthases synthesize the sphingolipid, sphingomyelin, through transfer of the phosphatidyl head group, phosphatidylcholine, on to the primary hydroxyl of ceramide. The reaction is bidirectional depending on the respective levels of the sphingolipid and ceramide. Golgi apparatus SMS1 directly and specifically recognizes the choline head group on the substrate, requiring two fatty chains on the choline-P donor molecule in order to be recognized efficiently as a substrate. Major form in macrophages. Required for cell growth in certain cell types. Suppresses BAX-mediated apoptosis and also prevents cell death in response to stimuli such as hydrogen peroxide, osmotic stress, elevated temperature and exogenously supplied sphingolipids. May protect against cell death by reversing the stress-inducible increase in levels of proapoptotic ceramide (By similarity).
Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.
Promotes cell proliferation. Modulates apoptotic pathways. Increases mitogen-activated protein kinase activity. Important for cell migration, and for normal structure and assembly of the Golgi complex. Important for KDR/VEGFR2 signaling. Required for normal cardiovascular development. Required for normal angiogenesis, vasculogenesis and hematopoiesis during embryonic development.
Belongs to the ligand-gated ion channel (TC 1.A.9) family.
Belongs to the bZIP family. Jun subfamily.
Interacts with FOS to form a dimer. Interacts with Gallid herpesvirus 2 MEQ protein.
Transcription factor that recognizes and binds to the enhancer heptamer motif 5'-TGA[CG]TCA-3'. May be involved in activated KRAS-mediated transcriptional activation of USP28. May bind to the USP28 promoter.
Defects in Talpid3 are the cause of the spontaneous mutant with pleiotropic phenotype including polydactylous limbs with many unpatterned digits, vascular defects, hypoteleorism, abnormal dorsoventral patterning of the neural tube, loss of endochondral bone formation and embryonic lethality.
Failure of formation of primary and motile cilia in ependymal cells of the prosencephalic choroid plexus. Centrosomes are rarely found near the cell surface but are often mislocalized deep within the cell and do not show coordinate orientation within group.
Required for ciliogenesis and sonic hedgehog/SHH signaling (PubMed:16702409, PubMed:19144723, PubMed:26386247). Independently, involved in regulation of cell intracellular organization. Involved in regulation of cell polarity (PubMed:26386247).
D-glucose and maltose competitively inhibit fructose transport. D-glucose, D-fructose and maltose inhibit deoxyglucose transport.
Facilitative hexose transporter that mediates the transport of glucose, fructose and galactose. Likely mediates the bidirectional transfer of glucose across the plasma membrane of hepatocytes and is responsible for uptake of glucose by the beta cells.
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.
Essentially expressed during embryogenesis.
Has mitogenic activity, and neurite extension activity for PC12 cells.
Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP).
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. Within the complex, functions as a proteasomal ubiquitin receptor.
May be a component of the linker structure that bridges the ciliary membrane and peripheral singlet microtubules.
The protein contains 2 transactivation domains (TAD). Each of these domains may be required for transcriptional activation of a subset of target genes.
Transcription regulator that syncronizes transcriptional and translational programs to promote macrophage invasion of tissues.
Belongs to the class-V pyridoxal-phosphate-dependent aminotransferase family. SerC subfamily.
Catalyzes the reversible conversion of 3-phosphohydroxypyruvate to phosphoserine and of 3-hydroxy-2-oxo-4-phosphonooxybutanoate to phosphohydroxythreonine.
Involved in the histone deacetylase (HDAC1)-dependent transcriptional repression activity.
Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family.
Acts as a nucleation-promoting factor 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.
The VCA (verprolin, cofilin, acidic) domain promotes actin polymerization by the Arp2/3 complex in vitro.
Expressed in heart at embryonic day 12 and 14 (at protein level). Expressed in heart at embryonic day 8.
RNA-binding protein implicated in the regulation of several post-transcriptional events. May be involved in mRNA translation repression and stability. Mediates exon inclusion in TNNT2 pre-mRNA.
Expressed in differentiated myotomal muscle progenitors in embryos at 3 days of development (at protein level). Expressed in somites in embryos at 3 and 3.5 days of development. Expressed in the mesodermal core of the first and second branchial arches at 3 days of development. Expressed in forelimbs and hindlimbs at 3.5 days of development. Expressed in non-muscle territories including lens and otic vesicle at 3 days of development.
Multifunctional RNA-binding protein involved in the regulation of pre-mRNA splicing, mRNA stability and mRNA translation important for cell fate decision and differentiation. Plays a major role in pre-mRNA alternative splicing regulation. Mediates preferentially muscle-specific exon inclusion in numerous mRNAs important for striated cardiac and skeletal muscle cell differentiation. 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. 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. Plays a role in the regulation of mRNA stability and mRNA translation to which it is bound. Involved in myogenic differentiation by regulating MYOG levels. Binds to a huge amount of mRNAs (By similarity). Involved in embryonic heart development and myogenic differentiation of somitic muscle progenitors (PubMed:25217815).
The RRM domain is necessary for mRNA stability and mRNA translation regulation.
High affinity receptor for urotensin-2 and urotensin-2B. The activity of this receptor is mediated by a G-protein that activate a phosphatidylinositol-calcium second messenger system.
Belongs to the metallo-dependent hydrolases superfamily. Phosphotriesterase family.
Binds 2 divalent metal cations per subunit.
Binds 1 [4Fe-4S] cluster. The cluster is coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine.
Catalytic tRNA acetyltransferase subunit 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) (By similarity). In the elongator complex, acts as a tRNA uridine(34) acetyltransferase by mediating formation of carboxymethyluridine in the wobble base at position 34 in tRNAs (By similarity).
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.
Belongs to the SLC13A/DASS transporter (TC 2.A.47) family. NADC subfamily.
Belongs to the phosphatidyl serine synthase family.
Catalyzes a base-exchange reaction in which the polar head group of phosphatidylethanolamine (PE) or phosphatidylcholine (PC) is replaced by L-serine (By similarity). Catalyzes mainly the conversion of phosphatidylcholine but also converts, in vitro and to a lesser extent, phosphatidylethanolamine (By similarity).
Belongs to the SMC family. RAD50 subfamily.
Detected in brain, ovary, rectum, small intestine, large intestine, liver, spleen, follicle and kidney (at protein level).
A pair of annexin repeats may form one binding site for calcium and phospholipid.
G proteins are composed of 3 units; alpha, beta and gamma.
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.
Belongs to the CSN7/EIF3M family. CSN7 subfamily.
Component 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 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, JUN, I-kappa-B-alpha/NFKBIA, ITPK1 and IRF8/ICSBP, 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.
Cytosolic dehydrogenase that catalyzes the irreversible oxidation of a wide range of aldehydes to their corresponding carboxylic acid (By similarity). Functions downstream of retinol dehydrogenases and catalyzes the oxidation of retinaldehyde into retinoic acid, the second step in the oxidation of retinol/vitamin A into retinoic acid. This pathway is crucial to control the levels of retinol and retinoic acid, two important molecules which excess can be teratogenic and cytotoxic (By similarity). Also oxidizes aldehydes resulting from lipid peroxidation like (E)-4-hydroxynon-2-enal/HNE, malonaldehyde and hexanal that form protein adducts and are highly cytotoxic. By participating for instance to the clearance of (E)-4-hydroxynon-2-enal/HNE in the lens epithelium prevents the formation of HNE-protein adducts and lens opacification. Functions also downstream of fructosamine-3-kinase in the fructosamine degradation pathway by catalyzing the oxidation of 3-deoxyglucosone, the carbohydrate product of fructosamine 3-phosphate decomposition, which is itself a potent glycating agent that may react with lysine and arginine side-chains of proteins (By similarity). Has also an aminobutyraldehyde dehydrogenase activity and is probably part of an alternative pathway for the biosynthesis of GABA/4-aminobutanoate in midbrain, thereby playing a role in GABAergic synaptic transmission (By similarity).
Belongs to the major facilitator superfamily.
Belongs to the complex I 51 kDa subunit family.
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.
Belongs to the lipase maturation factor family.
Involved in the maturation of specific proteins in the endoplasmic reticulum.
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).
Belongs to the peroxiredoxin-like PRXL2 family. PRXL2A subfamily.
Involved in redox regulation of the cell. Acts as an antioxidant. Inhibits TNFSF11-induced NFKB1 and JUN activation and osteoclast differentiation. May affect bone resorption and help to maintain bone mass (By similarity).
The active site Cys-88 corresponds to one of the redox-active cysteines of peroxiredoxins.
Belongs to the ClpA/ClpB family. Torsin subfamily.
Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. EF-Tu/EF-1A subfamily.
This protein promotes the GTP-dependent binding of aminoacyl-tRNA to the A-site of ribosomes during protein biosynthesis.
Belongs to the DEAD box helicase family.
Belongs to the PI3/PI4-kinase family. Type III PI4K subfamily.
Stabilizes the cyclin H-CDK7 complex to form a functional CDK-activating kinase (CAK) enzymatic complex.
Belongs to the POU transcription factor family. Class-3 subfamily.
Syntaxin that may be involved in targeting and fusion of Golgi-derived retrograde transport vesicles with the ER.
Component of the circadian clock oscillator which includes the CRY proteins, CLOCK or NPAS2, BMAL1 or BMAL2, CSNK1D and/or CSNK1E, TIMELESS and the PER proteins (By similarity). Forms a heterodimer with BMAL1 (PubMed:10931848). 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). Interaction with PER and CRY proteins requires translocation to the nucleus (By similarity). Interaction of the CLOCK-BMAL1 heterodimer with PER or CRY inhibits transcription activation (By similarity). Interacts with BMAL2 (PubMed:11554928).
Expressed in a circadian rhythm manner in the retina. Levels increase over daylight hours, reaching maximum levels between ZT12 and ZT18. Expression levels continue to oscillate during constant darkness, with levels increasing during subjective day to reach maximum levels between day/night transition. In the pineal gland, shows no robust circadian rhythm with only a slight increase in expression between ZT10-18.
Expressed in the retinal photoreceptor cells (at protein level). Isoform 1 is expressed in both the retina and pineal gland. Isoform 2 is expressed mainly in the pineal gland.
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 transcriptional activation of PER1/2/3 and CRY1/2.
Phosphorylation is dependent on the CLOCK-BMAL1 heterodimer formation. Phosphorylation enhances the transcriptional activity, alters the subcellular localization and decreases the stability of the heterodimer by promoting its degradation.
Sumoylation enhances its transcriptional activity and interaction with ESR1, resulting in up-regulation of ESR1 activity. Estrogen stimulates sumoylation. Desumoylation by SENP1 negatively regulates its transcriptional activity.
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 period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and BMAL1 or BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-BMAL1|BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G, which form a second feedback loop and which activate and repress BMAL1 transcription, respectively. CLOCK regulates the circadian expression of AANAT in the retinal photoreceptor cells. The preferred binding motif for the CLOCK-BMAL1 heterodimer is 5'-CACGTGA-3', which contains a flanking Ala residue in addition to the canonical 6-nucleotide E-box sequence (By similarity). CLOCK specifically binds to the half-site 5'-CAC-3', while BMAL1 binds to the half-site 5'-GTGA-3' (By similarity).
Ubiquitinated, leading to its proteasomal degradation.
Undergoes lysosome-mediated degradation in a time-dependent manner in the liver.
Receptor for cholecystokinin. Mediates pancreatic growth and enzyme secretion, smooth muscle contraction of the gall bladder and stomach. Has a 1000-fold higher affinity for CCK rather than for gastrin. It modulates feeding and dopamine-induced behavior in the central and peripheral nervous system. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system.
Belongs to the DNA polymerase type-B-like family.
Non-catalytic subunit of the KPC complex that acts as E3 ubiquitin-protein ligase.
Acts as a transcriptional activator that promotes transcription of muscle-specific target genes and plays a role in muscle differentiation. Induces fibroblasts to differentiate into myoblasts. Probable sequence specific DNA-binding protein (By similarity).
Belongs to the class I-like SAM-binding methyltransferase superfamily. TRM11 methyltransferase family.
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.
Belongs to the protein phosphatase inhibitor 1 family.
G-protein coupled receptor for CRH (corticotropin-releasing factor) and UCN (urocortin). Has high affinity for CRH and UCN. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and down-stream effectors, such as adenylate cyclase. Promotes the activation of adenylate cyclase, leading to increased intracellular cAMP levels.
Interacts (via N-terminal extracellular domain) with CRF and UCN.
The transmembrane domain is composed of seven transmembrane helices that are arranged in V-shape. Transmembrane helix 7 assumes a sharply kinked structure (By similarity).
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. The coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins (By similarity).
Binds two calcium ions per molecule with an affinity similar to that of the S100 proteins.
Heterotetramer of TRAP-alpha, TRAP-beta, TRAP-delta and TRAP-gamma.
TRAP proteins are part of a complex whose function is to bind calcium to the ER membrane and thereby regulate the retention of ER resident proteins.
Component of the conserved oligomeric Golgi complex which is composed of eight different subunits and is required for normal Golgi morphology and localization.
Plays a role in endosomal protein trafficking and in targeting proteins for lysosomal degradation. May also contribute to the regulation of gene expression in the nucleus. Binds DNA (in vitro) and may play a synergistic role in the nucleus in regulating the expression of numerous cytokines.
The LITAF domain is stabilized by a bound zinc ion. The LITAF domain contains an amphipathic helix that mediates interaction with lipid membranes.
Homodimer; homodimerization requires the C4-type zinc finger motif and decreases during mitosis in a phosphorylation-dependent manner.
Plays a role in determining ER morphology.
The C4-type zinc finger motif is necessary both for its ER three-way tubular junction localization and formation.
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.
Component of a complex that binds and activates STK11/LKB1. In the complex, required to stabilize the interaction between CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta) and STK11/LKB1.
Component of a trimeric complex composed of STK11/LKB1, STRAD (STRADA or STRADB) and CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta): the complex tethers STK11/LKB1 in the cytoplasm and stimulates its catalytic activity.
Belongs to the type I cytokine receptor family. Type 1 subfamily.
Defects in GHR are a cause of sex-linked dwarf chicken. A restriction fragment length polymorphism, and an aberrantly-sized transcript in liver leads to a GHR with undetectable GH-binding activity causing growth deficiency and other endocrine abnormalities.
On GH binding, phosphorylated on tyrosine residues in the cytoplasmic domain by JAK2.
On GH binding, proteolytically cleaved, in vitro, to produce GHBP.
On growth hormone (GH) binding, forms homodimers and binds JAK2 via a box 1-containing domain. Binding to SOCS3 inhibits JAK2 activation, binding to CIS and SOCS2 inhibits STAT5 activation.
On ligand binding, ubiquitinated on lysine residues in the cytoplasmic domain. This ubiquitination is not sufficient for GHR internalization (By similarity).
Proteolytically cleaved, in vitro, to release the growth hormone-binding protein (GHBP).
Receptor for pituitary gland growth hormone involved in regulating postnatal body growth. On ligand binding, couples to, and activates the JAK2/STAT5 pathway.
The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.
The box 1 motif is required for JAK interaction and/or activation.
The extracellular domain is the ligand-binding domain representing the growth hormone-binding protein (GHBP).
The soluble form (GHBP) acts as a reservoir of growth hormone in plasma and may be a modulator/inhibitor of GH signaling.
The ubiquitination-dependent endocytosis motif (UbE) is required for recruitment of the ubiquitin conjugation system on to the receptor and for its internalization.
Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is composed of 13 subunits: EIF3A, EIF3B, EIF3C, EIF3D, EIF3E, EIF3F, EIF3G, EIF3H, EIF3I, EIF3J, EIF3K, EIF3L and EIF3M.
Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is involved in protein synthesis of a specialized repertoire of mRNAs and, together with other initiation factors, stimulates binding of mRNA and methionyl-tRNAi to the 40S ribosome. The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation.
Binds single-stranded RNA. Involved in the process of mRNA degradation and in the positive regulation of mRNA decapping (By similarity).
The DFDF domain is unstructured by itself. It assumes a helical fold upon interaction with other proteins (By similarity).
Belongs to the universal ribosomal protein uL5 family.
Acts as a ligand for integrins, specifically ITGA5:ITGB1 and ITGAV:ITGB3; both integrins and the CD40 receptor are required for activation of CD40-CD40LG signaling, which have cell-type dependent effects, such as B-cell activation, NF-kappa-B signaling and anti-apoptotic signaling.
Cytokine that acts as a ligand to CD40/TNFRSF5 (By similarity). Costimulates T-cell proliferation and cytokine production (By similarity). Induces the activation of NF-kappa-B (By similarity). Mediates B-cell proliferation in the absence of co-stimulus as well as IgE production in the presence of IL4 (By similarity). Involved in immunoglobulin class switching (By similarity).
Cytokine that acts as a ligand to CD40/TNFRSF5. Costimulates T-cell proliferation and cytokine production. Involved in immunoglobulin class switching.
Homotrimer (By similarity). Homotrimer (By similarity). Interacts with CD28 (By similarity). CD40 ligand, soluble form: Exists as either a monomer or a homotrimer (By similarity). Forms a ternary complex between CD40 and integrins for CD40-CD40LG signaling (By similarity).
The soluble form derives from the membrane form by proteolytic processing.
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.
Expression in the pineal gland exhibits circadian rhythm. Maximum levels expressed at CT14, and between ZT14 and ZT18.
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 period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and BMAL1 or BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-BMAL1|BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G, which form a second feedback loop and which activate and repress BMAL1 transcription, respectively. The preferred binding motif for the CLOCK-BMAL1 heterodimer is 5'-CACGTGA-3', which contains a flanking Ala residue in addition to the canonical 6-nucleotide E-box sequence. CLOCK specifically binds to the half-site 5'-CAC-3', while BMAL1 binds to the half-site 5'-GTGA-3'.
Belongs to the phosphatase and actin regulator family.
Binds actin monomers (G actin) and plays a role in the reorganization of the actin cytoskeleton and in formation of actin stress fibers.
Binds three actin monomers via the three C-terminal RPEL repeats.
Expressed in the gizzard, and in neurons from central and peripheral nervous systems.
Interacts (via RPEL repeats) with ACTA1.
Belongs to the GST superfamily. Kappa family.
Belongs to the prokaryotic/mitochondrial release factor family.
Cell surface receptor for PLXNB1 that plays an important role in cell-cell signaling (By similarity). Regulates GABAergic synapse development (By similarity). Promotes the development of inhibitory synapses in a PLXNB1-dependent manner (By similarity). Modulates the complexity and arborization of developing neurites in hippocampal neurons by activating PLXNB1 and interaction with PLXNB1 mediates activation of RHOA (By similarity).
Homodimer (By similarity). Interacts with PLXNB1 (By similarity).
Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ11 subfamily.
Forms a complex composed of PDGFRL, TNK2 and GRB2.
Belongs to the N-acetylmuramoyl-L-alanine amidase 2 family.
Highly expressed in the developing spinal motor neurons.
Ligand-activated transcription factor. Activated by high concentrations of 9-cis-retinoic acid and all-trans-retinoic acid, but not by dexamethasone, cortisol or progesterone (in vitro) (By similarity). May be involved in motor neuron development.
Plays a role as translation enhancer and involved in cell cycle regulation.
The PUA RNA-binding domain is critical for cap binding, but not sufficient for translation enhancer function.
ESCRT-III-like protein required to recruit the ESCRT-III complex to the nuclear envelope (NE) during late anaphase (By similarity). Together with SPAST, the ESCRT-III complex promotes NE sealing and mitotic spindle disassembly during late anaphase (By similarity). Recruited to the reforming NE during anaphase by LEMD2 (By similarity). Plays a role in the endosomal sorting pathway (By similarity).
Belongs to the zinc-containing alcohol dehydrogenase family. Class-III subfamily.
Belongs to the F-actin-capping protein beta subunit family.
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. May play a role in the regulation of cell morphology and cytoskeletal organization.
Heterodimer of an alpha and a beta subunit. Component of the WASH complex (By similarity). Isoform 2 also is a component of dynactin complex from brain, which contains the actin-related protein ARP1.
Isoform 1 is detected in pectoral muscle, cardiac muscle and gizzard. Isoform 2 is detected in brain and liver (at protein level). Isoform 2 is the predominant isoform of nonmuscle tissues and isoform 1 is the predominant isoform of muscle tissues.
Initiates blood coagulation by forming a complex with circulating factor VII or VIIa. The [TF:VIIa] complex activates factors IX or X by specific limited proteolysis. TF plays a role in normal hemostasis by initiating the cell-surface assembly and propagation of the coagulation protease cascade.
Interacts with HSPE; the interaction, inhibited by heparin, promotes the generation of activated factor X and activates coagulation in the presence of activated factor VII.
Belongs to the RNA polymerase beta' chain family.
Component of the RNA polymerase III (Pol III) complex consisting of 17 subunits.
DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Largest and catalytic core component of RNA polymerase III which synthesizes small RNAs, such as 5S rRNA and tRNAs. Forms the polymerase active center together with the second largest subunit. A single-stranded DNA template strand of the promoter is positioned within the central active site cleft of Pol III. A bridging helix emanates from RPC1 and crosses the cleft near the catalytic site and is thought to promote translocation of Pol III by acting as a ratchet that moves the RNA-DNA hybrid through the active site by switching from straight to bent conformations at each step of nucleotide addition (By similarity).
Belongs to the mitochondrion-specific ribosomal protein mL53 family.
Belongs to the eIF4E-binding protein family.
Belongs to the proteasome subunit S9 family.
Belongs to the Mediator complex subunit 1 family.
Belongs to the universal ribosomal protein uL30 family.
Heterodimer composed of XRCC5/Ku80 and XRCC6/Ku70. Component of the core long-range non-homologous end joining (NHEJ) complex (also named DNA-PK complex) composed of PRKDC, LIG4, XRCC4, XRCC6/Ku70, XRCC5/Ku86 and NHEJ1/XLF. Additional component of the NHEJ complex includes PAXX. Following autophosphorylation, PRKDC dissociates from DNA, leading to formation of the short-range NHEJ complex, composed of LIG4, XRCC4, XRCC6/Ku70, XRCC5/Ku86 and NHEJ1/XLF.
Single-stranded DNA-dependent ATP-dependent helicase that plays a key role in DNA non-homologous end joining (NHEJ) by recruiting DNA-PK to DNA. Required for double-strand break repair and V(D)J recombination. Also has a role in chromosome translocation. Has a role in chromosome translocation. The DNA helicase II complex binds preferentially to fork-like ends of double-stranded DNA in a cell cycle-dependent manner. It works in the 3'-5' direction. During NHEJ, the XRCC5-XRRC6 dimer performs the recognition step: it recognizes and binds to the broken ends of the DNA and protects them from further resection. Binding to DNA may be mediated by XRCC6. The XRCC5-XRRC6 dimer acts as regulatory subunit of the DNA-dependent protein kinase complex DNA-PK by increasing the affinity of the catalytic subunit PRKDC to DNA by 100-fold. The XRCC5-XRRC6 dimer is probably involved in stabilizing broken DNA ends and bringing them together. The assembly of the DNA-PK complex to DNA ends is required for the NHEJ ligation step. Probably also acts as a 5'-deoxyribose-5-phosphate lyase (5'-dRP lyase), by catalyzing the beta-elimination of the 5' deoxyribose-5-phosphate at an abasic site near double-strand breaks. 5'-dRP lyase activity allows to 'clean' the termini of abasic sites, a class of nucleotide damage commonly associated with strand breaks, before such broken ends can be joined. The XRCC5-XRRC6 dimer together with APEX1 acts as a negative regulator of transcription (By similarity).
Belongs to the peptidase S1 family. Plasminogen subfamily.
Heterodimer with other nuclear receptors.
Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE) and modulates the transcription of its target genes, such as acyl-CoA oxidase. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis. May play a role in the regulation of circadian rhythm.
Transcription elongation factor that enhances transcription elongation by RNA polymerase II (RNAPII).
Promotes neurite-outgrowth. May be involved in intracellular vesicle traffic.
Specifically expressed in skeletal and cardiac muscle.
Required for vesicle-mediated transport. Catalyzes the fusion of transport vesicles within the Golgi cisternae. Is also required for transport from the endoplasmic reticulum to the Golgi stack. Seems to function as a fusion protein required for the delivery of cargo proteins to all compartments of the Golgi stack independent of vesicle origin.
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).
The C-terminal cysteine-rich domain mediates interaction with LRP5 and LRP6.
Belongs to the glycosyltransferase 31 family.
Activated by RHOA binding. Inhibited by Y-27632.
Protein kinase which is a key regulator of actin cytoskeleton and cell polarity.
Mediates selective neuronal growth and axon targeting. Probably serves as a recognition molecule for the formation of limbic connections (By similarity).
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 twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space.
As a component of the GATOR complex may function in the amino acid-sensing branch of the TORC1 signaling pathway.
Belongs to the PIH1 family. Kintoun subfamily.
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.
Vimentins are class-III intermediate filaments found in various non-epithelial cells, especially mesenchymal cells. Vimentin is attached to the nucleus, endoplasmic reticulum, and mitochondria, either laterally or terminally.
Belongs to the sodium channel auxiliary subunit SCN3B (TC 8.A.17) family.
Modulates channel gating kinetics. Causes unique persistent sodium currents. Inactivates the sodium channel opening more slowly than the subunit beta-1. Its association with NFASC may target the sodium channels to the nodes of Ranvier of developing axons and retain these channels at the nodes in mature myelinated axons.
Component of the GPI transamidase complex. May be involved in the recognition of either the GPI attachment signal or the lipid portion of GPI.
RING-type zinc finger-containing E3 ubiquitin ligase that assembles with melanoma antigen protein (MAGE) to catalyze the direct transfer of ubiquitin from E2 ubiquitin-conjugating enzyme to a specific substrate. Involved in maintenance of genome integrity, DNA damage response and DNA repair.
Belongs to the bacterial ribosomal protein bL33 family.
Ubiquitin ligase protein 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.
Homodimer; component of the NF-kappa-B c-Rel-c-Rel complex. Component of the NF-KAPPA-B p65-c-Rel complex.
Proto-oncogene that may play a role in differentiation and lymphopoiesis. NF-kappa-B is a pleiotropic transcription factor which is present in almost all cell types and is involved in many biological processed 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. The NF-kappa-B heterodimer RELA/p65-c-Rel is a transcriptional activator (By similarity).
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 (By similarity).
Present in an inactive conformation in the absence of bound ligand. Ligand binding leads to dimerization and activation by autophosphorylation on tyrosine residues (By similarity).
The second and third Ig-like domains directly interact with fibroblast growth factors (FGF) and heparan sulfate proteoglycans.
Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation and apoptosis. Plays an essential role in the regulation of chondrocyte differentiation, proliferation and apoptosis, and is required for normal skeleton development. Regulates both osteogenesis and postnatal bone mineralization by osteoblasts. Promotes apoptosis in chondrocytes, but can also promote cancer cell proliferation. Phosphorylates PLCG1, CBL and FRS2. 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 (By similarity).
Belongs to the carbon-nitrogen hydrolase superfamily. BTD/VNN family.
Belongs to the potassium channel family. A (Shaker) (TC 1.A.1.2) subfamily. Kv1.8/KCNA10 sub-subfamily.
Detected in brain, cochlear sensory epithelium, cochlear ganglion, tegumentum vasculosum. Detected at low levels in cochlear lagena.
First detected at very low levels at embryonic day 6. Detected at embryonic day 9 and 14, and 3 days after hatching.
Mediates voltage-dependent potassium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a potassium-selective channel through which potassium ions may pass in accordance with their electrochemical gradient. The channel activity is up-regulated by cAMP (By similarity).
The N-terminus may be important in determining the rate of inactivation of the channel while the tail may play a role in modulation of channel activity and/or targeting of the channel to specific subcellular compartments.
The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.
Belongs to the mitochondrion-specific ribosomal protein mL40 family.
Belongs to the uroporphyrinogen-III synthase family.
Belongs to the peptidase M67A family. CSN5 subfamily.
Binds three calcium ions (via EF-hands 2, 3 and 4) when calcium levels are high (PubMed:17997965). Binds Mg(2+) when calcium levels are low.
Retina, in rod and cone outer segments, and pineal gland.
Stimulates retinal guanylyl cyclase when free calcium ions concentration is low and inhibits guanylyl cyclase when free calcium ions concentration is elevated. This Ca(2+)-sensitive regulation of retinal guanylyl cyclase is a key event in recovery of the dark state of rod photoreceptors following light exposure.
Has broad-spectrum antibacterial activity. May be important in the antimicrobial defenses of chick reproductive system during follicle development in the ovary and egg formation in the oviduct.
Monoubiquitination of Lys-121 by the BRE1 gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 'Lys-4' and 'Lys-79' methylation.
Phosphorylated on Ser-15 during apoptosis; which facilitates apoptotic chromatin condensation.
Forms a complex with PECAM1 and GNAQ. Interacts with PECAM1.
Receptor for bradykinin. It is associated with G proteins that activate a phosphatidylinositol-calcium second messenger system.
All KH domains contribute binding to target mRNA. Domains KH3 and KH4 are the major RNA-binding modules, although KH1 and KH2 also contribute. They are also required for RNA-dependent homo- and heterooligomerization. The integrity of KH domains seems not to be required for localization to stress granules.
RNA-binding factor that may recruit target transcripts to cytoplasmic protein-RNA complexes (mRNPs). This transcript 'caging' into mRNPs allows mRNA transport and transient storage. It also modulates the rate and location at which target transcripts encounter the translational apparatus and shields them from endonuclease attacks or microRNA-mediated degradation. Preferentially binds to N6-methyladenosine (m6A)-containing mRNAs and increases their stability.
Strong expression in the bone marrow and testis. Widely expressed. Weak expression in the ovarian stroma, but not expressed in the ovarian follicles.
Belongs to the NADP-dependent oxidoreductase L4BD family.
Has intrinsic E3 ubiquitin ligase activity and promotes ubiquitination.
Transmembrane protein of the mitochondrial outer membrane that controls mitochondrial organization. May regulate the assembly of the MICOS (mitochondrial contact site and cristae organizing system) complex which is essential to the biogenesis and dynamics of mitochondrial cristae, the inwards folds of the inner mitochondrial membrane. Through its interaction with the EMC (endoplasmic reticulum membrane protein complex), could regulate mitochondrial lipid homeostasis and thereby mitochondrial fission.
Probable 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 condensation of N-methylguanine with 2 carbon atoms from pyruvate to form the tricyclic 4-demethylwyosine, an intermediate in wybutosine biosynthesis.
Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. LKB1 subfamily.
Catalytic component of a trimeric complex composed of STK11/LKB1, STRAD (STRADA or STRADB) and CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta).
Tumor suppressor serine/threonine-protein kinase that controls the activity of AMP-activated protein kinase (AMPK) family members, thereby playing a role in various processes such as cell metabolism, cell polarity, apoptosis and DNA damage response. Acts by phosphorylating the T-loop of AMPK family proteins, leading to promote their activity (By similarity).
Ubiquitously expressed in all tissues tested. High levels were observed in duodenum and skeletal muscle, lower levels in liver and pancreas.
Receptor for MSH (alpha, beta and gamma) and ACTH. The activity of this receptor is mediated by G proteins which activate adenylate cyclase.
May play a pivotal role in the formation and/or maintenance of lipid rafts. May regulate B-cell antigen receptor-mediated signaling.
Adapter involved in the TLR2 and TLR4 signaling pathways in the innate immune response.
Involved in the maintenance of the Golgi structure. May play a role in hematopoiesis (By similarity).
Belongs to the ELO family. ELOVL7 subfamily.
Catalyzes the first and rate-limiting reaction of the four reactions that constitute the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process allows the addition of 2 carbons to the chain of long- and very long-chain fatty acids (VLCFAs) per cycle. Condensing enzyme with higher activity toward C18 acyl-CoAs, especially C18:3(n-3) acyl-CoAs and C18:3(n-6)-CoAs. Also active toward C20:4-, C18:0-, C18:1-, C18:2- and C16:0-CoAs, and weakly toward C20:0-CoA. Little or no activity toward C22:0-, C24:0-, or C26:0-CoAs. May participate to the production of saturated and polyunsaturated VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators.
Plays a role in neuronal differentiation.
Belongs to the SMC family. SMC2 subfamily.
Central component of the condensin complex, a complex required for conversion of interphase chromatin into mitotic-like condense chromosomes. The condensin complex probably introduces positive supercoils into relaxed DNA in the presence of type I topoisomerases and converts nicked DNA into positive knotted forms in the presence of type II topoisomerases.
Forms a heterodimer with SMC4. Component of the condensin complex, which contains the SMC2 and SMC4 heterodimer, and probably some non SMC subunits that regulate the complex.
The flexible SMC hinge domain, which separates the large intramolecular coiled coil regions, allows the heterodimerization with SMC4, forming a V-shaped heterodimer.
Catalyzes the conversion of oxaloacetate (OAA) to phosphoenolpyruvate (PEP), the rate-limiting step in the metabolic pathway that produces glucose from lactate and other precursors derived from the citric acid cycle. Facilitates the recycling of lactate carbon in the liver.
In eukaryotes there are two isozymes: a cytoplasmic one and a mitochondrial one. In birds, PEPCK-M is the sole form of hepatic PEPCK, but it constitutes 60% of the enzyme in the kidney.
Chromatin reader component of some histone acetyltransferase (HAT) SAGA-type complexes like the TFTC-HAT, ATAC or STAGA complexes (By similarity). SGF29 specifically recognizes and binds methylated 'Lys-4' of histone H3 (H3K4me), with a preference for trimethylated form (H3K4me3) (By similarity). In the SAGA-type complexes, SGF29 is required to recruit complexes to H3K4me (By similarity). Also binds non-histone proteins that are methylated on Lys residues (By similarity).
Interacts with dimethylated and trimethylated 'Lys-4' of histone H3 (H3K4me2 and H3K4me3), with a preference for the trimethylated form (H3K4me3). Component of some SAGA-type complexes. Component of the ADA2A-containing complex (ATAC).
The SGF29 C-terminal (also named tudor-like) domain mediates binding to methylated 'Lys-4' of histone H3 (H3K4me).
The ARID domain mediates the interaction with DNA.
Transcription coactivator that binds to the 5'-AATA[CT]-3' core sequence and plays a key role in adipogenesis and liver development. Required for adipogenesis: regulates triglyceride metabolism in adipocytes by regulating expression of adipogenic genes (By similarity).
Belongs to the DNA/RNA non-specific endonuclease family.
Belongs to the class I-like SAM-binding methyltransferase superfamily. rRNA adenine N(6)-methyltransferase family.
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. Was first known to play a role in the regulation of the activity and subcellular location of SLC9A3. May enhance Wnt signaling (By similarity).
Belongs to the PTEN phosphatase protein family.
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.
In the C-terminal section; belongs to the MoaC family.
In the N-terminal section; belongs to the radical SAM superfamily. MoaA family.
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.
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.
Belongs to the universal ribosomal protein uL22 family.
G-protein coupled receptor for cannabinoids. Mediates many cannabinoid-induced effects in the central nervous system (CNS), as well as in peripheral tissues. Signaling typically involves reduction in cyclic AMP.
Neurotensin may play an endocrine or paracrine role in the regulation of fat metabolism. It causes contraction of smooth muscle.
Component of the UV-DDB complex which includes DDB1 and DDB2 (By similarity). 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, and a substrate receptor, such as CRBN (PubMed:25043012). DDB1 may recruit specific substrate targeting subunits to the DCX complex. These substrate targeting subunits are generally known as DCAF (DDB1- and CUL4-associated factor) or CDW (CUL4-DDB1-associated WD40-repeat) proteins (By similarity).
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 (By similarity). 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 (By similarity). The UV-DDB complex may recognize UV-induced DNA damage and recruit proteins of the nucleotide excision repair pathway (the NER pathway) to initiate DNA repair (By similarity). 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 (Probable). The functional specificity of the DCX E3 ubiquitin-protein ligase complex is determined by the variable substrate recognition component recruited by DDB1 (By similarity). May play a role in the regulation of the circadian clock (By similarity).
The core of the protein consists of three WD40 beta-propeller domains.
Belongs to the DEAD box helicase family. DDX18/HAS1 subfamily.
Belongs to the proteasome subunit S3 family.
Belongs to the multi antimicrobial extrusion (MATE) (TC 2.A.66.1) family.
Belongs to the ALG10 glucosyltransferase family.
May be involved in calcium-dependent ubiquitination and subsequent proteasomal degradation of target proteins. Probably serves as a molecular bridge in ubiquitin E3 complexes. Participates in the ubiquitin-mediated degradation of beta-catenin (CTNNB1).
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.
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.
Binds to actin filaments. Interacts with phosphotyrosine-containing proteins (PubMed:1708917).
Heart, gizzard, lung and skeletal muscle.
May act as a protein phosphatase and/or a lipid phosphatase. Involved in fibrillar adhesion formation. Plays a role in cell polarization and migration. May be involved in cartilage development and in linking signal transduction pathways to the cytoskeleton.
Acts as an inhibitor of serine/threonine-protein phosphatase 2A (PP2A) activity. Potentiates ubiquitin-mediated proteasomal degradation of serine/threonine-protein phosphatase 2A catalytic subunit alpha (PPP2CA). Inhibits PP2A-mediated dephosphorylation of WEE1, promoting ubiquitin-mediated proteolysis of WEE1, thereby releasing G2/M checkpoint.
Belongs to the ubiquitin-activating E1 family. ULA1 subfamily.
Heterodimer of UBA3 and NAE1. The complex binds NEDD8 and UBE2M (By similarity).
Regulatory subunit of the dimeric UBA3-NAE1 E1 enzyme. E1 activates NEDD8 by first adenylating its C-terminal glycine residue with ATP, thereafter linking this residue to the side chain of the catalytic cysteine, yielding a NEDD8-UBA3 thioester and free AMP. E1 finally transfers NEDD8 to the catalytic cysteine of UBE2M (By similarity).
Heme transporter that regulates intracellular heme availability through the endosomal or lysosomal compartment.
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. Acts as a positive regulator of transcription. May be involved in 3'-end cleavage and polyadenylation of pre-mRNAs. Binds DNA and RNA. Component of the tRNA-splicing ligase complex required to facilitate the enzymatic turnover of catalytic subunit RTCB (By similarity). Binds (via helicase ATP-binding domain) on both short and long poly(I:C) dsRNA (By similarity).
Belongs to the DEAD box helicase family. DDX1 subfamily.
Detected in embryonic retina, brain, heart and liver (at protein level). Detected in embryonic retina, brain, heart, kidney and liver.
The helicase domain is involved in the stimulation of RELA transcriptional activity.
Involved in the retrieval of endoplasmic reticulum membrane proteins from the early Golgi compartment.
Belongs to the eukaryotic RPA49/POLR1E RNA polymerase subunit family.
Belongs to the purine/pyrimidine phosphoribosyltransferase family.
Belongs to the sauvagine/corticotropin-releasing factor/urotensin I family.
Acts as a component of the essential kinetochore-associated NDC80 complex, which is required for chromosome segregation and spindle checkpoint activity.
Belongs to the ROX family. NO66 subfamily.
Oxygenase that can act as both a histone lysine demethylase and a ribosomal histidine hydroxylase (By similarity). Specifically demethylates 'Lys-4' (H3K4me) and 'Lys-36' (H3K36me) of histone H3, thereby playing a central role in histone code. Preferentially demethylates trimethylated H3 'Lys-4' (H3K4me3) and monomethylated H3 'Lys-4' (H3K4me1) residues, while it has weaker activity for dimethylated H3 'Lys-36' (H3K36me2). Also catalyzes demethylation of non-histone proteins (By similarity). Also catalyzes the hydroxylation of 60S ribosomal protein L8 on 'His-216', thereby playing a role in ribosome biogenesis (By similarity).
Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A4 subfamily.
Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into the pre-synaptic terminal for re-utilization. Plays a key role in mediating regulation of the availability of serotonin to other receptors of serotonergic systems. Terminates the action of serotonin and recycles it in a sodium-dependent manner.
Interacts (via cytoplasmic region) with ILK.
Belongs to the avidin/streptavidin family.
Belongs to the carotenoid oxygenase family.
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:19490105). Essential for the production of 11-cis retinal for both rod and cone photoreceptors (By similarity). 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).
Highly expressed in the retinal pigment epithelium (RPE)/ choroid of the 21 dpc embryos (at protein level).
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).
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.
The propeptide is processed by MMP14 (MT-MMP1) and MMP16 (MT-MMP3).
Acts as a negative mediator of apoptosis.
Belongs to the ubiquitin-conjugating enzyme family. UEV subfamily.
Belongs to the mitochondrion-specific ribosomal protein mS25 family.
Belongs to the bZIP family. Maf subfamily.
Highly expressed in the ovary, lower expression in the brain, heart and mesenterium.
Since it lacks a putative transactivation domain, it may behave as a transcriptional repressor when it dimerizes among itself. May also serve as a transcriptional activator by dimerizing with other (usually larger) basic-zipper proteins and recruiting them to specific DNA-binding sites. May be involved in the cellular stress response.
Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRA6 sub-subfamily.
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.
Generally pentameric. There are five types of GABA(A) receptor chains: alpha, beta, gamma, delta, and rho.
Belongs to the glycosyltransferase 8 family.
Glycosyltransferase which elongates the O-linked glucose attached to EGF-like repeats in the extracellular domain of Notch proteins by catalyzing the addition of xylose.
Involved in calcium binding and microtubule stabilization.
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.
Belongs to the cyclophilin-type PPIase family.
PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides.
Brain, spinal cord, gastrointestinal tract, spleen and leg muscle. Is not detected in the heart, liver, stomach, lung and kidney.
Receptor for extracellular adenine nucleotides such as ADP (PubMed:8508924). In platelets, binding to ADP leads to mobilization of intracellular calcium ions via activation of phospholipase C, a change in platelet shape, and ultimately platelet aggregation (By similarity).
Early limb development. First present in an asymmetric arc extending from the anterior border of the limb bud to the mesenchymal cells directly adjacent to the AER. Later abundantly expressed in the proximal anterior periphery and in the mid-proximal region of the posterior periphery. In older wing buds, detectable throughout the necrotic mesenchyme between the developing digits.
Probably plays a role in patterning events during embryonic limb development. May also be involved in programmed cell death.
Responsible for the release of ribosomes from messenger RNA at the termination of protein biosynthesis. May increase the efficiency of translation by recycling ribosomes from one round of translation to another.
Belongs to the peptidase C19 family. USP28 subfamily.
Deubiquitinase involved in DNA damage response checkpoint and MYC proto-oncogene stability. Involved in DNA damage induced apoptosis by specifically deubiquitinating proteins of the DNA damage pathway such as CLSPN. Also involved in G2 DNA damage checkpoint, by deubiquitinating CLSPN, and preventing its degradation by the anaphase promoting complex/cyclosome (APC/C). Specifically deubiquitinates MYC in the nucleoplasm, leading to prevent MYC degradation by the proteasome. Deubiquitinates ZNF304, hence may prevent ZNF304 degradation by the proteasome, leading to the activated KRAS-mediated promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs).
Required for protein import into peroxisomes.
Acts as both a transcriptional activator and repressor of the MYC gene.
Belongs to the CTCF zinc-finger protein family.
Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily.
Binding of the ligand triggers homo- and/or heterodimerization of the receptor triggering its autophosphorylation.
Endocytosis and inhibition of the activated EGFR by phosphatases constitute immediate regulatory mechanisms. Moreover, inducible feedback inhibitors may constitute alternative regulatory mechanisms for the EGFR signaling.
Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses (PubMed:3260329). Known ligands include EGF and TGFA/TGF-alpha (PubMed:3260329). Ligand binding triggers receptor homo- and/or heterodimerization and autophosphorylation on key cytoplasmic residues (By similarity). The phosphorylated receptor recruits adapter proteins like GRB2 which in turn activates complex downstream signaling cascades (By similarity). Activates at least 4 major downstream signaling cascades including the RAS-RAF-MEK-ERK, PI3 kinase-AKT, PLCgamma-PKC and STATs modules (By similarity). May also activate the NF-kappa-B signaling cascade (By similarity).
Transcriptional factor involved in bone development. Could be involved in apical ectodermal ridge activity, pattern formation, and cartilage differentiation. Binds to DNA.
Plays a role in the early steps of cytochrome c oxidase subunit II (MT-CO2/COX2) maturation and is required for the stabilization of COX20 and the newly synthesized MT-CO2/COX2 protein.
Belongs to the snRNP core protein family.
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.
Contributes to the organization of the actin cytoskeleton and cell shape (By similarity). Plays a role in the formation of lamellipodia and in cell migration (By similarity). Plays a role in the regulation of neuron morphology, axon growth and formation of neuronal growth cones, and may play a role in the regulation of neuronal spine density (By similarity). Plays a role in focal adhesion assembly and turnover (By similarity). Plays a role in intracellular protein transport and endocytosis, and in modulating the levels of potassium channels present at the cell membrane (By similarity). Plays a role in endocytosis via clathrin-coated pits (By similarity).
In normal cells, appears to be phosphorylated on serine and threonine; in cells expressing activated forms of pp60-src, they become heavily phosphorylated on tyrosine in vitro. Tyrosine phosphorylation in transformed cells may contribute to cellular growth regulation and transformation.
The SH3 motif may mediate binding to the cytoskeleton.
A cleavage occurs, separating the extracellular domain from the transmembrane segment. This process called 'ectodomain shedding' is thought to be involved in receptor desensitization, signal transduction and/or membrane localization (By similarity).
Belongs to the protein-tyrosine phosphatase family. Receptor class 2A subfamily.
Cell surface receptor that binds to glycosaminoglycans, including chondroitin sulfate proteoglycans and heparan sulfate proteoglycans (PubMed:11865065, PubMed:17178832). Binding to chondroitin sulfate and heparan sulfate proteoglycans has opposite effects on PTPRS oligomerization and regulation of neurite outgrowth (By similarity). Contributes to the inhibition of neurite and axonal outgrowth by chondroitin sulfate proteoglycans, also after nerve transection (PubMed:17967490). Plays a role in stimulating neurite outgrowth in response to the heparan sulfate proteoglycan GPC2. Required for normal brain development, especially for normal development of the pituitary gland and the olfactory bulb. Functions as tyrosine phosphatase (PubMed:17967490). Mediates dephosphorylation of NTRK1, NTRK2 and NTRK3 (PubMed:17967490). Plays a role in down-regulation of signaling cascades that lead to the activation of Akt and MAP kinases. Down-regulates TLR9-mediated activation of NF-kappa-B, as well as production of TNF, interferon alpha and interferon beta (By similarity).
Detected in embryonic brain, dorsal root ganglion and spinal cord (PubMed:7600997). Detected in embryonic retina (at protein level) (PubMed:11865065). Detected in embryonic brain, spinal cord, dorsal root ganglion, trigeminal ganglion, ganglia associated with the precardinal vein and vagus nerve, the inner and outer nuclear layer of the retina, limb, breast muscle, heart, gut and lung.
Homodimer (PubMed:17178832). Binding to large heparan sulfate proteoglycan structures promotes oligomerization. Binding to chondroitin sulfate proteoglycan does not lead to oligomerization (By similarity). Interacts (via Ig-like domains) with NTRK1 and NTRK3, but does not form detectable complexes with NTRK2 (PubMed:17967490, PubMed:25385546). Interacts (via extracellular domain) with the heparan sulfate proteoglycans AGRN and COL18A1 (PubMed:11865065).
Belongs to the SINA (Seven in absentia) family.
E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of target proteins. 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.
The RING-type zinc finger domain is essential for ubiquitin ligase activity.
The SBD domain (substrate-binding domain) mediates the interaction with substrate proteins. It is related to the TRAF family.
Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.
Belongs to the nuclear hormone receptor family.
Some glutamate residues at the C-terminus are polyglutamylated, resulting in polyglutamate chains on the gamma-carboxyl group (By similarity). 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 (By similarity).
Some glutamate residues at the C-terminus are polyglycylated, resulting in polyglycine chains on the gamma-carboxyl group. Glycylation is mainly limited to tubulin incorporated into axonemes (cilia and flagella) whereas glutamylation is prevalent in neuronal cells, centrioles, axonemes, and the mitotic spindle. Both modifications can coexist on the same protein on adjacent residues, and lowering polyglycylation levels increases polyglutamylation, and reciprocally. The precise function of polyglycylation is still unclear.
The MREI motif is common among all beta-tubulin isoforms and may be critical for tubulin autoregulation.
May play a role in the correct development and proper functioning of the peripheral and central nervous system and be involved in cell adhesion and intercellular communication.
Component of the MCM8-MCM9 complex, a complex involved in homologous recombination repair following DNA interstrand cross-links and plays a key role during gametogenesis. The MCM8-MCM9 complex probably acts as a hexameric helicase required to process aberrant forks into homologous recombination substrates and to orchestrate homologous recombination with resection, fork stabilization and fork restart.
Component of the MCM8-MCM9 complex, which forms a hexamer composed of MCM8 and MCM9.
Belongs to the LIMR family. LMBRD1 subfamily.
Lysosomal membrane chaperone required to export cobalamin (vitamin B12) from the lysosome to the cytosol, allowing its conversion to cofactors. Targets ABCD4 transporter from the endoplasmic reticulum to the lysosome. Then forms a complex with lysosomal ABCD4 and cytoplasmic MMACHC to transport cobalamin across the lysosomal membrane (By similarity). May play a role in mediating and regulating the internalization of the insulin receptor (By similarity).
Belongs to the complex I NDUFB2 subunit family.
Complex I is composed of 45 different subunits.
Homodimer (via the homeobox); binds DNA as homodimer.
The homeobox domain binds to double-stranded DNA.
Transcription factor required for the development of the heart and the spleen. Implicated in commitment to and/or differentiation of the myocardial lineage. Binds to the core DNA motif of promoter.
Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.
Expressed in bone marrow, spleen, bursa, thymus and brain. Weakly expressed in fibroblasts. Also expressed in embryonic liver.
Inactive tyrosine kinase involved in Wnt signaling. pathway (By similarity).
The protein kinase domain is predicted to be catalytically inactive.
May regulate a number of protein-protein interactions by competing for PDZ domain binding sites.
Found in a complex with at least ARL2, PPP2CB, PPP2R1A, PPP2R2A, PPP2R5E and TBCD. Interacts with PPP2CB (By similarity). Part of a 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. Interacts with ARL2; interaction is enhanced with the GDP-bound form of ARL2. Does not interact with ARL3, ARL4A and ARL4D. Interacts with beta tubulin. Interacts with TBCE (By similarity).
Tubulin-folding protein implicated in the first step of the tubulin folding pathway and required for tubulin complex assembly. Involved in the regulation of microtubule polymerization or depolymerization, it modulates microtubule dynamics by capturing GTP-bound beta-tubulin (TUBB). Its ability to interact with beta tubulin is regulated via its interaction with ARL2. Acts as a GTPase-activating protein (GAP) for ARL2. Induces microtubule disruption in absence of ARL2. Increases degradation of beta tubulin, when overexpressed in polarized cells. Promotes epithelial cell detachment, a process antagonized by ARL2. Induces tight adherens and tight junctions disassembly at the lateral cell membrane. Required for correct assembly and maintenance of the mitotic spindle, and proper progression of mitosis. Involved in neuron morphogenesis.
Belongs to the CDP-alcohol phosphatidyltransferase class-I family.
Catalyzes the hydrolytic deamination of enamine/imine intermediates that form during the course of normal metabolism. May facilitate the release of ammonia from these potentially toxic reactive metabolites, reducing their impact on cellular components. It may act on enamine/imine intermediates formed by several types of pyridoxal-5'-phosphate-dependent dehydratases including L-threonine dehydratase.
pH-dependent, voltage-insensitive, background potassium channel protein.
Netrins control guidance of CNS commissural axons and peripheral motor axons.
Involved in the 5-carboxymethylaminomethyl modification (mnm(5)s(2)U34) of the wobble uridine base in mitochondrial tRNAs.
Belongs to the complement C6/C7/C8/C9 family.
Acetylation is generally linked to gene activation. 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 (By similarity).
Asymmetric dimethylation at Arg-18 (H3R17me2a) is linked to gene activation. 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 (By similarity).
Butyrylation of histones marks active promoters and competes with histone acetylation. It is present during late spermatogenesis.
Dopaminylated by TGM2 at Gln-6 (H3Q5dop) in ventral tegmental area (VTA) neurons (By similarity). H3Q5dop mediates neurotransmission-independent role of nuclear dopamine by regulating relapse-related transcriptional plasticity in the reward system (By similarity).
Expressed during S phase, then expression strongly decreases as cell division slows down during the process of differentiation.
Lysine deamination at Lys-5 (H3K4all) to form allysine only takes place on H3K4me3 and results in gene repression.
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' (By similarity).
Monoubiquitinated by RAG1 in lymphoid cells, monoubiquitination is required for V(D)J recombination.
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 Tyr-42 (H3Y41ph) by JAK2 promotes exclusion of CBX5 (HP1 alpha) from chromatin (By similarity).
Serine ADP-ribosylation by PARP1 or PARP2 constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage. Serine ADP-ribosylation at Ser-11 (H3S10ADPr) promotes recruitment of CHD1L. H3S10ADPr is mutually exclusive with phosphorylation at Ser-11 (H3S10ph) and impairs acetylation at Lys-10 (H3K9ac).
Serotonylated by TGM2 at Gln-6 (H3Q5ser) during serotonergic neuron differentiation (By similarity). H3Q5ser is associated with trimethylation of Lys-5 (H3K4me3) and enhances general transcription factor IID (TFIID) complex-binding to H3K4me3, thereby facilitating transcription (By similarity).
Succinylation at Lys-80 (H3K79succ) by KAT2A takes place with a maximum frequency around the transcription start sites of genes. It gives a specific tag for epigenetic transcription activation. Desuccinylation at Lys-123 (H3K122succ) by SIRT7 in response to DNA damage promotes chromatin condensation and double-strand breaks (DSBs) repair.
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 HMGB1.
Component of the precatalytic spliceosome (spliceosome B complex) (By similarity). Component of the U4/U6-U5 tri-snRNP complex, a building block of the precatalytic spliceosome (spliceosome B complex) (By similarity). 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 (By similarity).
Plays 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).
ADP-ribosylhydrolase that preferentially hydrolyzes the scissile alpha-O-linkage attached to the anomeric C1'' position of ADP-ribose and acts on different substrates, such as proteins ADP-ribosylated on serine and threonine, free poly(ADP-ribose) and O-acetyl-ADP-D-ribose. Specifically acts as a serine mono-ADP-ribosylhydrolase by mediating the removal of mono-ADP-ribose attached to serine residues on proteins, thereby playing a key role in DNA damage response. Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage. Does not hydrolyze ADP-ribosyl-arginine, -cysteine, -diphthamide, or -asparagine bonds. Also able to degrade protein free poly(ADP-ribose), which is synthesized in response to DNA damage: free poly(ADP-ribose) acts as a potent cell death signal and its degradation by ADPRHL2 protects cells from poly(ADP-ribose)-dependent cell death, a process named parthanatos (By similarity). Also hydrolyzes free poly(ADP-ribose) in mitochondria. Specifically digests O-acetyl-ADP-D-ribose, a product of deacetylation reactions catalyzed by sirtuins. Specifically degrades 1''-O-acetyl-ADP-D-ribose isomer, rather than 2''-O-acetyl-ADP-D-ribose or 3''-O-acetyl-ADP-D-ribose isomers.
The protein undergoes a dramatic conformational switch from closed to open states upon substrate-binding, which enables specific substrate recognition for the 1''-O-linkage. The glutamate flap (Glu-41) blocks substrate entrance to Mg(2+) in the unliganded closed state. In presence of substrate, Glu-41 is ejected from the active site: this closed-to-open transition significantly widens the substrate-binding channel and precisely positions the scissile 1''-O-linkage for cleavage while securing tightly 2'- and 3'-hydroxyls of ADP-ribose.
Inhibitory receptor acting as a major negative regulator of T-cell responses. The affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of their cognate stimulatory coreceptor CD28.
Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis.
Monomer. Homodecamer; composed of 2 back to back homopentamers. The protein may exist as monomer in solution and oiligomerizes upon ligand binding.
Putative nucleotidyltransferase required for several aspects of embryonic development including normal development of the eye (By similarity). It is unclear whether it displays nucleotidyltransferase activity in vivo. Binds single-stranded RNA (ssRNA) (By similarity).
Dual specificity phosphatase able to dephosphorylate phosphotyrosine, phosphoserine and phosphothreonine residues, with a preference for phosphotyrosine as a substrate.
Belongs to the actin-binding proteins ADF family. Twinfilin subfamily.
Belongs to the short-chain dehydrogenases/reductases (SDR) family. 2,4-dienoyl-CoA reductase subfamily.
Scavenger receptor that displays several functions associated with host defense. Binds to carbohydrates (By similarity).
Belongs to the eukaryotic ribosomal protein eS1 family.
Component of the small ribosomal subunit. Mature ribosomes consist of a small (40S) and a large (60S) subunit. The 40S subunit contains about 33 different proteins and 1 molecule of RNA (18S). The 60S subunit contains about 49 different proteins and 3 molecules of RNA (28S, 5.8S and 5S).
Belongs to the Integrator subunit 10 family.
At stage 8 (4-6 somites) expressed in two prominent regions, the notochord and the one posterior to Hensen node. At stage 14 (20 somites) expressed in the lateral border of the segmental plate. As the somite stage proceeds, detected in the lateral and medial portion of a young and old somite respectively and is also localized in the notochord and the roof plate of the neural tube.
Inhibitor of bone morphogenetic proteins (BMP) signaling. Controls somitogenesis by sequestering the BMP-4 activity which in turn differentiates distinct subtypes of the mesoderm along the mediolateral axis.
Catalyzes the conversion of long-chain fatty acids to their active form acyl-CoAs for both synthesis of cellular lipids, and degradation via beta-oxidation.
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.
DNA-binding protein that specifically binds heat shock promoter elements (HSE) and activates transcription. HSF3 binds DNA constitutively only when the C-terminal region is deleted.
Expressed in most tissues. High levels are found in erythrocytes and low levels in liver.
Plays a role in vesicle-mediated protein trafficking to lysosomal compartments including the endocytic membrane transport and autophagic pathways. Believed to act as a core component of the putative HOPS and CORVET endosomal tethering complexes.
Belongs to the type II topoisomerase family.
Binds two Mg(2+) per subunit. The magnesium ions form salt bridges with both the protein and the DNA. Can also accept other divalent metal cations, such as Mn(2+) or Ca(2+).
Eukaryotic topoisomerase I and II can relax both negative and positive supercoils, whereas prokaryotic enzymes relax only negative supercoils.
Key decatenating enzyme that alters DNA topology by binding to two double-stranded DNA molecules, generating a double-stranded break in one of the strands, passing the intact strand through the broken strand, and religating the broken strand.
Key decatenating enzyme that alters DNA topology by binding to two double-stranded DNA molecules, generating a double-stranded break in one of the strands, passing the intact strand through the broken strand, and religating the broken strand. Plays a role in B-cell differentiation.
Expressed in hematopoietic and non hematopoietic cells.
Represses v-myb- and c-myb-mediated activation of the mim-1 gene, probably by competing with other myb proteins for binding sites. It is an inhibitory member of the myb family.
Catalyzes the formation of phosphoribosylamine from phosphoribosylpyrophosphate (PRPP) and glutamine.
In the C-terminal section; belongs to the purine/pyrimidine phosphoribosyltransferase family.
Component of the signal recognition particle (SRP) complex, a ribonucleoprotein complex that mediates the cotranslational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER). The SRP complex interacts with the signal sequence in nascent secretory and membrane proteins and directs them to the membrane of the ER.
Plays an important role in the organization of the cytoskeleton. Binds to and sequesters actin monomers (G actin) and therefore inhibits actin polymerization.
Actin-binding protein that regulates actin polymerization, filopodia dynamics and increases the branching of proximal dendrites of developing neurons.
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 Tyr-42 (H3Y41ph) by JAK2 promotes exclusion of CBX5 (HP1 alpha) from chromatin. Phosphorylation on Ser-32 (H3S31ph) is specific to regions bordering centromeres in metaphase chromosomes.
Serine ADP-ribosylation constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage. Serine ADP-ribosylation at Ser-11 (H3S10ADPr) is mutually exclusive with phosphorylation at Ser-11 (H3S10ph) and impairs acetylation at Lys-10 (H3K9ac).
Specific interaction of trimethylated form at 'Lys-36' (H3.3K36me3) with ZMYND11 is mediated by the encapsulation of Ser-32 residue with a composite pocket formed by the tandem bromo-PWWP domains (By similarity). Interacts with ZMYND11; when trimethylated at 'Lys-36' (H3.3K36me3).
Specifically enriched in modifications associated with active chromatin such as methylation at Lys-5 (H3K4me), Lys-37 (H3K36me) and Lys-80 (H3K79me). 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' (By similarity).
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 zmynd11; when trimethylated at 'Lys-36' (H3.3K36me3).
Variant histone H3 which replaces conventional H3 in a wide range of nucleosomes in active genes. Constitutes the predominant form of histone H3 in non-dividing cells and is incorporated into chromatin independently of DNA synthesis. Deposited at sites of nucleosomal displacement throughout transcribed genes, suggesting that it represents an epigenetic imprint of transcriptionally active chromatin. 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.
Plays an important role in the regulation of cell survival, cell division, angiogenesis, cell differentiation and cell migration. Functions as potent mitogen in vitro. Acts as a ligand for FGFR1 and integrins. Binds to FGFR1 in the presence of heparin leading to FGFR1 dimerization and activation via sequential autophosphorylation on tyrosine residues which act as docking sites for interacting proteins, leading to the activation of several signaling cascades. Binds to integrins. Its binding to integrins and subsequent ternary complex formation with integrins and FGFR1 are essential for FGF1 signaling.
Thin filament-associated protein that is implicated in the regulation and modulation of smooth muscle contraction. It is capable of binding to actin, calmodulin and tropomyosin. The interaction of calponin with actin inhibits the actomyosin Mg-ATPase activity.
Belongs to the GLI C2H2-type zinc-finger protein family.
Belongs to the protein arginine deiminase family.
Catalyzes the deimination of arginine residues of proteins.
As a component of the GATOR1 complex functions as an inhibitor of the amino acid-sensing branch of the TORC1 pathway.
Catalyzes the cleavage of citrate into oxaloacetate and acetyl-CoA, the latter serving as common substrate for de novo cholesterol and fatty acid synthesis.
In the C-terminal section; belongs to the succinate/malate CoA ligase alpha subunit family.
In the N-terminal section; belongs to the succinate/malate CoA ligase beta subunit family.
Belongs to the aldolase class II family. Adducin subfamily.
Exclusively expressed in the inner ear, where it is found in basilar papilla, clear cells, supporting cells, cuboidal cells and the lagena macula.
May form homomeric filament after self-association or heteromeric filament after association with alpha-tectorin.
One of the major non-collagenous components of the tectorial membrane. The tectorial membrane is an extracellular matrix of the inner ear that covers the neuroepithelium of the cochlea and contacts the stereocilia bundles of specialized sensory hair cells. Sound induces movement of these hair cells relative to the tectorial membrane, deflects the stereocilia and leads to fluctuations in hair-cell membrane potential, transducing sound into electrical signals.
The presence of a hydrophobic C-terminus preceded by a potential cleavage site strongly suggests that tectorins are synthesized as glycosylphosphatidylinositol-linked, membrane-bound precursors. Tectorins are targeted to the apical surface of the inner ear epithelia by the lipid and proteolytically released into the extracellular compartment.
Zona pellucida domain may enable to form filaments.
Detected in the developing chick nervous system.
Homotetramer, and heterotetramer with CRMP1, DPYSL3, DPYSL4 or DPYSL5. Interacts through its C-terminus with the C-terminus of CYFIP1/SRA1 (By similarity).
Lacks most of the conserved residues that are essential for binding the metal cofactor and hence for dihydropyrimidinase activity. Its enzyme activity is therefore unsure.
Plays a role in neuronal development and polarity, as well as in axon growth and guidance, neuronal growth cone collapse and cell migration. Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton (By similarity).
Belongs to the osteocalcin/matrix Gla protein family.
Gamma-carboxyglutamate residues are formed by vitamin K dependent carboxylation. These residues are essential for the binding of calcium.
Belongs to the NFYB/HAP3 subunit family.
Can be divided into 3 domains: the weakly conserved A domain, the highly conserved B domain thought to be involved in subunit interaction and DNA binding, and the Glu-rich C domain.
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.
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 (By similarity).
Belongs to the inositol 3,4-bisphosphate 4-phosphatase family.
Belongs to the mitochondrial pyruvate carrier (MPC) (TC 2.A.105) family.
Mediates the uptake of pyruvate into mitochondria.
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.
High levels in the developing ciliary and superior cervical ganglia.
May play a role in erythroid cell differentiation.
Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane.
Belongs to the HAD-like hydrolase superfamily. CbbY/CbbZ/Gph/YieH family.
Glycerol-3-phosphate phosphatase hydrolyzing glycerol-3-phosphate into glycerol. Thereby, regulates the cellular levels of glycerol-3-phosphate a metabolic intermediate of glucose, lipid and energy metabolism. Was also shown to have a 2-phosphoglycolate phosphatase activity and a tyrosine-protein phosphatase activity. However, their physiological relevance is unclear. In vitro, has also a phosphatase activity toward ADP, ATP, GDP and GTP.
Catalyzes the reduction of the C14-unsaturated bond of lanosterol, as part of the metabolic pathway leading to cholesterol biosynthesis (By similarity). Anchors the lamina and the heterochromatin to the inner nuclear membrane (By similarity).
Interacts with DNA (By similarity). Interaction with DNA is sequence independent with higher affinity for supercoiled and relaxed circular DNA than linear DNA (By similarity).
The Tudor domain may not recognize methylation marks, but rather bind unassembled free histone H3.
Belongs to the major facilitator superfamily. MFSD6 family.
In the C-terminal section; belongs to the eukaryotic ribosomal protein eS31 family.
In the N-terminal section; belongs to the ubiquitin family.
Ribosomal protein S27a is a component of the 40S subunit of the ribosome.
Ribosomal protein S27a is part of the 40S ribosomal subunit.
Ubiquitin Exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in proteotoxic stress response and cell cycle; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling (By similarity).
Ubiquitin is encoded by 4 different genes. Uba52 and Rps27a genes code for a single copy of ubiquitin fused to the ribosomal proteins L40 and S27a, respectively. UBB and UBC genes code for a polyubiquitin precursor with exact head to tail repeats, the number of repeats differ between species and strains.
Central scaffolding component of the centrioles ensuring their 9-fold symmetry. Required for centrosome biogenesis and duplication: required both for mother-centriole-dependent centriole duplication and deuterosome-dependent centriole amplification in multiciliated cells (By similarity).
Nine homodimers form a cartwheel structure with an internal diameter of 23 nM and radial spokes connecting to the microtubule triplets.
The 35 nM long coiled-coil domain mediates homodimerization while the globular N-terminus links the dimers at an angle of 40 degrees to form the inner ring.
Has a pivotal role in cytoprotective cellular mechanisms triggered by oxygen deprivation. May play a role as a molecular chaperone and participate in protein folding.
Belongs to the V-ATPase E subunit family.
Stabilizes the aggregates of proteoglycan monomers with hyaluronic acid in the extracellular cartilage matrix.
Interacts with PPIF; the interaction is impaired by CsA.
Belongs to the amiloride-sensitive sodium channel (TC 1.A.6) family. SCNN1A subfamily.
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.
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.
The long isoform has been found in cochlea, colon, and cartilage. The short isoform is only found in cochlea.
Belongs to the cytochrome c oxidase subunit 6c family.
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)).
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.
Plays a role in androgen-induced proliferative arrest. Required for maintenance of sister chromatid cohesion during mitosis (By similarity).
Brain and heart, and at a lower level in muscle and intestine, in the embryo. Lung and less so in brain and spleen, in adult chicken.
Immediate-early protein likely to play a role in cell growth regulation. Its overexpression is associated with tumorigenesis and expression of a N-terminal-truncated version of CCN3 gene in chicken embryonic fibroblasts (CEF) is sufficient to induce the transformation of CEF in vitro.
MAV1-induced nephroblastomas express a high level of NOV gene whose transcription is normally arrested in adult kidney.
Binds vitellogenin and LRPAP1 (alpha 2-macroglobulin).
Cleaved into a 85 kDa membrane-spanning subunit (LRP-85) and a 515 kDa large extracellular domain (LRP-515) that remains non-covalently associated.
Endocytic receptor involved in endocytosis and in phagocytosis of apoptotic cells. Involved in cellular lipid homeostasis. Involved in the plasma clearance of chylomicron remnants and activated LRPAP1 (alpha 2-macroglobulin), as well as the local metabolism of complexes between plasminogen activators and their endogenous inhibitors. Acts as an alpha-2-macroglobulin receptor.
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. 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. Required for the entry in S phase and for cell division.
Component of the MCM2-7 complex. The complex forms a toroidal hexameric ring with the proposed subunit order MCM2-MCM6-MCM4-MCM7-MCM3-MCM5. Component of the CMG helicase complex, a hexameric ring of related MCM2-7 subunits stabilized by CDC45 and the tetrameric GINS complex.
Belongs to the PNP/MTAP phosphorylase family. MTAP subfamily.
Catalyzes the reversible phosphorylation of S-methyl-5'-thioadenosine (MTA) to adenine and 5-methylthioribose-1-phosphate. Involved in the breakdown of MTA, a major by-product of polyamine biosynthesis. Responsible for the first step in the methionine salvage pathway after MTA has been generated from S-adenosylmethionine. Has broad substrate specificity with 6-aminopurine nucleosides as preferred substrates.
Belongs to the calcium channel subunit alpha-2/delta family.
Belongs to the biopterin-dependent aromatic amino acid hydroxylase family.
May be involved in the calcium-dependent regulation of rhodopsin phosphorylation. Binds three calcium ions (By similarity).
Belongs to the major facilitator superfamily. SLC46A family.
Belongs to the nucleobase:cation symporter-2 (NCS2) (TC 2.A.40) family.
Component of the oligosaccharyltransferase (OST) complex.
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. 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.
Belongs to the adaptor complexes large subunit family.
Component of the CENPA-HI complex, a centromeric complex involved in assembly of kinetochore proteins, mitotic progression and chromosome segregation.
Component of the CENPA-HI complex, at least composed of CENPH, CENPI, CENPK, CENPL, CENPM, CENPO and CENPP.
Phosphorylated in response to beta-adrenergic stimulation. Phosphorylation by PKA abolishes the inhibition of ATP2A2-mediated calcium uptake (By similarity).
Reversibly inhibits the activity of ATP2A2 in cardiac sarcoplasmic reticulum by decreasing the apparent affinity of the ATPase for Ca(2+). Modulates the contractility of the heart muscle in response to physiological stimuli via its effects on ATP2A2. Modulates calcium re-uptake during muscle relaxation and plays an important role in calcium homeostasis in the heart muscle. The degree of ATP2A2 inhibition depends on the oligomeric state of PLN. ATP2A2 inhibition is alleviated by PLN phosphorylation (By similarity).
Belongs to the AB hydrolase superfamily. Lipase family.
Belongs to the 2-oxoacid dehydrogenase family.
Binds 2 magnesium ions per subunit. The magnesium ions are essentially bound to the substrate and have few direct interactions with the protein.
Converts guanine to guanosine monophosphate, and hypoxanthine to inosine monophosphate. Transfers the 5-phosphoribosyl group from 5-phosphoribosylpyrophosphate onto the purine. Plays a central role in the generation of purine nucleotides through the purine salvage pathway (By similarity).
Belongs to the glycosyl hydrolase 23 family.
Granulocyte compartment of myelomonocytic cells.
Shows preference for N-acetylmuramic acid residues that are substituted with a peptide moiety. It acts only as a glycanohydrolase.
FABPs are thought to play a role in the intracellular transport of long-chain fatty acids and their acyl-CoA esters.
Forms a beta-barrel structure that accommodates hydrophobic ligands in its interior.
Highest expression in early stages of retinal development with a 50-100 fold decrease from day 3 to day 19 of retina maturation.
Belongs to the squalene monooxygenase family.
Catalyzes the stereospecific oxidation of squalene to (S)-2,3-epoxysqualene, and is considered to be a rate-limiting enzyme in steroid biosynthesis.
G-protein coupled opioid receptor that functions as receptor for endogenous alpha-neoendorphins and dynorphins, but has low affinity for beta-endorphins. Also functions as receptor for various synthetic opioids and for the psychoactive diterpene salvinorin A. 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 leads to the inhibition of adenylate cyclase activity. Inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. Plays a role in the perception of pain. Plays a role in mediating reduced physical activity upon treatment with synthetic opioids. Plays a role in the regulation of salivation in response to synthetic opioids. May play a role in arousal and regulation of autonomic and neuroendocrine functions.
Interacts with SLC9A3R1. Interacts with GABARAPL1.
May be a homodimer, which associates with multiple calmodulin or myosin light chains.
Neuronal and non-neuronal cells of the brain.
Processive actin-based motor that can move in large steps approximating the 36-nm pseudo-repeat of the actin filament. Involved in melanosome transport. Also mediates the transport of vesicles to the plasma membrane. May also be required for some polarization process involved in dendrite formation (By similarity).
Adapter protein that links membrane-bound small G-proteins to cytoplasmic effector proteins. Necessary for CDC42-mediated reorganization of the actin cytoskeleton and for RAC1-mediated membrane ruffling. Involved in the regulation of the actin cytoskeleton by WASF family members and the Arp2/3 complex. Plays a role in neurite growth. Acts syngeristically with ENAH to promote filipodia formation. Plays a role in the reorganization of the actin cytoskeleton in response to bacterial infection. Participates in actin bundling when associated with EPS8, promoting filopodial protrusions.
Ca(2+) release-activated Ca(2+) (CRAC) channel subunit which mediates Ca(2+) influx following depletion of intracellular Ca(2+) stores.
At stage 12, expressed throughout the invaginating optic vesicles and a subset of cells in the ventral spinal cord, presumably interneuron precursors. At stage 14, when the optic cup forms, expression is restricted to a subset of retinoblasts. At stage 15, expression along the ventral spinal and hindbrain intensifies and persists beyond stage 20.
Binds to the 37-bp core of the locus control region (LCR) of the red/green visual pigment gene cluster. May regulate the activity of the LCR and the cone opsin genes at earlier stages of development (By similarity). Dispensable in early retinal development (By similarity).
Restricted to bipolar cells of the retina and spinal cord.
Receptor for calcitonin-gene-related peptide (CGRP). Receptor specificity may be modulated by accessory proteins. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.
In the N-terminal section; belongs to the HesA/MoeB/ThiF family. UBA4 subfamily.
Plays a central role in 2-thiolation of mcm(5)S(2)U at tRNA wobble positions of cytosolic tRNA(Lys), tRNA(Glu) and tRNA(Gln). Also essential during biosynthesis of the molybdenum cofactor. Acts by mediating the C-terminal thiocarboxylation of sulfur carriers URM1 and MOCS2A. Its N-terminus first activates URM1 and MOCS2A as acyl-adenylates (-COAMP), then the persulfide sulfur on the catalytic cysteine is transferred to URM1 and MOCS2A to form thiocarboxylation (-COSH) of their C-terminus. The reaction probably involves hydrogen sulfide that is generated from the persulfide intermediate and that acts as nucleophile towards URM1 and MOCS2A. Subsequently, a transient disulfide bond is formed. Does not use thiosulfate as sulfur donor; NFS1 probably acting as a sulfur donor for thiocarboxylation reactions.
Belongs to the YY transcription factor family.
Belongs to the bZIP family. C/EBP subfamily.
Binds DNA as a dimer. Interacts (not methylated) with MED23, MED26, SMARCA2, SMARCB1 and SMARCC1 (PubMed:20111005).
Important transcription factor regulating the expression of genes involved in immune and inflammatory responses (PubMed:8467792). Also plays a significant role in adipogenesis, as well as in the gluconeogenic pathway, liver regeneration, and hematopoiesis. The consensus recognition site is 5'-T[TG]NNGNAA[TG]-3'. Its functional capacity is governed by protein interactions and post-translational protein modifications.
Important transcriptional activator regulating the expression of genes involved in immune and inflammatory responses. Binds to regulatory regions of several acute-phase and cytokines genes and probably plays a role in the regulation of acute-phase reaction, inflammation and hemopoiesis. The consensus recognition site is 5'-T[TG]NNGNAA[TG]-3'. Functions in brown adipose tissue (BAT) differentiation. Regulates the transcriptional induction of peroxisome proliferator-activated receptor gamma (PPARG). Binds to the MGF and MIM-1 promoters and activates the transcription of these genes.
Methylated. Methylation at Arg-3 by CARM1 and at Lys-39 by EHMT2, inhibit transactivation activity. Methylation is probably inhibited by phosphorylation at Thr-220.
Specifically expressed in myelomoncytic cells.
Belongs to the iodothyronine deiodinase family.
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).
Heterodimer with SLC30A6/ZNT6; form a functional zinc ion transmembrane transporter.
Together with SLC30A6 forms a functional proton-coupled zinc ion antiporter mediating zinc entry into the lumen of organelles along the secretory pathway (PubMed:15525635). By contributing to zinc ion homeostasis within the early secretory pathway, regulates the activation and folding of enzymes like alkaline phosphatases and enzymes involved in phosphatidylinositol glycan anchor biosynthesis (PubMed:15525635).
Functions as actin-binding component of the Arp2/3 complex which is involved in regulation of actin polymerization and together with an activating nucleation-promoting factor (NPF) mediates the formation of branched actin networks.
Belongs to the universal ribosomal protein uL29 family.
Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. PIM subfamily.
Proto-oncogene with serine/threonine kinase activity involved in cell survival and cell proliferation.
Can form homooligomers (monomers, dimers, trimers and tetramers) and heterooligomers with matrilin-1.
Expression is restricted to cartilaginous tissues.
Major component of the extracellular matrix of cartilage and may play a role in the formation of extracellular filamentous networks.
Belongs to the cyclic nucleotide phosphodiesterase family. PDE8 subfamily.
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.
Acts as a chaperonin for the core histones H3, H2B and H4. Associated with nucleolar ribonucleoprotein structures and bind single-stranded nucleic acids. It may function in the assembly and/or transport of ribosome. May stimulate endonuclease activity on apurinic/apyrimidinic (AP) double-stranded DNA. May inhibit endonuclease activity on AP single-stranded RNA (By similarity).
Decamer formed by two pentameric rings associated in a head-to-head fashion.
Belongs to the protein-tyrosine phosphatase family. Receptor class 4 subfamily.
Acts as a scaffolding protein at cell-cell junctions, thereby regulating various cellular and signaling processes.
Belongs to the glutathione peroxidase family.
A soluble form arises by proteolytic removal of the membrane anchor.
Catalyzes the oxidative cleavage of heme at the alpha-methene bridge carbon, released as carbon monoxide (CO), to generate biliverdin IXalpha, while releasing the central heme iron chelate as ferrous iron (PubMed:1996964, PubMed:2158889). Affords protection against programmed cell death and this cytoprotective effect relies on its ability to catabolize free heme and prevent it from sensitizing cells to undergo apoptosis (By similarity).
Catalyzes the oxidative cleavage of heme at the alpha-methene bridge carbon, released as carbon monoxide (CO), to generate biliverdin IXalpha, while releasing the central heme iron chelate as ferrous iron.
Inhibited by metalloporphyrins in the following order of decreasing potency: tin mesoporphyrin > tin protoporphyrin > zinc protoporphyrin > manganese protoporphyrin > cobalt protoporphyrin.
Component of the THO complex, which is composed of THOC1, THOC2, THOC3, THOC5, THOC6 and THOC7; together with at least ALYREF/THOC4, DDX39B, SARNP/CIP29 and CHTOP, THO forms the transcription/export (TREX) complex which seems to have a dynamic structure involving ATP-dependent remodeling. Interacts with THOC1, POLDIP3 and ZC3H11A.
Belongs to the peptidase C12 family. BAP1 subfamily.
Deubiquitinating enzyme that plays a key role in chromatin by mediating deubiquitination of histone H2A. Catalytic component of the PR-DUB complex, a complex that specifically mediates deubiquitination of histone H2A monoubiquitinated at 'Lys-119' (H2AK119ub1) (By similarity).
Expressed early in embryogenis in a sickle-shaped area in the posterior zone of the blastoderm. With the beginning of gastrulation, it is found in the primitive streak primordium, then in the young and medium-sized streak, however not in the mesoderm after its emergence. In the fully-extended streak, it is restricted to its middle, i.e. the prospective ventral mesoderm. It is then undetectable by in later stages.
Transcription factor that play a central role in proper axial mesendoderm morphogenesis and endoderm formation. Required for efficient differentiation of cells from the primitive streak stage to blood (By similarity).
Belongs to the protein-tyrosine phosphatase family. Non-receptor class 2 subfamily.
Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4) (By similarity). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events (By similarity). Histone deacetylases act via the formation of large multiprotein complexes (By similarity). Also functions as deacetylase for non-histone proteins. In addition to protein deacetylase activity, also has protein-lysine deacylase activity: acts as a protein decrotonylase by mediating decrotonylation ((2E)-butenoyl) of histones (By similarity).
Protein-lysine N-methyltransferase that methylates both histones and non-histone proteins, including p53/TP53 and RB1. Specifically trimethylates histone H3 'Lys-4' (H3K4me3) in vivo. The activity requires interaction with HSP90alpha. Shows even higher methyltransferase activity on p53/TP53. Monomethylates 'Lys-370' of p53/TP53, leading to decreased DNA-binding activity and subsequent transcriptional regulation activity of p53/TP53. Monomethylates RB1 at 'Lys-860'.
The N-terminal C2 domain associates with lipid membranes upon calcium binding.
Expressed preferentially in heart, skeletal muscle, retina, optical tectum and bursa of Fabricius.
Shows anti-apoptotic properties. Counteract the pro-apoptotic activity of BAX.
Belongs to the G-protein coupled receptor 1 family. Vasopressin/oxytocin receptor subfamily.
Receptor for neuropeptide Y and peptide YY.
Belongs to the cyclic nucleotide phosphodiesterase family.
The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits.
Belongs to the protein kinase superfamily. CK1 Ser/Thr protein kinase family. Casein kinase I subfamily.
Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. Can phosphorylate a large number of proteins. Participates in Wnt signaling. Phosphorylates DVL1. Central component of the circadian clock. May act as a negative regulator of circadian rhythmicity by phosphorylating PER1 and PER2. Retains PER1 in the cytoplasm (By similarity).
Monomer (By similarity). Component of the circadian core oscillator, which includes the CRY proteins, CLOCK, or NPAS2, BMAL1 or BMAL2, CSNK1E, and the PER proteins (By similarity).
Actin is a highly conserved protein that polymerizes to produce filaments that form cross-linked networks in the cytoplasm of cells. Actin exists in both monomeric (G-actin) and polymeric (F-actin) forms, both forms playing key functions, such as cell motility and contraction. In addition to their role in the cytoplasmic cytoskeleton, G- and F-actin also localize in the nucleus, and regulate gene transcription and motility and repair of damaged DNA.
Methylation at His-73 by SETD3 (PubMed:30626964). Methylation stabilizes actin filaments (PubMed:11955010).
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 (By similarity).
Polymerization of globular actin (G-actin) leads to a structural filament (F-actin) in the form of a two-stranded helix (By similarity). Each actin can bind to 4 others (By similarity).
Able to bind hyaluronan. However, its intracellular localization suggests that this interaction may not be relevant in vivo.
RNA-binding protein that plays a role in the regulation of transcription, pre-mRNA splicing and mRNA translation.
The C-terminal region is necessary for nucleus and cytoplasmic localization. The N-terminal region is necessary for nucleus and nuclear bodies localization.
Binds 3 calcium ions via the second, third and fourth EF-hand.
Found in embryos from 3 dpc to adult stages.
Neuronal calcium sensor, regulator of G protein-coupled receptor phosphorylation in a calcium dependent manner. Directly regulates GRK1 (RHOK), but not GRK2 to GRK5. Can substitute for calmodulin.
Post-mitotic neurons in the central and peripheral nervous system.
Protects DRG1 from proteolytic degradation.
Forms heterodimers either with the pro-apoptotic protein BAX or the anti-apoptotic protein BCL2.
Forms heterodimers either with the pro-apoptotic protein BAX or the anti-apoptotic protein Bcl-2.
Induces caspases and apoptosis. Counters the protective effect of BCL2.
Induces caspases and apoptosis. Counters the protective effect of Bcl-2 (By similarity).
Intact BH3 motif is required by BIK, BID, BAK, BAD and BAX for their pro-apoptotic activity and for their interaction with anti-apoptotic members of the Bcl-2 family.
Intact BH3 motif is required by BIK, BID, BAK, BAD and BAX for their pro-apoptotic activity and for their interaction with anti-apoptotic members of the Bcl-2 family. Apoptotic members of the Bcl-2 family.
Cysteine protease that plays essential roles in programmed cell death, development and innate immunity (PubMed:11953316). Acts as a non-canonical executioner caspase during apoptosis: localizes in the nucleus and cleaves the nuclear structural protein lamin-A/LMNA thereby inducing nuclear shrinkage and fragmentation (PubMed:11953316). Lamin-A/LMNA cleavage is required for chromatin condensation and nuclear disassembly during apoptotic execution (PubMed:11953316). Plays an essential role in defense against viruses by acting as a central mediator of the ZBP1-mediated pyroptosis, apoptosis, and necroptosis (PANoptosis), independently of its cysteine protease activity. PANoptosis is a unique inflammatory programmed cell death, which provides a molecular scaffold that allows the interactions and activation of machinery required for inflammasome/pyroptosis, apoptosis and necroptosis (By similarity).
During activation, the N-terminal prodomain is removed by cleavage (By similarity). Concomitantly, double cleavage gives rise to a large 18-kDa and a small 11-kDa subunit (By similarity). The two large and two small subunits then assemble to form the active CASP6 complex (By similarity). Intramolecular cleavage at Asp-191 is a prerequisite for CASP6 self-activation (By similarity).
Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 18 kDa (Caspase-6 subunit p18) and a 11 kDa (Caspase-6 subunit p11) subunit.
Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 18 kDa (p18) and a 11 kDa (p11) subunit.
The N-terminal disordered prodomain is required to prevent self-activation.
The Tri-arginine exosite is required to recruit substrates for hydrolysis.
Undergoes helix-strand structural transitions upon substrate-binding: the 130's region interconverts between an inactive helical state and the canonically active strand state. Other caspases rest constitutively in the strand conformation before and after substrate-binding.
Lamins are components of the nuclear lamina, a fibrous layer on the nucleoplasmic side of the inner nuclear membrane, which is thought to provide a framework for the nuclear envelope and may also interact with chromatin.
Belongs to the dihydroorotate dehydrogenase family. Type 2 subfamily.
Catalyzes the conversion of dihydroorotate to orotate with quinone as electron acceptor. Required for UMP biosynthesis via de novo pathway.
Histones H1 are necessary for the condensation of nucleosome chains into higher-order structures.
Belongs to the 2H phosphoesterase superfamily. CNPase family.
May participate in RNA metabolism in the myelinating cell, CNP is the third most abundant protein in central nervous system myelin.
Detected in the macrophage-like 10.4 cells.
M-shaped tetramer of two CD180-LY86 heterodimers.
May cooperate with CD180 and TLR4 to mediate the innate immune response to bacterial lipopolysaccharide (LPS) and cytokine production. Important for efficient CD180 cell surface expression (By similarity).
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 (By similarity).
Belongs to the dynactin 150 kDa subunit family.
Binds to microtubules and to cytoplasmic dynein. Binds preferentially to tyrosinated microtubules than to detyrosinated microtubules.
Plays a key role in dynein-mediated retrograde transport of vesicles and organelles along microtubules by recruiting and tethering dynein to microtubules. Binds to both dynein and microtubules providing a link between specific cargos, microtubules and dynein. Plays a role in metaphase spindle orientation.
Belongs to the DapA family. NanA subfamily.
Catalyzes the cleavage of N-acetylneuraminic acid (sialic acid) to form pyruvate and N-acetylmannosamine via a Schiff base intermediate. It prevents sialic acids from being recycled and returning to the cell surface. Involved in the N-glycolylneuraminic acid (Neu5Gc) degradation pathway.
Belongs to the hcp beta-lactamase family.
Component of the nuclear pore complex (NPC)-associated TREX-2 complex (transcription and export complex 2). Component of the SAGA transcription coactivator-HAT complex. Within the SAGA complex, participates to a subcomplex of SAGA called the DUB module (deubiquitination module).
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 to a subcomplex that specifically deubiquitinates histones. The SAGA complex is recruited to specific gene promoters by activators, where it is required for transcription. The TREX-2 complex functions in docking export-competent ribonucleoprotein particles (mRNPs) to the nuclear entrance of the nuclear pore complex (nuclear basket). TREX-2 participates in mRNA export and accurate chromatin positioning in the nucleus by tethering genes to the nuclear periphery.
Belongs to the protein-tyrosine phosphatase family. Receptor class 2B subfamily.
May play a role in the regulation of centrosome and Golgi apparatus positioning.
Detected at low levels in embryonic heart, brain and lung. Detected at high levels in hatchling heart and lung.
Heterohexamer; TGFB1, TGFB2 and TGFB3 homodimeric ligands assemble a functional receptor composed of two TGFBR1 and TGFBR2 heterodimers to form a ligand-receptor heterohexamer.
Phosphorylated on a Ser/Thr residue in the cytoplasmic domain.
Transmembrane serine/threonine kinase forming with the TGF-beta type I serine/threonine kinase receptor, TGFBR1, the non-promiscuous receptor for the TGF-beta cytokines TGFB1, TGFB2 and TGFB3. Transduces the TGFB1, TGFB2 and TGFB3 signal from the cell surface to the cytoplasm and is thus regulating a plethora of physiological and pathological processes including cell cycle arrest in epithelial and hematopoietic cells, control of mesenchymal cell proliferation and differentiation, wound healing, extracellular matrix production, immunosuppression and carcinogenesis. The formation of the receptor complex composed of 2 TGFBR1 and 2 TGFBR2 molecules symmetrically bound to the cytokine dimer results in the phosphorylation and the activation of TGFRB1 by the constitutively active TGFBR2. Activated TGFBR1 phosphorylates SMAD2 which dissociates from the receptor and interacts with SMAD4. The SMAD2-SMAD4 complex is subsequently translocated to the nucleus where it modulates the transcription of the TGF-beta-regulated genes. This constitutes the canonical SMAD-dependent TGF-beta signaling cascade. Also involved in non-canonical, SMAD-independent TGF-beta signaling pathways (By similarity).
Belongs to the eukaryotic ribosomal protein eL22 family.
Belongs to the CTL (choline transporter-like) family.
More abundant in heart, with lower levels detected in ovary and small intestine.
Transcriptional activator. Binds to the consensus sequence 5'-AGATAG-3' (By similarity).
Acts as a transcriptional repressor. Positively regulates neuronal differentiation. Represses transcription by binding to the E box-containing promoter (By similarity). Binds to delta 1-crystallin enhancer core and represses lens-specific transcription. It binds as well many other non-lens specific DNA sequences.
Belongs to the delta-EF1/ZFH-1 C2H2-type zinc-finger family.
Expression is developmentally regulated with high expression in mesoderm, nervous system and lens.
Expression starts after gastrulation, when organogenesis has just begun.
Interacts with PRKCI. Interacts with TRIP11 (By similarity). Interacts (in GTP-bound form) with GARIN1B (By similarity).
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.
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.
Expressed in the developing nervous system.
Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form. Activity on G(z)-alpha is inhibited by phosphorylation of the G-protein. Activity on G(z)-alpha and G(i)-alpha-1 is inhibited by palmitoylation of the G-protein (By similarity).
Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form. Activity on G(z)-alpha is inhibited by phosphorylation of the G-protein. Activity on G(z)-alpha and G(i)-alpha-1 is inhibited by palmitoylation of the G-protein.
Phosphorylated by cyclic GMP-dependent protein kinase.
Belongs to the peroxiredoxin family. AhpC/Prx1 subfamily.
Homodimer; disulfide-linked, upon oxidation. 5 homodimers assemble to form a ring-like decamer (By similarity). Interacts with GDPD5; forms a mixed-disulfide with GDPD5 (PubMed:19766572). Interacts with SESN1 and SESN2 (By similarity).
Reduced levels of PRDX1 by RNAi cause the loss of motor neurons but did not alter the number of motor neuron progenitors or the dorsal-ventral pattering of spinal progenitors, and did not compromise motor neuron survival.
The active site is a conserved redox-active cysteine residue, the peroxidatic cysteine (C(P)), which makes the nucleophilic attack on the peroxide substrate. The peroxide oxidizes the C(P)-SH to cysteine sulfenic acid (C(P)-SOH), which then reacts with another cysteine residue, the resolving cysteine (C(R)), to form a disulfide bridge. The disulfide is subsequently reduced by an appropriate electron donor to complete the catalytic cycle. In this typical 2-Cys peroxiredoxin, C(R) is provided by the other dimeric subunit to form an intersubunit disulfide. The disulfide is subsequently reduced by thioredoxin.
The enzyme can be inactivated by further oxidation of the cysteine sulfenic acid (C(P)-SOH) to sulphinic acid (C(P)-SO2H) instead of its condensation to a disulfide bond. It can be reactivated by forming a transient disulfide bond with sulfiredoxin SRXN1, which reduces the cysteine sulfinic acid in an ATP- and Mg-dependent manner.
Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively. Plays a role in cell protection against oxidative stress by detoxifying peroxides and as sensor of hydrogen peroxide-mediated signaling events. Might participate in the signaling cascades of growth factors and tumor necrosis factor-alpha by regulating the intracellular concentrations of H(2)O(2) (By similarity). Reduces an intramolecular disulfide bond in GDPD5 that gates the ability to GDPD5 to drive postmitotic motor neuron differentiation (PubMed:19766572).
Detected in brain, lung, aorta, heart, gizzard, stomach, oviduct, spleen, kidney and small intestine.
PP1 comprises a catalytic subunit, PPP1CA, PPP1CB or PPP1CC, and one or several targeting or regulatory subunits (By similarity). PPP1R12A mediates binding to myosin.
PP1 comprises a catalytic subunit, and one or several targeting or regulatory subunits.
Phosphorylated by CIT (Rho-associated kinase) and by ROCK2 on serine and threonine residues. Phosphorylation at Thr-695 leads to inhibition of myosin phosphatase activity. Phosphorylation at Thr-850 abolishes myosin binding. May be phosphorylated at Thr-695 by DMPK; may inhibit the myosin phosphatase activity.
Interacts with CREBBP in growing cells; the interaction acetylates IRF2 and regulates IRF2-dependent H4 promoter activity.
Specifically binds to the upstream regulatory region of type I IFN and IFN-inducible MHC class I genes (the interferon consensus sequence (ICS)) and represses those genes. Also acts as an activator for several genes including H4 and IL7. Constitutively binds to the ISRE promoter to activate IL7. Involved in cell cycle regulation through binding the site II (HiNF-M) promoter region of H4 and activating transcription during cell growth. Antagonizes IRF1 transcriptional activation (By similarity).
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.
Converted into plasmin by plasminogen activators, both plasminogen and its activator being bound to fibrin.
Plasmin dissolves the fibrin of blood clots and acts as a proteolytic factor in a variety of other processes including embryonic development, tissue remodeling, tumor invasion, and inflammation. In ovulation, weakens the walls of the Graafian follicle. It activates the urokinase-type plasminogen activator, collagenases and several complement zymogens, such as C1 and C5. Cleavage of fibronectin and laminin leads to cell detachment and apoptosis. Also cleaves fibrin, thrombospondin and von Willebrand factor. Its role in tissue remodeling and tumor invasion may be modulated by CSPG4. Binds to cells.
Homodimer and heterodimer. Efficient DNA binding requires dimerization with another bHLH protein (By similarity).
Belongs to the glycosyltransferase 4 family.
Catalyzes the initial step of dolichol-linked oligosaccharide biosynthesis in N-linked protein glycosylation pathway: transfers GlcNAc-1-P from UDP-GlcNAc onto the carrier lipid dolichyl phosphate (P-dolichol), yielding GlcNAc-P-P-dolichol.
May be involved in fusion of retrograde transport vesicles derived from an endocytic compartment with the Golgi complex.
Histone methyltransferase that specifically methylates 'Lys-4' of histone H3, when part of the SET1 histone methyltransferase (HMT) complex, but not if the neighboring 'Lys-9' residue is already methylated. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation.
Belongs to the DOK family. Type B subfamily.
Belongs to the thymidylate kinase family.
Catalyzes one step in the degradation of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA).
Belongs to the F-actin-capping protein alpha subunit family.
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.
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. CapZ may mediate the attachment of the barbed ends of actin filaments to the Z-line.
Heterodimer of an alpha and a beta subunit.
Heterodimer of an alpha and a beta subunit. Component of the WASH complex (By similarity).
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various alkaloids and psychoactive substances. 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.
Specific component of the STT3A-containing form 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. 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.
Specific component of the STT3A-containing form of the oligosaccharyltransferase (OST) complex.
Belongs to the SLC34A transporter family.
Involved in actively transporting phosphate into cells via Na(+) cotransport.
Cells of the T-lymphocyte lineage. Found in both cortical and medullary cells of the thymus. Expressed at relatively high levels also in spleen, bursa, intestine and lung and at very low levels in testis, brain and skeletal muscle.
High levels are induced within 4-8 hours of T-cell activation in spleen and thymus.
The ring finger is important for its antiapoptotic effect.
Belongs to the anion exchanger (TC 2.A.31) family.
Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex.
Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family.
Has a role in pre-mRNA splicing. Phosphorylates SF2/ASF.
Belongs to the methyltransferase superfamily. NTM1 family.
Catalyzes the oxidation of sulfhydryl groups in peptide and protein thiols to disulfides with the reduction of oxygen to hydrogen peroxide.
Expressed in the liver, gall bladder, kidney, small intestine, spleen, testis, ovary and male and female reproductive tracts. Not detected in the ovarian stroma and the theca and granulosa layers of the ovarian follicle.
Has bactericidal activity. Potent activity against E.coli, L.monocytogenes, S.typhimurium and S.pyogenes but mot against S.aureus.
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.
Belongs to the chromogranin/secretogranin protein family.
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).
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.
Plays a role in the formation and organization of tight junctions during the establishment of polarity in epithelial cells.
Cytosolic CRABPs may regulate the access of retinoic acid to the nuclear retinoic acid receptors.
Belongs to the VPS10-related sortilin family. SORCS subfamily.
Belongs to the ubiA prenyltransferase family.
Converts protoheme IX and farnesyl diphosphate to heme O.
Belongs to the PA-phosphatase related phosphoesterase family.
Belongs to the V-ATPase e1/e2 subunit family.
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.
V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex.
