Belongs to the snRNP Sm proteins 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. Component of both the pre-catalytic spliceosome B complex and activated spliceosome C complexes. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs. As part of the U7 snRNP it is involved in histone 3'-end processing.
Belongs to the anion exchanger (TC 2.A.31) family.
Sodium-independent anion exchanger which mediates the electroneutral exchange of chloride for bicarbonate ions across the cell membrane. May be involved in the regulation of intracellular pH, and the modulation of cardiac action potential.
Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family.
Belongs to the HAD-like hydrolase superfamily. MasA/MtnC family.
Bifunctional enzyme that catalyzes the enolization of 2,3-diketo-5-methylthiopentyl-1-phosphate (DK-MTP-1-P) into the intermediate 2-hydroxy-3-keto-5-methylthiopentenyl-1-phosphate (HK-MTPenyl-1-P), which is then dephosphorylated to form the acireductone 1,2-dihydroxy-3-keto-5-methylthiopentene (DHK-MTPene).
Deubiquitinating enzyme that removes conjugated ubiquitin from specific proteins to regulate different cellular processes.
Protects actin filaments from depolymerization.
Belongs to the immunoglobulin superfamily. LISCH7 family.
Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. EF-Tu/EF-1A subfamily.
Brain, placenta, lung, liver, kidney, pancreas but barely detectable in heart and skeletal muscle.
Found in a nuclear export complex with XPO5, EEF1A1, Ran and aminoacylated tRNA. Interacts with PARP1 and TXK. Interacts with KARS1. May interact with ERGIC2. Interacts with IFIT1 (via TPR repeats 4-7) (By similarity). May interact with ERGIC2. Interacts with IFIT1 (via TPR repeats 4-7) (By similarity). Interacts with DLC1, facilitating distribution to the membrane periphery and ruffles upon growth factor stimulation. Interacts with ZPR1; the interaction occurs in a epidermal growth factor (EGF)-dependent manner (By similarity). Interacts with PPP1R16B (By similarity). Interacts with SPHK1 and SPHK2; both interactions increase SPHK1 and SPHK2 kinase activity (By similarity).
Phosphorylated by TXK. Phosphorylation by PASK increases translation efficiency. Phosphorylated by ROCK2. Phosphorylation by TGFBR1 inhibits translation elongation.
Specifically inhibited by didemnin B, a natural product that triggers ribosome stalling by preventing aminoacyl-tRNA (aa-tRNA) release from EEF1A1 on the ribosome.
This protein promotes the GTP-dependent binding of aminoacyl-tRNA to the A-site of ribosomes during protein biosynthesis.
Translation elongation factor that catalyzes the GTP-dependent binding of aminoacyl-tRNA (aa-tRNA) to the A-site of ribosomes during the elongation phase of protein synthesis (PubMed:22017870, PubMed:27863242). Base pairing between the mRNA codon and the aa-tRNA anticodon promotes GTP hydrolysis, releasing the aa-tRNA from EEF1A1 and allowing its accommodation into the ribosome (PubMed:22017870, PubMed:27863242). The growing protein chain is subsequently transferred from the P-site peptidyl tRNA to the A-site aa-tRNA, extending it by one amino acid through ribosome-catalyzed peptide bond formation (PubMed:27863242). Also plays a role in the positive regulation of IFNG transcription in T-helper 1 cells as part of an IFNG promoter-binding complex with TXK and PARP1 (By similarity).
Trimethylated at Lys-79 by EEF1AKMT1. Methylated at Lys-165 by EEF1AKMT3, methylation by EEF1AKMT3 is dynamic as well as inducible by stress conditions, such as ER-stress, and plays a regulatory role on mRNA translation. Trimethylated at Lys-318 by EEF1AKMT2. Mono-, di-, and trimethylated at Lys-36 by EEF1AKMT4; trimethylated form is predominant. Methylation by EEF1AKMT4 contributes to the fine-tuning of translation rates for a subset of tRNAs. Trimethylated at Gly-2 by METTL13. Mono- and dimethylated at Lys-55 by METTL13; dimethylated form is predominant.
Ubiquitinated at Lys-385 by RNF14 in response to ribosome collisions (ribosome stalling), leading to its degradation by the proteasome and rescue of stalled ribosomes.
Belongs to the UDP-glycosyltransferase family.
Belongs to the cation diffusion facilitator (CDF) transporter (TC 2.A.4) family. SLC30A subfamily.
Belongs to the G-protein coupled receptor 1 family.
Belongs to the Cu-Zn superoxide dismutase family.
Destroys radicals which are normally produced within the cells and which are toxic to biological systems.
Homodimer; non-disulfide-linked (By similarity). Heterodimer with SOD1. The heterodimer CCS:SOD1 interacts with SLC31A1; this heterotrimer is Cu(1+)-mediated and its maintenance is regulated through SOD1 activation (By similarity).
Palmitoylation helps nuclear targeting and decreases catalytic activity.
Succinylation, adjacent to copper catalytic site, probably inhibits activity. Desuccinylation by SIRT5 enhances activity.
Belongs to the enoyl-CoA hydratase/isomerase family.
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 heparin-binding growth factors family.
Belongs to the SLC13A/DASS transporter (TC 2.A.47) family. NADC subfamily.
Belongs to the fatty acid desaturase type 1 family.
The histidine box domains are involved in binding the catalytic metal ions.
Belongs to the C/M/P thioester hydrolase family.
Belongs to the multi antimicrobial extrusion (MATE) (TC 2.A.66.1) family.
Mediates the efflux of cationic compounds such as the model cations, tetraethylammonium (TEA), the neurotoxin 1-methyl-4-phenylpyridinium (MPP), the platinum-based drugs cisplatin and oxaliplatin, the drugs procainamide, acyclovir and topotecan, or weak bases that are positively charged at physiological pH, such as cimetidine or the antidiabetic drug metformin.
Multidrug efflux pump that functions as a H(+)/organic cation antiporter (PubMed:17442726). Plays a physiological role in the excretion of cationic compounds including endogenous metabolites, drugs, toxins through the kidney and liver, into urine and bile respectively. Mediates the efflux of endogenous compounds such as creatinine, vitamin B1/thiamine, agmatine and estrone-3-sulfate. May also contribute to regulate the transport of cationic compounds in testis across the blood-testis-barrier (By similarity).
Predominantly expressed in kidney and liver.
Belongs to the activator 1 small subunits family.
Antiparallel disulfide-linked heterodimer of an alpha chain and a beta chain. Self-associates and forms higher oligomers. Interacts with a broad range of misfolded proteins, including APP, APOC2 and LYZ. Slightly acidic pH promotes interaction with misfolded proteins. Forms high-molecular weight oligomers upon interaction with misfolded proteins. Interacts with APOA1, LRP2, CLUAP1 and PON1. Interacts with the complement complex. Interacts (via alpha chain) with XRCC6. Interacts with SYVN1, COMMD1, BTRC, CUL1 and with ubiquitin and SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes. Interacts (via alpha chain) with BAX in stressed cells, where BAX undergoes a conformation change leading to association with the mitochondrial membrane. Does not interact with BAX in unstressed cells. Found in a complex with LTF, CLU, EPPIN and SEMG1. Interacts (immaturely glycosylated pre-secreted form) with HSPA5; this interaction promotes CLU stability and facilitates stress-induced CLU retrotranslocation from the secretory pathway to the mitochondria, thereby reducing stress-induced apoptosis by stabilizing mitochondrial membrane integrity. Interacts with BCL2L1; this interaction releases and activates BAX and promotes cell death. Interacts with TGFBR2 and ACVR1 (By similarity). Interacts (secreted form) with STMN3; this interaction may act as an important modulator during neuronal differentiation (By similarity). Interacts with VLDLR and LRP8 (By similarity).
Functions as extracellular chaperone that prevents aggregation of non native proteins. Prevents stress-induced aggregation of blood plasma proteins. Inhibits formation of amyloid fibrils by APP, APOC2, B2M, CALCA, CSN3, SNCA and aggregation-prone LYZ variants (in vitro). Does not require ATP. Maintains partially unfolded proteins in a state appropriate for subsequent refolding by other chaperones, such as HSPA8/HSC70. Does not refold proteins by itself. Binding to cell surface receptors triggers internalization of the chaperone-client complex and subsequent lysosomal or proteasomal degradation. When secreted, protects cells against apoptosis and against cytolysis by complement. Intracellular forms interact with ubiquitin and SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes and promote the ubiquitination and subsequent proteasomal degradation of target proteins. Promotes proteasomal degradation of COMMD1 and IKBKB. Modulates NF-kappa-B transcriptional activity (By similarity). Following stress, promotes apoptosis (By similarity). Inhibits apoptosis when associated with the mitochondrial membrane by interference with BAX-dependent release of cytochrome c into the cytoplasm. Plays a role in the regulation of cell proliferation. An intracellular form suppresses stress-induced apoptosis by stabilizing mitochondrial membrane integrity through interaction with HSPA5. Secreted form does not affect caspase or BAX-mediated intrinsic apoptosis and TNF-induced NF-kappa-B-activity (By similarity). Secreted form act as an important modulator during neuronal differentiation through interaction with STMN3 (By similarity). Plays a role in the clearance of immune complexes that arise during cell injury (By similarity).
Heavily N-glycosylated. About 30% of the protein mass is comprised of complex N-linked carbohydrate. Endoplasmic reticulum (ER) stress induces changes in glycosylation status and increases level of hypoglycosylated forms. Core carbohydrates are essential for chaperone activity. Non-secreted forms are hypoglycosylated or unglycosylated.
Polyubiquitinated, leading to proteasomal degradation. Under cellular stress, the intracellular level of cleaved form is reduced due to proteasomal degradation.