Heterotetramer of subunits RFC2, RFC3, RFC4 and RFC5 that can form a complex either with RFC1 or with RAD17. The former interacts with PCNA in the presence of ATP, while the latter has ATPase activity but is not stimulated by PCNA (By similarity).
The elongation of primed DNA templates by DNA polymerase delta and epsilon requires the action of the accessory proteins proliferating cell nuclear antigen (PCNA) and activator 1. This subunit binds ATP (By similarity).
Belongs to the type IB topoisomerase family.
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 the specific target site 5'-[CT]CCTTp site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(3'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 5'-OH DNA strand. The free DNA strand then undergoes passage around the unbroken strand thus removing DNA supercoils. Finally, in the religation step, the DNA 5'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone.
Belongs to the EGR C2H2-type zinc-finger protein family.
Hydrolyzes N(G),N(G)-dimethyl-L-arginine (ADMA) and N(G)-monomethyl-L-arginine (MMA) which act as inhibitors of NOS. Has therefore a role in the regulation of nitric oxide generation.
Belongs to the DEAD box helicase family. DEAH subfamily. FANCM sub-subfamily.
Component of the Fanconi anemia (FA) core complex. The FA core complex associates with Bloom syndrome (BLM) complex. This supercomplex between FA and BLM complexes has been called BRAFT.
DNA-dependent ATPase component of the Fanconi anemia (FA) core complex (By similarity). Required for the normal activation of the FA pathway, leading to monoubiquitination of the FANCI-FANCD2 complex in response to DNA damage, cellular resistance to DNA cross-linking drugs, and prevention of chromosomal breakage (PubMed:16116434, PubMed:19465393). In complex with CENPS and CENPX, binds double-stranded DNA (dsDNA), fork-structured DNA (fsDNA) and Holliday junction substrates (By similarity). Its ATP-dependent DNA branch migration activity can process branched DNA structures such as a movable replication fork (By similarity). This activity is strongly stimulated in the presence of CENPS and CENPX (By similarity). In complex with FAAP24, efficiently binds to single-strand DNA (ssDNA), splayed-arm DNA, and 3'-flap substrates (By similarity). In vitro, on its own, strongly binds ssDNA oligomers and weakly fsDNA, but does not bind to dsDNA (By similarity).
Phosphorylated; hyperphosphorylated in response to genotoxic stress.
Belongs to the metallo-dependent hydrolases superfamily. HutI family.
In the C-terminal section; belongs to the OMP decarboxylase family.
In the N-terminal section; belongs to the purine/pyrimidine phosphoribosyltransferase family.
Belongs to the snRNP Sm proteins family. SmF/LSm6 subfamily.
Constitutively phosphorylated (By similarity). Phosphorylated on tyrosine residues within the YXXM motifs by BTK and SYK. Isoform 1 and isoform 2 are phosphorylated on tyrosine residues, most likely within the YXXM motifs, via CD19 activation.
Homooligomer (By similarity). Interacts (phosphorylated on tyrosine residues within YXXM motifs) with PIK3R1 (via SH2 domain); required for BCR- and TLR-mediated activation of phosphoinositide 3-kinase.
It is unsure whether this isoform is produced by alternative splicing or alternative initiation.
Signaling adapter that contributes to B-cell development by linking B-cell receptor (BCR) signaling to the phosphoinositide 3-kinase (PI3K)-Akt signaling pathway. Has a complementary role to the BCR coreceptor CD19, coupling BCR and PI3K activation by providing a docking site for the PI3K subunit PIK3R1. Alternatively, links Toll-like receptor (TLR) signaling to PI3K activation, a process preventing excessive inflammatory cytokine production. Also involved in the activation of PI3K in natural killer cells. May be involved in the survival of mature B-cells via activation of REL.
The DBB domain is required for dimerization.
Belongs to the glycosyltransferase 25 family.
Belongs to the glutamine synthetase family.
A connexon is composed of a hexamer of connexins.
Belongs to the connexin family. Alpha-type (group II) subfamily.
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.
Acts as a sulfur carrier required for 2-thiolation of mcm(5)S(2)U at tRNA wobble positions of cytosolic tRNA(Lys), tRNA(Glu) and tRNA(Gln). Serves as sulfur donor in tRNA 2-thiolation reaction by being thiocarboxylated (-COSH) at its C-terminus by MOCS3. The sulfur is then transferred to tRNA to form 2-thiolation of mcm(5)S(2)U. Also acts as a ubiquitin-like protein (UBL) that is covalently conjugated via an isopeptide bond to lysine residues of target proteins. The thiocarboxylated form serves as substrate for conjugation and oxidative stress specifically induces the formation of UBL-protein conjugates.
C-terminal thiocarboxylation occurs in 2 steps, it is first acyl-adenylated (-COAMP) via the hesA/moeB/thiF part of the MOCS3 homolog, then thiocarboxylated (-COSH) via the rhodanese domain of the MOCS3 homolog.
Belongs to the LDH/MDH superfamily. MDH type 2 family.
Plus-end tracking protein (+TIP) that binds to the plus-end of microtubules and regulates the dynamics of the microtubule cytoskeleton. Promotes cytoplasmic microtubule nucleation and elongation. Involved in mitotic spindle positioning by stabilizing microtubules and promoting dynamic connection between astral microtubules and the cortex during mitotic chromosome segregation.
Belongs to the 'GDXG' lipolytic enzyme family.
Belongs to the ATP synthase subunit s family.
Homotetramer. Associates with ATP synthase.
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.
Involved in cytokinesis and spindle organization. May play a role in actin cytoskeleton organization and microtubule stabilization and hence required for proper cell adhesion and migration (By similarity).
May interact with both microtubules and actin cytoskeleton.
Dimer of an alpha chain and a beta chain linked by a disulfide bond. Interacts with SRPX2; the interaction increases HGF mitogenic activity.
Potent mitogen for mature parenchymal hepatocyte cells, seems to be a hepatotrophic factor, and acts as a growth factor for a broad spectrum of tissues and cell types. Activating ligand for the receptor tyrosine kinase MET by binding to it and promoting its dimerization.
Down-regulated by 1,25-dihydroxyvitamin D3.
Found in spleen, lung, intestine and brain.
Inhibited by sarcolipin (SLN), phospholamban (PLN) and myoregulin (MRLN) (By similarity). Enhanced by DWORF; DWORF increases activity by displacing sarcolipin (SLN), phospholamban (PLN) and myoregulin (MRLN) (By similarity).
Interacts with sarcolipin (SLN) (By similarity). Interacts with phospholamban (PLN) (By similarity). Interacts with myoregulin (MRLN). Interacts with DWORF (By similarity).
This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the transport of calcium. Transports calcium ions from the cytosol into the sarcoplasmic/endoplasmic reticulum lumen. Contributes to calcium sequestration involved in muscular excitation/contraction.
Transcriptional repressor that contribute to growth arrest during terminal macrophage differentiation by repressing target genes involved in Ras-dependent proliferation. Represses MMP1 promoter activity.
Belongs to the HAD-like hydrolase superfamily. PHOSPHO family.
Belongs to the calcium channel beta subunit family.
The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targeting.
Belongs to the class-I pyridine nucleotide-disulfide oxidoreductase family. PYROXD1 subfamily.
Belongs to the connexin family. Beta-type (group I) subfamily.
Binds calcium and zinc ions; this stabilizes the protein fold and is essential for protein-protein interactions mediated by this domain.
Cholesterylation is required for N-product targeting to lipid rafts and multimerization.
Expressed in developing midgut, lung and cartilage of developing long bones in the limb.
Interacts with BOC and CDON. Interacts with PTCH1 (By similarity). Interacts with glypican GPC3 (By similarity).
N-palmitoylation by HHAT of N-product is required for indian hedgehog protein N-product multimerization and full activity.
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-product (By similarity). The N-product is the active species in both local and long-range signaling, whereas the C-product is degraded in the reticulum endoplasmic (By similarity).
The C-terminal part of the indian 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 followed by the covalent attachment of a cholesterol moiety to the C-terminal of the newly generated N-product (By similarity). Both activities occur in the reticulum endoplasmic (By similarity).
The dually lipidated indian hedgehog protein N-product is a morphogen which is essential for a variety of patterning events during development. Binds to the patched (PTCH1) receptor, which functions in association with smoothened (SMO), to activate the transcription of target genes (By similarity). Plays a role in morphogenesis of the skeleton by coordinating growth and differentiation of the endochondral skeleton. Positively regulates PTHLH expression during endochondral bone formation preventing chondrocyte hypertrophy. In contrast, participates in normal chondrocyte proliferation in a PTHLH-independent pathway (PubMed:8662546).
In addition to cross linking of extracellular matrix proteins, it may have a direct role in tumor suppression.
Increases between day 8 and 16 of embryonic development, during aortic embryogenesis, in direct proportion to total protein synthesis.
Proteolytically cleaved by BMP1 which removes the propeptide (By similarity). Also proteolytically cleaved by ADAMTS2 and ADAMTS14, but not by ADAMTS3, at an additional cleavage site downstream of the BMP1 cleavage site (By similarity). The propeptide plays a role in directing the deposition of this enzyme to elastic fibers, via interaction with tropoelastin (By similarity). Cleavage by BMP1 to remove the propeptide does not increase enzymatic activity but increases binding to collagen (By similarity). Cleavage by ADAMTS2 produces a form with reduced collagen-binding activity (By similarity).
Responsible for the post-translational oxidative deamination of peptidyl lysine residues in precursors to fibrous collagen and elastin.
Sulfated at Tyr-190 and also at either Tyr-186 or Tyr-187 which enhances binding to collagen.
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.
Belongs to the GTR/RAG GTP-binding protein family.
Involved in the modulation of neuronal aggregation (By similarity). May be involved in developmental events during the formation of the central nervous system (By similarity).
Expressed broadly in cranial ectoderm. Also expressed in the developing somites and in other cranial placodes, including the olfactory, lens, otic placodes (lateral half of the vesicle) and epibranchial placodes. Low level of expression in all the mesoderm derivatives in the limb buds.
First detected as stage 6 in the forming neural tube and somites, but not in trunk surface ectoderm. By stage 8, expression persists in the cranial ectoderm and is up-regulated in the presomptive olfactory placodes. By stages 11-12, expression declines in the neural tube, but not in the cranial ectoderm; in somites, expressed all along the rostral-caudal axis as well as in presegmental mesenchyme caudal to the developing somites. Lens and otic placode expression first visible at stage 12, strongest at stages 13-16. Detected uniformly in ectoderm and mesenchyme of the limb primordia at stage 17. By stage 18, decrease of ectodermal, otic, lens and olfactory placode expression; expression appears in the epibranchial placodes. By stages 22-30, highest levels in the most distal mesoderm of the autopod, in the ventricular zone of the neural tube from the forebrain to the spinal cord, in the dermomyotomes and the tail buds.
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.
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.
The FZ domain is involved in binding with Wnt ligands.
Homo/heterodimer, or complexes of higher-order. The structure of beta-crystallin oligomers seems to be stabilized through interactions between the N-terminal arms.
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.
Belongs to the glycosyl hydrolase 29 family.
Belongs to the DEAD box helicase family. DDX6/DHH1 subfamily.
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. Plays a role in P-bodies to coordinate the storage of translationally inactive mRNAs in the cytoplasm and prevent their degradation.
Belongs to the proteasome subunit p55 family.
Belongs to the thiamine pyrophosphokinase family.
Belongs to the polyprenol kinase family.
As part of the KICSTOR complex may function in the amino acid-sensing branch of the TORC1 signaling pathway.
Heterodimer of a light chain and a heavy chain linked by a disulfide bond.
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.
Composed of two subunits: alpha (catalytic) and beta (accessory).
Expressed in embryo in skeletal muscle, heart, brain, retina, inner ear and skin at 19 dpc.
Expressed in skeletal muscle, intestine, heart, brain, retina, inner ear and skin.
Its function as a Na,K-ATPase beta-subunit will be lost in placental mammals.
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.
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.
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. Subunits alpha and beta form the catalytic core in F(1). Rotation of the central stalk against the surrounding alpha(3)beta(3) subunits leads to hydrolysis of ATP in three separate catalytic sites on the beta subunits.
Belongs to the DNA2/NAM7 helicase family.
Functions in the early steps of protein synthesis of a small number of specific mRNAs. Acts by directing the binding of methionyl-tRNAi to 40S ribosomal subunits. In contrast to the eIF-2 complex, it binds methionyl-tRNAi to 40S subunits in a codon-dependent manner, whereas the eIF-2 complex binds methionyl-tRNAi to 40S subunits in a GTP-dependent manner.
Belongs to the complex I LYR family. SDHAF3 subfamily.
Interacts with the iron-sulfur protein subunit within the SDH catalytic dimer.
Plays an essential role in the assembly of succinate dehydrogenase (SDH), an enzyme complex (also referred to as respiratory complex II) that is a component of both the tricarboxylic acid (TCA) cycle and the mitochondrial electron transport chain, and which couples the oxidation of succinate to fumarate with the reduction of ubiquinone (coenzyme Q) to ubiquinol. Promotes maturation of the iron-sulfur protein subunit of the SDH catalytic dimer, protecting it from the deleterious effects of oxidants. May act together with SDHAF1.
Belongs to the metallo-dependent hydrolases superfamily. Peptidase M19 family.
Potent stimulus of gastric acid, but not of pancreatic secretion.
GlcNAcylation at Ser-113 promotes monoubiquitination of Lys-121. It fluctuates in response to extracellular glucose, and associates with transcribed genes (By similarity).
Ca(2+) binding promotes protein stability and formation of the active homodimer.
Homodimer. Interacts with GPIHBP1 with 1:1 stoichiometry (By similarity). 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. Associates with lipoprotein particles in blood plasma. 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 (By similarity).
Key enzyme in triglyceride metabolism (By similarity). 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 (By similarity). Although it has both phospholipase and triglyceride lipase activities it is primarily a triglyceride lipase with low but detectable phospholipase activity (By similarity). Mediates margination of triglyceride-rich lipoprotein particles in capillaries (By similarity). Recruited to its site of action on the luminal surface of vascular endothelium by binding to GPIHBP1 and cell surface heparan sulfate proteoglycans (By similarity).
N-glycan at Asn-70 is a triantennary complex oligosaccharide containing sialic acid, galactose, mannose, and N-acetylglucosamine, the reducing GlcNAc being sulfated at C6.
Tyrosine nitration after lipopolysaccharide (LPS) challenge down-regulates the lipase activity.
Belongs to the NADPH--cytochrome P450 reductase family.
In the C-terminal section; belongs to the flavoprotein pyridine nucleotide cytochrome reductase family.
In the N-terminal section; belongs to the flavodoxin family.
This enzyme is required for electron transfer from NADP to cytochrome P450 in microsomes. It can also provide electron transfer to heme oxygenase and cytochrome B5.
Cysteine protease that plays a key role in autophagy by mediating both proteolytic activation and delipidation of ATG8 family proteins (PubMed:15140988). Required for canonical autophagy (macroautophagy), non-canonical autophagy as well as for mitophagy. The protease activity is required for proteolytic activation of ATG8 family proteins: cleaves the C-terminal amino acid of ATG8 proteins to reveal a C-terminal glycine. 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. Protease activity is also required to counteract formation of high-molecular weight conjugates of ATG8 proteins (ATG8ylation): acts as a deubiquitinating-like enzyme that removes ATG8 conjugated to other proteins, such as ATG3. In addition to the protease activity, also mediates delipidation of ATG8 family proteins. Catalyzes delipidation of PE-conjugated forms of ATG8 proteins during macroautophagy. 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).
The LIR motif (LC3-interacting region) is required for the interaction with ATG8 family proteins. Required for proteolytic activation and delipidation of ATG8 proteins.
Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A13 subfamily.
Belongs to the acyl carrier protein (ACP) family.
Carrier of the growing fatty acid chain in fatty acid biosynthesis.
Belongs to the complex I NDUFB5 subunit family.
May be involved in protein transport from Golgi to cell surface. The ZDHHC9-GOLGA7 complex is a palmitoyltransferase specific for HRAS and NRAS (By similarity).
Although the SET domain contains the active site of enzymatic activity, both pre-SET and post-SET domains are required for methyltransferase activity. The SET domain also participates in stable binding to heterochromatin (By similarity).
Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. Suvar3-9 subfamily.
Histone methyltransferase that specifically trimethylates 'Lys-9' of histone H3 using monomethylated H3 'Lys-9' as substrate. H3 'Lys-9' trimethylation represents a specific tag for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated histones. Mainly functions in heterochromatin regions, thereby playing a central role in the establishment of constitutive heterochromatin at pericentric and telomere regions. H3 'Lys-9' trimethylation is also required to direct DNA methylation at pericentric repeats. SUV39H1 is targeted to histone H3 via its interaction with RB1 and is involved in many processes (By similarity).
In the pre-SET domain, Cys residues bind 3 zinc ions that are arranged in a triangular cluster; some of these Cys residues contribute to the binding of two zinc ions within the cluster.
Belongs to the AB hydrolase superfamily. ABHD17 family.
Hydrolyzes fatty acids from S-acylated cysteine residues in proteins. Has depalmitoylating activity towards NRAS.
Palmitoylated on cysteine residues located in a cysteine cluster at the N-terminus which promotes membrane localization.
Accepts the ubiquitin-like proteins SUMO1, SUMO2 and SUMO3 from the UBLE1A-UBLE1B E1 complex and catalyzes their covalent attachment to other proteins with the help of an E3 ligase such as RANBP2 or CBX4. Essential for nuclear architecture and chromosome segregation.
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.
Heterohexamer of two PFD-alpha type and four PFD-beta type subunits.
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.
Belongs to the bZIP family. Fos subfamily.
Expression increases upon a variety of stimuli, including growth factors, cytokines, neurotransmitters, polypeptide hormones, stress and cell injury.
May be Tyr-phosphorylated in quiescent cells and dephosphorylated upon cell growth induction.
Nuclear phosphoprotein which forms a tight but non-covalently linked complex with the JUN/AP-1 transcription factor. FOS has a critical function in regulating the development of cells destined to form and maintain the skeleton. It is thought to have an important role in signal transduction, cell proliferation and differentiation. In growing cells, may activate phospholipid synthesis (By similarity).
Belongs to the small leucine-rich proteoglycan (SLRP) family. SLRP class II subfamily.
Plays an important role in generating and maintaining a transparent matrix within the corneal stroma.
Putative regulatory subunit of protein phosphatase 6 (PP6) that may be involved in the recognition of phosphoprotein substrates.
Belongs to the calcineurin regulatory subunit family. CHP subfamily.
Binds calcium via its EF-hands. Calcium-binding mediates a conformational change. Can also bind magnesium (By similarity).
Expressed in the bipotential gonad by E4.5 and expressed in both the testis and ovary by E5.5, but with expression higher in the testis. Expressed in the testis cords but also at low levels in the interstitium. In the ovary, expression is principally in the ovarian cortex, but also in the medulla. Also expressed in the embryonic brain, with expression highest in the region between the nasal placode and olfactory bulb. Also expressed in the embryonic heart and tail.
Functions as an integral cofactor in cell pH regulation by controlling plasma membrane-type Na(+)/H(+) exchange activity. Promotes the induction of hematopoietic stem cell differentiation toward megakaryocytic lineage. Essential for the coupling of ERK cascade activation with the expression of ETS family genes in megakaryocytic differentiation. Also involved in granulocytic differentiation in a ERK-dependent manner. Inhibits the phosphatase activity of calcineurin (By similarity).
Monomer (By similarity). Homodimer (By similarity).
Belongs to the protein phosphatase inhibitor 2 family.
Belongs to the TRAFAC class YlqF/YawG GTPase family. NOG2 subfamily.
GTPase that associates with pre-60S ribosomal subunits in the nucleolus and is required for their nuclear export and maturation.
The potassium channel is probably composed of a homo- or heterotetrameric complex of pore-forming alpha subunits that can associate with modulating beta subunits.
Part of the SNAPc complex composed of 5 subunits: SNAPC1, SNAPC2, SNAPC3, SNAPC4 and SNAPC5. SNAPC3 interacts with SNAPC1.
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.
Required for biogenesis of the 60S ribosomal subunit.
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.
Belongs to the PC-esterase family. CASD1 subfamily.
Belongs to the nuclear hormone receptor family. NR5 subfamily.
Belongs to the peptidase S26 family. IMP2 subfamily.
Heterodimer of 2 subunits, IMMPL1 and IMMPL2.
Belongs to the LDH/MDH superfamily. LDH family.
Interconverts simultaneously and stereospecifically pyruvate and lactate with concomitant interconversion of NADH and NAD(+).
Complexes with metalloproteinases (such as collagenases) and irreversibly inactivates them by binding to their catalytic zinc cofactor. May form part of a tissue-specific acute response to remodeling stimuli.
Acetylated on Lys-5, Lys-8 and Lys-12 when associated with the 5'-end of active genes.
Monoubiquitination of Lys-122 gives a specific tag for epigenetic transcriptional repression.
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. H2A or its variant H2AF forms a heterodimer with H2B (By similarity).
Variant histone H2A which replaces conventional H2A in a subset of nucleosomes. 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 the formation of constitutive heterochromatin. May be required for chromosome segregation during cell division (By similarity).
Belongs to the ubiquitin-activating E1 family. UBA5 subfamily.
E1-like enzyme which specifically catalyzes the first step in ufmylation. Activates UFM1 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 UFM1-E1 thioester and free AMP. Activates UFM1 via a trans-binding mechanism, in which UFM1 interacts with distinct sites in both subunits of the UBA5 homodimer. Trans-binding also promotes stabilization of the UBA5 homodimer, and enhances ATP-binding. Transfer of UFM1 from UBA5 to the E2-like enzyme UFC1 also takes place using a trans mechanism. Ufmylation is involved in reticulophagy (also called ER-phagy) induced in response to endoplasmic reticulum stress.
Homodimer; homodimerization is required for UFM1 activation. Interacts (via UIS motif) with UFM1; binds UFM1 via a trans-binding mechanism in which UFM1 interacts with distinct sites in both subunits of the UBA5 homodimer. Interacts (via C-terminus) with UFC1.
Belongs to the 6-phosphogluconate dehydrogenase family.
Catalyzes the oxidative decarboxylation of 6-phosphogluconate to ribulose 5-phosphate and CO(2), with concomitant reduction of NADP to NADPH.
Belongs to the metallo-dependent hydrolases superfamily. NagA family.
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. 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 (By similarity).
Belongs to the G-protein coupled receptor 1 family. FSH/LSH/TSH subfamily.
G protein-coupled receptor for follitropin, the follicle-stimulating hormone. Through cAMP production activates the downstream PI3K-AKT and ERK1/ERK2 signaling pathways.
Homotrimer. Functions as a homotrimer binding the FSH hormone heterodimer composed of CGA and FSHB.
May play a role in lipid transport protein in Schwann cells. May bind cholesterol.
Interacts with homodimeric PDGFA, PDGFB and PDGFC, and with heterodimers formed by PDGFA and PDGFB. Monomer in the absence of bound ligand.
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.
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.
Belongs to the argininosuccinate synthase family.
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.
Belongs to the C/M/P thioester hydrolase family.
Associates with the organic matrix of bone and cartilage. Thought to act as an inhibitor of bone formation.
In 16-day-old embryo, expressed at high level in the sternum and tibia, at low level in skeletal muscle, heart and gizzard. Not present in skin, liver and brain.
Requires vitamin K-dependent gamma-carboxylation for its function.
By lipopolysaccharide (LPS) in white blood cells, liver and spleen 3 hours after treatment. Decreases to basal levels 8 hours after treatment. By primary infection with E.acervulina and E.tenella.
Chickens susceptible to E.maxima infection show higher constitutive and post-infection levels in spleen and higher post-infection levels in small intestine than infection-resistant animals.
Expressed predominantly in bursa of Fabricius and cecal tonsils with low levels in thymus, liver and lung.
Expression is detected as early as embryonic day 12. Higher expression in spleen of post-hatch chickens than embryos. Gradual increase in expression in the spleen which peaks by day 7 post-hatch.
Homodimer. Interacts with IL10RA and IL10RB.
Major immune regulatory cytokine that acts on many cells of the immune system where it has profound anti-inflammatory functions, limiting excessive tissue disruption caused by inflammation. Mechanistically, IL10 binds to its heterotetrameric receptor comprising IL10RA and IL10RB leading to JAK1 and STAT2-mediated phosphorylation of STAT3. In turn, STAT3 translocates to the nucleus where it drives expression of anti-inflammatory mediators. Targets antigen-presenting cells (APCs) such as macrophages and monocytes and inhibits their release of pro-inflammatory cytokines including granulocyte-macrophage colony-stimulating factor /GM-CSF, granulocyte colony-stimulating factor/G-CSF, IL-1 alpha, IL-1 beta, IL-6, IL-8 and TNF-alpha. Interferes also with antigen presentation by reducing the expression of MHC-class II and co-stimulatory molecules, thereby inhibiting their ability to induce T cell activation (By similarity). In addition, controls the inflammatory response of macrophages by reprogramming essential metabolic pathways including mTOR signaling (By similarity).
Allosteric enzyme that catalyzes the rate-limiting step in glycogen catabolism, the phosphorolytic cleavage of glycogen to produce glucose-1-phosphate, and plays a central role in maintaining cellular and organismal glucose homeostasis.
Belongs to the glycogen phosphorylase family.
Saposin-A and saposin-C stimulate the hydrolysis of glucosylceramide by beta-glucosylceramidase (EC 3.2.1.45) and galactosylceramide by beta-galactosylceramidase (EC 3.2.1.46). Saposin-C apparently acts by combining with the enzyme and acidic lipid to form an activated complex, rather than by solubilizing the substrate.
Saposin-B stimulates the hydrolysis of galacto-cerebroside sulfate by arylsulfatase A (EC 3.1.6.8), GM1 gangliosides by beta-galactosidase (EC 3.2.1.23) and globotriaosylceramide by alpha-galactosidase A (EC 3.2.1.22). Saposin-B forms a solubilizing complex with the substrates of the sphingolipid hydrolases.
Saposin-D is a specific sphingomyelin phosphodiesterase activator (EC 3.1.4.12).
The lysosomal degradation of sphingolipids takes place by the sequential action of specific hydrolases. Some of these enzymes require specific low-molecular mass, non-enzymatic proteins: the sphingolipids activator proteins (coproteins).
This precursor is proteolytically processed to 4 small peptides, which are similar to each other and are sphingolipid hydrolase activator proteins.
Belongs to the bacterial ribosomal protein bL17 family.
May act as a transcriptional transactivator.
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.
Belongs to the amino acid-polyamine-organocation (APC) superfamily. Cationic amino acid transporter (CAT) (TC 2.A.3.3) family.
Exhibits ester hydrolase activity on the substrate p-nitrophenyl acetate.
Bifunctional glycosyltransferase with both alpha-1,3-xylosyltransferase and beta-1,3-glucuronyltransferase activities involved in the maturation of alpha-dystroglycan (DAG1) by glycosylation leading to DAG1 binding to laminin G-like domain-containing extracellular proteins with high affinity and in a phosphorylated-O-mannosyl trisaccharide dependent manner. Elongates the glucuronyl-beta-1,4-xylose-beta disaccharide primer structure by adding repeating units [-3-Xylose-alpha-1,3-GlcA-beta-1-] to produce a heteropolysaccharide (By similarity). Supports the maturation of DAG1 more effectively than LARGE1 (By similarity). In addition, can modify both heparan sulfate (HS)- and chondroitin/dermatan sulfate (CS/DS)-proteoglycans (PGs), namely GPC4, with a glycosaminoglycan (GAG)-like polysaccharide composed of xylose and glucuronic acid to confer laminin binding (By similarity).
Binds 2 Mn(2+) ions per subunit. The xylosyltransferase part binds one Mn(2+) and the beta-1,3-glucuronyltransferase part binds one Mn(2+).
In the C-terminal section; belongs to the glycosyltransferase 49 family.
In the N-terminal section; belongs to the glycosyltransferase 8 family.
Endoplasmic reticulum cargo receptor that mediates the export of lipoproteins by recruiting cargos into COPII vesicles to facilitate their secretion. Acts as a cargo receptor for lipoproteins bearing both APOB and APOA1, thereby regulating lipoprotein delivery and the maintenance of lipid homeostasis.
The di-lysine motif confers endoplasmic reticulum localization for type I membrane proteins.
Belongs to the rod/cone cGMP-PDE gamma subunit family.
Participates in processes of transmission and amplification of the visual signal. cGMP-PDEs are the effector molecules in G-protein-mediated phototransduction in vertebrate rods and cones.
Binds the telomeric double-stranded 5'-TTAGGG-3' repeat and plays a central role in telomere maintenance and protection against end-to-end fusion of chromosomes. Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection. Shelterin associates with arrays of double-stranded 5'-TTAGGG-3' 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 (By similarity).
Homodimer. Component of the shelterin complex (telosome) (By similarity). Interacts with TERF2IP/RAP1.
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.
Belongs to the NAD(P)-dependent epimerase/dehydratase family. Fucose synthase subfamily.
Catalyzes the two-step NADP-dependent conversion of GDP-4-dehydro-6-deoxy-D-mannose to GDP-fucose, involving an epimerase and a reductase reaction.
Belongs to the cyclin family. Cyclin C subfamily.
Component of the Mediator complex, a coactivator involved in regulated gene 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. Binds to and activates cyclin-dependent kinase CDK8 that phosphorylates the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAp II), which may inhibit the formation of a transcription initiation complex (By similarity).
Component of the Mediator complex. The cylin/CDK pair formed by CCNC/CDK8 also associates with the large subunit of RNA polymerase II (By similarity).
Belongs to the methyltransferase superfamily. METL family.
S-adenosyl-L-methionine-dependent methyltransferase.
Highly expressed in macrophages, peripheral blood lymphocytes (PBL) and peripheral blood mononuclear cells (PBMC). Weakly expressed in bursa, thymus, spleen, liver and brain.
Belongs to the queuine tRNA-ribosyltransferase family. QTRT2 subfamily.
Heterodimer of a catalytic subunit QTRT1 and an accessory subunit QTRT2.
Non-catalytic subunit of the queuine tRNA-ribosyltransferase (TGT) that catalyzes the base-exchange of a guanine (G) residue with queuine (Q) at position 34 (anticodon wobble position) in tRNAs with GU(N) anticodons (tRNA-Asp, -Asn, -His and -Tyr), resulting in the hypermodified nucleoside queuosine (7-(((4,5-cis-dihydroxy-2-cyclopenten-1-yl)amino)methyl)-7-deazaguanosine).
Belongs to the nonaspanin (TM9SF) (TC 9.A.2) family.
Belongs to the WD repeat DDB2/WDR76 family.
Component of the UV-DDB complex which includes DDB1 and DDB2 (By similarity). Component of the DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex DDB1-CUL4-ROC1 (also known as CUL4-DDB-ROC1 and CUL4-DDB-RBX1), which includes CUL4A or CUL4B, DDB1, DDB2 and RBX1. DDB2 may function as the substrate recognition module within this complex. A large number of other DCX complexes may also exist in which an alternate substrate targeting subunit replaces DDB2. These targeting subunits are generally known as DCAF (DDB1- and CUL4-associated factor) or CDW (CUL4-DDB1-associated WD40-repeat) proteins (By similarity).
Interblade loops of the WD repeat region mediate most of the interaction with DNA. A hairpin between blades 5 and 6 inserts into DNA minor groove and mediates recognition of lesions and separation of the damaged and undamaged strands (By similarity).
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. 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. The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches. Also functions as the substrate recognition module for the DCX (DDB2-CUL4-X-box) E3 ubiquitin-protein ligase complex DDB2-CUL4-ROC1 (also known as CUL4-DDB-ROC1 and CUL4-DDB-RBX1). The DDB2-CUL4-ROC1 complex may ubiquitinate histone H2A, histone H3 and histone H4 at sites of UV-induced DNA damage. The ubiquitination of histones may facilitate their removal from the nucleosome and promote subsequent DNA repair.
The DWD box is required for interaction with DDB1.
Belongs to the Rab3-GAP regulatory subunit family.
Can be detected by day 10-13 in ovo, the content is gradually increased throughout the ovo development and reached its peak after hatching.
Expressed in pectoralis and cardiac muscle.
Is a structural constituent of myofibrillar M-band in striated muscle.
Belongs to the Clp1 family. Clp1 subfamily.
Component of the tRNA splicing endonuclease complex. Component of pre-mRNA cleavage complex II (CF-II).
Polynucleotide kinase that can phosphorylate the 5'-hydroxyl groups of double-stranded RNA (dsRNA), single-stranded RNA (ssRNA), double stranded DNA (dsDNA) and double-stranded DNA:RNA hybrids. dsRNA is phosphorylated more efficiently than dsDNA, and the RNA component of a DNA:RNA hybrid is phosphorylated more efficiently than the DNA component. Plays a role in both tRNA splicing and mRNA 3'-end formation. Component of the tRNA splicing endonuclease complex: phosphorylates the 5'-terminus of the tRNA 3'-exon during tRNA splicing; this phosphorylation event is a prerequisite for the subsequent ligation of the two exon halves and the production of a mature tRNA. Its role in tRNA splicing and maturation is required for cerebellar development. Component of the pre-mRNA cleavage complex II (CF-II), which seems to be required for mRNA 3'-end formation. Also phosphorylates the 5'-terminus of exogenously introduced short interfering RNAs (siRNAs), which is a necessary prerequisite for their incorporation into the RNA-induced silencing complex (RISC). However, endogenous siRNAs and microRNAs (miRNAs) that are produced by the cleavage of dsRNA precursors by dicer1 already contain a 5'-phosphate group, so this protein may be dispensible for normal RNA-mediated gene silencing (By similarity).
Belongs to the cAMP-dependent kinase regulatory chain family.
Belongs to the mitochondrion-specific ribosomal protein mL37 family.
As part of a BORC-like complex may play a role in lysosomes movement and localization at the cell periphery. Associated with the cytosolic face of lysosomes, this complex may couple lysosomes to microtubule plus-end-directed kinesin motor.
Required for centrosome duplication and formation and function of the mitotic spindle.
Self-associates. Interacts with PAFAH1B1 (By similarity).
As part of the heterotrimeric replication protein A complex (RPA/RP-A), binds and stabilizes single-stranded DNA intermediates, that form during DNA replication or upon DNA stress. It prevents their reannealing and in parallel, recruits and activates different proteins and complexes involved in DNA metabolism. Thereby, it plays an essential role both in DNA replication and the cellular response to DNA damage.
Belongs to the replication factor A protein 1 family.
Component of the heterotrimeric canonical replication protein A complex (RPA).
Belongs to the organo anion transporter (TC 2.A.60) family.
Belongs to the SNF2/RAD54 helicase family. SMARCAL1 subfamily.
Catalyzes the transfer of a dimethylallyl group onto the adenine at position 37.
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.
Belongs to the autoinducer-2 exporter (AI-2E) (TC 2.A.86) family.
Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Iron is taken up in the ferrous form and deposited as ferric hydroxides after oxidation.
Activated by factor XIa, which excises the activation peptide. The propeptide can also be removed by snake venom protease.
Calcium binds to the gamma-carboxyglutamic acid (Gla) residues in the Gla domain. Calcium can also bind, with stronger affinity, to another site beyond the Gla domain. Under physiological ion concentrations, Ca(2+) is displaced by Mg(2+) from some of the gammaglutamate residues in the N-terminal Gla domain. This leads to a subtle conformation change that may affect the interaction with its binding protein.
Factor IX is a vitamin K-dependent plasma protein that participates in the intrinsic pathway of blood coagulation by converting factor X to its active form in the presence of Ca(2+) ions, phospholipids, and factor VIIIa.
Heterodimer of a light chain and a heavy chain; disulfide-linked.
The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains.
Identified in the spliceosome C complex.
Involved in pre-mRNA splicing, specifically in spliceosome disassembly during late-stage splicing events.
Belongs to the eukaryotic AdoMetDC family.
Binds 1 pyruvoyl group covalently per subunit.
Essential for biosynthesis of the polyamines spermidine and spermine. Promotes maintenance and self-renewal of embryonic stem cells, by maintaining spermine levels.
Activates an alternative mTOR signaling to regulate cell proliferation and migration.
Component of the ER membrane protein complex (EMC).
Belongs to the Rab3-GAP catalytic subunit family.
May play a role in anterograde transport of membrane proteins from the endoplasmic reticulum to the Golgi.
Component of the pre-catalytic and catalytic spliceosome complexes. Component of the postcatalytic spliceosome P complex.
Required for pre-mRNA splicing as component of the activated spliceosome. Involved in the first step of pre-mRNA splicing. Binds directly to the internal stem-loop (ISL) domain of the U6 snRNA and to the pre-mRNA intron near the 5' splice site during the activation and catalytic phases of the spliceosome cycle.
The C-terminal RRM domain and the zinc finger motif are necessary for RNA-binding.
Involved in BCR (B-cell antigen receptor)-mediated signaling in B-cells. May also be involved in FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast 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 such as calcium mobilization through the recruitment of GRB2.
Phosphorylated on tyrosines following cross-linking of BCR; which induces the recruitment of GRB2.
When phosphorylated, interacts with GRB2.
Belongs to the class-I aminoacyl-tRNA synthetase family.
Belongs to the Mediator complex subunit 14 family.
Belongs to the Toll-like receptor family.
Belongs to the ribose-phosphate pyrophosphokinase family.
Catalyzes the synthesis of phosphoribosylpyrophosphate (PRPP) that is essential for nucleotide synthesis.
Homodimer. The active form is probably a hexamer composed of 3 homodimers.
Component of a hexamer of two molecules each of IL6, IL6R and IL6ST; first binds to IL6R to associate with the signaling subunit IL6ST.
Cytokine with a wide variety of biological functions in immunity, tissue regeneration, and metabolism. Binds to IL6R, then the complex associates to the signaling subunit IL6ST/gp130 to trigger the intracellular IL6-signaling pathway. The interaction with the membrane-bound IL6R and IL6ST stimulates 'classic signaling', 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.
Component of a SWR1-like complex. Interacts with H2A.Z/H2AZ1 (By similarity).
Histone chaperone that specifically mediates the genome-wide removal of histone H2A.Z/H2AZ1 from the nucleosome: removes H2A.Z/H2AZ1 from its normal sites of deposition, especially from enhancer and insulator regions. Not involved in deposition of H2A.Z/H2AZ1 in the nucleosome. May stabilize the evicted H2A.Z/H2AZ1-H2B dimer, thus shifting the equilibrium towards dissociation and the off-chromatin state. Inhibits activity of protein phosphatase 2A (PP2A). Does not inhibit protein phosphatase 1. May play a role in cerebellar development and synaptogenesis (By similarity).
The H2A.Z-interacting domain (ZID) mediates a direct interaction with H2A.Z/H2AZ1.
Binds oxysterols in a pocket within their transmembrane domains and interacts with SCAP via transmembrane domains 3 and 4.
Interacts with SCAP; interaction is direct and only takes place in the presence of sterols; it prevents interaction between SCAP and the coat protein complex II (COPII). Associates with the SCAP-SREBP complex; association is mediated via its interaction with SCAP and only takes place in the presence of sterols.
Mediates feedback control of cholesterol synthesis.
Oxysterol-binding protein that mediates feedback control of cholesterol synthesis by controlling both endoplasmic reticulum to Golgi transport of SCAP and degradation of HMGCR. Acts as a negative regulator of cholesterol biosynthesis by mediating the retention of the SCAP-SREBP complex in the endoplasmic reticulum, thereby blocking the processing of sterol regulatory element-binding proteins (SREBPs). Binds oxysterol, including 22-hydroxycholesterol, 24-hydroxycholesterol, 25-hydroxycholesterol and 27-hydroxycholesterol, regulating interaction with SCAP and retention of the SCAP-SREBP complex in the endoplasmic reticulum. In presence of oxysterol, interacts with SCAP, retaining the SCAP-SREBP complex in the endoplasmic reticulum, thereby preventing SCAP from escorting SREBPs to the Golgi. Sterol deprivation reduces oxysterol-binding, disrupting the interaction between INSIG2 and SCAP, thereby promoting Golgi transport of the SCAP-SREBP complex, followed by processing and nuclear translocation of SREBPs. Also regulates cholesterol synthesis by regulating degradation of HMGCR.
The KxHxx motif mediates association with the coatomer complex.
Belongs to the PtdIns transfer protein family. PI transfer class IIA subfamily.
Palmitoylated. Cys-85 appears to be the main site, and palmitoylation is required for membrane association (By similarity).
Part of the SNARE core complex containing SNAP25, VAMP2 and STX1A. This complex binds CPLX1. Interacts with TRIM9, RIMS1 and SNAPIN. Binds STXBP6. Found in a ternary complex with STX1A and VAMP8. Associates with the BLOC-1 complex. Isoform 1 and isoform 2 interact with BLOC1S6 (By similarity). Interacts with alpha-synuclein/SNCA (By similarity).
t-SNARE involved in the molecular regulation of neurotransmitter release. May play an important role in the synaptic function of specific neuronal systems. Associates with proteins involved in vesicle docking and membrane fusion (By similarity).
Binds bacterial lipopolysaccharide (LPS). Has potent antimicrobial activity against Gram-positive and Gram-negative bacteria (in vitro). Has hemolytic activity (in vitro). May play a role in the innate immune response.
Detected in gizzard, liver, small intestine, large intestine, cloaca, bursa of Fabricius, gall bladder, lung, trachea, kidney, testis and bone marrow.
Belongs to the glycerophosphoryl diester phosphodiesterase family.
The MREC motif may be critical for tubulin autoregulation.
There are at least seven alpha tubulin genes (alpha-1 to alpha-6, and alpha-8), and a pseudogene (alpha-7) in chicken.
This tubulin does not have a C-terminal tyrosine.
Acetylated on Lys-5, Lys-8 and Lys-12 during interphase. Acetylation disappears at mitosis (By similarity).
Monomethylated on Lys-5 and Lys-8 by SETD6. SETD6 predominantly methylates Lys-8, lys-5 being a possible secondary site.
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. H2A or its variant H2AZ1 forms a heterodimer with H2B (By similarity).
Variant histone H2A which replaces conventional H2A in a subset of nucleosomes. 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 (By similarity).
Belongs to the SOS response-associated peptidase family.
Glu-127 is involved in sensing abasic sites in single-stranded DNA (ssDNA). His-202 stabilizes the abasic sites by forming a hydrogen bond with the O4' hydroxyl group.
Sensor of abasic sites in single-stranded DNA (ssDNA) required to preserve genome integrity by promoting error-free repair of abasic sites. Acts as an enzyme that recognizes and binds abasic sites in ssDNA at replication forks and chemically modifies the lesion by forming a covalent cross-link with DNA: forms a stable thiazolidine linkage between a ring-opened abasic site and the alpha-amino and sulfhydryl substituents of its N-terminal catalytic cysteine residue. The HMCES DNA-protein cross-link is then degraded by the proteasome. Promotes error-free repair of abasic sites by acting as a 'suicide' enzyme that is degraded, thereby protecting abasic sites from translesion synthesis (TLS) polymerases and endonucleases that are error-prone and would generate mutations and double-strand breaks. Has preference for ssDNA, but can also accommodate double-stranded DNA with 3' or 5' overhang (dsDNA), and dsDNA-ssDNA 3' junction (By similarity). Acts as a protease: mediates autocatalytic processing of its N-terminal methionine in order to expose the catalytic cysteine (By similarity).
Plays an important role in membrane trafficking through the secretory apparatus.
Plays an important role in membrane trafficking through the secretory apparatus. Not involved in endocytic trafficking to lysosomes.
Belongs to the PI3/PI4-kinase family. Type II PI4K subfamily.
Contributes to the overall PI4-kinase activity of the cell. This contribution may be especially significant in plasma membrane, endosomal and Golgi compartments. 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).
Belongs to the class I-like SAM-binding methyltransferase superfamily. TRM61 family.
Catalytic subunit of tRNA (adenine-N(1)-)-methyltransferase, which catalyzes the formation of N(1)-methyladenine at position 58 (m1A58) in initiator methionyl-tRNA.
First detected within the ventral eye at Hamburger-Hamilton (HH) stage 14 as the optic vesicle invaginates. Expression restricted to the ventral retina at HH stage 22 and at 4 dpc as well as later in development.
Transcription factor that plays a role in establishing dorsal-ventral polarity in the neural retina.
Associates with the cytoplasmic CCR4-NOT deadenylase complex to trigger ARE-containing mRNA deadenylation and decay processes.
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.
Belongs to the Nudix hydrolase family. DCP2 subfamily.
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. 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. 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.
Negative regulator of sphingolipid synthesis.
Required for normal vault structure. Vaults are multi-subunit structures that may act as scaffolds for proteins involved in signal transduction. Vaults may also play a role in nucleo-cytoplasmic transport (By similarity).
The vault ribonucleoprotein particle is a huge (400 A x 670 A) cage structure of 12.9 MDa. It consists of a dimer of half-vaults, with each half-vault comprising 39 identical major vault protein (MVP) chains, PARP4 and one or more vault RNAs (vRNAs) (By similarity).
Belongs to the acid sphingomyelinase family.
Growth factor active in angiogenesis, vasculogenesis and endothelial cell growth. Induces endothelial cell proliferation, promotes cell migration, inhibits apoptosis and induces permeabilization of blood vessels. Binds to the FLT1/VEGFR1 and KDR/VEGFR2 receptors, heparan sulfate and heparin (By similarity).
Homodimer; disulfide-linked (By similarity). Also found as heterodimer with PGF (By similarity).
Belongs to the mitochondrion-specific ribosomal protein mS23 family.
Cleavage by different proteases, such as granzyme B (GZMB), caspase-1 (CASP1), caspase-8 (CASP8) or caspase-9 (CASP9) generate the two active subunits. Its involvement in different programmed cell death processes is probably specified by the protease that activates CASP7 (By similarity). Cleaved and activated by initiator caspases (CASP8 and/or CASP9), leading to execution phase of apoptosis (By similarity). Cleavage and maturation by GZMB regulates granzyme-mediated programmed cell death (By similarity). Cleaved and activated by CASP1 in response to bacterial infection (By similarity).
During activation, the N-terminal disordered prodomain is removed by cleavage. Concomitantly, double cleavage gives rise to a large Caspase-7 subunit p20 and a small Caspase-7 subunit p11. The two large and two small subunits then assemble to form the active CASP7 complex. Can be cleaved and activated by different caspases, depending on the context (By similarity). Cleaved and activated by initiator caspases (CASP8 and/or CASP9), leading to execution phase of apoptosis (By similarity). Cleavage and maturation by GZMB regulates granzyme-mediated programmed cell death. Cleavage and maturation by CASP1 regulates pyroptosis (By similarity).
Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 20 kDa (p20) and a 11 kDa (p11) subunit.
Thiol protease involved in different programmed cell death processes, such as apoptosis, pyroptosis or granzyme-mediated programmed cell death, by proteolytically cleaving target proteins (PubMed:14583630). Has a marked preference for Asp-Glu-Val-Asp (DEVD) consensus sequences, with some plasticity for alternate non-canonical sequences (By similarity). Its involvement in the different programmed cell death processes is probably determined by upstream proteases that activate CASP7 (By similarity). Acts as an effector caspase involved in the execution phase of apoptosis: following cleavage and activation by initiator caspases (CASP8 and/or CASP9), mediates execution of apoptosis by catalyzing cleavage of proteins (PubMed:14583630). Compared to CASP3, acts as a minor executioner caspase and cleaves a limited set of target proteins (By similarity). Acts as a key regulator of the inflammatory response in response to bacterial infection by catalyzing cleavage and activation of the sphingomyelin phosphodiesterase SMPD1 in the extracellular milieu, thereby promoting membrane repair (By similarity).
Belongs to the eukaryotic RPB8 RNA polymerase subunit family.
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.
Receptor for netrin required for axon guidance. Mediates axon repulsion of neuronal growth cones in the developing nervous system upon ligand binding.
Belongs to the zona pellucida-binding protein Sp38 family.
May be implicated in the gamete interaction during fertilization.
Expressed in peripheral blood lymphocytes (PBL) and peripheral blood mononuclear cells (PBMC).
Deglycase activity does not require glutathione as a cofactor, however, glycated glutathione constitutes a PARK7 substrate.
Glyoxylase activity previously reported may reflect in fact its deglycase activity.
Protein and nucleotide deglycase that catalyzes the deglycation of the Maillard adducts formed between amino groups of proteins or nucleotides and reactive carbonyl groups of glyoxals. Thus, functions as a protein deglycase that repairs methylglyoxal- and glyoxal-glycated proteins, and releases repaired proteins and lactate or glycolate, respectively. Deglycates cysteine, arginine and lysine residues in proteins, and thus reactivates these proteins by reversing glycation by glyoxals. Acts on early glycation intermediates (hemithioacetals and aminocarbinols), preventing the formation of advanced glycation endproducts (AGE) that cause irreversible damage. Also functions as a nucleotide deglycase able to repair glycated guanine in the free nucleotide pool (GTP, GDP, GMP, dGTP) and in DNA and RNA. Is thus involved in a major nucleotide repair system named guanine glycation repair (GG repair), dedicated to reversing methylglyoxal and glyoxal damage via nucleotide sanitization and direct nucleic acid repair. Also displays an apparent glyoxalase activity that in fact reflects its deglycase activity. Plays an important role in cell protection against oxidative stress and cell death acting as oxidative stress sensor and redox-sensitive chaperone and protease. It is involved in neuroprotective mechanisms as well as cell growth and transformation. Its involvement in protein repair could also explain other unrelated functions. Eliminates hydrogen peroxide and protects cells against hydrogen peroxide-induced cell death. Required for correct mitochondrial morphology and function as well as for autophagy of dysfunctional mitochondria. Regulates astrocyte inflammatory responses, may modulate lipid rafts-dependent endocytosis in astrocytes and neuronal cells. Binds to a number of mRNAs containing multiple copies of GG or CC motifs and partially inhibits their translation but dissociates following oxidative stress. Metal-binding protein able to bind copper as well as toxic mercury ions, enhances the cell protection mechanism against induced metal toxicity (By similarity).
Sumoylated on Lys-130; which is essential for cell-growth promoting activity and transforming activity.
The protein deglycation activity has been ascribed to a TRIS buffer artifact by a publication, which has then been rebutted by clear biochemical experiments showing that PARK7 is a bona fide deglycase. Deglycase activity is even strengthened by a novel article that reports nucleotide deglycation activity.
Undergoes cleavage of a C-terminal peptide and subsequent activation of protease activity in response to oxidative stress.
Interacts with the prenylated catalytic subunits of PDE6, an oligomer composed of two catalytic chains and two inhibitory chains; has no effect on enzyme activity but promotes the release of the prenylated enzyme from cell membrane.
Promotes the release of prenylated target proteins from cellular membranes. Modulates the activity of prenylated or palmitoylated Ras family members by regulating their subcellular location. Required for normal ciliary targeting of farnesylated target proteins, such as INPP5E. Modulates the subcellular location of target proteins by acting as a GTP specific dissociation inhibitor (GDI). Increases the affinity of ARL3 for GTP by several orders of magnitude. Stabilizes ARL3-GTP by decreasing the nucleotide dissociation rate.
Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers beta-catenin signaling through inducing aggregation of receptor-ligand complexes into ribosome-sized signalsomes.
Homodimer; disulfide-linked. Forms phosphorylated oligomer aggregates on Wnt-signaling.
After cleavage, the post-translationally modified ChM-I is secreted as a glycoprotein.
Bifunctional growth regulator. May contribute to the rapid growth of cartilage and vascular invasion prior to the replacement of cartilage by bone during endochondral bone development. Plays a role as antiangiogenic factor in cardiac valves to suppress neovascularization (By similarity).
Expressed in the cartilage and in fetal precartilaginous tissues as well as in heart and eye.
Expression onset occurs between stage 10 and stage 13.
Belongs to the chemokine-like receptor (CMKLR) family.
Both ATG8-interaction motifs (AIM1 and AIM2) are required for the association with ATG8 family proteins.
Component of the signaling pathway of IL-1 and Toll-like receptors. Inhibits cell activation by microbial products. Connects the ubiquitin pathway to autophagy by functioning as a ubiquitin-ATG8 family adapter and thus mediating autophagic clearance of ubiquitin conjugates. The TOLLIP-dependent selective autophagy pathway plays an important role in clearance of cytotoxic polyQ proteins aggregates (By similarity). In a complex with TOM1, recruits ubiquitin-conjugated proteins onto early endosomes (By similarity). Binds to phosphatidylinositol 3-phosphate (PtdIns(3)P) (By similarity).
Interacts with ATG8 family proteins (via AIM motifs), and ubiquitin (via CUE domain). Found in a complex with TOM1; interacts (via N-terminus) with TOM1 (via GAT domain); the interactions leads to TOM1-recruitment to endosomes and inhibition of TOLLIP binding to PtdIns(3)P (By similarity).
The N-terminal TOM1-binding domain (residues 1-53) is a disordered domain that partially folds when bound to the GAT domain of TOM1.
Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ6 subfamily.
Belongs to the G-protein coupled receptor 2 family. Adhesion G-protein coupled receptor (ADGR) subfamily.
Belongs to the alkaline phosphatase family.
Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily.
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.
Binds to WNT proteins and inhibits their activities. May be involved in mesoderm segmentation.
Scaffolding protein that specifically recognizes and binds dimethylarginine-containing proteins. In nucleus, acts as a coactivator: recognizes and binds asymmetric dimethylation on the core histone tails associated with transcriptional activation (H3R17me2a and H4R3me2a) and recruits proteins at these arginine-methylated loci. In cytoplasm, may play a role in the assembly and/or disassembly of mRNA stress granules and in the regulation of translation of target mRNAs by binding Arg/Gly-rich motifs (GAR) in dimethylarginine-containing proteins (By similarity).
The Tudor domain specifically recognizes and binds asymmetric dimethylation of histone H3 'Arg-17' (H3R17me2a) and histones H4 'Arg-3', 2 tags for epigenetic transcriptional activation.
Functional P2XRs are organized as homomeric and heteromeric trimers.
Receptor for ATP that acts as a ligand-gated ion channel.
Belongs to the secreted frizzled-related protein (sFRP) family.
In embryo, expressed in developing neural structures as well as in heart, branchial arches and limb buds. First expressed at stage 7 in the neural plate with lower expression in the midline. By stage 9, expressed through out the developing neural tube with lower levels in the future posterior mesencephalon and rhombomere 3. In anterior regions, highest expression in the dorsal neural tube and, more posteriorly throughout the closing neural tube. Also expressed in the ectoderm flanking the neural tube. In the developing brain, expression found in the presumptive forbrain. By stage 12, expression restricted to the dorsal prosencephalon, hindbrain and posterior neural tube. In the placodes, first expressed at stage 11, in the otic placode. By stage 15, expressed in the olfactory and epibranchial placodes. In facial primordia, expression found at stage 2,0 throughout the ectoderm. By stage 24, high mesenchymal expression in a small region of the posterior maxillary primordia, and in the lateral region of the mandibular primordia. By stage 28, expressed in a subset of muscles, including the intermandibularis muscle and the muscle medial to the eye. In the developing trunk, expression found throughout the dermamyotome in the more developed somites. By stage 20, expression restricted to the small region in the dorsal medial lip in all somites. In addition, also expressed in the ventral lateral lip of the dermamyotome that gives rise to the muscles of the limbs and body wall. During limb development, expressed between stages 20 and 30, in the proximal mesenchyme in association with developing muscles. Between stages 27 and 30, expression found in mesenchyme containing undifferentiated myogenic cells. In the developing heart, expression restricted to the myocardial and endocardial cell layers of the trabeculae in the ventricular compartment between stages 20 and 28.
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 appears to be associated with myogenesis.
Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active subunit of TGF-beta-1, respectively.
Localized at tight junctions of both epithelial and endothelial cells. Highly expressed in lung and liver. Expressed at a lower level in brain.
May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier. Interacts with ZO-1.
The C-terminal is cytoplasmic and is important for interaction with ZO-1. Necessary for the tight junction localization. Involved in the regulation of the permeability barrier function of the tight junction. The second extracellular domain may also be implicated in the permeability barrier function of the tight junction.
Lipid-binding protein involved in the biosynthesis of coenzyme Q, also named ubiquinone, an essential lipid-soluble electron transporter for aerobic cellular respiration.
Belongs to the class I-like SAM-binding methyltransferase superfamily. RsmB/NOP family. TRM4 subfamily.
RNA cytosine C(5)-methyltransferase that methylates cytosine to 5-methylcytosine (m5C) in various RNAs, such as tRNAs, mRNAs and some long non-coding RNAs (lncRNAs). Involved in various processes, such as epidermal stem cell differentiation, testis differentiation and maternal to zygotic transition during early development: acts by increasing protein synthesis; cytosine C(5)-methylation promoting tRNA stability and preventing mRNA decay. Methylates cytosine to 5-methylcytosine (m5C) at positions 34 and 48 of intron-containing tRNA(Leu)(CAA) precursors, and at positions 48, 49 and 50 of tRNA(Gly)(GCC) precursors. tRNA methylation is required generation of RNA fragments derived from tRNAs (tRFs). Also mediates C(5)-methylation of mitochondrial tRNAs. Catalyzes cytosine C(5)-methylation of mRNAs, leading to stabilize them and prevent mRNA decay. Cytosine C(5)-methylation of mRNAs also regulates mRNA export. Also mediates cytosine C(5)-methylation of non-coding RNAs, such as vault RNAs (vtRNAs), promoting their processing into regulatory small RNAs. Required for proper spindle assembly and chromosome segregation, independently of its methyltransferase activity.
Belongs to the proton-activated chloride channel family.
Belongs to the UTP23/FCF1 family. FCF1 subfamily.
Catalyzes the final step in the metabolic pathway of hydroxyproline.
Involved in the second step of GPI biosynthesis. De-N-acetylation of N-acetylglucosaminyl-phosphatidylinositol.
Belongs to the WD repeat PROPPIN family.
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. Binds phosphatidylinositol 3-phosphate (PtdIns3P), and other phosphoinositides including PtdIns(3,5)P2, forming on membranes of the endoplasmic reticulum upon activation of the upstream ULK1 and PI3 kinases and is recruited at phagophore assembly sites where it regulates the elongation of nascent phagophores downstream of WIPI2.
The L/FRRG motif is required for recruitment to PtdIns3P.
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.
Mammalian complex I is composed of 45 different subunits.
Belongs to the cysteine dioxygenase family.
Catalyzes the oxidation of cysteine to cysteine sulfinic acid with addition of molecular dioxygen.
Although it shares weak sequence similarity with GTF2B/TFIIB, displays a similar subdomain organization as GTF2B/TFIIB, with a N-terminal zinc finger, a connecting region (composed of B-reader and B-linker regions), followed by 2 cyclin folds. The RRN7-type zinc finger plays an essential postrecruitment role in Pol I transcription at a step preceding synthesis of the first 40 nucleotides (By similarity).
Component of RNA polymerase I core factor complex that acts as a GTF2B/TFIIB-like factor and plays a key role in multiple steps during transcription initiation such as pre-initiation complex (PIC) assembly and postpolymerase recruitment events in polymerase I (Pol I) transcription. Binds rDNA promoters and plays a role in Pol I recruitment (By similarity).
Belongs to the PI3/PI4-kinase family. ATM subfamily.
Belongs to the proteasome subunit S10 family.
Component of the BCR(KLHL20) E3 ubiquitin ligase complex, at least composed of CUL3, KLHL20 and RBX1.
Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex involved in interferon response and anterograde Golgi to endosome transport. The BCR(KLHL20) E3 ubiquitin ligase complex mediates the ubiquitination of target proteins, leading to their degradation by the proteasome. It also specifically mediates 'Lys-33'-linked ubiquitination (By similarity).
Expressed by developing cerebellar Purkinje cells. Expression coincides with the growth of the dendritic tree, after Purkinje cells have finished their migration from the ventricular zone (from 15 dpc until 21 dpc). Expressed in the adult.
Found on the dendrites, somata and axons of developing Purkinje cells. Undetectable on other neurons like Golgi or granule cells.
It may be a cellular address molecule specific to Purkinje cells. It may represent a receptor or a subunit of a receptor complex.
Contributes to the transparency and refractive index of the lens. May act as a chaperone, preventing aggregation of various proteins under a wide range of stress conditions.
Heteropolymer composed of three CRYAA and one CRYAB subunits (By similarity). Inter-subunit bridging via zinc ions enhances stability, which is crucial as there is no protein turn over in the lens. Can also form homodimers and homotetramers (dimers of dimers) which serve as the building blocks of homooligomers (By similarity). 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).
Belongs to the Mediator complex subunit 10 family.
Belongs to the POU transcription factor family. Class-1 subfamily.
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.
Probable peripherally associated component of the endosomal sorting required for transport complex III (ESCRT-III).
Contains one Leu-Xaa-Xaa-Leu-Leu (LXXLL) motif that may mediate interaction with nuclear receptors.
F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein. Probably involved in vesicular trafficking via its association with the CART complex. Involved in tight junction assembly in epithelial cells. May also function as a transcriptional coactivator, stimulating transcription mediated by nuclear hormone receptors.
Homodimer; antiparallel. Component of the CART complex. May interact with nuclear receptors.
Transcripts are present at 3.5 dpc in the somitic cells, which give rise to the dorsal dermis by 5 dpc, and at 6.5 dpc to 8.5 dpc in the dorsal dermal and epidermal cells during the first stages of feather morphogenesis.
Belongs to the sirtuin family. Class III subfamily.
In contrast to class I sirtuins, class III sirtuins have only weak deacetylase activity. Difference in substrate specificity is probably due to a larger hydrophobic pocket with 2 residues (Tyr-101 and Arg-104) that bind to malonylated and succinylated substrates and define the specificity.
NAD-dependent lysine demalonylase, desuccinylase and deglutarylase that specifically removes malonyl, succinyl and glutaryl groups on target proteins. Has weak NAD-dependent protein deacetylase activity; however this activity may not be physiologically relevant in vivo.
Binds directly to activin and functions as an activin antagonist. Inhibits activin A signaling in the iris and regulates somatostatin phenotype in ciliary ganglion neurons. Specific inhibitor of the biosynthesis and secretion of pituitary follicle stimulating hormone (FSH).
Ciliary ganglion neurons. Levels are higher in the iris than the choroid.
Levels increase in the iris from embryonic day 9 (9 dpc) to 16 dpc in contrast to the choroid where it remains low relative to iris. During early hindbrain development strongly expressed in rhombomeres R2, R4, R5 and R6 but not in R3. Expression in R3 is seen at later stages and is dependent on neighboring interactions.
Binds 1 myo-inositol hexakisphosphate (IP6) per subunit.
Specifically deaminates adenosine-37 to inosine in tRNA-Ala.
Belongs to the major facilitator superfamily. Organophosphate:Pi antiporter (OPA) (TC 2.A.1.4) family.
Belongs to the AB hydrolase superfamily. AB hydrolase 2 family.
Belongs to the metallo-dependent hydrolases superfamily. Adenosine and AMP deaminases family.
Catalyzes the hydrolytic deamination of adenosine and 2-deoxyadenosine. Plays an important role in purine metabolism and in adenosine homeostasis. Modulates signaling by extracellular adenosine, and so contributes indirectly to cellular signaling events. May act as a positive regulator of T-cell coactivation (By similarity).
Belongs to the Mediator complex subunit 31 family.
Plays a role in mitochondrial morphogenesis.
Belongs to the class I-like SAM-binding methyltransferase superfamily. RNA M5U methyltransferase family.
Catalyzes the 2-thiolation of uridine at the wobble position (U34) of mitochondrial tRNA(Lys), tRNA(Glu) and tRNA(Gln). Required for the formation of 5-taurinomethyl-2-thiouridine (tm5s2U) of mitochondrial tRNA(Lys), tRNA(Glu), and tRNA(Gln) at the wobble position. ATP is required to activate the C2 atom of the wobble base.
During the reaction, ATP is used to activate the C2 atom of U34 by adenylation. After this, the persulfide sulfur on the catalytic cysteine is transferred to the C2 atom of the wobble base (U34) of mitochondrial tRNA(Lys), tRNA(Glu) and tRNA(Gln). The reaction probably involves hydrogen sulfide that is generated from the persulfide intermediate and that acts as nucleophile towards the activated C2 atom on U34. Subsequently, a transient disulfide bond is formed between the two active site cysteine residues (By similarity).
Monomer (By similarity). Interacts with LDB1.
Preferentially catalyzes the dephosphorylation of 'Ser-5' within the tandem 7 residue repeats in the C-terminal domain (CTD) of the largest RNA polymerase II subunit POLR2A. Negatively regulates RNA polymerase II transcription, possibly by controlling the transition from initiation/capping to processive transcript elongation. Recruited by REST to neuronal genes that contain RE-1 elements, leading to neuronal gene silencing in non-neuronal cells (By similarity).
Required for the post-translational delivery of tail-anchored (TA) proteins to the endoplasmic reticulum. Together with GET1/WRB, acts as a membrane receptor for soluble GET3/TRC40, which recognizes and selectively binds the transmembrane domain of TA proteins in the cytosol. Required for the stability of GET1. Stimulates calcium signaling in T cells through its involvement in elevation of intracellular calcium. Essential for the survival of peripheral follicular B cells.
Contains one covalently linked retinal chromophore. Upon light absorption, the covalently bound 11-cis-retinal is converted to all-trans-retinal. After hydrolysis of the Schiff base and release of the covalently bound all-trans-retinal, active rhodopsin is regenerated by binding of a fresh molecule of 11-cis-retinal.
Photoreceptor required for image-forming vision at low light intensity. Required for photoreceptor cell viability after birth (By similarity). Light-induced isomerization of 11-cis to all-trans retinal triggers a conformational change that activates signaling via G-proteins. Subsequent receptor phosphorylation mediates displacement of the bound G-protein alpha subunit by arrestin and terminates signaling (By similarity).
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.
Belongs to the complex I NDUFA12 subunit family.
Belongs to the dynein light chain Tctex-type family.
Interacts with SDHA within the SDH catalytic dimer.
Plays an essential role in the assembly of succinate dehydrogenase (SDH), an enzyme complex (also referred to as respiratory complex II) that is a component of both the tricarboxylic acid (TCA) cycle and the mitochondrial electron transport chain, and which couples the oxidation of succinate to fumarate with the reduction of ubiquinone (coenzyme Q) to ubiquinol. Required for flavinylation (covalent attachment of FAD) of the flavoprotein subunit SDHA of the SDH catalytic dimer.
Mediator of sterol homeostasis involved in sterol uptake, trafficking and distribution into membranes.
Belongs to the Orn/Lys/Arg decarboxylase class-II family.
Catalyzes the first and rate-limiting step of polyamine biosynthesis that converts ornithine into putrescine, which is the precursor for the polyamines, spermidine and spermine. Polyamines are essential for cell proliferation and are implicated in cellular processes, ranging from DNA replication to apoptosis.
Homodimer. Only the dimer is catalytically active, as the active sites are constructed of residues from both monomers.
Inhibited by antizymes (AZs) in response to polyamine levels. AZs inhibit the assembly of the functional homodimer by binding to ODC monomers and targeting them for ubiquitin-independent proteolytic destruction by the 26S proteasome.
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. GINS complex seems to bind preferentially to single-stranded DNA.
Belongs to the IMPDH/GMPR family. GuaC type 1 subfamily.
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.
Belongs to the grh/CP2 family. CP2 subfamily.
Binds the B-response element 5'-CAAGTCCAGGCAAGT-3' of the ENS1/ERNI promoter. May be the major transcription activator thus being essential for its expression.
Component of the SSP (stage selector protein) complex, which appears to be a heteromer of TFCP2 and 2 copies of NFE4.
Expressed in the epiblast at the pre-primitive streak stage. At the primitive streak stage, expressed in the extending primitive streak and in the prospective neural plate. At stages 7 and 8, expressed in the neural folds, somites and in the regressing primitive streak. At stage 12, ubiquitously expressed in the whole embryo.
Netrins control guidance of CNS commissural axons and peripheral motor axons. Promotes neurite outgrowth from commissural axons but acts as a chemorepellent for trochlear motor axons. These effects are mediated by distinct receptors.
May bind zinc and other divalent cations and recruit them to vesicular organelles.
Belongs to the Integrator subunit 8 family.
Belongs to the class I-like SAM-binding methyltransferase superfamily. C5-methyltransferase family.
Component of the FACT complex, a general chromatin factor that acts to reorganize nucleosomes. The FACT complex is involved in multiple processes that require DNA as a template such as mRNA elongation, DNA replication and DNA repair. During transcription elongation the FACT complex acts as a histone chaperone that both destabilizes and restores nucleosomal structure. It facilitates the passage of RNA polymerase II and transcription by promoting the dissociation of one histone H2A-H2B dimer from the nucleosome, then subsequently promotes the reestablishment of the nucleosome following the passage of RNA polymerase II.
Component of the FACT complex, a general chromatin factor that acts to reorganize nucleosomes. The FACT complex is involved in multiple processes that require DNA as a template such as mRNA elongation, DNA replication and DNA repair. During transcription elongation the FACT complex acts as a histone chaperone that both destabilizes and restores nucleosomal structure. It facilitates the passage of RNA polymerase II and transcription by promoting the dissociation of one histone H2A-H2B dimer from the nucleosome, then subsequently promotes the reestablishment of the nucleosome following the passage of RNA polymerase II. Binds specifically to double-stranded DNA (By similarity).
Component of the FACT complex, a stable heterodimer of SSRP1 and SUPT16H. Also a component of a CK2-SPT16-SSRP1 complex which forms following UV irradiation, composed of SSRP1, SUPT16H, CSNK2A1, CSNK2A2 and CSNK2B (By similarity).
Phosphorylates D-xylulose to produce D-xylulose 5-phosphate, a molecule that may play an important role in the regulation of glucose metabolism and lipogenesis.
Belongs to the pyrroline-5-carboxylate reductase family.
Belongs to the interleukin-1 receptor family.
Receptor for thyrotropin-releasing hormone (TRH). Upon ligand binding, this G-protein-coupled receptor triggers activation of the phosphatidylinositol (IP3)-calcium-protein kinase C (PKC) pathway.
Belongs to the potassium channel family. Calcium-activated (TC 1.A.1.3) subfamily. KCa1.1/KCNMA1 sub-subfamily.
Ethanol and carbon monoxide-bound heme increase channel activation. Heme inhibits channel activation (By similarity).
Homotetramer; which constitutes the calcium-activated potassium channel.
It is uncertain whether Met-1 is the initiator or if the sequence starts further upstream.
Potassium channel activated by both membrane depolarization or increase in cytosolic Ca(2+) that mediates export of K(+). It is also activated by the concentration of cytosolic Mg(2+). Its activation dampens the excitatory events that elevate the cytosolic Ca(2+) concentration and/or depolarize the cell membrane. It therefore contributes to repolarization of the membrane potential. Plays a key role in controlling excitability in a number of systems, such as regulation of the contraction of smooth muscle, the tuning of hair cells in the cochlea, regulation of transmitter release, and innate immunity. In smooth muscles, its activation by high level of Ca(2+), caused by ryanodine receptors in the sarcoplasmic reticulum, regulates the membrane potential. In cochlea cells, its number and kinetic properties partly determine the characteristic frequency of each hair cell and thereby helps to establish a tonotopic map. Highly sensitive to both iberiotoxin (IbTx) and charybdotoxin (CTX).
The RCK N-terminal domain mediates the homotetramerization, thereby promoting the assembly of monomers into functional potassium channel. It includes binding sites for Ca(2+) and Mg(2+) (By similarity).
The S0 segment is essential for the modulation by the accessory beta subunits.
The S4 segment, which is characterized by a series of positively charged amino acids at every third position, is part of the voltage-sensor.
The calcium bowl constitutes one of the Ca(2+) sensors and probably acts as a Ca(2+)-binding site. There are however other Ca(2+) sensors regions required for activation of the channel (By similarity).
The heme-binding motif mediates inhibition of channel activation by heme. Carbon monoxide-bound heme leads to increased channel activation (By similarity).
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).
The protein was initially thought to contain two functionally distinct parts: The core channel (from the N-terminus to the S9 segment) that mediates the channel activity, and the cytoplasmic tail (from the S9 segment to the C-terminus) that mediates the calcium sensing. The situation is however more complex, since the core channel contains binding sites for Ca(2+) and Mg(2+).
Belongs to the actin-binding proteins ADF family. GMF subfamily.
Belongs to the glycosyl hydrolase 31 family.
Component of an histone acetyltransferase complex.
Component of an histone acetyltransferase complex. Interacts with H3K4me3 and to a lesser extent with H3K4me2.
The PHD-type zinc finger mediates the binding to H3K4me3.
Belongs to the small leucine-rich proteoglycan (SLRP) family. SLRP class I subfamily.
Binds to type I and type II collagen, to fibronectin and TGF-beta. Forms a ternary complex with MFAP2 and ELN (By similarity).
May affect the rate of fibrils formation.
The attached glycosaminoglycan chain can be either chondroitin sulfate or dermatan sulfate depending upon the tissue of origin.
Belongs to the liprin family. Liprin-beta subfamily.
Belongs to the eukaryotic mitochondrial porin family.
Belongs to the DOK family. Type A subfamily.
DOK proteins are enzymatically inert adaptor or scaffolding proteins. They provide a docking platform for the assembly of multimolecular signaling complexes. Plays a role as negative regulator of the mobilization of calcium ions and of calcium signaling.
Homooligomer. Interacts with GRB2 and INPP5D/SHIP.
PTB domain mediates receptor interaction.
Tyrosine-phosphorylated in the presence of GRB2.
Belongs to the cyclin family. Cyclin E subfamily.
Essential for the control of the cell cycle at the G1/S (start) transition.
Interacts with CDK2 protein kinase to form a serine/threonine kinase holoenzyme complex. The cyclin subunit imparts substrate specificity to the complex (By similarity).
Phosphorylation by CDK2 triggers its release from CDK2 and degradation via the ubiquitin proteasome pathway.
Belongs to the DNA repair metallo-beta-lactamase (DRMBL) family.
Phosphorylation on undefined residues by PRKDC may stimulate endonucleolytic activity on 5' and 3' hairpins and overhangs. PRKDC must remain present, even after phosphorylation, for efficient hairpin opening (By similarity).
Required for V(D)J recombination, the process by which exons encoding the antigen-binding domains of immunoglobulins and T-cell receptor proteins are assembled from individual V, (D), and J gene segments. V(D)J recombination is initiated by the lymphoid specific RAG endonuclease complex, which generates site specific DNA double strand breaks (DSBs). These DSBs present two types of DNA end structures: hairpin sealed coding ends and phosphorylated blunt signal ends. These ends are independently repaired by the non homologous end joining (NHEJ) pathway to form coding and signal joints respectively. This protein exhibits single-strand specific 5'-3' exonuclease activity in isolation, and acquires endonucleolytic activity on 5' and 3' hairpins and overhangs when in a complex with PRKDC. The latter activity is required specifically for the resolution of closed hairpins prior to the formation of the coding joint. May also be required for the repair of complex DSBs induced by ionizing radiation, which require substantial end-processing prior to religation by NHEJ (By similarity).
Expressed in the dermatome. The expression domain is mutually exclusive to the other Wnt genes.
Ligand for members of the frizzled family of seven transmembrane receptors. May play a role in the formation of dermal structure, both limb and feather buds. Is likely to signal over only few cell diameters.
Palmitoleoylation is required for efficient binding to frizzled receptors. Depalmitoleoylation leads to Wnt signaling pathway inhibition.
May play a role in mitochondrial respiratory chain complex IV assembly. Probably involved in the biogenesis of the COX complex.
Belongs to the small GTPase superfamily. Rho family. CDC42 subfamily.
Plasma membrane-associated small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state.
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. Regulates cell migration. Plays a role in the extension and maintenance of the formation of thin, actin-rich surface projections called filopodia. Also plays a role in phagocytosis through organization of the F-actin cytoskeleton associated with forming phagocytic cups.
Belongs to the helicase family. Dicer subfamily.
Binds 2 magnesium or manganese ions per subunit.
Component of the RISC loading complex (RLC), or micro-RNA (miRNA) loading complex (miRLC), which is composed of DICER1, AGO2 and TARBP2; DICER1 and TARBP2 are required to process precursor miRNAs (pre-miRNAs) to mature miRNAs and then load them onto AGO2. Note that the trimeric RLC/miRLC is also referred to as RISC (By similarity).
Double-stranded RNA (dsRNA) endoribonuclease playing a central role in short dsRNA-mediated post-transcriptional gene silencing. Cleaves naturally occurring long dsRNAs and short hairpin pre-microRNAs (miRNA) into fragments of twenty-one to twenty-three nucleotides with 3' overhang of two nucleotides, producing respectively short interfering RNAs (siRNA) and mature microRNAs. SiRNAs and miRNAs serve as guide to direct the RNA-induced silencing complex (RISC) to complementary RNAs to degrade them or prevent their translation. Gene silencing mediated by siRNAs, also called RNA interference, controls the elimination of transcripts from mobile and repetitive DNA elements of the genome but also the degradation of exogenous RNA of viral origin for instance. The miRNA pathway on the other side is a mean to specifically regulate the expression of target genes (By similarity).
It is uncertain whether Met-1 or Met-11 is the initiator.
Belongs to the plasmodium circumsporozoite protein family.
In the vertebrate host, binds to highly sulfated heparan sulfate proteoglycans (HSPGs) on the surface of host hepatocytes and is required for sporozoite invasion of the host hepatocytes.
Involved in pre-mRNA alternative splicing regulation. Binds to CUG triplet repeat in RNA (By similarity).
Belongs to the glycosyltransferase 7 family.
Responsible for the synthesis of complex-type N-linked oligosaccharides in many glycoproteins as well as the carbohydrate moieties of glycolipids.
Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IB subfamily.
Hydrolase that deubiquitinates target proteins, such as p53/TP53. Deubiquitinates p53/TP53, and thereby modulates p53/TP53 stability, p53/TP53-dependent transcription regulation, cell growth repression and apoptosis. May be involved in cell proliferation during early embryonic development (By similarity). Involved in the regulation of WASH-dependent actin polymerization at the surface of endosomes and the regulation of endosomal protein recycling.
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.
Activated by magnesium and inorganic phosphate. Competitively or non-competitively inhibited by ADP, 2,3-bisphosphoglyceride or GDP (By similarity).
Homodimer. The active form is probably a hexamer composed of 3 homodimers (By similarity).
The RNA gate region regulates mRNA cap recognition to prevent promiscuous mRNA-binding before assembly of eif3d into the full eukaryotic translation initiation factor 3 (eIF-3) complex.
mRNA cap-binding component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is involved in protein synthesis of a specialized repertoire of mRNAs and, together with other initiation factors, stimulates binding of mRNA and methionyl-tRNAi to the 40S ribosome. The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation. In the eIF-3 complex, eif3d specifically recognizes and binds the 7-methylguanosine cap of a subset of mRNAs.
Expressed in the spinal cord of stage 22 embryos. Expressed during neurogenesis in the mantle zone of the spinal cord in domains corresponding to interneurons.
Functions as a transcriptional repressor. Regulates the proliferation and the differentiation of erythroid progenitors. Plays a role in granulocyte differentiation. May also function as an A-kinase-anchoring protein (By similarity).
Component of the signal recognition particle (SRP) complex, a ribonucleoprotein complex that mediates the cotranslational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER).
Belongs to the V-ATPase 116 kDa subunit family.
Detected in brain (at protein level). Highest expression in brain, intermediate levels in kidney, and relatively low levels in bone and liver.
Essential component of the vacuolar proton pump (V-ATPase), a multimeric enzyme that catalyzes the translocation of protons across the membranes. Required for assembly and activity of the V-ATPase.
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 (By similarity). 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). Required for assembly and activity of the vacuolar ATPase (By similarity).
V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex (By similarity). 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 (By similarity). 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 (By similarity).
Also able to convert testosterone (T) into 5-alpha-dihydrotestosterone (DHT).
Belongs to the steroid 5-alpha reductase family. Polyprenol reductase subfamily.
Plays a key role in early steps of protein N-linked glycosylation by being required for the conversion of polyprenol into dolichol. Dolichols are required for the synthesis of dolichol-linked monosaccharides and the oligosaccharide precursor used for N-glycosylation. Acts as a polyprenol reductase that promotes the reduction of the alpha-isoprene unit of polyprenols into dolichols in a NADP-dependent mechanism.
Tetrahedron-shaped homododecamer built from six homodimers.
Mediates the production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). Plays an important role in the regulation of intracellular signaling cascades.
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.
Belongs to the 3-hydroxyacyl-CoA dehydrogenase family.
Involved in several stages of intracellular trafficking.
Belongs to the bacterial ribosomal protein bS6 family.
Binds 3 Ca(2+) ions per subunit. Two of the Ca(2+) ions are bound to the C2 domain.
F-actin cross-linking protein is thought to anchor actin to a variety of intracellular structures. This is a bundling protein.
Homodimer; antiparallel (By similarity). Interacts with PDLIM4 (via PDZ domain) (PubMed:14729062).
Probable component of the nuclear pore complex (NPC).
Required for the export of mRNAs containing poly(A) tails from the nucleus into the cytoplasm.
The 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.
GTP-hydrolysis activating protein (GAP) for small GTPase RAB22A, converting active RAB22A-GTP to the inactive form RAB22A-GDP (By similarity). Plays a role in endocytosis and intracellular protein transport. Recruited by ANK2 to phosphatidylinositol 3-phosphate (PI3P)-positive early endosomes, where it inactivates RAB22A, and promotes polarized trafficking to the leading edge of the migrating cells. Part of the ANK2/RABGAP1L complex which is required for the polarized recycling of fibronectin receptor ITGA5 ITGB1 to the plasma membrane that enables continuous directional cell migration (By similarity).
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.
Expressed in brain, heart, eye, liver, kidney and skeletal muscle.
Belongs to the eukaryotic RPB7/RPC8 RNA polymerase subunit family.
Broad specificity aminopeptidase. Degrades a variety of peptides possessing various N-terminal amino acids including hydrophobic, basic and acidic amino acids. Preferentially hydrolyzes small peptides consisting of 4 or 5 amino acids. Hydrolyzes the N-terminal Xaa-Pro bonds in the chicken brain peptide Leu-Pro-Leu-Arg-PheNH2, the substance P fragment Arg-Pro-Lys-Pro and the bradykinin fragment Arg-Pro-Pro-Gly-Phe. Hydrolyzes the N-formylated peptides fMet-Leu-Phe, fMet-Ala-Gly-Ser-Glu and fMet-Nle-Leu-Phe-Nle-Tyr-Lys, but does not hydrolyze peptides with acetylation or pyroglutamic acid at N-terminus. Does not hydrolyze large peptides such as complete substance P, bradykinin or schistoFLRFamide.
Detected in the plasma and granule fractions of egg yolk (at protein level).
Fibronectins bind cell surfaces and various compounds including collagen, fibrin, heparin, DNA, and actin. Fibronectins are involved in cell adhesion, cell motility, opsonization, wound healing, and maintenance of cell shape (By similarity). Involved in osteoblast compaction through the fibronectin fibrillogenesis cell-mediated matrix assembly process, essential for osteoblast mineralization. Participates in the regulation of type I collagen deposition by osteoblasts (By similarity).
Forms covalent cross-links mediated by a transglutaminase, such as F13A or TGM2, between a glutamine and the epsilon-amino group of a lysine residue, forming homopolymers and heteropolymers (e.g. fibrinogen-fibronectin, collagen-fibronectin heteropolymers).
Mostly heterodimers or multimers of alternatively spliced variants, connected by 2 disulfide bonds near the carboxyl ends; to a lesser extent homodimers. Interacts with FBLN7 (By similarity).
Plasma FN (soluble dimeric form) is secreted by hepatocytes. Cellular FN (dimeric or cross-linked multimeric forms), made by fibroblasts, epithelial and other cell types, is deposited as fibrils in the extracellular matrix.
Expressed in embryonic day-15 eye, brain, skeletal muscle, heart and intestine, but virtually absent from embryonic day-15 liver.
Inhibits IGF-mediated growth and developmental rates (By similarity). IGF-binding proteins prolong the half-life of the IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs on cell culture. They alter the interaction of IGFs with their cell surface receptors.
The C-terminus is required for IGF-binding and growth inhibition.
Required for efficient export of polyadenylated RNA. Acts as component of the THO subcomplex of the TREX complex which is thought to couple mRNA transcription, processing and nuclear export, and which 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.
Belongs to the archaeal Rpo5/eukaryotic RPB5 RNA polymerase subunit family.
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.
Belongs to the V-ATPase V0D/AC39 subunit family.
Belongs to the CorA metal ion transporter (MIT) (TC 1.A.35) family.
Highly expressed in embryonic stomach, midgut and colon during the period of visceral smooth muscle cell differentiation; levels decrease rapidly thereafter (PubMed:22683258). mRNA already detected at stage 7-8 in the cardiogenic mesoderm, and become almost undetectable in the outer curvature of the ventricular region whereas remaining high in the developing atrial regions (PubMed:10096065).
RNA-binding protein involved in the regulation of smooth muscle cell differentiation and proliferation in the gastrointestinal system (PubMed:22683258, PubMed:25064856). Binds NOG mRNA, the major inhibitor of the bone morphogenetic protein (BMP) pathway (PubMed:25064856). Mediates an increase of NOG mRNA levels, thereby contributing to the negative regulation of BMP signaling pathway and promoting reversible dedifferentiation and proliferation of smooth muscle cells (PubMed:25064856).
Belongs to the beta-microseminoprotein family.
Interacts (via extracellular domain region) with trypsin.
Catalyzes the synthesis of carnosine and homocarnosine. Carnosine is synthesized more efficiently than homocarnosine.
Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MNB/DYRK subfamily.
Belongs to the strictosidine synthase family.
Expressed in the neural tube, dorsal root glanglia, spinal nerves and myotome at 4 dpc. Expressed in neuronal and glial cell populations as detected at 10 dpc (at protein level).
Mainly in the nervous system (at protein level).
May function as a linker between cadherin adhesion receptors and the cytoskeleton to regulate cell-cell adhesion and differentiation in the nervous system.
GTPase activator for the Rho-type GTPases by converting them to an inactive GDP-bound state.
Causes an allergic reaction in humans. Binds to IgE of egg-allergic patients. Immunoreactivity is lost by simulated gastric and gastroduodenal digestion (PubMed:23122126). Binds to rabbit anti-ovomucoid IgG antibody indicating the cross-reactivity between this protein and the ovomucoid protein from egg white (PubMed:6838526).
Expressed in liver of pre-laying and egg-laying hens throughout sexual maturation. Expression increases gradually from 13 weeks of age reaching its maximum at 15 weeks of age (pre-laying hens). A significant decrease in expression is observed in 41-week-old hens (egg-laying), a level that is significantly lower than that measured initially in 13-week-old pullets.
Expressed in oviduct (at protein level) (PubMed:3571241). Expressed in egg white (at protein level) (PubMed:6838526, PubMed:14519973, PubMed:23122126, PubMed:25436390). Expressed in egg yolk plasma of non-fertilized eggs (at protein level) (PubMed:22010862). Expressed in the magnum of the oviduct (at protein level) (PubMed:25436390). Expressed in oviduct (PubMed:3571241, PubMed:14609095). Expressed in liver (PubMed:3571241, PubMed:11572089, PubMed:22010862). Expressed in the cortico-medullary border region of the bursa of Fabricius by the bursal secretory dendritic-like cells (PubMed:15252730). Highly expressed in the magnum of the oviduct, and at a lower level in uterus. Weakly expressed in white isthmus and very weakly in infundibulum. Not expressed in duodenum and kidney (PubMed:22010862).
Expression is regulated by dietary stress. Significantly increased expression between days 0 to 5 in egg whites of eggs laid by corticosterone-fed hens (at protein level). Decreased expression at day 14 in the magnum of the oviduct in the corticosterone-fed laying hens (PubMed:25436390). Significantly increased expression by estrogen. Rapidly up-regulated within 0.5 hour after extrogen exposure with a peak at 1-4 hours and diminishing thereafter (PubMed:11572089). Up-regulated during sexual maturation of pullets (PubMed:22010862).
Prevents symptomatic gastoroenteritis in vivo in a mouse model of rotavirus infection. Significantly inhibits intestinal replication of EDIM strain of murine rotavirus in infant mice up to 4 days after intragastrical administration of the virus.
Seems to have at least five separate non-overlapping active inhibitory domains; two for trypsin, two for chymotrypsin and one for elastase. They can be bound to the domains simultaneously.
Serine protease inhibitor involved in antimicrobial egg defense preventing contamination of table eggs (non-fertilized eggs) and protecting the chick embryo (fertilized eggs) (Probable). Inhibits trypsin, chymotrypsin, elastase, subtilisin and a proteinase of fungus Aspergillus oryzae (PubMed:13944692, PubMed:6904299, PubMed:6838526, PubMed:14519973, PubMed:14609095, PubMed:22010862). Inhibits calcium-activated potassium channels KCNMA1 (bovine) and slo (Drosophila) (PubMed:8973172). Has antibacterial activity against B.thuringiensis LMSA 3.06.004, but not against S.aureus CIP 103 811, P.aeruginosa PAO1, B.cereus ATCC6464 or B.subtilis ATCC 6633 (PubMed:22010862).
The galactomannan conjugate of this protein prepared through the Maillard reaction shows almost the same inhibitory activity toward trypsin, chymotrypsin and elastase, with stronger heat and emulsion stability, and better emulsifying properties than the untreated protein. The conjugate can therefore be useful for industrial application.
Histone binding is mediated by the concave surface of the LRR region.
Interacts with histones H3 and H4. Interacts with KLF5; this interaction induces promoter region-specific histone incorporation and inhibition of histone acetylation by ANP32B.
Multifunctional protein that is involved in the regulation of many processes including cell proliferation, apoptosis, cell cycle progression or transcription. Regulates the proliferation of neuronal stem cells, differentiation of leukemic cells and progression from G1 to S phase of the cell cycle. As negative regulator of caspase-3-dependent apoptosis, may act as an antagonist of ANP32A in regulating tissue homeostasis. Exhibits histone chaperone properties, able to recruit histones to certain promoters, thus regulating the transcription of specific genes. Also plays an essential role in the nucleocytoplasmic transport of specific mRNAs via the uncommon nuclear mRNA export receptor XPO1/CRM1.
Involved in the modulation of mTOR signaling and expression of mTOR complex components. Involved in the regulation of cell proliferation and growth. Involved in the control of actin-cytoskeleton organization.
Homodimer, and heterodimer with SH3GLB1.
Plasma membrane anion exchange protein of wide distribution.
Biotransformation enzyme that catalyzes the hydrolysis of arene and aliphatic epoxides to less reactive and more water soluble dihydrodiols by the trans addition of water.
Converts big endothelin-1 to endothelin-1.
Component of the ESCRT-0 complex composed of STAM2 and HGS.
Involved in intracellular signal transduction mediated by EGF. As a protein associated with focal adhesions and actin filaments, it may play a role in EGF receptor-stimulated cytoskeletal reorganization. The ESCRT-0 complex binds ubiquitin and acts as sorting machinery that recognizes ubiquitinated receptors and transfers them to further sequential lysosomal sorting/trafficking processes (By similarity).
Phosphorylated in response to EGF and PDGF. Phosphorylated by SRC.
Troponin T is the tropomyosin-binding subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity.
Plays an important role in the regulation of embryonic development, cell proliferation, and cell differentiation.
May modify the assembly dynamics of microtubules, such that microtubules are slightly longer, but more dynamic.
Required for genome-wide de novo methylation and is essential for development. DNA methylation is coordinated with methylation of histones. It modifies DNA in a non-processive manner and also methylates non-CpG sites. Acts as a transcriptional corepressor for ZNF238. Can actively repress transcription through the recruitment of HDAC activity. Also has weak auto-methylation activity on some Cys residue in absence of DNA.
The PWWP domain is essential for targeting to pericentric heterochromatin.
Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily.
There are elevated levels of this protein in neural and hematopoietic tissues.
Belongs to the adenylosuccinate synthetase family.
Inhibited competitively by AMP and IMP and non-competitively by fructose 1,6-bisphosphate.
Plays an important role in the de novo pathway and in the salvage pathway of purine nucleotide biosynthesis. Catalyzes the first committed step in the biosynthesis of AMP from IMP.
Binds 1 divalent metal cation per subunit. Most active with Zn(2+) and Mn(2+) ions. The physiological cofactor is most likely Ca(2+) or Mg(2+).
Gluconolactonase with low activity towards other sugar lactones, including gulonolactone and galactonolactone. Catalyzes a key step in ascorbic acid (vitamin C) biosynthesis. Can also hydrolyze diisopropyl phosphorofluoridate and phenylacetate (in vitro). Calcium-binding protein. Modulates Ca(2+) signaling, and Ca(2+)-dependent cellular processes and enzyme activities (By similarity).
Part of TORC1 complex. Part of the TORC2 complex.
Subunit of TORC1 and TORC2, which regulate cell growth and survival in response to nutrient and hormonal signals.
Accessory 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. The beta subunit may assist in binding of the phospholipid substrate. Required for the proper folding, assembly and ER to Golgi exit of the ATP8A2:TMEM30A flippase complex. Required for the formation of the ATP8A2, ATP8B1 and ATP8B2 P-type ATPAse intermediate phosphoenzymes (By similarity).
Component of various P4-ATPase flippase complexes which consists of a catalytic alpha subunit and an accessory beta subunit.
The N-terminal domain seems to play a role in the reaction cycle of the catalytic subunit such as ATP8A2.
May regulate membrane morphogenesis in the endoplasmic reticulum (ER) by promoting ER sheet formation at the expense of ER tubules.
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.
Belongs to the cyclophilin-type PPIase family. PPIase B subfamily.
PPIase that catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and may therefore assist protein folding.
Belongs to the D-isomer specific 2-hydroxyacid dehydrogenase family.
Belongs to the protein-tyrosine phosphatase family. Receptor class 5 subfamily.
Belongs to the eukaryotic ribosomal protein eL13 family.
Component of the 60S large ribosomal subunit (LSU).
Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. The small ribosomal subunit (SSU) binds messenger RNAs (mRNAs) and translates the encoded message by selecting cognate aminoacyl-transfer RNA (tRNA) molecules. The large subunit (LSU) contains the ribosomal catalytic site termed the peptidyl transferase center (PTC), which catalyzes the formation of peptide bonds, thereby polymerizing the amino acids delivered by tRNAs into a polypeptide chain. The nascent polypeptides leave the ribosome through a tunnel in the LSU and interact with protein factors that function in enzymatic processing, targeting, and the membrane insertion of nascent chains at the exit of the ribosomal tunnel. As part of the LSU, it is probably required for its formation and the maturation of rRNAs.
Homodimer. Interacts with lamin-associated polypeptides IA, IB and 2.
Phosphorylated. Phosphorylation is increased before envelope disintegration and probably plays a role in regulating lamin associations (By similarity).
The structural integrity of the lamina is strictly controlled by the cell cycle, as seen by the disintegration and formation of the nuclear envelope in prophase and telophase, respectively.
Might be involved in growth regulation, and in myelinization in the peripheral nervous system.
Belongs to the major facilitator superfamily. Monocarboxylate porter (TC 2.A.1.13) family.
Proton-linked monocarboxylate transporter. Catalyzes the rapid transport across the plasma membrane of many monocarboxylates (By similarity).
Can be detected in regions including primordial retina and neuroepithelium by embryonic day 2 (2dpc). At 3 dpc, expressed in the nasal retina and pigment epithelium as well as in the telencephalon, and at 7 dpc is expressed in retinal ganglion cells. Levels begin to decline from 4 dpc and almost disappear by 10 dpc.
May determine the nasotemporal axis of the retina, and consequently specify the topographical projection of the retinal ganglion-cell axons to the tectum by controlling expression of their target genes.
Belongs to the DEAD box helicase family. DDX47/RRP3 subfamily.
In the C-terminal section; belongs to the peptidase M41 family.
In the N-terminal section; belongs to the AAA ATPase family.
Belongs to the CRF-binding protein family.
Binds CRF and inactivates it. May prevent inappropriate pituitary-adrenal stimulation in pregnancy.
Belongs to the uracil-DNA glycosylase (UDG) superfamily. SMUG1 family.
This enzyme is involved in nucleotide metabolism: it produces dUMP, the immediate precursor of thymidine nucleotides and it decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA.
Belongs to the Ca(2+):cation antiporter (CaCA) (TC 2.A.19) family. SLC24A subfamily.
Calcium, potassium:sodium antiporter that transports 1 Ca(2+) and 1 K(+) in exchange for 4 Na(+) (PubMed:10662833). Critical component of the visual transduction cascade, controlling the calcium concentration of outer segments during light and darkness. Light causes a rapid lowering of cytosolic free calcium in the outer segment of both retinal rod and cone photoreceptors and the light-induced lowering of calcium is caused by extrusion via this protein which plays a key role in the process of light adaptation (By similarity).
Retinal rods. Localizes to the inner segment of rod photoreceptors.
The uncleaved signal sequence is required for efficient membrane targeting and proper membrane integration and topology.
Belongs to the TAF9 family. CENP-S/MHF1 subfamily.
DNA-binding component of the Fanconi anemia (FA) core complex. Required for the normal activation of the FA pathway, leading to monoubiquitination of the FANCI-FANCD2 complex in response to DNA damage, cellular resistance to DNA cross-linking drugs, and prevention of chromosomal breakage (PubMed:20347428). In complex with CENPX (MHF heterodimer), crucial cofactor for FANCM in both binding and ATP-dependent remodeling of DNA. Stabilizes FANCM. In complex with CENPX and FANCM (but not other FANC proteins), rapidly recruited to blocked forks and promotes gene conversion at blocked replication forks. In complex with CENPT, CENPW and CENPX (CENP-T-W-S-X heterotetramer), involved in the formation of a functional kinetochore outer plate, which is essential for kinetochore-microtubule attachment and faithful mitotic progression (PubMed:19620631). As a component of MHF and CENP-T-W-S-X complexes, binds DNA and bends it to form a nucleosome-like structure. DNA-binding function is fulfilled in the presence of CENPX, with the following preference for DNA substates: Holliday junction > double-stranded > splay arm > single-stranded. Does not bind DNA on its own (By similarity).
Heterodimer with CENPX, sometimes called MHF; this interaction stabilizes both partners. MHF heterodimers can assemble to form tetrameric structures (PubMed:22304917). MHF also coassemble with CENPT-CENPW heterodimers at centromeres to form the tetrameric CENP-T-W-S-X complex (PubMed:22304917). Forms a discrete complex with FANCM and CENPX, called FANCM-MHF; this interaction, probably mediated by direct binding between CENPS and FANCM, leads to synergistic activation of double-stranded DNA binding and strongly stimulates FANCM-mediated DNA remodeling. Recruited by FANCM to the Fanconi anemia (FA) core complex, which consists of CENPS, CENPX, FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL, FANCM, FAAP24 and FAAP100. The FA core complex associates with Bloom syndrome (BLM) complex, which consists of at least BLM, DNA topoisomerase 3-alpha (TOP3A), RMI1/BLAP75, RPA1/RPA70 and RPA2/RPA32. The super complex between FA and BLM is called BRAFT. Component of the CENPA-CAD complex, composed of CENPI, CENPK, CENPL, CENPO, CENPP, CENPQ, CENPR and CENPS. The CENPA-CAD complex is probably recruited on centromeres by the CENPA-NAC complex, at least composed of CENPA, CENPC, CENPH, CENPM, CENPN, CENPT and CENPU (By similarity).
Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Alpha-2/CHRNA2 sub-subfamily.
Monovalent cation channel required for maintenance of rapid intracellular calcium release. May act as a potassium counter-ion channel that functions in synchronization with calcium release from intracellular stores.
Expressed in optic tectum and retina, less in neostriatum, hypothalamus and thalamus.
High affinity receptor for melatonin. The activity of this receptor is mediated by pertussis toxin sensitive G proteins that inhibits adenylate cyclase activity (By similarity).
Contaminating sequence. Sequence of unknown origin.
First observed at HH4 in mesodermal progenitor cells surrounding the area of Hensen node and in the primitive streak. Expressed in the presomitic mesoderm and dynamically expressed in forming somites. Detected in the developing intermediate mesoderm at HH9 and in the mesonephric tubules and ducts by stage HH18. Expressed in the developing nervous system. Also observed in the limb bud and the developing heart.
Tyrosine-protein phosphatase which dephosphorylates CTNNB1. May function in cell proliferation and migration and play a role in the maintenance of epithelial integrity (By similarity).
Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays contrasting roles in cell death and cell survival by functioning as a pro-apoptotic protein during DNA damage-induced apoptosis, but acting as an anti-apoptotic protein during cytokine receptor-initiated cell death, is involved in tumor suppression.
Interacts with PDPK1 (via N-terminal region), RAD9A, CDCP1, MUC1 and VASP.
Novel PKCs (PRKCD, PRKCE, PRKCH and PRKCQ) are calcium-insensitive, but activated by diacylglycerol (DAG) and phosphatidylserine.
Belongs to the G-protein coupled receptor 1 family. Muscarinic acetylcholine receptor subfamily. CHRM3 sub-subfamily.
Belongs to the eukaryotic release factor 1 family.
Belongs to the eukaryotic ATPase subunit F6 family.
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.
Cell surface proteoglycan that may bear both heparan sulfate and chondroitin sulfate. The multiple functional domains provide potential sites for mediating the adhesive cell-matrix interactions and cytoskeletal reorganization involved in limb chondrogenesis. Interaction with other matrix ligands as well as phosphorylation and shedding of the ectodomain might be involved in cell shape changes that occur during chondrogenesis. Furthermore, shedding of the ectodomain might break the adhesive interactions that promoted condensation, thus facilitating the deposition of cartilage matrix molecules.
Expressed in high amounts at the onset of limb cartilage differentiation.
O-glycosylated within the Thr/Ser-rich region which could interact with lectin domains on other molecules.
Proximal chondrogenic central core of embryonic limb buds where cartilage differentiation is being initiated.
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. DMPK subfamily.
Expressed in a variety of neuronal tissues, particularly in sensory cells including inner ear hair cells, photoreceptors and dorsal root ganglion neurons.
Regulator of G protein-coupled receptor (GPCR) signaling. Probably acts by regulating the activity of some 'R7' family protein (RGS6, RGS7, RGS9 and/or RGS11).
Belongs to the PDK/BCKDK protein kinase family.
Catalyzes the exchange of ADP and ATP across the membrane.
Actin-bundling protein. In the inner ear, it is required for stereocilia formation. Mediates liquid packing of actin filaments that is necessary for stereocilia to grow to their proper dimensions.
Belongs to the thiolase-like superfamily. Thiolase family.
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. This subunit plays a role in recruitment of the Nup107-160 subcomplex to the kinetochore.
Expressed in the developing retina, and in a tiny population of ventricular cells located in the ventral domain of the spinal cord and hindbrain. Retinal expression peaks at stage 29 (6 dpc).
The basic motif confers specificity for the CHRNB3 promoter.
Transcription factor that binds to DNA at the consensus sequence 5'-CAG[GC]TG-3' (By similarity). Positively regulates the determination of retinal ganglion cell fate and formation of the optic nerve and retino-hypothalamic tract (PubMed:11124117, PubMed:15342472, PubMed:16260616). Required for retinal circadian rhythm photoentrainment (By similarity). Plays a role in brainstem auditory signaling and binaural processing (By similarity). During retinal neurogenesis, activates its own transcription, as well as the transcription of CHRNB3 and BRN3 (PubMed:11172005).
Up-regulated by NGN2 and ATOH7. Down-regulated by HES1.
May act as transcription activator that binds DNA elements with the sequence 5'-CCCTATCGATCGATCTCTACCT-3'.
Occurs in almost all aerobically respiring organisms and serves to protect cells from the toxic effects of hydrogen peroxide.
ATP-binding component of the Arp2/3 complex, a multiprotein complex that mediates actin polymerization upon stimulation by nucleation-promoting factor (NPF). The Arp2/3 complex mediates the formation of branched actin networks in the cytoplasm, providing the force for cell motility (By similarity). Seems to contact the pointed end of the daughter actin filament (By similarity). 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 (By similarity). 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) (By similarity).
Belongs to the actin family. ARP3 subfamily.
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.
Mannosyltransferase involved in glycosylphosphatidylinositol-anchor biosynthesis. Transfers the first alpha-1,4-mannose to GlcN-acyl-PI during GPI precursor assembly (By similarity).
Mannosyltransferase involved in glycosylphosphatidylinositol-anchor biosynthesis. Transfers the first alpha-1,4-mannose to GlcN-acyl-PI during GPI precursor assembly.
Light chain 23 is expressed in chicken embryonic skeletal, cardiac, smooth muscles and in brain continuously from embryo to adult.
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.
Guanine nucleotide exchange factor (GEF), which can activate some, but not all, G-alpha proteins. Able to activate GNAI1, GNAO1 and GNAQ, but not GNAS by exchanging bound GDP for free GTP. Involved in regulation of microtubule pulling forces during mitotic movement of chromosomes by stimulating G(i)-alpha protein (By similarity).
Interacts with some GDP-bound G alpha proteins. Does not interact with G-alpha proteins when they are in complex with subunits beta and gamma (By similarity).
Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIB subfamily.
By vitamin D and 1,25-dihydroxyvitamin D3, and by calcium and phosphorous deficiency.
Catalyzes the hydrolysis of ATP coupled with the transport of calcium from the cytoplasm to the extracellular space thereby maintaining intracellular calcium homeostasis.
Displays temperature-dependent chaperone activity.
Belongs to the GHMP kinase family. Mevalonate kinase subfamily.
Catalyzes the phosphorylation of mevalonate to mevalonate 5-phosphate, a key step in isoprenoid and cholesterol biosynthesis.
Receptor for extracellular ADP > UTP > ATP = UDP. The activity of this receptor is mediated by G proteins which activate a phosphatidylinositol-calcium second messenger system.
After incorporation from serum via a specific receptor, it is cleaved into four fragments, heavy and light chain lipovitellins, phosphovitin and YGP40, and YGP40 is released into the yolk plasma before or during compartmentation of lipovitellin-phosvitin complex into the yolk granule.
Precursor of the major egg-yolk proteins that are sources of nutrients during early development of oviparous organisms.
Vitellogenin II is the most abundant of the three vitellogenins (I, II, and III).
Belongs to the class-I pyridoxal-phosphate-dependent aminotransferase family.
Biosynthesis of L-glutamate from L-aspartate or L-cysteine. Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system. Acts as a scavenger of glutamate in brain neuroprotection. The aspartate aminotransferase activity is involved in hepatic glucose synthesis during development and in adipocyte glyceroneogenesis. Using L-cysteine as substrate, regulates levels of mercaptopyruvate, an important source of hydrogen sulfide. Mercaptopyruvate is converted into H(2)S via the action of 3-mercaptopyruvate sulfurtransferase (3MST). Hydrogen sulfide is an important synaptic modulator and neuroprotectant in the brain.
In eukaryotes there are cytoplasmic, mitochondrial and chloroplastic isozymes.
Required for mRNA export from the nucleus to the cytoplasm. Acts as an adapter that uses the DDX39B/UAP56-NFX1 pathway to ensure efficient mRNA export and delivering to the nuclear pore (By similarity).
Belongs to the bZIP family. PAR subfamily.
Binds DNA as a homodimer or a heterodimer. Exists as a stable dimer in the absence of DNA.
Isoform 1 and isoform 3 are expressed in a variety of somatic tissues, including liver, heart, intestine, stomach and kidney. Both isoforms are also expressed in hepatoma (LMH) cells and in embryonic fibroblast cell lines. Isoform 2 and isoform 4 are expressed in adult heart and intestine.
Isoform 3 is expressed as early as embryonic day 10.
Produced by alternative splicing of isoform 1.
Produced by alternative splicing of isoform 2.
Transcription factor that binds to and transactivates the vitellogenin II (VTG2) promoter. Binds to the palindromic sequence 5'-GTTTACATAAAC-3'.
Induces bone formation in conjunction with TGF-beta-1 or TGF-beta-2.
Levels decrease at each developmental time point and further decrease during maturation into adulthood.
The composition of the N-linked chains or the substitution of the N-linked sites is different between embryonic and adult tissues.
Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. It can phosphorylate a large number of proteins. Participates in Wnt signaling. May play a role in segregating chromosomes during mitosis. May play a role in keratin cytoskeleton disassembly.
Belongs to the PMP-22/EMP/MP20 family. CACNG subfamily.
Regulates the activity of L-type calcium channels that contain CACNA1C as pore-forming subunit (By similarity). Regulates the trafficking and gating properties of AMPA-selective glutamate receptors (AMPARs), including GRIA1 and GRIA4. Promotes their targeting to the cell membrane and synapses and modulates their gating properties by slowing their rates of activation, deactivation and desensitization and by mediating their resensitization.
Component of the PAF1 complex, which at least consists of CDC73, PAF1, LEO1, CTR9 and RTF1.
Tumor suppressor probably involved in transcriptional and post-transcriptional control pathways. May be involved in cell cycle progression through the regulation of cyclin D1/PRAD1 expression. Component of the PAF1 complex (PAF1C) which has multiple functions during transcription by RNA polymerase II. PAF1C associates with RNA polymerase II, is involved in transcriptional elongation and in histone modifications including methylation on histone H3 'Lys-4' (H3K4me3) (By similarity).
Abundantly expressed at all embryonic stages but not present in adult tissues.
Catalyzes the transfer of N-acetylneuraminyl groups onto glycan chains in glycoproteins (PubMed:8034663). 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:8034663).
Heart, kidney, testes, brain, liver and lung.
Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type V subfamily.
Belongs to the phosphatase 2A regulatory subunit B56 family.
Appears to regulate cell differentiation within the neural tube. May regulate the differentiation of cell types along the dorsoventral axis of the neural tube, acting in conjunction with distinct ventralizing signals from the notochord and floor plate. Controls the cell differentiation in the neural tube in several ways: (1) promotes the differentiation of cell types that derive from the dorsal neural tube. (2) ensures that the dorsal neural tube is refractory to ventralizing species from the notochord. (3) can diffuse and influence the fate of cells in more ventral regions of the neural tube.
Expressed selectively in the dorsal neural tube. Lower levels seen in kidney and myotomal cells.
Is not expressed in neural cells at stages before neural tube closure. Is expressed at high levels in the dorsal third of the neural tube, beginning at the time of neural tube closure, but not by ventral neural cells or by nonneural cells. Dorsal restriction persists in the spinal cord at stages after the onset of neuronal differentiation. At later stages of spinal development, is restricted to the dorsomedial region of the spinal cord, including but not confined to the roof plate.
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.
Component of an alternative cap-binding complex (CBC) composed of NCBP1/CBP80 and NCBP3.
Belongs to the glyceraldehyde-3-phosphate dehydrogenase family.
Has both glyceraldehyde-3-phosphate dehydrogenase and nitrosylase activities, thereby playing a role in glycolysis and nuclear functions, respectively. Glyceraldehyde-3-phosphate dehydrogenase is a key enzyme in glycolysis that catalyzes the first step of the pathway by converting D-glyceraldehyde 3-phosphate (G3P) into 3-phospho-D-glyceroyl phosphate (By similarity). Participates in nuclear events including transcription, RNA transport, DNA replication and apoptosis. Nuclear functions are probably due to the nitrosylase activity that mediates cysteine S-nitrosylation of nuclear target proteins such as SIRT1, HDAC2 and PRKDC (By similarity).
S-nitrosylation of Cys-150 leads to translocation to the nucleus.
Belongs to the glycosyl hydrolase 65 family.
Catalyzes the hydrolysis of glucose from the disaccharide unit linked to hydroxylysine residues of collagen and collagen-like proteins.
The normal physiological role of BLM hydrolase is unknown, but it catalyzes the inactivation of the antitumor drug BLM (a glycopeptide) by hydrolyzing the carboxamide bond of its B-aminoalaninamide moiety thus protecting normal and malignant cells from BLM toxicity.
Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. Pelle subfamily.
Binds to the IL-1 type I receptor following IL-1 engagement, triggering intracellular signaling cascades leading to transcriptional up-regulation and mRNA stabilization.
Interacts with MYD88. IL-1 stimulation leads to the formation of a signaling complex which dissociates from the IL-1 receptor following the binding of PELI1.
Developmentally regulated in chick embryo.
Expressed in egg white (at protein level). Expressed in the magnum of the oviduct (at protein level) (PubMed:25436390). Preferentially synthesized in nonproliferating cells.
Siderocalin-like lipocalin tightly binding a variety of bacterial ferric siderophores, also binds long-chain unsaturated fatty acids such as linoleic acid, oleic acid, arachidonic acid and, with a lower affinity, long chain saturated fatty acids such as steraic acid. May act as an antibacterial factor, through dual ligand specificity, both as a siderophore-sequestrating molecule and a lysophosphatidic acid (LPA) sensor.
Detected ubiquitously at low levels throughout the developing embryo. Present initially in the limb mesoderm as the limb bud emerges from the body wall and up-regulated along the posterior margin of the developing limb bud with progression of the limb outgrowth. Higher levels are detected in limb buds, otic vesicles and pharyngeal arches. Isoform 1 is detected in lung, spleen, heart, breast muscle, cartilage and liver of the adult tissues. Isoform 3 is detected in adult lung, spleen, heart and breast muscle but not detected in cartilage and liver.
Found in newly hatched chick liver and decreases during postnatal development.
Multifunctional protein with various roles in different cellular compartments. May act in a redox sensitive manner. Associates with chromatin and binds DNA with a preference for non-canonical DNA structures such as single-stranded DNA. Can bend DNA and enhance DNA flexibility by looping thus providing a mechanism to promote activities on various gene promoters (By similarity). Binds to the delta-1 crystallin/ASL1 enhancer (PubMed:7904558). Proposed to be involved in the innate immune response to nucleic acids by acting as a cytoplasmic promiscuous immunogenic DNA/RNA sensor (By similarity).
Reduction/oxidation of cysteine residues Cys-23, Cys-45 and Cys-104 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 HMGB3 (HMGB3C23hC45hC104h), 2- disulfide HMGB3 (HMGB3C23-C45C104h) and 3- sulfonyl HMGB3 (HMGB3C23soC45soC104so).
Belongs to the class I-like SAM-binding methyltransferase superfamily. Cation-independent O-methyltransferase family.
Catalyzes the transfer of a methyl group onto N-acetylserotonin, producing melatonin (N-acetyl-5-methoxytryptamine).
Homodimer. Does not require RNA to homodimerize (By similarity).
RNA-binding protein that plays a central role in myelinization. Binds to the 5'-NACUAAY-N(1,20)-UAAY-3' RNA core sequence. Acts by regulating pre-mRNA splicing, mRNA export, mRNA stability and protein translation. Required to protect and promote stability of mRNAs which promotes oligodendrocyte differentiation. Participates in mRNA transport by regulating the nuclear export of MBP mRNA. Also involved in regulation of mRNA splicing of some pre-mRNA. Acts as a translational repressor (By similarity).
Belongs to the bacterial ribosomal protein bL32 family.
Belongs to the eukaryotic-type primase large subunit family.
Regulatory subunit of the DNA primase complex and component of the DNA polymerase alpha complex (also known as the alpha DNA polymerase-primase complex) which play an essential role in the initiation of DNA synthesis. The primase subunit of the polymerase alpha complex initiates DNA synthesis by oligomerising short RNA primers on both leading and lagging strands.
Belongs to the class I fructose-bisphosphate aldolase family.
Expressed in undifferentiated retina and lens (PubMed:12815627).
Plays a role in cortical progenitor cell proliferation and differentiation. May promote dendritic spine development of post-migratory cortical projection neurons by modulating the beta-catenin signaling pathway.
Component of the RMI complex, containing at least TOP3A, RMI1 and RMI2. The RMI complex interacts with BLM (By similarity).
Essential component of the RMI complex, a complex that plays an important role in the processing of homologous recombination intermediates. It is required to regulate sister chromatid segregation and to limit DNA crossover. Essential for the stability, localization, and function of BLM, TOP3A, and complexes containing BLM. In the RMI complex, it is required to target BLM to chromatin and stress-induced nuclear foci and mitotic phosphorylation of BLM.
Chondroitin sulfate- and hyaluronan-binding proteoglycan involved in the organization of interphotoreceptor matrix.
Detected in retina at 12 dpc with increased expression up to a peak at 16 dpc.
Highly glycosylated (N- and O-linked carbohydrates).
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 (By similarity).
Positive regulator of amino acid starvation-induced autophagy.
Adapter protein that provides a critical link between cell surface growth factor receptors and the Ras signaling pathway.
Associates with activated Tyr-phosphorylated EGF receptors and PDGF receptors via its SH2 domain. Also associates to other cellular Tyr-phosphorylated proteins such as SIT1, IRS1, SHC and LNK; probably via the concerted action of both its SH2 and SH3 domains. It also seems to interact with RAS in the signaling pathway leading to DNA synthesis. Binds to and translocates the guanine nucleotide exchange factors SOS (By similarity). Interacts with phosphorylated LAT2.
Belongs to the Mediator complex subunit 28 family.
Belongs to the eukaryotic ribosomal protein eL15 family.
Belongs to the ELO family. ELOVL2 subfamily.
Catalyzes the first and rate-limiting reaction of the four reactions that constitute the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process allows the addition of 2 carbons to the chain of long- and very long-chain fatty acids (VLCFAs) per cycle. Acts specifically toward polyunsaturated acyl-CoA with the higher activity toward C20:4(n-6) acyl-CoA. Condensing enzyme that catalyzes the synthesis of polyunsaturated very long chain fatty acid (C20- and C22-PUFA). May participate to the production of polyunsaturated VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators.
The C-terminal di-lysine motif may confer endoplasmic reticulum localization.
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.
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.
Belongs to the ABC transporter superfamily. ABCC family. CFTR transporter (TC 3.A.1.202) subfamily.
Epithelial ion channel that plays an important role in the regulation of epithelial ion and water transport and fluid homeostasis. Mediates the transport of chloride ions across the cell membrane. Channel activity is coupled to ATP hydrolysis. The ion channel is also permeable to HCO(3-); selectivity depends on the extracellular chloride concentration. Exerts its function also by modulating the activity of other ion channels and transporters. Contributes to the regulation of the pH and the ion content of the epithelial fluid layer.
Mitochondrial proton/calcium antiporter that mediates proton-dependent calcium efflux from mitochondrion (By similarity). Required for the maintenance of the tubular shape and cristae organization (By similarity).
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.
Ligand for members of the frizzled family of seven transmembrane receptors (Probable). Plays an important role in embryonic development (By similarity).
Predominantly expressed in the diencephalon neuromere D2.
Regulates intra- and extracellular levels of inorganic pyrophosphate (PPi), probably functioning as PPi transporter.
Belongs to the diphthine synthase family.
S-adenosyl-L-methionine-dependent methyltransferase that catalyzes four methylations of the modified target histidine residue in translation elongation factor 2 (EF-2), to form an intermediate called diphthine methyl ester. The four successive methylation reactions represent the second step of diphthamide biosynthesis.
Stimulates the RNA helicase activity of EIF4A in the translation initiation complex. Binds weakly mRNA.
Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.
Interacts with PXN/PAXILLIN (via LD motif 4).
Receptor-proximal protein kinase regulating integrin-mediated signal transduction. May act as a mediator of inside-out integrin signaling.
Belongs to the eukaryotic-type primase small subunit family.
Coordinately expressed in partially overlapping domains during wing development.
Belongs to the extended synaptotagmin family.
Component of the TFIID basal transcription factor complex, composed of TATA-box-binding protein TBP, and a number of TBP-associated factors (TAFs).
The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription. TFIID recognizes and binds promoters with or without a TATA box via its subunit TBP, a TATA-box-binding protein, and promotes assembly of the pre-initiation complex (PIC). The TFIID complex consists of TBP and TBP-associated factors (TAFs). Mediates both basal and activator-dependent transcription.
Acts as a transcriptional regulator (By similarity). Plays a significant role in the specification and morphogenesis of the sensory retina (By similarity). Mediates differentiation of V2a interneurons by repression of motor neuron gene transcription, via competitively binding to response elements that are activated by the ISL1-LHX3 complex (PubMed:27477290). May also participate in the development of the cells of the inner nuclear layer, particularly bipolar cells (By similarity).
Expressed throughout the invaginating optic vesicles at stage 12, and uniformly throughout the neural retina from stage 14 to stage 18. Expressed in the spinal cord from stage 15 to stage 20.
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. May be the terminally assembled subunit of Complex I.
Belongs to the complex I NDUFV3 subunit family.
Complex I is composed of 45 different subunits. This is a component of the flavoprotein-sulfur (FP) fragment of the enzyme.
Belongs to the fructosamine kinase family.
Belongs to the methylmalonyl-CoA epimerase family.
AMP and XMP inhibit AICAR formyltransferase activity (By similarity). AICAR formyltransferase activity is competitively inhibited by 2-[5-hydroxy-3-methyl-1-(2-methyl-4-sulfo-phenyl)-1H-pyrazol-4-ylazo]-4-sulfo-benzoic acid (326203-A) (PubMed:15355974). FAICAR cyclization is competitively inhibited by 1,5-dihydroimidazo[4,5-c][1,2,6]thiadiazin-4(3H)-one-2,2-dioxide and the corresponding nucleoside and nucleoside monophosphate (PubMed:17324932).
Bifunctional enzyme that catalyzes the last two steps of purine biosynthesis (PubMed:12501179). Acts as a transformylase that incorporates a formyl group to the AMP analog AICAR (5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide) to produce the intermediate formyl-AICAR (FAICAR) (PubMed:12501179). Can use both 10-formyldihydrofolate and 10-formyltetrahydrofolate as the formyl donor in this reaction. Also catalyzes the cyclization of FAICAR to IMP. Promotes insulin receptor/INSR autophosphorylation and is involved in INSR internalization (By similarity).
Homodimer (PubMed:11323713, PubMed:12501179). Associates with internalized INSR complexes on Golgi/endosomal membranes. Interacts with INSR; ATIC together with PRKAA2/AMPK2 and HACD3/PTPLAD1 is proposed to be part of a signaling network regulating INSR autophosphorylation and endocytosis (By similarity).
The IMP cyclohydrolase activity resides in the N-terminal region.
The de novo purine synthesis pathway includes 10 sequential steps, beginning with phosphoribosyl pyrophosphate and ending with inositol monophosphate (IMP), the first purin compound of the pathway.
Belongs to the type I cytokine receptor family. Type 3 subfamily.
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. Interacts with TAF10 via the histone fold. Interacts with TAF13, TBP, SAP130 and GCN5L2. Interacts with TBPL2.
The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription. TFIID recognizes and binds promoters with or without a TATA box via its subunit TBP, a TATA-box-binding protein, and promotes assembly of the pre-initiation complex (PIC). 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. The TFIID complex structure can be divided into 3 modules TFIID-A, TFIID-B, and TFIID-C. TAF3 forms the TFIID-A module together with TAF5 and TBP. Required in complex with TBPL2 for the differentiation of myoblasts into myocytes. The TAF3-TBPL2 complex replaces TFIID at specific promoters at an early stage in the differentiation process.
Belongs to the cytochrome c-type heme lyase family.
Lyase that catalyzes the covalent linking of the heme group to the cytochrome C apoprotein to produce the mature functional cytochrome.
Nuclease required for the repair of DNA interstrand cross-links (ICL). Acts as a 5'-3' exonuclease that anchors at a cut end of DNA and cleaves DNA successively at every third nucleotide, allowing to excise an ICL from one strand through flanking incisions.
Belongs to the protein kinase superfamily. NEK Ser/Thr protein kinase family. NIMA subfamily.
Found in a signaling complex consisting of at least ARHGEF2, NOD2 and RIPK2.
Serine/threonine/tyrosine kinase that plays an essential role in modulation of innate and adaptive immune responses. Upon stimulation by bacterial peptidoglycans, NOD1 and NOD2 are activated, oligomerize and recruit RIPK2 through CARD-CARD domains.
Hematopoietic growth factor that stimulates the proliferation and colony formation of normal and transformed avian cells of the myeloid lineage.
Probable component of a centromeric complex involved in assembly of kinetochore proteins, mitotic progression and chromosome segregation.
Belongs to the ELO family. ELOVL4 subfamily.
Catalyzes the first and rate-limiting reaction of the four reactions that constitute the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process allows the addition of 2 carbons to the chain of long- and very long-chain fatty acids (VLCFAs) per cycle. Condensing enzyme that specifically elongates C24:0 and C26:0 acyl-CoAs. May participate to the production of saturated and monounsaturated VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators.
Defect in TMEM263 may be a one of the causes of autosomal recessive dwarfism in Cornell K-strain white leghorns. A nonsense mutation truncates the protein and probably cause a dysfunctional protein. Autosomal dwarf chicken display small body stature by short shank length, with 30-40% reduced adult body weight despite normal hormonal concentration of GH and IGF1.
Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. PKD subfamily.
Belongs to the Mediator complex subunit 18 family.
Transcriptional regulator. Recognizes and binds to the DNA sequence 5'-GCG(T/G)GGGCG-3'(EGR-site) in the promoter region of target genes. Binds double-stranded target DNA, irrespective of the cytosine methylation status. Regulates the transcription of numerous target genes, and thereby plays an important role in regulating the response to growth factors, DNA damage, and ischemia. Plays a role in the regulation of cell survival, proliferation and cell death.
Belongs to the bZIP family. CNC subfamily.
CNC-type bZIP family transcription factor that translocates to the nucleus and regulates expression of target genes in response to various stresses. Heterodimerizes with small-Maf proteins (MAFF, MAFG or MAFK) and binds DNA motifs including the antioxidant response elements (AREs), which regulate expression of genes involved in oxidative stress response. Activates or represses expression of target genes, depending on the context (By similarity). Plays a key role in cholesterol homeostasis by acting as a sensor of cholesterol excess: in low cholesterol conditions, translocates into the nucleus and represses expression of genes involved in defense against cholesterol excess (By similarity). In excess cholesterol conditions, the endoplasmic reticulum membrane form of the protein directly binds cholesterol via its CRAC motif, preventing cleavage and release of the transcription factor NRF1, thereby allowing expression of genes promoting cholesterol removal (By similarity). Critical for redox balance in response to oxidative stress: acts by binding the AREs motifs on promoters and mediating activation of oxidative stress response genes (By similarity). Involved in proteasome homeostasis: in response to proteasome inhibition, mediates the 'bounce-back' of proteasome subunits by translocating into the nucleus and activating expression of genes encoding proteasome subunits (By similarity).
Cleaved at Leu-104 following retrotranslocation, releasing the protein from the endoplasmic reticulum membrane and forming the transcription factor NRF1 that translocates into the nucleus.
Endoplasmic reticulum membrane sensor that translocates into the nucleus in response to various stresses to act as a transcription factor (By similarity). Constitutes a precursor of the transcription factor NRF1 (By similarity). Able to detect various cellular stresses, such as cholesterol excess, oxidative stress or proteasome inhibition (By similarity). In response to stress, it is released from the endoplasmic reticulum membrane following cleavage and translocates into the nucleus to form the transcription factor NRF1 (By similarity). Acts as a key sensor of cholesterol excess: in excess cholesterol conditions, the endoplasmic reticulum membrane form of the protein directly binds cholesterol via its CRAC motif, preventing cleavage and release of the transcription factor NRF1, thereby allowing expression of genes promoting cholesterol removal (By similarity). Involved in proteasome homeostasis: in response to proteasome inhibition, it is released from the endoplasmic reticulum membrane, translocates to the nucleus and activates expression of genes encoding proteasome subunits (By similarity).
Interacts (via the bZIP domain) with small MAF protein (MAFF, MAFG or MAFK); required for binding to antioxidant response elements (AREs) on DNA.
The cholesterol recognition/amino acid consensus (CRAC) region directly binds cholesterol, as well as campesterol and 27-hydroxycholesterol. Has much lower affinity for epicholesterol.
Belongs to the metallo-beta-lactamase superfamily. Glyoxalase II family.
Only one single gene encoding glyoxalase II has been identified in vertebrates. In yeast and higher plants, separate genes encode the cytosolic and mitochondrial forms of glyoxalase II.
Produced by alternative initiation at Met-51 of isoform 1. Alternative initiation has been proven in human.
Thiolesterase that catalyzes the hydrolysis of S-D-lactoyl-glutathione to form glutathione and D-lactic acid.
GTP-binding protein involved in protein trafficking; may modulate vesicle budding and uncoating within the Golgi apparatus.
C-terminal Ser or Thr residues may be phosphorylated.
Receptor for angiotensin II, a vasoconstricting peptide, which acts as a key regulator of blood pressure and sodium retention by the kidney. The activated receptor in turn couples to G-alpha proteins G(q) (GNAQ, GNA11, GNA14 or GNA15) and thus activates phospholipase C and increases the cytosolic Ca(2+) concentrations, which in turn triggers cellular responses such as stimulation of protein kinase C.
Belongs to the acetyltransferase family. NAA40 subfamily.
Expressed during the differentiation of neuroepithelium, of myotomes to muscle and of surface extoderm. Expressed in the dorsal root ganglia (DRG).
Not expressed in hen anterior pituitary during the ovulatory cycle but expressed in the ovarian follicle.
On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Receptor for activin A, activin B and inhibin A. May modulate neuropeptide expression in dorsal root ganglia (DRG) neurons and ovarian follicle development.
Belongs to the EGF-CFC (Cripto-1/FRL1/Cryptic) family.
First detected in the early streak embryo, specifically in the epiblast layer. At the late streak stage, expression is condensed in the rostral half of the primitive streak. At HH stage 4 expression appeared for the first time in the mesendodermal layer of the presumptive prechordal plate rostrally and in the expanding mesoderm laterally. At HH stage 6, labeling in mesendodermal progenitors underlying the future forebrain level of the neuraxis reached its maximum, whereas mesoderm expression, which was restricted to the lateral plate, was accompanied by an underlying endodermal expression at the level of the heart-forming regions. Later gastrulation (HH stage 5-7) was marked by strong expression in the notochord, beneath the future floor plate of the neural tube. Expressed in Hensen node, within its mesenchymal core beneath the epiblast, and at a time when it is morphologically asymmetric.
May play a role in mesoderm and/or neural patterning during gastrulation.
Belongs to the NAD(P)-dependent epimerase/dehydratase family. GDP-mannose 4,6-dehydratase subfamily.
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.
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.
Belongs to the apolipoprotein O/MICOS complex subunit Mic27 family.
Component of the mitochondrial contact site and cristae organizing system (MICOS) complex (also known as MINOS or MitOS complex).
Belongs to the bacterial ribosomal protein bL34 family.
Component of the gamma-secretase complex.
Potential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral proteins such as Notch receptors.
GTPase possibly involved in regulation of the MEK/ERK pathway.
This promotes the activity of RNA polymerase II.
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 set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. The small Rab GTPase RAB11A regulates endocytic recycling (By similarity).
Belongs to the protein-tyrosine phosphatase family.
May play a role in cell cycle regulation. Dual specificity phosphatase active toward substrates containing either phosphotyrosine or phosphoserine residues.
Belongs to the glycosyltransferase 10 family.
At stage 10, expressed in the neural tube throughout the mesoderm. By early stage 13, expression becomes restricted to the lateral mesoderm in the trunk region and in the cranial region, to the dermomyotome, to the somatic mseoderm-derived pericardium and to a group of cells located ventral to the dermomyotome. Expression continues at high levels in the dermatome. In later stages, high expression found in the limb bud mesenchyme pharyngeal arches, the maxillary arches and the frontonasal mass and to a lesser extent, in the aorta, cardiac valve mesenchyme, the pericardial wall and the ventral foregut wall.
Expressed predominantly in the mesodermal cells of the limb bud, visceral arches and craniofacial process, and at lower levels, in cranial mesenchyme, upper and lower eyelids, somites and cartilage of vertebra. Also found in the heart, especially the developing semilunar and atrioventricular valves and in the brain, in a distinct region of the ventral part of the hypothalamus as well as in a broader region of the telencephalon.
May participate in maintenance of mesenchymal cell lineages derived from both mesoderm and the neural crest and in patterning of the limbs and the face.
Belongs to the ATG13 family. Metazoan subfamily.
Expression first appears at Hensen's node and subsequently in the axial and paraxial mesoderm. When the neural tube closes, strong expression is transiently found in the roof plate region from the rostral midbrain to the hindbrain.
Secreted scaffold protein that plays an essential role in dorsoventral patterning during early development. Stabilizes axial formation by restricting chordin (CHRD) activity on the dorsal side. Acts by facilitating the association between the tolloid proteases and their substrate chordin (CHRD), leading to enhance chordin (CHRD) degradation (By similarity).
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.
Variant histone H2A which replaces conventional H2A in a subset of nucleosomes.
In the C-terminal section; belongs to the sulfate adenylyltransferase family.
In the N-terminal section; belongs to the APS kinase family.
Catalyzes the 2-oxoglutarate and iron-dependent C4-lysyl hydroxylation of ETF1 at 'Lys-63' thereby promoting the translational termination efficiency of ETF1.
May play a role in mitochondrial aerobic respiration. May also regulate mitochondrial organization and fission.
Widely expressed in embryonic tissues with higher expression in cartilage and hypertrophic chondrocytes. Specifically expressed in hypertrophic chondrocytes (at protein level).
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. Involved in Rac1-signaling pathways leading to the modulation of gene expression.
Shares some similarity with tyrosine phosphatase proteins but it has probably no phosphatase activity.
Belongs to the nucleosome assembly protein (NAP) family.
Heterodimer; with a RXR molecule. Binds DNA preferentially as a RAR/RXR heterodimer.
In the developing embryo, expressed in the limb bud mesenchyme, in cranofacial mesenchyme, and in hindbrain neuroectoderm. At stages 20, 24 and 28 of embryonic development, expressed ununiformly in facial primordia. Present in lateral nasal processes, at edges and corners of frontonasal mass and in the anterior part of the maxillary primordia. Expressed in mesenchyme at all stages of facial development. In the developing limb, isoform Beta-1 is expressed limb bud mesenchyme and ectoderm, then become restricted within perichondrial regions and loose connective tissue of the limb, while isoform Beta-2, expressed in subsets of similar tissues, in the proximal limb mesenchyme and in the initial mesenchymal condensate. later abundantly expressed in cells lateral to the digit cartilage.
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) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 (By similarity). Required for limb and craniofacial development.
Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. SET7 subfamily.
Histone methyltransferase that specifically monomethylates 'Lys-4' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. Plays a central role in the transcriptional activation of genes.
Proton-coupled 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. Depending on the tissue and on cicumstances, mediates the import or export of lactic acid and ketone bodies. Required for normal nutrient assimilation, increase of white adipose tissue and body weight gain when on a high-fat diet. Plays a role in cellular responses to a high-fat diet by modulating the cellular levels of lactate and pyruvate, small molecules that contribute to the regulation of central metabolic pathways and insulin secretion, with concomitant effects on plasma insulin levels and blood glucose homeostasis.
Functions as an adapter molecule that links other proteins to the actin cytoskeleton. May function in facilitating interactions between SRC and actin filaments. May modulate changes in actin filament integrity and induce lamellipodia formation. Can cross-link actin filaments into both network and bundle structures.
Isoform 2 is specifically expressed in brain.
Monomer and homomultimer. Interacts via its C-terminus with F-actin; probably involving AFAP1 multimers. Interacts with activated SRC SH3-SH2 domains. May interact with FYN SH3-SH2 domains. Interacts via its PH 1 domain with PRKCA, PRKCB, PRKCI.
Phosphorylated on tyrosine residues by SRC.
Allosterically activated and regulated via the combined actions of GTP and dNTPs (dATP, dGTP, dTTP and dCTP): Allosteric site 1 binds GTP, while allosteric site 2 binds dNTP. Allosteric activation promotes the formation of highly active homotetramers.
Homodimer; in absence of GTP and dNTP. Homotetramer; in GTP- and dNTP-bound form (By similarity). Interacts with rbbp8/CtIP (By similarity).
Protein that acts both as a host restriction factor involved in defense response to virus and as a regulator of DNA end resection at stalled replication forks. Has deoxynucleoside triphosphate (dNTPase) activity, which is required to restrict infection by viruses: dNTPase activity reduces cellular dNTP levels to levels too low for retroviral reverse transcription to occur, blocking early-stage virus replication in dendritic and other myeloid cells. Functions during S phase at stalled DNA replication forks to promote the resection of gapped or reversed forks: acts by stimulating the exonuclease activity of MRE11, activating the ATR-CHK1 pathway and allowing the forks to restart replication. Its ability to promote degradation of nascent DNA at stalled replication forks is required to prevent induction of type I interferons, thereby preventing chronic inflammation. Ability to promote DNA end resection at stalled replication forks is independent of dNTPase activity.
Regulates (in vitro) the inhibition of rhodopsin phosphorylation in a calcium-dependent manner.
Widely expressed in the brain but not detectable in liver, heart or skeletal muscle.
Phospholipid scramblase involved in autophagy. Cycles between the preautophagosomal structure/phagophore assembly site (PAS) and the cytoplasmic vesicle pool and supplies membrane for the growing autophagosome. Lipid scramblase activity plays a key role in preautophagosomal structure/phagophore assembly by distributing the phospholipids that arrive through ATG2 from the cytoplasmic to the luminal leaflet of the bilayer, thereby driving autophagosomal membrane expansion.
May play a role in the regulation of the epithelial-mesenchymal transition.
Cysteine protease that plays a key role in autophagy by mediating both proteolytic activation and delipidation of ATG8 family proteins.
Cysteine protease that plays a key role in autophagy by mediating both proteolytic activation and delipidation of ATG8 family proteins. The protease activity is required for proteolytic activation of ATG8 family proteins: cleaves the C-terminal amino acid of ATG8 proteins to reveal a C-terminal glycine. 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. Protease activity is also required to counteract formation of high-molecular weight conjugates of ATG8 proteins (ATG8ylation): acts as a deubiquitinating-like enzyme that removes ATG8 conjugated to other proteins, such as ATG3. In addition to the protease activity, also mediates delipidation of ATG8 family proteins. Catalyzes delipidation of PE-conjugated forms of ATG8 proteins during macroautophagy.
The LIR motif (LC3-interacting region) is required for the interaction with the ATG8 family proteins. Required for proteolytic activation and delipidation of ATG8 proteins.
Belongs to the TALE/TGIF homeobox family.
Binds to the F' element of the APOVLDLII gene and represses its transcription.
Belongs to the pyrimidine 5'-nucleotidase family.
By norepinephrine/NE and adenosine which are released by the embryo under hypoxic conditions. By stimulation of beta-adrenergic/adenosine receptors in definitive red blood cells (RBC).
Expressed at low levels until 13 dpc and the expression rises transiently between 13 dpc and 16 dpc.
Nucleotidase which shows specific activity towards cytidine monophosphate (CMP) and 7-methylguanosine monophosphate (m(7)GMP). CMP seems to be the preferred substrate.
Belongs to the AAA ATPase family. RarA/MGS1/WRNIP1 subfamily.
Belongs to the chloride channel MCLC family.
Belongs to the mitochondrial Rho GTPase family.
Mitochondrial GTPase involved in mitochondrial trafficking. Probably involved in control of anterograde transport of mitochondria and their subcellular distribution (By similarity).
Ubiquitinated by PRKN in a PINK1-dependent manner, leading to its degradation.
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.
Expressed in muscle fibers and in neurons.
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 (By similarity).
Mainly expressed in neurons of the central nervous system during the second half of embryonic life. Expressed in mitral neurons of the olfactory bulbs, striatal neurons, Purkinje cells of the cerebellum, retinal neurons and neurons of the brainstem and spinal cord.
May be an adhesion-like molecule with anti-protease activity.
Involved in protein trafficking. May be involved in the down-regulation of membrane protein levels (By similarity).
Belongs to the tRNA pseudouridine synthase TruA family.
Acylated. Acylation may be a prerequisite for conversion of the monomeric 37 kDa laminin receptor precursor (37LRP) to the mature dimeric 67 kDa laminin receptor (67LR), and may provide a mechanism for membrane association.
Belongs to the universal ribosomal protein uS2 family.
Cleaved by stromelysin-3 (ST3) at the cell surface. Cleavage by stromelysin-3 may be a mechanism to alter cell-extracellular matrix interactions.
It is thought that in vertebrates 37/67 kDa laminin receptor acquired a dual function during evolution. It developed from the ribosomal protein SA, playing an essential role in the protein biosynthesis lacking any laminin binding activity, to a cell surface receptor with laminin binding activity.
Monomer (37LRP) and homodimer (67LR). Component of the small ribosomal subunit. Mature ribosomes consist of a small (40S) and a large (60S) subunit. The 40S subunit contains about 33 different proteins and 1 molecule of RNA (18S). The 60S subunit contains about 49 different proteins and 3 molecules of RNA (28S, 5.8S and 5S). Interacts with RPS21. Interacts with several laminins including at least LAMB1. Interacts with MDK.
Required for the assembly and/or stability of the 40S ribosomal subunit. Required for the processing of the 20S rRNA-precursor to mature 18S rRNA in a late step of the maturation of 40S ribosomal subunits. Also functions as a cell surface receptor for laminin. Plays a role in cell adhesion to the basement membrane and in the consequent activation of signaling transduction pathways. May play a role in cell fate determination and tissue morphogenesis.
This protein appears to have acquired a second function as a laminin receptor specifically in the vertebrate lineage.
Functions as actin-binding component of the Arp2/3 complex which is involved in regulation of actin polymerization and together with an activating nucleation-promoting factor (NPF) mediates the formation of branched actin networks. Seems to contact the mother actin filament.
Associates primarily with CDK7 and MAT1 to form the CAK complex. CAK can further associate with the core-TFIIH to form the TFIIH basal transcription factor.
Regulates CDK7, the catalytic subunit of the 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. Its expression and activity are constant throughout the cell cycle.
Belongs to the potassium channel HCN family.
Belongs to the WD repeat Groucho/TLE family.
Belongs to the ZP domain family. ZPC subfamily.
Component of the zona pellucida, which mediates species-specific sperm binding. Directly binds to sperm. Important for egg fertilization.
Detected in the ovarian perivitteline layer. Detected in granulosa cells in ovarian follicle (at protein level). Detected in granulosa cells in ovarian follicle.
Homodimer. Forms higher oligomers, once its C-terminus has been proteolytically removed. Forms heterooligomers with other zona pellucida glycoproteins (By similarity).
O-glycosylated. O-glycosylation at Thr-168 is important for efficient interaction with the sperm head.
Proteolytically cleaved before the transmembrane segment to yield the secreted ectodomain incorporated in the zona pellucida.
The ZP domain is involved in the polymerization of the ZP proteins to form the zona pellucida.
Brain endothelial cells, kidney epithelial cells and erythroblasts (at protein level).
Essential for normal retinal maturation and development (By similarity). Acts as a retinal cell surface receptor for NXNL1 and plays an important role in NXNL1-mediated survival of retinal cone photoreceptors (PubMed:25957687). In association with glucose transporter SLC16A1/GLUT1 and NXNL1, promotes retinal cone survival by enhancing aerobic glycolysis and accelerating the entry of glucose into photoreceptors (PubMed:25957687).
Interacts with NXNL1, SLC2A1 and SLC16A1.
Retinal cone photoreceptors (at protein level).
Signaling receptor for cyclophilins, essential for PPIA/CYPA and PPIB/CYPB-dependent signaling related to chemotaxis and adhesion of immune cells (By similarity). Plays an important role in targeting the monocarboxylate transporters SLC16A1/GLUT1, SLC16A3, SLC16A8, SLC16A11 and SLC16A12 to the plasma membrane (By similarity). Acts as a coreceptor for vascular endothelial growth factor receptor 2 (KDR/VEGFR2) in endothelial cells enhancing its VEGFA-mediated activation and downstream signaling (By similarity). Promotes angiogenesis through EPAS1/HIF2A-mediated up-regulation of VEGFA and KDR/VEGFR2 in endothelial cells (By similarity).
Belongs to the riboflavin transporter family.
Plasma membrane transporter mediating the uptake by cells of the water soluble vitamin B2/riboflavin that plays a key role in biochemical oxidation-reduction reactions of the carbohydrate, lipid, and amino acid metabolism.
In the C-terminal section; belongs to the formate--tetrahydrofolate ligase family.
In the N-terminal section; belongs to the tetrahydrofolate dehydrogenase/cyclohydrolase family.
Guanine nucleotide exchange factor. May be involved in cytoskeletal organization.
The PH domain mediates binding to membranes.
May for an interface between the RNA polymerase II enzyme and chaperone/scaffolding protein.
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.
Required for the localization of dynein and dynactin to the mitotic kintochore. Dynein is believed to control the initial lateral interaction between the kinetochore and spindle microtubules and to facilitate the subsequent formation of end-on kinetochore-microtubule attachments mediated by the NDC80 complex.
MARCKS is the most prominent cellular substrate for protein kinase C. This protein binds calmodulin, actin, and synapsin. MARCKS is a filamentous (F) actin cross-linking protein.
Belongs to the protease inhibitor I39 (alpha-2-macroglobulin) family.
Belongs to the dTDP-4-dehydrorhamnose reductase family. MAT2B subfamily.
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.
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.
Plays a role in the recycling mechanism in neurons of multiple receptors and acts at the level of early endosomes to promote sorting of receptors toward a recycling pathway.
Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. Chromokinesin subfamily.
Binds 1 [4Fe-4S] cluster (By similarity). In the presence of oxygen, the [4Fe-4S] cluster may be converted to [2Fe-2S] (By similarity).
Expressed in proliferating cells; neuroepithelium of embryos.
Iron-sulfur (Fe-S) cluster binding motor protein that has a role in chromosome segregation during mitosis (By similarity). Required for mitotic chromosomal positioning and bipolar spindle stabilization.
Involved in tetrahydrobiopterin biosynthesis. Seems to both prevent the formation of 7-pterins and accelerate the formation of quinonoid-BH2. Coactivator for HNF1A-dependent transcription. Regulates the dimerization of homeodomain protein HNF1A and enhances its transcriptional activity (By similarity). Also acts as a coactivator for HNF1B-dependent transcription (By similarity).
The major tissues expressing cDcoH are hypothalamus, kidney and liver.
Activated by multiple phosphorylations on threonine and serine residues.
Autophosphorylated on Ser-398, as part of the activation process.
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. S6 kinase subfamily.
Serine/threonine kinase that may play a role in mediating the growth-factor and stress induced activation of transcription.
Small and large intestine, spleen, stomach, and bursa, and to a lesser extent lung and kidney.
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).
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.
Exists in a dynamic equilibrium between monomeric (low affinity) and dimeric (high affinity) structures (By similarity). Interacts with PTPRS (PubMed:17967490, PubMed:25385546).
Expression occurs in the 2 dpc embryo with increasing levels later in development. In the 9 dpc embryo highest levels are found in brain and spinal cord with intermediate levels in eye, heart, gut and muscle. Low levels are found in kidney, liver, skin and yolk sac.
Receptor tyrosine kinase involved in nervous system and probably heart development. Upon binding of its ligand NTF3/neurotrophin-3, NTRK3 autophosphorylates and activates different signaling pathways, including the phosphatidylinositol 3-kinase/AKT and the MAPK pathways, that control cell survival and differentiation (By similarity). The KT and KD isoforms fail to stimulate transformation, process outgrowth or survival. Isoform KI25 exhibits tyrosine phosphorylation in the absence of ligand and is unable to mediate survival of neuronal cells (PubMed:8060621).
The kinase domain is of 19 aa instead of 39aa in the isoform alpha-KD due to a frameshift.
Part of the MIS12 complex which is required for normal chromosome alignment and segregation and for kinetochore formation during mitosis. Essential for proper kinetochore microtubule attachments.
Enriched in cardiac and skeletal muscle.
Isoform B has probably a transactivation capacity that is lacking in the other isoforms. Isoform D may be defective in DNA binding.
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 (By similarity). Binds m-cat elements from muscle-specific promoters and differentially activate transcription.
Was originally called TEF-1, but is the ortholog of mammalian TEF-3.
Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. GSK-3 subfamily.
Homotetramer. Component of activated, catalytic and post-catalytic spliceosomes. Component of the NTC complex (or PRP19-associated complex) which is associated with the spliceosome. Interacts with KHDC4 (By similarity).
Ubiquitin-protein ligase which is mainly involved pre-mRNA splicing and DNA repair. Required for pre-mRNA splicing as component of the spliceosome. Core component of the PRP19C/Prp19 complex/NTC/Nineteen complex which is part of the spliceosome and participates in its assembly, its remodeling and is required for its activity.
Involved in nucleolar processing of pre-18S ribosomal RNA. Has a role in the nuclear export of 40S pre-ribosomal subunit to the cytoplasm.
Expression is maximal at stages 24-31, then begins to decline. Expression is low by stage 37 and is absent by stage 39. Does not appear to be expressed in adults.
First expressed in the embryonic neural plate shortly before closure and expression continues in the neural tube. From stage 16 onwards, expressed throughout the CNS including the brain, with expression predominant in the undifferentiated cells of the neural epithelium. Also expressed at a low level in the retina and the gut epithelium. Highly expressed in the lens placode at stage 13 and in the lens at stage 17.
It is uncertain whether Met-1 or Met-4 is the initiator.
Transcriptional activator (PubMed:7628452). Binds to the consensus DNA sequence 5'-TCATTGTTGTTG-3' (PubMed:7628452). In cooperation with other transcription factors, binds to the promoter sequence of the crystallin gene to activate transcription in the lens (PubMed:7628452). Downstream SRRT target that mediates the promotion of neural stem cell self-renewal (By similarity). Keeps neural cells undifferentiated by counteracting the activity of proneural proteins and suppresses neuronal differentiation (PubMed:14517545). May function as a switch in neuronal development (PubMed:7748786).
Belongs to the clathrin heavy chain family.
Allosterically activated by ADP, AMP, or fructose 2,6-bisphosphate, and allosterically inhibited by ATP or citrate.
Belongs to the phosphofructokinase type A (PFKA) family. ATP-dependent PFK group I subfamily. Eukaryotic two domain clade "E" sub-subfamily.
Belongs to the phosphofructokinase type A (PFKA) family. ATP-dependent PFK group I subfamily. Eukaryotic two domain clade 'E' sub-subfamily.
Catalyzes the phosphorylation of D-fructose 6-phosphate to fructose 1,6-bisphosphate by ATP, the first committing step of glycolysis.
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.
Intramolecular interaction between the zinc finger domain and the CAP-Gly domains may inhibit interaction with tubulin.
Forms hydroxylysine residues in -Xaa-Lys-Gly- sequences in collagens. These hydroxylysines serve as sites of attachment for carbohydrate units and are essential for the stability of the intermolecular collagen cross-links.
Although strongly related to the nudix NUDT16 protein, lacks the Nudix box and is therefore not related to the rest of the family. Lacks a number of residues which are necessary for hydrolase activity and does not play a role in U8 snoRNA decapping activity.
Belongs to the Nudix hydrolase family. TIRR subfamily.
Interacts (via the cytoplasmic part) with syndecan-4 (SDC4), but not with other syndecan proteins (PubMed:10633082).
Key regulator of TP53BP1 required to stabilize TP53BP1 and regulate its recruitment to chromatin.
Myristoylated in vitro; additional evidence is however required to confirm myristoylation in vivo.
Ubiquitously expressed. Expressed in embryonic brain, eyes, gizzard, heart, intestine, kidney, liver, tibia and skin.
Detected in embryonic male and female gonads, heart, liver and muscle. Detected in adult brain, testis, ovary, heart, lung, spleen, kidney and muscle.
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). 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. Also mediates deadenylation-independent repression by promoting accessibility of miRNAs.
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. 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.
Belongs to the endothelin/sarafotoxin family.
Component of the CENPA-HI complex, a centromeric complex involved in assembly of kinetochore proteins, mitotic progression and chromosome segregation (By similarity). Involved in kinetochore assembly and required for recovery from spindle damage.
Component of the CENPA-HI complex, at least composed of CENPH, CENPI, CENPK, CENPL, CENPM, CENPO and CENPP. Component of a discrete complex composed of at least CENPO, CENPP, CENPQ, CENPR and CENPU.
Increases time to progress through G2/M phase.
Belongs to the universal ribosomal protein uS11 family.
Belongs to the glycerate kinase type-2 family.
Belongs to the class-V pyridoxal-phosphate-dependent aminotransferase family. MOCOS subfamily.
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.
Belongs to the pancreatic ribonuclease family.
Homodimer. Interacts with and forms a tight 1:1 complex with RNH1. Dimerization of two such complexes may occur (By similarity).
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). Binds to actin on the surface of endothelial cells; once bound, angiogenin is endocytosed and translocated to the nucleus. Stimulates ribosomal RNA synthesis including that containing the initiation site sequences of 45S rRNA. Angiogenin induces vascularization of normal and malignant tissues. Angiogenic activity is regulated by interaction with RNH1 in vivo.
Component of the DCX(DCAF12) E3 ubiquitin ligase complex, at least composed of CUL4 (CUL4A or CUL4B), DDB1, DCAF12 and RBX1.
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. 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. The DCX(DCAF12) complex specifically recognizes proteins with a diglutamate (Glu-Glu) at the C-terminus, leading to their ubiquitination and degradation.
The insulin-like growth factors, isolated from plasma, are structurally and functionally related to insulin but have a much higher growth-promoting activity. Acts as a ligand for integrin which is required for IGF2 signaling.
Belongs to the sulfotransferase 3 family.
Catalyzes the transfer of sulfate to the C2-position of selected hexuronic acid residues within the maturing heparan sulfate (HS). 2-O-sulfation within HS, particularly of iduronate residues, is essential for HS to participate in a variety of high-affinity ligand-binding interactions and signaling processes.
Expressed in heart, limb, head and trunk. At stages 20 and 24, it is expressed in the most regions of the first and second pharyngeal arche. In both wing and leg buds, it is detected at the overlying ectoderm and mesenchyme throughout stages 21, 23 and 24.
Binds 1 divalent metal cation per subunit; can use either Mg(2+) or Mn(2+).
Pyrophosphatase that hydrolyzes the non-canonical purine nucleotides inosine triphosphate (ITP), deoxyinosine triphosphate (dITP) as well as 2'-deoxy-N-6-hydroxylaminopurine triphosphate (dHAPTP) and xanthosine 5'-triphosphate (XTP) to their respective monophosphate derivatives. The enzyme does not distinguish between the deoxy- and ribose forms. Probably excludes non-canonical purines from RNA and DNA precursor pools, thus preventing their incorporation into RNA and DNA and avoiding chromosomal lesions.
Guanine nucleotide-binding protein that plays a crucial role in the cellular response to amino acid availability through regulation of the mTORC1 signaling cascade.
Involved in pre-mRNA splicing as component of the activated spliceosome.
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.
Cell-cycle-regulated enzyme of importance in nucleotide metabolism. Catalyzes the first enzymatic step in the salvage pathway converting thymidine into thymidine monophosphate. Transcriptional regulation limits expression to the S phase of the cell cycle and transient expression coincides with the oscillation in the intracellular dTTP concentration.
Homotetramer. Tetramerization from dimerization is induced by ATP and increases catalytic efficiency due to a high affinity for thymidine. Tetramerization is inhibited by phosphorylation at Ser-13. Interacts (via the KEN box) with FZR1.
KEN box sequence located in the C-terminal region is required for its mitotic degradation by the APC/C-FZR1 ubiquitin ligase and interaction capability with FZR1.
Phosphorylated on Ser-13 in mitosis. Phosphorylation of Ser-13 by CDK1 during mitosis reduces homotetramerization and catalytic efficiency when DNA replication is complete and intracellular TK1 is still present at a high level.
Polyubiquitinated. Postmitosis, ubiquitination leads to proteasomal degradation. The KEN box sequence located at the C-terminal region targets for degradation by the anaphase promoting complex (APC/C) activated and rate-limited by FZR1.
Two forms have been identified in animal cells, one in cytosol and one in mitochondria. Activity of the cytosolic enzyme is high in proliferating cells and peaks during the S-phase of the cell cycle; it is very low in resting cells.
Belongs to the NAD(P)-dependent epimerase/dehydratase family. UDP-glucuronic acid decarboxylase subfamily.
Belongs to the universal ribosomal protein uL4 family.
Belongs to the mitochondrion-specific ribosomal protein mL43 family.
By 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
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.
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). May act by forming a heterodimer with CTU1/ATPBD3 that ligates sulfur from thiocarboxylated URM1 onto the uridine of tRNAs at wobble position.
Early transcription factor that plays a key role in somitogenesis, paraxial mesoderm development and regulation of stem cell pluripotency. Essential for the mesenchymal to epithelial transition associated with somite formation. Required for somite morphogenesis, thereby regulating patterning of the axial skeleton and skeletal muscles. Also plays a key role in regulation of stem cell pluripotency. Promotes pluripotency exit of embryonic stem cells (ESCs) by priming ESCs for differentiation. Acts as a key regulator of self-renewal of hematopoietic stem cells (HSCs) by mediating HSCs quiescence and long-term self-renewal. Acts by forming a heterodimer with another helix-loop-helix (bHLH) protein, that binds DNA on E-box motifs (5'-CANNTG-3') and activates transcription of target genes.
First detected in a subpopulation of cells lateral to the primitive streak corresponding with the area of prospective segmental plate mesoderm and somites (PubMed:9187085, PubMed:9281340). Later in development, it is expressed throughout the segmental plate and newly formed somites and is restricted to the paraxial mesoderm (PubMed:9187085, PubMed:9281340). After somite formation, its expression decline in the lateral region of the somite (PubMed:9187085, PubMed:9281340). Later it is expressed at highest levels at the cranial and caudal edges of the more mature somites (PubMed:9187085, PubMed:9281340). As the dermomyotome and sclerotome formed, expression disappeared from the ventral regions of the somite, but persisted in the dermomyotome (PubMed:9187085, PubMed:9281340). When the dermomyotome developed further into the dermatome and myotome, expression is detected in both compartments, although more prominently in the dermatome (PubMed:9187085, PubMed:9281340). Expression was also detected in migrating precursors of tongue muscle and in the limb buds (PubMed:9187085, PubMed:9281340).
Heterodimer; efficient DNA binding requires dimerization with another bHLH protein.
Surface ectoderm and neural tube are the sources of inductive signals required for gene expression and for somite formation.
Belongs to the proteasome subunit S1 family.
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 and few additional components including PSMD1. Interacts with ADRM1.
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.
A connexon is composed of a hexamer of connexins. Interacts with TMEM65.
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. Plays an essential role in gap junction communication in the ventricles.
Belongs to the RNA 3'-terminal cyclase family. Type 2 subfamily.
Does not have cyclase activity. Plays a role in 40S-ribosomal-subunit biogenesis in the early pre-rRNA processing steps at sites A0, A1 and A2 that are required for proper maturation of the 18S RNA.
Detected in the theca layer of the ovarian follicle in the white follicle (WF), F1, F3, F5, and postovulatory follicle stages. In the vagina expression is higher in laying hens than in non-laying hens, and is higher in older laying hens than in young laying hens.
Expressed in circulating heterophil granulocytes and bone marrow (at protein level). Strong expression in the bone marrow, lung and testis. Moderate expression in the bursa and intestine. Low expression in the cloaca, gall bladder, brain, pancreas, trachea, air sacs and spleen. Expressed in the vagina, ovarian stroma and the theca layer of the ovarian follicle, but not in the granulosa layer of the ovarian follicle.
Not induced in the ovarian follicle by intravenous injection of LPS. Expression in cultured vaginal cells is increased by LPS and S.enteritidis.
Potent antibacterial activity against the Gram-negative bacterium E.coli ML-35, and against the Gram-positive bacterium L.monocytogenes EGD. Lacks antifungal activity against C.albicans.
Belongs to the V-ATPase C subunit family.
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.
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.
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.
Regulatory component of the SET1 complex implicated in the tethering of this complex to transcriptional start sites of active genes. Facilitates histone H3 'Lys-4' methylation (H3K4me) via recruitment of the SETD1A or SETD1B to the 'Ser-5' phosphorylated C-terminal domain (CTD) of RNA polymerase II large subunit (POLR2A). Part of a transcription termination checkpoint that promotes transcription termination of long non-coding RNAs (lncRNAs).
Belongs to the eukaryotic ribosomal protein eS27 family.
Belongs to the complex I NDUFB8 subunit family.
Involved in maintaining Golgi structure. Stimulates the formation of Golgi stacks and ribbons. Involved in intra-Golgi retrograde transport.
Expressed in the presomitic mesoderm preceding the formation of somites. At stage 4 expressed in and around the primitive streak. During subsequent development, expression domain persists, and gradually retracts in parallel to the retracting Hensen's node towards the caudal end. Expression begins to accumulate in gastrulating mesoderm and is later restricted to paraxial mesoderm, prior to the onset of somite formation. No expression is seen within somites, nor in the tailbud mesoderm.
Involved in specifying the paraxial, but not dorsal, mesoderm. May regulate the expression of T-box transcription factors required for mesoderm formation and differentiation (By similarity).
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.
Self-associates. Interacts with BBS9; the interaction mediates the association of LZTL1 with the BBsome complex and regulates BBSome ciliary trafficking.
Belongs to the nucleoporin interacting component (NIC) family.
Plays a role in the nuclear pore complex (NPC) assembly and/or maintenance.
Involved in the targeting and/or fusion of transport vesicles to their target membrane during transport of proteins from the early endosome to the lysosome. Required for heterotypic fusion of late endosomes with lysosomes and homotypic lysosomal fusion. Required for calcium regulated lysosomal exocytosis. Involved in the export of chylomicrons from the endoplasmic reticulum to the cis Golgi. Required for focal exocytosis of late endocytic vesicles during phagosome formation (By similarity).
Belongs to the glycosyl hydrolase 18 family. Chitinase class II subfamily.
Regulates the GDP/GTP exchange reaction of most RAB proteins by inhibiting the dissociation of GDP from them, and the subsequent binding of GTP.
Converts trimethyllysine (TML) into hydroxytrimethyllysine (HTML).
Accepts electrons from ETF and reduces ubiquinone.
Protein-histidine N-methyltransferase that specifically catalyzes 1-methylhistidine (pros-methylhistidine) methylation of target proteins (By similarity). Mediates methylation of proteins with a His-x-His (HxH) motif (where 'x' is preferably a small amino acid); 1-methylhistidine modification may affect the binding of zinc and other metals to its target proteins (By similarity).
Belongs to the glycogen debranching enzyme family.
Multifunctional enzyme acting as 1,4-alpha-D-glucan:1,4-alpha-D-glucan 4-alpha-D-glycosyltransferase and amylo-1,6-glucosidase in glycogen degradation.
Belongs to the dihydropyrimidine dehydrogenase family.
Binds 4 [4Fe-4S] clusters. Contains approximately 16 iron atoms per subunit.
Involved in pyrimidine base degradation. Catalyzes the reduction of uracil and thymine.
Belongs to the G-alpha family. G(q) subfamily.
Belongs to the ELO family. ELOVL6 subfamily.
Catalyzes the first and rate-limiting reaction of the four reactions that constitute the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process allows the addition of 2 carbons to the chain of long- and very long-chain fatty acids (VLCFAs) per cycle. Condensing enzyme that elongates fatty acids with 12, 14 and 16 carbons with higher activity toward C16:0 acyl-CoAs. Catalyzes the synthesis of unsaturated C16 long chain fatty acids and, to a lesser extent, C18:0 and those with low desaturation degree. May participate in the production of saturated and monounsaturated VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators.
Catalyzes the first and rate-limiting reaction of the four reactions that constitute the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process allows the addition of 2 carbons to the chain of long- and very long-chain fatty acids (VLCFAs) per cycle. Condensing enzyme that elongates fatty acids with 12, 14 and 16 carbons with higher activity toward C16:0 acyl-CoAs. Catalyzes the synthesis of unsaturated C16 long chain fatty acids and, to a lesser extent, C18:0 and those with low desaturation degree. May participate to the production of saturated and monounsaturated VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators.
The reaction is stimulated by the presence of HSD17B12, the enzyme catalyzing the second step of the elongation cycle.
Essential component of the PAM complex, a complex required for the translocation of transit peptide-containing proteins from the inner membrane into the mitochondrial matrix in an ATP-dependent manner.
Stimulates synthesis of cGMP in photoreceptors. Thought to mediate Ca(2+)-sensitive regulation of retinal guanylyl cyclase (GC), a key event in recovery of the dark state of rod photoreceptors following light exposure (By similarity).
Undergoes dimerization at low calcium ions concentration, while the presence of calcium ions inhibits its dimerization. Dimerization correlates with its ability to activate GC.
Belongs to the TRAFAC class dynamin-like GTPase superfamily. Very large inducible GTPase (VLIG) family.
Belongs to the AspA/AstE family. Aspartoacylase subfamily.
Component of the BCR(TNFAIP1) E3 ubiquitin ligase complex, at least composed of CUL3, TNFAIP1/BACURD2 and RBX1.
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 target proteins, leading to their degradation by the proteasome (By similarity).
Histone chaperone that facilitates histone deposition and histone exchange and removal during nucleosome assembly and disassembly. Cooperates with chromatin assembly factor 1 (CAF-1) to promote replication-dependent chromatin assembly. May also cooperate with HIRA to promote replication-independent chromatin assembly.
Interacts with CHAF1B, HIRA, histone H3 and histone H4.
Belongs to the formin homology family. Cappuccino subfamily.
In the developing limb bud, the protein is expressed in the apical ectodermal ridge and the mesenchymal compartment, predominantly in the posterior region. During kidney morphogenesis, expression is initially restricted to the epithelial compartment of the pronephros and mesonephros.
Is important for morphogenesis of limb and kidney and may be involved in determining dorsoventral neural tube polarity and motor neuron induction. It may also have a function in differentiated cells or be involved in maintaining specific differentiated states.
Present in the adult brain, kidney, brain, heart and intestine and throughout the embryo.
Belongs to the Prospero homeodomain family.
Expressed most actively in the developing lens and midgut and at lower levels in the developing brain, heart, muscle and retina.
First detected at stage 14 in the early lens placode. At later stages of development, it was observed throughout the lens, but it appeared more abundant around the bow region of the equator than in the anterior epithelium or the fibers. In the retina, expression was detected mainly in the inner nuclear layer during later stages of histogenesis.
The Prospero-type homeodomain and the adjacent Prospero domain act as a single structural unit, the Homeo-Prospero domain.
Transcription factor which may be involved in developmental processes such as cell fate determination, gene transcriptional regulation and progenitor cell regulation in a number of organs. May be essential in the development and function of the eye. May play a role in the regulation of the circadian rhythm by repressing the expression of clock genes.
Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-2 (TGF-beta-2) chains, which constitute the regulatory and active subunit of TGF-beta-2, respectively.
Belongs to the complex I NDUFA2 subunit family.
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 (By similarity).
Implicated in synaptic vesicle endocytosis. May recruit other proteins to membranes with high curvature (By similarity).
Monomer; in cytoplasm. Homodimer; when associated with membranes. Associates with MAP4K3. This interaction appears to regulate MAP4K3-mediated JNK activation (By similarity). Interacts with SYNJ1 and DNM1.
Belongs to the universal ribosomal protein uL23 family.
Belongs to the potassium channel family. KQT (TC 1.A.1.15) subfamily. Kv7.1/KCNQ1 sub-subfamily.
The rho chain is the major early embryonic beta-type hemoglobin chain.
Interacts with VGF-derived peptide TLQP-21.
Receptor for the chemotactic and inflammatory peptide anaphylatoxin C3a. This receptor stimulates chemotaxis, granule enzyme release and superoxide anion production.
Transaminase involved in tyrosine breakdown. Converts tyrosine to p-hydroxyphenylpyruvate.
Belongs to the calcineurin regulatory subunit family.
Belongs to the opioid neuropeptide precursor family.
Belongs to the chloride channel CLIC family.
Members of this family may change from a globular, soluble state to a state where the N-terminal domain is inserted into the membrane and functions as chloride channel. A conformation change of the N-terminal domain is thought to expose hydrophobic surfaces that trigger membrane insertion.
Belongs to the SMC family. SMC5 subfamily.
Sequence-specific transcription factor that binds gene promoters and activates their transcription (By similarity). Part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis (PubMed:1672266).
Belongs to the G-protein coupled receptor 3 family. GABA-B receptor subfamily.
The BTB/POZ domain seems to direct the protein to discrete regions in the nucleus.
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 (By similarity).
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. Binds to the minimal GLI-consensus sequence 5'-TGGGTGGTC-3' (By similarity).
Expressed in dorsal undifferentiated neural cells in the spinal cord at stages 8 and 23 (at protein level). Expressed in the dorsal neural tube along almost the entire rostrocaudal extent and dorsomedial somites at stage 8. Expressed in the dorsal hindbrain, spinal cord, midbrain and forebrain at stage 17. Expressed in somites and the dorsal CNS at stage 23.
May be involved in the development and regeneration of the musculoskeletal system.
Binds to actin filaments in muscle and non-muscle cells. Plays a central role, in association with the troponin complex, in the calcium dependent regulation of vertebrate striated muscle contraction. Smooth muscle contraction is regulated by interaction with caldesmon. In non-muscle cells is implicated in stabilizing cytoskeleton actin filaments.
Homodimer (PubMed:23832280). 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 (PubMed:15269838, PubMed:15313924).
The molecule is in a coiled coil structure that is formed by 2 polypeptide chains. The sequence exhibits a prominent seven-residues periodicity.
Cell surface receptor for Reelin (RELN) and apolipoprotein E (apoE)-containing ligands. Also binds alpha2-macroglobulin. LRP8 participates in transmitting the extracellular Reelin signal to intracellular signaling processes, by binding to DAB1 on its cytoplasmic tail. Reelin acts via both the VLDL receptor (VLDLR) and LRP8 to regulate DAB1 tyrosine phosphorylation and microtubule function in neurons. LRP8 has higher affinity for Reelin than VLDLR. LRP8 is thus a key component of the Reelin pathway which governs neuronal layering of the forebrain during embryonic brain development. Not required for endocytic uptake of SEPP1 in the kidney which is mediated by LRP2 (By similarity).
Homooligomer. Interacts with VLDLR. Reelin associates with two or more receptor molecules (By similarity). Interacts with DAB1 and JNK-interacting proteins. Interacts with SNX17 (By similarity). Interacts with PCSK9. Interacts with MDK; this interaction is calcium dependent (By similarity). Interacts with CLU (By similarity).
Tyrosine phosphorylated upon apoE binding.
Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. RAF subfamily.
Isoform 1 was present in all tissues tested: skeletal muscle, intestine, brain, gizzard, heart, lung, kidney, bone marrow, spleen and bursa of Fabricius. Isoform 2 was only detected in brain, heart and skeletal muscle. In brain and heart isoform 1 is more abundant than isoform 2. In skeletal muscle isoform 2 is more abundant than isoform 1.
Phosphorylation at Ser-259 inactivates kinase activity. Dephosphorylation of Ser-259 by a complex containing protein phosphatase 1 relieves inactivation, leading to stimulate RAF1 activity (By similarity).
Serine/threonine-protein kinase that acts as a regulatory link between the membrane-associated Ras GTPases and the MAPK/ERK cascade, and this critical regulatory link functions as a switch determining cell fate decisions. RAF1 activation initiates a mitogen-activated protein kinase (MAPK) cascade that comprises a sequential phosphorylation of the dual-specific MAPK kinases (MAP2K1/MEK1 and MAP2K2/MEK2) and the extracellular signal-regulated kinases (MAPK3/ERK1 and MAPK1/ERK2) (By similarity).
Belongs to the flavin monoamine oxidase family.
Histone demethylase that can demethylate both 'Lys-4' (H3K4me) and 'Lys-9' (H3K9me) of histone H3, thereby acting as a coactivator or a corepressor, depending on the context. Acts by oxidizing the substrate by FAD to generate the corresponding imine that is subsequently hydrolyzed. Acts as a corepressor by mediating demethylation of H3K4me, a specific tag for epigenetic transcriptional activation. Demethylates both mono- (H3K4me1) and di-methylated (H3K4me2) H3K4me. May play a role in the repression of neuronal genes. Alone, it is unable to demethylate H3K4me on nucleosomes and requires the presence of RCOR1/CoREST to achieve such activity.
The SWIRM domain may act as an anchor site for a histone tail.
Putative Notch ligand involved in the mediation of Notch signaling.
Anchored to cell periphery via its N-terminal PDZ domain.
Expressed in the presumptive fore- and hindlimb. Continues to be expressed in the limb mesenchyme throughout forelimb and hindlimb bud outgrowth. Expressed in the developing heart and eye.
Interacts with various PKC isoforms through the LIM zinc-binding domains. Interacts with TPM2 (By similarity). Interacts with TBX4 and TBX5.
May function as a scaffold on which the coordinated assembly of proteins can occur. May play a role as an adapter that, via its PDZ domain, localizes LIM-binding proteins to actin filaments of both skeletal muscle and nonmuscle tissues. May be involved in bone formation (By similarity).
The LIM zinc-binding 2 (LIM 2) interacts with TBX4.
The LIM zinc-binding 3 (LIM 3) domain provides the structural basis for recognition of tyrosine-containing tight turn structures (By similarity). This domain is necessary and sufficient for interaction with TBX5.
May be involved in the control of excitability of cortical neurons.
Belongs to the GST superfamily. Alpha family.
Highly expressed in ovary. Detected at lower levels in heart, lung, gizzard and testis.
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.
N-glycosylated. TLR2-1 is more heavily glycosylated than TLR2-2.
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). Does not respond to LPS and responds with less ability than TLR2-2 to mycoplasmal macrophage-activating lipopeptide-2kD (MALP-2).
Expressed in the posterior limb bud mesenchyme, the Hensen node, the notochord, and the floor plate of the neural tube.
First detectable at stage 17 during the initiation of limb bud formation. From that point onwards, the expression pattern exactly matches the location of the zone of polarizing activity (ZPA).
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 (By similarity). Interacts with DISP1 via its cholesterol anchor (By similarity). Interacts with SCUBE2 (By similarity).
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 (By similarity).
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 (By similarity). 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).
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).
The Cardin-Weintraub (CW) motif is required for heparan sulfate binding of the solubilized ShhNp (By similarity). The N-terminal palmitoylated peptide is cleaved at the Heparan sulfate-binding Cardin-Weintraub (CW) motif site (By similarity). The cleavage reduced the interactions with heparan sulfate. The cleavage is enhanced by SCUBE2 (By similarity).
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:7736596). 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 (By similarity). In the absence of SHH, PTCH1 represses the constitutive signaling activity of SMO (By similarity).
The lipidated N- and C-terminal peptides of ShhNp can be cleaved (shedding) (By similarity). The N-terminal palmitoylated peptide is cleaved at the Cardin-Weintraub (CW) motif site (By similarity). The cleavage reduced the interactions with heparan sulfate (By similarity). The cleavage is enhanced by SCUBE2 (By similarity).
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. Once released, the fully processed Shh can signal within embryonic tissues both at short and long-range.
E3 ubiquitin-protein ligase that regulates selective mitochondrial autophagy by mediating 'Lys-63'-linked polyubiquitination. 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. Responsible for the cotranslational ubiquitination and degradation of CFTR in the ERAD pathway. Also acts as a regulator of the innate antiviral response by catalyzing 'Lys-27'-linked polyubiquitination of CGAS, thereby promoting CGAS cyclic GMP-AMP synthase activity. Preferentially associates with the E2 enzymes UBE2J1 and UBE2J2 (By similarity).
The RING-type zinc finger domain is responsible for E3 ubiquitin ligase activity.
The transactivation domains TAM and TAC (for transactivation domain in the middle and at the C-terminus, respectively) are required to contact transcriptional coactivators and basal transcriptional machinery components and thereby induce gene transactivation.
Transcription factor that may play a role in central nervous system, limb and facial development. May be involved in male sex determination. Binds the consensus motif 5'-[AT][AT]CAA[AT]G-3'.
Belongs to the spermidine/spermine synthase family.
Small GTPase required for proper localization of RNA polymerase II (RNAPII). May act at an RNAP assembly step prior to nuclear import.
Small GTPase required for proper nuclear import of RNA polymerase II and III (RNAPII and RNAPIII). May act at an RNAP assembly step prior to nuclear import.
Strong expression in the tongue and bone marrow. Low expression in the esophagus, trachea, lung, brain and ovary. Expressed in the ovarian stroma, but not in the ovarian follicles.
Belongs to the MINDY deubiquitinase family. FAM188 subfamily.
Hydrolase that can remove 'Lys-48'-linked conjugated ubiquitin from proteins.
Belongs to the MICOS complex subunit Mic10 family.
C-terminal fragments could be released during apoptosis via caspase-3-dependent cleavage.
Plays a role in the regulation of the actin cytoskeleton through its interactions with actin capping protein (CP).
Belongs to the prenylcysteine oxidase family.
Involved in the replication of mitochondrial DNA. Associates with mitochondrial DNA.
Belongs to the glycosyltransferase 14 family. XylT subfamily.
Belongs to the 3-oxoacid CoA-transferase family.
Key enzyme for ketone body catabolism. Transfers the CoA moiety from succinate to acetoacetate. Formation of the enzyme-CoA intermediate proceeds via an unstable anhydride species formed between the carboxylate groups of the enzyme and substrate.
Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO), such as platelet dense granules and melanosomes. In concert with the AP-3 complex, the BLOC-1 complex is required to target membrane protein cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals. The BLOC-1 complex, in association with SNARE proteins, is also proposed to be involved in neurite extension. May play a role in intracellular vesicle trafficking, particularly in the vesicle-docking and fusion process.
Catalyzes the first step in the biosynthesis of NAD from nicotinic acid, the ATP-dependent synthesis of beta-nicotinate D-ribonucleotide from nicotinate and 5-phospho-D-ribose 1-phosphate.
Transiently phosphorylated on a His residue during the reaction cycle. Phosphorylation strongly increases the affinity for substrates and increases the rate of nicotinate D-ribonucleotide production. Dephosphorylation regenerates the low-affinity form of the enzyme, leading to product release.
Belongs to the transient receptor (TC 1.A.4) family. TrpV subfamily. TRPV1 sub-subfamily.
Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin.
Belongs to the mitochondrion-specific ribosomal protein mL42 family.
Binds the telomeric double-stranded 5'-TTAGGG-3' repeat.
Belongs to the peptidase C65 family. Otulin subfamily.
Belongs to the short-chain dehydrogenases/reductases (SDR) family. 17-beta-HSD 3 subfamily.
May catalyze the metabolism of steroid hormones and thus play an important role in sex differentiation, the emergence and maintenance of the secondary sexual characters, and the regulation of endocrine.
Belongs to the protein kinase superfamily. Tyr protein kinase family. SYK/ZAP-70 subfamily.
Belongs to the eukaryotic NMN adenylyltransferase family.
Belongs to the protein kinase superfamily. RIO-type Ser/Thr kinase family.
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). Inhibits the transactivation function of HIF-1A under both normoxic and hypoxia-mimicking conditions. The interaction with EMAP2 increases the proteasome-mediated HIF-1A degradation under the hypoxic conditions. Plays a role in hepatitis C virus internal ribosome entry site-mediated translation. Mediates nuclear translocation of the androgen receptor (AR) and thereby enhances androgen-mediated transactivation. Promotes MAVS degradation and thereby negatively regulates MAVS-mediated innate immune response.
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. PSMA7 interacts directly with the PSMG1-PSMG2 heterodimer which promotes 20S proteasome assembly. Interacts with HIF1A. Interacts with RAB7A. Interacts with PRKN. Interacts with ABL1 and ABL2. Interacts with EMAP2. Interacts with MAVS.
Substrate-binding subunit (component A) of the Rab geranylgeranyltransferase (GGTase) complex. Binds unprenylated Rab proteins and presents the substrate peptide to the catalytic component B. The component A is thought to be regenerated by transferring its prenylated Rab back to the donor membrane.
Expression in cultured vaginal cells is increased by LPS and S.enteritidis.
In the vagina expression is higher in laying hens than in non-laying hens, and is higher in older laying hens than in young laying hens.
Strongly expressed in the tongue, bone marrow, bursa of Fabricius and trachea. Also expressed in skin, esophagus and air sacs. Weak expression in the large intestine, kidney and ovary. Expressed in the vagina and ovarian stroma, but not in the ovarian follicle.
In vertebrates, 3 forms of this ubiquitous glycolytic enzyme are found, aldolase A in muscle, aldolase B in liver and aldolase C in brain.
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.
Acts both as a regulator of telomere function and as a transcription regulator. Involved in the regulation of telomere length and protection as a component of the shelterin complex (telosome). Does not bind DNA directly: recruited to telomeric double-stranded 5'-TTAGGG-3' repeats via its interaction with terf2. Independently of its function in telomeres, also acts as a transcription regulator: recruited to extratelomeric 5'-TTAGGG-3' sites via its association with terf2 or other factors, and regulates gene expression (By similarity).
Homodimer. Component of the shelterin complex (telosome) (By similarity). Interacts with terf2; the interaction is direct.
Shares a bidirectional promoter with KARS.
Belongs to the ROX family. MINA53 subfamily.
Oxygenase that can act as both a histone lysine demethylase and a ribosomal histidine hydroxylase.
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).
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 set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion. That Rab is mainly involved in the biosynthetic transport of proteins from the Golgi to the plasma membrane. Also plays a specific role in asymmetric protein transport to the plasma membrane within the polarized neuron and epithelial cells. In neurons, it is involved in axonogenesis through regulation of vesicular membrane trafficking toward the axonal plasma membrane while in epithelial cells, it regulates transport from the Golgi to the basolateral membrane. Moreover, may play a role in the basolateral recycling pathway and in phagosome maturation. Finally, may play a role in endoplasmic reticulum dynamics and morphology controlling tubulation along microtubules and tubules fusion (By similarity).
Belongs to the potassium channel family. A (Shaker) (TC 1.A.1.2) subfamily. Kv1.2/KCNA2 sub-subfamily.
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 (PubMed:30846601). This patch mediates recycling from the Golgi to the endoplasmic reticulum, probably via COPI vesicles (By similarity).
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 (By similarity). Binding is pH dependent, and is optimal at pH 5-5.4 (PubMed:30846601).
Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. Aurora subfamily.
Belongs to the G-protein coupled receptor 1 family. Muscarinic acetylcholine receptor subfamily. CHRM2 sub-subfamily.
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is adenylate cyclase inhibition. Signaling promotes phospholipase C activity, leading to the release of inositol trisphosphate (IP3); this then triggers calcium ion release into the cytosol.
This receptor has a high affinity for pirenzepine.
ATP-dependent DNA helicase that unwinds single- and double-stranded DNA in a 3'-5' direction (PubMed:28228481). Participates in DNA replication and repair (By similarity). Involved in 5'-end resection of DNA during double-strand break (DSB) repair (By similarity). Negatively regulates sister chromatid exchange (SCE) (By similarity). Stimulates DNA 4-way junction branch migration and DNA Holliday junction dissolution (By similarity). Binds DNA (PubMed:28228481). Binds single-stranded DNA (ssDNA), forked duplex DNA and DNA Holliday junction (By similarity).
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 (PubMed:28228481). Oligomer complexes dissociate into monomer in presence of ATP (PubMed:28228481).
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 (By similarity). The HRDC domain is required for single-stranded DNA (ssDNA) and DNA Holliday junction binding (By similarity).
Interacts with KATNA1. This interaction enhances the microtubule binding and severing activity of KATNA1 and also targets this activity to the centrosome.
Participates in a complex which severs microtubules in an ATP-dependent manner. May act to target the enzymatic subunit of this complex to sites of action such as the centrosome. Microtubule severing may promote rapid reorganization of cellular microtubule arrays and the release of microtubules from the centrosome following nucleation.
Belongs to the beta type-B retroviral polymerase family. HERV class-II K(HML-2) pol subfamily.
Detected in embryonic brain and orsal root ganglia.
Exists in a dynamic equilibrium between monomeric (low affinity) and dimeric (high affinity) structures. Interacts (phosphorylated upon activation by BDNF) with SHC1; mediates SHC1 phosphorylation and activation. Interacts (phosphorylated upon activation by BDNF) with PLCG1 and/or PLCG2; mediates PLCG1 phosphorylation and activation. Interacts with SH2B1 and SH2B2. Interacts with NGFR; may regulate the ligand specificity of the receptor (By similarity). Interacts with SORCS2; this interaction is important for normal targeting to post-synaptic densities in response to high-frequency stimulation (By similarity). Interacts (phosphorylated upon ligand-binding) with SH2D1A; regulates NTRK2. Interacts with SQSTM1 and KIDINS220 (By similarity). Interacts (phosphorylated upon ligand-binding) with FRS2; activates the MAPK signaling pathway (By similarity). Interacts with APPL1 (By similarity). Interacts with MAPK8IP3/JIP3 and KLC1; interaction with KLC1 is mediated by MAPK8IP3/JIP3 (By similarity).
It is unsure whether Leu-144 or Met-188 is the initiator of isoform 2.
Receptor tyrosine kinase involved in the development and the maturation of the central and the peripheral nervous systems through regulation of neuron survival, proliferation, migration, differentiation, and synapse formation and plasticity. Receptor for BDNF/brain-derived neurotrophic factor and NTF4/neurotrophin-4 (PubMed:8287802, PubMed:8670834). Alternatively can also bind NTF3/neurotrophin-3 which is less efficient in activating the receptor but regulates neuron survival through NTRK2. Upon ligand-binding, undergoes homodimerization, autophosphorylation and activation (PubMed:8670834). Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades. Through SHC1, FRS2, SH2B1, SH2B2 activates the GRB2-Ras-MAPK cascade that regulates for instance neuronal differentiation including neurite outgrowth. Through the same effectors controls the Ras-PI3 kinase-AKT1 signaling cascade that mainly regulates growth and survival. Through PLCG1 and the downstream protein kinase C-regulated pathways controls synaptic plasticity. Thereby, plays a role in learning and memory by regulating both short term synaptic function and long-term potentiation. PLCG1 also leads to NF-Kappa-B activation and the transcription of genes involved in cell survival. Hence, it is able to suppress anoikis, the apoptosis resulting from loss of cell-matrix interactions. May also play a role in neutrophin-dependent calcium signaling in glial cells and mediate communication between neurons and glia (By similarity).
Specifically activated by BDNF but not NTF3 and NTF4.
The neuronal activity and the influx of calcium positively regulate the kinase activity and the internalization of the receptor which are both important for active signaling. Regulated by NGFR that may control the internalization of the receptor. NGFR may also stimulate the activation by BDNF compared to NTF3 and NTF4. The formation of active receptors dimers able to fully transduce the ligand-mediated signal, may be negatively regulated by the formation of inactive heterodimers with the non-catalytic isoforms (By similarity).
Belongs to the mitochondrial carrier (TC 2.A.29) family. SLC25A38 subfamily.
Mitochondrial glycine transporter that imports glycine into the mitochondrial matrix. Plays an important role in providing glycine for the first enzymatic step in heme biosynthesis, the condensation of glycine with succinyl-CoA to produce 5-aminolevulinate (ALA) in the miochondrial matrix. Required during erythropoiesis.
Belongs to the galactose-1-phosphate uridylyltransferase type 1 family.
Belongs to the phospholipid scramblase family.
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.
Expression is maximal at stages 24-31, then begins to decline. Expression is low by stage 37 and disappears by stage 39. Does not appear to be expressed in adults.
Low level expression is seen in undifferentiated proliferating cells of the neural epithelium. Greater expression is seen in the maturing neurons after they leave the neural epithelium. Also expressed in the embryonic gut epithelium and adrenal medulla.
Transcription factor that acts as a transcriptional activator (By similarity). May function as a switch in neuronal development (PubMed:7748786).
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 beta subunit regulates, through assembly of alpha/beta heterodimers, the number of sodium pumps transported to the plasma membrane.
This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins. Nuclear ADRA1A-ADRA1B heterooligomers regulate phenylephrine (PE)-stimulated ERK signaling in cardiac myocytes.
Binds to telomerase (By similarity). Binds to the progesterone receptor (PubMed:8114727).
mRNA-binding protein involved in proper cytoplasmic distribution of mitochondria. Specifically binds mRNAs of nuclear-encoded mitochondrial proteins in the cytoplasm and regulates transport or translation of these transcripts close to mitochondria, playing a role in mitochondrial biogenesis.
Belongs to the aspartyl/asparaginyl beta-hydroxylase family.
Transcription factor that represses the transcription of a wide range of genes involved in cell proliferation and differentiation. Directly and specifically binds to the consensus sequence 5'-[GA][CA]GACCCCCCCCC-3' and represses transcription both by regulating the organization of chromatin and through the direct recruitment of transcription factors to gene regulatory regions (By similarity). May also play a role, independently of its transcriptional activity, in double-strand break repair via classical non-homologous end joining/cNHEJ and in alternative splicing (By similarity).
May regulate calcium-dependent activities in the endoplasmic reticulum lumen or post-ER compartment.
Belongs to the chaperonin (HSP60) family.
Chaperonin implicated in mitochondrial protein import and macromolecular assembly. Together with Hsp10, facilitates the correct folding of imported proteins. May also prevent misfolding and promote the refolding and proper assembly of unfolded polypeptides generated under stress conditions in the mitochondrial matrix. The functional units of these chaperonins consist of heptameric rings of the large subunit Hsp60, which function as a back-to-back double ring. In a cyclic reaction, Hsp60 ring complexes bind one unfolded substrate protein per ring, followed by the binding of ATP and association with 2 heptameric rings of the co-chaperonin Hsp10. This leads to sequestration of the substrate protein in the inner cavity of Hsp60 where, for a certain period of time, it can fold undisturbed by other cell components. Synchronous hydrolysis of ATP in all Hsp60 subunits results in the dissociation of the chaperonin rings and the release of ADP and the folded substrate protein.
Plays a role in transport between endoplasmic reticulum and Golgi.
Belongs to the WD repeat CDC20/Fizzy family.
Interacts with calmodulin; via its IQ motifs.
Represents an unconventional myosin. This protein should not be confused with the conventional myosin-1 (MYH1).
Unconventional myosin required during immune response for detection of rare antigen-presenting cells by regulating T-cell migration. Unconventional myosins are actin-based motor molecules with ATPase activity and serve in intracellular movements. Acts as a regulator of T-cell migration by generating membrane tension, enforcing cell-intrinsic meandering search, thereby enhancing detection of rare antigens during lymph-node surveillance, enabling pathogen eradication.
Cilium- and flagellum-specific protein that plays a role in axonemal structure organization and motility. May play a role in outer and inner dynein arm assembly.
F-type ATPases have 2 components, CF(1) - the catalytic core - and CF(0) - the membrane proton channel.
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.
Involved in protein trafficking. May serve as a receptor for ARFRP1.
Belongs to the aldo/keto reductase family.
Belongs to the SEC23/SEC24 family. SEC23 subfamily.
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.
Component of the signal peptidase complex paralog A (SPC-A) composed of a catalytic subunit SEC11A and three accessory subunits SPCS1, SPCS2 and SPCS3 (PubMed:2831945). Component of the signal peptidase complex paralog C (SPC-C) composed of a catalytic subunit SEC11C and three accessory subunits SPCS1, SPCS2 and SPCS3 (PubMed:2831945). The complex induces a local thinning of the ER membrane which is used to measure the length of the signal peptide (SP) h-region of protein substrates. This ensures the selectivity of the complex towards h-regions shorter than 18-20 amino acids (By similarity).
Essential component of the signal peptidase complex (SPC) which catalyzes the cleavage of N-terminal signal sequences from nascent proteins as they are translocated into the lumen of the endoplasmic reticulum (By similarity). Essential for the SPC catalytic activity, possibly by stabilizing and positioning the active center of the complex close to the lumenal surface (By similarity).
Expressed in hen oviduct (at protein level).
Belongs to the eukaryotic ribosomal protein eS10 family.
Non-catalytic component of the proteasome.
Component of the PI3K (PI3KC3/PI3K-III/class III phosphatidylinositol 3-kinase) complex (By similarity).
May be proteolytically processed by caspases; the C-terminal fragment(s) may induce apoptosis.
Plays a central role in autophagy (By similarity). Acts as core subunit of different PI3K complex forms that mediate formation of phosphatidylinositol 3-phosphate and are believed to play a role in multiple membrane trafficking pathways such as initiation of autophagosomes, maturation of autophagosomes and endocytosis (By similarity). Involved in regulation of degradative endocytic trafficking and required for the abcission step in cytokinesis, probably in the context of PI3KC3-C2 (By similarity).
May play a role in the structure and strength of both muscle and bone.
Heterotetramer of two epsilon chains and two alpha chains. Hemoglobin E (Hbe) contains a alpha-A chains while hemoglobin M (Hbm) contains alpha-D chains.
Heterotetramer of two alpha-D chains and two beta chains. The component D forms dimers of tetramers upon deoxygenation.
In birds, the alpha-D chain occurs in a minor hemoglobin component, called hemoglobin d, which is expressed in late embryonic and adult life.
Involved in oxygen transport from the lung to the various peripheral tissues.
Ref.6 chain was isolated from Hbm, the least abundant of the four early chick hemoglobins.
Belongs to the paired homeobox family. Bicoid subfamily.
May play an important role in development and maintenance of anterior structures. May play a role in determining left-right asymmetry and in vasculogenesis during avian embryogenesis.
Involved in transport of proteins from the cis/medial-Golgi to the trans-Golgi network.
Binds unfolded collagen in a complex with CYPB and CRTAP.
Expressed in embryonic dermis, tendon, cartilage, liver and kidney. Expression in the kidney is restricted to the calyx. In the liver, expression is restricted to the interlobular septum.
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 secretoty pathway of cells. Has growth suppressive activity in fibroblasts.
Belongs to the Mediator complex subunit 7 family.
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.
Component of the proteinaceous fiber-like linker between two centrioles, required for centrosome cohesion.
Belongs to the SelWTH family. Selenoprotein T subfamily.
May contain a selenide-sulfide bond between Cys-50 and Sec-53. This bond is speculated to serve as redox-active pair (By similarity).
Selenoprotein with thioredoxin reductase-like oxidoreductase activity.
Has a role in nuclear-cytoplasmic transport of proteins and mRNAs.
Belongs to the immunoglobulin superfamily. L1/neurofascin/NgCAM family.
Expressed in developing neural retina and embryonic brain tissue.
Heterodimer of an alpha and a beta chain.
This protein is a cell adhesion molecule involved in neuron-neuron adhesion, neurite fasciculation, outgrowth of neurites, etc. Specifically involved in the development of optic fibres in the retina.
Belongs to the immunoglobulin superfamily. MyBP family.
Binds to myosin; probably involved in interaction with thick myofilaments in the A-band.
Skeletal muscle. Seems to be also expressed in the slow tonic ald muscle. Not detected in gizzard or heart.
Heterooligomeric complex of about 850 to 900 kDa that forms two stacked rings, 12 to 16 nm in diameter. Interacts with PACRG (By similarity).
Molecular chaperone; assists the folding of proteins upon ATP hydrolysis. Known to play a role, in vitro, in the folding of actin and tubulin (By similarity).
Expressed in developing tectum (at protein level).
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-8 associates with beta-1.
Integrin alpha-8/beta-1 functions in the genesis of kidney and probably of other organs by regulating the recruitment of mesenchymal cells into epithelial structures. It recognizes the sequence R-G-D in a wide array of ligands including TNC, FN1, SPP1, TGFB1, TGFB3 and VTN. NPNT is probably its functional ligand in kidney genesis (By similarity). Neuronal receptor for TNC it mediates cell-cell interactions and regulates neurite outgrowth of sensory and motor neurons.
Prominently expressed on axons and on cells in contact with basal laminae in embryos.
Belongs to the DEAD box helicase family. DDX5/DBP2 subfamily.
Required for centrosome assembly and function (PubMed:12403812). Essential for the correct localization of several centrosomal proteins including CETN3 and PCNT (By similarity). Required to anchor microtubules to the centrosome (PubMed:12403812). Probably involved in the biogenesis of cilia (By similarity).
Required for the function of coenzyme Q in the respiratory chain. May serve as a chaperone or may be involved in the transport of Q6 from its site of synthesis to the catalytic sites of the respiratory complexes.
Belongs to the tubulin polyglutamylase family.
May be involved in the regulation of spermatogenesis. Stimulates CREM transcriptional activity in a phosphorylation-independent manner.
Belongs to the Integrator subunit 12 family.
Does not show transport activity towards bile acids or steroid sulfates.
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. Also involved in the regulation of cellular calcium homeostasis. Does not show transport activity towards bile acids or steroid sulfates.
Expressed in hemopoietic cells, but also in the fibroblasts, bone marrow, brain, eye and gut.
Probably binds two or three calcium ions.
Inhibits p53- and p73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain.
Belongs to the sepiapterin reductase family.
Cytokine that stimulates the growth and differentiation of hematopoietic precursor cells from various lineages, including granulocytes, macrophages, eosinophils and erythrocytes.
Monomer. The signaling GM-CSF receptor complex is a dodecamer of two head-to-head hexamers of two alpha, two beta, and two ligand subunits.
Tachykinins are active peptides which excite neurons, evoke behavioral responses, are potent vasodilators and secretagogues, and contract (directly or indirectly) many smooth muscles.
In the C-terminal section; belongs to the eukaryotic ribosomal protein eL40 family.
As cone-specific cGMP phosphodiesterase, it plays an essential role in light detection and cone phototransduction by rapidly decreasing intracellular levels of cGMP.
Composed of two alpha' subunits that are associated with 3 smaller proteins of 11, 13, and 15 kDa.
Belongs to the adenylate kinase family. AK2 subfamily.
Catalyzes the reversible transfer of the terminal phosphate group between ATP and AMP. Plays an important role in cellular energy homeostasis and in adenine nucleotide metabolism. Adenylate kinase activity is critical for regulation of the phosphate utilization and the AMP de novo biosynthesis pathways. Plays a key role in hematopoiesis.