Proteolytically cleaved on its way through the secretory system, probably within the Golgi lumen. Proteolytic cleavage is not necessary for its chaperone activity. All non-secreted forms are not proteolytically cleaved. Chaperone activity of uncleaved forms is dependent on a non-reducing envoronment.
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 dynactin subunit 4 family.
Lacks conserved residue(s) required for the propagation of feature annotation.
Belongs to the helicase family. RLR subfamily.
Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily.
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.
Belongs to the LDH/MDH superfamily. MDH type 2 family.
Belongs to the eukaryotic ribosomal protein eL21 family.
Belongs to the sulfotransferase 1 family.
Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the N-sulfonation of amines (PTHP, aniline, 4-chloroaniline, 2-naphthylamine).
Belongs to the GST superfamily. Omega family.
Exhibits glutathione-dependent thiol transferase activity. Has high dehydroascorbate reductase activity and may contribute to the recycling of ascorbic acid. Participates in the biotransformation of inorganic arsenic and reduces monomethylarsonic acid (MMA).
Belongs to the protein kinase superfamily.
Belongs to the PA-phosphatase related phosphoesterase family.
Belongs to the metallophosphoesterase superfamily. Purple acid phosphatase family.
Belongs to the flavoprotein pyridine nucleotide cytochrome reductase family.
Belongs to the DEAD box helicase family. DDX18/HAS1 subfamily.
The Q motif is unique to and characteristic of the DEAD box family of RNA helicases and controls ATP binding and hydrolysis.
Belongs to the glycosyltransferase 31 family.
Belongs to the glycosyltransferase 29 family.
Belongs to the polyadenylate-binding protein type-1 family.
Belongs to the bZIP family. CNC subfamily.
Belongs to the steroid 5-alpha reductase family.
Converts testosterone into 5-alpha-dihydrotestosterone and progesterone or corticosterone into their corresponding 5-alpha-3-oxosteroids. It plays a central role in sexual differentiation and androgen physiology.
Microtubule-binding protein that localizes to the microtubular manchette of elongating spermatids.
Mediator of sterol homeostasis involved in sterol uptake, trafficking and distribution into membranes.
By phenobarbital in each tissue with the exception of the kidney.
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.
Expressed constitutively in liver, lung, testes, and kidney.
Belongs to the glycosyltransferase 61 family.
Belongs to the intermediate filament family.
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) (By similarity).
The glycine cleavage system is composed of four proteins: P (GLDC), T (GCST), L (DLD) and H (GCSH). Interacts with GLDC (By similarity).
In the C-terminal section; belongs to the gamma-glutamyl phosphate reductase family.
In the N-terminal section; belongs to the glutamate 5-kinase family.
Component of the MIS12 complex composed of MIS12, DSN1, NSL1 and PMF1. Also interacts with KNL1, CBX3, CBX5, NDC80 and ZWINT.
Belongs to the alpha/beta interferon family.
May act as a specific coactivator for the mammalian TEFs.
Belongs to the ATPase gamma chain family.
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. 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.
Belongs to the bZIP family. C/EBP subfamily.
Belongs to the eukaryotic ribosomal protein eS10 family.
Belongs to the proteasome subunit S9 family.
Belongs to the class I fructose-bisphosphate aldolase family.
Catalyzes the aldol cleavage of fructose 1,6-biphosphate to form two triosephosphates dihydroxyacetone phosphate and D-glyceraldehyde 3-phosphate in glycolysis as well as the reverse stereospecific aldol addition reaction in gluconeogenesis. In fructolysis, metabolizes fructose 1-phosphate derived from the phosphorylation of dietary fructose by fructokinase into dihydroxyacetone phosphate and D-glyceraldehyde (By similarity). Acts as an adapter independently of its enzymatic activity, exerts a tumor suppressor role by stabilizing the ternary complex with G6PD and TP53 to inhibit G6PD activity and keep oxidative pentose phosphate metabolism in check (By similarity).
Homotetramer. Interacts with BBS1, BBS2, BBS4 and BBS7. Forms a ternary complex with G6PD and TP53; this interaction is direct.
In vertebrates, 3 forms of this ubiquitous glycolytic enzyme are found, aldolase A in muscle, aldolase B in liver and aldolase C in brain.
Belongs to the PPase class C family. Prune subfamily.
Auxillary component of the N-terminal acetyltransferase C (NatC) complex which catalyzes acetylation of N-terminal methionine residues. Involved in regulation of apoptosis and proliferation of smooth muscle cells.
Component of the N-terminal acetyltransferase C (NatC) complex, which is composed of NAA35, NAA38 and NAA30.
Belongs to the ATP-dependent AMP-binding enzyme family.
Interacts with CCND1 and GRAP2. May also interact with COPS5, RPLP0, SIRT6, SYF2 and TCF3.
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. S6 kinase subfamily.
Belongs to the major facilitator superfamily. Proton-dependent oligopeptide transporter (POT/PTR) (TC 2.A.17) family.
Interacts (via extracellular domain region) with trypsin.
Proton-coupled amino-acid transporter that transports oligopeptides of 2 to 4 amino acids with a preference for dipeptides (PubMed:8552623). Transports neutral and anionic dipeptides with a proton to peptide stoichiometry of 2:1 or 3:1 (By similarity). In kidney, involved in the absorption of circulating di- and tripeptides from the glomerular filtrate. Can also transport beta-lactam antibiotics, such as the aminocephalosporin cefadroxil, and other antiviral and anticancer drugs (PubMed:8552623). Transports the dipeptide-like aminopeptidase inhibitor bestatin (By similarity). Also able to transport carnosine (By similarity). Involved in innate immunity by promoting the detection of microbial pathogens by NOD-like receptors (NLRs) (By similarity). Mediates transport of bacterial peptidoglycans across the plasma membrane or, in macrophages, the phagosome membrane: catalyzes the transport of certain bacterial peptidoglycans, such as muramyl dipeptide (MDP), the NOD2 ligand (By similarity).
Strongly expressed in kidney. Also detected in brain, lung, liver and heart.
The extracellular domain (ECD) region specifically binds trypsin.
Belongs to the universal ribosomal protein uL6 family.
Component of the large ribosomal subunit.
Belongs to the protein kinase superfamily. CK1 Ser/Thr protein kinase family. Casein kinase I subfamily.
Belongs to the ligand-gated ion channel (TC 1.A.9) family.
Belongs to the eukaryotic ribosomal protein eL32 family.
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 nuclear hormone receptor family. NR4 subfamily.
Interacts with SFPQ, NCOR2, SIN3A and HADC1. The interaction with NCOR2 increases in the absence of PITX3. Interacts with PER2.
Belongs to the neutral ceramidase family.
May be involved in cell cycle regulation.
F-type ATPases have 2 components, CF(1) - the catalytic core - and CF(0) - the membrane proton channel. Component of an ATP synthase complex composed of ATP5PB, ATP5MC1, ATP5F1E, ATP5PD, ATP5ME, ATP5PF, ATP5MF, MT-ATP6, MT-ATP8, ATP5F1A, ATP5F1B, ATP5F1D, ATP5F1C, ATP5PO, ATP5MG, ATP5MK and ATP5MJ (By similarity). Interacts with PRICKLE3 (By similarity).
Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Part of the complex F(0) domain. Minor subunit located with subunit a in the membrane (By similarity).
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.
Cell-surface glycoprotein having a role in immunoadhesion. Mediates in the adhesion of blood neutrophils in cytokine-activated endothelium through interaction with SELPLG/PSGL1. May have a role in capillary morphogenesis.
Interacts with SELPLG/PSGL1 and PODXL2 through the sialyl Lewis X epitope. SELPLG sulfation appears not to be required for this interaction.
Catalyzes the formation of aromatic C18 estrogens from C19 androgens.
Belongs to the MIP/aquaporin (TC 1.A.8) family.
Belongs to the prenylcysteine oxidase family.
Belongs to the type-B carboxylesterase/lipase family.
Belongs to the archaeal Rpo12/eukaryotic RPC10 RNA polymerase subunit family.
Belongs to the calycin superfamily. Lipocalin family.
Contains a beta-barrel that binds various ligands in its interior.
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain (By similarity). Appears to function in modulating the activity of the immune system during the acute-phase reaction.
Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily.
May be a centrosome-associated protein. Interacts with MYOC; affects its secretion and its aggregation.
Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. Septin GTPase family.
Septins polymerize into heterooligomeric protein complexes that form filaments.
May be involved in transcriptional regulation.
Belongs to the chaperonin (HSP60) family.
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins.
Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRA2B sub-subfamily.
LSm subunits form a heteromer with a doughnut shape.
Plays a role in U6 snRNP assembly and function. Binds to the 3' end of U6 snRNA.
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.
Belongs to the class I-like SAM-binding methyltransferase superfamily. RsmB/NOP family.
Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.
Belongs to the AB hydrolase superfamily. Lipase family.
Belongs to the two pore domain potassium channel (TC 1.A.1.8) family.
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 (By similarity). Interacts (via N-terminus) with LMOD2 (via N-terminus) and TMOD1 (via N-terminus) (By similarity).
Phosphorylated at Ser-283 by DAPK1 in response to oxidative stress and this phosphorylation enhances stress fiber formation in endothelial cells.
The molecule is in a coiled coil structure that is formed by 2 polypeptide chains. The sequence exhibits a prominent seven-residues periodicity.
Belongs to the glycosyl hydrolase 22 family.
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.
Has a role in nuclear-cytoplasmic transport of proteins and mRNAs.
RNA-binding protein involved in pre-mRNA splicing.
Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ5 subfamily.
Belongs to the purine/pyrimidine phosphoribosyltransferase family.
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.
Belongs to the glutathione peroxidase family.