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 ATP binding. Assembling and dissambling the active center during each catalytic cycle provides an effective means to prevent ATP hydrolysis.
Homopentamer. Pentaxin (or pentraxin) have a discoid arrangement of 5 non-covalently bound subunits.
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/ATP5MC1. Therefore, participates in the early stage of mitochondrial ATP synthase biogenesis and also protects subunit c/ATP5MC1 against intramitochondrial proteolysis.
Cytoskeletal protein involved in actin-membrane attachment at sites of cell adhesion to the extracellular matrix (focal adhesion). Binds in vitro to vinculin as well as to the SH3 domain of c-SRC and, when tyrosine phosphorylated, to the SH2 domain of v-CRK.
Interacts (via LD motif 4) with PARVA/PARVIN and ILK.
Phosphorylated on tyrosine residues during integrin-mediated cell adhesion, embryonic development, fibroblast transformation and following stimulation of cells by mitogens.
Catalyzes the dephosphorylation of the nucleoside 5'-monophosphates deoxyadenosine monophosphate (dAMP), deoxycytidine monophosphate (dCMP), deoxyguanosine monophosphate (dGMP) and deoxythymidine monophosphate (dTMP).
Converts O-phosphoseryl-tRNA(Sec) to selenocysteinyl-tRNA(Sec) required for selenoprotein biosynthesis.
Homotetramer formed by a catalytic dimer and a non-catalytic dimer serving as a binding platform that orients tRNASec for catalysis. Each tetramer binds the CCA ends of two tRNAs which point to the active sites of the catalytic dimer.
Belongs to the cytochrome b5 family. MAPR subfamily.
Component of a progesterone-binding protein complex. Binds progesterone. Has many reported cellular functions (heme homeostasis, interaction with CYPs). May be required for the maintenance of uterine histoarchitecture and normal female reproductive lifespan. Intracellular heme chaperone. Regulates heme synthesis via interactions with FECH and acts as a heme donor for at least some hemoproteins.
Homodimer. Forms stable homodimer through hydrophobic heme-heme stacking interactions.
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).
The cytochrome b5 heme-binding domain lacks the conserved iron-binding His residues at positions 105 and 129.
Belongs to the eukaryotic ribosomal protein eL33 family.
Belongs to the glycoprotein hormones subunit beta family.
Belongs to the 5'(3')-deoxyribonucleotidase family.
May be a negative regulator of NF-kappa-B and p53-mediated gene transcription.
Associates with the 40S ribosomal subunit, the 80S ribosome and with polysomes.
Single-stranded DNA-binding protein that preferentially binds to the sterol regulatory element (SRE) sequence 5'-GTGCGGTG-3', and thereby mediates transcriptional repression (By similarity). Has a role as transactivator of the Myc promoter (By similarity). Binds single-stranded RNA in a sequence-specific manner (By similarity). Binds G-rich elements in target mRNA coding sequences (By similarity). Prevents G-quadruplex structure formation in vitro, suggesting a role in supporting translation by resolving stable structures on mRNAs (By similarity).
Heterodimer of a common alpha chain and a unique beta chain which confers biological specificity to thyrotropin, lutropin, follitropin and gonadotropin.
Indispensable for the control of thyroid structure and metabolism.
Component of the brain-specific heterotrimeric complex (LIN-10-LIN-2-LIN-7 complex) composed of at least APBA1, CASK, and LIN7, which associates with the motor protein KIF17 to transport vesicles along microtubules.
Plays a role in establishing and maintaining the asymmetric distribution of channels and receptors at the plasma membrane of polarized cells. Forms membrane-associated multiprotein complexes that may regulate delivery and recycling of proteins to the correct membrane domains (By similarity). The tripartite complex composed of LIN7 (LIN7A, LIN7B or LIN7C), CASK and APBA1 associates with the motor protein KIF17 to transport vesicles containing N-methyl-D-aspartate (NMDA) receptor subunit NR2B along microtubules (By similarity).
The L27 domain mediates interaction with CASK and is involved in the formation of multimeric complexes and the association of LIN7 to membranes.
The PDZ domain regulates endocytosis and recycling of the receptor at the membrane.
The kinase interacting site is required for proper delivery of ERBB2 to the basolateral membrane.
May play an important role in microtubule plus-end depolymerizing activity in mitotic cells.
Belongs to the potassium channel family. A (Shaker) (TC 1.A.1.2) subfamily. Kv1.4/KCNA4 sub-subfamily.
Adenosyl-L-methionine (AdoMet)-dependent tRNA (uracil-O(2)-)-methyltransferase.
Peroxisomal protease that mediates both the removal of the leader peptide from proteins containing a PTS2 target sequence and processes several PTS1-containing proteins. Catalyzes the processing of PTS1-proteins involved in the peroxisomal beta-oxidation of fatty acids.
The full-lengh TYSND1 is the active the proteolytic processing of PTS1- and PTS2-proteins and in self-cleavage, and intermolecular self-cleavage of TYSND1 down-regulates its protease activity.
Belongs to the eutherian X-chromosome-specific Armcx family.
Homodimer. Part of the multisubunit TRAPP (transport protein particle) complex (By similarity).
Involved in the maturation of mitochondrial 4Fe-4S proteins functioning late in the iron-sulfur cluster assembly pathway. Probably involved in the binding of an intermediate of Fe/S cluster assembly.
Filament-forming cytoskeletal GTPase. Required for normal organization of the actin cytoskeleton. Plays a role in the biogenesis of polarized columnar-shaped epithelium by maintaining polyglutamylated microtubules, thus facilitating efficient vesicle transport, and by impeding MAP4 binding to tubulin. Required for the progression through mitosis. Forms a scaffold at the midplane of the mitotic splindle required to maintain CENPE localization at kinetochores and consequently chromosome congression. During anaphase, may be required for chromosome segregation and spindle elongation. Plays a role in ciliogenesis and collective cell movements. In cilia, required for the integrity of the diffusion barrier at the base of the primary cilium that prevents diffusion of transmembrane proteins between the cilia and plasma membranes (By similarity).
Septins polymerize into heterooligomeric protein complexes that form filaments, and associate with cellular membranes, actin filaments and microtubules. GTPase activity is required for filament formation. Can form heterooligomers with other family members and form filaments (By similarity).
A palmitoylation site was proposed at Cys-77, but it was later shown that this cysteine is engaged in a disulfide bond.
Disulfide bonds have critical and distinct roles in secretion and activity. Loss of each conserved cysteine in WNT3A results in high molecular weight oxidized Wnt oligomers, which are formed through inter-Wnt disulfide bonding (By similarity).
Expressed in cornea. Isoform 1 is expressed in the primitive streak, dorsal neural tube, proximal otic vesicle, the apical ectodermal ridge and the epithelium of feather buds.
In the eye, the expression was observed at stage 23 in the ocular surface epithelium ventral to the corneal epithelium. Strongly expressed in the entire ocular surface at stage 26 including the corneal epithelium. Remained strongly expressed at stage 30.
Ligand for members of the frizzled family of seven transmembrane receptors (Probable). Functions in the canonical Wnt signaling pathway that results in activation of transcription factors of the TCF/LEF family (PubMed:17488271). Regulates chick apical ectodermal ridge formation (PubMed:17488271). Required for normal embryonic mesoderm development and formation of caudal somites. Required for normal morphogenesis of the developing neural tube (By similarity).
Palmitoleoylation is required for efficient binding to frizzled receptors (PubMed:22046319). Depalmitoleoylation leads to inhibit the Wnt signaling pathway (By similarity).
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.
Component of several multiprotein Golgi SNARE complexes.
Involved in transport from the ER to the Golgi apparatus as well as in intra-Golgi transport. It belongs to a super-family of proteins called t-SNAREs or soluble NSF (N-ethylmaleimide-sensitive factor) attachment protein receptor. May play a protective role against hydrogen peroxide induced cytotoxicity under glutathione depleted conditions in neuronal cells by regulating the intracellular ROS levels via inhibition of p38 MAPK (MAPK11, MAPK12, MAPK13 and MAPK14). Participates in docking and fusion stage of ER to cis-Golgi transport. Plays an important physiological role in VLDL-transport vesicle-Golgi fusion and thus in VLDL delivery to the hepatic cis-Golgi.
Calcium-regulated membrane-binding protein whose affinity for calcium is greatly enhanced by anionic phospholipids. It binds two calcium ions with high affinity.
Heterotetramer containing 2 light chains of S100A10/p11 and 2 heavy chains of ANXA2/p36.
It may cross-link plasma membrane phospholipids with actin and the cytoskeleton and be involved with exocytosis.
Belongs to the homogentisate dioxygenase family.
Belongs to the eukaryotic ribosomal protein eL30 family.
Adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions.
Homotrimer; disulfide-linked. Can bind to fibrinogen, fibronectin, laminin and type V collagen (By similarity).
May function to promote vesicle trafficking and/or fusion.
Expressed in smooth muscle cells of the upper digestive organs and their attached arteries and to craniofacial structures.
Interacts with serum response factor (SRF).
Transcription factor which is involved with the serum response factor (SRF) in the smooth muscle cell-specific transcription of the beta-tropomyosin gene in the upper digestive organs and their attached arteries.
Belongs to the peptidase M67A family. BRCC36 subfamily.
Component of the BRCA1-A complex. Component of the BRISC complex. Both the BRCA1-A complex and the BRISC complex bind polyubiquitin.
Metalloprotease that specifically cleaves 'Lys-63'-linked polyubiquitin chains. 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). Catalytic subunit of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys-63'-linked ubiquitin in various substrates. Mediates the specific 'Lys-63'-specific deubiquitination associated with the COP9 signalosome complex (CSN), via the interaction of the BRISC complex with the CSN complex. The BRISC complex is required for normal mitotic spindle assembly and microtubule attachment to kinetochores via its role in deubiquitinating NUMA1.
Bifunctional mRNA-capping enzyme exhibiting RNA 5'-triphosphate monophosphatase activity in the N-terminal part and mRNA guanylyltransferase activity in the C-terminal part. Catalyzes the first two steps of cap formation: by removing the gamma-phosphate from the 5'-triphosphate end of nascent mRNA to yield a diphosphate end, and by transferring the GMP moiety of GTP to the 5'-diphosphate terminus of RNA via a covalent enzyme-GMP reaction intermediate.
In the C-terminal section; belongs to the eukaryotic GTase family.
In the N-terminal section; belongs to the non-receptor class of the protein-tyrosine phosphatase family.
Phosphorylation at Ser-67 by GWL during mitosis is essential for interaction with PPP2R2D (PR55-delta) and subsequent inactivation of PP2A.
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).
Activated by calcium and magnesium and inhibited by other bivalent cations.
Belongs to the CDP-alcohol phosphatidyltransferase class-II family.
Functions in the biosynthesis of the anionic phospholipids phosphatidylglycerol and cardiolipin.
Belongs to the gamma-glutamylcyclotransferase family. ChaC subfamily.
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.
Belongs to the ELO family. ELOVL1 subfamily.
Catalyzes the first and rate-limiting reaction of the four reactions that constitute the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process allows the addition of 2 carbons to the chain of long- and very long-chain fatty acids (VLCFAs) per cycle. Condensing enzyme that exhibits activity toward saturated C18 to C26 acyl-CoA substrates, with the highest activity towards C22:0 acyl-CoA. May participate to the production of both saturated and monounsaturated VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators.
Belongs to the class V-like SAM-binding methyltransferase superfamily. SETD3 actin-histidine methyltransferase family.
Protein-histidine N-methyltransferase that specifically mediates 3-methylhistidine (tele-methylhistidine) methylation of actin at 'His-73'. Does not have protein-lysine N-methyltransferase activity and probably only catalyzes histidine methylation of actin.
The SET domain specifically recognizes and binds actin, suggesting that it does not accommodate substrates diverging from actin.
Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO), such as platelet dense granules and melanosomes. Plays a role in intracellular vesicle trafficking (By similarity).
Component of the biogenesis of lysosome-related organelles complex 1 (BLOC-1).
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. Has an acyl-CoA thioesterase activity towards the long chain fatty acyl-CoA thioester palmitoyl-CoA (hexadecanoyl-CoA; C16:0-CoA). Displays a substrate preference for fatty acyl-CoAs with chain-lengths C12-C18.
Belongs to the DPH1/DPH2 family. DPH1 subfamily.
Binds 1 [4Fe-4S] cluster per subunit. The cluster is coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine.
Catalyzes the first step of diphthamide biosynthesis, a post-translational modification of histidine which occurs in elongation factor 2.
Probable receptor for purines coupled to G-proteins.
Dually phosphorylated on Thr-183 and Tyr-185, which activates the enzyme.
Expressed in the neuroepithelium of developing brain at stages 16 to 26.
Responds to activation by environmental stress and pro-inflammatory cytokines by phosphorylating a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity (By similarity). May play a role in the development of the central nervous system during embryogenesis. May play a role in the regulation of the circadian clock (By similarity).
The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.
A soluble form is produced by proteolytic processing of the extracellular domain.
Acts in the early stages of hematopoiesis.
Ligand for the receptor-type protein-tyrosine kinase KIT. Plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis.
Ligand for the receptor-type protein-tyrosine kinase KIT. Plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. KITLG/SCF binding can activate several signaling pathways. Acts synergistically with other cytokines, probably interleukins (By similarity).
Belongs to the universal ribosomal protein uS5 family.
Component of the ribosome, a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. The small ribosomal subunit (SSU) binds messenger RNAs (mRNAs) and translates the encoded message by selecting cognate aminoacyl-transfer RNA (tRNA) molecules. The large subunit (LSU) contains the ribosomal catalytic site termed the peptidyl transferase center (PTC), which catalyzes the formation of peptide bonds, thereby polymerizing the amino acids delivered by tRNAs into a polypeptide chain. The nascent polypeptides leave the ribosome through a tunnel in the LSU and interact with protein factors that function in enzymatic processing, targeting, and the membrane insertion of nascent chains at the exit of the ribosomal tunnel. Plays a role in the assembly and function of the 40S ribosomal subunit. Mutations in this protein affects the control of translational fidelity. Involved in nucleolar processing of pre-18S ribosomal RNA and ribosome assembly.
Belongs to the transcriptional coactivator PC4 family.
General coactivator that functions cooperatively with TAFs and mediates functional interactions between upstream activators and the general transcriptional machinery. May be involved in stabilizing the multiprotein transcription complex. Binds single-stranded DNA. Also binds, in vitro, non-specifically to double-stranded DNA (ds DNA).
Belongs to the potassium channel family. V (TC 1.A.1.2) subfamily. Kv8.1/KCNV1 sub-subfamily.
Heteromultimer with KCNB1 and KCNB2. Interacts with KCNC4 and KCND1.
Potassium channel subunit that does not form functional channels by itself. Modulates KCNB1 and KCNB2 channel activity by shifting the threshold for inactivation to more negative values and by slowing the rate of inactivation. Can down-regulate the channel activity of KCNB1, KCNB2, KCNC4 and KCND1, possibly by trapping them in intracellular membranes.
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.
Expressed in embryonic stem cells. Expressed in the pluripotent cells of the epiblast. Detected at the junction of non-neuronal and neuronal ectoderm just before neural tube closure. Expressed in the ventral epidermis before ventral closure, in the intermediate mesoderm, gonads and the forming nephric duct and tubules of the mesonephros and metanephros.
Probable oocyte-specific oolemmal receptor involved in sperm and egg adhesion and fertilization. May act as a protease (By similarity).
Belongs to the deoxyhypusine hydroxylase family.
Catalyzes the hydroxylation of the N(6)-(4-aminobutyl)-L-lysine intermediate produced by deoxyhypusine synthase/DHPS on a critical lysine of the eukaryotic translation initiation factor 5A/eIF-5A. This is the second step of the post-translational modification of that lysine into an unusual amino acid residue named hypusine. Hypusination is unique to mature eIF-5A factor and is essential for its function.
Belongs to the eukaryotic ribosomal protein eS26 family.
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).
Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. CK2 subfamily.
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. Regulates numerous cellular processes, such as cell cycle progression, apoptosis and transcription, as well as viral infection. May act as a regulatory node which integrates and coordinates numerous signals leading to an appropriate cellular response. 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. Can also negatively regulate apoptosis. Phosphorylates the caspases CASP9 and CASP2 and the apoptotic regulator NOL3. Phosphorylation protects CASP9 from cleavage and activation by CASP8, and inhibits the dimerization of CASP2 and activation of CASP8 (By similarity). Plays an important role in the circadian clock function by phosphorylating BMAL1 (By similarity).
Tetramer composed of an alpha chain, an alpha' and two beta chains. Interacts with RNPS1 (By similarity).
Belongs to the small GTPase superfamily. Ras family. KappaB-Ras subfamily.
Belongs to the iron-containing alcohol dehydrogenase family. Hydroxyacid-oxoacid transhydrogenase subfamily.
Belongs to the sulfotransferase 1 family. Gal/GlcNAc/GalNAc subfamily.
The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2).
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.
Belongs to the complex I NDUFB1 subunit family.
Belongs to the class I-like SAM-binding methyltransferase superfamily. Cation-dependent O-methyltransferase family.
Belongs to the phage and mitochondrial RNA polymerase family.
DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.
Belongs to the universal ribosomal protein uL11 family.
Protein kinase that may play an important role in cellular stress response. May be involved in the regulation of processes such as cell survival, neuronal excitability and renal sodium excretion (By similarity).
Expression in the theca and granulosa layers of the F3 stage ovarian follicle is not affected by intravenous injection of LPS.
Strong expression in the testis, liver, gall bladder and kidney. Also expressed in the ovary and male and female reproductive tracts. Expressed in the ovarian stroma and the theca and granulosa layers of the ovarian follicle.
Belongs to the palmitoyl-protein thioesterase family.
Has no ubiquitin ligase activity on its own. The UBE2V2/UBE2N heterodimer catalyzes the synthesis of non-canonical poly-ubiquitin chains that are linked through 'Lys-63'. This type of poly-ubiquitination 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 (By similarity).
Belongs to the RNA polymerase beta chain family.
Belongs to the aconitase/IPM isomerase family.
Binds 1 [4Fe-4S] cluster per subunit. [4Fe-4S]-binding affects RNA-binding activity, thereby inhibiting activity of the protein.
RNA-binding protein that binds to iron-responsive elements (IRES), which are stem-loop structures found in the 5'-UTR of ferritin, and delta aminolevulinic acid synthase mRNAs, and in the 3'-UTR of transferrin receptor mRNA. Binding to the IRE element in ferritin results in the repression of its mRNA translation. Binding of the protein to the transferrin receptor mRNA inhibits the degradation of this otherwise rapidly degraded mRNA.
Ubiquitinated and degraded by the proteasome in presence of high level of iron and oxygen.
Heterooligomer of subunits alpha (IDH3A), beta (IDH3B), and gamma (IDH3G) in the apparent ratio of 2:1:1. The heterodimer containing one IDH3A and one IDH3B subunit and the heterodimer containing one IDH3A and one IDH3G subunit assemble into a heterotetramer (which contains two subunits of IDH3A, one of IDH3B and one of IDH3G) and further into the heterooctamer.
Belongs to the retinoblastoma protein (RB) family.
High levels are seen in the pancreas while lower levels are found in the liver, spleen and thymus.
N-glycosylated. Complex glycosylation with bisecting N-acetylglucosamine. Contains mainly N-acetylglucosamine (3.1-8.5%), mannose (2.9-4.6%), a small amount of galactose (1.1-4.35) and sialic acid (0.3-1.3%). Most abundant glycan is composed of a GlcNAc(2)Man(3) core, a bisecting GlcNAc and another 3 GlcNAc antannae located on the mannoses of the core. Site Asn-1639 exists both in glycosylated and non-glycosylated forms.
Ovomucin, the glycoprotein responsible for the gel properties of egg white, is composed for 2 subunits, alpha-ovomucin/MUC5B and beta-ovomucin/MUC6.
Can form homooligomers and heterooligomers with IGF2BP1 and IGF2BP3 in an RNA-dependent manner. Associates with the cytoskeleton, predominantly with actin filament bundles and occasionally with microtubules. In a heterologous system, interacts with ELAVL1, DHX9 and HNRNPU.
Domains KH3 and KH4 are the major RNA-binding modules, although KH1 and KH2 may also contribute to transcript binding. The contribution to RNA-binding of individual KH domains may be target-specific. KH1 and KH2, and possibly KH3 and KH4, promote the formation of higher ordered protein-RNA complexes, which may be essential for IGF2BP1 cytoplasmic retention. KH domains are required for RNA-dependent homo- and heterooligomerization and for localization to stress granules. KH3 and KH4 mediate association with the cytoskeleton. Two nuclear export signals (NES) have been identified in KH2 and KH4 domains, respectively. Only KH2 NES is XPO1-dependent. Both NES may be redundant, since individual in vitro mutations do not affect subcellular location of the full length protein.
Expressed in neurons and embryonic fibroblasts (at protein level).
Phosphorylated by SRC at Tyr-396. This residue is involved in ACTB mRNA binding, its phosphorylation impairs association with ACTB mRNA and hence abolishes translational repression. Phosphorylation occurs in close proximity to filopodia and in the growth cones of differentiated neuroglioblastoma cells.
RNA-binding factor that recruits target transcripts to cytoplasmic protein-RNA complexes (mRNPs). This transcript 'caging' into mRNPs allows mRNA transport and transient storage. It also modulates the rate and location at which target transcripts encounter the translational apparatus and shields them from endonuclease attacks or microRNA-mediated degradation. Preferentially binds to N6-methyladenosine (m6A)-containing mRNAs and increases their stability (By similarity). Plays a direct role in the transport and translation of transcripts required for axonal regeneration in adult sensory neurons (By similarity). Regulates localized beta-actin/ACTB mRNA translation in polarized cells, a crucial process for cell migration and neurite outgrowth. Co-transcriptionally associates with the ACTB mRNA in the nucleus. This binding involves by a conserved 54-nucleotide element in the ACTB mRNA 3'-UTR, known as the 'zipcode'. The ribonucleoparticle (RNP) thus formed is exported to the cytoplasm, binds to a motor protein and is transported along the cytoskeleton to the cell periphery. During transport, IGF2BP1 prevents beta-actin mRNA from being translated into protein. When the RNP complex reaches its destination near the plasma membrane, IGF2BP1 is phosphorylated by SRC. This releases the mRNA, allowing ribosomal 40S and 60S subunits to assemble and initiate ACTB protein synthesis. The monomeric ACTB protein then assembles into the subcortical actin cytoskeleton, which pushes the leading edge onwards. Binds MYC mRNA. Binding to MYC mRNA is enhanced by m6A-modification of the CRD (By similarity). Promotes the directed movement of cells by fine-tuning intracellular signaling networks. Binds to MAPK4 3'-UTR and inhibits its translation. Interacts with PTEN transcript open reading frame (ORF) and prevents mRNA decay. This combined action on MAPK4 (down-regulation) and PTEN (up-regulation) antagonizes HSPB1 phosphorylation, consequently it prevents G-actin sequestration by phosphorylated HSPB1, allowing F-actin polymerization. Hence enhances the velocity of cell migration and stimulates directed cell migration by PTEN-modulated polarization.
Belongs to the ubiquitin family. SUMO subfamily.
Cleavage of precursor form by a sentrin-specific protease is necessary for function.
Interacts with SAE2, UBE2I, RANBP2, PIAS1 and PIAS2 (By similarity). Covalently attached to a number of proteins (By similarity).
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. 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. Polymeric SUMO1 chains are also susceptible to polyubiquitination which functions as a signal for proteasomal degradation of modified proteins.
At stage 11, expressed in the surface ectoderm surrounding the optic vesicle. At stage 15, expressed in anterior/nasal side of the early retina. At stage 26, during the peak period of ganglion cell genesis, highly expressed in the nasal retina and the lens ectoderm.
DNA-binding protein that binds to the 5'-CAAG-3' core sequence. May function as a transcriptional repressor. Seems to act as a transcriptional antagonist of NKX2-5. May play an important role in the development of craniofacial structures such as the eye and ear.
Histone methyltransferase that specifically trimethylates 'Lys-20' of histone H4 to form trimethylated histone H4 lysine 20 (H4K20me3) which represents a specific tag for epigenetic transcriptional repression.
Carbon monoxide (CO) and the redox state of the cell can modulate the transcriptional activity of the NPAS2-BMAL1 heterodimer. NADH and NADPH enhance the DNA-binding activity of the heterodimer whereas CO binds the heme group in NPAS2 and inhibits the DNA-binding activity of the heterodimer.
Component of the circadian clock oscillator which includes the CRY proteins, CLOCK or NPAS2, BMAL1 or BMAL2, CSNK1D and/or CSNK1E, TIMELESS and the PER proteins. Efficient DNA binding requires dimerization with another bHLH protein. Forms a heterodimer with BMAL1 and this heterodimerization is required for E-box-dependent transactivation.
Exhibits a circadian rhythm in the retina with peak levels in early subjective night. No circadian rhythm pattern in the pineal gland.
Expressed in the retinal photoreceptor cells (at protein level). Expressed in the pineal gland and retina.
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 period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and BMAL1 or BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-BMAL1|BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G, which form a second feedback loop and which activate and repress BMAL1 transcription, respectively. NPAS2 positively regulates the circadian expression of AANAT in the retinal photoreceptor cells.
Belongs to the POU transcription factor family. Class-2 subfamily.
Transcription factor that binds to the octamer motif (5'-ATTTGCAT-3') and activates the promoters of the genes for some small nuclear RNAs (snRNA) and of genes such as those for histone H2B and immunoglobulins. Modulates transcription transactivation by NR3C1, AR and PGR (By similarity).
Belongs to the class-IV pyridoxal-phosphate-dependent aminotransferase family.
Belongs to the small GTPase superfamily. Ran family.
GTPase involved in nucleocytoplasmic transport, participating both to the import and the export from the nucleus of proteins and RNAs. Switches between a cytoplasmic GDP- and a nuclear GTP-bound state by nucleotide exchange and GTP hydrolysis. Nuclear import receptors such as importin beta bind their substrates only in the absence of GTP-bound RAN and release them upon direct interaction with GTP-bound RAN, while export receptors behave in the opposite way. Thereby, RAN controls cargo loading and release by transport receptors in the proper compartment and ensures the directionality of the transport. Interaction with RANBP1 induces a conformation change in the complex formed by XPO1 and RAN that triggers the release of the nuclear export signal of cargo proteins. RAN (GTP-bound form) triggers microtubule assembly at mitotic chromosomes and is required for normal mitotic spindle assembly and chromosome segregation. Required for normal progress through mitosis.
Mg(2+) interacts primarily with the phosphate groups of the bound guanine nucleotide.
Monomer. Interacts with RANGAP1, which promotes RAN-mediated GTP hydrolysis. Interacts with KPNB1. Interaction with KPNB1 inhibits RANGAP1-mediated stimulation of GTPase activity. Interacts with RCC1 which promotes the exchange of RAN-bound GDP by GTP. Interaction with KPNB1 inhibits RCC1-mediated exchange of RAN-bound GDP by GTP. Interacts (GTP-bound form) with TNPO1; the interaction is direct. Interacts (GTP-bound form) with TNPO3; the interaction is direct. Interacts with KPNB1 and with TNPO1; both inhibit RAN GTPase activity. Interacts (via C-terminus) with RANBP1, which alleviates the inhibition of RAN GTPase activity. Interacts with RANGRF, which promotes the release of bound guanine nucleotide. RANGRF and RCC1 compete for an overlapping binding site on RAN. Identified in a complex with KPNA2 and CSE1L; interaction with RANBP1 mediates dissociation of RAN from this complex. Interaction with both RANBP1 and KPNA2 promotes dissociation of the complex between RAN and KPNB1. Identified in a complex composed of RAN, RANGAP1 and RANBP1. Identified in a complex that contains TNPO1, RAN and RANBP1. Identified in a nuclear export complex with XPO1. Interaction with RANBP1 or RANBP2 induces a conformation change in the complex formed by XPO1 and RAN that triggers the release of the nuclear export signal of cargo proteins. Component of a nuclear export receptor complex composed of KPNB1, RAN, SNUPN and XPO1.
Belongs to the dynactin subunits 5/6 family. Dynactin subunit 6 subfamily.
Both the O-glycan-rich domain of the extracellular domain and the C-terminus PDZ-binding motif (DTHL) in the cytoplasmic tail harbor an apical sorting signal. The cytoplasmic domain is necessary for the apical membrane targeting and renal tubulogenesis. The large highly anionic extracellular domain allows to maintain open filtration pathways between neighboring podocyte foot processes (By similarity). The cytoplasmic C-terminus PDZ-binding motif (DTHL) is essential for interaction with SLC9A3R1 and for targeting SLC9A3R1 to the apical cell membrane. The extracellular domain is necessary for microvillus formation.
Expressed in thrombocytes, kidney podocytes, vascular endothelia and mono- and multipotent progenitors from the bone marrow (at protein level).
Expressed on the surface of extra- and intraembryonic hematopoietic cells, neural tube, aorta, glomerulus, liver, heart and coelomic cavity in 4 day old embryo; in each of these tissues, detection is restricted to cells comprising the lumenal surfaces of tissues or boundary elements between tissues such as in the liver capsule, aorta, mesonephros, coelomic cavity and the central canal of the neural tube. Expressed in multipotent progenitors of day three yolk sac (at protein level).
Involved in the regulation of both adhesion and cell morphology and cancer progression. Functions as an anti-adhesive molecule that maintains an open filtration pathway between neighboring foot processes in the podocyte by charge repulsion. Acts as a pro-adhesive molecule, enhancing the adherence of cells to immobilized ligands, increasing the rate of migration and cell-cell contacts in an integrin-dependent manner. Involved in the formation of a preapical plasma membrane subdomain to set up initial epithelial polarization and the apical lumen formation during renal tubulogenesis. Plays a role in cancer development and aggressiveness by inducing cell migration and invasion through its interaction with the actin-binding protein EZR. Affects EZR-dependent signaling events, leading to increased activities of the MAPK and PI3K pathways in cancer cells (By similarity). Induces the formation of apical actin-dependent microvilli.
N- and O-linked glycosylated. Sialoglycoprotein (By similarity).
Belongs to the steroid 5-alpha reductase family.
Component of some MLL1/MLL complex. Component of the PELP1 complex, composed of at least PELP1, TEX10 and WDR18. The complex interacts with pre-60S ribosome particles.
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.
Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of dopamine, small phenols such as 1-naphthol and p-nitrophenol and thyroid hormones, including 3,3'-diiodothyronine, triidothyronine (T3) and reverse triiodothyronine (rT3).
Proton-coupled folate symporter that mediates folate absorption using an H(+) gradient as a driving force (PubMed:34040256). Involved in the intestinal absorption of folates at the brush-border membrane of the proximal jejunum, and the transport from blood to cerebrospinal fluid across the choroid plexus (PubMed:34040256). Functions at acidic pH via alternate outward- and inward-open conformation states (PubMed:34040256). Protonation of residues in the outward open state primes the protein for transport (PubMed:34040256). Binding of folate promotes breaking of salt bridge network and subsequent closure of the extracellular gate, leading to the inward-open state and release of protons and folate (PubMed:34040256). Also able to transport antifolate drugs, such as methotrexate and pemetrexed (PubMed:34040256). Also acts as a lower-affinity, pH-independent heme carrier protein and constitutes the main importer of heme in the intestine (By similarity). Imports heme in the retina and retinal pigment epithelium, in neurons of the hippocampus, in hepatocytes and in the renal epithelial cells (By similarity).
Widely expressed, including brain, aorta, liver, kidney, spleen, small intestine, pancreas, ovary and testis.
ATP-dependent serine protease that mediates the selective degradation of misfolded, unassembled or oxidatively damaged polypeptides as well as certain short-lived regulatory proteins in the mitochondrial matrix. May also have a chaperone function in the assembly of inner membrane protein complexes. Participates in the regulation of mitochondrial gene expression and in the maintenance of the integrity of the mitochondrial genome. Binds to mitochondrial DNA in a site-specific manner.
Homohexamer or homoheptamer. Organized in a ring with a central cavity.
Component of the SWI5-SFR1 complex, a complex required for double-strand break repair via homologous recombination (By similarity). May act as a transcriptional modulator for ESR1 (By similarity).
Homodimer; mediated via the coiled-coil region.
Proteolytically cleaved by caspase-3 during apoptosis at Asp-325 resulting in a 37 kDa form. Proteolytic cleavage results in kinase activation and nuclear translocation of the truncated form (MST1/N) (By similarity).
Stress-activated, pro-apoptotic kinase which, following caspase-cleavage, enters the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation. Key component of the Hippo signaling pathway which plays a pivotal role 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 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. Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. Phosphorylates 'Ser-14' of histone H2B (H2BS14ph) during apoptosis. Phosphorylates FOXO3 upon oxidative stress, which results in its nuclear translocation and cell death initiation.
The C-terminal non-catalytic region inhibits the kinase activity, the enzyme is activated by caspase-cleavage. Homodimerization and autophosphorylation of Thr-182 is also required for full activation (By similarity).
Belongs to the metallothionein superfamily. Type 1 family.
Metallothioneins have a high content of cysteine residues that bind various heavy metals.
Efficient DNA binding requires dimerization with another bHLH protein. Forms heterodimers with TCF3 (By similarity).
Implicated in the genesis of hemopoietic malignancies. It may play an important role in hemopoietic differentiation.
Probably plays a crucial role in the binding of the barbed end of actin filaments to the plasma membrane.
May play an important role in spermatogenesis and/or testis development.
Associates with cyclin-T to form P-TEFb. Also associates with cyclin-K (By similarity).
Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.
Member of the cyclin-dependent kinase pair (CDK9/cyclin-T) complex, also called positive transcription elongation factor b (P-TEFb), which facilitates the transition from abortive to production elongation by phosphorylating the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAP II), SUPT5H and RDBP. The CDK9/cyclin-K complex has also a kinase activity toward CTD of RNAP II and can substitute for P-TEFb in vitro (By similarity).
First expressed the mesoderm of the emerging dorsal pancreatic bud at stage 17-18. Also expressed in the thyroid anlagen. Expression persists throughout the dorsal pancreatic mesoderm through 6 dpc as the pancreas continues to enlarge. After 6 dpc, the amount of mesoderm in the pancreas declines to a minimal level and little or no expression is seen. The expression in the mesoderm of the thyroid persists at least through 8 dpc in the development of this organ. Weakly expressed within the emerging lung buds and developing gut. Also expressed in developing carniofacial structures. At stage 17, expression is restricted to the cranial paraxial mesoderm. At stage 24, expressed in the corners of the frontonasal mass (globular processes) where the lip will fuse. At stage 26 through 29, becomes focused in the center of the frontonasal mass. At stage 30, further restricted to the future egg tooth. By stage 34, found in the egg tooth and structures derived from the frontonasal mass, such as the premaxillary mesenchyme (PubMed:26385749).
Serine protease inhibitor which displays weak inhibitory activity against trypsin (By similarity). May play a role in facial patterning during embryonic development (PubMed:26385749).
Up-regulated by Noggin/NOG and retinoic acid. May be a direct retinoic acid target.
Was named SugarCrisp after the breakfast cereal.
Component of the pre-catalytic and post-catalytic spliceosome complexes.
Required for pre-mRNA splicing as component of the spliceosome (By similarity). Binds double-stranded RNA (By similarity).
Carbamylation allows a single lysine to coordinate two divalent metal cations.
Detected in embryonic brain and liver, and at low levels in embryonic eye, heart, lung, intestine and skeletal muscle.
GTPase-activating protein for RHOA and CDC42.
Component of the NuA4 histone acetyltransferase (HAT) 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 (By similarity). NuA4 may also play a direct role in DNA repair when directly recruited to sites of DNA damage (By similarity).
Interacts with H3K4me3 and to a lesser extent with H3K4me2. Component of the NuA4 histone acetyltransferase complex.
Belongs to the Sp1 C2H2-type zinc-finger protein family.
Detected in early stages of embryos as an oval and 2 stripes at HH stage 5, which becomes two lateral stripes at HH stage 7, running along the anteroposterior body axis from the head ectoderm to the anterior region of the primitive streak. At HH stage 8, strong expression in the anterior neuroectoderm, which forms the central nervous system, is observed, and at HH stage 9, expressed in the most anterior region of the forebrain, midbrain, neural groove and Hensen's node. At HH stage 15-16, the expression is seen in the surface ectoderm of the limb-forming fields, in addition to the neural tube. The expression in the limb field became confined to the distal region of the limb at HH stage 16 and 17, with still scattered signal visible in the surface ectoderm of the limb bud. Strongly expressed in the apical ectodermal ridge (AER) and weakly in the ectoderm in the developing limb bud at HH stage 21. The expression in the AER is detected throughout later stages of limb development.
Transcription factor which plays a key role in limb development. Positively regulates FGF8 expression in the apical ectodermal ridge (AER) and contributes to limb outgrowth in embryos.
Belongs to the WD repeat G protein beta family. Ribosomal protein RACK1 subfamily.
Involved in the recruitment, assembly and/or regulation of a variety of signaling molecules. Interacts with a wide variety of proteins and plays a role in many cellular processes (By similarity).
Catalyzes phosphatidylcholine biosynthesis from CDP-choline. It thereby plays a central role in the formation and maintenance of vesicular membranes.
Nicotinic acid adenine dinucleotide phosphate (NAADP) binding protein.
Translation initiation regulator which may repress non-AUG initiated translation and repeat-associated non-AUG (RAN) initiated translation by acting as a competitive inhibitor of eukaryotic translation initiation factor 5 (EIF5) function.
tRNA nucleus export receptor which facilitates tRNA translocation across the nuclear pore complex.
Belongs to the SelWTH family. Selenoprotein W subfamily.
Expressed ubiquitously with predominant expression in the pituitary, spinal cord, sciatic nerve, cerebral cortex, cerebral nuclei, thalamus, cerebellum, muscle, cartilage, trachea, gizzard and artery. Weakly expressed in pancreas, testis, ovary, kidney and veins.
Plays a role as a glutathione (GSH)-dependent antioxidant. May be involved in a redox-related process. May play a role in the myopathies of selenium deficiency (By similarity).
Up-regulated by dietary selenium in cerebral tissue.
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.
Regulatory subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents in skeletal muscle. Regulates channel inactivation kinetics.
Belongs to the universal ribosomal protein uS12 family.
Component of the 40S small ribosomal subunit.
Belongs to the potassium channel family. B (Shab) (TC 1.A.1.2) subfamily. Kv2.1/KCNB1 sub-subfamily.
Belongs to the learning-associated protein family.
Regulates dendritic and spine growth and synaptic transmission.
Implicated in development of the cochlea.
Functions as a regulator of the biosynthesis of TSH in the anterior pituitary gland and as a neurotransmitter/ neuromodulator in the central and peripheral nervous systems.
LSm subunits form a heteromer with a doughnut shape.
Plays 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). The heptameric LSM2-8 complex binds specifically to the 3'-terminal U-tract of U6 snRNA.
Belongs to the argonaute family. Ago subfamily.
Required for RNA-mediated gene silencing (RNAi). Binds to short RNAs such as microRNAs (miRNAs) and represses the translation of mRNAs which are complementary to them. Lacks endonuclease activity and does not appear to cleave target mRNAs.
Required for RNA-mediated gene silencing (RNAi). Binds to short RNAs such as microRNAs (miRNAs) and represses the translation of mRNAs which are complementary to them. Possesses RNA slicer activity but only on select RNAs bearing 5'- and 3'-flanking sequences to the region of guide-target complementarity.
Endoplasmic reticulum chaperone that plays a key role in protein folding and quality control in the endoplasmic reticulum lumen (By similarity). Involved in the correct folding of proteins and degradation of misfolded proteins via its interaction with DNAJC10/ERdj5, probably to facilitate the release of DNAJC10/ERdj5 from its substrate (By similarity). Acts as a key repressor of the ERN1/IRE1-mediated unfolded protein response (UPR). In the unstressed endoplasmic reticulum, recruited by DNAJB9/ERdj4 to the luminal region of ERN1/IRE1, leading to disrupt the dimerization of ERN1/IRE1, thereby inactivating ERN1/IRE1. Accumulation of misfolded protein in the endoplasmic reticulum causes release of HSPA5/BiP from ERN1/IRE1, allowing homodimerization and subsequent activation of ERN1/IRE1 (By similarity). May also play a role in apoptosis and cell proliferation (By similarity).
Monomer and homooligomer; homooligomerization via the interdomain linker inactivates the chaperone activity and acts as a storage of HSPA5/BiP molecules (By similarity). Interacts with DNAJC10 (By similarity). Interacts with DNAJB9/ERdj4; leading to recruit HSPA5/BiP to ERN1/IRE1. Interacts with ERN1/IRE1; interaction takes place following interaction with DNAJB9/ERdj4 and leads to inactivate ERN1/IRE1 (By similarity).
The chaperone activity is regulated by ATP-induced allosteric coupling of the nucleotide-binding (NBD) and substrate-binding (SBD) domains (By similarity). In the ADP-bound and nucleotide-free (apo) states, the two domains have little interaction (By similarity). In contrast, in the ATP-bound state the two domains are tightly coupled, which results in drastically accelerated kinetics in both binding and release of polypeptide substrates (By similarity). J domain-containing co-chaperones (DNAJB9/ERdj4 or DNAJC10/ERdj5) stimulate the ATPase activity and are required for efficient substrate recognition by HSPA5/BiP. Homooligomerization inactivates participating HSPA5/BiP protomers and probably act as reservoirs to store HSPA5/BiP molecules when they are not needed by the cell (By similarity).
The interdomain linker regulates the chaperone activity by mediating the formation of homooligomers. Homooligomers are formed by engagement of the interdomain linker of one HSPA5/BiP molecule as a typical substrate of an adjacent HSPA5/BiP molecule. HSPA5/BiP oligomerization inactivates participating HSPA5/BiP protomers. HSPA5/BiP oligomers probably act as reservoirs to store HSPA5/BiP molecules when they are not needed by the cell. When the levels of unfolded proteins rise, cells can rapidly break up these oligomers to make active monomers.
Forms homodimers, and heterodimers with BAX, BAD, BAK and Bcl-X(L). Heterodimerization with BAX requires intact BH1 and BH2 motifs, and is necessary for anti-apoptotic activity (By similarity). Also interacts with APAF1 and RAF-1 (By similarity).
In adult chicken expressed, in thymus, spleen, kidney, heart, ovary and brain, with the highest levels in the thymus. In the embryo, highly levels expressed in all tissues with high levels in the bursa of Fabricius.
Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1).
The BH4 motif is required for anti-apoptotic activity and for interaction with RAF-1.
Transfers sialic acid from the donor of substrate CMP-sialic acid to galactose containing acceptor substrates.
Anticoagulant plasma protein; it is a cofactor to activated protein C in the degradation of coagulation factors Va and VIIIa. It helps to prevent coagulation and stimulating fibrinolysis.
Mitochondrial transporter that imports/exports pyrimidine nucleotides into and from mitochondria. Transports preferentially cytosine and uracil (deoxy)nucleoside mono-, di-, and triphosphates by uniport and antiport mechanism.
Involved in the regulation of homocysteine metabolism.
Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ2 subfamily.
Found in the apical basilar papilla of the inner ear, brain, muscle, cerebellum, heart and liver.
Homomultimeric and heteromultimeric association with KCNJ4/Kir2.3, resulting in an enhanced G-protein-induced current. Association, via its PDZ-recognition domain, with LIN7A, LIN7B, LIN7C, DLG1, CASK and APBA1 plays a key role in its localization and trafficking (By similarity).
Probably participates in establishing action potential waveform and excitability of neuronal and muscle tissues. 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 external barium.
At stage 7 of embryonic development, expressed in the neural plate with lower expression in the midline. At stage 9, expression restricted to the dorsal neural tube and cranial neural crest. At stage 12, expressed in the lateral plate mesoderm. In the developing trunk, expressed, from stages 9-12, in the ventral migrating neural crest with some expression at stage 12 in the dorsal streams From stage 15, expressed in the endocardial cells of the outflow tract of the developing heart. From stage 18, expression found in the epibranchial placodes, in endocardial and mesenchymal cells of the developing atrioventricular canal and of the outflow tract cushions. Expression in these regions of the developing heart continue until stage 26. During limb development, low expression found, by stage 18, in the developing limb buds, By stage 20, highly expressed in the ventral mesenchyme of both fore- and hind-limb buds. By stage 24, expression localized to the central core of the developing limb bud, which contains the chondrogenic precursors. Also expressed in the surrounding nonchondrogenic mesenchyme. Later expression confined to the perichondrium and to the epiphyses of the early developing skeletal elements.
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. SFRP3/FRZB appears to be involved in limb skeletogenesis. Antagonist of Wnt8 signaling. Regulates chondrocyte maturation and long bone development.
Could play an important role in morphogenesis and function of intestinal microvilli.
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).
Muscle contraction. Myosin is a protein that binds to F-actin and has ATPase activity that is activated by F-actin.
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).
Functions as a negative regulator of the PI3 kinase/PI3K activity associated with endosomal membranes. By modifying the phosphatidylinositol 3-phosphate/PtdInsP3 content of endosomal membranes may regulate endosome fusion, recycling, sorting and early to late endosome transport.
Belongs to the ribose 5-phosphate isomerase family.
Belongs to the DNA photolyase class-1 family.
Specifically hydrolyzes 7-methylguanosine monophosphate (m(7)GMP) to 7-methylguanosine and inorganic phosphate. The specific activity for m(7)GMP may protect cells against undesired salvage of m(7)GMP and its incorporation into nucleic acids. Also has weak activity for CMP. UMP and purine nucleotides are poor substrates (By similarity).
Expressed in a range of tissues including cerebrum, cerebellum, retina, cochlea, lung, liver and heart. Also expressed in the apical, medial and basal portions of the basillar papilla.
Cell adhesion, ankyrin-binding protein which may be involved in neurite extension, axonal guidance, synaptogenesis, myelination and neuron-glial cell interactions.
May be proteolytically cleaved at Arg-636.
There is one major 'early' isoform and multiple 'late' isoforms. Around 50 isoforms are found at different developmental stages.
Belongs to the protein-tyrosine phosphatase family. Receptor class 8 subfamily.
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. Downstream signaling adapters and intermediates may mediate positive and/or negative feedback regulation (By similarity).
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. 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 VAV1, PLCG1, PI-3-kinase, LCP2 and BLNK. 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. Activated upon BCR engagement, it phosphorylates and activates BLNK an adapter linking the activated BCR to downstream signaling adapters and effectors.
The SH2 domains mediate the interaction of SYK with the phosphorylated ITAM domains of transmembrane proteins.
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.
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 (By similarity).
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).
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).
Binds to actin and affects the structure of the cytoskeleton. At high concentrations, profilin prevents the polymerization of actin, whereas it enhances it at low concentrations. By binding to PIP2, it inhibits the formation of IP3 and DG.
Acts as a glycogen-targeting subunit for PP1 and regulates its activity. Activates glycogen synthase, reduces glycogen phosphorylase activity and limits glycogen breakdown.
Interacts with PPP1CC catalytic subunit of PP1 and associates with glycogen. Forms complexes with glycogen phosphorylase, glycogen synthase and phosphorylase kinase which is necessary for its regulation of PP1 activity.
The N-terminal region is required for binding to PP1, the central region is required for binding to glycogen and the C-terminal region is required for binding to glycogen phosphorylase glycogen synthase and phosphorylase kinase.
Belongs to the complex I NDUFS5 subunit family.
Mammalian complex I is composed of 45 different subunits. This is a component of the iron-sulfur (IP) fragment of the enzyme.
Homooligomer; probably required for localization to centrosomes.
Involved in the biogenesis of cilia (By similarity). Required for the recruitment of PLK1 to centrosomes and S phase progression (By similarity).
Belongs to the amiloride-sensitive sodium channel (TC 1.A.6) family. ASIC1 subfamily.
Channel opening involves a conformation change that affects primarily the extracellular domain and the second transmembrane helix and its orientation in the membrane. In the open state, the second transmembrane helix is nearly perpendicular to the plane of the membrane; in the desensitized state it is strongly tilted. Besides, the second transmembrane domain is discontinuously helical in the open state. The GAS motif of the selectivity filter is in an extended conformation, giving rise to a distinct kink in the polypeptide chain. A domain swap between subunits gives rise to a full-length transmembrane helix.
Homotrimer. Interacts with spider venom psalmotoxin 1 with a one to one stoichiometry. Interacts with the heterodimeric snake venom neurotoxin composed of MitTx-alpha and MitTx-beta.
Inhibited by the diuretic amiloride. Inhibited by Cs(1+) ions. Inhibited by the spider venom psalmotoxin-1; this locks the channel into its desensitized conformation. Channel activity is increased by the heterodimeric snake venom neurotoxin composed of MitTx-alpha and MitTx-beta; this slows channel closure and increases the magnitude of the steady-state current that is triggered by low pH.
Proton-gated sodium channel; it is activated by a drop of the extracellular pH and then becomes rapidly desensitized. Generates a biphasic current with a fast inactivating and a slow sustained phase. Has high selectivity for sodium ions and can also transport lithium ions with high efficiency. Can also transport potassium ions, but with lower efficiency. It is nearly impermeable to the larger rubidium and cesium ions.
Neuronal cell surface protein that may be involved in cell recognition and cell adhesion by forming intracellular junctions through binding to neuroligins. May play a role in formation or maintenance of synaptic junctions. May mediate intracellular signaling (By similarity). Plays a role in angiogenesis.
Belongs to the class I-like SAM-binding methyltransferase superfamily. RNA methyltransferase RlmE family. SPB1 subfamily.
Probable methyltransferase involved in the processing of the 34S pre-rRNA to 18S rRNA and in 40S ribosomal subunit formation.
RNA 2'-O-methyltransferase involved in the processing of the 34S pre-rRNA to 18S rRNA and in 40S ribosomal subunit formation.
Serum inducible, and cycloheximide superinducible.
Regulatory subunit of the ATP-dependent BRF-1 and BRF-5 ISWI chromatin remodeling complexes, which form ordered nucleosome arrays on chromatin and facilitate access to DNA during DNA-templated processes such as DNA replication, transcription, and repair (By similarity). Both complexes regulate the spacing of nucleosomes along the chromatin and have the ability to slide mononucleosomes to the center of a DNA template (By similarity). The BRF-1 ISWI chromatin remodeling complex has a lower ATP hydrolysis rate than the BRF-5 ISWI chromatin remodeling complex (By similarity). Chromatin reader protein (By similarity). Represses the expression of mitochondrial function-related genes, perhaps by transcriptional regulation (By similarity).
Key component of the cytosolic iron-sulfur protein assembly (CIA) complex, a multiprotein complex that mediates the incorporation of iron-sulfur cluster into apoproteins specifically involved in DNA metabolism and genomic integrity. In the CIA complex, MMS19 acts as an adapter between early-acting CIA components and a subset of cellular target iron-sulfur proteins.
Belongs to the sirtuin family. Class I subfamily.
Belongs to the glycosyl hydrolase 39 family.
Belongs to the eukaryotic ribosomal protein eS28 family.
Belongs to the cyclophilin-type PPIase family. PPIL2 subfamily.
Belongs to the calycin superfamily. Lipocalin family. Highly divergent.
Functions as transport protein in the blood stream.
Interacts with LRP2; LRP2 mediates APOM renal uptake and subsequent lysosomal degradation.
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.
Belongs to the ABC transporter superfamily. ABCC family. Conjugate transporter (TC 3.A.1.208) subfamily.
Interleukin-16 stimulates a migratory response in CD4+ lymphocytes, monocytes, and eosinophils. Primes CD4+ T-cells for IL-2 and IL-15 responsiveness. Also induces T-lymphocyte expression of interleukin 2 receptor. Ligand for CD4.
Non-covalent dimer of an alpha and a beta subunit. IL2R exists in 3 different forms: a high affinity dimer, an intermediate affinity monomer (beta subunit), and a low affinity monomer (alpha subunit). The high and intermediate affinity forms also associate with a gamma subunit.
Receptor for interleukin-2. The receptor is involved in the regulation of immune tolerance by controlling regulatory T cells (TREGs) activity. TREGs suppress the activation and expansion of autoreactive T-cells.
Accumulates steadily during G2 and is abruptly destroyed at mitosis.
Essential for the control of the cell cycle at the G2/M (mitosis) transition.
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.
Component of the NF-kappa-B RelB-p52 complex.
Constitutive processing is tightly suppressed by its C-terminal processing inhibitory domain, named PID, which contains the death domain.
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. 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 the kappa-B consensus sequence 5'-GGRNNYYCC-3', located in the enhancer region of genes involved in immune response and acute phase reactions. In concert with RELB, may play a role in the regulation of the circadian clock (By similarity).
NF-kappa-B p100 is one of the high-molecular-weight proteins complexed with the v-rel oncoprotein in transformed chicken spleen cells.
The C-terminus of p100 might be involved in cytoplasmic retention, inhibition of DNA-binding by p52 homodimers, and/or transcription activation.
The glycine-rich region (GRR) appears to be a critical element in the generation of p52.
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 (By similarity).
Belongs to the glycosyl hydrolase 2 family.
Extensively N-glycosylated. Contains a minor proportion of O-linked glycans.
Monomer. Forms large homooligomers. Interacts (via its cytoplasmic region) with HSPA8. Interacts with HSP90 in the lysosome lumen; this enhances LAMP2 stability (By similarity).
Plays an important role in chaperone-mediated autophagy, a process that mediates lysosomal degradation of proteins in response to various stresses and as part of the normal turnover of proteins with a long biological half-live. Functions by binding target proteins, such as GAPDH and MLLT11, and targeting them for lysosomal degradation (By similarity). Plays a role in lysosomal protein degradation in response to starvation (By similarity). Required for the fusion of autophagosomes with lysosomes during autophagy. Cells that lack LAMP2 express normal levels of VAMP8, but fail to accumulate STX17 on autophagosomes, which is the most likely explanation for the lack of fusion between autophagosomes and lysosomes. Required for normal degradation of the contents of autophagosomes. Required for efficient MHCII-mediated presentation of exogenous antigens via its function in lysosomal protein degradation; antigenic peptides generated by proteases in the endosomal/lysosomal compartment are captured by nascent MHCII subunits. Is not required for efficient MHCII-mediated presentation of endogenous antigens (By similarity).
Belongs to the adenomatous polyposis coli (APC) family.
Sodium-independent transporter of chloride and iodide.
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.
May play a role in anchoring the cytoskeleton to the plasma membrane.
Belongs to the peptidase C19 family. PAN2 subfamily.
Binds 2 metal cations per subunit in the catalytic exonuclease domain.
Catalytic 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 deadenlyation-dependent mRNA decaping and subsequent 5'-3' exonucleolytic degradation by XRN1.
Contains a pseudo-UCH domain. This ubiquitin C-terminal hydrolase (UCH)-like or ubiquitin specific protease (USP)-like domain is predicted to be catalytically inactive because it lacks the active site catalytic triad characteristic of thiol proteases, with residues at the equivalent structural positions that are incompatible with catalysis, and it cannot bind ubiquitin. It functions as a structural scaffold for intra- and intermolecular interactions in the complex.
Forms a heterotrimer with an asymmetric homodimer of the regulatory subunit PAN3 to form the poly(A)-nuclease (PAN) deadenylation complex.
Positively regulated by the regulatory subunit PAN3.
The linker, or PAN3 interaction domain (PID), between the WD40 repeats and the pseudo-UCH domain mediates interaction with PAN3.
Belongs to the mitochondrion-specific ribosomal protein mL51 family.
Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins (By similarity).
Expression is neuron-specific and found in cerebellum, forebrain, midbrain, tectum and spinal cord.
Is a key regulator of neurite extension through regulation of microtubule instabilily.
Binds calmodulin via its IQ domains. Interacts with APC2 (By similarity).
Required for normal renal development and establishment of left-right axis. Probably acts as a molecular switch between different Wnt signaling pathways. Inhibits the canonical Wnt pathway by targeting cytoplasmic disheveled for degradation by the ubiquitin-proteasome. This suggests that it is required in renal development to oppose the repression of terminal differentiation of tubular epithelial cells by Wnt signaling (By similarity).
The D-box (destruction box) mediate the interaction with APC proteins, and may act as a recognition signal for degradation via the ubiquitin-proteasome pathway.
Belongs to the ANT/ATPSC lysine N-methyltransferase family.
Belongs to the glycosyl hydrolase 13 family.
First detected in the lens placode at stage 11, when the head ectoderm makes contact with the optic vesicle. The expression remains restricted to the invaginating lens placode, and subsequently to the developing lens vesicle. In 8-day old embryo, almost exclusively expressed in lens with very weak expression in brain.
Forms homodimers or heterodimers. May interact (via leucine-zipper domain) with MAFB. May interact with FOS and JUN. Interacts with PCAF; this interaction impairs MAFA ubiquitination.
Transcription factor involved in transcription regulation during lens development, including that of crystallin and filensin/BFSP1 genes (PubMed:9525857). Binds to CRE-type MARE 5'-TGCTGACGTCAGCA-3' and TRE-type MARE 5'-TGCTGACTCAGCA-3' DNA sequences (PubMed:12970735).
Belongs to the class-I pyridoxal-phosphate-dependent aminotransferase family. Alanine aminotransferase subfamily.
Inhibited by the toxins okadaic acid, tautomycin and microcystin Leu-Arg. The phosphatase activity of the PPP1R15A-PP1 complex toward EIF2S1 is specifically inhibited by Salubrinal, a drug that protects cells from endoplasmic reticulum stress (By similarity).
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, PPP1R3B, PPP1R3C and PPP1R3D mediate binding to glycogen (By similarity).
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.
E3 ubiquitin-protein ligase that promotes the ubiquitination of different substrates.
Belongs to the inositol monophosphatase superfamily.
Mono-ADP-ribosyltransferase that mediates mono-ADP-ribosylation of target proteins and plays a key role in the response to DNA damage (PubMed:27530147). Mediates mono-ADP-ribosylation of glutamate, aspartate or lysine residues on target proteins (By similarity). In contrast to PARP1 and PARP2, it is not able to mediate poly-ADP-ribosylation (By similarity). 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 (By similarity). ADP-ribosylation follows DNA damage and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks (By similarity). 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 (By similarity). Associates with a number of DNA repair factors and is involved in the response to exogenous and endogenous DNA strand breaks (By similarity). Together with APLF, promotes the retention of the LIG4-XRCC4 complex on chromatin and accelerate DNA ligation during non-homologous end-joining (NHEJ) (By similarity). In addition to proteins, also able to ADP-ribosylate DNA: mediates DNA mono-ADP-ribosylation of DNA strand break termini via covalent addition of a single ADP-ribose moiety to a 5'- or 3'-terminal phosphate residues in DNA containing multiple strand breaks (By similarity).
The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription. TFIID recognizes and binds promoters with or without a TATA box via its subunit TBP, a TATA-box-binding protein, and promotes assembly of the pre-initiation complex (PIC). The TFIID complex consists of TBP and TBP-associated factors (TAFs).
Belongs to the argonaute family. Piwi subfamily.
Endoribonuclease that plays a central role in postnatal germ cells 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 govern the methylation and subsequent repression of transposons. Directly binds methylated piRNAs, a class of 24 to 30 nucleotide RNAs that are generated by a Dicer-independent mechanism and are primarily derived from transposons and other repeated sequence elements. Strongly prefers a uridine in the first position of their guide (g1U preference, also named 1U-bias). Besides their function in transposable elements repression, piRNAs are probably involved in other processes during meiosis such as translation regulation. Not involved in the piRNA amplification loop, also named ping-pong amplification cycle. Acts as an endoribonuclease that cleaves transposon messenger RNAs (By similarity).
Methylated on arginine residues; required for the interaction with Tudor domain-containing protein and subsequent localization to the meiotic nuage, also named P granule.
The PAZ domain specifically recognizes binds the 2'-O-methylated 3'-end of piRNAs. The MID region is required for recognition of uridine in the first position of piRNAs (g1U preference, also named 1U-bias).
Belongs to the complex I NDUFA5 subunit family.
Functions as a dosage-dependent inducer in mitotic control. Tyrosine protein phosphatase required for progression of the cell cycle.
Belongs to the acetyltransferase family. GCN5 subfamily.
Belongs to the proteasome subunit S2 family.
Binds to the intracellular domain of tumor necrosis factor type 1 receptor. The binding domain of TRAP1 and TRAP2 resides outside the death domain of TNFR1.
Belongs to the multiprotein complex Integrator. Component of the SOSS complex, composed of SOSS-B (SOSS-B1/NABP2 or SOSS-B2/NABP1), SOSS-A/INTS3 and SOSS-C/INIP (By similarity).
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. Required for efficient homologous recombination-dependent repair of double-strand breaks (DSBs) (By similarity).
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. Required for efficient homologous recombination-dependent repair of double-strand breaks (DSBs).
Functions together with ADGRA2 to enable brain endothelial cells to selectively respond to Wnt7 signals (WNT7A or WNT7B) (By similarity). Plays a key role in Wnt7-specific responses: required for central nervous system (CNS) angiogenesis and blood-brain barrier regulation (By similarity). Acts as a Wnt7-specific coactivator of canonical Wnt signaling by decoding Wnt ligands: acts by interacting specifically with the disordered linker region of Wnt7, thereby conferring ligand selectivity for Wnt7. ADGRA2 is then required to deliver RECK-bound Wnt7 to frizzled by assembling a higher-order RECK-ADGRA2-Fzd-LRP5-LRP6 complex. Also acts as a serine protease inhibitor (By similarity).
Interacts (via knot repeats) with WNT7A (via disordered linker region); the interaction is direct (By similarity). Interacts (via knot repeats) with WNT7B (via disordered linker region); the interaction is direct (By similarity). Interacts with ADGRA2; the interaction is direct (By similarity).
Localizes to the plasma membrane via its GPI-anchor (PubMed:23329048). Released from the plasma membrane following cleavage of the GPI-anchor by GDPD5/GPE2 (PubMed:23329048).
The Kazal-like domains mediate the serine protease inhibitor activity.
First detected at embryonic day 5 (5 dpc) in both apical and basolateral membranes. By 14 dpc the distribution is restricted to the basolateral surface of retinal pigment epithelium. Restricted to the basolateral membrane in adult.
Probable retinal pigment epithelium (RPE)-specific proton-coupled L-lactate transporter (Probable). May facilitate transport of lactate and H(+) out of the retina and could therefore play a role in pH and ion homeostasis of the outer retina (By similarity).
The two basolateral sorting signals (BSS) are required to direct SLC16A8 to the basolateral membrane.
May be involved in modulating alternative pre-mRNA splicing.
Plays a role in the recruitment of the exosome to pre-rRNA to mediate the 3'-5' end processing of the 5.8S rRNA.
Myristoylated in vitro; myristoylation is not essential for protein targeting to Golgi compartment.
Necessary for correct organization of Golgi apparatus.
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). The elongator complex catalyzes formation of carboxymethyluridine in the wobble base at position 34 in tRNAs.
First detected in the corneal epithelium and lens epithelium at 6.5 dpc and 12 dpc. At 12 dpc is present in the corneal endothelium and the limbal region. After 16 dpc and at hatching (H1), expression persisted in multiple anterior segment tissues, including the lens epithelium, the corneal endothelium, the iris, and the trabecular meshwork (at protein level).
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 (PubMed:12569128). 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 AES and TLE4-dependent manner (PubMed:12050133). 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. Plays a role in eye development by suppressing WNT1 expression and in dorsal-ventral patterning by repressing BMP signaling pathway (By similarity).
Belongs to the ATP-dependent DNA ligase family.
DNA ligase involved in DNA non-homologous end joining (NHEJ); required for double-strand break (DSB) repair and V(D)J recombination. Catalyzes the NHEJ ligation step of the broken DNA during DSB repair by resealing the DNA breaks after the gap filling is completed. Joins single-strand breaks in a double-stranded polydeoxynucleotide in an ATP-dependent reaction. LIG4 is mechanistically flexible: it can ligate nicks as well as compatible DNA overhangs alone, while in the presence of XRCC4, it can ligate ends with 2-nucleotides (nt) microhomology and 1-nt gaps. Forms a subcomplex with XRCC4; the LIG4-XRCC4 subcomplex is responsible for the NHEJ ligation step and XRCC4 enhances the joining activity of LIG4.
Interacts with XRCC4; the LIG4-XRCC4 subcomplex has a 1:2 stoichiometry (By similarity). Component of the core long-range non-homologous end joining (NHEJ) complex (also named DNA-PK complex) composed of PRKDC, LIG4, XRCC4, XRCC6/Ku70, XRCC5/Ku86 and NHEJ1/XLF (By similarity). Additional component of the NHEJ complex includes PAXX (By similarity). Following autophosphorylation, PRKDC dissociates from DNA, leading to formation of the short-range NHEJ complex, composed of LIG4, XRCC4, XRCC6/Ku70, XRCC5/Ku86 and NHEJ1/XLF (By similarity).
Belongs to the poly(A) polymerase family.
Binds 2 magnesium ions. Also active with manganese.
Polymerase that creates the 3'-poly(A) tail of mRNA's.
Interacts with multiple activated proteins of the tyrosine kinase signaling pathway including IGF1 receptor, insulin receptor and EPO receptor. Binding to JAK is mediated through the KIR and SH2 domains to a phosphorylated tyrosine residue within the JAK JH1 domain. Binds specific activated tyrosine residues of the leptin, EPO and gp130 receptors.
Phosphorylated on tyrosine residues after stimulation by the cytokines, IL-2, EPO or IGF1.
SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. SOCS3 is involved in negative regulation of cytokines that signal through the JAK/STAT pathway. Inhibits cytokine signal transduction by binding to tyrosine kinase receptors including IL6ST/gp130, LIF, erythropoietin, insulin, IL12, GCSF and leptin receptors. Binding to JAK2 inhibits its kinase activity and regulates IL6 signaling. Suppresses fetal liver erythropoiesis. Regulates onset and maintenance of allergic responses mediated by T-helper type 2 cells (By similarity). 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 and subsequent proteasomal degradation of target proteins (By similarity).
The ESS and SH2 domains are required for JAK phosphotyrosine binding. Further interaction with the KIR domain is necessary for signal and kinase inhibition.
The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes.
During embryonic development, expressed preferentially in epiblastic cells and germ cells. In pre-streak embryos, detected in the whole epiblast, but not in the forming hypoblast (stages XI through XIII) (at protein level). As the primitive streak starts to form, disappears from the primitive streak epiblast, but still expressed throughout the area pellucida epiblast (stage XIV -> 3+). At the end of gastrulation (stage 4+), quickly decreases in the epiblast and persists in a crescent anterior to the emerging head process (stages 4+ through 6). At stage 5, strongly expressed in some of the cells in the germinal crescent, probably corresponding primordial germ cells. At stage 7 (neurula stage), undetectable in differentiated cells (at protein level). As the neural plate forms (stages 6-8), expression in the epiblast is restricted to the anterior neural plate. At stage 33, still expressed in germ cells. At stages 42-43, expressed in gonads, as well as in brain, kidney and heart, but at much lower levels than in proliferating embryonic stem cells.
Strongly down-regulated during embryonic stem cell differentiation, induced either by retinoic acid treatment, or by cell adhesion prevention leading to embryoid body formation.
Transcription factor required for the maintenance of pluripotency and self-renewal of embryonic stem cells.
Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins.
Plays a role in mitochondrial aerobic respiration. Regulates mitochondrial organization and fission.
Calcium-dependent cell-adhesion protein. Required for inner ear neuroepithelial cell elaboration and cochlear function. Probably involved in the maintenance of normal retinal function (By similarity).
In the utricle, localizes to the distal region of the kinocilium and near the tips of the stereocilia.
May play a role in neurite outgrowth and neurogenesis.
Belongs to the universal ribosomal protein uS10 family.
Arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and symmetrical dimethylarginine (sDMA).
Belongs to the class I-like SAM-binding methyltransferase superfamily.
ATPase component of the INO80 complex which remodels chromatin by shifting nucleosomes and is involved in DNA repair.
Component of the INO80 chromatin-remodeling complex.
The DBINO region is involved in binding to DNA.
S-adenosyl-L-methionine-dependent methyltransferase that mediates N(3)-methylcytidine modification of residue 32 of the tRNA anticodon loop of tRNA(Thr)(UGU) and tRNA(Arg)(CCU). N(3)-methylcytidine methylation by METTL2 requires the N6-threonylcarbamoylation of tRNA (t6A37) by the EKC/KEOPS complex as prerequisite.
Detected at stage 15 in the presumptive dorsal-limb ectoderm. At stages 16-18 expression is restricted to the dorsal side with higher concentration at the dorsoventral boundary and later in the AER. Expression remains restricted to the dorsal ectoderm and the AER until stages 22-24 when it starts to fade in the dorsal ectoderm, but remains in the AER until the last stage examined (27).
Glycosyltransferase that initiates the elongation of O-linked fucose residues attached to EGF-like repeats in the extracellular domain of Notch molecules (By similarity). Plays an important role in limb outgrowth, it directs the formation and positioning of the apical ectodermal ridge (AER), one of the key organizer centers of vertebrate limb development (PubMed:9121551, PubMed:9121552).
Has a glutathione-disulfide oxidoreductase activity in the presence of NADPH and glutathione reductase. Reduces low molecular weight disulfides and proteins.
Belongs to the adenylate kinase family. AK6 subfamily.
Broad-specificity nucleoside monophosphate (NMP) kinase that catalyzes the reversible transfer of the terminal phosphate group between nucleoside triphosphates and monophosphates. May have a role in nuclear energy homeostasis. Has also ATPase activity. May be involved in regulation of Cajal body (CB) formation.
Monomer and homodimer. Interacts with COIL (via C-terminus).
Component of the Sin3/HDAC corepressor complex at least composed of BRMS1, BRMS1L, ING2, SAP30, SAP30L, HDAC1. Found in a complex composed of at least SINHCAF, SIN3A, HDAC1, SAP30, RBBP4, OGT and TET1.
Subunit of the Sin3 deacetylase complex (Sin3/HDAC), this subunit is important for the repression of genes encoding components of the TGF-beta signaling pathway. Core component of a SIN3A complex (composed of at least SINHCAF, SIN3A, HDAC1, SAP30, RBBP4, OGT and TET1) present in embryonic stem (ES) cells and is essential to maintain the complex on chromatin.
Belongs to the twisted gastrulation protein family.
Interacts with CHRD and BMP4. This interaction enhances CHRD/BMP4 complex formation. Interacts with BMP7 (By similarity).
May be involved in dorsoventral axis formation. Seems to antagonize BMP signaling by forming ternary complexes with CHRD and BMPs, thereby preventing BMPs from binding to their receptors. In addition to the anti-BMP function, also has pro-BMP activity, partly mediated by cleavage and degradation of CHRD, which releases BMPs from ternary complexes. May be an important modulator of BMP-regulated cartilage development and chondrocyte differentiation. May play a role in thymocyte development (By similarity).
The N-terminal domain is sufficient to interact with BMP4.
Component of the multisubunit TRAPP (transport protein particle) complex.
Involved in endoplasmic reticulum to Golgi apparatus trafficking at a very early stage.
Component of the CENPA-HI complex, a centromeric complex involved in assembly of kinetochore proteins, mitotic progression and chromosome segregation. Required for the localization of CENPC but not CENPA to the centromere. It however may be involved in incorporation of newly synthesized CENPA into centromeres via its interaction with the CENPA-NAC complex.
Component of the CENPA-HI complex, at least composed of CENPH, CENPI, CENPK, CENPL, CENPM, CENPO and CENPP. Interacts with NDC80.
Interacts with SAE2 and UBE2I. Covalently attached to a number of proteins (By similarity).
Polymeric chains can be formed through Lys-11 cross-linking.
Ubiquitin-like protein that can be covalently attached to proteins as a monomer or as 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 an E3 ligase such as PIAS1-4. 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. Polymeric SUMO2 chains are also susceptible to polyubiquitination which functions as a signal for proteasomal degradation of modified proteins (By similarity).
Belongs to the complex I 23 kDa subunit family.
Homotetramer. Interacts with HSC70 as well as DNAJ homologs and HSP90 (By similarity).
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).
Prenyltransferase that mediates the formation of menaquinone-4 (MK-4) and coenzyme Q10. MK-4 is a vitamin K2 isoform required for endothelial cell development. Mediates the conversion of phylloquinone (PK) into MK-4, probably by cleaving the side chain of phylloquinone (PK) to release 2-methyl-1,4-naphthoquinone (menadione; K3) and then prenylating it with geranylgeranyl pyrophosphate (GGPP) to form MK-4. Also plays a role in cardiovascular development independently of MK-4 biosynthesis, by acting as a coenzyme Q10 biosynthetic enzyme: coenzyme Q10, also named ubiquinone, plays an important antioxidant role in the cardiovascular system. Mediates biosynthesis of coenzyme Q10 in the Golgi membrane, leading to protect cardiovascular tissues from NOS3/eNOS-dependent oxidative stress.
Belongs to the eukaryotic ribosomal protein eS25 family.
Required for vesicular transport between the endoplasmic reticulum and the Golgi apparatus.
Belongs to the metallophosphoesterase superfamily. MPPE1 family.
Metallophosphoesterase required for transport of GPI-anchor proteins from the endoplasmic reticulum to the Golgi. Acts in lipid remodeling steps of GPI-anchor maturation by mediating the removal of a side-chain ethanolamine-phosphate (EtNP) from the second Man (Man2) of the GPI intermediate, an essential step for efficient transport of GPI-anchor proteins (By similarity).
Active NF-kappa-B is a heterodimer of an about 50 kDa DNA-binding subunit and the weak DNA-binding subunit p65. Two heterodimers might form a labile tetramer.
P105 is the precursor of the p50 subunit of the nuclear factor NF-kappa-B, which binds to the kappa-B consensus sequence 5'-GGRNNYYCC-3', located in the enhancer region of genes involved in immune response and acute phase reactions. The precursor protein itself does not bind to DNA.
S-nitrosylation of Cys-66 affects DNA binding.
The C-terminus of p105 might be involved in cytoplasmic retention, inhibition of DNA-binding by p50 homodimers, and/or transcription activation.
While translation occurs, the particular unfolded structure after the GRR repeat promotes the generation of p50 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 (By similarity).
Involved in the lipid remodeling steps of GPI-anchor maturation. Required for stable expression of GPI-anchored proteins at the cell surface.
Belongs to the type-B carboxylesterase/lipase family.
Belongs to the HAD-like hydrolase superfamily. EYA family.
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).
This protein binds tightly to and inhibits a variety of thiol proteases including ficin, papain, and cathepsins B, C, H, and L. Although isolated from egg white, it is also present in serum.
Binds to the receptor tyrosine kinases EPHA3, EPHA4 and EPHA5. Interacts with EPHA8; activates EPHA8 (By similarity).
Cell surface GPI-bound 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. With the EPHA2 receptor may play a role in bone remodeling through regulation of osteoclastogenesis and osteoblastogenesis (By similarity).
Expressed in a gradient across the tectum being more strongly expressed at the posterior pole.
Belongs to the concentrative nucleoside transporter (CNT) (TC 2.A.41) family.
Oxidation of Met-45 and Met-48 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 (By similarity).
Belongs to the phosphohexose mutase family.
Hepatic lectin is a membrane receptor protein that recognizes and binds exposed N-acetylglucosamine moieties of plasma glycoproteins, thus mediating their clearance (from the circulation) and endocytosis.
Some or all of the cysteines are involved in disulfide bonds.
Belongs to the dus family. Dus3 subfamily.
Belongs to the replication factor A protein 2 family.
Homodimer; disulfide-linked. Interacts with PDGFRB homodimers, and with heterodimers formed by PDGFRA and PDGFRB.
Plays a critical role in cardiac development. Acts as a key epigenetic regulator of gene expression during cardiac development via its dual activities as a methyltransferase and negative regulator of HDAC1.
Component of the 60-80S U3 small nucleolar ribonucleoprotein (U3 snoRNP). Required for the early cleavages during pre-18S ribosomal RNA processing.
Belongs to the centaurin gamma-like family.
Potent stimulator of insulin secretion and relatively poor inhibitor of gastric acid secretion.
Part of a complex that contains SEC61, SEC62 and SEC63.
Axon-associated cell adhesion molecule (AxCAM) which promotes neurite outgrowth by interaction with the AxCAM L1 (G4) of neuritic membrane. Contributes to the organization of axonal domains at nodes of Ranvier (By similarity).
Catalyzes the conversion of 4-hydroxyphenylpyruvic acid to homogentisic acid, one of the steps in tyrosine catabolism.
In the C-terminal section; belongs to the AIR carboxylase family. Class II subfamily.
In the N-terminal section; belongs to the SAICAR synthetase family.
Belongs to the mitochondrion-specific ribosomal protein mL54 family.
Belongs to the glucosamine/galactosamine-6-phosphate isomerase family.
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).
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 (By similarity). 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). 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 (By similarity). May play a role in neurite development and synaptic connectivity (By similarity).
Component of the MRN complex composed of two heterodimers RAD50/MRE11 associated with a single NBN. Component of the BASC complex, at least composed of BRCA1, MSH2, MSH6, MLH1, ATM, BLM, RAD50, MRE11 and NBN. Interacts with DCLRE1C/Artemis (By similarity).
Component of the MRN complex, which plays a central role in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity and meiosis. The complex possesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity, which are provided by MRE11. RAD50 may be required to bind DNA ends and hold them in close proximity. This could facilitate searches for short or long regions of sequence homology in the recombining DNA templates, and may also stimulate the activity of DNA ligases and/or restrict the nuclease activity of MRE11 to prevent nucleolytic degradation past a given point. The complex may also be required for DNA damage signaling via activation of the ATM kinase. In telomeres the MRN complex may modulate t-loop formation (By similarity).
Involved in DNA double-strand break repair (DSBR). Possesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity. Also involved in meiotic DSB processing.
Belongs to the V-ATPase proteolipid subunit family.
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.
Probable core 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. In the ESCRT-III complex, it probably serves as an acceptor for the ESCRT-II complex on endosomal membranes (By similarity).
Belongs to the methyltransferase superfamily. L-isoaspartyl/D-aspartyl protein methyltransferase family.
Initiates the repair of damaged proteins by catalyzing methyl esterification of L-isoaspartyl and D-aspartyl residues produced by spontaneous isomerization and racemization of L-aspartyl and L-asparaginyl residues in aging peptides and proteins.
Forms a well-packed pentamer with an overall cylindrical shape. The inner core of the pentamer is formed with the second transmembrane region and the second coiled-coil region: while the transmembrane regions pack into a five-helix bundle having a largely polar pore across the membrane, the coiled-coil outside the membrane forms a pentamer with a hydrophobic core. The inner core is wrapped by the first transmembrane region through contacts between the first and the second transmembrane regions. The second transmembrane is followed by the inner juxtamembrane region (IJMH) that orients at a wide angle relative to the second transmembrane. The two core domains are held together on the periphery by the outer juxtamembrane helix (OJMH).
Mitochondrial inner membrane calcium uniporter that mediates calcium uptake into mitochondria. Constitutes a pore-forming and calcium-conducting subunit. Mitochondrial calcium homeostasis plays key roles in cellular physiology and regulates cell bioenergetics, cytoplasmic calcium signals and activation of cell death pathways.
Interacts with the CDK4 and CDK6 protein kinases to form a serine/threonine kinase holoenzyme complex. The cyclin subunit imparts substrate specificity to the complex.
Phosphorylation at Thr-282 by MAP kinases is required for ubiquitination and degradation by the DCX(AMBRA1) complex.
Regulatory component of the cyclin D2-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase. Hypophosphorylates RB1 in early G(1) phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals.
Ubiquitinated by the DCX(AMBRA1) complex during the transition from G1 to S cell phase, leading to its degradation: ubiquitination is dependent on Thr-282 phosphorylation. The DCX(AMBRA1) complex represents the major regulator of CCND2 stability during the G1/S transition.
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 such as the reorganization of the actin cytoskeleton and in cell motility. Binds 2 calcium ions. Calcium binding is cooperative (By similarity).
NADH-cytochrome b5 reductases are involved in desaturation and elongation of fatty acids, cholesterol biosynthesis and drug metabolism.
Facilitative glucose transporter, which is responsible for constitutive or basal glucose uptake. Has a very broad substrate specificity; can transport a wide range of aldoses including both pentoses and hexoses. Most important energy carrier of the brain: present at the blood-brain barrier and assures the energy-independent, facilitative transport of glucose into the brain (By similarity). In association with BSG and NXNL1, promotes retinal cone survival by increasing glucose uptake into photoreceptors (PubMed:25957687).
Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosis, and in the regulation of embryonic development. Required for normal embryonic patterning, limb bud development, lung morphogenesis, osteogenesis and skin development. Plays an essential role in the regulation of osteoblast differentiation, proliferation and apoptosis, and is required for normal skeleton development. Promotes cell proliferation in keratinocytes and immature osteoblasts, but promotes apoptosis in differentiated osteoblasts. Phosphorylates PLCG1, FRS2 and PAK4. 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. FGFR2 signaling is down-regulated by ubiquitination, internalization and degradation. Mutations that lead to constitutive kinase activation or impair normal FGFR2 maturation, internalization and degradation lead to aberrant signaling. Over-expressed FGFR2 promotes activation of STAT1 (By similarity).
Ubiquitinated. FGFR2 is rapidly ubiquitinated after autophosphorylation, leading to internalization and degradation. Subject to degradation both in lysosomes and by the proteasome (By similarity).
Regulates NF-kappa-B transcription factor activity. Promotes growth of cardiomyocytes, but not cardiomyocyte proliferation. Promotes cardiac muscle hypertrophy. Plays a role in the regulation of the growth of actin filaments. Inhibits the activity of the F-actin-capping protein complex (By similarity).
Belongs to the universal ribosomal protein uL3 family.
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.
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase. Promotes cell proliferation.
Detected in bone marrow, liver and lung.
May bind bacterial lipopolysaccharide (LPS). May have antimicrobial activity and play a role in the innate immune response (By similarity).
Belongs to the diacylglycerol acyltransferase family.
Autophosphorylated on tyrosine residues. KITLG/SCF binding promotes autophosphorylation. Phosphorylated tyrosine residues are important for interaction with specific binding partners (By similarity).
High in the brain and testes and also present in the bursa of Fabricus, heart, kidney, lung, spleen thymus and ovary.
Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. In response to KITLG/SCF binding, KIT can activate several signaling pathways. Promotes phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, and subsequent activation of the kinase AKT1. Activated KIT also transmits signals via GRB2 and activation of RAS, RAF1 and the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. Promotes activation of STAT family members STAT1, STAT3, STAT5A and STAT5B. KIT promotes activation of PLCG1, leading to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. KIT signaling is modulated by protein phosphatases, and by rapid internalization and degradation of the receptor (By similarity).
Ubiquitinated. KIT is rapidly ubiquitinated after autophosphorylation induced by KITLG/SCF binding, leading to internalization and degradation.
ATP-binding RNA helicase involved in translation initiation. Part of the 43S pre-initiation complex that is required for efficient initiation on mRNAs of higher eukaryotes with structured 5'-UTRs by promoting efficient NTPase-dependent 48S complex formation. Specifically binds to the 40S ribosome near the mRNA entrance. Does not possess a processive helicase activity.
Belongs to the DEAD box helicase family. DEAH subfamily.
Part of the 43S pre-initiation complex (PIC).
Probably involved in signal transduction, in the nervous system. Required for the spatial learning process. May also be involved in neurite outgrowth (By similarity).
Belongs to the chloride channel (TC 2.A.49) family. ClC-2/CLCN2 subfamily.
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.
Belongs to the neutral sphingomyelinase family.
Acetylated by histone acetyltransferase p300, deacetylated by HDACs. Acetylation/deacetylation states regulate transcriptional activity. Acetylation appears to activate transcription. Alternate sumoylation and acetylation at Lys-541 also control transcriptional activity.
Interacts with HDAC1 and HDAC2; the interaction deacetylates SP3 and regulates its transcriptional activity (By similarity). Interacts with v-Jun.
Sumoylation represses transcriptional activity. Lys-541 is the major site. Sumoylation at this site promotes nuclear localization to the nuclear periphery, nuclear dots and PML nuclear bodies. Alternate sumoylation and acetylation at Lys-541 also control transcriptional activity (By similarity).
Transcriptional factor that can act as an activator or repressor depending on post-translational modifications. Binds to GT and GC boxes promoter elements. Competes with SP1 for the GC-box promoters. Weak activator of transcription (By similarity). Required for activation of SPARC transcription.
Interacts with GNAI1 and GNAQ (By similarity). Interacts with GNAZ and GNAI2. Forms a complex with mu-opioid receptors and G(alpha)z/i2 subunits, including GNAZ and GNAI2; the formation of this complex results in mu-opioid receptor desensitization (By similarity).
N- and O-glycosylated in synapsomal membranes.
Regulates G protein-coupled receptor signaling cascades, including signaling via muscarinic acetylcholine receptor CHRM2 and dopamine receptor DRD2 (By similarity). 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 GNAZ and GNAI2 subunits, accelerates their GTPase activity and regulates their signaling activities. Negatively regulates mu-opioid receptor-mediated activation of the G-proteins (By similarity).
Serine phosphorylated in synapsomal membranes.
Sumoylated with SUMO1 and SUM02 in synaptosomes. The sumoylated forms act as a scaffold for sequestering mu-opioid receptor-activated G(alpha) subunits.
Belongs to the prefoldin subunit alpha family.
Belongs to the universal ribosomal protein uL10 family.
Belongs to the methyltransferase superfamily. RsmH family.
Exclusively expressed in the cochlea of the inner ear, where it is found in cells of the tegmentum vasculosum, cuboidal cells, supporting cells and clear cells.
Specifically expressed at the late developmental stages in the cochlea.
Belongs to the Rieske iron-sulfur protein family.
Binds 1 [2Fe-2S] cluster per subunit. Fe-S cluster delivery to the Rieske protein is mediated by components of the iron sulfur (Fe-S) cluster assembly machinery that reside in the mitochondrial matrix (including HSC20 and LYRM7) (By similarity).
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. 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)) (By similarity). Incorporation of the Rieske protein UQCRFS1 is the penultimate step in complex III assembly. Interacts with TTC19, which is involved in the clearance of UQCRFS1 fragments (By similarity).
Component of the ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII). Subunit 9 corresponds to the mitochondrial targeting sequence (MTS) of Rieske protein UQCRFS1. It is retained after processing and incorporated inside complex III, where it remains bound to the complex and localizes between the 2 core subunits UQCRC1/QCR1 and UQCRC2/QCR2.
Component of the ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII). UQCRFS1 undergoes proteolytic processing once it is incorporated in the complex III dimer. One of the fragments, called subunit 9, corresponds to its mitochondrial targeting sequence (MTS) (By similarity). The proteolytic processing is necessary for the correct insertion of UQCRFS1 in the complex III dimer, but the persistence of UQCRFS1-derived fragments may prevent newly imported UQCRFS1 to be processed and assembled into complex III and is detrimental for the complex III structure and function (By similarity).
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. The Rieske protein is a catalytic core subunit containing a [2Fe-2S] iron-sulfur cluster. It cycles between 2 conformational states during catalysis to transfer electrons from the quinol bound in the Q(0) site in cytochrome b to cytochrome c1 (By similarity). Incorporation of UQCRFS1 is the penultimate step in complex III assembly (By similarity).
Proteolytic processing is necessary for the correct insertion of UQCRFS1 in the complex III dimer. Several fragments are generated during UQCRFS1 insertion, most probably due to the endogenous matrix-processing peptidase (MPP) activity of the 2 core protein subunits UQCRC1/QCR1 and UQCRC2/QCR2, which are homologous to the 2 mitochondrial-processing peptidase (MPP) subunits beta-MPP and alpha-MPP respectively. The action of the protease is also necessary for the clearance of the UQCRFS1 fragments.
Several peptides are generated during UQCRFS1 insertion. According to some authors, the identification of the transit peptide as the subunit 9, does not necessary imply that it must be considered as a structural subunit of the complex III dimer as additional fragments from UQCRFS1 are also present.
The Rieske protein is a high potential 2Fe-2S protein.
Belongs to the DEAD box helicase family. DEAH subfamily. DDX11/CHL1 sub-subfamily.
Substrate recognition and binding subunit of the essential mitochondrial processing protease (MPP), which cleaves the mitochondrial sequence off newly imported precursors proteins.
Belongs to the Mediator complex subunit 17 family.
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 (By similarity).
Enhances all basic T-cell responses to a foreign antigen, namely proliferation, secretion of lymphokines, up-regulation of molecules that mediate cell-cell interaction, and effective help for antibody secretion by B-cells. Essential both for efficient interaction between T and B-cells and for normal antibody responses to T-cell dependent antigens. Does not up-regulate the production of interleukin-2, but superinduces the synthesis of interleukin-10. Prevents the apoptosis of pre-activated T-cells. Plays a critical role in CD40-mediated class switching of immunoglobin isotypes.
Belongs to the archaeal Rpo6/eukaryotic RPB6 RNA polymerase subunit family.
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.
Belongs to the bacterial ribosomal protein bL28 family.
Plays a role in cytoskeletal rearrangements during the late wrapping and/or compaction phases of myelinogenesis as well as in maintenance and stability of myelin sheath in the adult. May play an important role in late-stage oligodendroglia maturation, myelin/Ranvier node formation during CNS development, and in the maintenance and plasticity of related structures in the mature CNS.
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 (By similarity). Acts as a MYO6/Myosin VI adapter protein that targets MYO6 to endocytic structures (By similarity). Together with MYO6, required for autophagosomal delivery of endocytic cargo, the maturation of autophagosomes and their fusion with lysosomes (By similarity). MYO6 links TOM1 with autophagy receptors, such as TAX1BP1; CALCOCO2/NDP52 and OPTN (By similarity). Binds to polyubiquitinated proteins via its GAT domain (By similarity). In a complex with TOLLIP, recruits ubiquitin-conjugated proteins onto early endosomes (By similarity). The Tom1-Tollip complex may regulate endosomal trafficking by linking polyubiquitinated proteins to clathrin (By similarity). Mediates clathrin recruitment to early endosomes (By similarity). 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 (By similarity). Acts as a phosphatidylinositol 5-phosphate (PtdIns(5)P) effector by binding to PtdIns(5)P, thereby regulating endosomal maturation (By similarity). PtdIns(5)P-dependent recruitment to signaling endosomes may block endosomal maturation (By similarity). Also inhibits Toll-like receptor (TLR) signaling and participates in immune receptor recycling (By similarity).
Expression is cooperatively activated by MYB and CEBPG.
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 (By similarity). Interacts (via GAT domain and the C-terminal part of the VHS domain) with UBC/ubiquitin (By similarity). Interacts (via clathrin box and C-terminus) with clathrin heavy chain (By similarity). Interacts with MYO6 (By similarity).
The GAT domain and the VHS domain are required for the interaction with polyubiquitinated proteins.
The VHS domain binds to phosphatidylinositol monophosphates (By similarity). The KRKK motif within the VHS domain is required for binding to phosphatidylinositol monophosphates, with a preference for phosphatidylinositol 5-phosphate (PtdIns(5)P) (By similarity).
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.
Belongs to the eIF-2B alpha/beta/delta subunits family.
May function in the transport of nucleosides and/or nucleoside derivatives between the cytosol and the lumen of an intracellular membrane-bound compartment.
The C-terminal domain is necessary for retention within intracellular membranes.
Belongs to the carnosine N-methyltransferase family.
Homodimer. Each monomer accommodates one molecule of carnosine in its active pocket, precisely anchoring the histidine imidazole ring such that only N1 is exposed and deprotonated for methylation.
N-methyltransferase that catalyzes the formation of anserine (beta-alanyl-N(Pi)-methyl-L-histidine) from carnosine. Anserine, a methylated derivative of carnosine (beta-alanyl-L-histidine), is an abundant constituent of vertebrate skeletal muscles. Also methylates other L-histidine-containing di- and tripeptides such as Gly-Gly-His, Gly-His and homocarnosine (GABA-His).
The Gly-Xaa-Gly-Xaa-Gly (GXGXG) motif binds the adenosyl part of S-adenosyl-L-methionine.
The carnosine-binding region forms hydrophobic and hydrogen bonds with carnosine, defining a flipping orientation of the imidazole ring so that N1 is present next to S-adenosyl-L-methionine for methylation.
Two different proteins belonging to two different protein families are able to mediate carnosine N-methyltransferase activity in chicken. This protein, which is conserved from human to yeast, and another protein (AC U3NEE3), which is not conserved in mammals.
Expressed in v-myb-transformed myelomonocytic cells.
Required for oligodendrocyte and motor neuron specification in the spinal cord.
Belongs to the helicase family. RAD25/XPB subfamily.
May form trimers with the co-SMAD SMAD4.
Transcriptional modulator activated by BMP (bone morphogenetic proteins) type 1 receptor kinase. SMAD5 is a receptor-regulated SMAD (R-SMAD) (By similarity).
Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A6 subfamily.
Belongs to the proteasome subunit p27 family.
Interacts with SARA (SMAD anchor for receptor activation); form trimers with another SMAD3 and the co-SMAD SMAD4.
Phosphorylated on serine by TGF-beta and activin type 1 receptor kinases.
The MH2 domain is sufficient to carry protein nuclear export.
Transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinase. SMAD3 is a receptor-regulated SMAD (R-SMAD) (By similarity).
Belongs to the XRCC4-XLF family. XLF subfamily.
Belongs to the uracil-DNA glycosylase (UDG) superfamily. UNG family.
Excises uracil residues from the DNA which can arise as a result of misincorporation of dUMP residues by DNA polymerase or due to deamination of cytosine.
Required for recruitment of CENPA to centromeres and normal chromosome segregation during mitosis.
ATP-dependent microtubule severing protein that specifically recognizes and cuts microtubules that are polyglutamylated. Preferentially recognizes and acts on microtubules decorated with short polyglutamate tails: severing activity increases as the number of glutamates per tubulin rises from one to eight, but decreases beyond this glutamylation threshold. Microtubule severing promotes reorganization of cellular microtubule arrays and the release of microtubules from the centrosome following nucleation. Required for membrane traffic from the endoplasmic reticulum (ER) to the Golgi and for completion of the abscission stage of cytokinesis. Also plays a role in axon growth and the formation of axonal branches.
Belongs to the AAA ATPase family. Spastin subfamily.
Homohexamer. The homohexamer is stabilized by ATP-binding. The homohexamer may adopt a ring conformation through which microtubules pass prior to being severed. Interacts with microtubules.
Catalyzes the phosphorylation of phosphatidylinositol 5-phosphate (PtdIns5P) on the fourth hydroxyl of the myo-inositol ring, to form phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). Has both ATP- and GTP-dependent kinase activities.
In rod outer segments, activated by light.
Phosphorylated in tyrosines. Phosphorylation is induced by light and increases kinase activity.
Belongs to the peroxisomal membrane protein PXMP2/4 family.
Belongs to the nuclear hormone receptor family. NR0 subfamily.
Expression increases in the spinal cord from 4 dpc to 16 dpc, with the highest level detected between 12 dpc and 16 dpc. Expression rapidly decreases after hatching.
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. Required for normal skin morphogenesis during embryonic development. Plays an important role in wound healing, in angiogenesis and blood vessel development (By similarity).
Homodimer; disulfide-linked. Interacts with PDGFRA homodimers, and with heterodimers formed by PDGFRA and PDGFRB (By similarity).
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 (By similarity).
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. Plays an indispensable role in the organization of KRT8/KRT18 filaments. Acts as an endogenous molecular chaperone for neuronal proteins including huntingtin. Suppresses aggregation and toxicity of polyglutamine-containing, aggregation-prone proteins. Also reduces cellular toxicity and caspase-3 activity.
Belongs to the aromatic-ring hydroxylase family. KMO subfamily.
Catalyzes the hydroxylation of L-kynurenine (L-Kyn) to form 3-hydroxy-L-kynurenine (L-3OHKyn). Required for synthesis of quinolinic acid.
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.
Expressed throughout follicle development with highest level in small white follicles. Expressed in granulosa cells, theca cells and post-ovulatory sacs of developing follicles.
Highest level in central region of the theca of developing follicles (at protein level). Expressed at highest level in brain and testis, at high level in kidney, lung and stroma, low level in spleen and adrenal gland (at protein level). Expressed in most tissue with highest levels in small ovarian follicles, brain and testis.
Implicated in endocytosis. May recruit other proteins to membranes with high curvature (By similarity).
Interacts with ARC (By similarity). Interacts with SYNJ1 and DNM1.
(Microbial infection) Interacts with, and is inhibited by fowl adenovirus 1 protein GAM-1.
Interacts with and sequesters the E2F1 transcription factor. Interacts with SUV39H1, KMT5B and KMT5C (By similarity).
Phosphorylated in G1, thereby releasing E2F1 which is then able to activate cell growth. Dephosphorylated at the late M phase. Phosphorylation of domain C promotes interaction between the C-terminal domain C and the Pocket domain, and thereby inhibits interactions with heterodimeric E2F/DP transcription factor complexes (By similarity).
Tumor suppressor that is a key regulator of the G1/S transition of the cell cycle. The hypophosphorylated form binds transcription regulators of the E2F family, preventing transcription of E2F-responsive genes. Both physically blocks E2Fs transactivating domain and recruits chromatin-modifying enzymes that actively repress transcription. Cyclin and CDK-dependent phosphorylation of RB1 induces its dissociation from E2Fs, thereby activating transcription of E2F responsive genes and triggering entry into S phase. RB1 also promotes the G0-G1 transition upon phosphorylation and activation by CDK3/cyclin-C.
Belongs to the bacterial ribosomal protein bS16 family.
Sequence-specific, AT-rich binding transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis.
Detected in eye lens fiber cells (at protein level). Detected in embryonic eye lens.
Required for the correct formation of lens intermediate filaments.
Part of the tectonic-like complex (also named B9 complex).
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).
Belongs to the ubiquitin-activating E1 family.
Heterodimer of SAE1 and UBA2/SAE2. The heterodimer corresponds to the two domains that are encoded on a single polypeptide chain in ubiquitin-activating enzyme E1. Interacts with UBE2I.
The heterodimer acts as an E1 ligase for SUMO1, SUMO2, SUMO3, and probably SUMO4. It mediates ATP-dependent activation of SUMO proteins followed by formation of a thioester bond between a SUMO protein and a conserved active site cysteine residue on UBA2/SAE2.
Belongs to the glycosyl hydrolase 56 family.
Belongs to the tyrosyl-DNA phosphodiesterase family.
Splice factor that binds to the single-stranded 3'AG at the exon/intron border and promotes its utilization in the second catalytic step. Involved in the regulation of alternative splicing and the utilization of cryptic splice sites.
Belongs to the mannose-6-phosphate isomerase type 1 family.
Homomultimerizes and interacts with various extracellular matrix components.
Incorporated into fibronectin-containing matrix fibers. May play a role in cell adhesion and migration along protein fibers within the extracellular matrix (ECM). Could be important for certain developmental processes and contribute to the supramolecular organization of ECM architecture, in particular to those of basement membranes.
Component of the telomerase ribonucleoprotein (RNP) complex that is essential for the replication of chromosome termini. Is a component of the double-stranded telomeric DNA-binding TRF1 complex that is involved in the regulation of telomere length by cis-inhibition of telomerase. Also acts as a single-stranded telomeric DNA-binding protein and thus may act as a downstream effector of the TRF1 complex and may transduce information about telomere maintenance and/or length to the telomere terminus. Binds to at least two telomeric single-stranded 5'-TTAGGG-3' repeats (G-strand). Its activity is TERT dependent but it does not increase TERT activity (By similarity).
Homodimer or homooligomer. Component of the telomerase ribonucleoprotein complex. Binds single-stranded telomeric DNA as a monomer (By similarity). Found in a complex with TERF1, TINF2 and TNKS1. Interacts with TNKS1 (By similarity).
Belongs to the synaptophysin/synaptobrevin family.
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.
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.
On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcription (By similarity). Positively regulates chondrocyte differentiation (PubMed:24129431, PubMed:14523231).
Component of the biogenesis of lysosome-related organelles complex-2 (or BLOC2) composed of HPS3, HPS5 and HPS6.
May regulate the synthesis and function of lysosomes and of highly specialized organelles, such as melanosomes and platelet dense granules.
Atypical Ras-like protein that acts as a potent regulator of NF-kappa-B activity by preventing the degradation of NF-kappa-B inhibitor beta (NFKBIB) by most signals, explaining why NFKBIB is more resistant to degradation.
In contrast to other members of the Ras family, the members of the KappaB-Ras subfamily do not contain the conserved Gly and Gln residues in positions 13 and 65, which are replaced by Ala and Leu residues, respectively, and are therefore similar to the constitutively active forms of oncogenic forms of Ras. This suggests that members of this family are clearly different from other small GTPases proteins.
In the C-terminal section; belongs to the MoeA family.
In the N-terminal section; belongs to the MoaB/Mog family.
Belongs to the TRAFAC class OBG-HflX-like GTPase superfamily. OBG GTPase family.
Belongs to the protein kinase superfamily. Tyr protein kinase family. Ephrin receptor subfamily.
Expressed at high levels in brain, with expression also detected in the kidney, lung, muscle and thymus.
Interacts with the src family kinase, p59-Fyn, through the major phosphorylation site at position Tyr-602 (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.
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 (By similarity).
Component of the RNF20/40 E3 ubiquitin-protein ligase complex that mediates monoubiquitination of 'Lys-120' of histone H2B (H2BK120ub1). H2BK120ub1 gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 'Lys-4' and 'Lys-79' methylation (H3K4me and H3K79me, respectively).
Component of the RNF20/40 complex (also known as BRE1 complex).
Necessary for protein translocation in the endoplasmic reticulum.
Component of the transition zone in primary cilia. Required for ciliogenesis.
Belongs to the universal ribosomal protein uS15 family.
Part of a SCF (SKP1-cullin-F-box) protein ligase complex.
Belongs to the Mediator complex subunit 4 family.
The inactive form of the enzyme is composed of two regulatory chains and two catalytic chains. Activation by cAMP produces two active catalytic monomers and a regulatory dimer that binds four cAMP molecules (By similarity).
The pseudophosphorylation site binds to the substrate-binding region of the catalytic chain but is not phosphorylated. The physiological significance of phosphorylations by other kinases is unclear (By similarity).
Belongs to the SMC family. SMC4 subfamily.
Belongs to the RRM HNRPC family. RALY subfamily.
Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRB4 sub-subfamily.
Belongs to the 2H phosphoesterase superfamily. USB1 family.
Phosphodiesterase responsible for the U6 snRNA 3' end processing. Acts as an exoribonuclease (RNase) responsible for trimming the poly(U) tract of the last nucleotides in the pre-U6 snRNA molecule, leading to the formation of mature U6 snRNA.
Belongs to the GST superfamily. Sigma family.
Bifunctional enzyme which catalyzes both the conversion of PGH2 to PGD2, a prostaglandin involved in smooth muscle contraction/relaxation and a potent inhibitor of platelet aggregation, and the conjugation of glutathione with a wide range of aryl halides, organic isothiocyanates and alpha,beta-unsaturated carbonyls. Also exhibits low glutathione-peroxidase activity towards cumene hydroperoxide and t-butyl hydroperoxide.
Glutathione is required for the prostaglandin D synthase activity.
Highly expressed in liver, kidney, small intestine and colon, moderately in pancreas, bone marrow, lung and ovary, and expressed at low levels in spleen, thymus, heart and brain. Not detected in oviduct or skin (at protein level) (PubMed:9657971). Expressed in liver (PubMed:11572089).
Significantly increased expression by estrogen. Up-regulated after 1 hour of exposure to estrogen. Expression persists through 72 hours.
Belongs to the ZIP transporter (TC 2.A.5) family.
Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Beta-2/CHRNB2 sub-subfamily.
Neuronal AChR seems to be composed of two different type of subunits: alpha and non-alpha (also called beta). A functional receptor seems to consist of two alpha-chains and three non-alpha chains. The pentamer alpha3-beta-2 interacts with the conotoxin BuIA and the conotoxin MII (By similarity).
Belongs to the glycosyltransferase 32 family.
Belongs to the threonine aldolase family.
Regulatory subunit of serine/threonine-protein phosphatase 4 (PP4).
Serine/threonine-protein phosphatase 4 (PP4) occurs in different assemblies of the catalytic and one or more regulatory subunits.
In contrast to isoform 1, does not bind poly-ADP-ribose.
Isoform that specifically binds poly-ADP-ribose and O-acetyl-ADP-ribose and plays a key role in NAD(+) metabolism. Able to bind to the ends of poly-ADP-ribose chains created by PARP1 and cap them. 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.
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.
Present in immature erythrocytes (at protein level).
The macro domain specifically binds poly-ADP-ribose.
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.
Protein sialyltransferase specifically expressed in goblet cells that plays a key role in intestinal host-commensal homeostasis (By similarity). Conjugates sialic acid with an alpha-2-6 linkage to N-acetylgalactosamine (GalNAc) glycan chains linked to serine or threonine in glycoproteins (PubMed:8288607).
Most abundant in thymus and detectable in brain, retina, kidney, lung and heart. Not detected in skeletal muscle and liver.
Receptor for members of the ephrin-B family.
Divided into three regions: a N-terminal motor (head) domain, followed by a neck domain consisting of a calmodulin-binding linker domain and a single IQ motif, and a C-terminal tail region with a three-helix bundle region, a SAH domain and a unique globular domain required for interaction with other proteins such as cargo-binding.
Homodimer; dimerization seems to implicate the unfolding of the three-helix bundle region creating an additional calmodulin binding site, and cargo binding (By similarity). Able to function as a monomer under specific conditions in vitro (By similarity). Forms a complex with CFTR and DAB2 in the apical membrane of epithelial cells (By similarity). Binding to calmodulin through a unique insert, not found in other myosins, located in the neck region between the motor domain and the IQ domain appears to contribute to the directionality reversal (By similarity). This interaction occurs only if the C-terminal lobe of calmodulin is occupied by calcium (By similarity). Interaction with F-actin/ACTN1 occurs only at the apical brush border domain of the proximal tubule cells (By similarity). Interacts with DAB2 (By similarity). In vitro, the C-terminal globular tail binds a C-terminal region of DAB2 (By similarity). Interacts with CFTR (By similarity). Interacts with OPTN (PubMed:15837803). Interacts with CABP5 (By similarity). Interacts (via residues 1139-1257) with TOM1 (via residues 397-488) (By similarity). Interacts with TAX1BP1 and CALCOCO2/NDP52 (By similarity). Interacts with TOM1L2 (By similarity).
Myosins are actin-based motor molecules with ATPase activity (By similarity). Unconventional myosins serve in intracellular movements (By similarity). Myosin 6 is a reverse-direction motor protein that moves towards the minus-end of actin filaments (By similarity). Has slow rate of actin-activated ADP release due to weak ATP binding (By similarity). Functions in a variety of intracellular processes such as vesicular membrane trafficking and cell migration (By similarity). Required for the structural integrity of the Golgi apparatus via the p53-dependent pro-survival pathway (By similarity). Appears to be involved in a very early step of clathrin-mediated endocytosis in polarized epithelial cells (By similarity). Together with TOM1, mediates delivery of endocytic cargo to autophagosomes thereby promoting autophagosome maturation and driving fusion with lysosomes (By similarity). Links TOM1 with autophagy receptors, such as TAX1BP1; CALCOCO2/NDP52 and OPTN (By similarity). May act as a regulator of F-actin dynamics (By similarity). May play a role in transporting DAB2 from the plasma membrane to specific cellular targets (By similarity). May play a role in the extension and network organization of neurites (By similarity). Modulates RNA polymerase II-dependent transcription (By similarity).
Originally predicted to contain a coiled coil domain but generally accepted to contain a stable SAH domain instead.
Phosphorylation in the motor domain, induced by EGF, results in translocation of MYO6 from the cell surface to membrane ruffles. Phosphorylated in vitro by p21-activated kinase (PAK).
Represents an unconventional myosin. This protein should not be confused with the conventional myosin-6 (MYH6).
The SAH (single alpha-helix) region is characterized by a high content of charged residues which are predicted to stabilize the alpha-helical structure by ionic bonds (By similarity). Its contribution to the mechanism confering the myosin movement on actin filaments is debated (By similarity).
Belongs to the eukaryotic ribosomal protein eL32 family.
Belongs to the protein kinase superfamily. Alpha-type protein kinase family.
Undergoes calcium/calmodulin-dependent intramolecular autophosphorylation, and this results in it becoming partially calcium/calmodulin-independent.
Belongs to the TGF-beta family. GDNF subfamily.
Slow skeletal muscle Tn-C can bind 3 calcium ions per molecule. Domain I does not bind calcium.
Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family. CACNA1D subfamily.
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.
Expressed in the basilar papilla of the cochlea.
The isoform alpha-1D gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group.
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 (By similarity). Interacts with RIMBP2.
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.
Component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes (By similarity). The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of E3 ligase complexes, leading to modify the Ubl ligase activity (By similarity).
Component of the CSN complex, probably composed of COPS1, COPS2, COPS3, COPS4, COPS5, COPS6, COPS7, COPS8 and COPS9.
This is a receptor for the anterior pituitary hormone prolactin.
Belongs to the fibroblast growth factor-binding protein family.
Palmitoylated by the ZDHHC9-GOLGA7 complex. A continuous cycle of de- and re-palmitoylation regulates rapid exchange between plasma membrane and Golgi.
Belongs to the PIGG/PIGN/PIGO family. PIGN subfamily.
Ethanolamine phosphate transferase involved in glycosylphosphatidylinositol-anchor biosynthesis. Transfers ethanolamine phosphate to the first alpha-1,4-linked mannose of the glycosylphosphatidylinositol precursor of GPI-anchor.
Belongs to the XRCC4-XLF family. XRCC4 subfamily.
E3 ubiquitin-protein ligase that mediates ubiquitination of several tyrosine-phosphorylated Src substrates. Associated component of the WMM complex, a complex that mediates N6-methyladenosine (m6A) methylation of RNAs, a modification that plays a role in the efficiency of mRNA splicing and RNA processing.
Homodimer (By similarity). Interacts with tyrosine-phosphorylated SRC substrates (By similarity). Component of the WMM complex, a N6-methyltransferase complex composed of a catalytic subcomplex, named MAC, and of an associated subcomplex, named MACOM. Component of the MACOM subcomplex (By similarity).
The HYB domain forms a phosphotyrosine-binding pocket upon dimerization, and mediates as well the recognition of its flanking acidic amino acids.
May associate with G-protein coupled receptors and regulate downstream signaling pathways.
In the embryo, the expression peak at E4.5 and decreases at later stages of development.
Seems to promote the survival of visceral and proprioceptive sensory neurons.
Belongs to the protein-tyrosine phosphatase family. Non-receptor class subfamily.
Belongs to the reverse transcriptase family. Telomerase subfamily.
Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes. It elongates telomeres. It is a reverse transcriptase that adds simple sequence repeats to chromosome ends by copying a template sequence within the RNA component of the enzyme.
Belongs to the universal ribosomal protein uL1 family.
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. 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. Specifically mediates the symmetric dimethylation of histone H4 'Arg-3' to form H4R3me2s. Plays a role in gene imprinting by being recruited by CTCFL at the H19 imprinted control region (ICR) and methylating histone H4 to form H4R3me2s, possibly leading to recruit DNA methyltransferases at these sites. May also play a role in embryonic stem cell (ESC) pluripotency. Also able to mediate the arginine methylation of histone H2A and myelin basic protein (MBP) in vitro; the relevance of such results is however unclear in vivo.
Belongs to the class I-like SAM-binding methyltransferase superfamily. Protein arginine N-methyltransferase family. PRMT7 subfamily.
Belongs to the glycosyl hydrolase 79 family.
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 (By similarity). Increases cell adhesion to the extracellular matrix (ECM), independent of its enzymatic activity.
Expressed, as early as 12 hours post fertilization, in cells migrating from the epiblast and forming the hypoblast layer. Later on at 72 h, preferentially expressed in cells of the developing vascular and nervous systems.
Heterodimer; the active enzyme is a heterodimer of the 60 kDa and 45 kDa proteolytic products.
Proteolytically cleaved to produce a 60 kDa and a 45 kDa product.
Specifically secreted during the embryonic period in the chicken proventriculus (glandular stomach).
Belongs to the AVIT (prokineticin) family.
Accessory component of the STT3B-containing form of the N-oligosaccharyl transferase (OST) complex which catalyzes the transfer of a high mannose oligosaccharide from a lipid-linked oligosaccharide donor to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains. Involved in N-glycosylation of STT3B-dependent substrates. Specifically required for the glycosylation of a subset of acceptor sites that are near cysteine residues. In its oxidized form proposed to form transient mixed disulfides with a glycoprotein substrate to facilitate access of STT3B to the unmodified acceptor site. Has also oxidoreductase-independent functions in the STT3B-containing OST complex possibly involving substrate recognition.
Accessory component of the STT3B-containing form of the oligosaccharyltransferase (OST) complex. 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. OST can form stable complexes with the Sec61 complex or with both the Sec61 and TRAP complexes.
May be involved in Mg(2+) transport in epithelial cells.
May play a role in terminal differentiation of skeletal muscle cells but not in the determination of cells to the myogenic lineage. May function in TGF-beta signaling (By similarity).
First expressed in splanchnic mesoderm of stage 4 embryos. At stage 6, strongly expressed along the neural fold in a region corresponding to the future neural crest. Expression in the neural fold continues during closure of the neural tube but diminishes after neural crest cells have left the neural tube.
Binds 1 divalent metal cation per subunit. Mg(2+) or Mn(2+).
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. 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 (By similarity).
Homodimer. Component of the RAG complex composed of core components RAG1 and RAG2 (By similarity).
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.
The RING-type zinc finger mediates the E3 ubiquitin-protein ligase activity.
Transcriptional coactivator involved in neuroepithelial stem cell differentiation and neurogenesis. Involved in particular in lens epithelial cell gene regulation and stress responses. May play an important role in lens epithelial to fiber cell terminal differentiation. May play a protective role during stress-induced apoptosis (By similarity).
Responsible for the synthesis of the sequence NeuAc-alpha-2,3-Gal-beta-1,3-GalNAc- found on sugar chains O-linked to Thr or Ser and also as a terminal sequence on certain gangliosides. SIAT4A and SIAT4B sialylate the same acceptor substrates but exhibit different Km values.
Belongs to the SIMIBI class G3E GTPase family. ZNG1 subfamily.
Acetylation at the major site Lys-195 is important for oligomerization and ability to degrade its target substrates. Deacetylated by SIRT1 (By similarity).
Implicated in immunoproteasome assembly and required for efficient antigen processing. The PA28 activator complex enhances the generation of class I binding peptides by altering the cleavage pattern of the proteasome (By similarity).
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).
Belongs to the GatB/GatE family. GatB subfamily.
Subunit of the heterotrimeric GatCAB amidotransferase (AdT) complex, composed of A (QRSL1), B (GATB) and C (GATC) subunits.
Belongs to the proteasome subunit S5A family.
Belongs to the class-I pyridine nucleotide-disulfide oxidoreductase family.
The active site is a redox-active disulfide bond.
Expressed principally in steroidogenic tissues as ovary (granulosa from the largest preovulatory follicle and stromal tissues) and adrenals.
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 (By similarity).
Belongs to the metallo-dependent hydrolases superfamily. ATZ/TRZ family.
Catalyzes the hydrolytic deamination of guanine, producing xanthine and ammonia.
Belongs to the krueppel C2H2-type zinc-finger protein family. Hic subfamily.
Binds specifically to the gamma F-1-binding motif of the gamma F-crystallin promoter. May have a regulatory role in sclerotome specification and/or differentiation. Isoform 2 functions as a transcriptional repressor in lens cells.
In the embryo of stage 11, expressed predominantly in the head mesenchyme surrounding the brain and in the paraxial mesoderm. Highly expressed in presomitic mesoderm and then over the entire epithelial somite. During somitic differentiation, expression becomes restricted to the sclerotome. In the developing lens, expression is most active at the beginning of lens fiber cell differentiation.
Isoform 1 is highly expressed in kidney and lung. Expression of isoform 2 is higher in the lens, retina and stomach, and extremely low in heart, muscle, kidney and lung. Isoform 3 is weakly expressed in heart, kidney and lens.
Homotrimer. Forms a complex with activator 1 heteropentamer in the presence of ATP. Interacts with DNMT1 (By similarity). Interacts with CHAF1A. Component of the replisome complex (By similarity).
Monoubiquitinated by the UBE2B-RAD18 complex on Lys-164. Monoubiquitination at Lys-164 also takes place in undamaged proliferating cells, and is mediated by the DCX(DTL) complex, leading to enhance PCNA-dependent translesion DNA synthesis (By similarity).
This protein is an auxiliary protein of DNA polymerase delta and is involved in the control of eukaryotic DNA replication by increasing the polymerase's processibility during elongation of the leading strand.
Belongs to the cyclic nucleotide phosphodiesterase family. PDE4 subfamily.
Belongs to the threonine synthase family.
Belongs to the kinesin light chain family.
Kinesin is a microtubule-associated force-producing protein that play a role in organelle transport.
Oligomeric complex composed of two heavy chains and two light chains.
Associates with the 60S ribosomal subunit.
Required for the assembly of mature ribosomes and ribosome biogenesis. Together with EFL1, triggers the GTP-dependent release of EIF6 from 60S pre-ribosomes in the cytoplasm, thereby activating ribosomes for translation competence by allowing 80S ribosome assembly and facilitating EIF6 recycling to the nucleus, where it is required for 60S rRNA processing and nuclear export. Required for normal levels of protein synthesis. May play a role in cellular stress resistance. May play a role in cellular response to DNA damage. May play a role in cell proliferation (By similarity).
Plays a role as an effector of the ADP-ribosylation factor-like protein 2, ARL2.
Catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein). Requires the presence of the other members of the gamma-secretase complex for protease activity. Plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins.
Heterogeneous proteolytic processing generates N-terminal (NTF) and C-terminal (CTF) fragments of approximately 35 and 20 kDa, respectively. During apoptosis, the C-terminal fragment (CTF) is further cleaved by a caspase.
Homodimer. The functional gamma-secretase complex is composed of at least four polypeptides: a presenilin homodimer (PSEN1 or PSEN2), nicastrin (NCSTN), APH1 (APH1A or APH1B) and PEN2. Such minimal complex is sufficient for secretase activity (By similarity). Predominantly heterodimer of a N-terminal (NTF) and a C-terminal (CTF) endoproteolytical fragment (By similarity). Interacts with CDH2 (PubMed:16046145).
Probable subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors.
Substrates, such as NOTCH1 and APP peptides, are bound between PSEN1 transmembrane domains and via the first lumenal loop and the cytoplasmic loop between the sixth and seventh transmembrane domains. Substrate binding causes a conformation change and formation of an intermolecular antiparallel beta-sheet between PSEN1 and its substrates.
The PAL motif is required for normal active site conformation.
Mitochondrial intermembrane chaperone that participates in the import and insertion of multi-pass transmembrane proteins into the mitochondrial inner membrane. May also be 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.
Involved in muscle differentiation (myogenic factor). Induces fibroblasts to differentiate into myoblasts. Probable sequence specific DNA-binding protein.
Component of the purine nucleotide cycle (PNC), which interconverts IMP and AMP to regulate the nucleotide levels in various tissues, and which contributes to glycolysis and ammoniagenesis. Catalyzes the first commited step in the biosynthesis of AMP from IMP.
Component of the purine nucleotide cycle (PNC), which interconverts IMP and AMP to regulate the nucleotide levels in various tissues, and which contributes to glycolysis and ammoniagenesis. Catalyzes the first committed step in the biosynthesis of AMP from IMP.
Plays an important role in the de novo pathway of purine nucleotide biosynthesis.
Component of the BAF complex. Interacts with acetylated histones H3 and H4. Component of neuron-specific chromatin remodeling complex (nBAF complex), a subfamily of ATP-dependent SWI/SNF chromatin remodeling complexes (By similarity).
Muscle-specific component of the BAF complex, a multiprotein complex involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology). Specifically binds acetylated lysines on histone 3 and 4. In the complex, it acts as a tissue-specific anchor between histone acetylations and methylations and chromatin remodeling. It thereby probably plays an essential role in heart and skeletal muscle development. Belongs to the neuron-specific chromatin remodeling complex (nBAF complex) and plays a role in neural development.
The PHD-type zinc fingers mediate the binding to acetylated histones.
Belongs to the Ikaros C2H2-type zinc-finger protein family.
Binds and activates the enhancer (delta-A element) of the CD3-delta gene. Functions in the specification and the maturation of the T-lymphocyte. Also interacts with a critical control element in the TDT (terminal deoxynucleotidyltransferase) promoter as well as with the promoters for other genes expressed during early stages of B- and T-cell development. Function is isoform-specific and is modulated by dominant-negative inactive isoforms (By similarity).
Expressed early in embryo from embryonic day 2 onwards.
Expressed in embryonic hematopoietic organs such as the bursa of Fabricius, thymus and spleen. In the adult, expressed in spleen, thymus, bursa and peripheral blood leukocytes.
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, PSMB5 displays a chymotrypsin-like activity.
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. Directly interacts with POMP. Interacts with ABCB1 and TAP1.
Belongs to the TRAPP small subunits family.
Part of the multisubunit transport protein particle (TRAPP) complex.
ATP-dependent RNA helicase which is a subunit of the eIF4F complex involved in cap recognition and is required for mRNA binding to ribosome. In the current model of translation initiation, eIF4A unwinds RNA secondary structures in the 5'-UTR of mRNAs which is necessary to allow efficient binding of the small ribosomal subunit, and subsequent scanning for the initiator codon (By similarity).
Belongs to the DEAD box helicase family. eIF4A subfamily.
eIF4F is a multi-subunit complex, the composition of which varies with external and internal environmental conditions. It is composed of at least EIF4A, EIF4E and EIF4G1/EIFFG3 (By similarity). Interacts with EIF4E (By similarity).
Key enzyme in purine degradation. Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species.
Belongs to the cyclophilin-type PPIase family. PPIL3 subfamily.
Catalyzes the ATP-dependent ligation of cysteine to tRNA(Cys).
Detected in the theca layer of the ovarian follicle in the white follicle (WF) stage, but decreases throughout the F1, F3, F5, and postovulatory follicle stages. Detected in the granulosa layer of the ovarian follicle in the white follicle (WF) stage, F1, F3, F5, and postovulatory follicle stages. In the vagina expression is higher in laying hens than in non-laying hens, and is higher in older laying hens than in young laying hens.
Has bactericidal activity. Potent activity against E.coli ML-35, L.monocytogenes EGD and C.albicans.
Induced in the theca layer of the F3 stage ovarian follicle by intravenous injection of LPS. Repressed in the granulosa layer of the F3 stage ovarian follicle by intravenous injection of LPS. Expression in cultured vaginal cells is increased by LPS and S.enteritidis. Expression in the kidney and liver is not affected by intravenous injection of LPS.
Strong expression in the bone marrow, lung, testis. Moderate expression in the bursa and intestine. Low expression in the cloaca, gall bladder, brain and pancreas. Expressed in the vagina, ovarian stroma and the theca and granulosa layers of the ovarian follicle.
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 (By similarity).
Receptor tyrosine kinase which binds promiscuously GPI-anchored 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. Among GPI-anchored ephrin-A ligands, EFNA5 is a cognate/functional ligand for EPHA7 and their interaction regulates brain development modulating cell-cell adhesion and repulsion. Has a repellent activity on axons and is for instance involved in the guidance of corticothalamic axons and in the proper topographic mapping of retinal axons to the colliculus. May also regulate brain development through a caspase(CASP3)-dependent proapoptotic activity. Forward signaling may result in activation of components of the ERK signaling pathway including MAP2K1, MAP2K2, MAPK1 and MAPK3 which are phosphorylated upon activation of EPHA7 (By similarity).
Within the nervous system, expression is restricted to prosomeres 1 and 2 in the diencephalon and all the rhombomeres in the hindbrain during segmentation stages. Later on, a superimposed pattern appears that correlates with the formation of several axonal tracts. In the somitic mesoderm, the expression correlates with segmentation and the guidance of both neural crest and motor axons through the sclerotomes.
Belongs to the adaptor complexes small subunit family.
A palmitoylation site was proposed at Cys-91, but it was later shown that this cysteine is engaged in a disulfide bond.
Expression in the met-mesencephalic region.
Forms a soluble 1:1 complex with AFM; this prevents oligomerization and is required for prolonged biological activity. The complex with AFM may represent the physiological form in body fluids (By similarity). Interacts with PORCN (PubMed:25451226).
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:25451226). Developmental protein that promotes cell proliferation in the developing spinal cord (PubMed:25451226). Has a role in osteoblast function, bone development and bone homeostasis (By similarity).
N-glycosylated. N-glycosylation favors subsequent palmitoleoylation.
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).
Belongs to the potassium channel family. G (TC 1.A.1.2) subfamily. Kv6.2/KCNG2 sub-subfamily.
Heterodimer with KCNB1. Does not form homomultimers (By similarity).
Potassium channel subunit. Modulates channel activity (By similarity).
Expressed predominantly in ovarian granulosa and thecal cell.
Catalyzes a salvage reaction resulting in the formation of AMP, that is energically less costly than de novo synthesis.
Positively regulates dimethylation of two adjacent adenosines in the loop of a conserved hairpin near the 3'-end of 18S rRNA.
Becomes activated when its major tyrosine phosphorylation site is not phosphorylated. It can also be activated by point mutations as well as by truncations at the C-terminal end or by other mutations. Heme regulates its activity by enhancing the phosphorylation on Tyr-527 (By similarity).
Dephosphorylated at Tyr-527 by PTPRJ. Phosphorylated on Tyr-527 by c-Src kinase (CSK). The phosphorylated form is termed pp60c-src. Dephosphorylated by PTPRJ at Tyr-416. Normally maintained in an inactive conformation with the SH2 domain engaged with Tyr-527, the SH3 domain engaged with the SH2-kinase linker, and Tyr-416 dephosphorylated. Dephosphorylation of Tyr-527 as a result of protein tyrosine phosphatase (PTP) action disrupts the intramolecular interaction between the SH2 domain and Tyr-527, Tyr-416 can then become autophosphorylated, resulting in SRC activation. Phosphorylation of Tyr-527 by CSK allows this interaction to reform, resulting in SRC inactivation (By similarity).
Expressed to high levels, and with a high degree of kinase activity, in certain fully differentiated cells such as neurons, platelets and macrophages. Isoform 1 is widely expressed. Isoform 2 is expressed only in the muscle.
Forms a complex with polyoma virus middle T antigen. Interacts with AFAP-110. Interacts with GJA1 and PXN.
Myristoylated at Gly-2, and this is essential for targeting to membranes.
Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. Due to functional redundancy between members of the SRC kinase family, identification of the specific role of each SRC kinase is very difficult. SRC appears to be one of the primary kinases activated following engagement of receptors and plays a role in the activation of other protein tyrosine kinase (PTK) families. Receptor clustering or dimerization leads to recruitment of SRC to the receptor complexes where it phosphorylates the tyrosine residues within the receptor cytoplasmic domains. Plays an important role in the regulation of cytoskeletal organization through phosphorylation of specific substrates involved in this process (Probable). When cells adhere via focal adhesions to the extracellular matrix, signals are transmitted by integrins into the cell resulting in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN) (By similarity). Also active at the sites of cell-cell contact adherens junctions and at gap junctions. Implicated in the regulation of pre-mRNA-processing (Probable). Might be involved not only in mediating the transduction of mitogenic signals at the level of the plasma membrane but also in controlling progression through the cell cycle via interaction with regulatory proteins in the nucleus (PubMed:1717492, PubMed:8550628). Involved in anchorage-independent cell growth (PubMed:19307596).
S-nitrosylation is important for activation of its kinase activity.
Sodium-dependent lysophosphatidylcholine (LPC) symporter, which plays an essential role for blood-brain barrier formation and function (By similarity). Specifically expressed in endothelium of the blood-brain barrier of micro-vessels and transports LPC into the brain (By similarity). Transport of LPC is essential because it constitutes the major mechanism by which docosahexaenoic acid (DHA), an omega-3 fatty acid that is essential for normal brain growth and cognitive function, enters the brain (By similarity). Transports LPC carrying long-chain fatty acids such LPC oleate and LPC palmitate with a minimum acyl chain length of 14 carbons (By similarity). Does not transport docosahexaenoic acid in unesterified fatty acid (By similarity).
Generally pentameric. There are five types of GABA(A) receptor chains: alpha, beta, gamma, delta, and rho. Interacts with SQSTM1.
Component of the cap-binding complex (CBC), which binds cotranscriptionally to the 5'-cap of pre-mRNAs and is involved in various processes such as pre-mRNA splicing, translation regulation, nonsense-mediated mRNA decay, RNA-mediated gene silencing (RNAi) by microRNAs (miRNAs) and mRNA export. The CBC complex is involved in mRNA export from the nucleus, leading to the recruitment of the mRNA export machinery to the 5'-end of mRNA and to mRNA export in a 5' to 3' direction through the nuclear pore. The CBC complex is also involved in mediating U snRNA and intronless mRNAs export from the nucleus. The CBC complex is essential for a pioneer round of mRNA translation, before steady state translation when the CBC complex is replaced by cytoplasmic cap-binding protein eIF4E. The pioneer round of mRNA translation mediated by the CBC complex plays a central role in nonsense-mediated mRNA decay (NMD), NMD only taking place in mRNAs bound to the CBC complex, but not on eIF4E-bound mRNAs. The CBC complex enhances NMD in mRNAs containing at least one exon-junction complex (EJC), promoting the interaction between UPF1 and UPF2. The CBC complex is also involved in 'failsafe' NMD, which is independent of the EJC complex, while it does not participate in Staufen-mediated mRNA decay (SMD). During cell proliferation, the CBC complex is also involved in microRNAs (miRNAs) biogenesis via its interaction with SRRT/ARS2 and is required for miRNA-mediated RNA interference. The CBC complex also acts as a negative regulator of PARN, thereby acting as an inhibitor of mRNA deadenylation. In the CBC complex, NCBP1/CBP80 does not bind directly capped RNAs (m7GpppG-capped RNA) but is required to stabilize the movement of the N-terminal loop of NCBP2/CBP20 and lock the CBC into a high affinity cap-binding state with the cap structure. Associates with NCBP3 to form an alternative cap-binding complex (CBC) which plays a key role in mRNA export. The conventional CBC with NCBP2 binds both small nuclear RNA (snRNA) and messenger (mRNA) and is involved in their export from the nucleus whereas the alternative CBC with NCBP3 does not bind snRNA and associates only with mRNA thereby playing a role only in mRNA export (By similarity).
Component of the nuclear cap-binding complex (CBC), a heterodimer composed of NCBP1/CBP80 and NCBP2/CBP20 that interacts with m7GpppG-capped RNA. Component of an alternative nuclear cap-binding complex (CBC) composed of NCBP1/CBP80 and NCBP3 (By similarity).
Belongs to the NADPH-dependent diflavin oxidoreductase NDOR1 family.
Interacts with CIAPIN1; as part of the cytosolic iron-sulfur (Fe-S) protein assembly (CIA) machinery.
NADPH-dependent reductase which is a central component of the cytosolic iron-sulfur (Fe-S) protein assembly (CIA) machinery. Transfers electrons from NADPH via its FAD and FMN prosthetic groups to the [2Fe-2S] cluster of CIAPIN1, another key component of the CIA machinery. In turn, this reduced cluster provides electrons for assembly of cytosolic iron-sulfur cluster proteins. It can also reduce the [2Fe-2S] cluster of CISD1 and activate this protein implicated in Fe/S cluster repair.
Multifunctional protein with various roles in different cellular compartments. May act in a redox sensitive manner (By similarity). Associates with chromatin and binds DNA with a preference to non-canonical DNA structures such as single-stranded DNA (PubMed:14672558). Can bent DNA and enhance DNA flexibility by looping thus providing a mechanism to promote activities on various gene promoters. Proposed to be involved in the innate immune response to nucleic acids by acting as a cytoplasmic promiscuous immunogenic DNA/RNA sensor. Involved in inflammatory response to antigenic stimulus coupled with pro-inflammatory activity (By similarity).
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 HMGB2 (HMGB2C23hC45hC106h), 2- disulfide HMGB2 (HMGB2C23-C45C106h) and 3- sulfonyl HMGB2 (HMGB2C23soC45soC106so).
Belongs to the NAD(P)H dehydrogenase (quinone) family.
Receptor for the cytotoxic ligand TNFSF10/TRAIL. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis.
Cytokine that may play a role in the development of the medial pallium and during optic nerve and pecten development by modulating BMP signaling.
In brain first detected at 6 dpc and persisted until 14 dpc. On 10 dpc brain, expressed in the dorsal region of the telencephalic hemispheres and cells located in the ventral diencephalon. On 14 dpc head, expressed in the meninges of the spinal cord. Expressed in the developing optic nerve and at the optic nerve/pecten junction.
Found in chondrogenic regions in the branchial arches, somites and limb buds at 22 dpc. At 28 dpc detected in the limbs, developing scapula, prevertebrae and ribs. Found in condensing mesenchyme of the forelimb at 25 dpc. Expressed in the condensing mesenchyme at the distal tips of the developing hindlimbs at 26 dpc.
Interacts with SNAI2; triggers neural crest delamination in a phosphorylation dependent manner. Interacts with UBE2I.
Phosphorylated at Ser-181 in the developing neural tube. Phosphorylation at either Ser-64 or Ser-181 is required for sumoylation, but phosphorylation is not dependent on sumoylation. Sumoylation is enhanced by PKA. Phosphorylation is required for interaction with SNAI2 to trigger neural crest delamination and for an efficient trunk neural crest delamination, whereas sumoylation plays a less significant role. Phosphorylation and sumoylation are induced by BMP signaling pathway.
Sumoylated at Lys-376; phosphorylation at either Ser-64 or Ser-181 is required for sumoylation. Sumoylation is induced by BMP signaling pathway.
Transcription factor that plays a key role in chondrocytes differentiation and skeletal development (PubMed:10340758, PubMed:9858536). Specifically binds the 5'-ACAAAG-3' DNA motif present in enhancers and super-enhancers and promotes expression of genes important for chondrogenesis, including COL2A1 (PubMed:10340758, PubMed:9858536). Plays a central role in successive steps of chondrocyte differentiation. Absolutely required for precartilaginous condensation, the first step in chondrogenesis during which skeletal progenitors differentiate into prechondrocytes (By similarity). Together with SOX5 and SOX6, required for overt chondrogenesis when condensed prechondrocytes differentiate into early stage chondrocytes, the second step in chondrogenesis (By similarity). Later, required to direct hypertrophic maturation and block osteoblast differentiation of growth plate chondrocytes: maintains chondrocyte columnar proliferation, delays prehypertrophy and then prevents osteoblastic differentiation of chondrocytes (By similarity). Also required for chondrocyte hypertrophy, both indirectly, by keeping the lineage fate of chondrocytes, and directly, by remaining present in upper hypertrophic cells (By similarity). Low lipid levels are the main nutritional determinant for chondrogenic commitment of skeletal progenitor cells: when lipids levels are low, FOXO transcription factors promote expression of SOX9, which induces chondrogenic commitment and suppresses fatty acid oxidation (By similarity). In addition to cartilage development, also acts as a regulator of proliferation and differentiation in epithelial stem/progenitor cells (By similarity). In response to bone morphogenetic protein stimulus, phosphorylation is induced and then sumoylation, allowing cooperation with SNAI2 to trigger neural crest delamination (PubMed:23382206).
Expressed in retina, brain and liver (PubMed:1356223). Little or no detectable expression in breast muscle, pancreas and spleen (PubMed:1356223).
Glutamate to glutamine ratio influences catalytic activity (PubMed:19895308). At glutamate to glutamine ratios greater than 4, decarboxylase activity ceases (PubMed:19895308). In the presence of manganese, synthetase activity is limited to concentrations between 10 mM and 20 mM, whereas decarboxylase activity is not affected (PubMed:19895308). Both catalytic activities are inhibited by avidin (PubMed:19895308).
Glutamine synthetase that catalyzes the ATP-dependent conversion of glutamate and ammonia to glutamine (PubMed:19895308). When expressed in liver, it may be involved in detoxifying intramitochondrially generated ammonia (PubMed:4401992). Also acts as glutamate decarboxylase by catalyzing the production of 4-aminobutanoate (gamma-aminobutyric acid, GABA) in a pyridoxal phosphate-independent manner (PubMed:19895308).
In the retina, down-regulated upon application of glutamate concentrations of 15 umol/eye or higher.
Weakly expressed in retina on embryonic day 18, with levels increasing until day 6 after hatching and then remaining high until day 21 (at protein level).
Contains one Leu-Xaa-Xaa-Leu-Leu (LXXLL) motif, which may be required for an association with nuclear receptors.
Putative Polycomb group (PcG) protein. PcG proteins act by forming multiprotein complexes, which are required to maintain the transcriptionally repressive state of homeotic genes throughout development. PcG proteins are not required to initiate repression, but to maintain it during later stages of development. They probably act via methylation of histones, rendering chromatin heritably changed in its expressibility. heritably changed in its expressibility. Involved in transcriptional regulation mediated by ligand-bound nuclear hormone receptors (By similarity).
RNA-binding protein, which probably plays a central role in gametogenesis in both males and females. Acts by binding to the 3'-UTR of mRNA, specifically recognizing GUU triplets, and promoting the translation of key transcripts (By similarity).
Glutathione S-transferase that catalyzes the nucleophilic attack of the sulfur atom of glutathione on the electrophilic groups of a wide range of exogenous and endogenous compounds. Involved in the formation of glutathione conjugates of both prostaglandin A2 (PGA2) and prostaglandin J2 (PGJ2). It also catalyzes the isomerization of D5-androstene-3,17-dione (AD) into D4-androstene-3,17-dione and may therefore play an important role in hormone biosynthesis. Through its glutathione-dependent peroxidase activity toward the fatty acid hydroperoxide (13S)-hydroperoxy-(9Z,11E)-octadecadienoate/13-HPODE it is also involved in the metabolism of oxidized linoleic acid.
Homodimer or heterodimer of GSTA1 and GSTA2.
May act as a positive regulator of T-cell coactivation. May act as a scaffolding protein within caveolar membranes. Interacts directly with G-protein alpha subunits and can functionally regulate their activity (By similarity).
Belongs to the immunoglobulin superfamily. BTN/MOG family.
RNA-binding protein involved in pre-mRNA splicing. Interacts with the PRP19C/Prp19 complex/NTC/Nineteen complex which is part of the spliceosome. Involved in regulating splice site selection. Binds preferentially RNA with A/C rich sequences and poly-C stretches.
The C-terminal part is necessary for the interaction with the PRP19C/Prp19 complex/NTC/Nineteen complex.
Belongs to the methyltransferase superfamily. Trimethylguanosine synthase family.
Belongs to the P-Pant transferase superfamily. AcpS family.
Assembly factor required for Rieske Fe-S protein UQCRFS1 incorporation into the cytochrome b-c1 (CIII) complex. Functions as a chaperone, binding to this subunit within the mitochondrial matrix and stabilizing it prior to its translocation and insertion into the late CIII dimeric intermediate within the mitochondrial inner membrane.
Belongs to the phenylalanyl-tRNA synthetase beta subunit family. Type 2 subfamily.
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 (By similarity).
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.
Belongs to the SLC12A transporter family.
Expression weakly detectable at 6 dpc embryo, reaches a maximum at 16 dpc and declines in the adult.
Forms homodimers and homotrimers. Interacts with CNTN1, NFASC and CSPG5.
Neural extracellular matrix (ECM) protein involved in interactions with different cells and matrix components. Involved in cell attachment and neurite formation. Interaction with CNTN1 enhances the neurite outgrowth.
The N-terminus cysteine-rich segment may mediate the formation of oligomers. The fibronectin type-III 2-3 mediate the binding to contactin 1. The fibronectin type-III 9 mediates the cell attachment. The fibronectin type-III 2-5 mediate NFASC binding. The fibrinogen C-terminal domain mediates interaction with CSPG5.
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.
ApoII mRNA induction by estrogen in kidney at day 11 is at 10% of the level in the liver but estrogen-responsiveness decreases later in development and is low in the adult.
Produced by the liver, secreted into the blood and then sequestred by receptor mediated endocytosis into growing oocytes.
Protein component of the very low density lipoprotein (VLDL) of egg-laying females. Potent lipoprotein lipase inhibitor, preventing the loss of triglycerides from VLDL on their way from the liver to the growing oocytes.
Phosphatase that acts on lipids with a phosphoinositol headgroup (By similarity). Has phosphatase activity towards phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate (By similarity).
Binds to prenylated RAB and Ras superfamily members.
Regulates intracellular concentrations of taurine and glutamate. Negatively modulates SLC1A1/EAAC1 glutamate transport activity by decreasing its affinity for glutamate in a PKC activity-dependent manner. May be involved in membrane traffic.
Belongs to the lariat debranching enzyme family.
Cleaves the 2'-5' phosphodiester linkage at the branch point of excised lariat intron RNA and converts them into linear molecules that can be subsequently degraded, thereby facilitating ribonucleotide turnover. Linked to its role in pre-mRNA processing mechanism, may also participate in retrovirus replication and have an antiviral cell-intrinsic defense function.
Together with NONO, required for the formation of nuclear paraspeckles. Acts as a coactivator during transcriptional activation. Binds to RNA. May act as a regulator the circadian clock (By similarity).
As a subunit of eukaryotic initiation factor 2 (eIF-2), involved in the early steps of protein synthesis. In the presence of GTP, eIF-2 forms a ternary complex with initiator tRNA Met-tRNAi and then recruits the 40S ribosomal complex and initiation factors eIF-1, eIF-1A and eIF-3 to form the 43S pre-initiation complex (43S PIC), a step that determines the rate of protein translation. The 43S PIC binds to mRNA and scans downstream to the initiation codon, where it forms a 48S initiation complex by codon-anticodon base pairing. This leads to the displacement of eIF-1 to allow GTPase-activating protein (GAP) eIF-5-mediated hydrolysis of eIF2-bound GTP. Hydrolysis of GTP and release of Pi, which makes GTP hydrolysis irreversible, causes the release of the eIF-2-GDP binary complex from the 40S subunit, an event that is essential for the subsequent joining of the 60S ribosomal subunit to form an elongation-competent 80S ribosome. In order for eIF-2 to recycle and catalyze another round of initiation, the GDP bound to eIF-2 must be exchanged with GTP by way of a reaction catalyzed by GDP-GTP exchange factor (GEF) eIF-2B.
Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. EIF2G subfamily.
The eukaryotic translation initiation factor 2 complex/eIF2 is a heterotrimer composed of an alpha, a beta and a gamma subunit.
Expressed in several tissues including testis.
Core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome (By similarity). 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 (By similarity). Component of the U1 snRNP (By similarity). 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 (By similarity). 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 (By similarity). 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 (By similarity). Component of the U11/U12 snRNPs that are part of the U12-type spliceosome (By similarity). 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 (By similarity). Forms a 6S pICln-Sm complex composed of CLNS1A/pICln, SNRPD1, SNRPD2, SNRPE, SNRPF and SNRPG; ring-like structure where CLNS1A/pICln mimics additional Sm proteins and which is unable to assemble into the core snRNP (By similarity). Identified in a histone pre-mRNA complex, at least composed of ERI1, LSM11, SLBP, SNRPB, SYNCRIP and YBX1 (By similarity). Interacts with TDRD3 and SNUPN (By similarity). Interacts with PRMT5; interaction leads to its symmetric arginine dimethylation (By similarity). Interacts with TDRD6; interaction promotes association with PRMT5 (By similarity). Interacts with SMN1; the interaction is direct (By similarity).
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 (By similarity). Component of both the pre-catalytic spliceosome B complex and activated spliceosome C complexes (By similarity). Is also a component of the minor U12 spliceosome (By similarity). As part of the U7 snRNP it is involved in histone pre-mRNA 3'-end processing (By similarity).
Belongs to the chibby family. SPERT subfamily.
Component of the SWI/SNF-B (PBAF) chromatin-remodeling complex.
Involved in transcriptional activation and repression of select genes by chromatin remodeling (alteration of DNA-nucleosome topology).
Belongs to the eukaryotic ribosomal protein eS24 family.
Belongs to the metallophosphoesterase superfamily. CPPED1 family.
Belongs to the peptidase M24A family. Methionine aminopeptidase eukaryotic type 2 subfamily.
Binds 2 divalent metal cations per subunit. Has a high-affinity and a low affinity metal-binding site. The true nature of the physiological cofactor is under debate. The enzyme is active with cobalt, zinc, manganese or divalent iron ions. Most likely, methionine aminopeptidases function as mononuclear Fe(2+)-metalloproteases under physiological conditions, and the catalytically relevant metal-binding site has been assigned to the histidine-containing high-affinity site.
Binds EIF2S1 at low magnesium concentrations. Interacts strongly with the eIF-2 gamma-subunit EIF2S3.
Contains approximately 12 O-linked N-acetylglucosamine (GlcNAc) residues. O-glycosylation is required for EIF2S1 binding.
Cotranslationally removes the N-terminal methionine from nascent proteins. The N-terminal methionine is often cleaved when the second residue in the primary sequence is small and uncharged (Met-Ala-, Cys, Gly, Pro, Ser, Thr, or Val).
Protects eukaryotic initiation factor EIF2S1 from translation-inhibiting phosphorylation by inhibitory kinases such as EIF2AK2/PKR and EIF2AK1/HCR. Plays a critical role in the regulation of protein synthesis.
Belongs to the nucleotide pyrophosphatase/phosphodiesterase family.
Belongs to the glycoprotein hormones subunit alpha family.
Belongs to the class-II aminoacyl-tRNA synthetase family. Type 2 subfamily.
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.
Belongs to the potassium channel family. D (Shal) (TC 1.A.1.2) subfamily. Kv4.2/KCND2 sub-subfamily.
Belongs to the small GTPase superfamily. Rho family.
Regulates a signal transduction pathway linking plasma membrane receptors to the assembly of focal adhesions and actin stress fibers. Serves as a microtubule-dependent signal that is required for the myosin contractile ring formation during cell cycle cytokinesis. Regulates apical junction formation in bronchial epithelial cells (By similarity).
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.
GTPase activator for the nuclear Ras-related regulatory protein RAP-1A (KREV-1), converting it to the putatively inactive GDP-bound state.
Belongs to the parathyroid hormone family.
PTH elevates calcium level by dissolving the salts in bone and preventing their renal excretion.
Acts as a transcriptional activator or repressor. Positively regulates the expression of alpha A crystallin genes during lens fiber cell differentiation. Binds to Maf recognition elements (MARE).
Expressed in kidney, brain, lung, gut, mesenterium, testis and ovary.
Expressed in the lens placode at stage 14. Expressed at stage 18 when the invaginating lens placode closes to form the lens vesicle.
Homodimer or heterodimer. Binds DNA as a homodimer or a heterodimer. Interacts with HOXD12, PAX6 and PRRX1; interaction is direct and inhibits its DNA-binding and transactivating activity.
The basic region and the leucine zipper structure are necessary for association with HOXD12 and PRRX1.
Expressed in the neural epithelium, otic placodes, optic placodes, branchial arches, and the olfactory placodes,.
Expression is pan-neuronal at stages 8-20. Expressed throughout the rostral neural ectoderm and along the rostrocaudal axis but is absent from the more lateral, non-neuronal ectoderm. Adjacent to the neural tube, detected at the optic and otic placodes. At stage 20, expression is observed in the branchial arches and olfactory placodes in addition to brain and optic and otic placodes.
Probable transcription regulator. Maybe involved in the in 45S precursor rRNA production (By similarity).
A cytochrome P450 monooxygenase that catalyzes the side-chain hydroxylation and cleavage of cholesterol to pregnenolone, the precursor of most steroid hormones. Catalyzes three sequential oxidation reactions of cholesterol, namely the hydroxylation at C22 followed with the hydroxylation at C20 to yield 20R,22R-hydroxycholesterol that is further cleaved between C20 and C22 to yield the C21-steroid pregnenolone and 4-methylpentanal. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate and reducing the second into a water molecule. Two electrons are provided by NADPH via a two-protein mitochondrial transfer system comprising flavoprotein FDXR (adrenodoxin/ferredoxin reductase) and nonheme iron-sulfur protein FDX1 or FDX2 (adrenodoxin/ferredoxin).
Belongs to the sodium:solute symporter (SSF) (TC 2.A.21) family.
Belongs to the mitochondrion-specific ribosomal protein mS26 family.
Belongs to the SLAIN motif-containing family.
Belongs to the methyltransferase superfamily. LCMT family.
Methylates the carboxyl group of the C-terminal leucine residue of protein phosphatase 2A catalytic subunits to form alpha-leucine ester residues.
Can act both with Mn(2+) and Mg(2+) as cofactor in vitro, but Mn(2+) is the preferred cofactor in vivo.
DNA primase and DNA polymerase required to tolerate replication-stalling lesions by bypassing them (PubMed:26626482). Required to facilitate mitochondrial and nuclear replication fork progression by initiating de novo DNA synthesis using dNTPs and acting as an error-prone DNA polymerase able to bypass certain DNA lesions (PubMed:26694751, PubMed:27230014). Shows a high capacity to tolerate DNA damage lesions such as 8oxoG and abasic sites in DNA (By similarity). Provides different translesion synthesis alternatives when DNA replication is stalled: able to synthesize DNA primers downstream of lesions, such as UV lesions, R-loops and G-quadruplexes, to allow DNA replication to continue (PubMed:26694751, PubMed:27230014, PubMed:26626482). Can also realign primers ahead of 'unreadable lesions' such as abasic sites and 6-4 photoproduct (6-4 pyrimidine-pyrimidinone), thereby skipping the lesion (By similarity). Also able to incorporate nucleotides opposite DNA lesions such as 8oxoG, like a regular translesion synthesis DNA polymerase (By similarity). Also required for reinitiating stalled forks after ultraviolet (UV) damage during nuclear DNA replication (By similarity). Required for mitochondrial DNA (mtDNA) synthesis and replication, by reinitiating synthesis after UV damage or in the presence of chain-terminating nucleotides (By similarity). In addition to its role in DNA damage response, also required to maintain efficient nuclear and mitochondrial DNA replication in unperturbed cells (By similarity).
The presence of an Asp-Aaa-Glu (DxE) motif in the metal-binding active site favors the use of Mn(2+) ions to achieve optimal incoming nucleotide stabilization, especially required during primer synthesis. Glu-118 is required to stabilize the incoming nucleotide at the 3'-site.
The zinc knuckle motif binds zinc and is required for the DNA primase activity. It facilitates the binding and selection of the 5'-nucleotide of the newly synthesized primer and the recognition of preferred initiation sites.
Belongs to the Mediator complex subunit 16 family.
Expressed in early stages of follicle development up to large white follicles with highest level in small white follicles.
Hens express reduced levels of SH3GL3 in ovarian follicles prior to uptake of yolk proteins.
Highest level in a region associated with endocytosis of yolk proteins in developing oocytes (at protein level). Highest level in small ovarian follicles. High levels in brain and testis. Lower level in adrenal glands.
Implicated in endocytosis. May recruit other proteins to membranes with high curvature (By similarity). Implicated in endocytosis of yolk proteins during oogenesis.
By treatment with lipopolysaccharides (LPS) or cytokines, but not in osteoclasts where they are induced by calcium and PMA (phorbol 12-myristate 13-acetate).
Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. NO may serve as both a paracrine and autocrine signal for modulating osteoclast bone resorption. Also has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such COX2 (By similarity).
Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the enzyme.
B-type lamins undergo a series of modifications, such as farnesylation and phosphorylation. Increased phosphorylation of the lamins occurs before envelope disintegration and probably plays a role in regulating lamin associations.
Asn-62 is fully glycosylated, whereas only less than 10% of Asn-293 seem to be glycosylated.
Expressed at high levels at the middle of the calcification stage of shell formation. Expression levels are similar at 3-4 hours post-oviposition prior to entry of the egg into the uterus and at 16-17 hours post-oviposition during eggshell calcification. Expressed in tibia from 5 dpc and in mandible from 7 dpc until the end of embryonic development at 19 dpc. Expression detected first in osteoblasts, in later stages both in osteoblasts and osteocytes, and by the end of embryonic development mainly in osteocytes.
In the eggshell, expressed mainly in the palisade and mammillary layers. Expression also detected in the hypertrophic zone of the epiphyseal growth plate, and in cortical and medullary bone (at protein level). Highly expressed in uterus. Not detected in the proximal oviduct, liver, magnum, duodenum and kidney.
Major component of the eggshell matrix. May play an important role in the regulation of calcite growth during eggshell calcification. May also regulate the mineralization process in developing and growing bones.
May play a role in the trafficking of a subset of G-protein coupled receptors.
Belongs to the Antp homeobox family. Deformed subfamily.
E1-like activating enzyme involved in the 2 ubiquitin-like systems required for cytoplasm to vacuole transport (Cvt) and autophagy. Activates ATG12 for its conjugation with ATG5 as well as the ATG8 family proteins for their conjugation with phosphatidylethanolamine. Both systems are needed for the ATG8 association to Cvt vesicles and autophagosomes membranes. Required for autophagic death induced by caspase-8 inhibition. Facilitates LC3-I lipidation with phosphatidylethanolamine to form LC3-II which is found on autophagosomal membranes (By similarity). Required for mitophagy which contributes to regulate mitochondrial quantity and quality by eliminating the mitochondria to a basal level to fulfill cellular energy requirements and preventing excess ROS production. Modulates p53/TP53 activity to regulate cell cycle and survival during metabolic stress (By similarity). Plays a role in regulating the liver clock and glucose metabolism by mediating the autophagic degradation of CRY1 (clock repressor) in a time-dependent manner (By similarity).
Homodimer. Interacts with ATG3 and ATG12. The complex, composed of ATG3 and ATG7, plays a role in the conjugation of ATG12 to ATG5 (By similarity).
The C-terminal part of the protein is essential for the dimerization and interaction with ATG3 and ATG12.
Acts as a sequence specific DNA binding transcriptional activator or repressor. The isoforms contain a varying set of transactivation and auto-regulating transactivation inhibiting domains thus showing an isoform specific activity. May be required in conjunction with TP73/p73 for initiation of p53/TP53 dependent apoptosis in response to genotoxic insults and the presence of activated oncogenes.
Binds DNA as a homotetramer. Isoform composition of the tetramer may determine transactivation activity.
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 (By similarity).
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.
Belongs to the eukaryotic ribosomal protein eS6 family.
Component of the 40S small ribosomal subunit (By similarity). Plays an important role in controlling cell growth and proliferation through the selective translation of particular classes of mRNA (By similarity).
Ribosomal protein S6 is the major substrate of protein kinases in eukaryote ribosomes. The phosphorylation is stimulated by growth factors, tumor promoting agents, and mitogens. It is dephosphorylated at growth arrest.
Belongs to the glycosyltransferase 22 family.
Heterodimer. Interacts with a catalytic subunit and with G beta gamma proteins (By similarity).
Regulatory subunit of the PI3K gamma complex.
The heterodimerization region allows the binding to the catalytic subunit.
Calcium-binding or N-myristoylation are necessary for the Na(+)/H(+) exchange activities.
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. Inhibits serum- and GTPase-stimulated Na(+)/H(+) exchange. Plays a role as an inhibitor of ribosomal RNA transcription. Acts as a negative regulator of the calcineurin/NFAT signaling pathway.
Growth hormone plays an important role in growth control.
Key transcriptional regulator of type I interferon (IFN)-dependent immune responses which plays a critical role in the innate immune response against DNA and RNA viruses. 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. May activate transcription by complex formation with other transcriptional factors, possibly members of the STAT family. Binds specifically to the IFN-stimulated response element (ISRE) but not to the IRF-1 binding site PRD-I.
Widely expressed with higher expression in lung, spleen and intestine.
Belongs to the complex I NDUFC2 subunit family.
Belongs to the Tim17/Tim22/Tim23 family.
Component of the TIM23 complex, at least composed of TIM23, TIM17, TIM50 and TIM21.
Essential component of the TIM23 complex, a complex that mediates the translocation of transit peptide-containing proteins across the mitochondrial inner membrane.
Belongs to the SRP receptor beta subunit family.
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 (By similarity).
Glycosyltransferase that catalyze the transfer of GlcNAc from UDP-GlcNAc to the GlcNAcbeta1-2Manalpha1-3 arm of the core structure of N-linked glycans through a beta1-4 linkage and participates in the production of tri- and tetra-antennary N-linked sugar chains (By similarity). Involved in glucose transport by mediating SLC2A2/GLUT2 glycosylation, thereby controlling cell-surface expression of SLC2A2 in pancreatic beta cells (By similarity).
May serve as a multifunctional regulator for innate immune signaling pathways.
Acts as an antagonist of FGF-induced retinal lens fiber differentiation (By similarity). Inhibits TGFB-induced epithelial-to-mesenchymal transition in retinal lens epithelial cells (By similarity). May play an important role in FGF-mediated patterning of the mid/hindbrain region by acting to modulate the signaling effects of FGF8 (PubMed:10662503).
At the 4- to 5-somite stage (4/5S) found in the embryo in scattered cells across the neural plate in the presumptive mid/ hindbrain region (PubMed:10662503). At 7/8S found in the isthmus and throughout the presumptive r1 territory. Between 10-14S stage found throughout the R1 region and at the isthmic constriction (PubMed:10662503). By 26S the anterior limit of expression extends into the posterior midbrain region and this pattern of expression is maintained at later stages (PubMed:10662503).
The Cys-rich domain is responsible for the localization of the protein to the membrane ruffles.
Belongs to the PpiC/parvulin rotamase family. PIN4 subfamily.
Belongs to the IspD/TarI cytidylyltransferase family. IspD subfamily.
Belongs to the TMEM97/sigma-2 receptor family.
Intracellular orphan receptor that binds numerous drugs and which is highly expressed in various proliferating cells. Corresponds to the sigma-2 receptor, which is thought to play important role in regulating cell survival, morphology and differentiation. May play a role as a regulator of cellular cholesterol homeostasis. May function as sterol isomerase. May alter the activity of some cytochrome P450 proteins.
Expressed in embryonic fibroblasts and chondrocytes.
May be involved in transcription regulation of the alpha 2(I) collagen gene where it binds to the single-stranded polypyrimidine sequences in the promoter region.
The GINS complex plays an essential role in the initiation of DNA replication.
Catalytic component of the tRNA-splicing ligase complex.
Catalytic subunit of the tRNA-splicing ligase complex that acts by directly joining spliced tRNA halves to mature-sized tRNAs by incorporating the precursor-derived splice junction phosphate into the mature tRNA as a canonical 3',5'-phosphodiester. May act as an RNA ligase with broad substrate specificity, and may function toward other RNAs.
Ligation probably proceeds through 3 nucleotidyl transfer steps, with 2',3'-cyclic phosphate termini being hydrolyzed to 3'-P termini in a step that precedes 3'-P activation with GMP. In the first nucleotidyl transfer step, RTCB reacts with GTP to form a covalent RTCB-histidine-GMP intermediate with release of PPi; in the second step, the GMP moiety is transferred to the RNA 3'-P; in the third step, the 5'-OH from the opposite RNA strand attacks the activated 3'-P to form a 3',5'-phosphodiester bond and release GMP.
Expressed at high levels in adult intestine, spleen, thymus and testis with lower levels in skeletal muscle and eye. In the embryo, expressed at higher levels until day 10 with lower levels in later stages.
Phosphorylates the deoxyribonucleosides deoxycytidine, deoxyguanosine and deoxyadenosine (PubMed:27906638). Displays highest activity against deoxycytidine followed by deoxyadenosine and then deoxyguanosine (PubMed:27906638). Shows only very minor activity against deoxyuridine and deoxythymidine (PubMed:27906638).
Homodimer in cis. Does not appear to form trans-homodimers.
Transmembrane protein which can modulate activity of various signaling pathways, probably via binding to integrin ITGAV:ITGB3. Mediates heterophilic cell-cell interactions in vitro.
Totally down-regulated in transformed cells. May therefore take part in the control of cell growth and differentiation.
Part of the endoplasmic reticulum membrane protein complex (EMC) that enables the energy-independent insertion into endoplasmic reticulum membranes of newly synthesized membrane proteins. Preferentially accommodates proteins with transmembrane domains that are weakly hydrophobic or contain destabilizing features such as charged and aromatic residues. Involved in the cotranslational insertion of multi-pass membrane proteins in which stop-transfer membrane-anchor sequences become ER membrane spanning helices. It is also required for the post-translational insertion of tail-anchored/TA proteins in endoplasmic reticulum membranes. 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. By regulating the insertion of various proteins in membranes, it is indirectly involved in many cellular processes.
Can cause an allergic reaction in humans.
During storage of fertilized and non-fertilized eggs or under alkaline conditions, the native ovalbumin conformer (N-ovalbumin) is transformed into a thermostabilized conformer, S-ovalbumin. Ser-165, Ser-237 and Ser-321 take on a D-configuration in this conformer and may be responsible for the thermostability.
Major protein of egg white. Expressed in the magnum of the oviduct (at protein level) (PubMed:25436390).
Non-inhibitory serpin. Storage protein of egg white.
The uncleaved signal peptide becomes available for membrane translocation of ovalbumin when the nascent chain is 50 to 60 residues long. The hydrophobic sequence, which lies between residues 27 and 43, folds back on the preceding residues to form an amphipathic hairpin structure which is the signal element recognized by the membrane.
Undergoes proteolytic cleavage first at the canonical P1-P1' site, and then at the P8-P7 site by subtilisin.
Unlike other serpins, after protease cleavage at the P-P' site, ovalbumin does not have the ability to undergo the conformational transition into the loop-inserted reactive-center-containing thermostabilized form. The bulky arginine residue (Arg-340) at the hinge region appears to be responsible for this lack of loop-inserted conformational change, but not for the absence of serpin inhibitory activity.
Detected in bursa of Fabricius, in filamentous structures surrounding the basal and lateral surfaces of bursal M cells (at protein level). Detected in bursa of Fabricius, in secretory enterocytes of the interfollicular bursal epithelium, but not in M cells.
Has potent antimicrobial activity against Gram-positive and Gram-negative bacteria (in vitro). May play a role in the innate immune response.
Potential calcium-dependent cell-adhesion protein.
Transiently expressed in the nascent hindlimb bud between Hamburger-Hamilton stages 15 and 19. Also found in the basal plate of rhombomeres 3 and 5, in pharyngeal and in foregut mesenchyme and in all facial primordia except for the mandibular arches.
(Microbial infection) Plays an essential role in efficient replication and spread of Marek's disease virus, by facilitating viral cell-to-cell spread.
Lysosomal membrane glycoprotein which plays an important role in lysosome biogenesis, autophagy, and cholesterol homeostasis. Presents carbohydrate ligands to selectins. Also implicated in tumor cell metastasis.
Belongs to the CoA-transferase III family.
Acts on tyrosine phosphorylated proteins, low-MW aryl phosphates and natural and synthetic acyl phosphates.
Belongs to the low molecular weight phosphotyrosine protein phosphatase family.
Belongs to the WD repeat LIS1/nudF family.
Can self-associate. Component of the cytosolic PAF-AH (I) heterotetrameric enzyme, which is composed of PAFAH1B1 (beta), PAFAH1B2 (alpha2) and PAFAH1B3 (alpha1) subunits. The catalytic activity of the enzyme resides in the alpha1 (PAFAH1B3) and alpha2 (PAFAH1B2) subunits, whereas the beta subunit (PAFAH1B1) has regulatory activity. Trimer formation is not essential for the catalytic activity (By similarity). Interacts with dynein, dynactin, NDE1 and NDEL1.
Dimerization mediated by the LisH domain may be required to activate dynein.
Expressed in the intermediate and lateral mesoderm, posterior neural tube, notochord and somites of stage 9 embryos. Expressed in the neural tube, roof plate, notochord, somites, dermomymotomes and eye of stage 20 embryos. This expression pattern persists in stage 27 embryos, where expression is also seen in the heart, intestine and dorsal aorta. Weakly and uniformly expressed in the stage 35 embryo.
Regulatory subunit (beta subunit) of the cytosolic type I platelet-activating factor (PAF) acetylhydrolase (PAF-AH (I)), an enzyme that catalyzes the hydrolyze of the acetyl group at the sn-2 position of PAF and its analogs and participates in PAF inactivation. Regulates the PAF-AH (I) activity in a catalytic dimer composition-dependent manner (By similarity). 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 end. Required for several dynein- and microtubule-dependent processes such as the maintenance of Golgi integrity, the peripheral transport of microtubule fragments and the coupling of the nucleus and centrosome. May be required for proliferation of neuronal precursors and neuronal migration.
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.
Binds TNC and TNR. The 80 kDa form but not the 140 kDa form can bind TNC and TNR when expressed at the cell surface.
Different forms exist: the 140 kDa form (also reported as 130 kDa), which probably consists of the entire protein, and the 38 and 80 kDa forms, which are probably cleaved in their N-terminus. Increase in synaptic activity, results in shedding of the extracellular domain and expression at the cell surface of a 38 kDa form. A form of 200 kDa has also been reported, which is probably hyperglycosylated.
Expressed in astroglial and neuronal surfaces in different parts of the embryonic brain. Expressed in adult brain and retina (at protein level).
May function as a growth and differentiation factor involved in neuritogenesis and more particularly in neurite extension.
O-glycosylated; contains chondroitin sulfate glycans. Part-time proteoglycan, the 200 kDa form is the only one containing chondroitin sulfate glycans.
The 80 kDa and 200 kDa forms were detected only during embryonic development. The 80 kDa form reaches a maximum of expression at 14 dpc/15 dpc and then decreases gradually. The 140 kDa form is already detected at 7 dpc. The 130 and 140 kDa forms reach their maximal expression at 20 dpc (at protein level).
Translation initiation regulator which may repress repeat-associated non-AUG (RAN) initiated translation probably by acting as a competitive inhibitor of eukaryotic translation initiation factor 5 (EIF5) function (By similarity). Enhances histone H4 gene transcription but does not seem to bind DNA directly (By similarity).
Belongs to the HAD-like hydrolase superfamily. SerB family.
Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis.
Belongs to the dermatan-sulfate isomerase family.
Dually phosphorylated on Thr-626 and Tyr-628, which activates the enzyme.
Phosphorylates microtubule-associated protein 2 (MAP2). May promote entry in the cell cycle (By similarity).
E3 ubiquitin-protein ligase which targets misfolded chaperone substrates towards proteasomal degradation (By similarity). Collaborates with ATXN3 in the degradation of misfolded chaperone substrates: ATXN3 restricting the length of ubiquitin chain attached to STUB1/CHIP substrates and preventing further chain extension (By similarity).
The U-box domain is required for the ubiquitin protein ligase activity.
Abundant in the cochlea of the inner ear, where it is found in the cells of the tegmentum vasculosum. Lower levels also found in the heart and forebrain.
Belongs to the DEAD box helicase family. DDX55/SPB4 subfamily.
Belongs to the glycosyltransferase 47 family.
Involved in the development of the organizer region in the gastrula (Hensen node in chicken).
Is first expressed in the Koller's sickle (a crescent shaped thickening located at the edge of the posterior marginal zone), and then it is detected in Hensen node which is considered as the chick organizer. Later expression is seen in the anterior most region of the head process (cells that contribute to the prechordal plate at the midline of the pharyngeal mesendoderm).
Belongs to the Integrator subunit 2 family.
This parvalbumin has an isoelectric point of 4.6.
The uracil binding region known from UPRTases is missing.
Belongs to the phosphatidylserine decarboxylase family. PSD-B subfamily. Eukaryotic type I sub-subfamily.
Catalyzes the formation of phosphatidylethanolamine (PtdEtn) from phosphatidylserine (PtdSer). Plays a central role in phospholipid metabolism and in the interorganelle trafficking of phosphatidylserine.
Heterodimer of a large membrane-associated beta subunit and a small pyruvoyl-containing alpha subunit.
Is synthesized initially as an inactive proenzyme. Formation of the active enzyme involves a self-maturation process in which the active site pyruvoyl group is generated from an internal serine residue via an autocatalytic post-translational modification. Two non-identical subunits are generated from the proenzyme in this reaction, and the pyruvate is formed at the N-terminus of the alpha chain, which is derived from the carboxyl end of the proenzyme. The autoendoproteolytic cleavage occurs by a canonical serine protease mechanism, in which the side chain hydroxyl group of the serine supplies its oxygen atom to form the C-terminus of the beta chain, while the remainder of the serine residue undergoes an oxidative deamination to produce ammonia and the pyruvoyl prosthetic group on the alpha chain. During this reaction, the Ser that is part of the protease active site of the proenzyme becomes the pyruvoyl prosthetic group, which constitutes an essential element of the active site of the mature decarboxylase.
Activated through phosphorylation by atr or atm in response to DNA damage or inhibition of DNA replication.
Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. NIM1 subfamily.
Phosphorylated by ATR in a RAD17-dependent manner in response to ultraviolet irradiation and inhibition of DNA replication. Phosphorylated by ATM in response to ionizing irradiation (By similarity). Phosphorylation at Ser-345 induces a change in the conformation of the protein and activates the kinase activity. Phosphorylation at Ser-345 also increases binding to 14-3-3 proteins and promotes nuclear retention (PubMed:12554671).
Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest and activation of DNA repair in response to the presence of DNA damage or unreplicated DNA (PubMed:12554671). May also negatively regulate cell cycle progression during unperturbed cell cycles. This regulation is achieved by a number of mechanisms that together help to preserve the integrity of the genome. Recognizes the substrate consensus sequence [R-X-X-S/T]. Binds to and phosphorylates CDC25A, CDC25B and CDC25C. This inhibits their activity through proteasomal degradation, nucleo-cytoplasmic shuttling and inhibition by proteins of the 13-3-3 family. Inhibition of CDC25 leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. May promote DNA repair, regulate chromatin assembly and the transcription of genes that regulate cell-cycle progression. May also play a role in replication fork maintenance (By similarity).
The autoinhibitory region (AIR) inhibits the activity of the kinase domain.
Plays a role in U6 snRNP assembly and function. Binds to the 3' end of U6 snRNA.
Pancreatic hormone is synthesized in pancreatic islets of Langerhans and acts as a regulator of pancreatic and gastrointestinal functions.
Plays a key role in glucose metabolism and homeostasis. Regulates blood glucose by increasing gluconeogenesis and decreasing glycolysis.
Potent stimulator of glucose-dependent insulin release. Plays important roles on gastric motility and the suppression of plasma glucagon levels. May be involved in the suppression of satiety and stimulation of glucose disposal in peripheral tissues, independent of the actions of insulin. Has growth-promoting activities on intestinal epithelium. May also regulate the hypothalamic pituitary axis (HPA) via effects on LH, TSH, CRH, oxytocin, and vasopressin secretion. Increases islet mass through stimulation of islet neogenesis and pancreatic beta cell proliferation.
Produced in the A cells of the islets of Langerhans in response to a drop in blood sugar concentration.
Proglucagon is post-translationally processed in a tissue-specific manner in pancreatic A cells and intestinal L cells. In pancreatic A cells, the major bioactive hormone is glucagon cleaved by PCSK2/PC2. In the intestinal L cells PCSK1/PC1 liberates GLP-1 and GLP-2. GLP-1 is further N-terminally truncated by post-translational processing in the intestinal L cells resulting in GLP-1(7-37) GLP-1-(7-36)amide (By similarity).
Stimulates intestinal growth and up-regulates villus height in the small intestine, concomitant with increased crypt cell proliferation and decreased enterocyte apoptosis. The gastrointestinal tract, from the stomach to the colon is the principal target for GLP-2 action. Plays a key role in nutrient homeostasis, enhancing nutrient assimilation through enhanced gastrointestinal function, as well as increasing nutrient disposal. Stimulates intestinal glucose transport and decreases mucosal permeability.
Belongs to the fatty acid desaturase CarF family.
Interacts with DEGS1; the interaction increases synthesis of chromophore-precursors by DEGS1.
Soluble retinoid carrier essential the proper function of both rod and cone photoreceptors. Participates in the regeneration of active 11-cis-retinol and 11-cis-retinaldehyde, from the inactive 11-trans products of the rhodopsin photocycle and in the de novo synthesis of these retinoids from 11-trans metabolic precursors. The cycling of retinoids between photoreceptor and adjacent pigment epithelium cells is known as the 'visual cycle'.
Prolyl 3-hydroxylase that catalyzes the post-translational formation of 3-hydroxyproline on collagens (By similarity). Contributes to proline 3-hydroxylation of collagen COL4A1 and COL1A1 in tendons, the eye sclera and in the eye lens capsule (By similarity). Has high activity with the type IV collagen COL4A1, and lower activity with COL1A1. Catalyzes hydroxylation of the first Pro in Gly-Pro-Hyp sequences where Hyp is 4-hydroxyproline. Has no activity on substrates that lack 4-hydroxyproline in the third position (By similarity).
Catalyzes the conjugation of GSH to a wide variety of electrophilic alkylating agents. Also involved in the metabolism of lipid hydroperoxides, prostaglandins and leukotriene A4 and in binding of non-substrate hydrophobic ligands such as bile acids, a number of drugs and thyroid hormones. This GST does not exhibit peroxidase activity.
Homodimer or heterodimer (with a subunit from group CL-4).
The variations were found from AA sequencing and imply there are multiple forms of CL-3.
Detected in the anterior parencephalon and secondary prosencephalon at stages 20 and 24. Expressed in the ventricular epithelium of the spinal cord at the latest stages.
Expressed in differentiating lens fiber cells.
Ligand for members of the frizzled family of seven transmembrane receptors that functions in the canonical Wnt/beta-catenin signaling pathway (By similarity). Required for normal fusion of the chorion and the allantois during placenta development (By similarity). Required for central nervous system (CNS) angiogenesis and blood-brain barrier regulation (By similarity).
Heterodimer of a B chain and an A chain linked by two disulfide bonds.
Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synthesis in liver.
Accessory subunit that is involved in the functional assembly of the mitochondrial respiratory chain complex I. Complex I has an NADH dehydrogenase activity with ubiquinone as an immediate electron acceptor and mediates the transfer of electrons from NADH to the respiratory chain.
Belongs to the complex I NDUFB10 subunit family.
Functions as component of the Arp2/3 complex which is involved in regulation of actin polymerization and together with an activating nucleation-promoting factor (NPF) mediates the formation of branched actin networks. Arp2/3 complex plays a critical role in the control of cell morphogenesis via the modulation of cell polarity development.
Melanocytes and retinal pigmented epithelium.
Plays a role in melanin biosynthesis. Catalyzes the conversion of L-dopachrome into 5,6-dihydroxyindole-2-carboxylic acid (DHICA).
In the C-terminal section; belongs to the aldehyde dehydrogenase family. ALDH1L subfamily.
In the N-terminal section; belongs to the GART family.
Expressed more highly in male embryonic day 3 (3 dpc) and 5 dpc whole embryos, paired urogenital system at 7 dpc and gonads at 9 dpc than in females.
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 (By similarity).
Highly expressed in ovary. Also detected in brain, heart, lung, liver, spleen and kidney, and at low levels in gizzard, muscle, testis and proventriculus.
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. Mediates the response to mycoplasmal macrophage-activating lipopeptide-2kD (MALP-2).
Expressed in mesoderm- and, to a lesser extent, in ectoderm-derived tissues.
Major protein of plasma HDL, also found in chylomicrons.
Participates in the reverse transport of cholesterol from tissues to the liver for excretion by promoting cholesterol efflux from tissues and by acting as a cofactor for the lecithin cholesterol acyltransferase (LCAT).
Belongs to the polyribonucleotide nucleotidyltransferase family.
Belongs to the eukaryotic ribosomal protein eL43 family.
Expressed in the limb mesenchyme throughout stages 16 to 32. Expressed in the prospective wing bud at stage 16. Expressed in the leg bud at stage 17. Expressed in the forebrain throughout stages 14 to 21.
Extensively phosphorylated on serine residues in the RS domain.
Necessary for the splicing of pre-mRNA. It is required for formation of the earliest ATP-dependent splicing complex and interacts with spliceosomal components bound to both the 5'- and 3'-splice sites during spliceosome assembly. It also is required for ATP-dependent interactions of both U1 and U2 snRNPs with pre-mRNA.
Chemorepulsive axon guidance protein required for the development of spinal cord and forebrain commissures. Acts as a chemorepulsive guidance protein for commissural axons during development. Able to inhibit or repel neurite outgrowth from dorsal spinal cord and cortical explants in vitro. Binds directly to the neurites and growth cones.
Expressed transiently during development of the brain and spinal cord, especially in the roof plate and the dorsal lip of the dermomyotome. Also present at the dorsolateral basement membrane of the spinal cord (at protein level).
Binds and promotes bundling of vimentin filaments originating from the Golgi.
Folate-dependent enzyme, that displays both transferase and deaminase activity. Serves to channel one-carbon units from formiminoglutamate to the folate pool.
Homooctamer, including four polyglutamate binding sites. The subunits are arranged as a tetramer of dimers, and form a planar ring-shaped structure.
In the C-terminal section; belongs to the cyclodeaminase/cyclohydrolase family.
In the N-terminal section; belongs to the formiminotransferase family.
Belongs to the acetyltransferase family. GNA1 subfamily.
Belongs to the universal ribosomal protein uS4 family.
Homodimer, and heterodimer with SH3GLB2. Binds BAX. Binds DNM1, HTT, AMPH, BIN1 and ARFGAP1 (By similarity).
May be required for normal outer mitochondrial membrane dynamics. Required for coatomer-mediated retrograde transport in certain cells. May recruit other proteins to membranes with high curvature. May promote membrane fusion (By similarity).
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.
May play a role in microtubule-mediated transport or vesicle function.
Has E3 ubiquitin ligase activity towards IGBP1, promoting its monoubiquitination, which results in deprotection of the catalytic subunit of protein phosphatase PP2A, and its subsequent degradation by polyubiquitination.
Mediates cell surface interactions during nervous system development. Interaction with TNR enhances the neurite outgrowth.
Component of the BCR(KLHL9-KLHL13) E3 ubiquitin ligase complex, at least composed of CUL3, KLHL9, KLHL13 and RBX1. Interacts with AURKB (By similarity).
Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex required for mitotic progression and cytokinesis. The BCR(KLHL9-KLHL13) E3 ubiquitin ligase complex mediates the ubiquitination of AURKB and controls the dynamic behavior of AURKB on mitotic chromosomes and thereby coordinates faithful mitotic progression and completion of cytokinesis (By similarity).
Catalytic subunit of H/ACA small nucleolar ribonucleoprotein (H/ACA snoRNP) complex, which catalyzes pseudouridylation of rRNA. This involves the isomerization of uridine such that the ribose is subsequently attached to C5, instead of the normal N1. 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.
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. 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. The complex binds a box H/ACA small nucleolar RNA (snoRNA), which may target the specific site of modification within the RNA substrate.
May play role in the regulation of alternative splicing. May have hydrolase activity.
Centrosomal protein required for establishing a robust mitotic centrosome architecture that can endure the forces that converge on the centrosomes during spindle formation. Required for stabilizing the expanded pericentriolar material around the centriole.
Acts as a component of the essential kinetochore-associated NDC80 complex, which is required for chromosome segregation and spindle checkpoint activity (PubMed:12829748). Required for kinetochore integrity and the organization of stable microtubule binding sites in the outer plate of the kinetochore (By similarity). The NDC80 complex synergistically enhances the affinity of the SKA1 complex for microtubules and may allow the NDC80 complex to track depolymerizing microtubules (By similarity).
Component of the NDC80 complex, which is composed of at least NDC80/HEC1 and CDCA1.
Belongs to the protein kinase superfamily. Tyr protein kinase family. Fes/fps subfamily.
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 (By similarity).
Belongs to the glycosyl hydrolase 27 family.
Belongs to the succinate dehydrogenase/fumarate reductase iron-sulfur protein family.
Iron-sulfur protein (IP) subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q).
Belongs to the TRAFAC class OBG-HflX-like GTPase superfamily. OBG GTPase family. NOG subfamily.
Involved in the biogenesis of the 60S ribosomal subunit.
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. Component of HBO1 complexes, which specifically mediate acetylation of histone H3 at 'Lys-14' (H3K14ac), and have reduced activity toward histone H4. Component of the MOZ/MORF complex which has a histone H3 acetyltransferase activity (By similarity).
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. Component of HBO1 complexes, which specifically mediate acetylation of histone H3 at 'Lys-14' (H3K14ac), and have reduced activity toward histone H4. Component of the MOZ/MORF complex which has a histone H3 acetyltransferase activity.
Component of the NuA4 histone acetyltransferase complex. Component of the hbo1 complex. Component of the moz/morf complex (By similarity).
Component of the NuA4 histone acetyltransferase complex. Component of the hbo1 complex. Component of the moz/morf complex.
Forms a stable but non-covalent complex with a regulatory subunit and with a cyclin. Interacts with catalytically active CCNB1 and RALBP1 during mitosis to form an endocytotic complex during interphase.
Phosphorylation at Tyr-15 by WEE1 and WEE2 inhibits the protein kinase activity and acts negative regulator of entry into mitosis (G2 to M transition).
Plays a key role in the control of the eukaryotic cell cycle by modulating the centrosome cycle as well as mitotic onset; promotes G2-M transition, and regulates G1 progress and G1-S transition via association with multiple interphase cyclins. Required in higher cells for entry into S-phase and mitosis. May play a role in regulating the amplitude of the cyclic expression of circadian clock genes.
Thr-14 and Tyr-15 are phosphorylated maximally during G2 phase, but dephosphorylated abruptly at the G2/M transition. Phosphorylation at Thr-14 and Tyr-15 inactivates the enzyme. During M phase it is also phosphorylated on Thr-161. Finally during G1 phase it is phosphorylated on Ser-277.
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 (By similarity).
P0 forms a pentameric complex by interaction with dimers of P1 and P2.
Ribosomal protein P0 is the functional equivalent of E.coli protein L10.
Disappears after the cartilage development.
May play a role in intercellular signaling and in connecting cells with the extracellular matrix. May take part in the regulation of cell motility, growth and differentiation. Binds hyaluronic acid.
Prechondrogenic condensation area of developing limb buds.
Cell adhesion molecule that mediates both heterotypic cell-cell contacts via its interaction with CD6, as well as homotypic cell-cell contacts. Promotes T-cell activation and proliferation via its interactions with CD6 (By similarity). Contributes to the formation and maturation of the immunological synapse via its interactions with CD6 (By similarity). Mediates homotypic interactions with cells that express ALCAM (PubMed:1931049, PubMed:22421359). Mediates attachment of dendritic cells onto endothelial cells via homotypic interaction. Inhibits endothelial cell migration and promotes endothelial tube formation via homotypic interactions. Required for normal organization of the lymph vessel network. Required for normal hematopoietic stem cell engraftment in the bone marrow. Plays a role in hematopoiesis; required for normal numbers of hematopoietic stem cells in bone marrow. Promotes in vitro osteoblast proliferation and differentiation (By similarity). Promotes neurite extension, axon growth and axon guidance; axons grow preferentially on surfaces that contain ALCAM (PubMed:1873027, PubMed:22421359). Mediates outgrowth and pathfinding for retinal ganglion cell axons (PubMed:22421359).
Detected in embryo (PubMed:1931049, PubMed:1608932). Detected in embryonic spinal cord and embryonic brain (PubMed:1873027, PubMed:1313497). Within the spinal cord it is localized to axons in the dorsal funiculus, midline floor plate cells, and motoneurons (PubMed:1873027). Detected in embryonic epithelia and brain (PubMed:1608932). After hatching, detected in bursa of Fabricius and thymus (PubMed:1608932). Detected on embryonic retinal ganglion cell axon growth cones (at protein level) (PubMed:22421359). Detected in embryonic retina and in the optic fiber layer, which is composed of retinal ganglion cell axons and their growth cones (PubMed:22421359).
Homodimer. Interacts (via extracellular domain) with CD6 (via extracellular domain). Homodimerization and interaction with CD6 involve the same region and cannot occur simultaneously. The affinity for CD6 is much higher than the affinity for self-association.
The CD6 binding site is located in the N-terminal Ig-like domain.
Widely expressed during embryonic development.
Expressed predominantly in the lung, and faintly in the kidney, liver, brain, spleen, gizzard, and intestine.
Serine/threonine-protein kinase that plays an essential role in the regulation of actin filament dynamics. Acts downstream of several Rho family GTPase signal transduction pathways. Involved in astral microtubule organization and mitotic spindle orientation during early stages of mitosis by mediating phosphorylation of TPPP.
Component of the ESCRT-I complex (endosomal sorting complex required for transport I).
Component of the ESCRT-I complex, a regulator of vesicular trafficking process. Required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies (By similarity).
Belongs to the Ca(2+):cation antiporter (CaCA) (TC 2.A.19) family. SLC8 subfamily.
Mainly in the liver (adult), mainly in the muscle (embryo).
This protein binds beta-galactoside. Its physiological function is not yet known. It may be involved in the regulation of differentiation.
Specifies dorsal cell fate during limb development.
Phosphorylation of Ser-529 is sharply increased upon progesterone treatment, whereas phosphorylation of Ser-210 and Ser-259 is modestly induced by progesterone.
Sumoylation is hormone-dependent and represses transcriptional activity. Sumoylation on all three sites is enhanced by PIAS3. Desumoylated by SENP1. Sumoylation on Lys-385, the main site of sumoylation, is repressed by ubiquitination on the same site (By similarity).
Ubiquitinated. Ubiquitination is increased by progesterone and represses sumoylation at the same site (By similarity).
Associates with GIRK2, GIRK3 or GIRK4 to form a G-protein activated heteromultimer pore-forming unit. The resulting inward current is much larger (By similarity).
Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ3 subfamily.
This potassium channel is controlled by G proteins. 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. This receptor plays a crucial role in regulating the heartbeat (By similarity).
Appears to promote immune maturation in bone marrow cells in culture. Binds two calcium ions.
This parvalbumin has an isoelectric point of 4.3.
SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. CIS is involved in the negative regulation of cytokines that signal through the JAK-STAT5 pathway such as erythropoietin, prolactin and interleukin 3 (IL3) receptor. Inhibits STAT5 trans-activation by suppressing its tyrosine phosphorylation. May be a 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 (By similarity).
Expressed in optic cup at stages 10-19 and in nephric tubules from stage 10 to 20 and more. Expression in interdigital space begins at stage 20.
Expressed in the developing kidney, interdigital spaces and optic cup.
Interacts (via FZ domain) with TSKU; TSKU competes with WNT2B for binding to FZD4, inhibiting Wnt signaling and repressing peripheral eye development.
Receptor for Wnt proteins (By similarity). Most 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 (By similarity). 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 (By similarity). Both pathways seem to involve interactions with G-proteins (By similarity). May be involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues (By similarity).
By synaptic activity. Transcript level significantly increased in auditory cortex as well as two higher-associative brain regions by auditory imprinting stimulus in newborn chicks.
Expressed at various levels throughout the brain.
Homooligomer; homooligomerizes into virion-like capsids.
Master regulator of synaptic plasticity that self-assembles into virion-like capsids that encapsulate RNAs and mediate intercellular RNA transfer in the nervous system. ARC protein is released from neurons in extracellular vesicles that mediate the transfer of ARC mRNA into new target cells, where ARC mRNA can undergo activity-dependent translation. ARC capsids are endocytosed and are able to transfer ARC mRNA into the cytoplasm of neurons. Acts as a key regulator of synaptic plasticity: required for protein synthesis-dependent forms of long-term potentiation (LTP) and depression (LTD) and for the formation of long-term memory. Regulates synaptic plasticity by promoting endocytosis of AMPA receptors (AMPARs) in response to synaptic activity: this endocytic pathway maintains levels of surface AMPARs in response to chronic changes in neuronal activity through synaptic scaling, thereby contributing to neuronal homeostasis. Acts as a postsynaptic mediator of activity-dependent synapse elimination in the developing cerebellum by mediating elimination of surplus climbing fiber synapses. Accumulates at weaker synapses, probably to prevent their undesired enhancement. This suggests that ARC-containing virion-like capsids may be required to eliminate synaptic material.
Palmitoylation anchors the protein into the membrane by allowing direct insertion into the hydrophobic core of the lipid bilayer.
The protein is evolutionarily related to retrotransposon Gag proteins: it contains large N- and C-terminal domains that form a bi-lobar architecture similar to the capsid domain of human immunodeficiency virus (HIV) gag protein. It contains structural elements found within viral Gag polyproteins originated from the Ty3/gypsy retrotransposon family and retains the ability to form virion-like capsid structures that can mediate mRNA transfer between cells. Tetrapod and fly Arc protein-coding genes originated independently from distinct lineages of Ty3/gypsy retrotransposons.
The dystroglycan complex is involved in a number of processes including laminin and basement membrane assembly, sarcolemmal stability, cell survival, peripheral nerve myelination, nodal structure, cell migration, and epithelial polarization.
Transmembrane protein that plays important roles in connecting the extracellular matrix to the cytoskeleton. Acts as a cell adhesion receptor in both muscle and non-muscle tissues. Receptor for both DMD and UTRN and, through these interactions, scaffolds axin to the cytoskeleton. Also functions in cell adhesion-mediated signaling and implicated in cell polarity.
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-V (ITGAV) associates with either beta-1 (ITGB1), beta-3 (ITGB3), beta-5 (ITGB5), beta-6 (ITGB6) or beta-8 (ITGB8) (By similarity). Interacts with RAB25. Interacts with CIB1 (By similarity). Integrins ITGAV:ITGB3 and ITGAV:ITGB5 interact with FBLN5 (via N-terminus) (By similarity). ITGAV:ITGB3 and ITGAV:ITGB5 interact with CCN3 (By similarity). ITGAV:ITGB3 interacts with ADGRA2 (By similarity). ITGAV:ITGB3 interacts with FGF2; it is likely that FGF2 can simultaneously bind ITGAV:ITGB3 and FGF receptors (By similarity). ITGAV:ITGB3 is found in a ternary complex with CX3CR1 and CX3CL1. ITGAV:ITGB3 is found in a ternary complex with NRG1 and ERBB3. ITGAV:ITGB3 is found in a ternary complex with FGF1 and FGFR1. ITGAV:ITGB3 is found in a ternary complex with IGF1 and IGF1R (By similarity). ITGAV:ITGB3 interacts with IGF2 (By similarity). ITGAV:ITGB3 and ITGAV:ITGB6 interact with FBN1 (By similarity). ITGAV:ITGB3 interacts with CD9, CD81 and CD151 (via second extracellular domain) (By similarity). ITGAV:ITGB6 interacts with TGFB1 (By similarity).
The alpha-V (ITGAV) integrins are receptors for vitronectin, cytotactin, fibronectin, fibrinogen, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin, TGFB1 and vWF. They recognize the sequence R-G-D in a wide array of ligands. Alpha-V integrins may play a role in embryo implantation, angiogenesis and wound healing (By similarity). ITGAV:ITGB3 binds to fractalkine (CX3CL1) and may act as its coreceptor in CX3CR1-dependent fractalkine signaling. ITGAV:ITGB3 binds to NRG1 (via EGF domain) and this binding is essential for NRG1-ERBB signaling. ITGAV:ITGB3 binds to FGF1 and this binding is essential for FGF1 signaling. ITGAV:ITGB3 binds to FGF2 and this binding is essential for FGF2 signaling. ITGAV:ITGB3 binds to IGF1 and this binding is essential for IGF1 signaling. ITGAV:ITGB3 binds to IGF2 and this binding is essential for IGF2 signaling. ITGAV:ITGB3 binds to IL1B and this binding is essential for IL1B signaling. ITGAV:ITGB3 binds to PLA2G2A via a site (site 2) which is distinct from the classical ligand-binding site (site 1) and this induces integrin conformational changes and enhanced ligand binding to site 1. ITGAV:ITGB3 and ITGAV:ITGB6 act as receptors for fibrillin-1 (FBN1) and mediate R-G-D-dependent cell adhesion to FBN1 (By similarity). Integrin alpha-V/beta-6 or alpha-V/beta-8 (ITGAV:ITGB6 or ITGAV:ITGB8) mediates R-G-D-dependent release of transforming growth factor beta-1 (TGF-beta-1) from regulatory Latency-associated peptide (LAP), thereby playing a key role in TGF-beta-1 activation (By similarity). ITGAV:ITGB3 acts as a receptor for CD40LG (By similarity).
Acts as component of the retromer cargo-selective complex (CSC). The CSC is believed to be the core functional component of retromer or respective retromer complex variants acting to prevent missorting of selected transmembrane cargo proteins into the lysosomal degradation pathway.
Acts as component of the retromer cargo-selective complex (CSC). The CSC is believed to be the core functional component of retromer or respective retromer complex variants acting to prevent missorting of selected transmembrane cargo proteins into the lysosomal degradation pathway. Retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) (By similarity). Acts also as component of the retriever complex. The retriever complex is an heterotrimeric complex related to retromer cargo-selective complex (CSC) and essential for retromer-independent retrieval and recycling of numerous cargos such as integrins. In the endosomes, retriever complex drives the retrieval and recycling of NxxY-motif-containing cargo proteins by coupling to SNX17, a cargo essential for the homeostatic maintenance of numerous cell surface proteins associated with processes that include cell migration, cell adhesion, nutrient supply and cell signaling (By similarity).
Component of the heterotrimeric retromer cargo-selective complex (CSC) which is believed to associate with variable sorting nexins to form functionally distinct retromer complex variants (By similarity). Component of the heterotrimeric retriever complex (By similarity).
Catalyzes the oxidative ring opening of 3-hydroxyanthranilate to 2-amino-3-carboxymuconate semialdehyde, which spontaneously cyclizes to quinolinate.
Belongs to the non-repetitive/WGA-negative nucleoporin family.
Regulates mitogenic signal transduction by dephosphorylating both Thr and Tyr residues on MAP kinases ERK1 and ERK2.
Belongs to the Mediator complex subunit 21 family.
Forms a channel through the mitochondrial outer membrane that allows diffusion of small hydrophilic molecules.
Interacts with ARMC12 in a TBC1D21-dependent manner.
Belongs to the CCR4/nocturin family. TTRAP/TDP2 subfamily.
Binds 1 magnesium or manganese ion per subunit.
Can partially complement the absence of TDP1 due to its weak 3'-tyrosyl DNA phosphodiesterase activity.
DNA repair enzyme that can remove a variety of covalent adducts from DNA through hydrolysis of a 5'-phosphodiester bond, giving rise to DNA with a free 5' phosphate. Catalyzes the hydrolysis of dead-end complexes between DNA and the topoisomerase 2 (TOP2) active site tyrosine residue. Hydrolyzes 5'-phosphoglycolates on protruding 5' ends on DNA double-strand breaks (DSBs) due to DNA damage by radiation and free radicals. The 5'-tyrosyl DNA phosphodiesterase activity can enable the repair of TOP2-induced DSBs without the need for nuclease activity, creating a 'clean' DSB with 5'-phosphate termini that are ready for ligation (By similarity). Has also 3'-tyrosyl DNA phosphodiesterase activity, but less efficiently and much slower than TDP1.
Component of pre-catalytic, catalytic and post-catalytic spliceosomes. Associates with the spliceosome prior to recognition of the 3'-splice site for step II, probably during catalysis of step I.
Required for pre-mRNA splicing as component of the spliceosome. 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.
Belongs to the eukaryotic release factor 1 family. Pelota subfamily.
Cotranslational quality control factor involved in the No-Go Decay (NGD) pathway. Required for 48S complex formation from 80S ribosomes and dissociation of vacant 80S ribosomes. Recognizes stalled ribosomes and promotes dissociation of elongation complexes assembled on non-stop mRNAs; this triggers endonucleolytic cleavage of the mRNA, a mechanism to release non-functional ribosomes and to degrade damaged mRNAs as part of the No-Go Decay (NGD) pathway. Upon mitochondrial damage is recruited to the ribosome/mRNA-ribonucleoprotein complex associated to mitochondrial outer membrane thereby enabling the recruitment of autophagy receptors and induction of mitophagy.
The N-terminal domain has the RNA-binding Sm fold. It harbors the endoribonuclease activity.
Phosphorylated on some or all of the serine and threonine residues present in the C-terminal region.
Produces a slow and prolonged phototransduction response consistent with the non-visual function of pineal photoreception.
5'-3' exonuclease that plays a central role in telomere maintenance and protection during S-phase. Participates in the protection of telomeres against non-homologous end-joining (NHEJ)-mediated repair, thereby ensuring that telomeres do not fuse. Plays a key role in telomeric loop (T loop) formation by being recruited by TERF2 at the leading end telomeres and by processing leading-end telomeres immediately after their replication via its exonuclease activity: generates 3' single-stranded overhang at the leading end telomeres avoiding blunt leading-end telomeres that are vulnerable to end-joining reactions and expose the telomere end in a manner that activates the DNA repair pathways (By similarity). May be required for DNA interstrand cross-link repair (PubMed:15572677). Possesses beta-lactamase activity, catalyzing the hydrolysis of penicillin G and nitrocefin (By similarity). Exhibits no activity towards other beta-lactam antibiotic classes including cephalosporins (cefotaxime) and carbapenems (imipenem) (By similarity).
Interacts with TERF2; the interaction is direct.
The TBM domain mediates interaction with TERF2.
The N-terminus is blocked. N,N,N-trimethylalanine, found in other myosin light chains would not have been detected in the N-terminal tryptic peptide in PubMed:6709041 and PubMed:7238855 because it would remain trimethylated and ninhydrin negative after hydrolysis.