Cargo receptor involved in protein vesicular trafficking and quality control in the endoplasmic reticulum (ER) and Golgi. The p24 protein family is a group of transmembrane proteins that bind coat protein complex I/COPI and coat protein complex II/COPII involved in vesicular trafficking between the membranes (By similarity). Acts at the lumenal side for incorporation of secretory cargo molecules into transport vesicles and involved in vesicle coat formation at the cytoplasmic side. Mainly functions in the early secretory pathway and cycles between the ER, ER-Golgi intermediate compartment (ERGIC) and Golgi, mediating cargo transport through COPI and COPII-coated vesicles (PubMed:9990005, PubMed:9813083). In COPII vesicle-mediated anterograde transport, involved in the transport of GPI-anchored proteins by acting together with TMED2 as their cargo receptor; the function specifically implies SEC24C and SEC24D of the COPII vesicle coat and lipid raft-like microdomains of the ER (By similarity). Recognizes GPI anchors structural remodeled in the ER by the GPI inositol-deacylase/PGAP1 and the metallophosphoesterase MPPE1/PGAP5 (By similarity). In COPI vesicle-mediated retrograde transport, involved in the biogenesis of COPI vesicles and vesicle coat recruitment (PubMed:9990005, PubMed:9813083, PubMed:18182008). Involved in trafficking of amyloid beta A4 protein and soluble APP-beta release (independent from the modulation of gamma-secretase activity) (By similarity). Involved in the KDELR2-mediated retrograde transport of the toxin A subunit (CTX-A-K63)together with COPI and the COOH terminus of KDELR2 (PubMed:9813083). On Golgi membranes, acts as primary receptor for ARF1-GDP, a GTP-binding protein involved in COPI-vesicle formation. Increases coatomer-dependent GTPase-activating activity of ARFGAP2 which mediates the hydrolysis of ARF1-bound GTP and therefore modulates protein trafficking from the Golgi apparatus. Involved in the exocytic trafficking of G protein-coupled receptors F2LR1/PAR2 (trypsin and tryspin-like enzyme receptor), OPRM1 (opioid receptor) and P2RY4 (UTD and UDP receptor) from the Golgi to the plasma membrane, thus contributing to receptor resensitization. In addition to its cargo receptor activity, may also act as a protein channel after oligomerization, facilitating the post-translational entry of leaderless cytoplasmic cargo into the ERGIC. Involved in the translocation into ERGIC, the vesicle entry and the secretion of leaderless cargos (lacking the secretion signal sequence), including the mature form of interleukin 1/IL-1 family members, the alpha-crystallin B chain HSPB5, the carbohydrate-binding proteins galectin-1/LGALS1 and galectin-3/LGALS3, the microtubule-associated protein Tau/MAPT, and the annexin A1/ANXA1; the translocation process is dependent on cargo protein unfolding and enhanced by chaperones HSP90AB1 and HSP90B1/GRP9. Could also associates with the presenilin-dependent gamma-secretase complex in order to regulate gamma-cleavages of the amyloid beta A4 protein to yield amyloid-beta 40/Abeta40 (By similarity).
Ectopic expression of TMED10 alone does not result in its proper cis-Golgi network localization. Interaction of TMED10 with TMED2 is both necessary and sufficient for transport of the couple to the cis-Golgi network, and TMED3 and/or TMED9 contribute to facilitating the process.
Endoplasmic reticulum-Golgi intermediate compartment membrane
Predominantly dimeric and to a lesser extent monomeric in the ER (PubMed:18182008). Monomer and dimer in ERGIC and cis-Golgi network. Forms homooligomer (via GOLD domain); the assembly is promoted by direct binding with leaderless cargos and may form a protein channel that facilitates cargo entry into the ERGIC. Forms heterooligomeric complexes with other members of the p24 family such as TMED2, TMED7 and TMED9 (By similarity). Interacts (via GOLD domain) with TMED2 (via GOLD domain); the complex is required for export of TMED10 from the ER to the cis-Golgi network; the complex is proposed to be involved in cis-Golgi network dynamics and / or biogenesis. Associates with the COPI vesicle coat subunits (coatomer) (PubMed:9990005, PubMed:9813083, PubMed:18182008). Tetramerization of the cytoplasmic domain at the Golgi membrane in vitro; the complex is proposed to interact with COPI coatomer and induce budding of the vesicles (PubMed:18182008). Interacts with COPG1; the interaction involves TMED10 homodimer. Interacts with ARF1 (GDP-bound); the interaction probably involves a TMED10 oligomer. Interacts with SEC23A, SEC24B, SEC24C and SEC24D components of the coat protein complex II/COPII, indicative of an association of TMED10 with the COPII vesicle coat. Interacts with CD59. Interacts with MPPE1/PGAP5; the complex might recruit and sort GPI-anchored proteins to the ER-exit site, or the interaction might lead to recycling of PGAP5 between the ER and the Golgi. Interacts with F2LR1/PAR2 (By similarity). Interacts with KDELR2/ERD2; the interaction is disrupted by KDELR2 ligand (PubMed:9813083) (By similarity). Found in a complex composed at least of SURF4, TMED2 and TMED10. Associates with the presenilin-dependent gamma-secretase complex. Interacts with STX17; the interaction is direct. Interacts with IL-1; the interaction is direct. Interacts with RAB21 (active GTP-bound form); the interaction is indirect and regulates TMED10 abundance and localization at the Golgi (By similarity).
The GOLD domain is required for proper p24 heterooligomeric complex formation and efficient transport of GPI-anchored proteins.
The lumenal domain mediates localization to the plasma membrane by partially overriding the ER retention by the cytoplasmic domain.
P450 can be induced to high levels in liver and other tissues by various foreign compounds, including drugs, pesticides, and carcinogens.
Belongs to the beta/gamma-crystallin family.
Belongs to the tetraspanin (TM4SF) family.
Interacts with calcium ATPase ATP2A1/SERCA1 (PubMed:23362265, PubMed:23455422, PubMed:23455424). Interact with ATP2A2; the inhibition decreases ATP2A1 Ca(2+) affinity. Interacts with VMP1; VMP1 competes with PLN and SLN to prevent them from forming an inhibitory complex with ATP2A2 (By similarity).
Reversibly inhibits the activity of ATP2A1 and ATP2A2 in sarcoplasmic reticulum by decreasing the apparent affinity of the ATPase for Ca(2+). Modulates calcium re-uptake during muscle relaxation and plays an important role in calcium homeostasis in muscle (PubMed:23362265, PubMed:9575189). Required for muscle-based, non-shivering thermogenesis (By similarity).
Belongs to the mitochondrial pyruvate carrier (MPC) (TC 2.A.105) family.
Mediates the uptake of pyruvate into mitochondria.
Hydrolyzes the toxic metabolites of a variety of organophosphorus insecticides. Capable of hydrolyzing a broad spectrum of organophosphate substrates and lactones, and a number of aromatic carboxylic acid esters. Mediates an enzymatic protection of low density lipoproteins against oxidative modification.
The preferential association of PON1 with HDL is mediated in part by its signal peptide, by binding phospholipids directly, rather than binding apo AI. The retained signal peptide may allow transfer of the protein between phospholipid surfaces.
There are two allelic forms, allozyme A and B, which differ in their substrate specificity. Both forms have similar arylesterase activity but allozyme B possesses greater paraoxonase activity. Allozyme A is better at protecting LDL from oxidation.
Belongs to the SLAIN motif-containing family.
Hemoglobin epsilon chain is a beta-type chain found in early embryos.
Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily.
Can bind about 5 Ca(2+) ions per subunit.
Tubulin is the major constituent of microtubules. The gamma chain is found at microtubule organizing centers (MTOC) such as the spindle poles or the centrosome. Pericentriolar matrix component that regulates alpha/beta chain minus-end nucleation, centrosome duplication and spindle formation.
Belongs to the Toll-like receptor family.
Participates in the innate immune response to microbial agents. Specifically recognizes diacylated and triacylated lipopeptides. Cooperates with TLR2 to mediate the innate immune response to bacterial lipoproteins or lipopeptides.
Belongs to the universal ribosomal protein uL15 family.
Receptor for adenosine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase.
Belongs to the inositol monophosphatase superfamily.
Belongs to the class-II pyridoxal-phosphate-dependent aminotransferase family.
Belongs to the carbon-nitrogen hydrolase superfamily. BTD/VNN family.
Belongs to the CoA-transferase III family.
Belongs to the eukaryotic ribosomal protein eL29 family.
Interacts with IL8. Interacts with GNAI2.
Receptor to interleukin-8, which is a powerful neutrophils chemotactic factor. Binding of IL-8 to the receptor causes activation of neutrophils. This response is mediated via a G-protein that activates a phosphatidylinositol-calcium second messenger system.
Was originally thought to be the receptor for fMet-Leu-Phe (N-formyl peptide receptor).
Homodimer. Interacts with DLG4; the interaction possibly being prevented by the association between NOS1 and CAPON. Forms a ternary complex with CAPON and RASD1. Forms a ternary complex with CAPON and SYN1. Interacts with ZDHHC23. Interacts with NOSIP; which may impair its synaptic location (By similarity). Interacts with HTR4 (By similarity). Interacts with SLC6A4. Interacts with VAC14 (By similarity). Interacts (via N-terminal domain) with DLG4 (via N-terminal tandem pair of PDZ domains). Interacts with SLC6A4. Forms a complex with ASL, ASS1 and SLC7A1; the complex regulates cell-autonomous L-arginine synthesis and citrulline recycling while channeling extracellular L-arginine to nitric oxide synthesis pathway (By similarity). Interacts with DMD; localizes NOS1 to sarcolemma in muscle cells (By similarity). Interacts with DYNLL1; inhibits the nitric oxide synthase activity (By similarity).
Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In the brain and peripheral nervous system, NO displays many properties of a neurotransmitter. Probably has nitrosylase activity and mediates cysteine S-nitrosylation of cytoplasmic target proteins such SRR (By similarity).