Highly expressed in testis, brain and liver and to a lesser extent in lung and heart.
Transfers sialic acid from CMP-sialic acid to galactose-containing acceptor substrates.
Oligomer of 24 subunits. There are two types of subunits: L (light) chain and H (heavy) chain. The major chain can be light or heavy, depending on the species and tissue type. 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.
Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Has ferroxidase activity. Iron is taken up in the ferrous form and deposited as ferric hydroxides after oxidation. Also plays a role in delivery of iron to cells. Mediates iron uptake in capsule cells of the developing kidney (By similarity).
Maintains high levels of reduced glutathione in the cytosol.
General regulator of phagocytosis. Required to uptake Gram negative bacterium by macrophages.
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. May play an important role in retinal development.
Detected only after some degree of neuronal differentiation has taken place and persists at least up to the newly hatched stage.
Cell surface proteoglycan that bears heparan sulfate. Regulates exosome biogenesis in concert with SDCBP and PDCD6IP.
Belongs to the class I-like SAM-binding methyltransferase superfamily. mRNA cap 0 methyltransferase family.
In the N-terminal section; belongs to the dsDNA virus mRNA guanylyltransferase family.
Mitochondrial GTPase that mediates the disassembly of ribosomes from messenger RNA at the termination of mitochondrial protein biosynthesis. Acts in collaboration with MRRF. GTP hydrolysis follows the ribosome disassembly and probably occurs on the ribosome large subunit. Not involved in the GTP-dependent ribosomal translocation step during translation elongation.
GTP-binding protein involved in protein trafficking; regulates endocytic recycling and cytoskeleton remodeling. May modulate vesicle budding and uncoating within the Golgi apparatus. May contribute to the regulation of dendritic branching, filopodia extension and dendritic spine development (By similarity).
Acts both as coactivator and as corepressor. May play a role in chromatin remodeling. Participates in the Wnt signaling pathway. Transcriptional corepressor that down-regulates the expression of target genes. Binds to target promoters, leading to increased histone H3 acetylation. Coactivator for TP53-mediated activation of transcription of a set of target genes. Required for TP53-mediated cell-cycle arrest in response to oncogene activation. Inhibits cell cycle progression from G1 to S phase (By similarity).
Monomethylation at Lys-86 (K86me1) 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.
Plays a role in lysosome motility. In neurons, mediates the anterograde axonal long-range transport of presynaptic lysosome-related vesicles required for presynaptic biogenesis and synaptic function (By similarity). May play a role in chromosome segregation (By similarity).
Developing spinal cord and developing visual system. Collapsin-1, -2, -3, and -5 bind to overlapping but distinct axon tracts.
Induces the collapse and paralysis of neuronal growth cones. Could potentially act as repulsive cues toward specific neuronal populations. Binds to neuropilin.
Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting. VAP cleaves the fusion proteins of Sendai virus, NDV, and influenza virus a at a specific single arginine-containing site, and plays a key role in the viral spreading in the allantoic sac.
The activation peptide is cleaved by factor IXa (in the intrinsic pathway), or by factor VIIa (in the extrinsic pathway).
The two chains are formed from a single-chain precursor by the excision of two Arg residues and are held together by 1 or more disulfide bonds.
The vitamin K-dependent, enzymatic carboxylation of some glutamate residues allows the modified protein to bind calcium.
Plays an important role in the regulation of dynamic actin-based, cytoskeletal activities. Agonist-dependent changes in LASP1 phosphorylation may also serve to regulate actin-associated ion transport activities, not only in the parietal cell but also in certain other F-actin-rich secretory epithelial cell types.
Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A9 subfamily.
Transcriptional repressor that binds to the promoter region of target genes. Plays a role in the regulation of the cell cycle and of the Wnt pathway. Binds preferentially to the sequence 5'-TTCATTCATTCA-3'. Binding to the histone H1.0 promoter is enhanced by interaction with RB1. Disrupts the interaction between DNA and TCF4.
Belongs to the U1 small nuclear ribonucleoprotein C family.
Component of the U1 snRNP. The U1 snRNP is composed of the U1 snRNA and 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 3 U1 snRNP-specific proteins SNRNP70/U1-70K, SNRPA/U1-A and SNRPC/U1-C. SNRPC/U1-C interacts with U1 snRNA and the 5' splice-site region of the pre-mRNA.
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. SNRPC/U1-C is directly involved in initial 5' splice-site recognition for both constitutive and regulated alternative splicing. The interaction with the 5' splice-site seems to precede base-pairing between the pre-mRNA and the U1 snRNA. Stimulates commitment or early (E) complex formation by stabilizing the base pairing of the 5' end of the U1 snRNA and the 5' splice-site region.
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. snrpc/U1-C is directly involved in initial 5' splice-site recognition for both constitutive and regulated alternative splicing. The interaction with the 5' splice-site seems to precede base-pairing between the pre-mRNA and the U1 snRNA. Stimulates E complex formation by stabilizing the base pairing of the 5' end of the U1 snRNA and the 5' splice-site region.
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 3 U1 snRNP-specific proteins SNRNP70/U1-70K, SNRPA/U1-A and SNRPC/U1-C. SNRPC/U1-C interacts with U1 snRNA and the 5' splice-site region of the pre-mRNA.
Exhibits phosphohistidine phosphatase activity.
May play a structural role at sites of cell adhesion in maintaining cell shape and motility. May be involved in signal transduction from cell adhesion sites to the nucleus (By similarity).
Involved in the post-translational conjugation of arginine to the N-terminal aspartate or glutamate of a protein. This arginylation is required for degradation of the protein via the ubiquitin pathway.
Expressed in the liver, kidney, gall bladder, testis, ovary and male and femae reproductive tracts. Expressed in the ovarian stroma and the theca and granulosa layers of the ovarian follicle.
Induced in the theca layer of the F3 stage ovarian follicle by intravenous injection of LPS. Expression in the granulosa layer of the ovarian follicle is not affected by intravenous injection of LPS.
Plays a critical role in eye formation by regulating the initial specification of retinal cells and/or their subsequent proliferation.
Exact function not known, component of the outer membrane of the vitelline layer of the egg. Seems to be able to synthesize N-acetylchito-oligosaccharides (n=14-15) from hexasaccharides of N-acetylglucosamine in a manner similar to the transferase activity of lysozyme.
Interacts (when phosphorylated at Ser-62) with PPP2R2D.
Phosphorylation at Ser-62 by GWL during mitosis is essential for interaction with PPP2R2D (PR55-delta) and subsequent inactivation of PP2A.
Protein phosphatase inhibitor that specifically inhibits protein phosphatase 2A (PP2A) during mitosis. When phosphorylated at Ser-62 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).
N-linked glycan at Asn-41 consists of GlcNAc(beta1-2)Man(alpha1-3)[GlcNAc(beta1-4)][Man(alpha1-?)Man(alpha1-6)] Man(beta1-4)GlcNAc(beta1-4)GlcNAc.
Synthesized in hen oviduct and concentrated in egg white (where it represents 0.05% of the total protein).
The biological function of avidin is not known. Forms a strong non-covalent specific complex with biotin (one molecule of biotin per subunit of avidin).
Developing nervous system; optic tectum (layers D and E of SGFS), amacrine cells of retina, neurites of dorsal root ganglia. Also expressed in non-neuronal cells, e.g. blood vessels in the entire embryo.
Receptor involved in the development of the cardiovascular system, in angiogenesis, in the formation of certain neuronal circuits and in organogenesis outside the nervous system (By similarity). Mediates the chemorepulsant activity of semaphorins. Binding to VEGFA initiates a signaling pathway needed for motor neuron axon guidance and cell body migration, including for the caudal migration of facial motor neurons from rhombomere 4 to rhombomere 6 during embryonic development (By similarity). Regulates mitochondrial iron transport via interaction (By similarity).
Collagen VI acts as a cell-binding protein.
Trimers composed of three different chains: alpha 1(VI), alpha 2(VI), and alpha 3(VI).
COPII is composed of at least 5 proteins: the SEC23/24 complex, the SEC13/31 complex and SAR1. SEC13 and SEC31 make a 2:2 tetramer that forms the edge element of the COPII outer coat. The tetramer self-assembles in multiple copies to form the complete polyhedral cage. Interacts (via WD 8) with SEC13 (By similarity).
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 (By similarity).
Belongs to the dynein heavy chain family.
Calcium-regulated, actin-modulating protein that binds to the plus (or barbed) ends of actin monomers or filaments, preventing monomer exchange (end-blocking or capping). It can promote the assembly of monomers into filaments (nucleation) as well as sever filaments already formed (By similarity). Plays a role in ciliogenesis (By similarity).
Comprises six structurally related gelsolin-like (G1-G6) domains, that, in a calcium-free environment, are packed together to form a compact globular structure in which the putative actin-binding sequences are not sufficiently exposed to enable binding to occur. Binding calcium may release the connections that join the N- and C-terminal halves of gelsolin, enabling each half to bind actin relatively independently. G1 and G4 bind two Ca(2+) in a type I and in a type II manner. G2, G3, G5 and G6 bind only one Ca(2+) in a type II manner. Type I Ca(2+) binding sites are shared between actin and gelsolin-like repeats G1 and G4. Type I binding governs the strength of interactions between gelsolin and actin by direct participation at the binding interface. Ca(2+) binding to G2 and G6 disrupts the interactions between G2 and G6, releases the C-terminal tail, and induces large interdomain rearrangements that result in the exposure of the F-actin-binding site on G2 and contributes to the activation of gelsolin. Binding to phosphoinositides may inhibit the severing and capping properties of gelsolin.
Highly expressed in homogene cells of the basilar papilla. Also detected in subcutaneous layer of the skin.
Belongs to the FMN-dependent alpha-hydroxy acid dehydrogenase family.
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.
Binds promoter DNA and regulates initiation of transcription. Required for normal mitochondrial transcription, and for normal assembly of mitochondrial respiratory complexes. Required for normal mitochondrial function (By similarity).
Contains about seven structural repeats of about 35 residues, where each repeat contains three helices. The repeats form a superhelical structure with a solenoid shape (By similarity).
Belongs to the arginase family. Agmatinase subfamily.
Can bind at least three actin monomers and thereby provides a nucleus for actin filament formation. Interacts (via N-terminus) with tropomyosin alpha (TPM1) (via N-terminus). May also interact with TPM2 (via N-terminus).
First detected in myocardium at HH stage 14. Detected in myocardium and somites at HH stage 17 and 19.
Mediates nucleation of actin filaments and thereby promotes actin polymerization (By similarity). Plays a role in the regulation of actin filament length (PubMed:20736303). Required for normal sarcomere organization in the heart, and for normal heart function (By similarity).
Component of complex II composed of four subunits: the flavoprotein (FP) SDHA, iron-sulfur protein (IP) SDHB, and a cytochrome b560 composed of SDHC and SDHD.
Membrane-anchoring subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q).
Belongs to the mitochondrion-specific ribosomal protein mL50 family.
Activated by phosphorylation on Thr-181.
Phosphorylated at Thr-181 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39.
Phosphorylates IRS1 in insulin-stimulated adipocytes, potentially modulating the efficiency of insulin signal transduction. Inhibits CREB activity by phosphorylating and repressing the CREB-specific coactivators, CRTC1-3 (By similarity).
Ubiquitously expressed in embryonic tissue.
Belongs to the FAD-dependent oxidoreductase 2 family. FRD/SDH subfamily.
Flavoprotein (FP) subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q).
Conversion of pregnenolone and progesterone to their 17-alpha-hydroxylated products and subsequently to dehydroepiandrosterone (DHEA) and androstenedione. Catalyzes both the 17-alpha-hydroxylation and the 17,20-lyase reaction.
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. Required for proper focal adhesion assembly. Involved in the regulation of cell migration.
Belongs to the glycosyltransferase 39 family.
Transfers mannose from Dol-P-mannose to Ser or Thr residues on proteins.
Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. It can phosphorylate a large number of proteins. Participates in Wnt signaling (By similarity).
Receptor for the thyroid-stimulating hormone (TSH) or thyrotropin. Also acts as a receptor for the heterodimeric glycoprotein hormone (GPHA2:GPHB5) or thyrostimulin. The activity of this receptor is mediated by G proteins which activate adenylate cyclase. Plays a central role in controlling thyroid cell metabolism.
Belongs to the activator 1 large subunit family.
Acts as a ligand for FGFR1, FGFR2, FGFR3 and FGFR4 (By similarity). Also acts as an integrin ligand which is required for FGF2 signaling (By similarity). Plays an important role in the regulation of cell survival, cell division, cell differentiation and cell migration (By similarity). Functions as a potent mitogen in vitro (By similarity). Can induce angiogenesis (By similarity).
Belongs to the archaeal Rpo10/eukaryotic RPB10 RNA polymerase subunit family.
Belongs to the class IV-like SAM-binding methyltransferase superfamily. RNA methyltransferase NEP1 family.
Weakly binds calcium but binds zinc very tightly-distinct binding sites with different affinities exist for both ions on each monomer. Physiological concentrations of potassium ion antagonize the binding of both divalent cations, especially affecting high-affinity calcium-binding sites. Binds to and initiates the activation of STK38 by releasing autoinhibitory intramolecular interactions within the kinase. Interaction with AGER after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53/TP53 signaling. Could assist ATAD3A cytoplasmic processing, preventing aggregation and favoring mitochondrial localization. May mediate calcium-dependent regulation on many physiological processes by interacting with other proteins, such as TPR-containing proteins, and modulating their activity.
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.
Belongs to the lyase 1 family. Argininosuccinate lyase subfamily.
Delta crystallin, the principal crystallin in embryonic lens, is found only in birds and reptiles. This protein may also function as an enzymatically active argininosuccinate lyase.
It is uncertain if this gene is expressed.
Dephosphorylates 26S nuclear proteasomes, thereby decreasing their proteolytic activity. The dephosphorylation may prevent assembly of the core and regulatory particles (CP and RP) into mature 26S proteasome (By similarity).
The Ubiquitin-like domain mediates interaction with proteasomes.
Belongs to the SLC43A transporter (TC 2.A.1.44) family.
Buffers cytosolic calcium. May stimulate a membrane Ca(2+)-ATPase and a 3',5'-cyclic nucleotide phosphodiesterase.
Highly abundant in supporting cells. Also present in hair cells.
This protein has four functional calcium-binding sites; potential sites II and VI have lost affinity for calcium.
Belongs to the DEAD box helicase family. DDX52/ROK1 subfamily.
Component of the cleavage factor Im (CFIm) complex that functions as an activator of the pre-mRNA 3'-end cleavage and polyadenylation processing required for the maturation of pre-mRNA into functional mRNAs. CFIm contributes to the recruitment of multiprotein complexes on specific sequences on the pre-mRNA 3'-end, so called cleavage and polyadenylation signals (pA signals). Most pre-mRNAs contain multiple pA signals, resulting in alternative cleavage and polyadenylation (APA) producing mRNAs with variable 3'-end formation. The CFIm complex acts as a key regulator of cleavage and polyadenylation site choice during APA through its binding to 5'-UGUA-3' elements localized in the 3'-untranslated region (UTR) for a huge number of pre-mRNAs. Plays a role in mRNA export.
Component of the cleavage factor Im (CFIm) complex.
Belongs to the galactose-3-O-sulfotransferase family.
Serine hydrolase involved in the detoxification of formaldehyde.
Microtubule-stabilizing protein that may play an important role during reorganization of microtubules during polarization and differentiation of epithelial cells.
In the central section; belongs to the inositol 1,4,5-trisphosphate 5-phosphatase family.
Belongs to the ATPase gamma chain family.
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(1) domain and the central stalk which is part of the complex rotary element. The gamma subunit protrudes into the catalytic domain formed of alpha(3)beta(3). Rotation of the central stalk against the surrounding alpha(3)beta(3) subunits leads to hydrolysis of ATP in three separate catalytic sites on the beta subunits.
Heterodimer with RPLP2 at the lateral ribosomal stalk of the large ribosomal subunit.
Belongs to the BPI/LBP/Plunc superfamily. BPI/LBP family.
Catalyzes the conversion of the 17-keto group of estrone, 4- and 5-androstenes and 5-alpha-androstanes into their 17-beta-hydroxyl metabolites and the conversion of the 3-keto group of 3-, 3,17- and 3,20- diketosteroids into their 3-hydroxyl metabolites. Exhibits reductive 3-beta-hydroxysteroid dehydrogenase activity toward 5-beta-androstanes, 5-beta-pregnanes, 4-pregnenes and bile acids. May also reduce endogenous and exogenous alpha-dicarbonyl compounds and xenobiotic alicyclic ketones.
Inhibited by flavonoids including apigenin, luteolin, genistein, kaempferol and quercetin and also by carbenoxolone, zearalenone, glycyrrhetinic, curcumin and flufenamic acid.
Different forms of hen transferrin are distinguished by their carbohydrate composition. Ovotransferrin and embryo serum transferrin but not adult serum transferrin, have bisecting N-acetylglucosamine. Transferrin secreted by embryo hepatocytes in primary culture is marked by the presence of (alpha1-6) fucosylation of the core N-acetylglucosamine. Serum transferrins also differ in the number of attached neuraminic acid residues. In both embryo forms, sialylation occurs on the Man (alpha 1-3)-linked antennae.
Expressed in the magnum of the oviduct (at protein level).
Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. Responsible for the transport of iron from sites of absorption and heme degradation to those of storage and utilization. There are two forms of hen transferrin, ovotransferrin, found in the ovoducts and, serum transferrin, secreted by the liver. Serum transferrin may also have a role in stimulating cell proliferation and is regulated by iron levels. Ovotransferrin has a bacteriostatic function and, is not controlled by iron levels.
Up-regulated by dietary stress. Increased expression at day 14 in the magnum of the oviduct in the corticosterone-fed laying hens (at protein level).
Belongs to the 5'-3' exonuclease family. XRN2/RAT1 subfamily.
Possesses 5'->3' exoribonuclease activity. May promote the termination of transcription by RNA polymerase II (By similarity).
Synthesizes selenophosphate from selenide and ATP.
Substrate-specific adapter for CUL3 E3 ubiquitin-protein ligase complex.
Belongs to the archaeal Rpo3/eukaryotic RPB3 RNA polymerase subunit family.
Ribosome biogenesis factor. May be required for both optimal rDNA transcription and pre-rRNA processing (By similarity).
Belongs to the bombesin/neuromedin-B/ranatensin family.
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-6 associates with either beta-1 (ITGB1) or beta-4 (ITGB4) to form ITGA6:ITGB1 and ITGA6:ITGB4, respectively.
Integrin alpha-6/beta-1 (ITGA6:ITGB1) is a receptor for laminin on platelets. Integrin alpha-6/beta-1 (ITGA6:ITGB1) is present in oocytes and is involved in sperm-egg fusion. 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.
Its primary physiological function is unclear. Has cytoprotective activity against internal or environmental stresses. May play a role in neuronal development and synaptic plasticity. May be required for neuronal myelin sheath maintenance. May play a role in iron uptake and iron homeostasis. Soluble oligomers are toxic to cultured neuroblastoma cells and induce apoptosis (in vitro). Association with GPC1 (via its heparan sulfate chains) targets PRNP to lipid rafts. Also provides Cu(2+) or Zn(2+) for the ascorbate-mediated GPC1 deaminase degradation of its heparan sulfate side chains (By similarity).
Monomer and homodimer. Has a tendency to aggregate into amyloid fibrils containing a cross-beta spine, formed by a steric zipper of superposed beta-strands. Soluble oligomers may represent an intermediate stage on the path to fibril formation. Copper binding may promote oligomerization.
Belongs to the complex I 20 kDa subunit family.
Cell adhesion protein that promotes the attachment of spinal cord and sensory neuron cells and the outgrowth of neurites in vitro. May contribute to the growth and guidance of axons in both the spinal cord and the PNS (By similarity). Somite-derived spondin 1 is an inhibitory signal involved in patterning the segmental migration of neural crest cells and their topographical segregation within the rostral somites in vitro. May be required to prevent the lateral drifting of the commissural axons after having crossed the floor plate.
Belongs to the purine nucleoside phosphorylase YfiH/LACC1 family.
Expressed in the dorsal ectoderm overlying the developing spinal cord.
Expressed in the region posterior to the Hensen node at stage 6. Detected in the dorsal domain of the neural tube and the CNS of the developing embryo. In the developing limb, expression starts at stage 18 in the posterior-dorsal region of the distal mesenchyme, and gradually expands to the anterior-distal region. Also found in the feather bud and branchial arch.
Receptor for Wnt proteins. Functions in the canonical Wnt/beta-catenin signaling pathway. Activation by WNT7A induces expression of beta-catenin target genes (PubMed:11142678). The canonical Wnt/beta-catenin 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 (PubMed:11142678). 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 (Probable).
Belongs to the ubiquitin-conjugating enzyme family. FTS subfamily.
Lacks the conserved Cys residue necessary for ubiquitin-conjugating enzyme E2 activity.
May function to promote vesicle trafficking and/or fusion. May also regulate apoptosis (By similarity).
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 (By similarity). Has ribonuclease activity (By similarity).
Belongs to the mitochondrion-specific ribosomal protein mL46 family.
The histidine box domains are involved in binding the catalytic metal ions.
Belongs to the non-lysosomal glucosylceramidase family.
Non-lysosomal glucosylceramidase that catalyzes the hydrolysis of glucosylceramide (GlcCer) to free glucose and ceramide.
DNA-binding protein that promotes DNA condensation into transcriptionally inactive heterochromatin in terminally differentiated avian blood cells. Promotes tight packing of nucleosomes into spherical clusters by binding to linker DNA and subsequent oligomerization. Acts as a cysteine protease inhibitor towards CTSL (cathepsin L1) and CTSV (cathepsin L2), but does not inhibit serine proteases.
Detected in all major blood cell types. Highly expressed in granulocytes (at protein level).
Homodimer and homooligomer. Interaction with DNA promotes oligomerization.
Functions as guanine nucleotide exchange factor (GEF) for RAB11A.
Interacts with GDP-bound and nucleotide-free forms of RAB11A.
The N-terminal half of the protein mediates interaction with RAB11A and functions as guanine nucleotide exchange factor. Four long alpha-helices (interrupted by a central kink) assemble into coiled coils, giving rise to a 'V' shape.
By phenobarbital (PubMed:2424910). Significantly increased expression by estrogen. Rapidly up-regulated within 0.5 hour after extrogen exposure with a peak at 1-4 hours. Expression is significantly decreased below control level after 30 hours (PubMed:11572089).
Direct ligand for the ERBB tyrosine kinase receptors. The multiple isoforms perform diverse functions: cysteine-rich domain containing isoforms (isoform 2-isoform 4) probably regulate the expression of nicotinic acetylcholine receptors at developing interneuronal synapses. Isoform Ig-NRG is required for the initial induction and/or maintenance of the mature levels of acetylcholine receptors at neuromuscular synapses (PubMed:8453670, PubMed:9491987). Binds to ERBB3 and integrins to form a complex which is essential for NRG1-ERBB signaling (By similarity).
ERBB receptor binding is elicited entirely by the EGF-like domain.
Extensive glycosylation precedes the proteolytic cleavage.
Isoform 2-isoform 4 are detected at embryonic day 4 (ED4) in both visceral and somatic motor neurons of spinal cord and is highest at ED6. Isoform 1 is not expressed until ED 6 in spinal cord. At ED 11 both isoforms display comparable levels.
Proteolytic cleavage close to the plasma membrane on the external face leads to the release of the soluble growth factor form.
The EGF-like domain is replaced by a cysteine-rich domain (CRD).
The cytoplasmic domain may be involved in the regulation of trafficking and proteolytic processing. Regulation of the proteolytic processing involves initial intracellular domain dimerization (By similarity).
Chaperone protein which promotes assembly of the 20S proteasome as part of a heterodimer with psmg2.
Involved in an early step of the mitochondrial complex IV assembly process.
Component of the U5 snRNP complex that is required for spliceosome assembly and for pre-mRNA splicing.
Affects the rate of fibrils formation. May have a primary role in collagen fibrillogenesis (By similarity).
Belongs to the peptidase C69 family. Secernin subfamily.
Expressed broadly in the spinal cord, including the ventral portion of the ventricular zone, and motor neurons. Expressed also in the dorsal root ganglion and boundary cap cells at dorsal and ventral roots. In the early embryonic brain, is first expressed in the prosencephalon and the ventral mesencephalon, and later in the telencephalon, the rostral part of the mesencephalon and some parts of the hindbrain. Expressed also in the ventral part of the neural retina and trigeminal and facial nerves.
Functional component of the Nogo receptor signaling complex (RTN4R/NGFR) in RhoA activation responsible for some inhibition of axonal regeneration by myelin-associated factors. Is also an important negative regulator of oligodentrocyte differentiation and axonal myelination (By similarity).
Homotetramer. Forms ternary complex with RTN4R/NGFR and RTN4R/TNFRSF19 (By similarity).
N-glycosylated. Contains predominantly high-mannose glycans (By similarity).
Fatty acid synthetase is a multifunctional enzyme that catalyzes the de novo biosynthesis of long-chain saturated fatty acids starting from acetyl-CoA and malonyl-CoA in the presence of NADPH. This multifunctional protein contains 7 catalytic activities and a site for the binding of the prosthetic group 4'-phosphopantetheine of the acyl carrier protein ([ACP]) domain.
Transcriptional activator that mediates FGF signaling during neural development (PubMed:14651851). Plays a role in the regulation of cell movement (By similarity). Does not bind DNA by itself (By similarity).
Belongs to the eukaryotic ribosomal protein eL27 family.
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.
Like erythrocyte spectrin, the spectrin-like proteins are capable of forming dimers which can further associate to tetramers. Interacts with ACP1 (By similarity).
Morphologically, spectrin-like proteins appear to be related to spectrin, showing a flexible rod-like structure. They can bind actin but seem to differ in their calmodulin-binding activity. In nonerythroid tissues, spectrins, in association with some other proteins, may play an important role in membrane organization.
Phosphorylation of Tyr-1176 decreases sensitivity to cleavage by calpain in vitro.
Transposase-derived protein that may have nuclease activity (Potential). Does not have transposase activity.
Expressed in the tongue, crop, crop mucosa, coprodeum, urodeum, proctoderm, colon, lung, ovary, uterus, testis, vitelline membrane, kidney, ureter, liver and skin.
Homotrimer; disulfide-linked. Interacts with MASP1; probably triggers the lectin pathway of complement.
Lectin that plays a role in innate immunity, apoptosis and embryogenesis. 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. Primarily recognizes the terminal disaccharide of the glycan. Also recognizes a subset of fucosylated glycans and lipopolysaccharides. 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. 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. 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.
Belongs to the chloride channel (TC 2.A.49) family. ClC-3/CLCN3 subfamily.
Acts as a repressor in the regulation of translation initiation of poly(A)-containing mRNAs. Its inhibitory activity on translation is mediated via its action on PABPC1. Displaces the interaction of PABPC1 with poly(A) RNA and competes with PAIP1 for binding to PABPC1. Its association with PABPC1 results in disruption of the cytoplasmic poly(A) RNP structure organization (By similarity).
Only the PABPC1-interacting motif-1 (PAM1) interferes with the binding of PABPC1 to poly(A) RNA and translation initiation.
Ubiquitinated, leading to its degradation by the proteasome.
Belongs to the SLC35G solute transporter family.
Belongs to the tenascin family. Teneurin subfamily.
Binds to the plasma membrane and may be internalized by a receptor- and caveolae-mediated endocytosis manner to reach cytosolic compartments in a dynamin-dependent manner.
Cytoplasmic proline-rich regions could serve as docking domains for intracellular SH3-containing proteins.
Derives from the plasma membrane form by proteolytic cleavage and translocates to the nucleus.
Derives from the plasma membrane form by proteolytic processing. Further proteolytic cleavage may be generated (By similarity).
EGF-like domains 2 and 5 which have an odd number of cysteines might enable the formation of intermolecular disulfide bonds.
Expressed in mitral cell, glomerular layer of the olfactory bulb, hippocampus, posteromedial cortex piriformis, nucleus rotundu, laminae 2 and 5 within the inner plexiform layer of the retina, stratum griseum, nucleus laminaris and magnocellularis in the hindbrain and Purkinje cells at embryonic day (E) 17 (at protein level). At 14 dpc, it is concentrated in the retina, the optic tectum and in specific nuclei in the dorsal diencephalon, it is concentrated in the stratum griseum centrale. Expression is seen in diencephalon, concentrated in the rotund nucleus and in the neighboring ovoid nucleus. Similar expression patterns are seen at 17 dpc.
Expressed in the neurons of the developing visual system and in fetal brain.
Homodimer; disulfide-linked. Heterodimer with other teneurins (By similarity). Ten-1 ICD interacts with SORBS1 (via third SH3 domain). Interacts with MBD1 isoform 2.
Involved in neural development, regulating the establishment of proper connectivity within the nervous system. May function as a cellular signal transducer (By similarity).
Plays a role in the regulation of neuroplasticity in the limbic system. Mediates a rapid reorganization of actin- and tubulin-based cytoskeleton elements with an increase in dendritic arborization and spine density formation of neurons in the hippocampus and amygdala. Induces BDNF transcription inhibition in neurons. Activates the mitogen-activated protein (MAP) kinase 2 (MEK2) and extracellular signal-regulated kinase (ERK) cascade (By similarity).
Expressed first preferentially in atrium and later also in the subepicardial compact layer of the ventricles.
Expression was first detected at HH stage 10 and was initially expressed throughout the heart. With heart looping at HH stage 11, expression was restricted to the atrial compartment and absent from the presumptive ventricular segments. The atrial-specific expression was still observed at stage 17. During HH stages 17-24, increased expression in the subepicardial compact layer was seen. At HH stage 30, expression was seen intensely in the whole myocardium with the exception of the outflow tract.
May play a role in the maintenance of heart function mediated, at least in part, through cAMP-binding. May play a role in the regulation of KCNK2-mediated current amplitude (By similarity).
Acts as a plasma-membrane magnesium transporter.
Belongs to the SLC41A transporter family.
Fatty acylated. Heavily palmitoylated in the cysteine string motif (By similarity).
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).
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).
Sumoylated by SUMO1 and SUM02 in synaptosomes. The sumoylated forms act as a scaffold for sequestering mu-opioid receptor-activated G(alpha) subunits (By similarity).
Actin-binding protein involved in motile and morphological processes. Inhibits actin polymerization, likely by sequestering G-actin (By similarity).
Interacts with G-actin; ADP-actin form and capping protein (CP).
Monomer and homodimer; homodimerization is induced by binding of the substrate.
DNA-binding protein that specifically recognizes consensus sequences at the breakpoint junctions in chromosomal translocations, mostly involving immunoglobulin (Ig)/T-cell receptor gene segments. Seems to recognize single-stranded DNA ends generated by staggered breaks occurring at recombination hot spots (By similarity).
Exhibits both single-stranded and double-stranded endoribonuclease activity. May act as an activator of RNA-induced silencing complex (RISC) by facilitating endonucleolytic cleavage of the siRNA passenger strand (By similarity).
Ring-shaped heterooctamer of six TSN and two TSNAX subunits, DNA/RNA binding occurs inside the ring.
Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. The alpha and alpha' chains contain the catalytic site. Participates in Wnt signaling (By similarity).
Tetramer composed of an alpha chain, an alpha' and two beta chains.
Binds free fatty acids and their coenzyme A derivatives, bilirubin, and some other small molecules in the cytoplasm. May be involved in intracellular lipid transport. Binds 2 molecules of cholate per subunit.
Belongs to the alkaline ceramidase family.
Hydrolyzes the sphingolipid ceramide into sphingosine and free fatty acid.
Component of the Golgi-associated retrograde protein (GARP) complex Component of the endosome-associated retrograde protein (EARP) complex.
Involved in retrograde transport from early and late endosomes to the late Golgi. The GARP complex is required for the maintenance of protein retrieval from endosomes to the TGN, acid hydrolase sorting, lysosome function, endosomal cholesterol traffic and autophagy. Acts as component of the EARP complex that is involved in endocytic recycling.
Belongs to the class VI-like SAM-binding methyltransferase superfamily. Isoprenylcysteine carboxyl methyltransferase family.
Catalyzes the post-translational methylation of isoprenylated C-terminal cysteine residues.
Binds 1 potassium ion per subunit. The potassium ion interacts primarily with the substrate.
Binds 2 magnesium ions per subunit. The magnesium ions interact primarily with the substrate.
Catalyzes the formation of S-adenosylmethionine from methionine and ATP.
Interacts with TIMELESS, which impairs TIMELESS self-association.
Plays an important role in the control of DNA replication and the maintenance of replication fork stability.
Plays an important role in the control of DNA replication and the maintenance of replication fork stability. Important for cell survival after DNA damage or replication stress. May be required fin the replication checkpoint induced by hydroxyurea or ultraviolet light (By similarity).
Endonuclease that specifically degrades the RNA of RNA-DNA hybrids.
Belongs to the membrane-bound acyltransferase family. Sterol o-acyltransferase subfamily.
Belongs to the adenylate kinase family. UMP-CMP kinase subfamily.
Catalyzes the phosphorylation of pyrimidine nucleoside monophosphates at the expense of ATP. Plays an important role in de novo pyrimidine nucleotide biosynthesis. Has preference for UMP and CMP as phosphate acceptors. Also displays broad nucleoside diphosphate kinase activity.
Composed of a heavy chain (beta) and a light chain (alpha). Component of an NADPH oxidase complex composed of a heterodimer formed by the membrane proteins CYBA and CYBB and the cytosolic subunits NCF1, NCF2 and NCF4. Interacts with NCF1 (via SH3 domain).
Critical component of the membrane-bound oxidase of phagocytes that generates superoxide. Associates with NOX3 to form a functional NADPH oxidase constitutively generating superoxide.
Plays a role in vesicle-mediated protein trafficking to lysosomal compartments including the endocytic membrane transport pathways.
Belongs to the protein prenyltransferase subunit beta family.
Catalyzes the transfer of a geranylgeranyl moiety from geranylgeranyl diphosphate to both cysteines of proteins with the C-terminal sequence -XXCC, -XCXC and -CCXX.
Binds to various extracellular matrix proteins.
Isoform 2 is expressed in the lens placode at stage 14. Isoform 1 is expressed in the lens vesicle at stage 17. Isoform 1 and isoform 2 are expressed in the lens, isthmus, cranial neuronal tube, dermatome and vitelin vein at stage 19. Isoform 1 and isoform 2 are expressed in the lens equatorial region during 4.5 dpc to 10 dpc.
Promotes cell adhesion and matrix assembly (By similarity). May play a role in eye formation.
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).
GTPase activating protein. May play a role in clathrin-dependent retrograde transport from early endosomes to the trans-Golgi network (By similarity).
May interact with clathrin heavy chains.
Autoinhibited by a module composed of four alpha helices (HI-1, HI-2, H4, and H5) that flank the DNA-binding ETS domain, reducing the affinity for DNA.
Binds DNA as a homodimer; homodimerization is required for transcription activation.
Transcription factor. Directly controls the expression of cytokine and chemokine genes in a wide variety of different cellular contexts.
Belongs to the UDP-glucose/GDP-mannose dehydrogenase family.
Catalyzes the formation of UDP-alpha-D-glucuronate, a constituent of complex glycosaminoglycans (By similarity). Required for the biosynthesis of chondroitin sulfate and heparan sulfate. Required for embryonic development via its role in the biosynthesis of glycosaminoglycans (By similarity).
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.
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.
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.
Required for normal spindle assembly. Plays a key role in mother-centriole-dependent centriole duplication. Plays a role in DNA damage response. Following DNA damage, such as double-strand breaks (DSBs), is removed from centrosomes; this leads to the inactivation of spindle assembly and delay in mitotic progression.
Belongs to the thiolase-like superfamily. Beta-ketoacyl-ACP synthases family.
Ca(2+) release-activated Ca(2+)-like (CRAC-like) channel subunit which mediates Ca(2+) influx and increase in Ca(2+)-selective current by synergy with the Ca(2+) sensor, STIM1.
Probably involved in the organization of the actin cytoskeleton by acting downstream of CDC42, inducing actin filament assembly.
Belongs to the U2 small nuclear ribonucleoprotein A family.
Homodimer or heterodimer (Potential). But, in contrast to other members of this family, cannot be disulfide-linked.
Belongs to the band 7/mec-2 family. Flotillin subfamily.
Catalyzes the hydrolysis of pseudosubstrates such as p-nitrocatechol sulfate and p-nitrophenyl sulfate (By similarity). Catalyzes the hydrolysis of the 2-sulfate groups of the 2-O-sulfo-D-glucuronate residues of chondroitin sulfate, heparin and heparitin sulfate (By similarity). Acts selectively on 2-sulfoglucuronate and lacks activity against 2-sulfoiduronate (By similarity).
Co-chaperone that binds to numerous kinases and promotes their interaction with the Hsp90 complex, resulting in stabilization and promotion of their activity.
Adapter protein involved in the Toll-like receptor and IL-1 receptor signaling pathway in the innate immune response.
Expressed in spleen, liver, kidney, bursa of Fabricius, lung and brain (at protein level). Expressed in cecum, heart, spleen, liver, kidney, female reproductive tract, thymus, bursa of Fabricius, muscle and lung.
The intermediate domain (ID) is required for the phosphorylation and activation of IRAK.
The 26S proteasome is involved in the ATP-dependent degradation of ubiquitinated proteins. The regulatory (or ATPase) complex confers ATP dependency and substrate specificity to the 26S complex.
Functions as component of the Arp2/3 complex which is involved in regulation of actin polymerization and together with an activating nucleation-promoting factor (NPF) mediates the formation of branched actin networks.
Belongs to the metallo-beta-lactamase superfamily. RNA-metabolizing metallo-beta-lactamase-like family. CPSF2/YSH1 subfamily.
May play an essential role in Wnt signaling pathway. May be required for Wnt-dependent patterning processes (By similarity).
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.
Binds DNA via the 2 GATA-type zinc fingers.
Expressed only in definitive (adult) erythrocytes within the red cell lineage, and is also abundantly expressed in T-lymphocytes and brain.
Secreted growth factor that mediates its signal through cell-surface proteoglycan and non-proteoglycan receptors (By similarity). Binds cell-surface proteoglycan receptor via their chondroitin sulfate (CS) groups (By similarity). Thereby regulates many processes like cell proliferation, cell survival, cell growth, cell differentiation and cell migration (By similarity).
Belongs to the eukaryotic GSH synthase family.
Binds to the LIM domain of a wide variety of LIM domain-containing transcription factors.
Due to intron retention. Lacks LIM-binding domain.
First expressed at stages 15-16 in presumptive limb mesoderm. As limb outgrowth proceeds, expressed in the entire limb bud, concentrating in the distal mesoderm throughout limb development. Both hindlimbs and forelimbs exhibit similar expression patterns.
The dimerization domain is located in the N-terminus.
Nuclear chaperone required for maturation and nuclear export of pre-60S ribosome subunits.
Regulator of deubiquitinating complexes, which acts as a strong activator of USP1, USP12 and USP46. Enhances the USP1-mediated deubiquitination of FANCD2; USP1 being almost inactive by itself. Activates deubiquitination by increasing the catalytic turnover without increasing the affinity of deubiquitinating enzymes for the substrate. Also activates deubiquitinating activity of complexes containing USP12. Docks at the distal end of the USP12 fingers domain and induces a cascade of structural changes leading to the activation of the enzyme. Together with RAD51AP1, promotes DNA repair by stimulating RAD51-mediated homologous recombination. Binds single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA). DNA-binding is required both for USP1-mediated deubiquitination of FANCD2 and stimulation of RAD51-mediated homologous recombination: both WDR48/UAF1 and RAD51AP1 have coordinated role in DNA-binding during these processes.Together with ATAD5 and by regulating USP1 activity, has a role in PCNA-mediated translesion synthesis (TLS) by deubiquitinating monoubiquitinated PCNA. Together with ATAD5, has a role in recruiting RAD51 to stalled forks during replication stress.
The WD repeats are required for the interaction with deubiquitinating enzymes USP1, USP12 and USP46.
Belongs to the myelin basic protein family.
In the optic lobe, first detected at embryonic day 14. Expression strongly increases between embryonic days 16 and 18, reaches a maximum at postnatal day 1, and then declines again to the adult level.
Is, with PLP, the most abundant protein component of the myelin membrane in the CNS. Has a role in both the formation and stabilization of this compact multilayer arrangement of bilayers. Each splice variant and charge isomer may have a specialized function in the assembly of an optimized, biochemically functional myelin membrane (By similarity).
Several charge isomers are produced as a result of optional post-translational modifications, such as phosphorylation of serine or threonine residues, deamidation of glutamine or asparagine residues, citrullination and methylation of arginine residues. Chicken MBP contains 4 charge components denoted as C1, C2, C3 and C8. C1 lacks any phosphorylation sites, whereas C2 and C3 contain respectively 10 and 8 phosphorylation sites and arginine residues modified to citrulline. All three charge components contain deamidated glutamines and asparagine, and a methylated arginine.
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.
Belongs to the pectinacetylesterase family. Notum subfamily.
Part of an E3 ubiquitin ligase complex for neddylation. Promotes neddylation of cullin components of E3 cullin-RING ubiquitin ligase complexes. Acts by binding to cullin-RBX1 complexes in the cytoplasm and promoting their nuclear translocation, enhancing recruitment of E2-NEDD8 (UBE2M-NEDD8) thioester to the complex, and optimizing the orientation of proteins in the complex to allow efficient transfer of NEDD8 from the E2 to the cullin substrates.
Expression is first detected in the prechordal mesoderm of stage 4 gastrulas.
In the developing embryo, expressed in the anterior head-fold, the anterior neural plate and optic vesicle. At later stages expression is maintained in the eye, while brain expression becomes limited. Not expressed in the lens placode.
Belongs to the sulfotransferase 1 family. NDST subfamily.
E3 ubiquitin-protein ligase mediating 'Lys-63'-linked polyubiquitination of RRAGA in response to amino acid starvation. Thereby, regulates mTORC1 signaling and plays a role in the cellular response to amino acid availability. Also mediates 'Lys-48'-linked polyubiquitination of target proteins and their subsequent targeting to the proteasome for degradation.
Homodimer. Heterodimer; with a rar molecule.
Receptor for retinoic acid that acts as a transcription factor. Forms homo- or heterodimers with retinoic acid receptors (rars) and binds to target response elements in response to their ligands, all-trans or 9-cis retinoic acid, to regulate gene expression in various biological processes.
Associates with GIRK2, GIRK3 or GIRK4 to form a G-protein activated heteromultimer pore-forming unit. The resulting inward current is much larger.
This potassium channel is controlled by G proteins. 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. This receptor plays a crucial role in regulating the heartbeat.
Binds 1 5,10-methenyltetrahydrofolate (MTHF) non-covalently per subunit.
Binds 1 FAD per subunit. Only a minority of the protein molecules contain bound FAD. Contrary to the situation in photolyases, the FAD is bound in a shallow, surface-exposed pocket.
Component of the circadian core oscillator, which includes the CRY proteins, CLOCK or NPAS2, BMAL1 or BMAL2, CSNK1E, and the PER proteins.
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 period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and BMAL1 or BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-BMAL1|BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G, which form a second feedback loop and which activate and repress BMAL1 transcription, respectively. CRY1 and CRY2 have redundant functions but also differential and selective contributions at least in defining the pace of the SCN circadian clock and its circadian transcriptional outputs. More potent transcriptional repressor in cerebellum and liver than CRY2, though more effective in lengthening the period of the SCN oscillator. On its side, CRY2 seems to play a critical role in tuning SCN circadian period by opposing the action of CRY1. With CRY2, is dispensable for circadian rhythm generation but necessary for the development of intercellular networks for rhythm synchrony. Capable of translocating circadian clock core proteins such as PER proteins to the nucleus (By similarity). Interacts with CLOCK-BMAL1 independently of PER proteins and is found at CLOCK-BMAL1-bound sites, suggesting that CRY may act as a molecular gatekeeper to maintain CLOCK-BMAL1 in a poised and repressed state until the proper time for transcriptional activation (By similarity). Represses CLOCK-BMAL1-mediated transcriptional activation (PubMed:11684328).
Up-regulated by light. Higher levels in light/dark cycle than in total darkness.
Belongs to the eukaryotic ribosomal protein eL19 family.
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. However, the CST complex has been shown to be involved in several aspects of telomere replication.
Probably catalyzes the deacetylation of acetylated carbohydrates an important step in the degradation of oligosaccharides.
Component of the spliceosome B complex. Associated with U2 snRNPs. Binds splicing factors SNRPB, SNRPC and SF1 (By similarity).
Involved in pre-mRNA splicing as a component of the spliceosome. May play a role in cross-intron bridging of U1 and U2 snRNPs in the mammalian A complex.
Comprised of 3 domains; an N-terminal DNA-binding domain, a centrally located transcriptional activation domain and a C-terminal domain involved in transcriptional repression.
Transcriptional activator; DNA-binding protein that specifically recognize the sequence 5'-YAAC[GT]G-3'. Plays an important role in the control of proliferation and differentiation of hematopoietic progenitor cells.
Truncation of either the N- or C-terminal of C-Myb leads to increased transformation and transactivation potential.
Receptor for Dickkopf proteins. Cooperates with DKK1/2 to inhibit Wnt/beta-catenin signaling by promoting the endocytosis of Wnt receptors LRP5 and LRP6.
Binds specifically to the 3'-terminal U-tract of U6 snRNA.
Belongs to the aldo/keto reductase family. Glutamate--cysteine ligase light chain subfamily.
Heterodimer of a catalytic heavy chain and a regulatory light chain.
Component of the origin recognition complex (ORC) that binds origins of replication. DNA-binding is ATP-dependent. ORC is required to assemble the pre-replication complex necessary to initiate DNA replication.
Component of the origin recognition complex (ORC).
Homodimerization via the leucine zipper domains is required for autophosphorylation.
Expressed at high levels in bursa of fabricus, thymus and spleen. Also found in the liver, intestine, heart and brain.
Specifically binds 5-hydroxymethylcytosine (5hmC), suggesting that it acts as a specific reader of 5hmC.
Undergoes proteolytic processing during lymphocyte apoptosis.
Catalyzes the reversible synthesis of acetylcholine (ACh) from acetyl CoA and choline at cholinergic synapses.
Detected in brain and in embryonic retina.
Phosphorylated by LATS1 and LATS2; leading to cytoplasmic translocation and inactivation.
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 (By similarity). Plays a key role in tissue tension and 3D tissue shape by regulating cortical actomyosin network formation (By similarity).
Expressed at sites of mineralization in bone and cartilage. Highly expressed in hypertrophic chondrocytes compared to non-chondrogenic tissues. Expressed in chondrocytes but not in heart, liver, lung, kidney, spleen, muscle, adipose tissues not duodenum. In diaphyseal cortical bone, it is expressed in the osteoid layer of the periosteum, forming surfaces of growing osteons, and newly formed osteocytes, whereas it is not expressed in the endosteum and closed osteons. In growth plate cartilage, it is limited to the early hypertrophic chondrocytes and the ossification groove of Ranvier. Highly expressed on the mineralization surfaces of the cartilage remnants and trabecular bone within the primary spongiosa. Expressed in 17-day-old embryonic calvaria, the osteoid present on the intramembranous and periosteal bone surfaces but not in soft tissues examined.
Phosphatase that has a high activity toward phosphoethanolamine (PEA) and phosphocholine (PCho) (By similarity). Involved in the generation of inorganic phosphate for bone mineralization (PubMed:15050893).
Up-regulated 5-fold during chondrocyte terminal differentiation.
Belongs to the class-II pyridoxal-phosphate-dependent aminotransferase family.
Modulates the action of platelet-activating factor (PAF) by hydrolyzing the sn-2 ester bond to yield the biologically inactive lyso-PAF. Has a specificity for substrates with a short residue at the sn-2 position. It is inactive against long-chain phospholipids.
Expressed in ovarian follicle granulosa cells (PubMed:9545511, PubMed:8828833). Expressed in ovarian follicle theca cells (PubMed:8828833).
Expression levels are very low in 3-5mm, 6-8mm and 9-12mm ovarian follicles, but subsequently increase rapidly with high levels detected during F3, F2 and F1 preovulatory stages.
Receptor for lutropin-choriogonadotropic hormone. The activity of this receptor is mediated by G proteins which activate adenylate cyclase.
Belongs to the carbohydrate kinase PfkB family.
Protein transport. Acts, in coordination with RAB6A, to regulate intra-Golgi retrograde trafficking (By similarity). It is involved in autophagy, acting as a modulator of autophagosome formation (By similarity).
Actin cytoskeleton-organizing protein that plays a role in the formation of cell projections (By similarity). Plays a role in dendritic spine morphogenesis and organization, including the localization of the dopamine receptor DRD1 to the dendritic spines (By similarity). Involved in synaptic plasticity (By similarity).
Drebrins are classified into two forms of the embryonic type (E1 and E2) and one form of the adult type (A). The time course of their appearance are different from each other. Their structures are closely related.
Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ5 subfamily.
Deposition-and-exchange histone chaperone specific for H2AZ1, specifically chaperones H2AZ1 and deposits it into nucleosomes. As component of the SRCAP complex, mediates the ATP-dependent exchange of histone H2AZ1/H2B dimers for nucleosomal H2A/H2B, leading to transcriptional regulation of selected genes by chromatin remodeling.
Belongs to the immunoglobulin superfamily. AMIGO family.
Acts as a transcriptional activator that promotes transcription of muscle-specific target genes and plays a role in muscle differentiation. 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).
Efficient DNA binding requires dimerization with another bHLH protein. Seems to form active heterodimers with ITF-2.
Belongs to the gamma-glutamylcyclotransferase family.
Catalyzes the formation of 5-oxo-L-proline from L-gamma-glutamyl-L-epsilon-lysine.
Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIC subfamily.
Belongs to the type I cytokine receptor family. Type 4 subfamily.
Non-covalent dimer of an alpha and a beta subunit. IL2R exists in 3 different forms: a high affinity dimer, an intermediate affinity monomer (beta subunit), and a low affinity monomer (alpha subunit). The high and intermediate affinity forms also associate with a gamma subunit. Interacts with SHB upon interleukin stimulation.
Allosterically activated by various compounds including ATP, 2,3-BPG/2,3-Bisphosphoglyceric acid and Ap4A/P1,P4-bis(5'-adenosyl) tetraphosphate. Binding of an allosteric activator is a prerequisiste to magnesium and substrate binding. Inhibited by inorganic phosphate (By similarity). Inhibited by inosine, guanosine, p-chloromercuribenzoate and NaF (PubMed:6060459).
Broad specificity cytosolic 5'-nucleotidase that catalyzes the dephosphorylation of 6-hydroxypurine nucleoside 5'-monophosphates (PubMed:6060459). 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 (By similarity). Has the highest activities for IMP and GMP followed by dIMP, dGMP and XMP (PubMed:6060459). Could also catalyze the transfer of phosphates from pyrimidine monophosphates but with lower efficiency (By similarity). Through these activities regulates the purine nucleoside/nucleotide pools within the cell (PubMed:6060459).
Belongs to the proteasome subunit S5B/HSM3 family.
Catalytic subunit of the type B histone acetyltransferase (HAT) complex, composed of RBBP7 and HAT1. Interacts with histones H4 and H2A.
Histone acetyltransferase that plays a role in different biological processes including cell cycle progression, glucose metabolism, histone production or DNA damage repair. Coordinates histone production and acetylation via H4 promoter binding. Acetylates histone H4 at 'Lys-5' (H4K5ac) and 'Lys-12' (H4K12ac) and, to a lesser extent, histone H2A at 'Lys-5' (H2AK5ac).
The exocyst complex is composed of EXOC1, EXOC2, EXOC3, EXOC4, EXOC5, EXOC6, EXOC7 and EXOC8.
Belongs to the acireductone dioxygenase (ARD) family.
Binds either 1 Fe or Ni cation per monomer. Iron-binding promotes an acireductone dioxygenase reaction producing 2-keto-4-methylthiobutyrate, while nickel-binding promotes an acireductone dioxygenase reaction producing 3-(methylsulfanyl)propanoate.
Catalyzes 2 different reactions between oxygen and the acireductone 1,2-dihydroxy-3-keto-5-methylthiopentene (DHK-MTPene) depending upon the metal bound in the active site. Fe-containing acireductone dioxygenase (Fe-ARD) produces formate and 2-keto-4-methylthiobutyrate (KMTB), the alpha-ketoacid precursor of methionine in the methionine recycle pathway. Ni-containing acireductone dioxygenase (Ni-ARD) produces methylthiopropionate, carbon monoxide and formate, and does not lie on the methionine recycle pathway.
E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and transfers it to its substrates.
Expressed preferentially in neural tissue.
In quiescent cells, maintained in an inactive state via an intramolecular interaction between the protein kinase and N-terminal domains. Following mitogen-mediated cell activation, binds via its RGB domain to active HRAS (GTP-bound) which releases the inhibitory intramolecular interaction between the two domains. This allows the MAP2K1-mediated dimerization of KSR1 or KSR2, and BRAF which activates BRAF.
Protein kinase involved in the activation of the MAP signaling cascade. May play a role in transducing specific signals in neural cells.
Belongs to the peptidase C19 family. USP16 subfamily.
Specifically deubiquitinates 'Lys-120' of histone H2A (H2AK119Ub), a specific tag for epigenetic transcriptional repression, thereby acting as a coactivator. 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. Regulates Hox gene expression via histone H2A deubiquitination. Prefers nucleosomal substrates. Does not deubiquitinate histone H2B.
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.
May be involved in the transport of retinol between the photoreceptors and the pigmented epithelium.
Belongs to the sterol desaturase family.
Catalyzes the first step in the removal of the two C-4 methyl groups of 4,4-dimethylzymosterol.
The histidine box domains may contain the active site and/or be involved in metal ion binding.
Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin-protein ligase complex that controls progression through mitosis and the G1 phase of the cell cycle.
Belongs to the WD repeat RBAP46/RBAP48/MSI1 family.
Binds directly to helix 1 of the histone fold of histone H4, a region that is not accessible when H4 is in chromatin. Also interacts with histone H2B and HAT1.
Core histone-binding subunit that may target chromatin remodeling factors, histone acetyltransferases and histone deacetylases to their histone substrates in a manner that is regulated by nucleosomal DNA.
Component of the PAF1 complex, which at least consists of CDC73, PAF1, LEO1, CTR9, RTF1 and SKIC8 (By similarity). The PAF1 complex interacts with PHF5A (By similarity).
Belongs to the mitochondrion-specific ribosomal protein mS33 family.
Histone H5 performs the same function as H1, being necessary for the condensation of nucleosome chains into higher order structures, and replaces histone H1 in certain cells.
Can activate or inhibit Wnt signaling in a context-dependent manner. Activates the canonical Wnt pathway whereby acts through Disheveled proteins and beta-catenin. Antagonises Wnt signaling through the canonical pathways presumably by blocking accessibility of certain WNTs to their receptors. Induces posterior neural markers via components of the canonical Wnt pathway.
Expression was first detected broadly at stage 9, and then localized in the posterior surface ectoderm overlying the presomitic mesoderm by stage 10-11 embryo.
In all hematopoietic tissues except peripheral blood erythrocytes and in the liver and lung.
Recognizes the DNA sequence 5'-ATTAA-3'. Transcriptional repressor. May play a role in hematopoietic differentiation.
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 (By similarity). During early stages of lens development, interacts with the C-terminus of MIP (PubMed:14762116).
Phosphorylated on Ser-364; which inhibits cleavage by caspase-3.
Proteolytically cleaved by caspase-3 during lens development.
Structural component of eye lens gap junctions (PubMed:8049527). 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:8049527).
Belongs to the KIF-binding protein family.
Required for organization of axonal microtubules, and axonal outgrowth and maintenance during peripheral and central nervous system development.
Activated by phosphorylation on Ser/Thr catalyzed by MAP kinase kinase kinases (RAF).
Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily.
Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. Activates the ERK1 and ERK2 MAP kinases (By similarity).
Detected in trachea, lung, proventriculus, duodenum, jejunum, ileum, caeca, colon, caecal tonsil, bursa of Fabricius, kidney, ovary, testis, thymus, liver, spleen, bone marrow, skin, uropygial gland, muscle and brain.
Belongs to the WD repeat DCAF13/WDSOF1 family.
Possible role in ribosomal RNA processing. May function as a substrate receptor for CUL4-DDB1 E3 ubiquitin-protein ligase complex (By similarity).
Belongs to the RNA cytidine acetyltransferase family. NAT10 subfamily.
RNA cytidine acetyltransferase with specificity toward both 18S rRNA and tRNAs. Catalyzes the formation of N(4)-acetylcytidine (ac4C) in 18S rRNA. Required for early nucleolar cleavages of precursor rRNA at sites A0, A1 and A2 during 18S rRNA synthesis. Catalyzes the formation of ac4C in serine and leucine tRNAs. Requires the tRNA-binding adapter protein THUMPD1 for full tRNA acetyltransferase activity but not for 18S rRNA acetylation.
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.
Responsible for the deiodination of T4 (3,5,3',5'-tetraiodothyronine) into RT3 (3,3',5'-triiodothyronine) and of T3 (3,5,3'-triiodothyronine) into T2 (3,3'-diiodothyronine).
Restricts trafficking of FAF2 from the endoplasmic reticulum to lipid droplets (By similarity). May negatively regulate the canonical Wnt signaling pathway in the lymphocytes (By similarity).
Belongs to the FAD-dependent oxidoreductase family.
Regulates the chamber-specific expression of myosin isoforms by activating the expression of the ventricle myosin heavy chain-1 (Vmhc1) and suppressing the expression of the atrial myosin heavy chain-1 (Amhc1) in the ventricles. May play a critical role in establishing chamber-specific gene expression in the developing heart.
Ventricles of the heart, developing feather buds, retina, hindbrain.
Autophosphorylates upon activation by EFNA5.
Highly expressed in the developing brain and embryonic tissues. In adult, the greatest levels of expression occur in the brain. It is expressed in a graded manner across the retina with the highest expression at its temporal pole. Detectable in all other adult tissues examined, except the liver.
Receptor tyrosine kinase which binds promiscuously 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 for ephrin-A ligands it binds preferentially EFNA5. Upon activation by EFNA5 regulates cell-cell adhesion, cytoskeletal organization and cell migration. Plays a role in cardiac cells migration and differentiation probably through activation by EFNA1. Involved in the retinotectal mapping of neurons. May also control the segregation but not the guidance of motor and sensory axons during neuromuscular circuit development.
Belongs to the JHDM3 histone demethylase family.
Component of the spliceosome B complex. Interacts with IK.
Involved in pre-mRNA splicing as a component of the spliceosome (By similarity). Regulates alternative splicing of the HSPG2 pre-mRNA (By similarity). Required for normal accumulation of IK (By similarity). Required for normal mitotic spindle assembly and normal progress through mitosis (By similarity).
The WD repeats assemble into a seven-bladed WD propeller.
Belongs to the HAD-like hydrolase superfamily.
Catalyzes the attachment of tyrosine to tRNA(Tyr) in a two-step reaction: tyrosine is first activated by ATP to form Tyr-AMP and then transferred to the acceptor end of tRNA(Tyr).
The nuclear localization signal, which mediates localization to the nucleus, is also important for interacting with tRNA(Tyr), suggesting that it is sterically blocked when tRNA(Tyr) is bound.
Contains two independent C-terminal transactivation domains, NTAD and CTAD, which function synergistically. Their transcriptional activity is repressed by an intervening inhibitory domain (ID) (By similarity).
Efficient DNA binding requires heterodimerization of an alpha and a beta/ARNT subunit.
Functions as a master transcriptional regulator of the adaptive response to hypoxia. Under hypoxic conditions, activates the transcription of over 40 genes, including erythropoietin, glucose transporters, glycolytic enzymes, vascular endothelial growth factor, HILPDA, and other genes whose protein products increase oxygen delivery or facilitate metabolic adaptation to hypoxia. Plays an essential role in embryonic vascularization, tumor angiogenesis and pathophysiology of ischemic disease.
In normoxia, is hydroxylated on Asn-788, thus abrogating interaction with CREBBP and EP300 and preventing transcriptional activation.
In normoxia, is hydroxylated on Pro-402 and Pro-562. The hydroxylated prolines promote interaction with VHL, initiating rapid ubiquitination and subsequent proteasomal degradation. Under hypoxia, proline hydroxylation is impaired and ubiquitination is attenuated, resulting in stabilization (By similarity).
Induced by reactive oxygen species (ROS).
The iron and 2-oxoglutarate dependent 3-hydroxylation of asparagine is (S) stereospecific within HIF CTAD domains.
Belongs to the MsrA Met sulfoxide reductase family.
Key enzyme involved in DNA replication and DNA repair in nucleus and mitochondrion. Involved in Okazaki fragments processing by cleaving long flaps that escape FEN1: flaps that are longer than 27 nucleotides are coated by replication protein A complex (RPA), leading to recruit DNA2 which cleaves the flap until it is too short to bind RPA and becomes a substrate for FEN1. Also involved in 5'-end resection of DNA during double-strand break (DSB) repair by mediating the cleavage of 5'-ssDNA, while the 3'-ssDNA cleavage is prevented by the presence of RPA. Also involved in DNA replication checkpoint independently of Okazaki fragments processing. Possesses different enzymatic activities, such as single-stranded DNA (ssDNA)-dependent ATPase, 5'-3' helicase and endonuclease activities. While the ATPase and endonuclease activities are well-defined and play a key role in Okazaki fragments processing and DSB repair, the 5'-3' DNA helicase activity is subject to debate. According to various reports, the helicase activity is weak and its function remains largely unclear. Helicase activity may promote the motion of DNA2 on the flap, helping the nuclease function (By similarity).
In the embryo is expressed in the developing hindbrain and is accumulated in rhombomere boundary regions and in the rhombomere 2, 4 and 6.
Involved in microtubule stabilization in many cell types, including neuronal cells. Specifically has microtubule cold stabilizing activity. Involved in dendrite morphogenesis and maintenance by regulating lysosomal trafficking (By similarity).
The N- and C-terminal barrels adopt an identical fold despite having only 13% of conserved residues.
The N-terminal region may be exposed to the interior of the granule, whereas the C-terminal portion may be embedded in the membrane. During phagocytosis and degranulation, proteases may be released and activated and cleave BPI at the junction of the N- and C-terminal portions of the molecule, providing controlled release of the N-terminal antibacterial fragment when bacteria are ingested.
The cytotoxic action of BPI is limited to many species of Gram-negative bacteria; this specificity may be explained by a strong affinity of the very basic N-terminal half for the negatively charged lipopolysaccharides that are unique to the Gram-negative bacterial outer envelope.
Acts as a transcriptional regulator (PubMed:7528105). 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. Binds to insulin gene enhancer sequences (By similarity). Defines subclasses of motoneurons that segregate into columns in the spinal cord and select distinct axon pathways (PubMed:7528105). Acts in conjunction with LHX1, LHX3 and ISL2 (PubMed:7528105). Binds to insulin gene enhancer sequences (By similarity). Essential for heart development (By similarity).
Expressed in motor neurons between stages 34 and 35 (at protein level). Expressed prior to the formation of distinct motor axon pathways and before the segregation of motor neurons into columns. Expressed throughout the median motor column and the medial subdivision of the lateral motor column (LMCm).
Transcription factor and proto-oncogene whose activation results in up-regulation of target genes, such as IGFII, leading to uncontrolled cell proliferation.
Lipoproteins are powerful coactivators of PM20D1 activity in vitro and NAA biosynthesis in vivo.
Secreted enzyme that regulates the endogenous N-fatty acyl amino acid (NAAs) tissue and circulating levels by functioning as a bidirectional NAA synthase/hydrolase. It condenses free fatty acids and free amino acids to generate NAAs and bidirectionally catalyzes the reverse hydrolysis reaction. Some of these NAAs stimulate oxidative metabolism via mitochondrial uncoupling, increasing energy expenditure in a UPC1-independent manner. Thereby, this secreted protein may indirectly regulate whole body energy expenditure. PM20D1 circulates in tight association with both low- and high-density (LDL and HDL,respectively) lipoprotein particles.
Heterodimer with uroplakin-3A (UPK3A) or uroplakin-3B (UPK3B).
Detected in limb buds at embryonic stages 22-23 (at protein level).
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) acts as an activator (GLI3A) while GLI3R, its C-terminally truncated form, acts as a repressor.
Phosphorylation is essential for its proteolytic processing.
The repressor form (GLI3R), a C-terminally truncated form is generated from the full-length GLI3 protein (GLI3FL) through proteolytic processing.
Accessory component of both the DNA polymerase delta complex and the DNA polymerase zeta complex. As a component of the trimeric and tetrameric DNA polymerase delta complexes (Pol-delta3 and Pol-delta4, respectively), plays a role in high fidelity genome replication, including in lagging strand synthesis, and repair. Required for optimal Pol-delta activity. Stabilizes the Pol-delta complex and plays a major role in Pol-delta stimulation by PCNA. Pol-delta3 and Pol-delta4 are characterized by the absence or the presence of POLD4. They exhibit differences in catalytic activity. Most notably, Pol-delta3 shows higher proofreading activity than Pol-delta4. Although both Pol-delta3 and Pol-delta4 process Okazaki fragments in vitro, Pol-delta3 may also be better suited to fulfill this task, exhibiting near-absence of strand displacement activity compared to Pol-delta4 and stalling on encounter with the 5'-blocking oligonucleotides. Pol-delta3 idling process may avoid the formation of a gap, while maintaining a nick that can be readily ligated. Along with DNA polymerase kappa, DNA polymerase delta carries out approximately half of nucleotide excision repair (NER) synthesis following UV irradiation. In this context, POLD3, along with PCNA and RFC1-replication factor C complex, is required to recruit POLD1, the catalytic subunit of the polymerase delta complex, to DNA damage sites. Under conditions of DNA replication stress, required for the repair of broken replication forks through break-induced replication (BIR). Involved in the translesion synthesis (TLS) of templates carrying O6-methylguanine or abasic sites performed by Pol-delta4, independently of DNA polymerase zeta (REV3L) or eta (POLH). Facilitates abasic site bypass by DNA polymerase delta by promoting extension from the nucleotide inserted opposite the lesion. Also involved in TLS, as a component of the tetrametric DNA polymerase zeta complex. Along with POLD2, dramatically increases the efficiency and processivity of DNA synthesis of the DNA polymerase zeta complex compared to the minimal zeta complex, consisting of only REV3L and REV7.
Component of both the DNA polymerase delta and DNA polymerase zeta complexes. The tetrameric DNA polymerase delta complex (Pol-delta4), which consists of POLD1/p125, POLD2/p50, POLD3/p66/p68 and POLD4/p12, with POLD1 bearing DNA polymerase and 3' to 5' proofreading exonuclease activities.
The PIP-box mediates the interaction with PCNA.
Homodimer; disulfide-linked. Can also form homotetramers.
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.
(Microbial infection) Interacts with newcastle disease virus protein HN; this interaction inhibits viral adsorption rather than internalization.
Mainly in the intestine (adult), mainly in the skin (embryo).
This protein binds beta-galactoside. May participate in host antiviral defense through specific interaction with glycans on the viral envelope glycoproteins.
Adds the eighth mannose residue in an alpha-1,6 linkage onto the dolichol-PP-oligosaccharide precursor (dolichol-PP-Man(7)GlcNAc(2)) required for protein glycosylation.
Belongs to the ubiquitin-activating E1 family. UBA3 subfamily.
Catalytic subunit of the dimeric E1 enzyme, which activates NEDD8.
Fatty acyl-coenzyme A (CoA) diphosphatase that hydrolyzes fatty acyl-CoA to yield acyl-4'-phosphopantetheine and adenosine 3',5'-bisphosphate (By similarity). Mediates the hydrolysis of a wide range of CoA esters, including choloyl-CoA and branched-chain fatty-acyl-CoA esters and at low substrate concentrations medium and long-chain fatty-acyl-CoA esters are the primary substrates (By similarity). Highest activity seen with medium-chain acyl-CoA esters and higher rates of activity seen with the unsaturated acyl-CoA esters compared with the saturated esters (By similarity). Exhibits decapping activity towards dpCoA-capped RNAs in vitro (By similarity).
Catalyzes the reduction of D-erythrulose to D-threitol with the concomitant oxidation of NAD(P)H to NAD(P)(+). NADH is less effective than NADPH. May also catalyze the reduction of L-xylulose.
Highly expressed in kidney, and also found in high amounts in liver and testis. Low expression seen in all other tissues tested.
Belongs to the Mediator complex subunit 24 family.
May associate with CD21. May regulate the release of Ca(2+) from intracellular stores (By similarity).
May associate with CD21. May regulate the release of Ca(2+) from intracellular stores.
Heterotetramer of 2 alpha (or alpha-D) and 2 beta chains.
Involved in oxygen transport from the lung to the various peripheral tissues. The beta chain is a component of adult hemoglobin A and D.
May be involved in photoreceptor outer segment disk morphogenesis.
Belongs to the AB hydrolase superfamily. LDAH family.
Probable serine lipid hydrolase associated with lipid droplets. Appears to lack cholesterol esterase activity. Appears to lack triglyceride lipase activity.
The catalytic activity is unsure despite catalytic sites being conserved.
Belongs to the peroxisomal targeting signal receptor family.
In addition to promoting peroxisomal translocation of proteins containing a PTS1 peroxisomal targeting signal, mediates peroxisomal import of proteins containing a C-terminal PTS2-type peroxisomal targeting signal via its interaction with PEX7. Interaction with PEX7 only takes place when PEX7 is associated with cargo proteins containing a PTS2 peroxisomal targeting signal. PEX7 along with PTS2-containing cargo proteins are then translocated through the PEX13-PEX14 docking complex together with PEX5.
Interacts (via WxxxF/Y and LVxEF motifs) with PEX14; promoting translocation through the PEX13-PEX14 docking complex (By similarity). Interacts with PEX7, promoting peroxisomal import of proteins containing a C-terminal PTS2-type peroxisomal targeting signal (By similarity).
Monoubiquitinated at Cys-11 by PEX2 during PEX5 passage through the retrotranslocation channel (By similarity). Cys-11 monoubiquitination acts as a recognition signal for the PEX1-PEX6 complex and is required for PEX5 extraction and export from peroxisomes. When PEX5 recycling is compromised, polyubiquitinated by PEX10 during its passage through the retrotranslocation channel, leading to its degradation (By similarity).
Receptor that mediates peroxisomal import of proteins containing a C-terminal PTS1-type tripeptide peroxisomal targeting signal (SKL-type). Binds to cargo proteins containing a PTS1 peroxisomal targeting signal in the cytosol, and translocates them into the peroxisome matrix by passing through the PEX13-PEX14 docking complex along with cargo proteins. PEX5 receptor is then retrotranslocated into the cytosol, leading to release of bound cargo in the peroxisome matrix, and reset for a subsequent peroxisome import cycle.
The TPR repeats mediate interaction with proteins containing a C-terminal PTS1-type tripeptide peroxisomal targeting signal (SKL-type).
The WxxxF/Y motifs mediate interaction with PEX14, promoting association with the PEX13-PEX14 docking complex.
The amphipathic helix 1 and 2 (AH1 and AH2, respectively) are required for PEX5 retrotranslocation and recycling. AH2 mediates interaction with lumenal side of the PEX2-PEX10-PEX12 ligase complex, while AH1 is required for extraction from peroxisomal membrane by the PEX1-PEX6 AAA ATPase complex.
The color pigments are found in the cone photoreceptor cells.
Visual pigments are the light-absorbing molecules that mediate vision. They consist of an apoprotein, opsin, covalently linked to cis-retinal.
Belongs to the V-ATPase H subunit family.
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.
Belongs to the SSU72 phosphatase family.
May be involved in the C-terminal domain of RNA polymerase II dephosphorylation, RNA processing and termination.
Belongs to the GTP-binding elongation factor family. LepA subfamily.
Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. LepA subfamily.
Promotes mitochondrial protein synthesis. May act as a fidelity factor of the translation reaction, by catalyzing a one-codon backward translocation of tRNAs on improperly translocated ribosomes. Binds to mitochondrial ribosomes in a GTP-dependent manner.
Cell surface GPI-bound 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. Induces compartmentalized signaling within a caveolae-like membrane microdomain when bound to the extracellular domain of its cognate receptor. This signaling event requires the activity of the Fyn tyrosine kinase. Activates the EPHA3 receptor to regulate cell-cell adhesion and cytoskeletal organization. With the receptor EPHA2 may regulate lens fiber cells shape and interactions and be important for lens transparency maintenance. May function actively to stimulate axon fasciculation (By similarity). Induces growth cone collapse and repulsion of retinal ganglion cell axons.
Expressed in a graded fashion across the tectum being more strongly expressed towards the posterior pole.
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 to sites in the 5'-flanking sequence of its coding region with various affinities. The consensus sequences of the high and low affinity binding sites are 5'-TAATGA[CG]-3' and 5'-CTAATTTT-3'.
The proline stretch works as a part of the transcriptional activation domain.
Tautomerization of D-dopachrome with decarboxylation to give 5,6-dihydroxyindole (DHI).
E3 ubiquitin-protein ligase involved in Golgi membrane fusion and regulation of small GTPases. Acts as a regulator of Golgi membrane dynamics during the cell cycle: recruited to Golgi membrane by Rab proteins and regulates postmitotic Golgi membrane fusion. Acts by mediating ubiquitination during mitotic Golgi disassembly, ubiquitination serving as a signal for Golgi reassembly later, after cell division.
Belongs to the WD repeat PAAF1/RPN14 family.
Inhibits proteasome 26S assembly and activity by impairing the association of the 19S regulatory complex with the 20S core.
Interacts with proteasome 26S subunit ATPases.
Does not bind lactose, and may not bind carbohydrates.
Most of the residues in the galectin domain that have been shown to be critical for carbohydrate-binding in other galectins are not conserved.
May act as a positive regulator of ERK phosphorylation downstream of fibroblast growth factor-receptor activation. May induce both caspase-dependent apoptosis and caspase-independent cell death.
Widely expressed with the highest expression in brain and ovary.
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.
SEC16A and SEC16B are each present in multiple copies in a heteromeric complex.
Belongs to the adenylate kinase family. AK1 subfamily.
Catalyzes the reversible transfer of the terminal phosphate group between ATP and AMP (PubMed:2161682, PubMed:2229026, PubMed:2542324, PubMed:1958702). Exhibits nucleoside diphosphate kinase catalyzing the production of ATP, CTP, GTP, UTP, dATP, dCTP, dGTP and dTTP from the corresponding diphosphate substrates with either ATP or GTP as phosphate donor (By similarity). Also catalyzes at a very low rate the synthesis of thiamine triphosphate (ThTP) from thiamine diphosphate (ThDP) and ADP (PubMed:2229026, PubMed:8431472).
Belongs to the Cu-Zn superoxide dismutase family.
Component of the origin recognition complex (ORC) that binds origins of replication. DNA-binding is ATP-dependent, however specific DNA sequences that define origins of replication have not been identified so far. ORC is required to assemble the pre-replication complex necessary to initiate DNA replication.
Visual signal transduction is mediated by a G-protein coupled cascade using cGMP as second messenger. This protein can be activated by cGMP which leads to an opening of the cation channel and thereby causing a depolarization of rod photoreceptors.
Belongs to the DDOST 48 kDa subunit family.
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. 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).
Symmetrically cleaves beta-carotene into two molecules of retinal using a dioxygenase mechanism.
Detected in embryonic spinal cord, in the brachial and lumbar section of motor neurons (at protein level). Detected in ventro-lateral portion of embryonic spinal cord, in the brachial and lumbar section of embryonic motor neurons. Detected in embryonic adductor motor neurons and embryonic dorsal root ganglion. Detected in the caudal half of newly generated somites and in presomitic mesoderm.
Belongs to the complex I NDUFA13 subunit family.
Complex I functions in the transfer of electrons from NADH to the respiratory chain. Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis.
Divalent metal cations. Prefers Ca(2+) or Mg(2+).
Serum endocuclease secreted into body fluids by a wide variety of exocrine and endocrine organs (PubMed:12739897). Expressed by non-hematopoietic tissues and preferentially cleaves protein-free DNA (By similarity). Among other functions, seems to be involved in cell death by apoptosis (By similarity). Binds specifically to G-actin and blocks actin polymerization (By similarity).
Autophosphorylated on tyrosine residues.
Belongs to the protein kinase superfamily. Tyr protein kinase family. AXL/UFO subfamily.
Detected in embryonic retina (at protein level). detected in brain, retina, kidney and in retinal Mueller glia-like cells.
Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to several ligands. Regulates many physiological processes including cell survival, migration and differentiation. Ligand binding at the cell surface induces dimerization and autophosphorylation of TYRO3 on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, enhances PI3-kinase activity and activates the AKT survival pathway, including nuclear translocation of NF-kappa-B and up-regulation of transcription of NF-kappa-B-regulated genes (By similarity).
Involved in vitamin D transport and storage, scavenging of extracellular G-actin, enhancement of the chemotactic activity of C5 alpha for neutrophils in inflammation and macrophage activation.
Belongs to the G-alpha family. G(s) subfamily.
May act as a specific coactivator for the mammalian TEFs.
Kinase that can phosphorylate various inositol polyphosphate such as Ins(3,4,5,6)P4 or Ins(1,3,4)P3. Phosphorylates Ins(3,4,5,6)P4 at position 1 to form Ins(1,3,4,5,6)P5. This reaction is thought to have regulatory importance, since Ins(3,4,5,6)P4 is an inhibitor of plasma membrane Ca(2+)-activated Cl(-) channels, while Ins(1,3,4,5,6)P5 is not. Also phosphorylates Ins(1,3,4)P3 on O-5 and O-6 to form Ins(1,3,4,6)P4, an essential molecule in the hexakisphosphate (InsP6) pathway. Also acts as an inositol polyphosphate phosphatase that dephosphorylates Ins(1,3,4,5)P4 and Ins(1,3,4,6)P4 to Ins(1,3,4)P3, and Ins(1,3,4,5,6)P5 to Ins(3,4,5,6)P4. May also act as an isomerase that interconverts the inositol tetrakisphosphate isomers Ins(1,3,4,5)P4 and Ins(1,3,4,6)P4 in the presence of ADP and magnesium. Probably acts as the rate-limiting enzyme of the InsP6 pathway. Modifies TNF-alpha-induced apoptosis by interfering with the activation of TNFRSF1A-associated death domain. Plays an important role in MLKL-mediated necroptosis. Produces highly phosphorylated inositol phosphates such as inositolhexakisphosphate (InsP6) which bind to MLKL mediating the release of an N-terminal auto-inhibitory region leading to its activation. Essential for activated phospho-MLKL to oligomerize and localize to the cell membrane during necroptosis.
Allosterically activated by fructose 1,6-bisphosphate.
Glycolytic enzyme that catalyzes the transfer of a phosphoryl group from phosphoenolpyruvate (PEP) to ADP, generating ATP.
This activity is regulated by glucose levels.
Belongs to the transaldolase family. Type 1 subfamily.
Catalyzes the rate-limiting step of the non-oxidative phase in the pentose phosphate pathway. Catalyzes the reversible conversion of sedheptulose-7-phosphate and D-glyceraldehyde 3-phosphate into erythrose-4-phosphate and beta-D-fructose 6-phosphate.
Mediates sulfate transport with high affinity. Mediates oxalate transport. Mediates bicarbonate transport. Does not accept succinate as cosubstrate.
TFIIA is a component of the transcription machinery of RNA polymerase II and plays an important role in transcriptional activation.
NPY is implicated in the control of feeding and in secretion of gonadotrophin-release hormone.
Receptor for adenosine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase.
Acts as a transcriptional activator or repressor. Positively regulates the expression of alpha-A crystallin genes during lens fiber cell differentiation. Binds to Maf recognition elements (MARE).
Expressed in brain, thymus, gut, lung, mesenterium, spleen, kidney, ovary and bursa.
Expressed in the lens placode at stages 5, 8 and 14. Expressed at stage 18 when the invaginating lens placode closes to form the lens vesicle.
Homodimer or heterodimer with other bHLH-Zip transcription factors (By similarity). Binds DNA as a homodimer or heterodimer. Self-associates; the interaction requires the intact MAFB leucine-zipper domain. Interacts with FOS, HOXD12 and PRRX1.
APOA1 is the most potent activator in plasma. Also activated by APOE, APOC1 and APOA4 (By similarity).
Central enzyme in the extracellular metabolism of plasma lipoproteins. Synthesized mainly in the liver and secreted into plasma where it converts cholesterol and phosphatidylcholines (lecithins) to cholesteryl esters and lysophosphatidylcholines on the surface of high and low density lipoproteins (HDLs and LDLs). The cholesterol ester is then transported back to the liver. Also produced in the brain by primary astrocytes, and esterifies free cholesterol on nascent APOE-containing lipoproteins secreted from glia and influences cerebral spinal fluid (CSF) APOE- and APOA1 levels. Together with APOE and the cholesterol transporter ABCA1, plays a key role in the maturation of glial-derived, nascent lipoproteins. Required for remodeling high-density lipoprotein particles into their spherical forms (By similarity). Has a preference for plasma 16:0-18:2 or 18:O-18:2 phosphatidylcholines (PubMed:8820107).
Detected in blood plasma (at protein level) (PubMed:7592817, PubMed:8820107). Expressed in liver, brain and adrenal glands. Lower expression in testes. In laying hens, expressed higher in brain than in liver. In roosters, higher levels in liver than in brain (PubMed:7592817).
Expressed in liver during embryogenesis. Levels higher in liver than in brain up to 15 weeks after hatching. In the brain, first detected at 11 weeks after hatching and increasing levels from 15 weeks to maturity (25 weeks). Expression in the liver is much lower throughout these later stages of hatching.
In the C-terminal section; belongs to the peptidyl-alpha-hydroxyglycine alpha-amidating lyase family.
In the N-terminal section; belongs to the copper type II ascorbate-dependent monooxygenase family.
Belongs to the acetyltransferase family.
Enzyme which catalyzes the acetylation of polyamines. Substrate specificity: norspermidine = spermidine >> spermine > N(1)-acetylspermine. This highly regulated enzyme allows a fine attenuation of the intracellular concentration of polyamines. Also involved in the regulation of polyamine transport out of cells.
Preferentially expressed in the dorsal-temporal quadrant of the developing retina. There was a sharp increase in retinal SSAT levels during the transition stage from proliferation (7 dpc) to early differentiation (10 dpc). SSAT was found in Muller glial cells and its distribution pattern in these cells closely followed the three differentiation axis of the developing retina, with a central-dorsal-temporal preference.
Belongs to the eukaryotic ATPase epsilon family.
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(1) domain and of the central stalk which is part of the complex rotary element. Rotation of the central stalk against the surrounding alpha(3)beta(3) subunits leads to hydrolysis of ATP in three separate catalytic sites on the beta subunits.
Interacts with RET in the pituitary gland; this interaction prevents the formation of the AIP-survivin complex.
May play a positive role in AHR-mediated (aromatic hydrocarbon receptor) signaling, possibly by influencing its receptivity for ligand and/or its nuclear targeting.
Belongs to the Mrp/NBP35 ATP-binding proteins family.
Expressed prior to the formation of distinct motor axon pathways and before the segregation of motor neurons into columns. Expression is confined to the motor neurons in the lateral subdivision of the lateral motor column (LMC).
The LIM domains exert a negative regulatory function and disruption of the LIM domains produces an activated form. In addition, two activation domains and a negative regulatory domain exist C-terminally to the homeobox (By similarity).
Transcriptional factor that defines subclasses of motoneurons that segregate into columns in the spinal cord and select distinct axon pathways. Acts in conjunction with ISL-2.
In the mitochondria, together with PHB, forms large ring complexes (prohibitin complexes) in the inner mitochondrial membrane (IMM) and functions as chaperone protein that stabilizes mitochondrial respiratory enzymes and maintains mitochondrial integrity in the IMM, which is required for mitochondrial morphogenesis, neuronal survival, and normal lifespan.
In the nucleus, serves as transcriptional co-regulator.
Protein with pleiotropic attributes mediated in a cell-compartment- and tissue-specific manner, which include the plasma membrane-associated cell signaling functions, mitochondrial chaperone, and transcriptional co-regulator of transcription factors and sex steroid hormones in the nucleus.
The mitochondrial prohibitin complex consists of two subunits (PHB1 and PHB2), assembled into a membrane-associated ring-shaped supercomplex of approximately 1 mDa.
A cytoplasmic form lacking the first 232 amino acids has been characterized.
Both the membrane and cytoplasmic forms seem to be myristoylated.
Parallel homodimers formed between the membrane-bound and the cytosolic form, and also between 2 cytosolic forms.
Receptor for kinesin thus involved in kinesin-driven vesicle motility.
E3 ubiquitin-protein ligase that cooperates with the microRNAs (miRNAs) machinery and promotes embryonic stem cells proliferation and maintenance. Binds to miRNAs and participates in post-transcriptional repression of transcripts. Required to maintain proliferation and prevent premature differentiation of neural progenitor cells during early neural development.
Expression is strong at early stages and decreases as development proceeds. At stage 9, expressed in the segmental plate mesoderm. At stage 15, expressed in branchial axs. At stage 19-27, expressed in branchial axs, limb buds and tail buds. At stage 27-29, expressed in the tips of digits.
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.
Heterohexamer; disulfide linked. Contains 2 sets of 3 non-identical chains (alpha, beta and gamma). The 2 heterotrimers are in head to head conformation with the N-termini in a small central domain.
Accepts the ubiquitin-like protein NEDD8 from the UBA3-NAE1 E1 complex and catalyzes its covalent attachment to other proteins. The specific interaction with the E3 ubiquitin ligase RBX2, but not RBX1, suggests that the RBX2-UBE2F complex neddylates specific target proteins, such as CUL5.
Belongs to the ubiquitin-conjugating enzyme family. UBE2F subfamily.
Belongs to the DNA polymerase type-Y family.
Deoxycytidyl transferase involved in DNA repair. Transfers a dCMP residue from dCTP to the 3'-end of a DNA primer in a template-dependent reaction. May assist in the first step in the bypass of abasic lesions by the insertion of a nucleotide opposite the lesion. Required for normal induction of mutations by physical and chemical agents (By similarity). May play a role in homologous recombination and immunoglobulin gene conversion.
Deoxycytidyl transferase involved in DNA repair. Transfers a dCMP residue from dCTP to the 3'-end of a DNA primer in a template-dependent reaction. May assist in the first step in the bypass of abasic lesions by the insertion of a nucleotide opposite the lesion. Required for normal induction of mutations by physical and chemical agents.
The C-terminal domain is necessary for protein interactions.
Contributes to the regulation of axonal growth (By similarity). May play an important role in regulating the production of neural crest cells by the neural tube.
Expressed in a graded pattern in the closing neural tube. Subsequently becomes restricted to the dorsal neural folds and migrating neural crest.
Homotetramer; disulfide-linked. Dimer of dimers, giving rise to a V-shaped homotretramer. Component of the AMPAR complex.
The protein contains a globular N-terminal tetramerization domain, a long stalk formed by the coiled coil region and a C-terminal olfactomedin-like domain. Interactions between dimers are mediated by the coiled coil region. The dimers interact mostly via the N-terminal tetramerization domain, giving rise to a V-shaped overall architecture of the tetramer.
Somatostatin inhibits the release of somatotropin.
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. STRAP plays a role in the cellular distribution of the SMN complex (By similarity).
Belongs to the GTP cyclohydrolase I type 2/NIF3 family.
Homodimer. Interacts with COPS2. Interacts with THOC7.
May function as a transcriptional corepressor through its interaction with COPS2, negatively regulating the expression of genes involved in neuronal differentiation.
Binds tightly to hydroxyapatite. Appears to form an integral part of the mineralized matrix. Probably important to cell-matrix interaction. Promotes Arg-Gly-Asp-dependent cell attachment (By similarity).
It is possible that the segments of clustered carboxyl groups mediate the strong binding to hydroxyapatite.
Phosphorylated on serine and threonine residues.
Since they lack a putative transactivation domain, the small Mafs behave as transcriptional repressors when they dimerize among themselves. However, they act as transcriptional activators by dimerizing with other (usually larger) basic-zipper proteins and recruiting them to specific DNA-binding sites. Small Maf proteins heterodimerize with Fos and may act as competitive repressors of the NF-E2 transcription factor.
Belongs to the oxygen-dependent FAD-linked oxidoreductase family.
Oxidizes L-gulono-1,4-lactone to hydrogen peroxide and L-xylo-hexulonolactone which spontaneously isomerizes to L-ascorbate.
Belongs to the eukaryotic ribosomal protein eL6 family.
Belongs to the myo-inositol 1-phosphate synthase family.
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. 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 (By similarity). Together with RNF135 and UBE2N, may catalyze the viral RNA-dependent 'Lys-63'-linked polyubiquitination of RIGI to activate the downstream signaling pathway that leads to interferon beta production (By similarity).
Belongs to the phosphatase 2A regulatory subunit B family.
Belongs to the RNase H2 subunit B family.
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.
The RNase H2 complex is a heterotrimer composed of the catalytic subunit RNASEH2A and the non-catalytic subunits RNASEH2B and RNASEH2C.
Associates with the 60S ribosomal subunit of the 80S translational complex.
Belongs to the peptidase M24A family. Methionine aminopeptidase type 1 subfamily.
Binds 2 divalent metal cations per subunit. Has a high-affinity and a low affinity metal-binding site. The true nature of the physiological cofactor is under debate. The enzyme is active with zinc, cobalt, manganese or divalent iron ions. Has high activity with zinc; zinc cofactor is transferred into the active site region by the ZNG1 zinc chaperone.
Belongs to the Mediator complex subunit 22 family.
Belongs to the RNA 3'-terminal cyclase family. Type 1 subfamily.
Catalyzes the conversion of 3'-phosphate to a 2',3'-cyclic phosphodiester at the end of RNA. The mechanism of action of the enzyme occurs in 3 steps: (A) adenylation of the enzyme by ATP; (B) transfer of adenylate to an RNA-N3'P to produce RNA-N3'PP5'A; (C) and attack of the adjacent 2'-hydroxyl on the 3'-phosphorus in the diester linkage to produce the cyclic end product. The biological role of this enzyme is unknown but it is likely to function in some aspects of cellular RNA processing.
Interacts with phosphorylated C-terminal heptapeptide repeat domain (CTD) of the largest RNA polymerase II subunit POLR2A, and participates in dephosphorylation of the CTD by RPAP2. May act as a negative regulator of cyclin-D1 (CCND1) and cyclin-E (CCNE1) in the cell cycle.
May form a heterodimer with RPRD1B. Associates with the RNA polymerase II subunit POLR2A (via CTD phosphorylated at 'Ser-2' and 'Ser-7' of the heptad repeats).
Belongs to the glycosyl hydrolase 20 family.
Latency-associated peptide: Homodimer; disulfide-linked. Latency-associated peptide: Interacts with Transforming growth factor beta-3 (TGF-beta-3) chain; interaction is non-covalent and maintains (TGF-beta-3) in a latent state (By similarity). Latency-associated peptide: Interacts (via cell attachment site) with integrins, leading to release of the active TGF-beta-3 (By similarity). Transforming growth factor beta-3: Homodimer; disulfide-linked (By similarity). Transforming growth factor beta-3: Interacts with TGF-beta receptors (TGFBR1 and TGFBR2), leading to signal transduction (By similarity).
Required to maintain the Transforming growth factor beta-3 (TGF-beta-3) chain in a latent state during storage in extracellular matrix (By similarity). Associates non-covalently with TGF-beta-3 and regulates its activation via interaction with 'milieu molecules', such as LTBP1 and LRRC32/GARP, that control activation of TGF-beta-3 (By similarity). Interaction with integrins results in distortion of the Latency-associated peptide chain and subsequent release of the active TGF-beta-3 (By similarity).
Transforming growth factor beta-3 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-3 (TGF-beta-3) chains, which constitute the regulatory and active subunit of TGF-beta-3, respectively.
Transforming growth factor beta-3 proprotein: The precursor proprotein is cleaved in the Golgi apparatus to form Transforming growth factor beta-3 (TGF-beta-3) and Latency-associated peptide (LAP) chains, which remain non-covalently linked, rendering TGF-beta-3 inactive.
Transforming growth factor beta-3: Multifunctional protein that regulates embryogenesis and cell differentiation and is required in various processes such as secondary palate development (By similarity). Activation into mature form follows different steps: following cleavage of the proprotein in the Golgi apparatus, Latency-associated peptide (LAP) and Transforming growth factor beta-3 (TGF-beta-3) chains remain non-covalently linked rendering TGF-beta-3 inactive during storage in extracellular matrix (By similarity). At the same time, LAP chain interacts with 'milieu molecules', such as LTBP1 and LRRC32/GARP that control activation of TGF-beta-3 and maintain it in a latent state during storage in extracellular milieus (By similarity). TGF-beta-3 is released from LAP by integrins: integrin-binding results in distortion of the LAP chain and subsequent release of the active TGF-beta-3 (By similarity). Once activated following release of LAP, TGF-beta-3 acts by binding to TGF-beta receptors (TGFBR1 and TGFBR2), which transduce signal (By similarity).
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.
Enterostatin has a biological activity as a satiety signal.
Forms a 1:1 stoichiometric complex with pancreatic lipase.
May have a vitamin D3 hydroxylase regulatory function.
Component of the nuclear pore complex (NPC), which plays a key role in de novo assembly and insertion of NPC in the nuclear envelope. Required for NPC and nuclear envelope assembly, possibly by forming a link between the nuclear envelope membrane and soluble nucleoporins, thereby anchoring the NPC in the membrane.
Forms pentamers. Component of the PI(3,5)P2 regulatory complex/PAS complex, at least composed of PIKFYVE, FIG4 and VAC14. VAC14 nucleates the assembly of the complex and serves as a scaffold by pentamerizing into a star-shaped structure, which can bind a single copy each of PIKFYVE and FIG4 and coordinates their activities. Interacts with NOS1.
Scaffold protein component of the PI(3,5)P2 regulatory complex which regulates both the synthesis and turnover of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2). Pentamerizes into a star-shaped structure and nucleates the assembly of the complex. The pentamer binds a single copy each of PIKFYVE and FIG4 and coordinates both PIKfyve kinase activity and FIG4 phosphatase activity, being required to maintain normal levels of phosphatidylinositol 3-phosphate (PtdIns(3)P) and phosphatidylinositol 5-phosphate (PtdIns(5)P). Plays a role in the biogenesis of endosome carrier vesicles (ECV) / multivesicular bodies (MVB) transport intermediates from early endosomes.
The C-terminal domain (residues 523-782) mediates pentameric interactions and is necessary for the formation and maintenance of the PI(3,5)P2 regulatory complex.
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.
Receptor for neurturin. Mediates the NRTN-induced autophosphorylation and activation of the RET receptor. Also able to mediate GDNF signaling through the RET tyrosine kinase receptor (By similarity).
Binds to the ATPase domain of HSP/HSC70 chaperones.
Co-chaperone for HSP/HSP70 proteins. It functions as a nucleotide-exchange factor promoting the release of ADP from HSP70, thereby activating HSP70-mediated protein refolding.
The fifth BAG domain is responsible for the interaction with HSP70 nucleotide-binding domain.
Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a p18 subunit and a p12 subunit.
Involved in the activation cascade of caspases responsible for apoptosis execution. Might function by either activating some proteins required for cell death or inactivating proteins necessary for cell survival.
Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2 domains.
Calcium sensor that participates in triggering neurotransmitter release at the synapse (By similarity). May have a regulatory role in the membrane interactions during trafficking of synaptic vesicles at the active zone of the synapse. It binds acidic phospholipids with a specificity that requires the presence of both an acidic head group and a diacyl backbone. May play a role in dendrite formation by melanocytes.
May have a regulatory role in the membrane interactions during trafficking of synaptic vesicles at the active zone of the synapse. It binds acidic phospholipids with a specificity that requires the presence of both an acidic head group and a diacyl backbone.
The first C2 domain mediates Ca(2+)-dependent phospholipid binding.
The second C2 domain mediates interaction with SV2A and probably with STN2.
Belongs to the eukaryotic ribosomal protein eS17 family.
Negatively regulates the PAK1 kinase. PAK1 is a member of the PAK kinase family, which has been shown to play a positive role in the regulation of signaling pathways involving MAPK8 and RELA. PAK1 exists as an inactive homodimer, which is activated by binding of small GTPases such as CDC42 to an N-terminal regulatory domain. PAK1IP1 also binds to the N-terminus of PAK1, and inhibits the specific activation of PAK1 by CDC42. May be involved in ribosomal large subunit assembly.
Belongs to the gluconokinase GntK/GntV family.
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' (By similarity).
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 (By similarity). May also play a role in limb development.
Belongs to the sulfotransferase 6 family.
Expressed in the developing wing bud. At stage 31, widely expressed with a lower level in the heart.
Lysosomal transporter which is essential for liver homeostasis. Required to maintain stability and lysosomal localization of GLMP.
The dileucine internalization motif is required for lysosomal localization.
Involved in retrograde transport of recycling endosomes.
The PH domain specifically binds phosphatidylserine, which is enriched in recycling endosome membranes, it doesn't recognize PIPs.
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.
Component of the cleavage and polyadenylation specificity factor (CPSF) complex that play a key role in pre-mRNA 3'-end formation, recognizing the AAUAAA signal sequence and interacting with poly(A) polymerase and other factors to bring about cleavage and poly(A) addition. CPSF4 binds RNA polymers with a preference for poly(U).
Component of the cleavage and polyadenylation specificity factor (CPSF) complex.
Interacts with UBA5. Interacts with UFC1.
Ubiquitin-like modifier which can be covalently attached via an isopeptide bond to lysine residues of substrate proteins as a monomer or a lysine-linked polymer. The so-called ufmylation, requires the UFM1-activating E1 enzyme UBA5, the UFM1-conjugating E2 enzyme UFC1, and the UFM1-ligase E3 enzyme UFL1. Ufmylation is involved in reticulophagy (also called ER-phagy) induced in response to endoplasmic reticulum stress.
Belongs to the class I-like SAM-binding methyltransferase superfamily. EEF2KMT family.
Can form homooligomers (monomers, dimers and tetramers).
Key regulator of RAB11-dependent vesicular trafficking during neurite extension through polarized membrane transport. Promotes axonal elongation and contributes to the establishment of neuronal cell polarity. Involved in nerve growth factor-induced neurite formation in VAPA-dependent manner. Contributes to both the formation and stabilization of the tubular ER network. Involved in ER morphogenesis by regulating the sheet-to-tubule balance and possibly the density of tubule interconnections.
ADP-ribosylated by tankyrase TNKS and TNKS2. Poly-ADP-ribosylated protein is recognized by RNF146, followed by ubiquitination at 'Lys-48' and subsequent activation of the Wnt signaling pathway.