Stimulated by calcium/calmodulin. Inhibited by DYNLL1 that prevents the dimerization of the protein. Inhibited by NOSIP.
Tetrahydrobiopterin (BH4). May stabilize the dimeric form of the enzyme.
The PDZ domain participates in protein-protein interaction, and is responsible for targeting nNos to synaptic membranes. Mediates interaction with VAC14.
Ubiquitinated; mediated by STUB1/CHIP in the presence of Hsp70 and Hsp40 (in vitro).
Belongs to the glycosyl hydrolase 13 family. GlgB subfamily.
Belongs to the inositol phosphokinase (IPK) family.
Interacts with UBC9, RAN, RBM8A, eIF-1A and PAX6.
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.
Belongs to the terpene cyclase/mutase family.
Belongs to the V-ATPase D 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 (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). May play a role in cilium biogenesis through regulation of the transport and the localization of proteins to the cilium (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 the accessory subunits ATP6AP1/Ac45 and ATP6AP2/PRR (By similarity). Interacts with SNX10 (By similarity).
Found in high and low molecular mass forms. Each consists of two chains, A and B. The high molecular mass form contains a long chain A which is cleaved to yield a short chain A. Forms heterodimer with SERPINA5. Binds LRP1B; binding is followed by internalization and degradation. Interacts with MRC2. Interacts with PLAUR. In complex with SERPINE1, interacts with PLAUR/uPAR. Interacts with SORL1 and LRP1, either alone or in complex with SERPINE1; these interactions are abolished in the presence of LRPAP1/RAP. The ternary complex composed of PLAUR-PLAU-PAI1 also interacts with SORLA.
Phosphorylation of Ser-325 abolishes proadhesive ability but does not interfere with receptor binding.
Produced as an inactive single-chain protein (pro-uPA or sc-uPA), is processed into the active disulfide-linked two-chain form of PLAU/uPA by a proteolytic event mediated, at least, by TMPRSS4.
Specifically cleaves the zymogen plasminogen to form the active enzyme plasmin.
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.
Transposase-derived protein that may have nuclease activity (Potential). Does not have transposase activity.
Activated by N-ethylmaleimide (NEM). Inhibited by furosemide and bumetanide.
Belongs to the SLC12A transporter family.
Homodimer. Heteromultimer with other K-Cl cotransporters.
Mediates electroneutral potassium-chloride cotransport when activated by cell swelling (PubMed:8663127). May contribute to cell volume homeostasis in single cells. May be involved in the regulation of basolateral Cl(-) exit in NaCl absorbing epithelia (Probable).
Phosphorylated, phosphorylation may regulate transporter activity.
Acetylated at Ser-565 by SPHK1. During neuroinflammation, acetylation by SPHK1 promotes neuronal secretion of specialized preresolving mediators (SPMs), especially 15-R-lipoxin A4, which results in an increase of phagocytic microglia.
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.
Dual cyclooxygenase and peroxidase in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate, AA, C20:4(n-6)), with a particular role in the inflammatory response. The cyclooxygenase activity oxygenates AA to the hydroperoxy endoperoxide prostaglandin G2 (PGG2), and the peroxidase activity reduces PGG2 to the hydroxy endoperoxide prostaglandin H2 (PGH2), the precursor of all 2-series prostaglandins and thromboxanes. This complex transformation is initiated by abstraction of hydrogen at carbon 13 (with S-stereochemistry), followed by insertion of molecular O2 to form the endoperoxide bridge between carbon 9 and 11 that defines prostaglandins. The insertion of a second molecule of O2 (bis-oxygenase activity) yields a hydroperoxy group in PGG2 that is then reduced to PGH2 by two electrons. Similarly catalyzes successive cyclooxygenation and peroxidation of dihomo-gamma-linoleate (DGLA, C20:3(n-6)) and eicosapentaenoate (EPA, C20:5(n-3)) to corresponding PGH1 and PGH3, the precursors of 1- and 3-series prostaglandins. In an alternative pathway of prostanoid biosynthesis, converts 2-arachidonoyl lysophopholipids to prostanoid lysophopholipids, which are then hydrolyzed by intracellular phospholipases to release free prostanoids. Metabolizes 2-arachidonoyl glycerol yielding the glyceryl ester of PGH2, a process that can contribute to pain response. Generates lipid mediators from n-3 and n-6 polyunsaturated fatty acids (PUFAs) via a lipoxygenase-type mechanism. Oxygenates PUFAs to hydroperoxy compounds and then reduces them to corresponding alcohols. Plays a role in the generation of resolution phase interaction products (resolvins) during both sterile and infectious inflammation. Metabolizes docosahexaenoate (DHA, C22:6(n-3)) to 17R-HDHA, a precursor of the D-series resolvins (RvDs). As a component of the biosynthetic pathway of E-series resolvins (RvEs), converts eicosapentaenoate (EPA, C20:5(n-3)) primarily to 18S-HEPE that is further metabolized by ALOX5 and LTA4H to generate 18S-RvE1 and 18S-RvE2. In vascular endothelial cells, converts docosapentaenoate (DPA, C22:5(n-3)) to 13R-HDPA, a precursor for 13-series resolvins (RvTs) shown to activate macrophage phagocytosis during bacterial infection. In activated leukocytes, contributes to oxygenation of hydroxyeicosatetraenoates (HETE) to diHETES (5,15-diHETE and 5,11-diHETE). Can also use linoleate (LA, (9Z,12Z)-octadecadienoate, C18:2(n-6)) as substrate and produce hydroxyoctadecadienoates (HODEs) in a regio- and stereospecific manner,being (9R)-HODE ((9R)-hydroxy-(10E,12Z)-octadecadienoate) and (13S)-HODE ((13S)-hydroxy-(9Z,11E)-octadecadienoate) its major products (By similarity). During neuroinflammation, plays a role in neuronal secretion of specialized preresolving mediators (SPMs) 15R-lipoxin A4 that regulates phagocytic microglia (By similarity).
Highest expression in kidney and urinary bladder.
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.
S-nitrosylation by NOS2 (iNOS) activates enzyme activity. S-nitrosylation may take place on different Cys residues in addition to Cys-526.
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.
Belongs to the major facilitator superfamily. MFSD6 family.
Belongs to the adaptor complexes medium subunit family.
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.
Involved in iron cellular uptake. Seems to be internalized and then recycled back to the cell membrane. Binds a single atom of iron per subunit. Could also bind zinc (By similarity).
E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. It is unclear whether it also mediates the formation of other types of polyubiquitin chains. The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. Regulates centrosomal microtubule nucleation. Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle. Required for FANCD2 targeting to sites of DNA damage. Inhibits lipid synthesis by binding to inactive phosphorylated ACACA and preventing its dephosphorylation. Contributes to homologous recombination repair (HRR) via its direct interaction with PALB2, fine-tunes recombinational repair partly through its modulatory role in the PALB2-dependent loading of BRCA2-RAD51 repair machinery at DNA breaks. Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8. Acts as a transcriptional activator.
Heterodimer with BARD1. Part of the BRCA1-associated genome surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the MRE11-RAD50-NBN protein (MRN) complex. This association could be a dynamic process changing throughout the cell cycle and within subnuclear domains. Component of the BRCA1-A complex, at least composed of BRCA1, BARD1, UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1. Interacts (via the BRCT domains) with ABRAXAS1 (phosphorylated form); this is important for recruitment to sites of DNA damage. Can form a heterotetramer with two molecules of ABRAXAS1 (phosphorylated form). Component of the BRCA1-RBBP8 complex. Interacts (via the BRCT domains) with RBBP8 ('Ser-327' phosphorylated form); the interaction ubiquitinates RBBP8, regulates CHEK1 activation, and involves RBBP8 in BRCA1-dependent G2/M checkpoint control on DNA damage. Associates with RNA polymerase II holoenzyme. Interacts with SMC1A, NELFB, DCLRE1C, CLSPN. CHEK1, CHEK2, BAP1, BRCC3, UBXN1 and PCLAF. Interacts (via BRCT domains) with BRIP1 (phosphorylated form). Interacts with FANCD2 (ubiquitinated form). Interacts with H2AX (phosphorylated on 'Ser-140'). Interacts (via the BRCT domains) with ACACA (phosphorylated form); the interaction prevents dephosphorylation of ACACA. Part of a BRCA complex containing BRCA1, BRCA2 and PALB2. Interacts directly with PALB2; the interaction is essential for its function in HRR. Interacts directly with BRCA2; the interaction occurs only in the presence of PALB2 which serves as the bridging protein. Interacts (via the BRCT domains) with LMO4; the interaction represses the transcriptional activity of BRCA1. Interacts (via the BRCT domains) with CCAR2 (via N-terminus); the interaction represses the transcriptional activator activity of BRCA1. Interacts with EXD2. Interacts (via C-terminus) with DHX9; this interaction is direct and links BRCA1 to the RNA polymerase II holoenzyme.
Belongs to the complement C6/C7/C8/C9 family.
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. C8A inserts into the target membrane, but does not form pores by itself (By similarity).
Heterotrimer of 3 chains: alpha, beta and gamma. The alpha and gamma chains are disulfide bonded. Component of the membrane attack complex (MAC). MAC assembly is initiated by proteolytic cleavage of C5 into C5a and C5b. C5b sequentially binds C6, C7, C8 and multiple copies of the pore-forming subunit C9 (By similarity).
Belongs to the G-alpha family. G(s) subfamily.
Belongs to the zinc-containing alcohol dehydrogenase family.
Associates with the RNA polymerase II complex. Interacts with transcribing RNA polymerase II phosphorylated on 'Ser-7' on CTD.
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.