Component of the beta-catenin destruction complex required for regulating CTNNB1 levels through phosphorylation and ubiquitination, and modulating Wnt-signaling. Controls dorsoventral patterning via two opposing effects; down-regulates CTNNB1 to inhibit the Wnt signaling pathway and ventralize embryos, but also dorsalizes embryos by activating a Wnt-independent JNK signaling pathway.
Ubiquitinated by RNF146 when poly-ADP-ribosylated, leading to its degradation and subsequent activation of the Wnt signaling pathway.
Catalyzes the conversion of hemimercaptal, formed from methylglyoxal and glutathione, to S-lactoylglutathione.
In the embryonic brachial spinal cord, selectively expressed by medial lateral motor column neurons, some populations of dorsal root ganglion neurons, and interneurons.
Interacts heterophilically through its MAM domain with proteins in axon-rich regions and through its Ig-like domains with proteins in differentiating muscle.
Required for radial migration of cortical neurons in the superficial layer of the neocortex.
Vesicular soluble NSF attachment protein receptor (v-SNARE) mediating vesicle docking and fusion to a specific acceptor cellular compartment. Functions in endoplasmic reticulum to Golgi transport; as part of a SNARE complex composed of GOSR1, GOSR2 and STX5. Functions in early/recycling endosome to TGN transport; as part of a SNARE complex composed of BET1L, GOSR1 and STX5. Has a S-palmitoyl transferase activity.
Belongs to the archaeal Rpo11/eukaryotic RPB11/RPC19 RNA polymerase subunit family.
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.
Autophosphorylation at Tyr-424 maintains enzyme activity.
Non-receptor protein tyrosine kinase that is involved in the regulation of cell growth and survival, apoptosis, cell-cell adhesion, cytoskeleton remodeling, differentiation, G2/M progression and cytokinesis.
Palmitoylation at Cys-3 promotes membrane localization.
Controls reversibly actin polymerization and depolymerization in a pH-sensitive manner. It has the ability to bind G- and F-actin in a 1:1 ratio of cofilin to actin. It is the major component of intranuclear and cytoplasmic actin rods.
The phosphorylation of Ser-24 may prevent recognition of the nuclear localization signal.
Belongs to the Antp homeobox family. Proboscipedia subfamily.
Allosterically activated by benzodiazepines, the neuroanesthetic alphaxalone and pentobarbital (By similarity). Inhibited by the antagonist bicuculline (By similarity).
Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRA1 sub-subfamily.
Heteropentamer, formed by a combination of alpha, beta, gamma, delta and rho chains.
Ligand-gated chloride channel which is a component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the brain (By similarity). Plays an important role in the formation of functional inhibitory GABAergic synapses in addition to mediating synaptic inhibition as a GABA-gated ion channel (By similarity). Functions also as histamine receptor and mediates cellular responses to histamine (By similarity).
The extracellular domain contributes to synaptic contact formation.
Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, cullin-4 (CUL4A or CUL4B), DDA1 and RBX1.
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. In the DCX complexes, acts as a scaffolding subunit required to stabilize the complex.
Component of the DRB sensitivity-inducing factor complex (DSIF complex), which regulates mRNA processing and transcription elongation by RNA polymerase II. DSIF 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 (By similarity).
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 WHSC2/NELFA, COBRA1/NELFB, TH1L/NELFD and RDBP/NELFE, and this interaction occurs following prior binding of DSIF to RNA polymerase II. Also interacts with SUPT6H (By similarity).
Phosphorylated. Phosphorylation by P-TEFb alleviates transcriptional pausing. Phosphorylation may also stimulate interaction with PIN1. Bulk phosphorylation occurs predominantly in mitosis (By similarity).
Probably involved in transcriptional repression (By similarity). May play a role in the maintenance of the circadian clock periodicity (By similarity).
The RRM domains can bind to both DNA and RNA.
Belongs to the TFIIE beta subunit family.
Recruits TFIIH to the initiation complex and stimulates the RNA polymerase II C-terminal domain kinase and DNA-dependent ATPase activities of TFIIH. Both TFIIH and TFIIE are required for promoter clearance by RNA polymerase.
Tetramer of two alpha and two beta chains.
Plays a role in vesicular protein sorting.
Homotrimer; trimerization probably requires binding to phosphatidylinositol 4,5-bisphosphate (PIP2).
At stage 18, expressed throughout the dorsal central nervous system (CNS), both within the brain and the spinal neural. Strongest expression is observed within the tectum and the cerebellar primordium. Expressed also in the somites, the heart, the branchial arches, and the limb buds.
May play an important role in neural development; the dorsomedial roof of the third ventricle.
Acts as a transcriptional regulator involved in heart developmental processes.
Expression detected from stage 2 in the primitive streak. During subsequent stages of primitive streak formation (stages 2-4), expression seen in the extraembryonic mesoderm and lateral mesoderm, and weakly in the elongating primitive streak. Concomitant with the onset of node and streak regression (stage 5), the expression in the lateral mesoderm extends to the anterior limit of the mesodermal cell layer. After gastrulation, continuously expressed in the heart-forming region and also detected in other regions such as the allantois, optic vesicle, hindbrain and ventral neural tube.
Receptor for MSH (alpha, beta and gamma) and ACTH. The activity of this receptor is mediated by G proteins which activate adenylate cyclase. This receptor is a possible mediator of the immunomodulation properties of melanocortins.
A hemichannel or connexon is composed of a hexamer of connexins. A functional gap junction is formed by the apposition of two hemichannels (By similarity). During early stages of lens development, interacts with the C-terminus of MIP (PubMed:14762116).
Structural component of lens fiber gap junctions (PubMed:7678009). 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:7678009).
Serves as a reserve supply of oxygen and facilitates the movement of oxygen within muscles.
Belongs to the methylmalonyl-CoA mutase family.
Catalyzes the reversible isomerization of methylmalonyl-CoA (MMCoA) (generated from branched-chain amino acid metabolism and degradation of dietary odd chain fatty acids and cholesterol) to succinyl-CoA (3-carboxypropionyl-CoA), a key intermediate of the tricarboxylic acid cycle.
Interacts with RIMS1, RIMS2, CACNA1D and CACNA1B, and potentially with other Ca(2+) channel alpha-1 isoforms.
Plays a role in the synaptic transmission as bifunctional linker that interacts simultaneously with RIMS1, RIMS2, CACNA1D and CACNA1B.
The SH3 domains mediate binding to a proline-rich motif in RIMS1, RIMS2, CACNA1D and CACNA1B.
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 slowing their rates of activation, deactivation and desensitization. Does not show subunit-specific AMPA receptor regulation and regulates all AMPAR subunits. Thought to stabilize the calcium channel in an inactivated (closed) state.
Belongs to the cyclin family. Cyclin L subfamily.
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).
Belongs to the sulfatase-modifying factor family.
In the N-terminal section; belongs to the AlaDH/PNT family.
Receptor for inositol 1,4,5-trisphosphate, a second messenger that mediates the release of intracellular calcium.
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.
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. 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. Protects cells against lipotoxicity.
Acts as an activator of hypoxia-induced mitophagy, an important mechanism for mitochondrial quality control.
Belongs to the ATP:guanido phosphotransferase family.
Exists as an octamer composed of four MTCK homodimers.
Mitochondrial creatine kinase binds cardiolipin.
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.
Phosphorylation on Tyr-10 modulates pumping activity.
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.
Acetylated. Positively correlates with ability to bind RNA (By similarity).
Methylated by HRMT1L2. Required for nuclear localization (By similarity).
Recruited and tyrosine phosphorylated by several receptor systems, for example the T-cell, leptin and insulin receptors. Once phosphorylated, functions as an adapter protein in signal transduction cascades by binding to SH2 and SH3 domain-containing proteins. Role in G2-M progression in the cell cycle. Represses CBP-dependent transcriptional activation apparently by competing with other nuclear factors for binding to CBP. Also acts as a putative regulator of mRNA stability and/or translation rates and mediates mRNA nuclear export. Plays a role in the regulation of alternative splicing and influences mRNA splice site selection and exon inclusion.
Self-associates to form homooligomers when bound to RNA, oligomerization appears to be limited when binding to proteins.
The KH domain is required for binding to RNA.
Tyrosine phosphorylated by several non-receptor tyrosine kinases including LCK, FYN and JAK3.
Binds 2 divalent metal cations per subunit with RNAase activity being higher in presence of Mn(2+) than of Mg(2+) or Co(2+).
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. During miRNA-mediated repression the complex seems also to act as translational repressor during translational initiation. Additional complex functions may be a consequence of its influence on mRNA expression (By similarity).
Phosphorylated by CK2 and this positively regulates its activity.
Sumoylation represses the transcriptional activity and displays enhanced resistance to protein degradation. Inactivates the tumor suppressor activity. Elevated levels in tumor cells. Major site is Lys-271. Sumoylation is enhanced by PIAS3. Desumoylated by SENP1 in tumor cells and appears to compete with ubiquitination on C-terminal sites (By similarity).
Transcriptional regulator that specifically binds to the upstream regulatory region of type I IFN and IFN-inducible MHC class I genes (the interferon consensus sequence (ICS)) and activates those genes (By similarity). Acts as a tumor suppressor (By similarity).
Ubiquitinated. Appears to compete with sumoylation on C-terminal sites (By similarity).
Serine peptidase whose precise substrate specificity remains unclear (By similarity). Does not cleave peptides after a arginine or lysine residue (By similarity). Regulates trans-Golgi network morphology and sorting by regulating the membrane binding of the AP-1 complex (By similarity). May play a role in the regulation of synaptic vesicle exocytosis (By similarity).
May participate in suppression of cell proliferation and induces apoptotic cell death through activation of interleukin-1-beta converting enzyme (ICE)-like proteases.
Mediates ATP-dependent export of organic anions and drugs from the cytoplasm. Confers resistance to anticancer drugs. Hydrolyzes ATP with low efficiency (By similarity).
Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide and other xenobiotics. Hydrolyzes ATP with low efficiency.
Alkaline phosphatase that metabolizes various phosphate compounds and plays a key role in skeletal mineralization and adaptive thermogenesis (By similarity). Has broad substrate specificity and can hydrolyze a considerable variety of compounds: however, only a few substrates, such as diphosphate (inorganic pyrophosphate; PPi) and pyridoxal 5'-phosphate (PLP) are natural substrates (By similarity). Plays an essential role in skeletal and dental mineralization via its ability to hydrolyze extracellular diphosphate, a potent mineralization inhibitor, to phosphate: it thereby promotes hydroxyapatite crystal formation and increases inorganic phosphate concentration (By similarity). Catalyzes dephosphorylation of PLP to pyridoxal (PL), the transportable form of vitamin B6, in order to provide a sufficient amount of PLP in the brain, an essential cofactor for enzymes catalyzing the synthesis of diverse neurotransmitters (By similarity). Additionally, also able to mediate ATP degradation in a stepwise manner to adenosine, thereby regulating the availability of ligands for purinergic receptors (By similarity). Involved in the establishment and growth of feather germs (PubMed:8563025).
Calcium-binding is structural and does not influence the alkaline phosphatase activity. At very high concentrations, calcium can however substitute for zinc at zinc-binding sites, leading to strongly reduced enzyme activity.
Mediates the post-translational oxidative deamination of lysine residues on target proteins leading to the formation of deaminated lysine (allysine).
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.
One of the alpha chains that assemble within the acetylcholine receptor, a pentamer of two alpha chains, a beta, a delta, and a gamma or epsilon chains.
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.
Belongs to the lambda interferon family.
Cytokine which plays a critical role in the antiviral host defense, predominantly in the epithelial tissues. Acts as a ligand for the heterodimeric class II cytokine receptor composed of IL10RB and IFNLR1, and receptor engagement leads to the activation of the JAK/STAT signaling pathway resulting in the expression of IFN-stimulated genes (ISG), which mediate the antiviral state. Has a restricted receptor distribution and therefore restricted targets: is primarily active in epithelial cells and this cell type-selective action is because of the epithelial cell-specific expression of its receptor IFNLR1. Exhibits antiviral activity against the H5N1 influenza A virus. Induces the expression of the antiviral MX protein in epithelial-rich tissues, such as intestine, trachea and lung.
Ligand binding induces cleavage by matrix metalloproteinases (MMPs) such as MMP7/MMP9, producing an EphB2/N-terminal fragment (NTF) and a C-terminal long fragment (EphB2-LF). EphB2-LF is further cleaved by MMPs, producing EphB2/CTF1 which is further cleaved by the PS1/gamma-secretase producing EphB2/CTF2.
Receptor tyrosine kinase which binds promiscuously transmembrane ephrin-B 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. Functions in axon guidance during development. In addition to axon guidance, also regulates dendritic spines development and maturation and stimulates the formation of excitatory synapses (By similarity).
Wide tissue distribution throughout development and sustained expression in adult brain. The longer form (CEK5+) is specifically expressed in the central nervous system.
Belongs to the DHHC palmitoyltransferase family. AKR/ZDHHC17 subfamily.
Belongs to the class-I aminoacyl-tRNA synthetase family. Glutamate--tRNA ligase type 1 subfamily.
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).
Belongs to the V-ATPase G subunit family.
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.
Belongs to the MoaE family. MOCS2B subfamily.
Catalytic subunit of the molybdopterin synthase complex, a complex that catalyzes the conversion of precursor Z into molybdopterin. Acts by mediating the incorporation of 2 sulfur atoms from thiocarboxylated MOCS2A into precursor Z to generate a dithiolene group.
Heterotetramer; composed of 2 small (MOCS2A) and 2 large (MOCS2B) subunits.
This protein is produced by a bicistronic gene which also produces the large subunit (MOCS2A).
Belongs to the complex I 24 kDa subunit family.
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.
By contrast to classical cadherins, homodimerization in trans is not mediated by cadherin EC1 domain strand-swapping, but instead through a homophilic adhesive interface which joins two elongated EC1-EC2 domains through a region near their Ca2+-binding sites to form a tetrahedral, X-like shape.
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. May act as a negative regulator of neural cell growth.
Neural tissues. Also found in muscles; kidney and retina.
Belongs to the DPH1/DPH2 family. DPH2 subfamily.
Binds 1 [4Fe-4S] cluster per subunit. The cluster facilitates the reduction of the catalytic iron-sulfur cluster in the DPH1 subunit.
Component of the 2-(3-amino-3-carboxypropyl)histidine synthase complex composed of DPH1, DPH2, DPH3 and a NADH-dependent reductase.
Required for the first step of diphthamide biosynthesis, a post-translational modification of histidine which occurs in elongation factor 2 (By similarity). DPH1 and DPH2 transfer a 3-amino-3-carboxypropyl (ACP) group from S-adenosyl-L-methionine (SAM) to a histidine residue, the reaction is assisted by a reduction system comprising DPH3 and a NADH-dependent reductase (By similarity). Facilitates the reduction of the catalytic iron-sulfur cluster found in the DPH1 subunit (By similarity).
Interacts with PIP5K1C and NRAP (By similarity). Binds with high affinity to vinculin VCL and with low affinity to integrins (PubMed:14702644, PubMed:12535520, PubMed:8937989, PubMed:20610383). Interacts with APBB1IP; this inhibits VCL binding (By similarity). Interacts with F-actin (PubMed:8937989). Interacts with LAYN (PubMed:9786953). Interacts with THSD1.
Probably involved in connections of major cytoskeletal structures to the plasma membrane. Talin is a high molecular weight cytoskeletal protein concentrated at regions of cell-substratum contact and, in lymphocytes, at cell-cell contacts.
Catalyzes the formation of L-carnitine from gamma-butyrobetaine.
Belongs to the actin family. ARP5 subfamily.
Component of the chromatin remodeling INO80 complex.
Proposed core component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair.
Belongs to the complex I NDUFB3 subunit family.
Plays an important role in the regulation of interdigestive gastrointestinal motility and indirectly causes rhythmic contraction of duodenal and colonic smooth muscle.
Required for proper homologous chromosome pairing and efficient cross-over and intragenic recombination during meiosis.
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 is involved in polarized vesicular trafficking and neurotransmitter release.
Acts specifically as a negative regulator of skeletal muscle growth.
Acyl-CoA dehydrogenase, that exhibits maximal activity towards saturated C22-CoA. Probably participates in beta-oxydation and energy production but could also play a role in the metabolism of specific fatty acids to control fatty acids composition of cellular lipids in brain.
Brain and kidney, with trace levels in lungs.
Interacts with ODC1 and thereby sterically blocks ODC homodimerization.
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 homodimer, and targets the monomers for ubiquitin-independent proteolytic destruction by the 26S proteasome.
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. This cadherin may play a important role in endothelial cell biology through control of the cohesion and organization of the intercellular junctions.
Interacts with PRMT5. Interacts with FBXO10. Interacts with FBXO11.
Transcription factor that mediates a transcriptional program in various innate and adaptive immune tissue-resident lymphocyte T cell types such as tissue-resident memory T (Trm), natural killer (trNK) and natural killer T (NKT) cells and negatively regulates gene expression of proteins that promote the egress of tissue-resident T-cell populations from non-lymphoid organs. Plays a role in the development, retention and long-term establishment of adaptive and innate tissue-resident lymphocyte T cell types in non-lymphoid organs, such as the skin and gut, but also in other nonbarrier tissues like liver and kidney, and therefore may provide immediate immunological protection against reactivating infections or viral reinfection. Binds specifically to the PRDI element in the promoter of the beta-interferon gene. Drives the maturation of B-lymphocytes into Ig secreting cells. Associates with the transcriptional repressor ZNF683 to chromatin at gene promoter regions.
Belongs to the ribonuclease III family. Mitochondrion-specific ribosomal protein mL44 subfamily.
Isoform 1 is expressed in heart and in tissues enriched in smooth muscle including arteries, stomach, gizzard, intestine, and lung. Isoform 2 is skeletal muscle-specific. Isoform 1 and isoform 2 are up-regulated during myogenic differentiation.
May play a role in the organization of actin filament arrays within muscle cells.
Ca(2+)-dependent actin filament-severing protein that has a regulatory function in exocytosis by affecting the organization of the microfilament network underneath the plasma membrane. In vitro, also has barbed end capping and nucleating activities in the presence of Ca(2+). Severing activity is inhibited by phosphatidylinositol 4,5-bis-phosphate (PIP2) (By similarity). Required for megakaryocyte differentiation, maturation, polyploidization and apoptosis with the release of platelet-like particles (By similarity). Plays a role in osteoclastogenesis (OCG) and actin cytoskeletal organization in osteoclasts (By similarity). Regulates chondrocyte proliferation and differentiation (PubMed:17097081). Inhibits cell proliferation and tumorigenesis. Signaling is mediated by MAPK, p38 and JNK pathways (By similarity).
Expressed in the pre-hypertrophic and hypertrophic cartilage of the embryonic growth plate.
Up-regulated in pre-hypertrophic and hypertrophic chondrocytes during the embryonic development of long bones.
Belongs to the universal ribosomal protein uS8 family.
Belongs to the tRNA-intron endonuclease family.
Constitutes one of the two catalytic subunit of the tRNA-splicing endonuclease complex, a complex responsible for identification and cleavage of the splice sites in pre-tRNA. It cleaves pre-tRNA at the 5'- and 3'-splice sites to release the intron. The products are an intron and two tRNA half-molecules bearing 2',3'-cyclic phosphate and 5'-OH termini. There are no conserved sequences at the splice sites, but the intron is invariably located at the same site in the gene, placing the splice sites an invariant distance from the constant structural features of the tRNA body.
Constitutes one of the two catalytic subunit of the tRNA-splicing endonuclease complex, a complex responsible for identification and cleavage of the splice sites in pre-tRNA. It cleaves pre-tRNA at the 5'- and 3'-splice sites to release the intron. The products are an intron and two tRNA half-molecules bearing 2',3'-cyclic phosphate and 5'-OH termini. There are no conserved sequences at the splice sites, but the intron is invariably located at the same site in the gene, placing the splice sites an invariant distance from the constant structural features of the tRNA body. Probably carries the active site for 5'-splice site cleavage. The tRNA splicing endonuclease is also involved in mRNA processing via its association with pre-mRNA 3'-end processing factors, establishing a link between pre-tRNA splicing and pre-mRNA 3'-end formation, suggesting that the endonuclease subunits function in multiple RNA-processing events (By similarity).
tRNA splicing endonuclease is a heterotetramer composed of SEN2, SEN15, SEN34/LENG5 and SEN54.
Component of the RMI complex, containing at least TOP3A, RMI1 and RMI2.
Essential component of the RMI complex, a complex that plays an important role in the processing of homologous recombination intermediates to limit DNA crossover formation in cells. Promotes TOP3A binding to double Holliday junctions (DHJ) and hence stimulates TOP3A-mediated dissolution. Required for BLM phosphorylation during mitosis. Within the BLM complex, required for BLM and TOP3A stability (By similarity).
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.
Catalyzes the post-translational formation of 4-hydroxyproline in -Xaa-Pro-Gly- sequences in collagens and other proteins.
Heterotetramer of two alpha-2 chains and two beta chains (the beta chain is the multi-functional PDI).
Required for proper 34S pre-rRNA processing and 60S ribosome subunit assembly.
Binds free fatty acids and their coenzyme A derivatives, bilirubin, and some other small molecules in the cytoplasm. May be involved in intracellular lipid transport.
Belongs to the glycosyl hydrolase 22 family.
In the egg white and polymorphonuclear leukocytes.
Lysozyme C is capable of both hydrolysis and transglycosylation; it shows also a slight esterase activity. It acts rapidly on both peptide-substituted and unsubstituted peptidoglycan, and slowly on chitin oligosaccharides.
Lysozymes have primarily a bacteriolytic function; those in tissues and body fluids are associated with the monocyte-macrophage system and enhance the activity of immunoagents. Has bacteriolytic activity against M.luteus.
Numerous polymorphisms have been identified in various strains, predominantly at positions 49 and 71 (PubMed:19845599). The sequence shown here is that of red jungle fowl (PubMed:15592404).
Belongs to the WD repeat NOL10/ENP2 family.
E3 ubiquitin-protein ligase required for accumulation of repair proteins to sites of DNA damage. Acts with UBE2N/UBC13 to amplify the RNF8-dependent histone ubiquitination. Recruited to sites of DNA damage at double-strand breaks (DSBs) by binding to ubiquitinated histone H2A and ubiquitinates histone H2A and H2AX, leading to amplify the RNF8-dependent H2A ubiquitination and promoting the formation of 'Lys-63'-linked ubiquitin conjugates. This leads to concentrate ubiquitinated histones H2A and H2AX at DNA lesions to the threshold required for recruitment of TP53BP1 and BRCA1. Catalyzes monoubiquitination of 'Lys-13' and 'Lys-15' of nucleosomal histone H2A (H2AK13Ub and H2AK15Ub, respectively).
The MIU motif (motif interacting with ubiquitin) mediates the interaction with both 'Lys-48'- and 'Lys-63'-linked ubiquitin chains. The UMI motif mediates interaction with ubiquitin with a preference for 'Lys-63'-linked ubiquitin. The specificity for different types of ubiquitin is mediated by juxtaposition of ubiquitin-binding motifs (MIU and UMI motifs) with LR motifs (LRMs).
Belongs to the nucleoporin Nup85 family.
Component of the nuclear pore complex (NPC).
Functions as a component of the nuclear pore complex (NPC).
Abundantly expressed in the retina (at protein level) (PubMed:11991949, PubMed:18466325, PubMed:18786170). Localizes to the photoreceptor layer of the interphotoreceptor matrix of the retina (at protein level) (PubMed:11991949).
Chondroitin sulfate-, heparin- and hyaluronan-binding protein (PubMed:11991949, PubMed:18466325, PubMed:18786170). May serve to form a basic macromolecular scaffold comprising the insoluble interphotoreceptor matrix (By similarity).
Expression is first detected in embryonic retina at 15 dpc and increases with developmental age.
Highly glycosylated (N- and O-linked carbohydrates and sialic acid).
Component of the multiprotein chromatin-remodeling complexes SWI/SNF. Component of neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex) (By similarity). Component of the BAF (SWI/SNF) chromatin remodeling complex. Component of the SWI/SNF-B (PBAF) chromatin remodeling complex. Binds to double-stranded DNA.
Involved in chromatin-remodeling. Core component of the BAF (SWI/SNF) complex. This ATP-dependent chromatin-remodeling complex plays important roles in cell proliferation and differentiation, in cellular antiviral activities and inhibition of tumor formation. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex) and may play a role in neural development (By similarity).
The N-terminal DNA-binding region is structurally similar to winged helix domains.
In the C-terminal section; belongs to the saccharopine dehydrogenase family.
Seems to be involved in the development of cranial sensory innervation from peripheral ganglia.
Belongs to the lyase 1 family. Adenylosuccinate lyase subfamily.
Catalyzes two non-sequential steps in de novo AMP synthesis: converts (S)-2-(5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido)succinate (SAICAR) to fumarate plus 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide, and thereby also contributes to de novo IMP synthesis, and converts succinyladenosine monophosphate (SAMP) to AMP and fumarate.
Homotetramer. Residues from neighboring subunits contribute catalytic and substrate-binding residues to each active site.
Significantly increased expression by estrogen. Rapidly up-regulated within 0.5 hour after extrogen exposure with a peak at 1-4 hours and diminishing thereafter.
5' to 3' RNA helicase contributing to UPF1 mRNA target degradation by translocation along 3' UTRs. Required for microRNA (miRNA)-mediated gene silencing by the RNA-induced silencing complex (RISC). Required for both miRNA-mediated translational repression and miRNA-mediated cleavage of complementary mRNAs by RISC. In cooperation with FMR1, regulates miRNA-mediated translational repression by AGO2 (By similarity). May function as a messenger ribonucleoprotein (mRNP) clearance factor (By similarity).
Belongs to the DNA2/NAM7 helicase family. SDE3 subfamily.
Probable RNA helicase. Required for RNA-mediated gene silencing by the RNA-induced silencing complex (RISC). Required for both miRNA-mediated translational repression and miRNA-mediated cleavage of complementary mRNAs by RISC (By similarity).
Heterodimer with IL12A; disulfide-linked. The heterodimer is known as interleukin IL-12.
Plasma RBP has the same C-terminal sequence as the egg-white RBP, which suggests that the C-terminal residues are cleaved off upon incorporation into the oocyte.
Plasma and yolk RBPS have the same carbohydrate components, whereas egg-white RBP has a different, ovomucoid-type carbohydrate chain.
Required for the transport of riboflavin to the developing oocyte.
Yolk RBP is synthesized in the liver; egg-white RBP is synthesized in the oviduct.
Part of the endoplasmic reticulum membrane protein complex (EMC) that enables the energy-independent insertion into endoplasmic reticulum membranes of newly synthesized membrane proteins.
Belongs to the glycosyltransferase 13 family.
Participates in O-mannosyl glycosylation by catalyzing the addition of N-acetylglucosamine to O-linked mannose on glycoproteins. Catalyzes the synthesis of the GlcNAc(beta1-2)Man(alpha1-)O-Ser/Thr moiety on alpha-dystroglycan and other O-mannosylated proteins, providing the necessary basis for the addition of further carbohydrate moieties. Is specific for alpha linked terminal mannose.
The manganese ion interacts primarily with the substrate UDP-N-acetylglucosamine.
The stem domain mediates specific interaction with beta-linked N-acetylglucosamine moieties of O-glycosylated proteins. It also interacts with its product, N-acetyl-beta-D-glucosaminyl-(1->2)-O-alpha-D-mannosylprotein.
G-protein coupled receptor for 5-hydroxytryptamine (serotonin).
Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones.
Belongs to the POU transcription factor family.
Belongs to the class I-like SAM-binding methyltransferase superfamily. EFM5 family.
Protein-lysine methyltransferase that selectively catalyzes the trimethylation of EEF1A at 'Lys-79'.
Was originally thought to be an N(6)-adenine-specific DNA methyltransferase based on primary sequence and predicted secondary structure.
Belongs to the amidinotransferase family.
Catalyzes the biosynthesis of guanidinoacetate, the immediate precursor of creatine. Creatine plays a vital role in energy metabolism in muscle tissues. May play a role in embryonic and central nervous system development (By similarity).
Transiently induced by estrogen, with levels peaking an hour after hormone injection.
May play a role in Cajal bodies formation.
Catalyzes the adenylation of flavin mononucleotide (FMN) to form flavin adenine dinucleotide (FAD) coenzyme.
In the C-terminal section; belongs to the PAPS reductase family. FAD1 subfamily.
Detected in intestine, cardiac muscle, lung and brain (at protein level). Expressed in all tissues tested, including, gizzard, liver, cardiac muscle, skeletal muscle and skin.
Regulates the morphogenesis and endocytosis of caveolae (By similarity). Lipid-binding protein that is able to promote the tubulation of the phosphatidic acid-containing membranes it preferentially binds. Plays a role in intracellular vesicle-mediated transport. Involved in the endocytosis of cell-surface receptors like the EGF receptor, contributing to its internalization in the absence of EGF stimulus.
The F-BAR domain forms a coiled coil and mediates membrane-binding and membrane tubulation. In the autoinhibited conformation, interaction with the SH3 domain inhibits membrane tubulation mediated by the F-BAR domain (By similarity).
Avian ovomucoid consists of three homologous, tandem Kazal family inhibitory domains.
Serine protease inhibitor. Inhibits trypsin.
Belongs to the aldolase class II family. MtnB subfamily.
Catalyzes the dehydration of methylthioribulose-1-phosphate (MTRu-1-P) into 2,3-diketo-5-methylthiopentyl-1-phosphate (DK-MTP-1-P). Functions in the methionine salvage pathway. May play a role in apoptosis.
Belongs to the eukaryotic ribosomal protein eS21 family.
Belongs to the zinc-containing alcohol dehydrogenase family. Class-I subfamily.
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.
Proteolytic processing yields a number of bioactive forms, consisting either solely of the mature alpha chain, of the most N-terminal propeptide linked through a disulfide bond to the mature alpha chain, or of the entire proprotein.
The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO2.
Component of the dolichol-phosphate mannose (DPM) synthase complex.
Regulatory subunit of the dolichol-phosphate mannose (DPM) synthase complex; essential for the ER localization.
Probable acetyltransferase, which acetylates the inositol ring of phosphatidylinositol during biosynthesis of GPI-anchor.
Binds to two alpha/beta-tubulin heterodimers.
Involved in the regulation of the microtubule (MT) filament system by destabilizing microtubules. It prevents assembly and promotes disassembly of microtubules (By similarity).
Many different phosphorylated forms are observed depending on specific combinations among the sites which can be phosphorylated. MAPK is responsible for the phosphorylation of stathmin in response to NGF (By similarity).
May play a role in the regulation of neutrophil polarization.
First detected at 0.5 days of embryonic development (at protein level). Detected at higher levels from 1 to 2.5 days of embryonic development (at protein level). First detected at 0.5 days of embryonic development. Levels increase strongly from 1 to 2.5 days of embryonic development.
Molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. Plays a pivotal role in the protein quality control system, ensuring the correct folding of proteins, the re-folding of misfolded proteins and controlling the targeting of proteins for subsequent degradation. This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, mediated by co-chaperones. The affinity of HSP70 for polypeptides is regulated by its nucleotide bound state. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a conformational change that increases its affinity for substrate proteins. HSP70 goes through repeated cycles of ATP hydrolysis and nucleotide exchange, which permits cycles of substrate binding and release (By similarity). May play a role in regulating apoptosis during embryonic development.
Up-regulated by insulin in cultured embryos.
The small GTPases Rab are key regulators of intracellular membrane trafficking, from the formation of transport vesicles to their fusion with membranes (By similarity). 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 (By similarity). Required for the localization of ZFYVE1 to lipid droplets and for its function in mediating the formation of endoplasmic reticulum-lipid droplets (ER-LD) contacts (By similarity). Also required for maintaining endoplasmic reticulum structure (By similarity). Plays a role in apical endocytosis/recycling (By similarity). Plays a key role in eye and brain development and neurodegeneration (By similarity).
Calsequestrin is a high-capacity, moderate affinity, calcium-binding protein and thus acts as an internal calcium store in muscle. Calcium ions are bound by clusters of acidic residues at the protein surface, especially at the interface between subunits. Can bind around 60 Ca(2+) ions. Regulates the release of lumenal Ca(2+) via the calcium release channel RYR2; this plays an important role in triggering muscle contraction. Plays a role in excitation-contraction coupling in the heart and in regulating the rate of heart beats.
Was initially identified as a laminin-binding protein (PubMed:3417768), but later studies indicate that this is highly unlikely (PubMed:1825466 and PubMed:2302244).
Delta crystallin, the principal crystallin in embryonic lens, is found only in birds and reptiles.
Stimulates the adrenal glands to release cortisol.
A Gly-transPro motif from one monomer fits into the active site of the other monomer to allow specific chiral rejection of most L-amino acids except L-Ala. The trans conformation of the motif is maintained by Arg-150.
Deacylates mischarged D-aminoacyl-tRNAs (By similarity). Also deacylates mischarged glycyl-tRNA(Ala), protecting cells against glycine mischarging by AlaRS (By similarity). Probably acts by rejecting L-amino acids from its binding site rather than specific recognition of D-amino acids (By similarity). Catalyzes the hydrolysis of D-tyrosyl-tRNA(Tyr), has no activity on correctly charged L-tyrosyl-tRNA(Tyr) (By similarity). By recycling D-aminoacyl-tRNA to D-amino acids and free tRNA molecules, this enzyme counteracts the toxicity associated with the formation of D-aminoacyl-tRNA entities in vivo and helps enforce protein L-homochirality. In contrast to DTD1, deacylates L-Ala mischarged on tRNA(Thr)(G4.U69) by alanine-tRNA ligase AARS (PubMed:29410408). Can deacylate L-Ala due to a relaxed specificity for substrate chirality caused by the trans conformation of the Gly-Pro motif in the active site (PubMed:29410408). Also hydrolyzes correctly charged, achiral, glycyl-tRNA(Gly) in vitro, although in vivo EEF1A1/EF-Tu may protect cognate achiral glycyl-tRNA(Gly) from DTD2-mediated deacetylation (By similarity).
Phosphorylates the deoxyribonucleosides deoxyadenosine, deoxycytidine and deoxyguanosine (PubMed:27906638). Shows highest activity against deoxyguanosine followed by deoxycytidine and then deoxyadenosine (PubMed:27906638). Shows only very minor activity against deoxyuridine and deoxythymidine (PubMed:27906638).
May be involved in the morphogenesis of retina outer segment disks and the development and maintenance of the retina ultrastructure.
Mitochondrial membrane ATP synthase (F1F0 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, F1 - containing the extramembraneous catalytic core, and F0 - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F1 is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Part of the complex F0 domain. Minor subunit located with subunit a in the membrane.
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. Involved in peroxisome biogenesis. Regulates the transport of peroxisomal biogenesis factors PEX3 and PEX16 from the ER to peroxisomes.
Belongs to the opioid growth factor receptor family.
Because S100A10 induces the dimerization of ANXA2/p36, it may function as a regulator of protein phosphorylation in that the ANXA2 monomer is the preferred target (in vitro) of tyrosine-specific kinase.
Does not appear to bind calcium. Contains 2 ancestral calcium site related to EF-hand domains that have lost their ability to bind calcium.
Belongs to the mitochondrion-specific ribosomal protein mL41 family.
Has deubiquitinating activity towards 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains.
Belongs to the PUR DNA-binding protein family.
Involved in pre-mRNA splicing and processing events.
Plays a role as a transcriptional activator or repressor. Specifically binds to the upstream regulatory region of type I IFN and IFN-inducible MHC class I genes (the interferon consensus sequence (ICS)). Plays a regulatory role in cells of the immune system (By similarity).
Belongs to the Mediator complex subunit 8 family.
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 play a role as a target recruitment subunit in E3 ubiquitin-protein ligase complexes and thus in ubiquitination and subsequent proteasomal degradation of target proteins.
Rab9 effector required for endosome to trans-Golgi network (TGN) transport.
Transfers mannose from GDP-mannose to dolichol monophosphate to form dolichol phosphate mannose (Dol-P-Man) which is the mannosyl donor in pathways leading to N-glycosylation, glycosyl phosphatidylinositol membrane anchoring, and O-mannosylation of proteins; catalytic subunit of the dolichol-phosphate mannose (DPM) synthase complex.
Guanine nucleotide exchange factor (GEF), which can activate some, but not all, G-alpha proteins by exchanging bound GDP for free GTP.
Interacts with some GDP-bound G alpha proteins. Does not interact with G-alpha proteins when they are in complex with subunits beta and gamma.
May be involved in fusion of ER-derived transport vesicles with the Golgi complex.
Belongs to the metallo-beta-lactamase superfamily. RNA-metabolizing metallo-beta-lactamase-like family. INTS11 subfamily.
Catalytic component of the Integrator complex, a complex involved in the small nuclear RNAs (snRNA) U1 and U2 transcription and in their 3'-box-dependent processing. Mediates the snRNAs 3' cleavage.
The HXHXDH motif is essential for the endoribonuclease activity of the CPSF complex.
Seems to antagonize the function of BMP4 by binding to it and preventing its interaction with receptors.
Hydrolase that can remove conjugated ubiquitin from proteins and participates in endoplasmic reticulum-associated degradation (ERAD) for misfolded lumenal proteins. May act by triming the ubiquitin chain on the associated substrate to facilitate their threading through the VCP/p97 pore. Ubiquitin moieties on substrates may present a steric impediment to the threading process when the substrate is transferred to the VCP pore and threaded through VCP's axial channel. Mediates deubiquitination of 'Lys-27'-, 'Lys-29'- and 'Lys-33'-linked polyubiquitin chains. Also able to hydrolyze 'Lys-11'-linked ubiquitin chains. Cleaves both polyubiquitin and di-ubiquitin.
Heterodimer with IL12B; disulfide-linked. The heterodimer is known as interleukin IL-12.
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 (By similarity).
Autophosphorylated at two clusters, the T2609 cluster and the S2056 cluster. Autophosphorylated on Ser-2055, Thr-2609, Thr-2638 and Thr-2647. Ser-2055 and Thr-2609 are DNA damage-inducible phosphorylation sites (inducible with ionizing radiation, IR) dephosphorylated by PPP5C (By similarity). Autophosphorylation induces a conformational change that leads to remodeling of the DNA-PK complex, requisite for efficient end processing and DNA repair (By similarity). Autophosphorylation in trans within DNA-PK complexes loaded on DNA ends leads to the dissociation of PRKDC from DNA and the transition into the short-range NHEJ complex (By similarity). Autophosphorylation of the T2609 cluster is required for hematopoietic development and protein synthesis in erythrocytes precursors (By similarity).
DNA-PK is a heterotrimer of PRKDC and the Ku dimer (composed of XRCC6/Ku70 and XRCC5/Ku86). Component of the core long-range non-homologous end joining (NHEJ) complex (also named DNA-PK complex) composed of PRKDC, LIG4, XRCC4, XRCC6/Ku70, XRCC5/Ku86 and NHEJ1/XLF. Additional component of the NHEJ complex includes PAXX. Following autophosphorylation, PRKDC dissociates from DNA.
Serine/threonine-protein kinase that acts as a molecular sensor for DNA damage. Involved in DNA nonhomologous end joining (NHEJ) required for double-strand break (DSB) repair and V(D)J recombination. Must be bound to DNA to express its catalytic properties. Promotes processing of hairpin DNA structures in V(D)J recombination by activation of the hairpin endonuclease artemis (DCLRE1C). Recruited by XRCC5 and XRCC6 to DNA ends and is required to (1) protect and align broken ends of DNA, thereby preventing their degradation, (2) and sequester the DSB for repair by NHEJ. Act as a scaffold protein to aid the localization of DNA repair proteins to the site of damage. The assembly of the DNA-PK complex at DNA ends is also required for the NHEJ ligation step. Found at the ends of chromosomes, suggesting a further role in the maintenance of telomeric stability and the prevention of chromosomal end fusion. As part of the DNA-PK complex, involved in the early steps of ribosome assembly by promoting the processing of precursor rRNA into mature 18S rRNA in the small-subunit processome (By similarity). Recognizes the substrate consensus sequence [ST]-Q. Phosphorylates 'Ser-139' of histone variant H2AX, thereby regulating DNA damage response mechanism (By similarity).
Catalyzes the hydroxylation of 2-polyprenyl-3-methyl-6-methoxy-1,4-benzoquinol (DMQH2) during ubiquinone biosynthesis. Has also a structural role in the COQ enzyme complex, stabilizing other COQ polypeptides. Involved in lifespan determination in a ubiquinone-independent manner.
Component of a multi-subunit COQ enzyme complex, composed of at least COQ3, COQ4, COQ5, COQ6, COQ7 and COQ9. Interacts with ADCK4 and COQ6. Interacts with COQ9.
Troponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity.
Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols. Displays enzymatic activity towards endogenous metabolites such as aromatic and aliphatic aldehydes, ketones, monosaccharides and bile acids. Acts as an aldehyde-detoxification enzyme (By similarity). Displays no reductase activity towards retinoids (By similarity).
Acts as an axon-specific repulsive guidance molecule in the retinotectal system. Repulsive for a subset of axons of the temporal half of the retina. Provides thus positional information for the temporal axons invading the optic tectum in the stratum opticum.
Autocatalytically cleaved at low pH; the two chains remain linked via two disulfide bonds.
Belongs to the repulsive guidance molecule (RGM) family.
Expressed in the periventricular layer surrounding the tectal ventricle (9 dpc). Forms a spatial gradient with increasing concentration from the anterior to posterior pole of the embryonic optic tectum.
Associates with MYD88 and IRAK2 to form a ternary complex called the Myddosome.
Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens.
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 (By similarity). 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) (By similarity).
Belongs to the 'GDSL' lipolytic enzyme family. IAH1 subfamily.
May be a 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.
DNA-dependent ATPase and 5' to 3' DNA helicase required for the maintenance of chromosomal stability. Acts late in the 'Fanconi anemia' pathway of DNA repair, after FANCD2 ubiquitination. Probably not involved in the repair of DNA double-strand breaks by homologous recombination.
Autophosphorylation of CAMK2 plays an important role in the regulation of the kinase activity.
CAMK2 is composed of four different chains: alpha, beta, gamma, and delta. The different isoforms assemble into homo- or heteromultimeric holoenzymes composed of 8 to 12 subunits (By similarity).
CaM-kinase II (CAMK2) is a prominent kinase in the central nervous system.
Belongs to the queuosine salvage protein family.
Binds fibroblast growth factor and E-selectin (cell-adhesion lectin on endothelial cells mediating the binding of neutrophils) (By similarity). Binds fibroblast growth factor (FGF). May be involved in intracellular FGF trafficking and the regulation of cellular responses to FGFS (PubMed:1448090).
Fucosylation is essential for binding to E-selectin.
N-glycosylated. Contains sialic acid residues.
Gizzard, uterus, intestine, esophagus, aorta, and trace amounts in brain, liver and heart.
Involved in autophagic vesicle formation. Conjugation with ATG12, through a ubiquitin-like conjugating system involving ATG7 as an E1-like activating enzyme and ATG10 as an E2-like conjugating enzyme, is essential for its function. The ATG12-ATG5 conjugate acts as an E3-like enzyme which is required for lipidation of ATG8 family proteins and their association to the vesicle membranes. Involved in mitochondrial quality control after oxidative damage, and in subsequent cellular longevity. Plays a critical role in multiple aspects of lymphocyte development and is essential for both B and T lymphocyte survival and proliferation. Required for optimal processing and presentation of antigens for MHC II. Involved in the maintenance of axon morphology and membrane structures, as well as in normal adipocyte differentiation. Promotes primary ciliogenesis through removal of OFD1 from centriolar satellites and degradation of IFT20 via the autophagic pathway.
May play an important role in the apoptotic process, possibly within the modified cytoskeleton. Its expression is a relatively late event in the apoptotic process, occurring downstream of caspase activity. Plays a crucial role in IFN-gamma-induced autophagic cell death by interacting with FADD.
Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO), such as platelet dense granules and melanosomes. Plays a role in intracellular vesicle trafficking. Plays a role in synaptic vesicle trafficking and in neurotransmitter release. May be required for normal dopamine homeostasis in the cerebral cortex, hippocampus, and hypothalamus. Plays a role in the regulation of cell surface exposure of DRD2. Contributes to the regulation of dopamine signaling. May play a role in actin cytoskeleton reorganization and neurite outgrowth (By similarity).
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.
Belongs to the dihydrofolate reductase family.
Belongs to the AB hydrolase superfamily.
Demethylates proteins that have been reversibly carboxymethylated. Demethylates PPP2CB (in vitro) and PPP2CA. Binding to PPP2CA displaces the manganese ion and inactivates the enzyme.
GAP activity stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidic acid.
GTPase-activating protein (GAP) for ADP ribosylation factor 6 (ARF6).
GTPase-activating protein for the ADP ribosylation factor family.
PH domain binds phospholipids including phosphatidic acid, phosphatidylinositol 3-phosphate, phosphatidylinositol 3,5-bisphosphate (PIP2) and phosphatidylinositol 3,4,5-trisphosphate (PIP3). May mediate protein binding to PIP2 or PIP3 containing membranes.
The BAR domain mediates homodimerization, it can neither bind membrane nor impart curvature, but instead requires the neighboring PH domain to achieve these functions.
Belongs to the polyadenylate-binding protein type-1 family.
Regulator of histone methyltransferase complexes that plays an essential role in embryonic development, including heart and liver development, neural tube fusion process and hematopoiesis. Acts as an accessory subunit for the core PRC2 (Polycomb repressive complex 2) complex, which mediates histone H3K27 (H3K27me3) trimethylation on chromatin. Binds DNA and mediates the recruitment of the PRC2 complex to target genes in embryonic stem cells, thereby playing a key role in stem cell differentiation and normal embryonic development (By similarity). In cardiac cells, it is required to repress expression of cyclin-D1 (CCND1) by activating methylation of 'Lys-9' of histone H3 (H3K9me) by the GLP1/EHMT1 and G9a/EHMT2 histone methyltransferases. Also acts as a transcriptional repressor of ANF via its interaction with GATA4 and NKX2-5. Participates in the negative regulation of cell proliferation signaling. Does not have histone demethylase activity (By similarity).
The ARID domain is required to target the PRC2 complex to its target genes.
Expressed in hen anterior pituitary during the ovulatory cycle and in the ovarian follicle.
Probable C-mannosyltransferase that mediates C-mannosylation of tryptophan residues on target proteins.
Belongs to the class-II aminoacyl-tRNA synthetase family. Phe-tRNA synthetase alpha subunit type 2 subfamily.
Heterotetramer; dimer of two heterodimers formed by FARSA and FARSB.
Belongs to the glycosyl hydrolase 13 family. GlgB subfamily.
Belongs to the SRC/p160 nuclear receptor coactivator family.
Although the final Cys may be farnesylated, the terminal tripeptide is probably not removed, and the C-terminus is not methylated.
Phosphorylase b kinase catalyzes the phosphorylation of serine in certain substrates, including troponin I. The alpha chain may bind calmodulin.
Belongs to the archaeal rpoM/eukaryotic RPA12/RPB9/RPC11 RNA polymerase family.
Component of the RNA polymerase II (Pol II) complex consisting of 12 subunits.
Cilium- and flagellum-specific protein that plays a role in axonemal structure organization and motility (By similarity). Involved in the regulation of the size and morphology of cilia. Required for axonemal microtubules polyglutamylation (By similarity).
Belongs to the V-ATPase D subunit family.
May be nitrosylated on several cysteine residues, depending on the oxidation state. Nitrosylated Cys-73 may serve as donor for nitrosylation of target proteins (By similarity).
Participates in various redox reactions through the reversible oxidation of its active center dithiol to a disulfide and catalyzes dithiol-disulfide exchange reactions (By similarity). Plays a role in the reversible S-nitrosylation of cysteine residues in target proteins, and thereby contributes to the response to intracellular nitric oxide. Nitrosylates the active site Cys of CASP3 in response to nitric oxide (NO), and thereby inhibits caspase-3 activity. Induces the FOS/JUN AP-1 DNA binding activity in ionizing radiation (IR) cells through its oxidation/reduction status and stimulates AP-1 transcriptional activity (By similarity).
Component of the uniplex complex. Interacts (via the transmembrane region) with MCU (via the first transmembrane region); the interaction is direct.
Essential regulatory subunit of the mitochondrial calcium uniporter complex (uniplex), a complex that mediates calcium uptake into mitochondria.
Amino acid transporter that specifically mediates the pH-dependent export of the cationic amino acids arginine, histidine and lysine from lysosomes.
The di-leucine motif mediates lysosomal localization.
Strong transcriptional activator; DNA-binding protein that specifically recognize the sequence 5'-YAAC[GT]G-3'. Could have a role in the proliferation and/or differentiation of neurogenic, spermatogenic and B-lymphoid cells.
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(i)-alpha and G(o)-alpha, but not to G(s)-alpha.
Belongs to the eukaryotic initiation factor 4E family.
Essential component of the SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex, which mediates the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. In the SCF complex, serves as an adapter that links the F-box protein to CUL1 (By similarity).
RNA-dependent helicase. Plays an important role in the assembly of the mitochondrial large ribosomal subunit. Required for optimal function of the zinc-finger antiviral protein ZC3HAV1. Associates with mitochondrial DNA. Involved in nervous system development and differentiation through its involvement in the up-regulation of a number of genes which are required for neurogenesis, including GSC, NCAM1, neurogenin, and NEUROD.
Acts as a ligand of the ADGRL1 receptor (By similarity). 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. May also mediate axon guidance and heterophilic cell-cell adhesion. May function as a cellular signal transducer.
Derives from the membrane form by proteolytic processing.
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.
Expressed in external plexiform layer and laminae 1 and 3 within the inner plexiform layer (at protein level). Expression started to be detectable in 4-day-old embryos, both in the body as well as the head (brain) of the embryos. Expressed in neurons of the inner plexiform layer (IPL), the optic fiber layer (OFL) and the optic nerve at 11 dpc. Expressed in the neurons of the entire retinal ganglion cell layer at 12 dpc. Expressed by the neurons of the thalamofugal visual pathway at 18 dpc. Expressed in the developing limb buds, somites, and craniofacial mesenchyme at 19 dpc. In the limbs, expressed transiently in the apical ectodermal ridge (AER) and later at sites of tendon morphogenesis. Also found in the notochord, dorsal neural tube, and dorsomedial lip of the somite as well as the flank mesoderm.
Homodimer; disulfide-linked (Probable). Heterodimer with other teneurins (By similarity).
Forms a distorted beta-barrel structure, with two helices that are packed against the outer surface of the barrel. Porphyrins are expected to bind to a hydrophobic patch on the outer surface of the beta-barrel structure (By similarity).
May bind free porphyrinogens that may be present in the cell and thus facilitate removal of these potentially toxic compound. Binds with a high affinity to one molecule of heme or porphyrins. It binds metalloporphyrins, free porphyrins and N-methylprotoporphyrin with similar affinities (By similarity).
IGF-binding proteins prolong the half-life of the IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs on cell culture. They alter the interaction of IGFs with their cell surface receptors.
Belongs to the glycosyltransferase 31 family. Beta3-Gal-T subfamily.
Glycosyltransferase that generates the core 1 O-glycan Gal-beta1-3GalNAc-alpha1-Ser/Thr (T antigen), which is a precursor for many extended O-glycans in glycoproteins.
Involved in pH regulation to eliminate acids generated by active metabolism or to counter adverse environmental conditions. Major proton extruding system driven by the inward sodium ion chemical gradient. Plays an important role in signal transduction (By similarity).
Belongs to the cyclic nucleotide phosphodiesterase family. PDE1 subfamily.
Component of the chromosomal passenger complex (CPC) composed of at least BIRC5/survivin, CDCA8/borealin, INCENP and AURKB; in the complex binds directly to AURKB via the IN box, and forms a triple-helix bundle-based subcomplex with BIRC5 and CDCA8 via its N-terminus. The initially reported homodimerization is questioned as the SAH domain is shown to be monomeric. Interacts with CBX5.
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. Acts as a scaffold regulating CPC localization and activity. The C-terminus associates with AURKB, the N-terminus associated with BIRC5/survivin and CDCA8/borealin tethers the CPC to the inner centromere, and the microtubule binding activity within the central SAH domain directs AURKB toward substrates near microtubules. The flexibility of the SAH domain is proposed to allow AURKB to follow substrates on dynamic microtubules while ensuring CPC docking to static chromatin. Activates AURKB.
Originally predicted to contain a coiled coil domain but shown to contain a stable SAH domain instead.
The IN box mediates interaction with AURKB and AURKC.
The SAH (single alpha-helix) region is characterized by a high content of charged residues which are predicted to stabilize the alpha-helical structure by ionic bonds. It can refold after extension suggesting an in vivo force-dependent function. The isolated SAH domain is monomeric.
Belongs to the methylthiotransferase family. CDKAL1 subfamily.
Binds 1 or 2 [4Fe-4S] cluster. One cluster is coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine.
Catalyzes the methylthiolation of N6-threonylcarbamoyladenosine (t(6)A), leading to the formation of 2-methylthio-N6-threonylcarbamoyladenosine (ms(2)t(6)A) at position 37 in tRNAs that read codons beginning with adenine.
DNA-binding protein that regulates the transcription of several genes and is involved in heart development and limb pattern formation. May bind to the core DNA motif of promoters.
Early in the developing heart, uniformly expressed throughout the entire cardiac crescent. Upon formation of the linear heart tube, expressed in a graded fashion, stronger near the posterior end and weaker at the anterior end. As the heart tube loops, asymmetric expression continues; it is expressed in the presumptive left ventricle, but not the right ventricle or outflow tract. This pattern of expression is maintained in more mature hearts (PubMed:10373308). First detected in the presumptive wing and leg mesoderm respectively at around stages 14-15. As limb outgrowth proceeds, expressed throughout the mesoderm and in the wing (PubMed:9550719).
Monomer. Homodimer (via the T-box); binds DNA as homodimer.
The T-Box domain binds to double-stranded DNA.
Acyl-CoA binding protein which acts as the peroxisome receptor for pexophagy but is dispensable for aggrephagy and nonselective autophagy. Binds medium- and long-chain acyl-CoA esters (By similarity).
Acyl-CoA binding protein which acts as the peroxisome receptor for pexophagy but is dispensable for aggrephagy and nonselective autophagy. Binds medium- and long-chain acyl-CoA esters.
Belongs to the XPG/RAD2 endonuclease family. FEN1 subfamily.
Interacts with PCNA. Three molecules of FEN1 bind to one PCNA trimer with each molecule binding to one PCNA monomer. PCNA stimulates the nuclease activity without altering cleavage specificity.
Phosphorylated. Phosphorylation upon DNA damage induces relocalization to the nuclear plasma.
Structure-specific nuclease with 5'-flap endonuclease and 5'-3' exonuclease activities involved in DNA replication and repair. During DNA replication, cleaves the 5'-overhanging flap structure that is generated by displacement synthesis when DNA polymerase encounters the 5'-end of a downstream Okazaki fragment. It enters the flap from the 5'-end and then tracks to cleave the flap base, leaving a nick for ligation. Also involved in the long patch base excision repair (LP-BER) pathway, by cleaving within the apurinic/apyrimidinic (AP) site-terminated flap. Acts as a genome stabilization factor that prevents flaps from equilibrating into structures that lead to duplications and deletions. Also possesses 5'-3' exonuclease activity on nicked or gapped double-stranded DNA, and exhibits RNase H activity. Also involved in replication and repair of rDNA and in repairing mitochondrial DNA.
Activated by 200-1000 micromolar concentrations of calcium and inhibited by calpastatin.
Calcium-regulated non-lysosomal thiol-protease which catalyze limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction.
Forms a heterodimer with a small (regulatory) subunit (CAPNS1).
COPII is composed of at least five proteins: the Sec23/24 complex, the Sec13/31 complex and Sar1.
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.
The Gelsolin-like repeat mediates interaction with proteins containing PPP motifs.
Calcium, potassium:sodium antiporter that transports 1 Ca(2+) and 1 K(+) in exchange for 4 Na(+) (PubMed:10662833). Required for learming and memory by regulating neuronal Ca(2+), which is essential for the development of synaptic plasticity (By similarity).
Retinal cones (PubMed:10662833). Found in the cone inner segment layer and in a subpopulation of ganglion cells (PubMed:10662833).
Catalyzes the pyridoxal 5'-phosphate (PLP)-dependent condensation of succinyl-CoA and glycine to form aminolevulinic acid (ALA), with CoA and CO2 as by-products.
Belongs to the fatty acyl-CoA reductase family.
Catalyzes the reduction of saturated and unsaturated C16 or C18 fatty acyl-CoA to fatty alcohols. It plays an essential role in the production of ether lipids/plasmalogens which synthesis requires fatty alcohols. In parallel, it is also required for wax monoesters production since fatty alcohols also constitute a substrate for their synthesis.
Catalyzes the dehydration of the S-form of NAD(P)HX at the expense of ATP, which is converted to ADP. Together with NAD(P)HX epimerase, which catalyzes the epimerization of the S- and R-forms, the enzyme allows the repair of both epimers of NAD(P)HX, a damaged form of NAD(P)H that is a result of enzymatic or heat-dependent hydration.
Binds to CNTF (GPA). The alpha subunit provides the receptor specificity.
Heterotrimer of the alpha subunit, LIFR and IL6ST.
Highly expressed in nervous system. Also found in skeletal muscle.
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.
Ligand-gated chloride channel which is a component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the brain (By similarity). Plays an important role in the formation of functional inhibitory GABAergic synapses in addition to mediating synaptic inhibition as a GABA- gated ion channel (By similarity).
Recruiter that couples transcriptional factors to general transcription apparatus and thereby modulates transcription regulation and chromatin formation. Can both act as an activator or a repressor depending on the context. Mediates MBD1-dependent transcriptional repression, probably by recruiting complexes containing histone methyltransferase activity. May belong to a complex that represses transcription and couples DNA methylation and histone H3 'Lys-9' trimethylation (H3K9me3) (By similarity).
Belongs to the PPP phosphatase family. PP-2B subfamily.
Belongs to the NFYA/HAP2 subunit family.
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.
Interacts with the cohesin complex. Binds chromatin in a cohesin-dependent manner (By similarity).
May regulate sister chromatid cohesion during mitosis and couple it to DNA replication.
Plays a role in mitochondrial and peroxisomal fission. Promotes the recruitment and association of the fission mediator dynamin-related protein 1 (DNM1L) to the mitochondrial surface.
A soluble form may be derived from the membrane form by proteolytic processing.
At stage 13 it is detected in the presomitic mesoderm, transiently observed before segmentation, and in the rostral part of the neural tube. Up-regulated in the neural tube, the retina and the otic vesicle from this stage on. At stage 17 a distinct stripe pattern was clear in the hindbrain and the spinal chord. Also found in the neuroepithelium of the midbrain and forebrain. The expression was down-regulated with the termination of neurogenesis at stage 36.
Glycosyltransferase that initiates the elongation of O-linked fucose residues attached to EGF-like repeats in the extracellular domain of Notch molecules. Essential mediator of somite segmentation and patterning.
Belongs to the calcium channel flower family.
Belongs to the Mediator complex subunit 6 family.
Component of the DRB sensitivity-inducing factor complex (DSIF complex), which regulates transcription elongation by RNA polymerase II.
Shows a remarkable charge distribution with the N-terminus being highly negatively charged, and the cytoplasmic C-terminus positively charged.
TRAP proteins are part of a complex whose function is to bind calcium to the ER membrane and thereby regulate the retention of ER resident proteins. May be involved in the recycling of the translocation apparatus after completion of the translocation process or may function as a membrane-bound chaperone facilitating folding of translocated proteins.
Belongs to the small GTPase superfamily. RGK family.
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.
Interacts with mitochondrial contact site and cristae organizing system (MICOS) complex components IMMT/MIC60 and MICOS10/MIC10 (By similarity). Interacts with mitochondrial outer membrane sorting assembly machinery (SAM) complex components SAMM50 and MTX1 (By similarity).
Belongs to the proteasome subunit S11 family.
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 PSMD13, a base containing 6 ATPases and few additional components.
May play a role in cell-cell or cell-ligand interactions during synaptogenesis and other events in the brain.
Since they lack a putative transactivation domain, the small Mafs behave as transcriptional repressors when they dimerize among themselves. However, they seem to serve as transcriptional activators by dimerizing with other (usually larger) basic-zipper proteins and recruiting them to specific DNA-binding sites. Small Maf proteins heterodimerize with Fos and may act as competitive repressors of the NF-E2 transcription factor. Transcription factor, component of erythroid-specific transcription factor NF-E2. May be involved in signal transduction of extracellular H(+) (By similarity).
Sumoylation at Lys-14 is required for active transcriptional repression.
A 10-fold increase in expression levels is seen by 1 week post-hatch and declines slightly between 3 and 4 weeks post-hatch.
Contains a putative mitochondrial transit peptide at positions 1-20.
Expressed at high levels in the liver, intestine and ovarian granulosa cells.
In the N-terminal section; belongs to the thiolase-like superfamily. Thiolase family.
Levels remain unchanged during day 20 embryo to 4 weeks post-hatch.
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 (By similarity). 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).
Plays a crucial role in the peroxisomal oxidation of branched-chain fatty acids. 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) (By similarity). 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).
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.
Seems to facilitate zinc transport from the cytoplasm into the Golgi apparatus. Partly regulates cellular zinc homeostasis (By similarity). Required with ZNT5 for the activation of zinc-requiring enzymes, alkaline phosphatases (ALPs). Transports zinc into the lumens of the Golgi apparatus and the vesicular compartments where ALPs locate, thus, converting apoALPs to holoALPs. Required with ZNT5 and ZNT6 for the activation of TNAP.
Belongs to the POU transcription factor family. Class-4 subfamily.
May play a role in specifying terminally differentiated neuronal phenotypes.
Essential for the assembly of the distal half of centrioles, required for centriole elongation.
Belongs to the MsrB Met sulfoxide reductase family.
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 residues.
Binding partner of the GTPase-activating protein FLCN: involved in the cellular response to amino acid availability by regulating the mTORC1 signaling cascade controlling the MiT/TFE factors TFEB and TFE3 (By similarity). In low-amino acid conditions, component of the lysosomal folliculin complex (LFC) on the membrane of lysosomes, which inhibits the GTPase-activating activity of FLCN, thereby inactivating mTORC1 and promoting nuclear translocation of TFEB and TFE3. Upon amino acid restimulation, disassembly of the LFC complex liberates the GTPase-activating activity of FLCN, leading to activation of mTORC1 and subsequent cytoplasmic retention of TFEB and TFE3 (By similarity). Required to promote FLCN recruitment to lysosomes and interaction with Rag GTPases. In addition to its role in mTORC1 signaling, also acts as a co-chaperone of HSP90AA1/Hsp90: inhibits the ATPase activity of HSP90AA1/Hsp90, leading to activate both kinase and non-kinase client proteins of HSP90AA1/Hsp90. Acts as a scaffold to load client protein FLCN onto HSP90AA1/Hsp90 (By similarity).
Homodimer and homomultimer. Heterodimer and heteromultimer with FNIP2 (By similarity). Component of the lysosomal folliculin complex (LFC) (By similarity).
Associates with pre-60S ribosomal particles.
Involved in the biogenesis of the 60S ribosomal subunit in the nucleus.
Belongs to the transient receptor (TC 1.A.4) family. LTrpC subfamily. TRPM2 sub-subfamily.
'Pegasus' was the winged horse in Greek mythology.
Transcriptional repressor that binds the core 5'GNNTGTNG-3' DNA consensus sequence.
Belongs to the AAA ATPase family. Katanin p60 subunit A1 subfamily. A-like 2 sub-subfamily.
Severs microtubules in vitro in an ATP-dependent manner. This activity may promote rapid reorganization of cellular microtubule arrays.
Homodimer (By similarity). Interacts with PCNA (PubMed:9302295).
Methylates CpG residues. Preferentially methylates hemimethylated DNA. It is responsible for maintaining methylation patterns established in development. Mediates transcriptional repression by direct binding to HDAC2. Plays a role in promoter hypermethylation and transcriptional silencing of tumor suppressor genes (TSGs) or other tumor-related genes. Also required to maintain a transcriptionally repressive state of genes in undifferentiated embryonic stem cells (ESCs). Associates at promoter regions of tumor suppressor genes (TSGs) leading to their gene silencing.
More abundant in stomach, and in small intestine. Lower levels in lung, liver, ovary and heart.
Belongs to the tRNA nucleotidyltransferase/poly(A) polymerase family.
Homodimer. Found in a multi-helicase-TICAM1 complex at least composed of DHX36, DDX1, DDX21 and TICAM1.
Involved in innate immunity against invading pathogens. Adapter used by TLR3, TLR4 (through TICAM2) and TLR5 to mediate NF-kappa-B and interferon-regulatory factor (IRF) activation, and to induce apoptosis. Ligand binding to these receptors results in TRIF recruitment through its TIR domain. Distinct protein-interaction motifs allow recruitment of the effector proteins TBK1, TRAF6 and RIPK1, which in turn, lead to the activation of transcription factors IRF3 and IRF7, NF-kappa-B and FADD respectively. Phosphorylation by TBK1 on the pLxIS motif leads to recruitment and subsequent activation of the transcription factor IRF3 to induce expression of type I interferon and exert a potent immunity against invading pathogens. 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.
The N-terminal region is essential for activation of the IFNB promoter activity.
Belongs to the glycosyltransferase 6 family.
May catalyze the formation of some glycolipid via the addition of N-acetylgalactosamine (GalNAc) in alpha-1,3-linkage to some substrate. Glycolipids probably serve for adherence of some pathogens (By similarity).
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).
Belongs to the Mediator complex subunit 13 family.
Component of the Mediator complex, a coactivator involved in 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.
Adds a GMP to the 5'-end of tRNA(His) after transcription and RNase P cleavage.
Belongs to the tRNA(His) guanylyltransferase family.
Part of a specialized transcription system that mediates the transcription of most ribosomal proteins through the 5'-TCT-3' motif which is a core promoter element at these genes. Seems to also mediate the transcription of NF1. Does not bind the TATA box (By similarity).
Present in the brain, heart, liver and gizzard.
Belongs to the CND1 (condensin subunit 1) family.
Regulatory subunit of the condensin complex, a complex required for conversion of interphase chromatin into mitotic-like condense chromosomes. The condensin complex probably introduces positive supercoils into relaxed DNA in the presence of type I topoisomerases and converts nicked DNA into positive knotted forms in the presence of type II topoisomerases.
Activated by micromolar concentrations of calcium and inhibited by calpastatin.
Heterodimer of large (catalytic) and a small (regulatory) subunit.
This protein was previously thought to be M-calpain but has since been found to be an intermediate form between the M and Mu types.
Expression levels increase dramatically during smooth muscle maturation.
Glycine-rich repeats mediate the association with the actin cytoskeleton.
Heat stable protein, that interacts with zyxin/ZYX. May be a component of a signal transduction pathway that mediates adhesion-stimulated changes in gene expression.
Most prominent in tissues that are enriched in smooth muscle cells, such as gizzard, stomach, and intestine. Lower level in the heart, no expression in liver, skeletal muscle, or brain.
Belongs to the universal ribosomal protein uS19 family.
Expressed in the large intestine, kidney liver, gall bladder, testis, ovary and male and female reproductive tracts. Expressed in the ovarian stroma and the theca and granulosa layers of the ovarian follicle.
Induced in the theca layer of the F3 stage ovarian follicle by intravenous injection of LPS. Repressed in the granulosa layer of the F3 stage ovarian follicle by intravenous injection of LPS.
Mostly restricted to cells of the nervous system. Expressed in NGF-dependent neurons of the PNS, but also found in subpopulations of CNS neurons, like spinal cord motoneurons, retinal ganglia cells and EGL cells of the cerebellum.
Specific expression in peripheral nervous system, including nerve growth factor-dependent sensory and sympathetic neurons, as well as enteric neurons.
Belongs to the phospholipase B-like family.
Belongs to the eukaryotic RPB4 RNA polymerase subunit family.
Belongs to the SMC family. SMC3 subfamily.
Central component of cohesin, a complex required for chromosome cohesion during the cell cycle. The cohesin complex may form 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. Cohesion is coupled to DNA replication and is involved in DNA repair. The cohesin complex also plays an important role in spindle pole assembly during mitosis and in chromosomes movement.
G-protein coupled opioid receptor that functions as receptor for the endogenous neuropeptide nociceptin. 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 via G proteins mediates inhibition of adenylate cyclase activity and calcium channel activity. Arrestins modulate signaling via G proteins and mediate the activation of alternative signaling pathways that lead to the activation of MAP kinases. Plays a role in modulating nociception and the perception of pain. Plays a role in the regulation of locomotor activity by the neuropeptide nociceptin.
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 (By similarity).
Component of a mSin3A corepressor complex that contains SIN3A, SAP130, SUDS3/SAP45, ARID4B/SAP180, HDAC1 and HDAC2.
The C-terminus may interact with HDAC-dependent and HDAC-independent corepressors.
The N-terminus may interact with a transcriptional coactivator.
May function as a transcription factor involved in cell differentiation.
Catalyzes the isomerization of citrate to isocitrate via cis-aconitate.
Aquaporins facilitate the transport of water and small neutral solutes across cell membranes.
Belongs to the MIP/aquaporin (TC 1.A.8) family. AQP11/AQP12 subfamily.
Belongs to the eukaryotic ribosomal protein eL34 family.
UTP--glucose-1-phosphate uridylyltransferase catalyzing the conversion of glucose-1-phosphate into UDP-glucose, a crucial precursor for the production of glycogen.
ATP-dependent DNA helicase implicated in telomere-length regulation, DNA repair and the maintenance of genomic stability. Acts as an anti-recombinase to counteract toxic recombination and limit crossover during meiosis. Regulates meiotic recombination and crossover homeostasis by physically dissociating strand invasion events and thereby promotes noncrossover repair by meiotic synthesis dependent strand annealing (SDSA) as well as disassembly of D loop recombination intermediates. Also disassembles T loops and prevents telomere fragility by counteracting telomeric G4-DNA structures, which together ensure the dynamics and stability of the telomere.
Belongs to the helicase family. RAD3/XPD subfamily.
Belongs to the GHMP kinase family. GalK subfamily.
Belongs to the ZP domain family. ZPB subfamily.
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.
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.
Belongs to the terpene cyclase/mutase family.
May play a role in preventing exon skipping, ensuring the accuracy of splicing and regulating alternative splicing.
Guanine nucleotide exchange factor (GEF) for RAB14.
Belongs to the inositol 1,4,5-trisphosphate 5-phosphatase type I family.
Belongs to the CMP-NeuNAc synthase family.
Necessary for efficient RNA polymerase II transcription elongation past template-encoded arresting sites. The arresting sites in DNA have the property of trapping a certain fraction of elongating RNA polymerases that pass through, resulting in locked ternary complexes. Cleavage of the nascent transcript by S-II allows the resumption of elongation from the new 3'-terminus.
Expressed in optic tectum, neostriatum, hypothalamus, thalamus and pineal gland, less in cerebellum and retina.
Acts as a transcriptional regulator in bone development. Binds to DNA (By similarity). Morphogenetic role.
Acts as a phosphoinositide 5- and phosphoinositide 6-phosphatase and regulates cellular levels of inositol pentakisphosphate (InsP5) and inositol hexakisphosphate (InsP6) (PubMed:9472008). 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 (By similarity). May play a role in bone development (endochondral ossification) (By similarity). May play a role in the transition of chondrocytes from proliferation to hypertrophy (PubMed:8660956, PubMed:9472008).
Belongs to the histidine acid phosphatase family. MINPP1 subfamily.
Monogastric animals cannot hydrolyze dietary inositol hexakisphosphate (InsP6) which makes up the bulk of organic phosphates in soybean, grains and other plant seeds which are the primary source of animal feed. The high activity of the chicken protein toward InsP6 offers a genetic strategy for improving InsP6 digestion in poultry and reducing the pollution that results from high phosphate content in manure.
Present in growth plate chondrocytes but not detectable in articular chondrocytes (at protein level) (PubMed:9472008). Spatially restricted to chondrocytes in the lower portion of the proliferative zone and the upper portion of the hypertrophic zone in the growth plate of long bones (at protein level) (PubMed:9472008). Weakly expressed in kidney, liver, lung, skin and spleen, and not detected in brain, heart and muscle (PubMed:8660956).
Repressed by parathyroid hormone-related protein PTHLH/PTHRP.
On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators. Receptor for activin (By similarity).
Belongs to the ADP-ribosyl cyclase family.
Expressed at relatively high levels in brain and muscle, moderate levels in lung, bursa, and heart and virtually absent in liver. Collapsin-1, -2, -3, and -5 bind to overlapping but distinct axon tracts.
Induces the collapse and paralysis of neuronal growth cones. Could serve as a ligand that guides specific growth cones by a motility-inhibiting mechanism. Binds to neuropilin.
Belongs to the glutamate--cysteine ligase type 3 family.
Acts as guanine nucleotide exchange factor (GEF) for RhoA and RhoB GTPases.
Belongs to the complex I LYR family. LYRM9 subfamily.
Interacts (via LIM domain) with PTPN13 (By similarity). Interacts (via PDZ domain) with ACTN1 (PubMed:14729062).
Suppresses SRC activation by recognizing and binding to active SRC and facilitating PTPN13-mediated dephosphorylation of SRC 'Tyr-419' leading to its inactivation. Inactivated SRC dissociates from this protein allowing the initiation of a new SRC inactivation cycle. Involved in reorganization of the actin cytoskeleton (By similarity). In nonmuscle cells, binds to ACTN1 (alpha-actinin-1), increases the affinity of ACTN1 to F-actin (filamentous actin), and promotes formation of actin stress fibers. Involved in regulation of the synaptic AMPA receptor transport in dendritic spines of hippocampal pyramidal neurons directing the receptors toward an insertion at the postsynaptic membrane. Links endosomal surface-internalized GRIA1-containing AMPA receptors to the alpha-actinin/actin cytoskeleton. Increases AMPA receptor-mediated excitatory postsynaptic currents in neurons (By similarity).
Belongs to the IPP isomerase type 1 family.
Catalyzes the 1,3-allylic rearrangement of the homoallylic substrate isopentenyl (IPP) to its highly electrophilic allylic isomer, dimethylallyl diphosphate (DMAPP).
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 (By similarity).
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 (By similarity). Its actin-bundling activity is inhibited by tropomyosin.
Monomer. Homodimer (By similarity). Associates with F-actin; the association with F-actin is inhibited by tropomyosin.
Phosphorylated on tyrosine residues. 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. Tyrosine phosphorylation is induced by epidermal growth factor (EGF) and stimulates cell migration (By similarity).
Specifically expressed in epithelial cells. Component of brush border microvilli.
Constituent of the membrane attack complex (MAC) that plays a key role in the innate and adaptive immune response by forming pores in the plasma membrane of target cells.
Interacts with XAF1, the interaction increases XAF1 stability and proapoptotic effects, and may regulate IFN signaling.
Belongs to the JHDM2 histone demethylase family.
Histone demethylase that specifically demethylates 'Lys-9' of histone H3, thereby playing a central role in histone code. Preferentially demethylates mono- and dimethylated H3 'Lys-9' residue, with a preference for dimethylated residue, while it has weak or no activity on trimethylated H3 'Lys-9'. Demethylation of Lys residue generates formaldehyde and succinate (By similarity).
Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs are known to mediate the association with nuclear receptors.
The JmjC domain and the C6-type zinc-finger are required for the demethylation activity.
Efficient DNA binding requires dimerization with another bHLH protein. Binds DNA as a heterodimer with MYC or MAD. Component of some MLL1/MLL complex (By similarity).
Transcription regulator. Forms a sequence-specific DNA-binding protein complex with MYC or MAD which recognizes the core sequence 5'-CAC[GA]TG-3'. The MYC-MAX complex is a transcriptional activator, whereas the MAD-MAX complex is a repressor (By similarity).
Belongs to the small membrane AKAP family.
Belongs to the class-II fumarase/aspartase family. Fumarase subfamily.
Catalyzes the hydration of fumarate to L-malate in the tricarboxylic acid (TCA) cycle to facilitate a transition step in the production of energy in the form of NADH.
Belongs to the glycosyltransferase 18 family.
Belongs to the Glu/Leu/Phe/Val dehydrogenases family.
Oxysterol-binding protein that mediates feedback control of cholesterol synthesis by controlling both endoplasmic reticulum to Golgi transport of SCAP and degradation of HMGCR. Acts as a negative regulator of cholesterol biosynthesis by mediating the retention of the SCAP-SREBP complex in the endoplasmic reticulum, thereby blocking the processing of sterol regulatory element-binding proteins (SREBPs). Binds oxysterol, including 25-hydroxycholesterol, regulating interaction with SCAP and retention of the SCAP-SREBP complex in the endoplasmic reticulum. In presence of oxysterol, interacts with SCAP, retaining the SCAP-SREBP complex in the endoplasmic reticulum, thereby preventing SCAP from escorting SREBPs to the Golgi. Sterol deprivation reduces oxysterol-binding, disrupting the interaction between INSIG1 and SCAP, thereby promoting Golgi transport of the SCAP-SREBP complex, followed by processing and nuclear translocation of SREBPs. Also regulates cholesterol synthesis by regulating degradation of HMGCR.
Belongs to the class I-like SAM-binding methyltransferase superfamily. BUD23/WBSCR22 family.
Receptor for the neuromedin-U and neuromedin-S neuropeptides.
Monokine with inflammatory and chemokinetic properties.
Expressed in a broad spectrum of hematopoietic organs, such as thymus and bursa. Lower levels of expression detected in the kidney.
Inhibits translation initiation and cap-dependent translation. May excert its function by hindering the interaction between EIF4A and EIF4G. Inhibits the helicase activity of EIF4A. Binds RNA (By similarity). Does not seem to be involved in apoptosis.
Core 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. Acts as a positive regulator of Wnt signaling pathway by promoting beta-catenin (CTNNB1) nuclear accumulation.
Homodimer; may also form higher oligomers (By similarity). 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. 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. Interacts with RANBP9. Part of a complex consisting of RANBP9, MKLN1 and GID8. Interacts with CTNNB1, AXIN1 and GSK3B (By similarity).
Component of a complex required to localize phosphatidylinositol 4-kinase (PI4K) to the plasma membrane. The complex acts as a regulator of phosphatidylinositol 4-phosphate (PtdIns(4)P) synthesis.
Component of a phosphatidylinositol 4-kinase (PI4K) complex.
Expressed in embryonic fibroblast, hematopoietic, erythroid, myeloid and lymphoid cells.
Phosphorylated by tyrosine-protein kinases.
This PTPase activity may directly link growth factor receptors and other signaling proteins through protein-tyrosine phosphorylation (By similarity). The SH2 regions may interact with other cellular components to modulate its own phosphatase activity against interacting substrates (By similarity). May play a positive role during the stages of erythroid cell proliferation (PubMed:8921851).
Belongs to the protease inhibitor I27 (calpastatin) family.
Specific inhibition of calpain (calcium-dependent cysteine protease). Plays a key role in postmortem tenderization of meat and have been proposed to be involved in muscle protein degradation in living tissue.
Disulfide isomerase which catalyzes the formation, isomerization, and reduction or oxidation of disulfide bonds.
Scaffold protein that may play a role in cell adhesion, cell spreading and in the reorganization of the actin cytoskeleton. May play a role in the regulation of cell proliferation. May inhibit cell growth (By similarity).
The N-terminal and the C-terminal halves of the protein can associate with each other, thereby hindering interactions with other proteins.
Belongs to the cytochrome c oxidase subunit 6A family.
Expressed uniformly in the embryonic hindbrain.
May be involved in macrophage-mediated cellular proliferation. It is mitogenic for fibroblasts and smooth muscle but not endothelial cells. It is able to bind EGF receptor/EGFR with higher affinity than EGF itself and is a far more potent mitogen for smooth muscle cells than EGF (By similarity). Plays an important role in the proper development of cranial nerves by inhibiting the migration of the cranial neural crest cells (NCCs) into the odd-numbered neuromeres (r3 and r5) of the hindbrain Plays a role in mediating v-Jun-induced oncogenic transformation.
Strongly induced in embryonic fibroblasts transformed by v-Jun.
Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Alpha-6/CHRNA6 sub-subfamily.
Acts as a transcriptional activator that mediates transcriptional activation by binding to E box-containing promoter (5'-CANNTG-3') (PubMed:9310321, PubMed:9740021). Acts as a differentiation factor during neurogenesis (PubMed:9310321). Induces photoreceptor cell overproduction in vivo and de novo generation in vitro (PubMed:9740021). May play a role in photoreceptor cell production (PubMed:9740021).
In the spinal cord it is found in neurons that are migrating or have reached their final position. Expressed in cells located at the outer portion of the developing retinal neuroepithelium, the location where prospective photoreceptors reside.
Belongs to the copper type II ascorbate-dependent monooxygenase family.
Expressed in neural crest at all developmental stages, and in developing somite and myotome.
ATP-dependent serine protease that mediates the selective degradation of misfolded and unassembled polypeptides in the peroxisomal matrix. Necessary for type 2 peroxisome targeting signal (PTS2)-containing protein processing and facilitates peroxisome matrix protein import.
Orphan nuclear receptor. Component of a cascade required for the development of the hypothalamic-pituitary-adrenal-gonadal axis. Acts as a coregulatory protein that inhibits the transcriptional activity of other nuclear receptors through heterodimeric interactions. May also have a role in the development of the embryo and in the maintenance of embryonic stem cell pluripotency.
This is a receptor for bradykinin. Could be a factor in chronic pain and inflammation.
Component of the DRTF1/E2F transcription factor complex. Forms heterodimers with DP family members. The E2F1 complex binds specifically hypophosphorylated retinoblastoma protein RB1. During the cell cycle, RB1 becomes phosphorylated in mid-to-late G1 phase, detaches from the DRTF1/E2F complex, rendering E2F transcriptionally active. Viral oncoproteins, notably E1A, T-antigen and HPV E7, are capable of sequestering RB1, thus releasing the active complex.
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. E2F1 binds preferentially RB1 in a cell-cycle dependent manner. It can mediate both cell proliferation and TP53/p53-dependent apoptosis. Blocks adipocyte differentiation by binding to specific promoters repressing CEBPA binding to its target gene promoters. Positively regulates transcription of RRP1B.
Adhesion plaque protein. Binds alpha-actinin and the CRP protein. May be a component of a signal transduction pathway that mediates adhesion-stimulated changes in gene expression.
Required for the maintenance of pluripotency and self-renewal of embryonic stem cells. Transcriptional activator that binds the DNA consensus sequence 5'-ATGCAAAT-3'.
Strongly down-regulated during embryonic stem cell differentiation induced either by retinoic acid treatment, or by cell adhesion prevention leading to embryoid body formation.
Widely expressed during embryonic development (at protein level). In pre-primitive streak stage embryos, expressed in the epiblast and in a salt-and-pepper fashion in the forming hypoblast (stages XI and XIII) (at protein level). As the primitive streak starts to form, strongly expressed in the epiblast of the streak itself (stage XIV) and in the mesoderm emerging from it, whereas expression in the lower layer tends to decrease (stages 2 through 4+). Expression in the area opaca is lost by stage 3+. At later stages, continues to be expressed in the mesoderm, but not detected in the endoderm (stages 5 through 8). At stage 5, expressed in all cells of the germinal crescent. At stage 8 and subsequently, strongly expressed in the neural plate and neural tube with particularly strong expression in the anterior hindbrain/posterior midbrain. At stage 9 and subsequently, still expressed in neural tissue and in primordial germ cells (at protein level). At stage 33, still expressed in germ cells. At stages 42-43, expressed in male and female gonads, as well as in spleen and brain, but at much lower levels than in proliferating embryonic stem cells.
Belongs to the phosphoglycerate kinase family.
Catalyzes one of the two ATP producing reactions in the glycolytic pathway via the reversible conversion of 1,3-diphosphoglycerate to 3-phosphoglycerate. In addition to its role as a glycolytic enzyme, it seems that PGK-1 acts as a polymerase alpha cofactor protein (primer recognition protein). May play a role in sperm motility.
Belongs to the pseudouridine synthase TruD family.
Acetylated on Lys-545 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-545 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.
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:10931848). 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). 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). Interacts with NPAS2 (PubMed:10931848).
Exhibits circadian rhythm expression in the pineal gland. Maximum levels between ZT13 and ZT16 during light/dark cycle. Similar expression in constant darkness. Expression in the retinal photoreceptor cells oscillates in a circadian manner.
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.
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-97 by CK2 is essential for its nuclear localization, its interaction with CLOCK and controls CLOCK nuclear entry. Dephosphorylation at Ser-85 is important for dimerization with CLOCK and transcriptional activity.
Sumoylated on Lys-266 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.
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 period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and BMAL1 or BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-BMAL1|BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G, which form a second feedback loop and which activate and repress BMAL1 transcription, respectively (By similarity). The preferred binding motif for the CLOCK-BMAL1 heterodimer is 5'-CACGTGA-3', which contains a flanking Ala residue in addition to the canonical 6-nucleotide E-box sequence (By similarity). CLOCK specifically binds to the half-site 5'-CAC-3', while BMAL1 binds to the half-site 5'-GTGA-3'. Essential for the rhythmic interaction of CLOCK with ASS1 and plays a critical role in positively regulating CLOCK-mediated acetylation of ASS1 (By similarity). Plays a role in protecting against lethal sepsis by limiting the expression of immune checkpoint protein CD274 in macrophages in a PKM2-dependent manner (By similarity).
Ubiquitinated, leading to its proteasomal degradation. Deubiquitinated by USP9X.
Reduces the ATPase activity of VCP. Necessary for the fragmentation of Golgi stacks during mitosis and for VCP-mediated reassembly of Golgi stacks after mitosis. May play a role in VCP-mediated formation of transitional endoplasmic reticulum (tER). Inhibits the activity of CTSL (in vitro). Together with UBXN2B/p37, regulates the centrosomal levels of kinase AURKA/Aurora A levels during mitotic progression by promoting AURKA removal from centrosomes in prophase. Also, regulates spindle orientation during mitosis.
Belongs to the complex I 75 kDa subunit family.
Intramembrane-cleaving aspartic protease (I-CLiP) that cleaves type II membrane signal peptides in the hydrophobic plane of the membrane.
The PAL motif is required for normal active site conformation. The catalytic domains embedded in the membrane are in the opposite orientation to that of the presenilin protein family; therefore, it is predicted to cleave type II-oriented substrate peptides like the prototypic protease SPP.
Heterodimer with BIN1. Binds SH3GLB1 (By similarity).
Is abundant in the forebrain and cerebellum. It is also found in the adrenal gland, anterior and posterior pituitary.
May participate in mechanisms of regulated exocytosis in synapses and certain endocrine cell types. May control the properties of the membrane associated cytoskeleton.
Divalent metal cations. Prefers magnesium or manganese.
Belongs to the NAD-dependent glycerol-3-phosphate dehydrogenase family.
Belongs to the alpha-ketoglutarate dehydrogenase family.
Active at low pH (under pH 4.6): proton channel activity is activated by luminal side protons. Polyunsaturated fatty acids, such as arachidonic acid, also activate the channel activity.
Composed of two modules of six transmembranes, forming a homodimer with a tetrameric architecture. The six transmembrane regions of each module are tightly packed within each subunit without undergoing domain swapping. Forms a central ion-conduction pore lined by the side chains of the pore-lining helices. Conserved isoleucine residues (Ile-44 in the first module and Ile-271 in the second module) in the center of the pore serve as the gate in the closed conformation. In the widened channel in the open conformation, the same residues establish a constriction essential for potassium selectivity.
Proton-activated proton channel that catalyzes proton efflux from endosomes and lysosomes to maintain a steady-state pH. Activated at low pH (under pH 4.6) by luminal side protons: selectively mediates lysosomal proton release from lysosomes, eliciting a proton leak that balances V-ATPase activity to maintain pH homeostasis. Regulation of lumenal pH stability is required for autophagosome-lysosome fusion. May also act as a potassium channel at higher pH, regulating potassium conductance in endosomes and lysosomes. The potassium channel activity is however unclear as it was tested in non-physiological conditions for a lysosomal channel.
Essential component of the renin-angiotensin system (RAS), a potent regulator of blood pressure, body fluid and electrolyte homeostasis.
Deubiquitinating enzyme involved in protein homeostasis maintenance, transcription, cytoskeleton regulation, myogenesis and degradation of misfolded chaperone substrates (By similarity). Binds long polyubiquitin chains and trims them, while it has weak or no activity against chains of 4 or less ubiquitins (By similarity). Involved in degradation of misfolded chaperone substrates via its interaction with STUB1/CHIP: recruited to monoubiquitinated STUB1/CHIP, and restricts the length of ubiquitin chain attached to STUB1/CHIP substrates and preventing further chain extension (By similarity). Interacts with key regulators of transcription and represses transcription: acts as a histone-binding protein that regulates transcription (By similarity). Regulates autophagy via the deubiquitination of 'Lys-402' of BECN1 leading to the stabilization of BECN1 (By similarity).
The UIM domains bind ubiquitin and interact with various E3 ubiquitin-protein ligase, such as STUB1/CHIP (By similarity). They are essential to limit the length of ubiquitin chains (By similarity).
Seems to be required for maximal rate of protein biosynthesis. Enhances ribosome dissociation into subunits and stabilizes the binding of the initiator Met-tRNA(I) to 40 S ribosomal subunits.
Detected in outer membrane of the vitelline layer of the egg (at protein level). Expressed in the liver, gall bladder, kidney, testis, ovary and male and female reproductive tracts. Expressed in the ovarian stroma, but not in the ovarian follicles. No expression is detected in bone marrow.
May be involved in the translation of target mRNAs by scanning and recognition of the initiation codon. Involved in translation initiation; promotes recruitment of aminoacetyled initiator tRNA to P site of 40S ribosomes. Can promote release of deacylated tRNA and mRNA from recycled 40S subunits following ABCE1-mediated dissociation of post-termination ribosomal complexes into subunits (By similarity).
The full-length protein can bind eight Ca(2+) ions via the annexin repeats. Calcium binding causes a major conformation change that modifies dimer contacts and leads to surface exposure of the N-terminal phosphorylation sites; in the absence of Ca(2+), these sites are buried in the interior of the protein core. The N-terminal region becomes disordered in response to calcium-binding.
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. Does not hydrolyze SUMO1 or ISG15 ubiquitin-like proteins.
Component of the large ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. Binds to G-rich structures in 28S rRNA and in mRNAs. Plays a regulatory role in the translation apparatus; inhibits cell-free translation of mRNAs.
E3 ubiquitin-protein ligase that regulates cell proliferation (PubMed:20015074). Involved in apoptosis regulation. Mediates ER stress-induced activation of JNK signaling pathway and apoptosis by promoting ERN1 activation and splicing of XBP1 mRNA (By similarity).
Expressed in skeletal muscle tissue during embryonic development and for 2 weeks after hatching; becomes undetectable 3 weeks after hatching (at protein level).
The RING-type zinc finger domain is required for E3 ligase activity and for promoting ER stress-induced JNK activation and apoptosis.
Widely expressed (at protein level). Lowest levels in the liver, moderate levels in the heart, intestine and spleen, and high levels in skeletal muscle, kidney, proventriculus and brain. Also expressed in inner ear after noise exposure.
Belongs to the methyltransferase superfamily. HEN1 family.
Methyltransferase that adds a 2'-O-methyl group at the 3'-end of piRNAs, a class of 24 to 30 nucleotide RNAs that are generated by a Dicer-independent mechanism and are primarily derived from transposons and other repeated sequence elements. This probably protects the 3'-end of piRNAs from uridylation activity and subsequent degradation. Stabilization of piRNAs is essential for gametogenesis.
Calcium-selective channel required to prevent calcium stores from overfilling.
Strongly expressed in early embryonic neural tissues (brain, spinal cord, dorsal root ganglia); less in other tissues such as cells around cartilage, myocardium, lung mesenchymal cells, and liver. After hatching expression is restricted to neural tissues including retina.
Receptor for interleukin-7. Also acts as a receptor for thymic stromal lymphopoietin (TSLP).
The IL7 receptor is a heterodimer of IL7R and IL2RG. The TSLP receptor is a heterodimer of CRLF2 and IL7R.
Maintains stem cell potency. Increases STAT3 phosphorylation and controls ERK phosphorylation. May act as a scaffold, increasing STAT3 recruitment onto endosomes.
The OCIA domain is necessary and sufficient for endosomal localization.
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 (By similarity).
The AP-3 complex associates with the BLOC-1 complex.
Belongs to the eukaryotic ribosomal protein eL36 family.
Belongs to the MMS22 family. MMS22L subfamily.
Antiapoptotic factor that may have a role in protein assembly.
Belongs to the Engrailed homeobox family.
Acts as a cytokine involved in enhancing production of interferon-gamma and interleukin-12 and reducing production of interleukin-10 and is essential in the pathway that leads to type I immunity.
Extensively phosphorylated on serine residues.
Major non-collagenous bone protein that binds tightly to hydroxyapatite. Appears to form an integral part of the mineralized matrix. Probably important to cell-matrix interaction.
Belongs to the methyltransferase TRM13 family.
tRNA methylase which 2'-O-methylates cytidine(4) in tRNA(Pro) and tRNA(Gly)(GCC), and adenosine(4) in tRNA(His).
May be involved in the unfolded protein response (UPR) during ER stress.
May modulate splice site selection during alternative splicing of pre-mRNAs. Regulates transcription and acts as corepressor. Recruits repressors to the histone deacetylase complex (HDAC) (By similarity).
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. Involved in an early step of the formation of preautophagosomal structures.
Receptor specific to the heptapeptide core common to adrenocorticotropic hormone and alpha-, beta-, and gamma-MSH. Plays a central role in energy homeostasis and somatic growth. This receptor is mediated by G proteins that stimulate adenylate cyclase (cAMP).
Molecular chaperone that functions in the processing and transport of secreted proteins (By similarity). Has ATPase activity (By similarity).
Belongs to the amidase family. GatA subfamily.
Involved in the early part of the secretory pathway.
May have a roles as negative regulator of innate antiviral response.
Belongs to the succinate/malate CoA ligase alpha subunit family.
Heterodimer of an alpha and a beta subunit. Different beta subunits determine nucleotide specificity. Together with the ATP-specific beta subunit SUCLA2, forms an ADP-forming succinyl-CoA synthetase (A-SCS). Together with the GTP-specific beta subunit SUCLG2 forms a GDP-forming succinyl-CoA synthetase (G-SCS).
Succinyl-CoA synthetase functions in the citric acid cycle (TCA), coupling the hydrolysis of succinyl-CoA to the synthesis of either ATP or GTP and thus represents the only step of substrate-level phosphorylation in the TCA. The alpha subunit of the enzyme binds the substrates coenzyme A and phosphate, while succinate binding and specificity for either ATP or GTP is provided by different beta subunits.
Belongs to the immunoglobulin superfamily.
Belongs to the glutaminyl-peptide cyclotransferase family.
Acts as a component of the essential kinetochore-associated NDC80 complex, which is required for chromosome segregation and spindle checkpoint activity (PubMed:12829748). Required for kinetochore integrity and the organization of stable microtubule binding sites in the outer plate of the kinetochore. The NDC80 complex synergistically enhances the affinity of the SKA1 complex for microtubules and may allow the NDC80 complex to track depolymerizing microtubules. May play a role in chromosome congression and may be essential for the end-on attachment of the kinetochores to spindle microtubules (By similarity).
Component of the NDC80 complex, which is composed of at least NDC80/HEC1 and CDCA1. Interacts with CENPH.
Component of the circadian clock oscillator which includes the CRY proteins, CLOCK or NPAS2, BMAL1 or BMAL2, CSNK1E, and the PER proteins. Interacts directly with PER3, and through a C-terminal domain, with CRY1 and CRY2.
Exhibits circadian rhythm expression. Peak levels in early morning and low levels at early night.
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 period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndrome and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and BMAL1 or BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-BMAL1|BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1/2 and RORA/B/G, which form a second feedback loop and which activate and repress BMAL1 transcription, respectively. PER1 and PER2 proteins transport CRY1 and CRY2 into the nucleus with appropriate circadian timing, but also contribute directly to repression of clock-controlled target genes through interaction with several classes of RNA-binding proteins, helicases and others transcriptional repressors. PER appears to regulate circadian control of transcription by at least three different modes. First, interacts directly with the CLOCK-BMAL1 at the tail end of the nascent transcript peak to recruit complexes containing the SIN3-HDAC that remodel chromatin to repress transcription. Second, brings H3K9 methyltransferases such as SUV39H1 and SUV39H2 to the E-box elements of the circadian target genes, like PER2 itself or PER1. The recruitment of each repressive modifier to the DNA seems to be very precisely temporally orchestrated by the large PER complex, the deacetylases acting before than the methyltransferases. Additionally, large PER complexes are also recruited to the target genes 3' termination site through interactions with RNA-binding proteins and helicases that may play a role in transcription termination to regulate transcription independently of CLOCK-BMAL1 interactions (By similarity).
A long coiled coil structure formed by 3 polypeptide chains connects the central nodule to the C-terminal domains (distal nodules). The long C-terminal ends of the alpha chains fold back, contributing a fourth strand to the coiled coil structure.
Cleaved by the protease thrombin to yield monomers which, together with fibrinogen alpha (FGA) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in hemostasis as one of the primary components of blood clots.
Conversion of fibrinogen to fibrin is triggered by thrombin, which cleaves fibrinopeptides A and B from alpha and beta chains, and thus exposes the N-terminal polymerization sites responsible for the formation of the soft clot. The soft clot is converted into the hard clot by factor XIIIA which catalyzes the epsilon-(gamma-glutamyl)lysine cross-linking between gamma chains (stronger) and between alpha chains (weaker) of different monomers.
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.
May be involved in the regulation of Rho-mediated signaling pathways and in cell cycle regulation.
Belongs to the SNF2/RAD54 helicase family. ISWI subfamily.
Seems to play a negative regulatory role in 5-phosphoribose 1-diphosphate synthesis.
Expressed in heart at embryonic day 14 (at protein level). Expressed in heart at embryonic day 8.
RNA-binding protein that may be involved in pre-mRNA alternative splicing, mRNA translation activation and stability.
Belongs to the glycosyltransferase 41 family. O-GlcNAc transferase subfamily.
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.
Belongs to the metallo-dependent hydrolases superfamily. Adenosine and AMP deaminases family. ADGF subfamily.
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).
Belongs to the complex I NDUFB6 subunit family.
Involved in DNA repair and mitotic recombination.
Associates with PLCG1, VAV1 and NCK1 in a B-cell antigen receptor-dependent fashion. Interacts through its SH2 domain with CD79A (By similarity). Interacts with VAV3, PLCG2 and GRB2.
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 is required for both Ca(2+) and MAPK signaling pathways (By similarity). Phosphorylation of Tyr-103, Tyr-194 and Tyr-205 facilitates PLCG1 binding. Phosphorylation of Tyr-115 facilitates BTK binding. Phosphorylation of Tyr-91 facilitates VAV1 and NCK1 binding.