Cytosolic prostaglandin synthase that catalyzes the oxidoreduction of prostaglandin endoperoxide H2 (PGH2) to prostaglandin E2 (PGE2). Molecular chaperone that localizes to genomic response elements in a hormone-dependent manner and disrupts receptor-mediated transcriptional activation, by promoting disassembly of transcriptional regulatory complexes. Facilitates HIF alpha proteins hydroxylation via interaction with EGLN1/PHD2, leading to recruit EGLN1/PHD2 to the HSP90 pathway.
Probably forms a complex composed of chaperones HSP90 and HSP70, co-chaperones STIP1/HOP, CDC37, PPP5C, PTGES3/p23, TSC1 and client protein TSC2. Binds to the progesterone receptor. Interacts with TERT; the interaction, together with HSP90AA1, is required for correct assembly and stabilization of the telomerase holoenzyme complex. Interacts (via PXLE motif) with EGLN1/PHD2, recruiting EGLN1/PHD2 to the HSP90 pathway to facilitate HIF alpha proteins hydroxylation. Interacts with HSP90AA1, FLCN, FNIP1 and FNIP2.
Proteolytically cleaved by caspase-7 (CASP7) in response to apoptosis, leading to its inactivation.
Belongs to the metallo-dependent hydrolases superfamily. Hydantoinase/dihydropyrimidinase family.
Scaffolding protein that specifically recognizes and binds dimethylarginine-containing proteins. Plays a role in the regulation of translation of target mRNAs by binding Arg/Gly-rich motifs (GAR) in 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, acts as an antiviral factor that participates in the assembly of stress granules together with G3BP1.
Electroneutral Cl(-)/HCO3(-) antiporter that favors chloride ion entry and efflux of hydrogencarbonate and sodium ion across the basolateral membrane and may participat in salivary secretion (PubMed:11102437). Also mediates Cl(-)/HCO3(-) exchange activity in the presence of K(+) as well as Cs(+), Li(+), and Rb(+). Does not contribute to Cl(-)/HCO3(-) exchanger in the apical membrane of the upper villous epithelium (By similarity).
Highly expressed in kidney (PubMed:11102437). Expressed in the outer medulla and the inner medulla in the kidney cortex (PubMed:11102437). Only expressed in beta-intercalated cells (PubMed:11102437).
Inhibits p53- and p73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain.
Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRA1D sub-subfamily.
Interacts with FLNA (via filamin repeat 21); increases PKA-mediated phosphorylation of FLNA.
Palmitoylated. Palmitoylation by ZDHHC21 may increase the expression of the receptor and regulate downstream signaling.
This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium.
Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood. Major zinc transporter in plasma, typically binds about 80% of all plasma zinc (By similarity). Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity). Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity). Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli (By similarity). Does not prevent iron uptake by the bacterial siderophore aerobactin (By similarity).
Interacts with FCGRT; this interaction regulates ALB homeostasis (By similarity). Interacts with TASOR (By similarity). In plasma, occurs in a covalently-linked complex with chromophore-bound alpha-1-microglobulin; this interaction does not prevent fatty acid binding to ALB.
Phosphorylated by FAM20C in the extracellular medium.
Ubiquitin-protein ligase which is mainly involved pre-mRNA splicing and DNA repair. Required for pre-mRNA splicing as component of the spliceosome.
Cytochrome b5 is a membrane-bound hemoprotein functioning as an electron carrier for several membrane-bound oxygenases.
A connexon is composed of a hexamer of connexins.
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 acyl-protein thioesterase hydrolyzing fatty acids from S-acylated cysteine residues in proteins such as trimeric G alpha proteins or HRAS (By similarity). Has depalmitoylating activity toward KCNMA1 (By similarity). Could also depalmitoylate ADRB2 (By similarity). Acts as a lysophospholipase hydrolyzing various lysophospholipids including lysophosphatidylcholine (lyso-PC), lysophosphatidylethanolamine (lyso-PE), lysophosphatidylinositol (lyso-PI) and lysophosphatidylserine (lyso-PS) (By similarity). Has much higher thioesterase activity than lysophospholipase activity (By similarity). Contributes to the production of lysophosphatidic acid (LPA) during blood coagulation by recognizing and cleaving plasma phospholipids to generate lysophospholipids which in turn act as substrates for ENPP2 to produce LPA (By similarity).
Belongs to the AB hydrolase superfamily. AB hydrolase 2 family.
Belongs to the universal ribosomal protein uS17 family.
Activated by Ca(2+)/calmodulin. Binding of calmodulin results in conformational change that relieves intrasteric autoinhibition and allows autophosphorylation of Thr-287 which turns the kinase in a constitutively active form and confers to the kinase a Ca(2+)-independent activity.
Autophosphorylation of Thr-287 following activation by Ca(2+)/calmodulin. Phosphorylation of Thr-287 locks the kinase into an activated state (By similarity).
Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily.
CAMK2 is composed of 4 different chains: alpha (CAMK2A), beta (CAMK2B), gamma (CAMK2G), and delta (CAMK2D). The different isoforms assemble into homo- or heteromultimeric holoenzymes composed of 12 subunits with two hexameric rings stacked one on top of the other. Interacts with RRAD and CACNB2 (By similarity).
Calcium/calmodulin-dependent protein kinase involved in the regulation of Ca(2+) homeostatis and excitation-contraction coupling (ECC) in heart by targeting ion channels, transporters and accessory proteins involved in Ca(2+) influx into the myocyte, Ca(2+) release from the sarcoplasmic reticulum (SR), SR Ca(2+) uptake and Na(+) and K(+) channel transport. Targets also transcription factors and signaling molecules to regulate heart function. In its activated form, is involved in the pathogenesis of dilated cardiomyopathy and heart failure. Contributes to cardiac decompensation and heart failure by regulating SR Ca(2+) release via direct phosphorylation of RYR2 Ca(2+) channel on 'Ser-2808'. In the nucleus, phosphorylates the MEF2 repressor HDAC4, promoting its nuclear export and binding to 14-3-3 protein, and expression of MEF2 and genes involved in the hypertrophic program. Is essential for left ventricular remodeling responses to myocardial infarction. In pathological myocardial remodeling acts downstream of the beta adrenergic receptor signaling cascade to regulate key proteins involved in ECC. Regulates Ca(2+) influx to myocytes by binding and phosphorylating the L-type Ca(2+) channel subunit beta-2 CACNB2. In addition to Ca(2+) channels, can target and regulate the cardiac sarcolemmal Na(+) channel Nav1.5/SCN5A and the K+ channel Kv4.3/KCND3, which contribute to arrhythmogenesis in heart failure. Phosphorylates phospholamban (PLN/PLB), an endogenous inhibitor of SERCA2A/ATP2A2, contributing to the enhancement of SR Ca(2+) uptake that may be important in frequency-dependent acceleration of relaxation (FDAR) and maintenance of contractile function during acidosis. May participate in the modulation of skeletal muscle function in response to exercise, by regulating SR Ca(2+) transport through phosphorylation of PLN/PLB and triadin, a ryanodine receptor-coupling factor. In response to interferon-gamma (IFN-gamma) stimulation, catalyzes phosphorylation of STAT1, stimulating the JAK-STAT signaling pathway (By similarity).
The CAMK2 protein kinases contain a unique C-terminal subunit association domain responsible for oligomerization.
Belongs to the class-I aminoacyl-tRNA synthetase family.
Belongs to the Arg-specific ADP-ribosyltransferase family.
Has ADP-ribosyltransferase activity toward GLP1R.
Primarily in skeletal and cardiac muscle.
May be involved in tissue injury and remodeling. Has significant elastolytic activity. Can accept large and small amino acids at the P1' site, but has a preference for leucine. Aromatic or hydrophobic residues are preferred at the P1 site, with small hydrophobic residues (preferably alanine) occupying P3 (By similarity).
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.
Belongs to the SLC34A transporter family.
Interacts via its C-terminal region with NHERF4. Interacts with NHERF1. Interacts with TMEM174; regulates SLC34A1 internalization by PTH and FGF23 (By similarity).
Involved in actively transporting phosphate into cells via Na(+) cotransport in the renal brush border membrane (PubMed:7733319). The cotransport has a Na(+):Pi stoichiometry of 3:1 and is electrogenic (By similarity).
Transport activity is significantly increased in response to dietary phosphate deprivation.
Associates with the pre-60S ribosomal particle.
Belongs to the universal ribosomal protein uL10 family.
Component of the ribosome assembly machinery. Nuclear paralog of the ribosomal protein P0, it binds pre-60S subunits at an early stage of assembly in the nucleolus, and is replaced by P0 in cytoplasmic pre-60S subunits and mature 80S ribosomes.
Belongs to the G-protein coupled receptor T2R family.
Belongs to the pancreatic ribonuclease family.
Interacts with STIM1; the interaction is inhibit by th interaction of STIM1 with EFHB.
Negative regulator of store-operated Ca(2+) entry (SOCE) involved in protecting cells from Ca(2+) overfilling. In response to cytosolic Ca(2+) elevation after endoplasmic reticulum Ca(2+) refilling, promotes a slow inactivation of STIM (STIM1 or STIM2)-dependent SOCE activity: possibly act by facilitating the deoligomerization of STIM to efficiently turn off ORAI when the endoplasmic reticulum lumen is filled with the appropriate Ca(2+) levels, and thus preventing the overload of the cell with excessive Ca(2+) ions.
Belongs to the round spermatid basic protein 1 family.
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family.
Belongs to the copper transporter (Ctr) (TC 1.A.56) family. SLC31A subfamily.
Belongs to the shaker potassium channel beta subunit family.
Belongs to the GST superfamily. Mu family.
Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.
Well expressed in rabbit liver, brain and kidney.
Belongs to the eukaryotic ribosomal protein eL43 family.
Belongs to the heme-copper respiratory oxidase family.
Binds 2 heme A groups non-covalently per subunit.
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)) (By similarity). As a newly synthesized protein, rapidly incorporates into a multi-subunit assembly intermediate in the inner membrane, called MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase) complex, whose core components are COA3/MITRAC12 and COX14. Within the MITRAC complex, interacts with COA3 and with SMIM20/MITRAC7; the interaction with SMIM20 stabilizes the newly synthesized MT-CO1 and prevents its premature turnover. Interacts with TMEM177 in a COX20-dependent manner (By similarity).
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 an important role in the regulation of interdigestive gastrointestinal motility and indirectly causes rhythmic contraction of duodenal and colonic smooth muscle.
Component of the nuclear pore complex (NPC)-associated TREX-2 complex (transcription and export complex 2), composed of at least ENY2, GANP, PCID2, DSS1, and either centrin CETN2 or CETN3. TREX-2 contains 2 ENY2 chains. The TREX-2 complex interacts with the nucleoporin NUP153. Component of some SAGA transcription coactivator-HAT complexes, at least composed of ATXN7, ATXN7L3, ENY2, GCN5L2, SUPT3H, TAF10, TRRAP and USP22. Within the SAGA complex, ENY2, ATXN7, ATXN7L3, and USP22 form an additional subcomplex of SAGA called the DUB module (deubiquitination module). Interacts directly with ATXN7L3, GANP and with the RNA polymerase II. Interacts strongly with ATXN7L3 and ATXN7L3B.
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 both histones H2A and H2B. The SAGA complex is recruited to specific gene promoters by activators such as MYC, where it is required for transcription. Required for nuclear receptor-mediated transactivation. 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 band 7/mec-2 family. Flotillin subfamily.
Heterooligomeric complex of flotillin-1 and flotillin-2 and caveolin-1 and caveolin-2. Interacts with ECPAS.
May act as a scaffolding protein within caveolar membranes, functionally participating in formation of caveolae or caveolae-like vesicles.
Belongs to the amiloride-sensitive sodium channel (TC 1.A.6) family. SCNN1B 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. Interacts with NEDD4 (via WW domains). Interacts with NEDD4L (via WW domains). Interacts with WWP1 (via WW domains). Interacts with WWP2 (via WW domains). Interacts with the full-length immature form of PCSK9 (pro-PCSK9). Interacts (N-glycosylated) with BPIFA1; the interaction is direct and inhibits the proteolytic processing of SCNN1A and SCNN1G and the activation of ENaC.
N-glycosylated. N-glycosylation is required for interaction with BPIFA1.
Phosphorylated on serine and threonine residues. Aldosterone and insulin increase the basal level of phosphorylation.
Sodium permeable non-voltage-sensitive ion channel inhibited by the diuretic amiloride. Mediates the electrodiffusion of the luminal sodium (and water, which follows osmotically) through the apical membrane of epithelial cells. Plays an essential role in electrolyte and blood pressure homeostasis, but also in airway surface liquid homeostasis, which is important for proper clearance of mucus. Controls the reabsorption of sodium in kidney, colon, lung and sweat glands. Also plays a role in taste perception.
Belongs to the bacterial ribosomal protein bS18 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.
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 cyclic nucleotide phosphodiesterase family.
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.
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).
Fatty acylated at Met-1 and Lys-238. The acyl modifications, in decreasing order of ion abundance, are: oleoyl (C18:1) > palmitoyl (C16:0) > stearoyl (C18:0) > eicosenoyl (C20:1) > dihomo-gamma-linolenoyl (C20:3) > palmitoleoyl (C16:1) > eicosadienoyl (C20:2).
Homotetramer. Homooctamer formed by head-to-head interaction between homotetramers from adjoining membranes. Interacts with CALM; one CALM molecule interacts with the cytoplasmic domains of two aquaporins, leading to channel closure. Interacts (via C-terminus) with BFSP1 (via C-terminus) in aged lens fiber cells (By similarity).
Subject to partial proteolytic cleavage in the eye lens core. Partial proteolysis promotes interactions between tetramers from adjoining membranes (By similarity).
Water channel. Channel activity is down-regulated by CALM when cytoplasmic Ca(2+) levels are increased. 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. Plays a role in cell-to-cell adhesion and facilitates gap junction coupling (By similarity).
Belongs to the FAD-dependent oxidoreductase family.
Belongs to the proton-activated chloride channel family.
Contains an N-terminal region composed of octamer repeats. At low copper concentrations, the sidechains of His residues from three or four repeats contribute to the binding of a single copper ion. Alternatively, a copper ion can be bound by interaction with the sidechain and backbone amide nitrogen of a single His residue. The observed copper binding stoichiometry suggests that two repeat regions cooperate to stabilize the binding of a single copper ion. At higher copper concentrations, each octamer can bind one copper ion by interactions with the His sidechain and Gly backbone atoms. A mixture of binding types may occur, especially in the case of octamer repeat expansion. Copper binding may stabilize the conformation of this region and may promote oligomerization.
Found in high quantity in the brain of humans and animals infected with degenerative neurological diseases such as kuru, Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler syndrome (GSS), scrapie, bovine spongiform encephalopathy (BSE), transmissible mink encephalopathy (TME), etc.
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. Interacts with GRB2, APP, ERI3/PRNPIP and SYN1. Mislocalized cytosolically exposed PrP interacts with MGRN1; this interaction alters MGRN1 subcellular location and causes lysosomal enlargement. Interacts with KIAA1191.
The normal, monomeric form has a mainly alpha-helical structure. The disease-associated, protease-resistant form forms amyloid fibrils containing a cross-beta spine, formed by a steric zipper of superposed beta-strands. Disease mutations may favor intermolecular contacts via short beta strands, and may thereby trigger oligomerization.
Belongs to the gastrin/cholecystokinin family.
Gastrin stimulates the stomach mucosa to produce and secrete hydrochloric acid and the pancreas to secrete its digestive enzymes. It also stimulates smooth muscle contraction and increases blood circulation and water secretion in the stomach and intestine.
Dimer of either two alpha chains, or two beta chains, or one alpha and one beta chain (By similarity). The S100B dimer binds two molecules of STK38 (By similarity). Interacts with CACYBP in a calcium-dependent manner (By similarity). Interacts with ATAD3A; this interaction probably occurs in the cytosol prior to ATAD3A mitochondrial targeting. Interacts with S100A6. The S100B dimer interacts with two molecules of CAPZA1. Interacts with AGER. Interacts with PPP5C (via TPR repeats); the interaction is calcium-dependent and modulates PPP5C activity. Interacts with TPPP; this interaction inhibits TPPP dimerization (By similarity). Interacts with isoform CLSTN3beta of CLSTN3; interaction promotes secretion (By similarity).
Small zinc- and- and calcium-binding protein that is highly expressed in astrocytes and constitutes one of the most abundant soluble proteins in brain. Weakly binds calcium but binds zinc very tightly-distinct binding sites with different affinities exist for both ions on each monomer (By similarity). Physiological concentrations of potassium ion antagonize the binding of both divalent cations, especially affecting high-affinity calcium-binding sites (By similarity). Acts as a neurotrophic factor that promotes astrocytosis and axonal proliferation. Involved in innervation of thermogenic adipose tissue by acting as an adipocyte-derived neurotrophic factor that promotes sympathetic innervation of adipose tissue (By similarity). Binds to and initiates the activation of STK38 by releasing autoinhibitory intramolecular interactions within the kinase (By similarity). Interaction with AGER after myocardial infarction may play a role in myocyte apoptosis by activating ERK1/2 and p53/TP53 signaling (By similarity). Could assist ATAD3A cytoplasmic processing, preventing aggregation and favoring mitochondrial localization. May mediate calcium-dependent regulation on many physiological processes by interacting with other proteins, such as TPR-containing proteins, and modulating their activity (By similarity).
Belongs to the nuclear hormone receptor family. NR5 subfamily.
Activated by an increase in cytosolic calcium levels that induce a conformational change of the N-terminal regulatory domain, uncapping the channel and allowing transport. Inhibited by bathophenanthroline, mersalyl, p-hydroxymercuribenzoate, bromcresol purple and tannic acid.
Belongs to the mitochondrial carrier (TC 2.A.29) family.
Electroneutral antiporter that mediates the transport of adenyl nucleotides through the inner mitochondrial membrane. Originally identified as an ATP-magnesium/inorganic phosphate antiporter, it also acts as a broad specificity adenyl nucleotide antiporter. By regulating the mitochondrial matrix adenyl nucleotide pool could adapt to changing cellular energetic demands and indirectly regulate adenyl nucleotide-dependent metabolic pathways. In vitro, a low activity is also observed with guanyl and pyrimidine nucleotides. May play a role in protecting cells against oxidative stress-induced cell death, by buffering calcium levels in the mitochondrial matrix through the formation of calcium-phosphate precipitates.
Linker region/H9 could directly block the transport of substrates across the transporter.
Mainly expressed in colon. Also expressed in the small intestine proximal to the ileum. Weakly expressed in kidney but not in the liver.
The C-terminal mitochondrial carrier domain/transmembrane domain/TMD bears the transmembrane transporter activity.
The regulatory N-terminal domain/NTD formed of two pairs of fused calcium-binding EF-hands, binds calcium in the mitochondrial intermembrane space and regulates the antiporter activity of the transmembrane domain/TMD. In absence of calcium, the apo form of the N-terminal domain is intrinsically disordered and binds to the transmembrane domain, inhibiting the transporter activity. Binding of calcium leads to a major conformational change and abolishes the interaction with the transmembrane domain and the inhibition of the transporter activity.
Belongs to the universal ribosomal protein uS11 family.
Belongs to the ABC transporter superfamily. ABCG family. Eye pigment precursor importer (TC 3.A.1.204) subfamily.
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.
Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIC subfamily.
Belongs to the eukaryotic ribosomal protein eL14 family.
Belongs to the potassium channel KCNE family.
Neurotensin may play an endocrine or paracrine role in the regulation of fat metabolism. It causes contraction of smooth muscle.