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 (By similarity). Plays a critical role in B-cell development in the bursa. Plays an important role in BCR-induced apoptosis.
Highly expressed in the bursa, very low expression in ovary and spleen. Expression was variable among B-cell lines. Highly expressed in immature B-cell lines such as DT40 and CL18, low expression was seen in relatively mature B-cell lines, such as 293B9 and 249L4. No expression was seen in T-cell lines.
Calcium-regulated non-lysosomal thiol-protease.
Belongs to the glycosyl hydrolase 18 family.
Belongs to the bacterial ribosomal protein bL27 family.
Stimulates the secretion of gonadotropins.
Forms a homodimer or a heterodimer with a related family member, such as STAT1. Interacts with OCAD1 (By similarity).
Involved in the gp130-mediated signaling pathway.
Transcription factor that binds to the interleukin-6 (IL-6)-responsive elements identified in the promoters of various acute-phase protein genes.
Heterotetramer of two alpha chains and two beta chains.
This alpha chain is from the adult major tetrameric component, which has been called hemoglobin A or AII.
Belongs to the protein kinase superfamily. Tyr protein kinase family. CSK subfamily.
Non-receptor tyrosine-protein kinase that plays an important role in the regulation of cell growth, differentiation, migration and immune response. Phosphorylates tyrosine residues located in the C-terminal tails of Src-family kinases (SFKs). Upon tail phosphorylation, Src-family members engage in intramolecular interactions between the phosphotyrosine tail and the SH2 domain that result in an inactive conformation. To inhibit SFKs, CSK is recruited to the plasma membrane via binding to transmembrane proteins or adapter proteins located near the plasma membrane (By similarity).
Phosphorylated at Ser-364 by PKA, leading to increased activity. Autophosphorylated (By similarity).
The architecture of this protein is similar to that of Src-family kinases (SFKs) with one N-terminal SH3 domain, one SH2 domain, and a C-terminal kinase domain.
Required for organization of the cellular microtubule array and microtubule anchoring at the centrosome. 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 end. Positively regulates lysosome peripheral distribution and ruffled border formation in osteoclasts.
Involved in the transfer of neutral lipids, including cholesteryl ester and triglyceride, among lipoprotein particles. Allows the net movement of cholesteryl ester from high density lipoproteins/HDL to triglyceride-rich very low density lipoproteins/VLDL, and the equimolar transport of triglyceride from VLDL to HDL.
Belongs to the peptidase M67A family. MYSM1 subfamily.
Binds double-stranded DNA via the SANT domain. The SWIRM domain does not bind double-stranded DNA (By similarity).
Metalloprotease that specifically deubiquitinates monoubiquitinated histone H2A, a specific tag for epigenetic transcriptional repression, thereby acting as a coactivator. Preferentially deubiquitinates monoubiquitinated H2A in hyperacetylated nucleosomes. Deubiquitination of histone H2A leads to facilitate the phosphorylation and dissociation of histone H1 from the nucleosome. Acts as a coactivator by participating in the initiation and elongation steps of androgen receptor (AR)-induced gene activation (By similarity).
Transcription factor that plays a central role in developing and mature glia. Specifically activates expression of myelin genes, during oligodendrocyte (OL) maturation, thereby playing a central role in oligodendrocyte maturation and CNS myelination.
Abundantly expressed during development of the central nervous system, in particular in proliferating neuroblasts and in cells at the initial stages of differentiation. Also expressed at high levels in morphogenetically active regions such as limb buds, somites and mesonephric tubules. Expression decreases once cellular differentiation is over.
Efficient DNA binding requires dimerization with another bHLH protein. Forms homo- or heterooligomers with myogenin, E12 and ITF2 proteins (By similarity).
Transcriptional regulator. Involved in the initiation of neuronal differentiation. Activates transcription by binding to the E box-containing promoter (By similarity).
Catalyzes the rate-limiting reaction in the biogenesis of long-chain fatty acids. Carries out three functions: biotin carboxyl carrier protein, biotin carboxylase and carboxyltransferase.
May play some role in mitochondrial processes.
Required for 40S ribosome biogenesis. Involved in nucleolar processing of pre-18S ribosomal RNA and ribosome assembly.
Belongs to the dolichyldiphosphatase family.
Required for efficient N-glycosylation. Necessary for maintaining optimal levels of dolichol-linked oligosaccharides. Hydrolyzes dolichyl pyrophosphate at a very high rate and dolichyl monophosphate at a much lower rate. Does not act on phosphatidate.
Plays a role in the regulatory network through which muscle cells coordinate their structural and functional states during growth, adaptation, and repair.
Lys-50 undergoes hypusination, a unique post-translational modification that consists in the addition of a butylamino group from spermidine to lysine side chain and leads to the formation of a hypusine residue. eIF-5As are the only known proteins to undergo this modification, which is essential for their function.
eIF-5A seems to be the only eukaryotic protein to have a hypusine residue which is a post-translational modification of a lysine by the addition of a butylamino group.
mRNA-binding protein involved in translation elongation. Has an important function at the level of mRNA turnover, probably acting downstream of decapping. Critical for the efficient synthesis of peptide bonds between consecutive proline residues. Can resolve ribosomal stalling caused by consecutive prolines during translation (By similarity). 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. Functions as a regulator of apoptosis. Mediates effects of polyamines on neuronal process extension and survival. May play an important role in brain development and function, and in skeletal muscle stem cell differentiation (By similarity).
mRNA-binding protein involved in translation elongation. Has an important function at the level of mRNA turnover, probably acting downstream of decapping. Critical for the efficient synthesis of peptide bonds between consecutive proline residues. Can resolve ribosomal stalling caused by consecutive prolines during translation. 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. Functions as a regulator of apoptosis.
Keratin-binding protein required for epithelial cell polarization. Required for ciliogenesis (By similarity).
In the C-terminal section; belongs to the GART family.
In the N-terminal section; belongs to the GARS family.
In the central section; belongs to the AIR synthase family.
The C-terminal GART domain carries the phosphoribosylglycinamide formyltransferase activity.
The N-terminal ATP-grasp domain carries the phosphoribosylamine--glycine ligase activity.
The central AIRS domain carries the phosphoribosylformylglycinamidine cyclo-ligase activity.
Trifunctional enzyme that catalyzes three distinct reactions as part of the 'de novo' inosine monophosphate biosynthetic pathway.
Belongs to the class I-like SAM-binding methyltransferase superfamily. NNMT/PNMT/TEMT family.
Binds directly to large unilamellar vesicles (LUVs) containing phosphatidylinositol 4,5-bisphosphate (PIP2) or inositol 1,4,5-trisphosphate (InsP3). The PIP2-binding site corresponds to a putative PH domain present in its tail domain (By similarity).
Interacts (via its IQ motifs) with CALM.
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).
Allosterically activated by benzodiazepines (By similarity). Activated by pentobarbitol (By similarity). Inhibited by the antagonist bicuculline (By similarity). Inhibited by zinc ions (By similarity).
Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRG2 sub-subfamily.
This subunit carries the benzodiazepine binding site.
Belongs to the UNC119-binding protein family.
Monomethylation at Lys-85 (K85me1) 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.
Oxidation of Met-45 and Met-48 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.
Expressed in the cardiac crescent and later in the myocardium in stages 4 to 25.
Pro-inflammatory cytokine. Involved in the innate immune response to bacterial pathogens. The expression of MIF at sites of inflammation suggests a role as mediator in regulating the function of macrophages in host defense. Counteracts the anti-inflammatory activity of glucocorticoids. Has phenylpyruvate tautomerase and dopachrome tautomerase activity (in vitro), but the physiological substrate is not known. It is not clear whether the tautomerase activity has any physiological relevance, and whether it is important for cytokine activity (By similarity).
Belongs to the importin beta family. Importin beta-1 subfamily.
Converts acetoacetate to acetoacetyl-CoA in the cytosol (By similarity). Ketone body-utilizing enzyme, responsible for the synthesis of cholesterol and fatty acids (By similarity).
Belongs to the dynactin subunit 2 family.
Modulates cytoplasmic dynein binding to an organelle, and plays a role in prometaphase chromosome alignment and spindle organization during mitosis. Involved in anchoring microtubules to centrosomes. May play a role in synapse formation during brain development.
Component of the DREAM complex (By similarity). Binds directly to histone H4, probably via helix 1 of the histone fold, a region that is not accessible when histone H4 is in chromatin (PubMed:11112423). Interacts with CHAF1A, HDAC1, HDAC2, HDAC3 and HIRA (PubMed:10347232, PubMed:15527972, PubMed:17065558). May also interact with HAT1 (PubMed:11112423, PubMed:11160883).
Core histone-binding subunit that may target chromatin assembly factors, chromatin remodeling factors and histone deacetylases to their histone substrates in a manner that is regulated by nucleosomal DNA.
DIDS- and thiosulfate- sensitive anion exchanger mediating chloride, sulfate and oxalate transport.
Belongs to the potassium channel family. Calcium-activated (TC 1.A.1.3) subfamily. KCa4.1/KCNT1 sub-subfamily.
Generates outwardly rectifying currents that are suppressed by elevation of intracellular calcium.
Scaffold protein for the de novo synthesis of iron-sulfur (Fe-S) clusters within mitochondria, which is required for maturation of both mitochondrial and cytoplasmic [2Fe-2S] and [4Fe-4S] proteins.
Enhances the transcriptional activities of several nuclear receptors.
Catalyzes the conversion of GlcNAc-6-P into GlcNAc-1-P during the synthesis of uridine diphosphate/UDP-GlcNAc, a sugar nucleotide critical to multiple glycosylation pathways including protein N- and O-glycosylation.
F-actin regulator involved in anterograde Golgi to endosome transport: upon ubiquitination via 'Lys-33'-linked ubiquitin chains by the BCR(KLHL20) E3 ubiquitin ligase complex, interacts with EPS15 and localizes to the trans-Golgi network, where it promotes actin polymerization, thereby facilitating post-Golgi trafficking. May play a role in the maintenance of the Golgi apparatus morphology.
At stage 11, expressed in the medial sites of the embryonic right and left coelom, as well as in the medial region of the forming somites. Between stages 14 and 16, expression in the presumptive wing field, with strongest expression at stage 15. At stage 17, a faint expression is detected in the posterior region of the nascent limb bud. Expressed in the ocular surface ectoderm, including the corneal epithelium, starting from the onset of the lens vesicle closing at stage 16.
Detected at the marginal tip of the developing retina (PubMed:12490564). Expressed in the intermediate and the lateral plate mesoderm in the presumptive chick forelimb region. Expressed in the eye, head ectoderm, prospective forelimb mesenchyme, lung bud, pharyngeal arches, the brain and otic vesicle.
Ligand for members of the frizzled family of seven transmembrane receptors (PubMed:12490564). Functions in the canonical Wnt/beta-catenin signaling pathway (PubMed:12490564). Acts as an upstream regulator of FGF10 in the lateral plate mesoderm during limb initiation in the embryo (PubMed:11290326).
Belongs to the JARID1 histone demethylase family.
Both the JmjC domain and the JmjN domain are required for enzymatic activity (By similarity). However ARID and PHD-type 1 domain are not required for activity per se but contributed to recognition of the H3(1-21)K4me2 substrate peptide (By similarity).
Histone demethylase that demethylates 'Lys-4' of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 'Lys-9' or H3 'Lys-27'. Demethylates trimethylated, dimethylated and monomethylated H3 'Lys-4'. Acts as a transcriptional corepressor. May repress the CLOCK-BMAL1 heterodimer-mediated transcriptional activation of the core clock component PER2.
The 2 first PHD-type zinc finger domains are required for transcription repression activity.
Homooligomer. Homodimer; becomes monomeric upon activation. Heterooligomer.
Small heat shock protein which functions as a molecular chaperone probably maintaining denatured proteins in a folding-competent state. Plays a role in stress resistance and actin organization.
Smooth, cardiac and skeletal muscle, hardly detectable in fibroblasts or focal contacts.
Expressed in muscle, kidney, brain, stomach and intestine at 6 dpc. Levels increase in the brain from 6 dpc to 18 dpc, and decrease in muscle and intestine. Levels in the kidney remain constant. From 10 dpc, expression also found in heart, lung, skin and liver. Levels in the liver increase dramatically at 18 dpc. At 18 dpc, highest expression found in kidney and brain. In the embryonic central nervous system, the spinal cord expressed the highest levels. Lower levels found in the medulla oblongata, pons, cerebellum and midbrain, and very low levels in the forebrain.
Receptor for persephin. Mediates the GDNF-induced autophosphorylation and activation of the RET receptor (By similarity).
Belongs to the class I-like SAM-binding methyltransferase superfamily. MenG/UbiE family.
Component of a multi-subunit COQ enzyme complex, composed of at least COQ3, COQ4, COQ5, COQ6, COQ7 and COQ9.
Methyltransferase required for the conversion of 2-polyprenyl-6-methoxy-1,4-benzoquinol (DDMQH2) to 2-polyprenyl-3-methyl-6-methoxy-1,4-benzoquinol (DMQH2).
Belongs to the AAA ATPase family. BCS1 subfamily.
Belongs to the RecA family. RAD51 subfamily.
Expressed at high levels in lymphoid and reproductive organs.
Forms linear homooligomers, giving rise to a RAD51 nucleoprotein filament, which is essential for strand-pairing reactions during DNA recombination.
Plays an important role in homologous strand exchange, a key step in DNA repair through homologous recombination (HR). Binds to single-stranded DNA in an ATP-dependent manner to form nucleoprotein filaments which are essential for the homology search and strand exchange. Catalyzes the recognition of homology and strand exchange between homologous DNA partners to form a joint molecule between a processed DNA break and the repair template. Recruited to resolve stalled replication forks during replication stress. Also involved in interstrand cross-link repair.
Appears to be essential for maintaining mitochondrial cristae formation and mitochondrial function by acting via YME1L1 in a kinase-independent manner to regulate essential mitochondrial structural proteins OPA1 and IMMT (By similarity). The action of this enzyme 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) (Probable).
Interacts with MRAP; increasing ligand-sensitivity and generation of cAMP. Interacts with MRAP2; competing with MRAP for binding to MC2R and impairing the binding of corticotropin (ACTH).
Belongs to the eukaryotic ribosomal protein eL39 family.
Belongs to the protein-tyrosine phosphatase family. Receptor class 3 subfamily.
Found on the apical surfaces of retinal Mueller cells, renal tubule cells and intestinal brush border cells.
Tyrosine phosphatase which dephosphorylates or contributes to the dephosphorylation of several substrates (By similarity). Plays a role in cell adhesion, migration, proliferation and differentiation (By similarity). May influence the potential of nonsensory supporting cells to either proliferate or differentiate into hair cells (PubMed:10366616).
Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4), and some other non-histone substrates. 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. Participates in the BCL6 transcriptional repressor activity by deacetylating the H3 'Lys-27' (H3K27) on enhancer elements, antagonizing EP300 acetyltransferase activity and repressing proximal gene expression. Also functions as deacetylase for non-histone targets. In addition to protein deacetylase activity, also acts as protein-lysine deacylase by recognizing other acyl groups: catalyzes removal of (2E)-butenoyl (crotonyl) and 2-hydroxyisobutanoyl (2-hydroxyisobutyryl) acyl groups from lysine residues, leading to protein decrotonylation and de-2-hydroxyisobutyrylation, respectively.
Belongs to the proteasome inhibitor PI31 family.
Plays an important role in control of proteasome function. Inhibits the hydrolysis of protein and peptide substrates by the 20S proteasome. Also inhibits the activation of the proteasome by the proteasome regulatory proteins PA700 and PA28.
Binds to the 60S ribosomal subunit and prevents its association with the 40S ribosomal subunit to form the 80S initiation complex in the cytoplasm. May also be involved in ribosome biogenesis.
Monomer. Associates with the 60S ribosomal subunit.
Belongs to the pseudouridine synthase Pus10 family.
Proteolytically removes the C-terminal three residues of farnesylated proteins.
Expressed in both the developing central nervous system and peripheral nervous system.
Expression in the developing nervous system is transient and restricted to cells lining the ventricular zone that have ceased proliferation but have not yet begun to migrate into the outer layers. In retina, neurom is also transiently expressed in cells as they withdraw from the mitotic cycle, but persists in horizontal and bipolar neurons until full differentiation. In the peripheral nervous system, its expression closely follows cell proliferation.
Probably acts as a transcriptional activator. Mediates neuronal differentiation. Required for the regulation of amacrine cell fate specification in the retina (By similarity).
Serine or threonine phosphorylation within the basic region may regulate neurogenic activity.
Expressed from day 7-8.5 during feather morphogenesis in dermal and epidermal cells. Also expressed in heart from day 8.5-14.5. At later stages, when the feather follicle forms, expression still abundant in the epidermis, especially in the feather barb ridges.
Heterodimer; with an RXR molecule. Binds DNA preferentially as a RAR/RXR heterodimer.
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) composed of tandem 5'-AGGTCA-3' sites known as DR1-DR5 (By similarity). Required for hindbrain patterning and appears to be required for skin development.
May act as a scaffolding protein within caveolar membranes. Interacts directly with G-protein alpha subunits and can functionally regulate their activity.
Receptor for netrin required for axon guidance (By similarity). Mediates axon repulsion of neuronal growth cones in the developing nervous system upon ligand binding (By similarity). Involved in dorsal root ganglion axon projection towards the spinal cord (PubMed:28483977).
Expressed in the lens, otic placode (medial wall of the vesicle) and in epibranchial placode. Also expressed in the developing somites (dermomyotome).
Receptor for Wnt proteins. Functions in the canonical Wnt/beta-catenin signaling pathway. The canonical Wnt/beta-catenin 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 (By similarity). 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 (Probable).
Somites and placodal expression appears at stage 9. At this stage, more obvious expression is detected in the neural tube (midbrain and rostral hindbrain), and persists through about stage 15. Strongly expressed in the ectoderm and around the otic placodes at stage 12. At stage 16, otic expression declines, expression in epibranchial placodes begins and peaks at stage 20. Expression in the lens of the eye is first seen at about stage 15, more evident at stage 16. At stage 17, seen in the ectoderm and mesenchyme of the limb primordia. Detected at stage 20 in the lip of the optic cup, in the mesenchyme surrounding the eye, in the ectoderm overlying the lens and in the ectoderm caudal and ventral of the olfactory placodes. From stages 20-30, expressed in cartilage and in the dermomyotomes and migrating sclerotomal cells forming vertebrae.
Functions as a GTPase-activating protein for the small GTPases RHOA, RHOB, RHOC and CDC42, terminating their downstream signaling. This induces morphological changes and detachment through cytoskeletal reorganization, playing a critical role in biological processes such as cell migration and proliferation. Also functions in vivo as an activator of the phospholipase PLCD1. Active DLC1 increases cell migration velocity but reduces directionality.
Interacts with EF1A1, facilitates EF1A1 distribution to the membrane periphery and ruffles upon growth factor stimulation and suppresses cell migration.
Acts as transcriptional coactivator. Enhances estrogen-dependent transactivation mediated by estrogen receptors.
Expressed in the pre-somitic mesoderm, mesonephric tubules, Wolfan ducts and collecting tubules of the developing urogenital system. Also expressed in the cranial sensory ganglia, pineal gland and eye.
Acts as decoy receptor for TNFSF11/RANKL and thereby neutralizes its function in osteoclastogenesis.
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.
Expressed in almost all tissues and found enriched in various region of the brain, retina, heart, gizzard, gut and sperm.
Reversibly catalyzes the transfer of phosphate between ATP and various phosphogens (e.g. creatine phosphate) (PubMed:8525081, PubMed:20026305). 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 (Probable).
Belongs to the EF-1-beta/EF-1-delta family.
EF-1 is composed of 4 subunits: alpha, beta, delta, and gamma.
EF-1-beta and EF-1-delta stimulate the exchange of GDP bound to EF-1-alpha to GTP.
Phosphorylation affects the GDP/GTP exchange rate.
Catalyzes the reduction of fatty acyl-CoA to fatty alcohols.
Belongs to the PPase class C family. Prune subfamily.
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.
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 (By similarity).
Major acute phase reactant. Apolipoprotein of the HDL complex.
Catalyzes the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PtdIns-4,5-P2) to phosphatidylinositol-4-phosphate (PtdIns-4-P).
Belongs to the Mediator complex subunit 20 family.
Belongs to the eukaryotic ribosomal protein eS4 family.
Belongs to the nucleoporin Nup84/Nup107 family.
Dipeptidyl carboxypeptidase that removes dipeptides from the C-terminus of a variety of circulating hormones, such as angiotensin I, bradykinin or enkephalins, thereby playing a key role in the regulation of blood pressure, electrolyte homeostasis or synaptic plasticity (By similarity). Composed of two similar catalytic domains, each possessing a functional active site, with different selectivity for substrates (By similarity). Plays a major role in the angiotensin-renin system that regulates blood pressure and sodium retention by the kidney by converting angiotensin I to angiotensin II, resulting in an increase of the vasoconstrictor activity of angiotensin (By similarity). Also able to inactivate bradykinin, a potent vasodilator, and therefore enhance the blood pressure response (By similarity). Acts as a regulator of synaptic transmission by mediating cleavage of neuropeptide hormones, such as substance P, neurotensin or enkephalins (By similarity). Catalyzes degradation of different enkephalin neuropeptides (Met-enkephalin, Leu-enkephalin, Met-enkephalin-Arg-Phe and possibly Met-enkephalin-Arg-Gly-Leu) (By similarity). Also acts as a regulator of hematopoietic stem cell differentiation by mediating degradation of hemoregulatory peptide N-acetyl-SDKP (AcSDKP) (By similarity).
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.
Belongs to the DEAD box helicase family. DDX42 subfamily.
At stage 21, expressed in leg buds in a superficial proximomedial domain, expression is enhanced by stage 23. By stage 29, expression is elaborated to include both leg and wing. By stage 35, expressed in all muscle-to-bone attachment sites. Expressed also in a wing aponeurosis, a tendinous element arranged in flattened bands, and in some of the flattened sheets of connective tissue associated with muscle.
Efficient DNA binding requires dimerization with another bHLH protein. Dimerizes and binds the E-box consensus sequence with E12.
Expressed in the intersomitic, the superficial proximomedial limb mesenchyme and the subectodermal mesenchyme.
Plays an early essential role in mesoderm formation, as well as a later role in formation of somite-derived chondrogenic lineages.
Only one chromosomal locus was found, suggesting that the pi gene either does not exist or is an allele of the pi' gene.
The pi' chain is the counterpart of the alpha chain in the major early embryonic hemoglobin P.
A central region that included the first H15 (linker histone H1/H5 globular) domain binds at the entry/exit site of the nucleosomal DNA.
Component of heterochromatin that maintains heterochromatin integrity during G1/S progression and regulates the duration of G1 phase to critically influence cell proliferative capacity.
Belongs to the protein prenyltransferase subunit alpha family.
Belongs to the DEAD box helicase family. DDX54/DBP10 subfamily.
Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the transfer of sulfate to position 6 of the N-acetylgalactosamine (GalNAc) residue of chondroitin (PubMed:7629189). Chondroitin sulfate constitutes the predominant proteoglycan present in cartilage and is distributed on the surfaces of many cells and extracellular matrices (PubMed:7629189). Catalyzes with a lower efficiency the sulfation of Gal residues of keratan sulfate, another glycosaminoglycan (PubMed:7629189). Can also catalyze the sulfation of the Gal residues in sialyl N-acetyllactosamine (sialyl LacNAc) oligosaccharides (PubMed:9147050).
May function as a general inhibitor of the histone deacetylase HDAC1.
The glycine cleavage system catalyzes the degradation of glycine. The H protein (GCSH) shuttles the methylamine group of glycine from the P protein (GLDC) to the T protein (GCST).
The glycine cleavage system is composed of four proteins: P (GLDC), T (GCST), L (DLD) and H (GCSH). Interacts with GLDC.
General coactivator that functions cooperatively with TAFs and mediates functional interactions between upstream activators and the general transcriptional machinery. May be involved in stabilizing the multiprotein transcription complex. Binds single-stranded DNA. Also binds, in vitro, non-specifically to double-stranded DNA (ds DNA) (By similarity).
Phospholipid scramblase involved in lipid homeostasis and membrane dynamics processes. Has phospholipid scramblase activity toward cholesterol and phosphatidylserine, as well as phosphatidylethanolamine and phosphatidylcholine. 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. In addition to autophagy, involved in other processes in which phospholipid scramblase activity is required (By similarity). Required for normal motor neuron development (By similarity).
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.
Belongs to the major facilitator superfamily. Spinster (TC 2.A.1.49) family.
May serve as a transcriptional repressor.
Belongs to the GTP cyclohydrolase I family.
GTP shows a positive allosteric effect, and tetrahydrobiopterin inhibits the enzyme activity. Zinc is required for catalytic activity. Inhibited by Mg(2+).
May positively regulate nitric oxide synthesis in endothelial cells. May be involved in dopamine synthesis. May modify pain sensitivity and persistence.
Toroid-shaped homodecamer, composed of two pentamers of five dimers.
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 (By similarity).
Acts as component of the THO subcomplex of the TREX complex which is thought to couple mRNA transcription, processing and nuclear export, and which 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 (By similarity).
Component of the THO complex, which is composed of THOC1, THOC2, THOC3, THOC5, THOC6 and THOC7; together with at least ALYREF/THOC4, DDX39B, SARNP/CIP29 and CHTOP, THO forms the transcription/export (TREX) complex which seems to have a dynamic structure involving ATP-dependent remodeling.
May be involved in cell differentiation.
Belongs to the TNF receptor-associated factor family. A subfamily.
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 (By similarity).
The APC/C is composed of at least 12 subunits.
Deubiquitinating enzyme that may play a role in the ubiquitin-dependent regulation of different cellular processes.
Belongs to the AAA ATPase family. PCH2 subfamily.
Plays a key role in chromosome recombination and chromosome structure development during meiosis. Required at early steps in meiotic recombination that leads to non-crossovers pathways. Also needed for efficient completion of homologous synapsis by influencing crossover distribution along the chromosomes affecting both crossovers and non-crossovers pathways (By similarity).
Protein kinase which regulates actin filament dynamics. Phosphorylates and inactivates the actin binding/depolymerizing factor cofilin, thereby stabilizing the actin cytoskeleton. Required for motility of the axon growth cone.
Expressed in the digestive tract throughout development in the epithelia of proventriculus and glandular structures. In 13 day embryo, strongly expressed in esophagus with moderate expression in proventriculus and lung. Weak expression in gizzard, small intestine, lung and dorsal skin. In embryos over 13 days old, observed in ectodermal, endodermal epithelium and also in neural and mesodermal tissues (i.e. notochord), floorplate in the neural tube, somatic mesoderm, splanchnic mesoderm and dermatome. In more developed embryos, expression was localized in the anterior lobe of the pituitary gland, notochord and hypothalamus of the diencephalon (derived from the floor plate of the neural tube). Also localized in the mesonephric mesoderm and lateral plate mesoderm.
Heterotetramer of two type I and two type II keratins. Interacts with PNN and the actin-binding domain of DMD (By similarity).
Involved in the organization of myofibers. Together with KRT8, helps to link the contractile apparatus to dystrophin at the costameres of striated muscle (By similarity).
This keratin differs from all other IF proteins in lacking the C-terminal tail domain.
Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. MCAK/KIF2 subfamily.
Plus end-directed microtubule-dependent motor required for normal brain development. May regulate microtubule dynamics during axonal growth. Required for normal progression through mitosis. Required for normal congress of chromosomes at the metaphase plate. Required for normal spindle dynamics during mitosis. Promotes spindle turnover. Implicated in formation of bipolar mitotic spindles. Has microtubule depolymerization activity (By similarity).
Chaperone protein which promotes assembly of the 20S proteasome as part of a heterodimer with PSMG1.
Nuclear receptor that acts as a key metabolic sensor by regulating the expression of genes involved in bile acid synthesis, cholesterol homeostasis and triglyceride synthesis. Together with the oxysterol receptors NR1H3/LXR-alpha and NR1H2/LXR-beta, acts as an essential transcriptional regulator of lipid metabolism (By similarity). Activates the transcription of CYP2C38 (By similarity).
Acts as a transcriptional regulator (By similarity). Represses PER2 transcription through a recognition sequence in the promoter (PubMed:11427718, PubMed:15182670). Component of the circadian clock that may contribute to the rhythmic expression of PER2 gene in a light-dependent and time-of-day-dependent manner (PubMed:11427718, PubMed:15182670).
Belongs to the bZIP family. NFIL3 subfamily.
Expression is regulated by light and circadian rhythms in the pineal gland (at protein level).
Homodimer (By similarity). Binds DNA as a dimer (By similarity).
Phosphorylated. Phosphorylated on Ser-182. Phosphorylation may require prime phosphorylation(s). Phosphorylation takes place at specific times of the day. Phosphorylation leads to its down-regulation through proteasome-dependent degradation.
Component of HBO1 complexes, which specifically mediate acetylation of histone H3 at 'Lys-14' (H3K14ac), and have reduced activity toward histone H4. Through chromatin acetylation it may function in DNA replication.
Homodimer. Component of the HBO1 complex.
Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. NR1/GRIN1 subfamily.
Has a negative effect on cell proliferation.
Calcium-dependent lectin involved in innate immune defense. Binds mannose, fucose and N-acetylglucosamine on different microorganisms and activates the lectin complement pathway.
In contrast to mammals, which contain two copies of MBL (MBL1 and MBL2), chicken genome only contains one copy of MBL.
Oligomeric complex of 3 or more homotrimers.
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. May play a role in the formation of epithelial cell junctions.
Was originally thought to have an internal disulfide bond.
May be involved in copper-dependent ATP7A trafficking between the trans-Golgi network and vesicles in the cell periphery.
Homodimer. Component of the BCR(KLHL7) E3 ubiquitin ligase complex (By similarity).
Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex. The BCR(KLHL7) complex acts by mediating ubiquitination and subsequent degradation of substrate proteins. Probably mediates 'Lys-48'-linked ubiquitination (By similarity).
ATP-dependent RNA helicase. Involved in pre-mRNA splicing as component of the spliceosome. Core component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junctions on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. The EJC marks the position of the exon-exon junction in the mature mRNA for the gene expression machinery and the core components remain bound to spliced mRNAs throughout all stages of mRNA metabolism thereby influencing downstream processes including nuclear mRNA export, subcellular mRNA localization, translation efficiency and nonsense-mediated mRNA decay (NMD). Its RNA-dependent ATPase and RNA-helicase activities are induced by CASC3, but abolished in presence of the MAGOH-RBM8A heterodimer, thereby trapping the ATP-bound EJC core onto spliced mRNA in a stable conformation. The inhibition of ATPase activity by the MAGOH-RBM8A heterodimer increases the RNA-binding affinity of the EJC. Involved in translational enhancement of spliced mRNAs after formation of the 80S ribosome complex. Binds spliced mRNA in sequence-independent manner, 20-24 nucleotides upstream of mRNA exon-exon junctions. Shows higher affinity for single-stranded RNA in an ATP-bound core EJC complex than after the ATP is hydrolyzed. Involved in the splicing modulation of BCL2L1/Bcl-X (and probably other apoptotic genes); specifically inhibits formation of proapoptotic isoforms; the function is different from the established EJC assembly. Involved in craniofacial development.
Identified in the spliceosome C complex. Part of the mRNA splicing-dependent exon junction complex (EJC) complex; the core complex contains CASC3, EIF4A3, MAGOH and RBM8A. Interacts with CASC3, MAGOH, NXF1, RBM8A and ALYREF/THOC4. May interact with NOM1. Interacts with POLDIP3. Interacts with CWC22 and PRPF19 in an RNA-independent manner. Direct interaction with CWC22 is mediated by the helicase C-terminal domain. Full interaction with CWC22 occurs only when EIF4A3 is not part of the EJC and prevents EIF4A3 binding to RNA. Interacts with NCBP3.
Component of centromeric nucleosomes, where DNA is wrapped around a histone octamer core. The octamer contains two molecules each of H2A, H2B, CENPA and H4 assembled in one CENPA-H4 heterotetramer and two H2A-H2B heterodimers. CENPA modulates the DNA-binding characteristics of nucleosomes so that protruding DNA ends have higher flexibility than in nucleosomes containing conventional histone H3.
Histone H3-like nucleosomal protein that is specifically found in centromeric nucleosomes (PubMed:14563550). Replaces conventional H3 in the nucleosome core of centromeric chromatin that serves as an assembly site for the inner kinetochore. 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. May serve as an epigenetic mark that propagates centromere identity through replication and cell division (By similarity). Required for recruitment and assembly of kinetochore proteins, and as a consequence required for progress through mitosis, chromosome segregation and cytokinesis (PubMed:15870271).
Present in all interphase cells with a punctate pattern in the nucleus. Aligned along the metaphase plate in metaphase cells and becomes concentrated at the poles in anaphase cells (at protein level).
First expressed in the early primitive streak. By stage 4, in Hensen node, early prechordal plate and notochord. Also expressed in early development in the neural plate ectoderm immediately anterior to Hensen node. Expression not detected after stage 10-12.
May be involved in the initial formation of the chordamesoderm.
May play a specific role in the development of tissues.
Belongs to the NAD(P)-dependent epimerase/dehydratase family.
Catalyzes two distinct but analogous reactions: the reversible epimerization of UDP-glucose to UDP-galactose and the reversible epimerization of UDP-N-acetylglucosamine to UDP-N-acetylgalactosamine. The reaction with UDP-Gal plays a critical role in the Leloir pathway of galactose catabolism in which galactose is converted to the glycolytic intermediate glucose 6-phosphate. It contributes to the catabolism of dietary galactose and enables the endogenous biosynthesis of both UDP-Gal and UDP-GalNAc when exogenous sources are limited. Both UDP-sugar interconversions are important in the synthesis of glycoproteins and glycolipids.
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). 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. Also catalyzes the formation of 'Lys-48'-linked polyubiquitin chains, leading to degradation of substrate proteins. In addition to its function in damage signaling, also plays a role in higher-order chromatin structure by mediating extensive chromatin decondensation.
Homodimer. Forms a E2-E3 ubiquitin ligase complex composed of the RNF8 homodimer and a E2 heterodimer of UBE2N and UBE2V2.
The FHA domain specifically recognizes and binds ATM-phosphorylated MDC1.
Interacts with CACNA1C in vitro; however the relevance of the interaction in vivo is unclear.
Regulates the composition and fluidity of the plasma membrane (By similarity). Inhibits the incorporation of membrane-fluidizing phospholipids containing omega-3 long-chain polyunsaturated fatty acids (LCPUFA) and thereby promotes membrane rigidity (By similarity). Does not appear to have any effect on LCPUFA synthesis (By similarity).
Was originally proposed to be a calcium channel facilitator (PubMed:23673622). However, a more recent study shows that this protein regulates membrane phospholipid homeostasis (By similarity). Therefore, any effects on calcium flux are most likely a secondary consequence of defects in membrane composition or fluidity (By similarity).
Found in articular chondrocytes. Expressed in a variety of tissues.
Necessary for efficient 3-hydroxylation of fibrillar collagen prolyl residues.
Autophosphorylates on tyrosine residues.
Phosphorylated on serine/threonine residues. Phosphorylation on Thr-31 and Ser-367 by ATM in response to genotoxic stress disrupts MDM2 binding and prevents MDM2-mediated ubiquitination and subsequent proteasome degradation, thus promoting p53/TP53-mediated apoptosis (By similarity).
Serine/threonine-protein kinase involved in the control of mitotic transition and the regulation of cellular growth and/or development.
Ubiquitination in nucleus by MDM2 in normal conditions leads to proteasome degradation.
Abundant in several brain regions, including the ectostriatum, nucleus rotundus and hyperstriatum ventrale.
Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRG4 sub-subfamily.
Appears to regulate cell growth through interactions with the extracellular matrix and cytokines. Binds calcium and copper, several types of collagen, albumin, thrombospondin, PDGF and cell membranes. There are two calcium binding sites; an acidic domain that binds 5 to 8 Ca(2+) with a low affinity and an EF-hand loop that binds a Ca(2+) ion with a high affinity (By similarity).
Detected in aorta, skeletal muscle, calvarium, vertebra, anterior limb, kidney, heart, brain, skin and lung.
Belongs to the cytidine and deoxycytidylate deaminase family. ADAT2 subfamily.
Probably participates in deamination of adenosine-34 to inosine in many tRNAs.
Neurofilaments usually contain three intermediate filament proteins: NEFL, NEFM, and NEFH which are involved in the maintenance of neuronal caliber. May additionally cooperate with other neuronal intermediate filament proteins to form neuronal filamentous networks (By similarity).
Phosphorylation seems to play a major role in the functioning of the larger neurofilament polypeptides (NF-M and NF-H), the levels of phosphorylation being altered developmentally and coincident with a change in the neurofilament function.
There are a number of repeats of the tripeptide K-S-P, NFM is phosphorylated on a number of the serines in this motif. It is thought that phosphorylation of NFM results in the formation of interfilament cross bridges that are important in the maintenance of axonal caliber.
Ca(2+) or Mg(2+). Has lower efficiency with Mg(2+).
Canalicular ectonucleoside NTPDase responsible for the main hepatic NTPDase activity. Ectonucleoside ATPases catalyze the hydrolysis of gamma- and beta-phosphate residues of nucleotides, playing a central role in concentration of extracellular nucleotides.
Inhibits cell proliferation by negative regulation of the G1/S transition. Has been shown to mediate cell death which is not of the classical apoptotic type and to regulate expression of components of the plasminogen pathway (By similarity).
Belongs to the type II (or gamma) interferon family.
Produced by lymphocytes activated by specific antigens or mitogens. IFN-gamma, in addition to having antiviral activity, has important immunoregulatory functions. It is a potent activator of macrophages, it has antiproliferative effects on transformed cells and it can potentiate the antiviral and antitumor effects of the type I interferons (By similarity).
Homodimer. Heterodimer of an alpha (TPM1, TPM3 or TPM4) and a beta (TPM2) chain.
Belongs to the liprin family. Liprin-alpha subfamily.
Required to suppress inappropriate homologous recombination, thereby playing a central role DNA repair and in the maintenance of genomic stability.
Contributes to various developmental events through its interactions with multiple signaling pathways (PubMed:15363410, PubMed:16943268, PubMed:21856951). Dorsalizing factor involved in the induction of Hensen's node by inhibiting bone morphogenetic proteins during gastrulation and by enhancing DVR1/VG1 activity (PubMed:15363410, PubMed:16943268). Wnt signaling inhibitor which competes with WNT2B for binding to Wnt receptor FZD4 and represses WNT2B-dependent development of the peripheral eye (PubMed:21856951).
During embryonic development, expressed in the middle primitive streak and Hensen's node (PubMed:15363410). Expressed in the peripheral region of the developing eye (PubMed:21856951). Expressed in the presomitic mesoderm during somitogenesis in a NOTCH-dependent manner (PubMed:26299926).
Expressed throughout the emerging primitive streak at stage 2 (PubMed:16943268). At stage 3, expressed in both the anterior and posterior parts of the primitive streak (PubMed:16943268). At stage 4, expressed in Hensen's node and the anterior part of the primitive streak (PubMed:16943268). At all stages, expressed at lower levels than isoform 2 (PubMed:16943268).
Expressed throughout the emerging primitive streak at stage 2 (PubMed:16943268). At stage 3, expressed in both the anterior and posterior parts of the primitive streak (PubMed:16943268). At stage 4, expressed in Hensen's node and throughout the anterior, middle and posterior part of the primitive streak with a peak of expression in the middle part (PubMed:16943268). At all stages, expressed at higher levels than isoform 1 (PubMed:16943268).
Forms a ternary complex with chordin/CHRD and BMP4.
In the presomitic mesoderm (PSM), expression is first detected at stage 7 where the first somite pair originates from both sides of the neural tube (PubMed:26299926). At stage 15, expression is detected in the anterior PSM (PubMed:26299926). During stage 18, also expressed in the newly forming somites and the PSM that reaches beyond the leg bud (PubMed:26299926). At stage 23, expressed in the somites and PSM near the tip of the tail and also in the wing and leg buds (PubMed:26299926).
Interacts with FZD4 (via FZ domain); competes with WNT2B for binding to FZD4, inhibiting Wnt signaling and repressing peripheral eye development (PubMed:21856951). Interacts with BMP4; shows stronger interaction with BMP4 than isoform 2 (PubMed:16943268). Interacts with DVR1/VG1; the interaction is inhibited by BMP4 (PubMed:16943268). Interacts with BMP7 (PubMed:15363410).
Interacts with FZD4 (via FZ domain); competes with WNT2B for binding to FZD4, inhibiting Wnt signaling and repressing peripheral eye development (PubMed:21856951). Interacts with BMP4; shows weaker interaction with BMP4 than isoform 1 (PubMed:16943268). Interacts with DVR1/VG1; the interaction is inhibited by BMP4 (PubMed:16943268). Interacts with BMP7 (PubMed:16943268).
Shows strong bone morphogenetic protein antagonistic activity.
Shows weak bone morphogenetic protein antagonistic activity.
This factor is named 'Tsukushi' because its expression pattern in chick embryos is similar to the shape of the Japanese horsetail plant, tsukushi.
C1q associates with the proenzymes C1r and C1s to yield C1, the first component of the serum complement system. The collagen-like regions of C1q interact with the Ca(2+)-dependent C1r(2)C1s(2) proenzyme complex, and efficient activation of C1 takes place on interaction of the globular heads of C1q with the Fc regions of IgG or IgM antibody present in immune complexes.
Belongs to the eukaryotic ribosomal protein eL21 family.
Belongs to the eukaryotic ribosomal protein eS12 family.
Acid protease active in intracellular protein breakdown. In chicken it is a key enzyme for yolk formation as it is capable of catalyzing intra oocytic break down of protein components of both vitellogenin and VLDL.
Consists of a light chain and a heavy chain.
Oocytic yolk, preovulatory follicles, liver.
May contribute to the transcriptional control of cell growth and differentiation.
Oxidizes L-tryptophan to 5-hydroxy-l-tryptophan in the rate-determining step of serotonin biosynthesis.
E3 ubiquitin-protein ligase involved in ubiquitin fusion degradation (UFD) pathway and regulation of DNA repair. Part of the ubiquitin fusion degradation (UFD) pathway, a process that mediates ubiquitination of protein at their N-terminus, regardless of the presence of lysine residues in target proteins.
Expressed in muscle, but also in brain. Weakly expressed in kidney, gizzard, intestine and testis.
From 7.0 dpc, expressed in muscle but also in brain and liver. Skeletal myogenesis is a major site of expression during normal embryogenesis. In addition, the ganglia of the developing peripheral nervous system and various embryonic epithelia, including those of kidney, lung and gut are also sites of expression. Declined slowly to adult.
Monomer (By similarity). Homodimer (Probable). Interacts with LRP4; the heterodimer forms an AGRIN receptor complex that binds AGRIN resulting in activation of MUSK (By similarity).
Receptor tyrosine kinase which plays a central role in the formation and the maintenance of the neuromuscular junction (NMJ), the synapse between the motor neuron and the skeletal muscle. Recruitment of AGRIN by LRP4 to the MUSK signaling complex induces phosphorylation and activation of MUSK, the kinase of the complex. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. May also play a role within the central nervous system by mediating cholinergic responses, synaptic plasticity and memory formation (By similarity).
ATP dependent phosphorylation of adenosine and other related nucleoside analogs to monophosphate derivatives.
Involved in the processing of hormone and other protein precursors at sites comprised of pairs of basic amino acid residues. Substrates include POMC, renin, enkephalin, dynorphin, somatostatin, insulin and AGRP.
Belongs to the potassium channel family. A (Shaker) (TC 1.A.1.2) subfamily. Kv1.5/KCNA5 sub-subfamily.
Adenine glycosylase active on G-A mispairs.
Plays an important role in the regulation of embryonic development, cell proliferation, cell differentiation and cell migration. Involved in initiation, outgrowth and patterning of the limbs.
Expressed prior to the formation of distinct motor axon pathways and before the segregation of motor neurons into columns. Expression restricted to the medial subdivision of the median motor column (MMCm).
Transcription factor (By similarity). Defines subclasses of motoneurons that segregate into columns in the spinal cord and select distinct axon pathways. Acts in conjunction with LIM-1, ISL-1 and ISL-2.
Antiparallel disulfide-linked heterodimer of an alpha chain and a beta chain. Self-associates and forms higher oligomers.
Functions as extracellular chaperone that prevents aggregation of non native proteins. Prevents stress-induced aggregation of blood plasma proteins.
Belongs to the inositol 1,4,5-trisphosphate 5-phosphatase type II family.
A dimer in solution, it spans the membrane asymmetrically and appears to be tetrameric.
Functions both as a transporter that mediates electroneutral anion exchange across the cell membrane and as a structural protein. Major integral membrane glycoprotein of the erythrocyte membrane; required for normal flexibility and stability of the erythrocyte membrane and for normal erythrocyte shape via the interactions of its cytoplasmic domain with cytoskeletal proteins, glycolytic enzymes, and hemoglobin. Functions as a transporter that mediates the 1:1 exchange of inorganic anions across the erythrocyte membrane. Mediates chloride-bicarbonate exchange in the kidney, and is required for normal acidification of the urine.
Activated by phosphorylation on a serine residue.
Selectively hydrolyzes arachidonyl phospholipids in the sn-2 position releasing arachidonic acid. Together with its lysophospholipid activity, it is implicated in the initiation of the inflammatory response.
Stimulated by agonists such as ATP, EGF, thrombin and bradykinin as well as by cytosolic Ca(2+).
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).
Catalyzes the hydrolysis of GTP bound to the 40S ribosomal initiation complex (40S.mRNA.Met-tRNA[F].eIF-2.GTP) with the subsequent joining of a 60S ribosomal subunit resulting in the release of eIF-2 and the guanine nucleotide. The subsequent joining of a 60S ribosomal subunit results in the formation of a functional 80S initiation complex (80S.mRNA.Met-tRNA[F]).
The association of the DR1/DRAP1 heterodimer with TBP results in a functional repression of both activated and basal transcription of class II genes. This interaction precludes the formation of a transcription-competent complex by inhibiting the association of TFIIA and/or TFIIB with TBP. Can bind to DNA on its own (By similarity).
Detected in serum (at protein level). Detected in liver and choroid plexus.
Homotetramer. Dimer of dimers. In the homotetramer, subunits assemble around a central channel that can accommodate two ligand molecules.
Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain.
Acts as guanine nucleotide exchange factor (GEF) for CDC42. Promotes formation of GPHN clusters.
Belongs to the WD repeat striatin family.
May be involved in regulating transcriptional activation of cardiac genes during the aging process. May play a role in biosynthesis and/or processing of SLC2A4 in adipose cells.
Aquaporins contain two tandem repeats each containing two membrane-spanning helices and a pore-forming loop with the signature motif Asn-Pro-Ala (NPA). Each tandem repeat contains a loop and a short helix that enter and leave the lipid bilayer on the same side (By similarity).
Homotetramer. Homooctamer formed by head-to-head interaction between homotetramers from adjoining membranes (By similarity). During early stages of lens development, interacts through its C-terminal region with Cx56 and GJA8/Cx45.6 (PubMed:14762116).
Major component of lens fiber gap junctions.
Water channel. May be responsible for regulating the osmolarity of the lens. Interactions between homotetramers from adjoining membranes may stabilize cell junctions in the eye lens core.
Catalyzes the GTP-dependent ribosomal translocation step during translation elongation. During this step, the ribosome changes from the pre-translocational (PRE) to the post-translocational (POST) state as the newly formed A-site-bound peptidyl-tRNA and P-site-bound deacylated tRNA move to the P and E sites, respectively. Catalyzes the coordinated movement of the two tRNA molecules, the mRNA and conformational changes in the ribosome.
Diphthamide is 2-[3-carboxyamido-3-(trimethyl-ammonio)propyl]histidine (By similarity).
Phosphorylation by EF-2 kinase completely inactivates EF-2.
Catalyzes the exchange of eukaryotic initiation factor 2-bound GDP for GTP.
Complex of five different subunits; alpha, beta, gamma, delta and epsilon.
Required for mannose-6-phosphate-dependent trafficking of lysosomal enzymes. LYSET bridges GlcNAc-1-phosphate transferase (GNPTAB), to the membrane-bound transcription factor site-1 protease (MBTPS1), thus allowing proteolytic activation of the GNPTAB. GNPTAB is involved in the regulation of M6P-dependent Golgi-to-lysosome trafficking of lysosomal enzymes. LYSET is thus an essential factor for maturation and delivery of lysosomal hydrolases.
Forms a complex with PIGT, PIGS, PIGU and GAA1.
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.
Component of the chaperonin-containing T-complex (TRiC), a heterooligomeric complex of about 850 to 900 kDa that forms two stacked rings, 12 to 16 nm in diameter.
Component of the chaperonin-containing T-complex (TRiC), a molecular chaperone complex that assists the folding of proteins upon ATP hydrolysis.
Associates with the V0 complex of the vacuolar ATPase (V-ATPase) (By similarity). Interacts with ATP6AP2 (By similarity).
Required for the assembly of the V0 complex of the vacuolar ATPase (V-ATPase) in the endoplasmic reticulum.
Belongs to the glycosyltransferase group 1 family. Glycosyltransferase 4 subfamily.
Neuroendocrine peptide which is a critical regulator of cellular and organ growth, development, migration, differentiation and survival and of epithelial calcium ion transport.
Osteostatin is a potent inhibitor of osteoclastic bone resorption.
There are several secretory forms, including osteostatin, arising from endoproteolytic cleavage of the initial translation product. Each of these secretory forms is believed to have one or more of its own receptors that mediates the normal paracrine, autocrine and endocrine actions (By similarity).
Belongs to the phytoene/squalene synthase family.
Catalyzes the condensation of 2 farnesyl pyrophosphate (FPP) moieties to form squalene.
Belongs to the glycosyltransferase group 1 family.
Mannosylates Man(2)GlcNAc(2)-dolichol diphosphate and Man(1)GlcNAc(2)-dolichol diphosphate to form Man(3)GlcNAc(2)-dolichol diphosphate.
mRNA splicing factor that regulates the formation of epithelial cell-specific isoforms. Specifically regulates the expression of FGFR2-IIIb, an epithelial cell-specific isoform of FGFR2. Acts by directly binding specific sequences in mRNAs. Binds the GU-rich sequence motifs in the ISE/ISS-3, a cis-element regulatory region present in the mRNA of FGFR2 (By similarity).
Expressed in the brain and, to much less but significant extents, in the pituitary and adrenal glands.
Mg(2+) is required for catalysis and for stabilizing the dimer.
Homomultimers may associate with EGR1 bound to DNA.
May be involved in cell cycle regulation.
Divalent transition metal (iron and manganese) transporter involved in iron metabolism and host resistance to certain pathogens. Macrophage-specific membrane transport function. Controls 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 (By similarity).
In response to lymphokine or bacterial products.
Macrophages; spleen and thymus and at lower level in liver and lung.
Acts as a RAC1 guanine nucleotide exchange factor (GEF).
Belongs to the RIN (Ras interaction/interference) family.
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. ZP3 is essential for sperm binding and zona matrix formation.
Exhibits some circadian rhythm expression. Levels increase slightly during subjective day peaking at 10 hours. Levels decrease between 14 hours and 18 hours to peak again at 20 hours-22 hours.
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 period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and BMAL1 or BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-BMAL1|BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1/2, RORA/B/G, which form a second feedback loop and which activate and repress BMAL1 transcription, respectively. CRY1 and CRY2 have redundant functions but also differential and selective contributions at least in defining the pace of the SCN circadian clock and its circadian transcriptional outputs. Less potent transcriptional repressor in cerebellum and liver than CRY1, though less effective in lengthening the period of the SCN oscillator. Seems to play a critical role in tuning SCN circadian period by opposing the action of CRY1. With CRY1, dispensable for circadian rhythm generation but necessary for the development of intercellular networks for rhythm synchrony (By similarity). Represses CLOCK-BMAL1-mediated transcriptional activation (PubMed:11684328).
Directly interacts with tubulin-gamma; this interaction determines centrosomal localization.
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.
Belongs to the mitochondrion-specific ribosomal protein mS29 family.
Belongs to the glycosyltransferase 61 family.
O-linked mannose beta-1,4-N-acetylglucosaminyltransferase that transfers UDP-N-acetyl-D-glucosamine to the 4-position of the mannose to generate N-acetyl-D-glucosamine-beta-1,4-O-D-mannosylprotein. Involved 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 (By similarity).
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).
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).
Component of the ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), a multisubunit enzyme composed of 3 respiratory subunits cytochrome b, cytochrome c1 and Rieske protein, 2 core protein subunits, and additional low-molecular weight protein subunits.
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.
May be required for DNA interstrand cross-link repair.
Adapter protein able to interact with different proteins and involved in different biological processes. Mediates the interaction between the error-prone DNA polymerase zeta catalytic subunit REV3L and the inserter polymerase REV1, thereby mediating the second polymerase switching in translesion DNA synthesis. Translesion DNA synthesis releases the replication blockade of replicative polymerases, stalled in presence of DNA lesions. May also play a role in signal transduction in response to DNA damage. May regulate the activation of the anaphase promoting complex APC thereby regulating progression through the cell cycle. Component of the shieldin complex, which plays an important role in repair of DNA double-stranded breaks (DSBs). 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 (By similarity). Through transcriptional regulation may play a role in epithelial-mesenchymal transdifferentiation.
Homooligomer. Interacts with REV1. Interacts with FZR1 (in complex with the anaphase promoting complex APC). May interact with CDC20 (By similarity). Heterodimer with REV3L. This dimer forms the minimal DNA polymerase zeta complex (Pol-zeta2), with REV3L bearing DNA polymerase catalytic activity, although its activity is very low in this context. Component of the tetrameric Pol-zeta complex (Pol-zeta4), which consists of REV3L, MAD2L2, POLD2 and POLD3; Pol-zeta4 is the fully active form of DNA polymerase zeta. Component of the shieldin complex, consisting of SHLD1, SHLD2, SHLD3 and MAD2L2/REV7. 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.
Probably involved in protein and RNA export from the nucleus.
Belongs to the cyclin family. Cyclin Y subfamily.
Belongs to the actin family. ARP8 subfamily.
Component of the chromatin remodeling INO80 complex; specifically part of a complex module associated with the DBINO domain of INO80. Exists as monomers and dimers, but the dimer is most probably the biologically relevant form required for stable interactions with histones that exploits the twofold symmetry of the nucleosome core.
Plays an important role in the functional organization of mitotic chromosomes. Exhibits low basal ATPase activity, and unable to polymerize.
Interacts with BSG; interaction mediates SLC16A3 targeting to the plasma membrane.
Proton-dependent transporter of monocarboxylates such as L-lactate and pyruvate (By similarity). Plays a predominant role in the L-lactate efflux from highly glycolytic cells (By similarity).
Two basolateral sorting signals (BSS) in its C-terminal cytoplasmic tail are required to direct SLC16A3 to the basolateral membrane.
Was initially thought to be considered to be a low affinity lactate transporter with negligible affinity for pyruvate (By similarity). However, it was later shown that SLC16A3 is a high affinity lactate transporter with physiologically relevant affinity for pyruvate (By similarity).
Dioxygenase that can both act as a arginine demethylase and a lysyl-hydroxylase. Acts as a lysyl-hydroxylase that catalyzes 5-hydroxylation on specific lysine residues of target proteins such as U2AF2/U2AF65 and LUC7L2. Regulates RNA splicing by mediating 5-hydroxylation of U2AF2/U2AF65, affecting the pre-mRNA splicing activity of U2AF2/U2AF65. Hydroxylates its own N-terminus, which is required for homooligomerization. In addition to peptidyl-lysine 5-dioxygenase activity, may act as an RNA hydroxylase, as suggested by its ability to bind single strand RNA. Also acts as an arginine demethylase which preferentially demethylates asymmetric dimethylation. Demethylates histone H3 at 'Arg-2' (H3R2me) and histone H4 at 'Arg-3' (H4R3me), including mono-, symmetric di- and asymmetric dimethylated forms, thereby playing a role in histone code. However, histone arginine demethylation may not constitute the primary activity in vivo. In collaboration with BRD4, interacts with the positive transcription elongation factor b (P-TEFb) complex in its active form to regulate polymerase II promoter-proximal pause release for transcriptional activation of a large cohort of genes. Demethylates other arginine methylated-proteins such as ESR1. Has no histone lysine demethylase activity (By similarity). Required for differentiation of multiple organs during embryogenesis. Acts as a key regulator of hematopoietic differentiation (By similarity).
Hydroxylates its own N-terminus; hydroxylation is required for homooligomerization.
The nuclear localization signal motifs are necessary and sufficient to target it into the nucleus.
Abundant in oocytes; much less in heart and skeletal muscle.
Homooligomer. Binds to the extracellular matrix protein Reelin/RELN. Interacts with LRP8 (By similarity). Interacts with LDLRAP1 (By similarity). Interacts with SNX17 (By similarity). Interacts with DAB1. Interacts with PCSK9. Interacts with PAFAH1B3 and PAFAH1B2, the catalytic complex of (PAF-AH (I)) heterotetrameric enzyme; these interactions may modulate the Reelin pathway. Interacts with STX5; this interaction mediates VLDLR translocation from the endoplasmic reticulum to the plasma membrane. Interacts with CLU (By similarity).
Multifunctional cell surface receptor that binds VLDL and transports it into cells by endocytosis and therefore plays an important role in energy metabolism. Binds also to a wide range of other molecules including Reelin/RELN or apolipoprotein E/APOE-containing ligands as well as clusterin/CLU. In the off-state of the pathway, forms homooligomers or heterooligomers with LRP8. Upon binding to ligands, homooligomers are rearranged to higher order receptor clusters that transmit the extracellular RELN signal to intracellular signaling processes by binding to DAB1 (By similarity). This interaction results in phosphorylation of DAB1 leading to the ultimate cell responses required for the correct positioning of newly generated neurons. Later, mediates a stop signal for migrating neurons, preventing them from entering the marginal zone (By similarity).
Acts as a transcriptional regulator. Binds DNA and RNA (By similarity).
Cobalamin (vitamin B12) cytosolic chaperone that catalyzes the reductive decyanation of cyanocob(III)alamin (cyanocobalamin, CNCbl) to yield cob(II)alamin and cyanide, using FAD or FMN as cofactors and NADPH as cosubstrate. Cyanocobalamin constitutes the inactive form of vitamin B12 introduced from the diet, and is converted into the active cofactors methylcobalamin (MeCbl) involved in methionine biosynthesis, and 5'-deoxyadenosylcobalamin (AdoCbl) involved in the TCA cycle. Forms a complex with the lysosomal transporter ABCD4 and its chaperone LMBRD1, to transport cobalamin across the lysosomal membrane into the cytosol. The processing of cobalamin in the cytosol occurs in a multiprotein complex composed of at least MMACHC, MMADHC, MTRR (methionine synthase reductase) and MTR (methionine synthase) which may contribute to shuttle safely and efficiently cobalamin towards MTR in order to produce methionine. Also acts as a glutathione transferase by catalyzing the dealkylation of the alkylcob(III)alamins MeCbl and AdoCbl, using the thiolate of glutathione for nucleophilic displacement to generate cob(I)alamin and the corresponding glutathione thioether. The conversion of incoming MeCbl or AdoCbl into a common intermediate cob(I)alamin is necessary to meet the cellular needs for both cofactors. Cysteine and homocysteine cannot substitute for glutathione in this reaction.
Monomer in the absence of bound substrate. Homodimer; dimerization is triggered by binding to FMN or adenosylcobalamin. Heterodimer with MMADHC.
Component of the cap-binding complex (CBC), which binds co-transcriptionally to the 5' cap of pre-mRNAs and is involved in various processes such as pre-mRNA splicing, translation regulation, nonsense-mediated mRNA decay, RNA-mediated gene silencing (RNAi) by microRNAs (miRNAs) and mRNA export. The CBC complex is involved in mRNA export from the nucleus, leading to the recruitment of the mRNA export machinery to the 5' end of mRNA and to mRNA export in a 5' to 3' direction through the nuclear pore. The CBC complex is also involved in mediating U snRNA and intronless mRNAs export from the nucleus. The CBC complex is essential for a pioneer round of mRNA translation, before steady state translation when the CBC complex is replaced by cytoplasmic cap-binding protein eIF4E. The pioneer round of mRNA translation mediated by the CBC complex plays a central role in nonsense-mediated mRNA decay (NMD), NMD only taking place in mRNAs bound to the CBC complex, but not on eIF4E-bound mRNAs. The CBC complex enhances NMD in mRNAs containing at least one exon-junction complex (EJC), promoting the interaction between upf1 and upf2. The CBC complex is also involved in 'failsafe' NMD, which is independent of the EJC complex, while it does not participate in Staufen-mediated mRNA decay (SMD). During cell proliferation, the CBC complex is also involved in microRNAs (miRNAs) biogenesis via its interaction with srrt/ars2, thereby being required for miRNA-mediated RNA interference. The CBC complex also acts as a negative regulator of parn, thereby acting as an inhibitor of mRNA deadenylation. In the CBC complex, ncbp2/cbp20 recognizes and binds capped RNAs (m7GpppG-capped RNA) but requires ncbp1/cbp80 to stabilize the movement of its N-terminal loop and lock the CBC into a high affinity cap-binding state with the cap structure. The conventional cap-binding complex with NCBP2 binds both small nuclear RNA (snRNA) and messenger (mRNA) and is involved in their export from the nucleus.
Belongs to the GST superfamily. Zeta family.
Microtubule-associated protein with the capacity to bundle and stabilize microtubules. May associate with chromosomes and promote the organization of mitotic spindle microtubules around them (By similarity).
Associates with the RNA polymerase II complex.
Protein phosphatase that displays CTD phosphatase activity and regulates transcription of snRNA genes. Recognizes and binds phosphorylated 'Ser-7' of the C-terminal heptapeptide repeat domain (CTD) of the largest RNA polymerase II subunit POLR2A, and mediates dephosphorylation of 'Ser-5' of the CTD, thereby promoting transcription of snRNA genes.
May act as a transcription factor for cell pluripotency and differentiation in the embryo.
Organ-common type isozyme is found in many different tissues.
Belongs to the glucosamine/galactosamine-6-phosphate isomerase family. 6-phosphogluconolactonase subfamily.
Hydrolysis of 6-phosphogluconolactone to 6-phosphogluconate.
Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. IF-2 subfamily.
One of the essential components for the initiation of protein synthesis. Protects formylmethionyl-tRNA from spontaneous hydrolysis and promotes its binding to the 30S ribosomal subunits. Also involved in the hydrolysis of GTP during the formation of the 70S ribosomal complex.
Detected in distal ectodermal cells at Hamburger Hamilton stage 18 (18HH). Becomes restricted to the apical ectodermal ridge (AER) (at protein level). At stage 11HH, detected in neural ectoderm, developing optic placodes, the neural crest around the otic placodes, and along the anterior-posterior axis in somites. Detected in the ectoderm of the limb bud at 16HH to 18HH. Becomes restricted to the dermomyotome closer to the neural tube at stage 18HH. At 19HH and 23HH, detected in the apical ectodermal ridge, the developing eye and branchial arches.
Modulates the structure and function of the apical ectodermal ridge (AER) that controls embryonic limb development (PubMed:21575622). Functions in cell-cell adhesion, cell migration and axon guidance, exerting an attractive or repulsive role depending on its interaction partners. Plays a role in the spatial organization of brain neurons. Plays a role in vascular development. Plays a role in cell-cell adhesion via its interaction with latrophilins that are expressed at the surface of adjacent cells. Mediates axon attraction towards cells expressing NTN1. Mediates axon growth cone collapse and plays a repulsive role in neuron guidance via its interaction with UNC-5 family members. Plays a role in the regulation of the density of glutamaergic synapses. Plays a role in fibroblast growth factor-mediated signaling cascades. Required for normal morphogenesis during embryonic development, but not for normal embryonic patterning (By similarity).
Proteolytic cleavage in the juxtamembrane region gives rise to a soluble ectodomain. Cleavage is probably effected by a metalloprotease.
Belongs to the TRAFAC class OBG-HflX-like GTPase superfamily. OBG GTPase family. YchF/OLA1 subfamily.
Hydrolyzes ATP, and can also hydrolyze GTP with lower efficiency. Has lower affinity for GTP.
As part of a cytosolic protein quality control complex, the BAG6/BAT3 complex, maintains misfolded and hydrophobic patches-containing proteins in a soluble state and participates in their proper delivery to the endoplasmic reticulum or alternatively can promote their sorting to the proteasome where they undergo degradation. The BAG6/BAT3 complex is involved in the post-translational delivery of tail-anchored/type II transmembrane proteins to the endoplasmic reticulum membrane. Recruited to ribosomes, it interacts with the transmembrane region of newly synthesized tail-anchored proteins and together with SGTA and ASNA1 mediates their delivery to the endoplasmic reticulum. Client proteins that cannot be properly delivered to the endoplasmic reticulum are ubiquitinated and sorted to the proteasome. Similarly, the BAG6/BAT3 complex also functions as a sorting platform for proteins of the secretory pathway that are mislocalized to the cytosol either delivering them to the proteasome for degradation or to the endoplasmic reticulum. The BAG6/BAT3 complex also plays a role in the endoplasmic reticulum-associated degradation (ERAD), a quality control mechanism that eliminates unwanted proteins of the endoplasmic reticulum through their retrotranslocation to the cytosol and their targeting to the proteasome. It maintains these retrotranslocated proteins in an unfolded yet soluble state condition in the cytosol to ensure their proper delivery to the proteasome.
Belongs to the oligoribonuclease family.
Belongs to the FAD-dependent glycerol-3-phosphate dehydrogenase family.
Calcium-responsive mitochondrial glycerol-3-phosphate dehydrogenase which seems to be a key component of the pancreatic beta-cell glucose-sensing device.
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.
Component of the endosome-associated retrograde protein (EARP) complex.
Catalyzes the reversible hydration of carbon dioxide.
Can form homo- and heteropolymers with other CLDN. Homopolymers interact with CLDN1 and CLDN2 homopolymers. Directly interacts with TJP1/ZO-1, TJP2/ZO-2 and TJP3/ZO-3.
Binds with high affinity to CRF receptors 2-alpha and 2-beta.
Suppresses food intake, delays gastric emptying and decreases heat-induced edema. Might represent an endogenous ligand for maintaining homeostasis after stress.
Found in a mRNA splicing-dependent exon junction complex (EJC). Found in a complex with SR proteins. Found in a mRNP complex with RNPS1. Component of the PSAP complex consisting of RNPS1, SAP18 and PNN. Interacts with PNISR, CTBP1, CTBP2, KRT8, KRT18, KRT19, PS1D/PNO40, PPIG, RNPS1, SFRS4 and SRRM2. Identified in the spliceosome C complex.
Microtubule-binding centrosomal protein required for centriole cohesion, independently of the centrosome-associated protein/CEP250 and rootletin/CROCC linker. In interphase, required for anchoring microtubule at the mother centriole subdistal appendages and for centrosome positioning. During mitosis, may be involved in spindle assembly and chromatin alignment by regulating the organization of spindle microtubules into a symmetrical structure. Plays a non-essential role in ciliogenesis.
The N-terminal 3D structure (head domain) resembles that of NHEJ1/XLF, PAXX, SASS6 and XRCC4.
The coiled-coil domain is involved in microtubule-binding.
Belongs to the HIBADH-related family. NP60 subfamily.
Cytokine-like nuclear factor with chromatin gene reader activity involved in chromatin modification and regulation of gene expression. Acts as a nucleosome-destabilizing factor that is recruited to genes during transcriptional activation. Recognizes and binds histone H3 without a preference for specific epigenetic markers and also binds DNA. Interacts with KDM1B and promotes its histone demethylase activity by facilitating the capture of H3 tails, they form a multifunctional enzyme complex that modifies transcribed chromatin and facilitates Pol II transcription through nucleosomes.
Homotetramere. Binds to mononucleosomes.
In the dehydrogenase domain, the conserved NAD(P)H-binding sites and sequence similarity to plant dehydrogenases suggest that this protein may have oxidoreductase activity. However, since the active site is not conserved, the dehydrogenase domain seems to serve as a catalytically inert oligomerization module.
The A.T hook DNA-binding domain is required for the interaction with MAPK14.
The PWWP domain is a H3 reader and strongly binds DNA.
ATP-binding component of the Arp2/3 complex, a multiprotein complex that mediates actin polymerization upon stimulation by nucleation-promoting factor (NPF) (By similarity). The Arp2/3 complex mediates the formation of branched actin networks in the cytoplasm, providing the force for cell motility (By similarity). Seems to contact the pointed end of the daughter actin filament (By similarity). 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 (By similarity). 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) (By similarity).
Belongs to the actin family. ARP2 subfamily.
The leucine-zipper is required for dimerization and transcriptional repression.
Expressed in the dorsal somite derivatives of the chicken as well as in the dorsal subpopulation of trunk crest cells.
Negative regulator of the Wnt signaling pathway. Inhibits Wnt signaling in a cell-autonomous manner and functions upstream of beta-catenin.
Cell adhesion molecule involved in the establishment and/or maintenance of cell integrity. Involved in the formation and regulation of the tight junction (TJ) paracellular permeability barrier in epithelial cells. Induces primordial adhesive contact and aggregation of epithelial cells in a Ca(2+)-independent manner. Involved in epithelial movement during corneal sheet formation and regeneration. May play a role in VAMP3-mediated vesicular transport and recycling of receptor molecules. May play a role in the regulation of cell shape and movement by modulating the Rho-GTPase activity. May be involved in skeletal muscle and heart development as well as in the maintenance of heart function (By similarity). May also be involved in striated muscle regeneration and in the regulation of cell spreading.
Expressed during heart development in the proepicardial organ, migrating proepicardial strands, delaminated mesenchymal cells and vascular smooth muscle. Expressed in epithelial precursors of the cornea, lens and retina of the developing eye (at protein level). Expressed in the left ventricular segment of the tubular heart at stage 11. Expressed in the myotome, notochord and ventral half of the neuronal tube.
Expressed in the heart and skeletal muscle (at protein level). Isoform 1 and isoform 4: expressed in heart, muscle, brain, stomach, kidney, lung and spleen.
Homodimer. Homodimerization requires the C-terminus cytoplasmic region.
Belongs to the peptidase S9B family. DPPIV subfamily.
Belongs to the complex I NDUFA8 subunit family.
May be involved in microtubule polymerization, and spindle function by stabilizing microtubules and anchoring them at centrosomes.
The N-terminal domain may form a hydrophobic cleft involved in microtubule binding and the C-terminal may be involved in the formation of mutually exclusive complexes with APC and DCTN1.
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.
Catalyzes both phosphatidylcholine and phosphatidylethanolamine biosynthesis from CDP-choline and CDP-ethanolamine, respectively. Involved in protein-dependent process of phospholipid transport to distribute phosphatidyl choline to the lumenal surface. Has a higher cholinephosphotransferase activity than ethanolaminephosphotransferase activity.
Component of the CENPA-CAD complex, composed of CENPI, CENPK, CENPL, CENPO, CENPP, CENPQ, CENPR and CENPS. The CENPA-CAD complex is probably recruited on centromeres by the CENPA-NAC complex, at least composed of CENPA, CENPC, CENPH, CENPM, CENPN, CENPT and CENPU (By similarity). Identified in a centromeric complex containing histones H2A, H2B, H3 and H4, and at least CENPA, CENPB, CENPC, CENPT, CENPN, HJURP, SUPT16H, SSRP1 and RSF1 (By similarity). Interacts (via N-terminus) with the NDC80 complex (By similarity). Heterodimer with CENPW; this dimer coassembles with CENPS-CENPX heterodimers at centromeres to form the tetrameric CENP-T-W-S-X complex (PubMed:19070575, PubMed:21464230, PubMed:22304917).
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 (By similarity). The CENPA-NAC complex recruits the CENPA-CAD (nucleosome distal) complex and may be involved in incorporation of newly synthesized CENPA into centromeres (By similarity). Part of a nucleosome-associated complex that binds specifically to histone H3-containing nucleosomes at the centromere, as opposed to nucleosomes containing CENPA. Component of the heterotetrameric CENP-T-W-S-X complex that binds and supercoils DNA, and plays an important role in kinetochore assembly. CENPT has a fundamental role in kinetochore assembly and function. It is one of the inner kinetochore proteins, with most further proteins binding downstream. Required for normal chromosome organization and normal progress through mitosis.
The largest part of the sequence forms an elongated and flexible stalk structure that is connected to a C-terminal globular domain with a histone-type fold.
Belongs to the inorganic phosphate transporter (PiT) (TC 2.A.20) family.
Sodium-phosphate symporter which plays a fundamental housekeeping role in phosphate transport.
Heterodimer with SRP9; binds RNA as heterodimer. Component of a signal recognition particle (SRP) complex that consists of a 7SL RNA molecule of 300 nucleotides and six protein subunits: SRP72, SRP68, SRP54, SRP19, SRP14 and SRP9.
Component of a CRL2 E3 ubiquitin-protein ligase complex, also named ECS (Elongin BC-CUL2/5-SOCS-box protein) complex.
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. 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. The CRL2(FEM1B) complex specifically recognizes proteins ending with -Gly-Leu-Asp-Arg, leading to their ubiquitination and degradation.
Functions as a stress-inducible and DNA-binding transcription factor that plays a central role in the transcriptional activation of the heat shock response (HSR), leading to the expression of a large class of molecular chaperones heat shock proteins (HSPs) that protect cells from cellular insults' damage (PubMed:8455593). In unstressed cells, is present in a HSP90-containing multichaperone complex that maintains it in a non-DNA-binding inactivated monomeric form. Upon exposure to heat and other stress stimuli, undergoes homotrimerization and activates HSP gene transcription through binding to site-specific heat shock elements (HSEs) present in the promoter regions of HSP genes. Upon heat shock stress, forms a chromatin-associated complex with TTC5/STRAP and p300/EP300 to stimulate HSR transcription, therefore increasing cell survival (By similarity). Activation is reversible, and during the attenuation and recovery phase period of the HSR, returns to its unactivated form. Binds to inverted 5'-NGAAN-3' pentamer DNA sequences. Binds to chromatin at heat shock gene promoters. Also serves several other functions independently of its transcriptional activity. Involved in the repression of Ras-induced transcriptional activation of the c-fos gene in heat-stressed cells. Positively regulates pre-mRNA 3'-end processing and polyadenylation of HSP70 mRNA upon heat-stressed cells. Plays a role in nuclear export of stress-induced mRNA. Plays a role in the regulation of mitotic progression. Also plays a role as a negative regulator of non-homologous end joining (NHEJ) repair activity in a DNA damage-dependent manner. Involved in stress-induced cancer cell proliferation.
In unstressed cells, spontaneous homotrimerization is inhibited. Intramolecular interactions between the hydrophobic repeat HR-A/B and HR-C regions are necessary to maintain HSF1 in the inactive, monomeric conformation. In heat stressed cells, HSF1 homotrimerization occurs through formation of a three-stranded coiled-coil structure generated by intermolecular interactions between HR-A/B regions allowing DNA-binding activity. The D domain is necessary for translocation to the nucleus. 9aaTAD is a transactivation motif present in a large number of yeast and animal transcription factors.
Low expression found in most tissues with the exception of blood and liver. Highest levels are found in the pigmental layer of retina and in the lymphoblastoid cell line MSB-1.
Monomer; cytoplasmic latent and transcriptionally inactive monomeric form in unstressed cells. Homotrimer; in response to stress, such as heat shock, homotrimerizes and translocates into the nucleus, binds to heat shock element (HSE) sequences in promoter of heat shock protein (HSP) genes and acquires transcriptional ability.
Interacts with MPDZ. Interacts with ARRB2.
Belongs to the cytochrome c oxidase IV family.
Component of the cytochrome c oxidase (complex IV, CIV), a multisubunit enzyme composed of 14 subunits.
Component of the cytochrome c oxidase, the last enzyme in the mitochondrial electron transport chain which drives oxidative phosphorylation.
Belongs to the mitochondrion-specific ribosomal protein mS31 family.
Its expression is associated with the early G1 phase of the cell cycle.
Mediates the side-chain deamidation of N-terminal glutamine residues to glutamate, an important step in N-end rule pathway of protein degradation. Conversion of the resulting N-terminal glutamine to glutamate renders the protein susceptible to arginylation, polyubiquitination and degradation as specified by the N-end rule. Does not act on substrates with internal or C-terminal glutamine and does not act on non-glutamine residues in any position. Does not deaminate acetylated N-terminal glutamine. With the exception of proline, all tested second-position residues on substrate peptides do not greatly influence the activity. In contrast, a proline at position 2, virtually abolishes deamidation of N-terminal glutamine.
Receptor for endothelin-1. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of binding affinities for ET-A is: ET1 > ET2 >> ET3.
Co-chaperone required during spermatogenesis to repress transposable elements and prevent 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 govern the methylation and subsequent repression of transposons. Acts as a co-chaperone via its interaction with HSP90 and is required for the piRNA amplification process, the secondary piRNA biogenesis. May be required together with HSP90 in removal of 16 nucleotide ping-pong by-products from Piwi complexes, possibly facilitating turnover of Piwi complexes.
Activity detectable in embryos by day 14. Increases until 7 days post-hatching, then decreases again.
Belongs to the aspartate/ornithine carbamoyltransferase superfamily. OTCase family.
By diet of egg yolk in animals which have a high level of OTC activity due to presence of OCB gene.
Catalyzes the second step of the urea cycle, the condensation of carbamoyl phosphate with L-ornithine to form L-citrulline (PubMed:7332529). The urea cycle ensures the detoxification of ammonia by converting it to urea for excretion (Probable).
Cleavage of the precursor form to the active form occurs only in the kidney.
Expressed in kidney, brain, heart, liver, pancreas, gizzard, small intestine and breast muscle. More abundant in mitochondrion-rich organs (heart, liver and brain) than in other organs. Activity is only detected in the kidney.
Inhibition by ornithine increases at higher pH.
Ornithine transcarbamylase activity varies within and between different breeds of chicken.
At stage 8, detected in the cardiac crescent. At stage 10, expressed throughout the cardiac tube and the sinus venosus. By stage 15, expressed homogeneously in the various regions of the heart, including the atria, future left ventricle, bulbus cordis and truncus arteriosus, and in the forming branchial arches. Expression persists through stage 20, but decreases thereafter.
Transcription factor (By similarity). Plays an essential role in cardiac morphogenesis (PubMed:8533092).
Belongs to the shaker potassium channel beta subunit family.
Cytoplasmic potassium channel subunit that modulates the characteristics of the channel-forming alpha-subunits (By similarity). Modulates action potentials via its effect on the pore-forming alpha subunits (By similarity). Promotes expression of the pore-forming alpha subunits at the cell membrane, and thereby increases channel activity (By similarity). Mediates closure of delayed rectifier potassium channels by physically obstructing the pore via its N-terminal domain and increases the speed of channel closure for other family members (By similarity). Binds NADPH; this is required for efficient down-regulation of potassium channel activity (By similarity). Has NADPH-dependent aldoketoreductase activity (By similarity). Oxidation of the bound NADPH strongly decreases N-type inactivation of potassium channel activity (By similarity).
Homotetramer (By similarity). Interaction with tetrameric potassium channel alpha subunits gives rise to a heterooctamer (Probable).
In the inner ear, expression detected in the otocyst at embryonic day 3 and in the whole cochlea at E 6. Expressed throughout embryonic development and adulthood.
The N-terminal domain of the beta subunit mediates closure of delayed rectifier potassium channels by physically obstructing the pore.
Associated component of the MCM complex that acts as a regulator of DNA replication. Binds to the MCM complex during late S phase and promotes the disassembly of the MCM complex from chromatin, thereby acting as a key regulator of pre-replication complex (pre-RC) unloading from replicated DNA. Can dissociate the MCM complex without addition of ATP; probably acts by destabilizing interactions of each individual subunits of the MCM complex. Required for sister chromatid cohesion (By similarity).
Interacts with the MCM complex: associates with the MCM3-7 complex which lacks MCM2, while it does not interact with the MCM complex when MCM2 is present (MCM2-7 complex).
May antagonize Nodal signaling and subsequent organization of axial structures during mesodermal patterning.
Bifunctional glycosyltransferase with both alpha-1,3-xylosyltransferase and beta-1,3-glucuronyltransferase activities involved in the maturation of alpha-dystroglycan (DAG1) by glycosylation leading to DAG1 binding to laminin G-like domain-containing extracellular proteins with high affinity. Elongates the glucuronyl-beta-1,4-xylose-beta disaccharide primer structure initiated by B4GAT1 by adding repeating units [-3-Xylose-alpha-1,3-GlcA-beta-1-] to produce a heteropolysaccharide. Requires the phosphorylation of core M3 (O-mannosyl trisaccharide) by POMK to elongate the glucuronyl-beta-1,4-xylose-beta disaccharide primer (By similarity). Plays a key role in skeletal muscle function and regeneration (By similarity).
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. cAMP subfamily.
Part of the E2F6.com-1 complex in G0 phase composed of E2F6, MGA, MAX, TFDP1, CBX3, BAT8, EUHMTASE1, RING1, RNF2, MBLR, BAT8 and YAF2.
Putative Polycomb group (PcG) protein. PcG proteins maintain the transcriptionally repressive state of genes, probably via a modification of chromatin, rendering it heritably changed in its expressibility. Its association with a chromatin-remodeling complex suggests that it may contribute to prevent expression of genes that trigger the cell into mitosis. Binds to monomethylated and dimethylated 'Lys-20' on histone H4. Binds histone H3 peptides that are monomethylated or dimethylated on 'Lys-4', 'Lys-9' or 'Lys-27'.
Bifunctional iron sensor that switches between 2 activities depending on iron availability. Iron deprivation, promotes its mRNA binding activity through which it regulates the expression of genes involved in iron uptake, sequestration and utilization. Binds to iron-responsive elements (IRES) in the untranslated region of target mRNAs preventing for instance the translation of ferritin and aminolevulinic acid synthase and stabilizing the transferrin receptor mRNA.
Conversely, when cellular iron levels are high, binds a 4Fe-4S cluster which precludes RNA binding activity and promotes the aconitase activity, the isomerization of citrate to isocitrate via cis-aconitate.
Belongs to the ligand-gated ion channel (TC 1.A.9) family. Acetylcholine receptor (TC 1.A.9.1) subfamily. Alpha-9/CHRNA9 sub-subfamily.
Expressed in hair cells of the cochlea (at protein level). Expressed in hair cells of the cochlea.
Ionotropic receptor that may play a role in the modulation of auditory stimuli. Agonist binding induces a conformation change that leads to the 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.
Belongs to the TRAFAC class YlqF/YawG GTPase family. LSG1 subfamily.
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 (By similarity).
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.
Forms part of a macromolecular complex that catalyzes the attachment of specific amino acids to cognate tRNAs during protein synthesis.
Monomer; also part of a multisubunit complex that groups tRNA ligases for Arg, Asp, Glu, Gln, Ile, Leu, Lys, Met and Pro.
The alpha-helical N-terminus (residues 1-72) mediates interaction with AIMP1 and thereby contributes to the assembly of the multisynthetase complex.
Belongs to the type II cytokine receptor family.
Together with IFNAR2, forms the heterodimeric receptor for type I interferons (including interferons alpha, beta, epsilon, omega and kappa). Type I interferon binding activates the JAK-STAT signaling cascade. Can also act independently of IFNAR2: form an active IFNB1 receptor by itself and activate a signaling cascade that does not involve activation of the JAK-STAT pathway.
Dominant regulator of apoptotic cell death. The long form displays cell death repressor activity, whereas the short isoform promotes apoptosis. Also acts as a regulator of G2 checkpoint and progression to cytokinesis during mitosis (By similarity).
Highest expression in organs with lymphoid development.
The BH4 motif seems to be involved in the anti-apoptotic function. Intact BH1 and BH2 motifs are required for anti-apoptotic activity (By similarity).
Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A15 subfamily.
Catalyzes the ferrous insertion into protoporphyrin IX.
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.
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).
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. E-cadherin is a ligand for integrin alpha-E/beta-7.
Cytochrome b5 is a membrane-bound hemoprotein functioning as an electron carrier for several membrane-bound oxygenases.
Belongs to the connexin family. Gamma-type subfamily.
This is the major myelin protein from the central nervous system. It plays an important role in the formation or maintenance of the multilamellar structure of myelin.
3'-5' DNA helicase and substrate-recognition component of the SCF(FBH1) E3 ubiquitin ligase complex that plays a key role in response to stalled/damaged replication forks (By similarity). Involved in genome maintenance by acting as an anti-recombinogenic helicase and preventing extensive strand exchange during homologous recombination: promotes RAD51 filament dissolution from stalled forks, thereby inhibiting homologous recombination and preventing excessive recombination (PubMed:17283053). Also promotes cell death and DNA double-strand breakage in response to replication stress: promotes the endonucleolytic DNA cleavage following prolonged replication stress via its helicase activity, possibly to eliminate cells with excessive replication stress.
Belongs to the helicase family. UvrD subfamily.
Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBH1) (By similarity).
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. Activation by Wnt5A stimulates PKC activity via a G-protein-dependent mechanism. Involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues. Together with FZD3, may be 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).
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).
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. 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.
Component of the ribosomal small subunit processome for the biogenesis of ribosomes, functions in pre-ribosomal RNA (pre-rRNA) processing (By similarity). Essential for embryonic development in part through the regulation of p53 pathway. Controls the expansion growth of digestive organs and liver (By similarity). Also involved in the sympathetic neuronal development (By similarity). Mediates, with CAPN3, the proteasome-independent degradation of p53/TP53 (By similarity).
Interacts with CAPN3; the interaction is required for CAPN3 translocation to the nucleolus.
Phosphorylated. Phosphorylation is required to promote p53/TP53 degradation in the nucleolus which promotes cell cycle progression and liver development.
Belongs to the NUP186/NUP192/NUP205 family.
Interacts with DDX4, PIWIL1, RANBP9 and TDRD1.
Associates with NXF1, NXF2, NXF3 and NXF5.
Regulator of protein export for NES-containing proteins. Also plays a role in mRNA nuclear export (By similarity).
Mediates the voltage-dependent proton permeability of excitable membranes. Forms a proton-selective channel through which protons may pass in accordance with their electrochemical gradient (By similarity).
The C-terminal coiled coil region mediates homodimerization. It is essential for normal subcellular localization (By similarity).
The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Unlike other voltage-gated ion channels it lacks the pore domain (By similarity).
Adapter protein required for Golgi and endoplasmic reticulum biogenesis. Involved in Golgi and endoplasmic reticulum maintenance during interphase and in their reassembly at the end of mitosis. Regulates the centrosomal levels of kinase AURKA/Aurora A during mitotic progression by promoting AURKA removal from centrosomes in prophase. Also, regulates spindle orientation during mitosis.
Key decatenating enzyme that alters DNA topology by binding to two double-stranded DNA molecules, generating a double-stranded break in one of the strands, passing the intact strand through the broken strand, and religating the broken strand (By similarity). May play a role in the regulation of circadian rhythm (By similarity).
Catalyzes the final step of the nicotinamide adenine dinucleotide (NAD) de novo synthesis pathway, the ATP-dependent amidation of deamido-NAD using L-glutamine as a nitrogen source.
In the C-terminal section; belongs to the NAD synthetase family.
Belongs to the protease inhibitor I47 (latexin) family.
Component of the matrix of the eggshell.
Expressed at high levels in the uterine and isthmus regions of the oviduct, and concentrated in the eggshell.
Belongs to the protein kinase superfamily. Tyr protein kinase family. FAK subfamily.
Interacts with ARHGAP26, GRB7, DCC, PIK3R1, PXN and SRC. Interacts with the ARP2/3 complex.
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, 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), ephrin receptors, 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. Regulates P53/TP53 activity and stability. Phosphorylates SRC; this increases SRC kinase activity. Isoform 2 (FRNK) does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling.
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. Isoform 2 is phosphorylated on serine or threonine residues, but apparently not on tyrosine residues.
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 TAE226.
The C-terminal region is the site of focal adhesion targeting (FAT) sequence which mediates the localization of FAK1 to focal adhesions.
RNA-binding component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is involved in protein synthesis of a specialized repertoire of mRNAs and, together with other initiation factors, stimulates binding of mRNA and methionyl-tRNAi to the 40S ribosome. The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation.
RNA-binding protein that inhibits processing of pre-let-7 miRNAs and regulates translation of mRNAs that control developmental timing, pluripotency and metabolism. Seems to recognize a common structural G-quartet (G4) feature in its miRNA and mRNA targets (By similarity). 'Translational enhancer' that drives specific mRNAs to polysomes and increases the efficiency of protein synthesis. Its association with the translational machinery and target mRNAs results in an increased number of initiation events per molecule of mRNA and, indirectly, in mRNA stabilization. Suppressor of microRNA (miRNA) biogenesis, including that of let-7. Binds specific target miRNA precursors (pre-miRNAs), recognizing an 5'-GGAG-3' motif found in their terminal loop, and recruits uridylyltransferase. This results in the terminal uridylation of target pre-miRNAs. Uridylated pre-miRNAs fail to be processed by Dicer and undergo degradation (By similarity). Localized to the periendoplasmic reticulum area, binds to a large number of spliced mRNAs and inhibits the translation of mRNAs destined for the ER, reducing the synthesis of transmembrane proteins, ER or Golgi lumen proteins, and secretory proteins. Binds to and enhances the translation of mRNAs for several metabolic enzymes, increasing glycolysis and oxidative phosphorylation. Which, with the let-7 repression may enhance tissue repair in adult tissue (By similarity).
The CCHC zinc fingers interact with the GGAG motif at the 3' end of let-7 miRNAs precursors, more generally they bind the 5'-NGNNG-3' consensus motif with micromolar affinity. The CSD domain recognizes the loop at the 5' end. The flexible linker allows accommodating variable sequences and lengths among let-7 family members (By similarity).
Belongs to the cyclin-dependent kinase 5 activator family.
Belongs to the eukaryotic ribosomal protein eS8 family. Ribosome biogenesis protein NSA2 subfamily.
Component of the pre-66S ribosomal particle.
Involved in the biogenesis of the 60S ribosomal subunit. May play a part in the quality control of pre-60S particles.
Functions as an U snRNP-specific nuclear import adapter. Involved in the trimethylguanosine (m3G)-cap-dependent nuclear import of U snRNPs. Binds specifically to the terminal m3G-cap U snRNAs.
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) (By similarity). Innate immune response is triggered in response to non-CpG double-stranded DNA from viruses and bacteria delivered to the cytoplasm (By similarity). 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:30842659). Upon binding of c-di-GMP or cGAMP, STING1 oligomerizes and is able to activate both NF-kappa-B and IRF3 transcription pathways to induce expression of type I interferon and exert a potent anti-viral state (PubMed:30842659). In addition to promote the production of type I interferons, plays a direct role in autophagy (By similarity). Following cGAMP-binding, STING1 buds from the endoplasmic reticulum into COPII vesicles, which then form the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) (By similarity). The ERGIC serves as the membrane source for LC3 lipidation, leading to formation of autophagosomes that target cytosolic DNA or DNA viruses for degradation by the lysosome (By similarity). The autophagy- and interferon-inducing activities can be uncoupled and autophagy induction is independent of TBK1 phosphorylation (By similarity). Exhibits 2',3' phosphodiester linkage-specific ligand recognition: can bind both 2'-3' linked cGAMP and 3'-3' linked cGAMP but is preferentially activated by 2'-3' linked cGAMP (By similarity).
Homodimer; forms a homodimer in absence of cyclic nucleotide (c-di-GMP or cGAMP) (PubMed:30842659). Homotetramer; in presence of cyclic nucleotide (c-di-GMP or cGAMP), forms tetramers and higher-order oligomers through side-by-side packing (PubMed:30842659). Interacts (when phosphorylated) with IRF3; following activation and phosphorylation on the pLxIS motif by TBK1, recruits IRF3 (By similarity).
In absence of cGAMP, the transmembrane and cytoplasmic regions interact to form an integrated, domain-swapped dimeric assembly (PubMed:30842659). 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) (By similarity). 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 (PubMed:30842659). 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 (PubMed:30842659). 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 (By similarity).
Phosphorylation by TBK1 leads to activation and production of IFN-beta (Probable). 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 (Probable). 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 (Probable).
The N-terminal domain interacts with glycerophospholipids and phospholipids.
The pLxIS motif constitutes an IRF3-binding motif: following phosphorylation by TBK1, the phosphorylated pLxIS motif of STING1 recruits IRF3. IRF3 is then phosphorylated and activated by TBK1 to induce type-I interferons and other cytokines.
Activity is regulated by phosphorylation at Ser-49 and Ser-52, which stabilizes the eIF-2/GDP/eIF-2B complex and prevents the eIF-2B-mediated exchange of GDP for GTP, thereby preventing the formation of the 43S pre-initiation complex (PIC). This results in the global attenuation of 5' cap-dependent protein synthesis and concomitant translation of ISR-specific mRNAs that contain a short upstream open reading frame (uORF) in their 5' UTR.
Functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA. This complex binds to a 40S ribosomal subunit, followed by mRNA binding to form a 43S pre-initiation complex. Junction of the 60S ribosomal subunit to form the 80S initiation complex is preceded by hydrolysis of the GTP bound to eIF-2 and release of an eIF-2-GDP binary complex. In order for eIF-2 to recycle and catalyze another round of initiation, the GDP bound to eIF-2 must exchange with GTP by way of a reaction catalyzed by eIF-2B. EIF2S1/eIF-2-alpha is a key component of the integrated stress response (ISR), required for adaptation to various stress: phosphorylation by metabolic-stress sensing protein kinases in response to stress converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, leading to a attenuation of cap-dependent translation, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activators ATF4 and QRICH1.
Heterotrimer composed of an alpha, a beta and a gamma chain.
Phosphorylation at Ser-49 and Ser-52 stabilizes the eIF-2/GDP/eIF-2B complex and prevents GDP/GTP exchange reaction, thus impairing the recycling of eIF-2 between successive rounds of initiation and leading to global inhibition of translation, while concomitantly initiating the preferential translation of integrated stress response (ISR)-specific mRNAs.
Catalyzes the ATP-dependent amination of UTP to CTP with either L-glutamine or ammonia as the source of nitrogen.
Involved in the initiation of DNA replication. Also participates in checkpoint controls that ensure DNA replication is completed before mitosis is initiated.
Acts as an inhibitor of the small GTPase RHOA and plays several roles in the regulation of myoblast and hair cell differentiation, lymphocyte T proliferation and neutrophil polarization. Plays a role in fetal mononuclear myoblast differentiation by promoting filopodia and myotube formation. Maintains naive T lymphocytes in a quiescent state and prevents chemokine-induced T lymphocyte responses, such as cell adhesion, polarization and migration. Involved also in the regulation of neutrophil polarization, chemotaxis and adhesion. Required for normal development of inner and outer hair cell stereocilia within the cochlea of the inner ear. Plays a role for maintaining the structural organization of the basal domain of stereocilia. Involved in mechanosensory hair cell function. Required for normal hearing.
Homooligomer; homooligomerization is regulated by RHOC and leads to the formation of concatemers through the association of N- and C-termini. Interacts with NCAM.
Expressed in inner ear structures; the spindle-shaped cells of the basilar papilla. Weaker expression found in the inferior and superior fibrocartilaginous plates and skeletal muscle.
Plays a role in the control of cell shape and motility in the trabecular meshwork.
Homohexamer (via C-terminus) which assembled in a ring-like structure. Homoheptamer which assembled in a ring-like structure. Oligomerization is Mg(2+), nucleotide and DNA-independent, however, Mg(2+) and nucleotide stabilize the homohexameric form.
Mitochondrial helicase involved in mtDNA replication and repair. Might have a role in mtDNA repair. 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. Preferentially unwinds DNA substrates with pre-existing 5'-and 3'- single-stranded tails but is also active on a 5'- flap substrate. Can dissociate the invading strand of immobile or mobile D-loop DNA structures irrespective of the single strand polarity of the third strand. In addition to its DNA strand separation activity, also has DNA strand annealing, DNA strand-exchange and DNA branch migration activities.
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.
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.
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.
Ionotropic receptor with a probable role in the modulation of auditory stimuli.
Generates hydrogen peroxide which is required for the activity of thyroid peroxidase/TPO and lactoperoxidase/LPO. Plays a role in thyroid hormones synthesis and lactoperoxidase-mediated antimicrobial defense at the surface of mucosa. May have its own peroxidase activity through its N-terminal peroxidase-like domain.
In the N-terminal section; belongs to the peroxidase family.
May act as a nuclear transcription factor that negatively regulates the expression of cardiac genes.
Expressed in the developing wing bud. At stage 31, widely expressed with a higher level in limb and head.
Activated by phosphorylation at Ser-350, Thr-571 and Thr-690 by MAP kinases, and by further autophosphorylation of Ser-202, Ser-366 and Ser-371 by the activated C-terminal kinase domain. The active N-terminal kinase domain finally phosphorylates downstream substrates, as well as Ser-740, Ser-742 and Ser-748 in its own C-terminal region (By similarity).
Enzyme activity requires the presence of both kinase domains.
Ser-366 and Thr-571 phosphorylation is required for kinase activity. Ser-366 and Ser-202 are autophosphorylated by the C-terminal kinase domain, and their phosphorylation is essential for the catalytic activity of the N-terminal kinase domain. Phosphorylated at Ser-350, Thr-571 and Thr-690 by MAP kinases. Autophosphorylated at Ser-740, Ser-742 and Ser-748 by the N-terminal kinase domain.
Serine/threonine-protein kinase that is required for the mitogen or stress-induced phosphorylation of the transcription factors CREB1 and ATF1 and that contributes to gene activation by histone phosphorylation. Phosphorylates CREB1 and ATF1 in response to mitogenic or stress stimuli such as UV-C irradiation, epidermal growth factor (EGF) and anisomycin. Directly represses transcription via phosphorylation of 'Ser-1' of histone H2A. Phosphorylates 'Ser-10' of histone H3 in response to mitogenics, stress stimuli and EGF, which results in the transcriptional activation of several immediate early genes, including proto-oncogenes c-fos/FOS and c-jun/JUN. May also phosphorylate 'Ser-28' of histone H3. Mediates the mitogen- and stress-induced phosphorylation of high mobility group protein 1 (HMGN1/HMG14) (By similarity).
Widely expressed with high levels in heart, brain and placenta. Less abundant in lung, kidney and liver.
For the sake of clarity sequence features are annotated only for the first chain, and are not repeated for each of the following chains.
Belongs to the DHHC palmitoyltransferase family. ERF2/ZDHHC9 subfamily.
Binds to the receptor tyrosine kinase EPHB2. Interacts with GRIP1 and GRIP2 (By similarity).
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 (By similarity).
Inducible phosphorylation of tyrosine residues in the cytoplasmic domain.
Belongs to the flagellar radial spoke RSP3 family.