Belongs to the endothelin/sarafotoxin family.
Endothelins are endothelium-derived vasoconstrictor peptides (By similarity). Probable ligand for G-protein coupled receptors EDNRA and EDNRB which activates PTK2B, BCAR1, BCAR3 and, GTPases RAP1 and RHOA cascade in glomerular mesangial cells (By similarity). Also binds the DEAR/FBXW7-AS1 receptor (By similarity).
Belongs to the methyltransferase superfamily. NTM1 family.
C-type lectin domains 3-5 mediate the interaction with phospholipase PLA2G1B.
Interacts with sPLA2-IB/PLA2G1B; this interaction mediates intracellular signaling as well as clearance of extracellular sPLA2-IB/PLA2G1B via endocytotic pathway (By similarity). Interacts with sPLA2-X/PLA2G10; this interaction mediates sPLA2-X/PLA2G10 clearance and inactivation (By similarity).
Lung, skeletal muscle, brain, kidney and heart.
Receptor for secretory phospholipase A2 (sPLA2). Also able to bind to snake PA2-like toxins. Although its precise function remains unclear, binding of sPLA2 to its receptor participates in both positive and negative regulation of sPLA2 functions as well as clearance of sPLA2. Binding of sPLA2-IB/PLA2G1B induces various effects depending on the cell type, such as activation of the mitogen-activated protein kinase (MAPK) cascade to induce cell proliferation, the production of lipid mediators, selective release of arachidonic acid in bone marrow-derived mast cells. In neutrophils, binding of sPLA2-IB/PLA2G1B can activate p38 MAPK to stimulate elastase release and cell adhesion. May be involved in responses in pro-inflammatory cytokine productions during endotoxic shock. Also has endocytic properties and rapidly internalizes sPLA2 ligands, which is particularly important for the clearance of extracellular sPLA2s to protect their potent enzymatic activities. The soluble secretory phospholipase A2 receptor form is circulating and acts as a negative regulator of sPLA2 functions by blocking the biological functions of sPLA2-IB/PLA2G1B and sPLA2-X/PLA2G10.
The endocytosis signal probably mediates endocytosis via clathrin-coated pits.
The secretory phospholipase A2 receptor form may be produced by the action of metalloproteinases. It contains all extracellular domains and only lacks transmembrane and cytosolic regions. It is however unclear whether this form is produced by proteolytic cleavage as suggested by some experiments, or by alternative splicing (By similarity).
Belongs to the 'GDXG' lipolytic enzyme family.
Belongs to the aldo/keto reductase family.
Catalyzes the stereospecific NADPH-dependent reduction of the C4-C5 double bond of bile acid intermediates and steroid hormones carrying a delta(4)-3-one structure to yield an A/B cis-ring junction. This cis-configuration is crucial for bile acid biosynthesis and plays important roles in steroid metabolism. Capable of reducing a broad range of delta-(4)-3-ketosteroids from C18 (such as, 17beta-hydroxyestr-4-en-3-one) to C27 (such as, 7alpha-hydroxycholest-4-en-3-one).
Subject to inhibition by high substrate concentrations. Inhibited by testosterone concentrations above 10 uM. Inhibited by the primary and secondary bile acids chenodeoxycholic acid and ursodeoxycholic acid.
It is uncertain whether Met-1 or Met-30 is the initiator.
Multidrug efflux pump that functions as a H(+)/organic cation antiporter (PubMed:17442726). Mediates the efflux of cationic compounds, such as the model cations, tetraethylammonium (TEA) and 1-methyl-4-phenylpyridinium (MPP+), the platinum-based drug oxaliplatin or weak bases that are positively charged at physiological pH, cimetidine or the antidiabetic drug metformin. Mediates the efflux of the endogenous compounds creatinine, thiamine and estrone-3-sulfate. Plays a physiological role in the excretion of drugs, toxins and endogenous metabolites through the kidney (By similarity).
Receptor for ATP that acts as a ligand-gated ion channel.
Belongs to the cytochrome c oxidase subunit 2 family.
Binds a dinuclear copper A center per subunit.
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)) (By similarity). Found in a complex with TMEM177, COA6, COX18, COX20, SCO1 and SCO2. Interacts with TMEM177 in a COX20-dependent manner. Interacts with COX20. Interacts with COX16 (By similarity).
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)) (By similarity). Found in a complex with TMEM177, COA6, COX18, COX20, SCO1 and SCO2. Interacts with TMEM177 in a COX20-dependent manner. Interacts with COX20. Interacts with COX16.
Belongs to the TRAFAC class dynamin-like GTPase superfamily. GB1/RHD3 GTPase family.
Catalyzes the N-demethylation of benzphetamine to formaldehyde.
During ontogenesis, there is a transition from the alpha/alpha homodimer to the alpha/beta heterodimer in striated muscle cells.
Glycolytic enzyme that catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate. Appears to have a function in striated muscle development and regeneration.
Mammalian enolase is composed of 3 isozyme subunits, alpha, beta and gamma, which can form homodimers or heterodimers which are cell-type and development-specific. Interacts with PNKD (By similarity).
Mg(2+) is required for catalysis and for stabilizing the dimer.
The alpha/alpha homodimer is expressed in embryo and in most adult tissues. The alpha/beta heterodimer and the beta/beta homodimer are found in striated muscle, and the alpha/gamma heterodimer and the gamma/gamma homodimer in neurons.
Catalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate in the presence of divalent cations and probably participates in glycogen synthesis from carbohydrate precursors, such as lactate.
Homotetramer. Interacts with ALDOA; the interaction blocks inhibition by physiological concentrations of AMP and reduces inhibition by Ca(2+). Interacts with alpha-actinin and F-actin.
Subject to complex allosteric regulation. The enzyme can assume an active R-state, or an inactive T-state. Intermediate conformations may exist. AMP acts as allosteric inhibitor. Fructose 2,6-bisphosphate acts as competitive inhibitor. Strongly inhibited by Ca(2+).
Belongs to the MPDU1 (TC 2.A.43.3) family.
Required for normal utilization of mannose-dolichol phosphate (Dol-P-Man) in the synthesis of N-linked and O-linked oligosaccharides and GPI anchors.
Homotrimer (By similarity). Interacts with CMTM6 (By similarity).
Divalent metal cations. Prefers magnesium or manganese.
Either free or part of the secretory IgA (sIgA) complex that consists of two, four or five IgA monomers, and two additional non-Ig polypeptides, namely the JCHAIN and the secretory component (the proteolytic product of PIGR). Free secretory component interacts with bacterial antigens toxA of C. difficile and eae of E. coli.
Interacts (mainly via CDR1-like domain) with dimeric IgA. Interacts (mainly via CDR2-like domain) with pentameric IgM.
Mediates selective transcytosis of polymeric IgA and IgM across mucosal epithelial cells. Binds polymeric IgA and IgM at the basolateral surface of epithelial cells. The complex is then transported across the cell to be secreted at the apical surface. During this process, a cleavage occurs that separates the extracellular (known as the secretory component) from the transmembrane segment.
N-glycosylated. N-glycosylation is required for anchoring IgA molecules to mucus, but is not necessary for Ig binding.
The Ig-like V-type 1/D1 domain contains three complementarity determining region-like loops CDR1-3, which mediate interaction with IgA and IgM.
Three allotypes are known: allotype T61, allotype T62 and allotype T63. The sequence shown is that of allotype T62.
Through its N-linked glycans ensures anchoring of secretory IgA (sIgA) molecules to mucus lining the epithelial surface to neutralize extracellular pathogens. On its own (free form) may act as a non-specific microbial scavenger to prevent pathogen interaction with epithelial cells.
Belongs to the sulfotransferase 2 family.
Cadherins are calcium-dependent cell adhesion proteins.
Belongs to the cytochrome c oxidase subunit 3 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)).
Belongs to the universal ribosomal protein uL18 family.
Belongs to the GST superfamily. Zeta family.
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.
Belongs to the phosphatase 2A regulatory subunit B family.
PP2A consists of a common heterodimeric core enzyme, composed of a 36 kDa catalytic subunit (subunit C) and a 65 kDa constant regulatory subunit (PR65 or subunit A), that associates with a variety of regulatory subunits. Proteins that associate with the core dimer include three families of regulatory subunits B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56 families), the 48 kDa variable regulatory subunit, viral proteins, and cell signaling molecules (By similarity). Found in a complex with at least ARL2, PPP2CB, PPP2R1A, PPP2R2A, PPP2R5E and TBCD (By similarity). Interacts with TP53 (By similarity). Interacts with IER5 (By similarity). Interacts with MFHAS1; the interaction is direct (By similarity). Interacts with PABIR1/FAM122A (By similarity). Interacts with CRTC3 (By similarity).
The B regulatory subunit might modulate substrate selectivity and catalytic activity, and also might direct the localization of the catalytic enzyme to a particular subcellular compartment. Essential for serine/threonine-protein phosphatase 2A-mediated dephosphorylation of WEE1, preventing its ubiquitin-mediated proteolysis, increasing WEE1 protein levels, and promoting the G2/M checkpoint.
Belongs to the glycoprotein hormones subunit beta family.
Heterodimer. The active follitropin is a heterodimer composed of an alpha chain/CGA shared with other hormones and a unique beta chain/FSHB shown here.
Together with the alpha chain CGA constitutes follitropin, the follicle-stimulating hormone, and provides its biological specificity to the hormone heterodimer. Binds FSHR, a G protein-coupled receptor, on target cells to activate downstream signaling pathways. Follitropin is involved in follicle development and spermatogenesis in reproductive organs.
Belongs to the D-isomer specific 2-hydroxyacid dehydrogenase family.
Belongs to the Ca(2+):cation antiporter (CaCA) (TC 2.A.19) family. SLC8 subfamily.
Belongs to the eukaryotic/archaeal RNase P protein component 2 family.
Component of ribonuclease P, a protein complex that generates mature tRNA molecules by cleaving their 5'-ends.
Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. RAF subfamily.
Belongs to the DZIP C2H2-type zinc-finger protein family.
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. In the epoxidation of arachidonic acid it generates only 14,15- and 11,12-cis-epoxyeicosatrienoic acids.
Belongs to the parathyroid hormone family.
Neuroendocrine peptide which is a critical regulator of cellular and organ growth, development, migration, differentiation and survival and of epithelial calcium ion transport. Regulates endochondral bone development and epithelial-mesenchymal interactions during the formation of the mammary glands and teeth. Required for skeletal homeostasis. Promotes mammary mesenchyme differentiation and bud outgrowth by modulating mesenchymal cell responsiveness to BMPs. Up-regulates BMPR1A expression in the mammary mesenchyme and this increases the sensitivity of these cells to BMPs and allows them to respond to BMP4 in a paracrine and/or autocrine fashion. BMP4 signaling in the mesenchyme, in turn, triggers epithelial outgrowth and augments MSX2 expression, which causes the mammary mesenchyme to inhibit hair follicle formation within the nipple sheath (By similarity).
Osteostatin is a potent inhibitor of osteoclastic bone resorption.
PTHrP interacts with PTH1R (via N-terminal extracellular domain).
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 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.
Fetal skeletal muscle, esophagus, kidney, and lung.
Interacts (via Link domain) with inter-alpha-inhibitor (I-alpha-I) component bikunin. Interacts with ITIH2/HC2; this interaction is required for transesterification of the HC to hyaluronan. Interacts (via Link and CUB domains) with ITIH1. Chondroitin sulfate may be required for the stability of the complex. Interacts (via Link domain) with various C-X-C and C-C chemokines including PF4, CXCL8, CXCL11, CXCL12, CCL2, CCL7, CCL19, CCL21, and CCL27; this interaction interferes with chemokine binding to glycosaminoglycans. Interacts (primarily via Link domain) with BMP2; this interaction is inhibited by hyaluronan. Interacts (via both Link and CUB domains) with TNFSF11. Interacts (via CUB domain) with FN1 (via type III repeats 9-14); this interaction enhances fibronectin fibril assembly. TNFAIP6 may act as a bridging molecule between FN1 and THBS1.
Major regulator of extracellular matrix organization during tissue remodeling (By similarity). Catalyzes the transfer of a heavy chain (HC) from inter-alpha-inhibitor (I-alpha-I) complex to hyaluronan. Cleaves the ester bond between the C-terminus of the HC and GalNAc residue of the chondroitin sulfate chain in I-alpha-I complex followed by transesterification of the HC to hyaluronan. In the process, potentiates the antiprotease function of I-alpha-I complex through release of free bikunin (By similarity). Acts as a catalyst in the formation of hyaluronan-HC oligomers and hyaluronan-rich matrix surrounding the cumulus cell-oocyte complex, a necessary step for oocyte fertilization (By similarity). Assembles hyaluronan in pericellular matrices that serve as platforms for receptor clustering and signaling. Enables binding of hyaluronan deposited on the surface of macrophages to LYVE1 on lymphatic endothelium and facilitates macrophage extravasation. Alters hyaluronan binding to functionally latent CD44 on vascular endothelium, switching CD44 into an active state that supports leukocyte rolling (By similarity). Modulates the interaction of chemokines with extracellular matrix components and proteoglycans on endothelial cell surface, likely preventing chemokine gradient formation. In a negative feedback mechanism, may limit excessive neutrophil recruitment at inflammatory sites by antagonizing the association of CXCL8 with glycosaminoglycans on vascular endothelium (By similarity). Has a role in osteogenesis and bone remodeling. Inhibits BMP2-dependent differentiation of mesenchymal stem cell to osteoblasts. Protects against bone erosion during inflammation by inhibiting TNFSF11/RANKL-dependent osteoclast activation (By similarity).
The CUB domain is necessary for calcium ion binding and transesterification reaction. It is required for binding to FN1.
The Link domain interacts with various extracellular matrix components, including heparin, heparan sulfates, hyaluronan and I-alpha-I complex. It is required for binding to various chemokines.
Belongs to the metallothionein superfamily. Type 1 family.
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.
Metallothioneins have a high content of cysteine residues that bind various heavy metals; these proteins are transcriptionally regulated by both heavy metals and glucocorticoids.
Belongs to the chloride channel CLIC family.
Can insert into membranes and form chloride ion channels. Channel activity depends on the pH. Membrane insertion seems to be redox-regulated and may occur only under oxydizing conditions (By similarity).
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 (By similarity).
Monomer. Homodimer (in vitro). Interacts with TRAPPC2. Dimerization requires a conformation change that leads to the exposure of a large hydrophobic surface. In vivo, this may lead to membrane insertion (By similarity).
Belongs to the interleukin-1 receptor family.
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. Regulates the release of 5-hydroxytryptamine in the brain, and thereby affects neural activity. May also play a role in regulating the release of other neurotransmitters. May play a role in vasoconstriction (By similarity).
Homodimer. Heterodimer with HTR1B (By similarity).
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.
Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. GSK-3 subfamily.
Heterotetramer of TRAP-alpha, TRAP-beta, TRAP-delta and TRAP-gamma. Interacts with palmitoylated calnexin (CALX), the interaction is required for efficient folding of glycosylated proteins (By similarity).
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 SNF2/RAD54 helicase family. ISWI subfamily.
Belongs to the Integrator subunit 12 family.
Belongs to the multiprotein complex Integrator, at least composed of INTS1, INTS2, INTS3, INTS4, INTS5, INTS6, INTS7, INTS8, INTS9/RC74, INTS10, INTS11/CPSF3L and INTS12.
Belongs to the paired homeobox family. Bicoid subfamily.
Mannosyltransferase involved in glycosylphosphatidylinositol-anchor biosynthesis. Transfers the first alpha-1,4-mannose to GlcN-acyl-PI during GPI precursor assembly.
Belongs to the glycosyltransferase 8 family. Glycogenin subfamily.
Detected in heart, skeletal muscle, brain and testis, and at lower levels in kidney.
Divalent metal ions. Required for self-glucosylation. Manganese is the most effective.
Homodimer (PubMed:12051921, PubMed:15849187, PubMed:22226635, PubMed:22128147). Interacts (via C-terminus) with glycogen synthase GYS1 (By similarity). Interacts (via C-terminus) with glycogen synthase GYS2 (By similarity). This interaction is required for GYS2-mediated glycogen synthesis (By similarity).
Self-glucosylates, via an inter-subunit mechanism, to form an oligosaccharide primer that serves as substrate for glycogen synthase.
Self-glycosylated by the transfer of glucose residues from UDP-glucose to itself, forming an alpha-1,4-glycan of around 10 residues attached to Tyr-195.
Transcription elongation factor that enhances transcription elongation by RNA polymerase II (RNAPII).
Transcription elongation factor which increases mitochondrial RNA polymerase processivity. Regulates transcription of the mitochondrial genome, including genes important for the oxidative phosphorylation machinery.
Belongs to the G-protein coupled receptor 2 family.
Prion-like protein that has PrP(C)-like neuroprotective activity. May act as a modulator for the biological actions of normal and abnormal PrP.
Belongs to the tumor necrosis factor family.
S-nitrosylation inhibits channel currents and ATP release.
Structural component of the gap junctions and the hemichannels.
Essential component of the mitotic checkpoint, which prevents cells from prematurely exiting mitosis. Required for the assembly of the dynein-dynactin and MAD1-MAD2 complexes onto kinetochores. Its function related to the spindle assembly machinery is proposed to depend on its association in the mitotic RZZ complex.
Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols with a broad range of catalytic efficiencies.
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, monosacharides, bile acids and xenobiotics substrates. Key enzyme in the polyol pathway, catalyzes reduction of glucose to sorbitol during hyperglycemia. Reduces steroids and their derivatives and prostaglandins. Displays low enzymatic activity toward all-trans-retinal, 9-cis-retinal, and 13-cis-retinal. Catalyzes the reduction of diverse phospholipid aldehydes such as 1-palmitoyl-2-(5-oxovaleroyl)-sn -glycero-3-phosphoethanolamin (POVPC) and related phospholipid aldehydes that are generated from the oxydation of phosphotidylcholine and phosphatdyleethanolamides. Plays a role in detoxifying dietary and lipid-derived unsaturated carbonyls, such as crotonaldehyde, 4-hydroxynonenal, trans-2-hexenal, trans-2,4-hexadienal and their glutathione-conjugates carbonyls (GS-carbonyls).
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 NDUFB8 subunit family.
Complex I is composed of 45 different subunits.
Belongs to the concentrative nucleoside transporter (CNT) (TC 2.A.41) family.
Due to its high apparent affinity but slow transport, adenosine could act as a negative regulator of pyrimidine transport under some conditions.
N-glycosylated. N-glycosylation is required for localization to the plasma membrane and the transporter activity.
Sodium and pyrimidine nucleoside symporter of the plasma membrane that imports uridine, thymidine and cytidine into cells by coupling their transport to the transmembrane sodium electrochemical gradient (PubMed:11028933). Also transports adenosine, an atypical substrate transported with high apparent affinity, but low maximum velocity. Therefore, exhibits the transport characteristics of the nucleoside transport system cit or N2 subtype (N2/cit). Involved in renal nucleoside (re)absorption (By similarity).
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.
Belongs to the universal ribosomal protein uS14 family.
Component of the 40S small ribosomal subunit.
E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins.
ATP dependent phosphorylation of adenosine and other related nucleoside analogs to monophosphate derivatives.
Belongs to the carbohydrate kinase PfkB family.
Belongs to the copper/topaquinone oxidase family.
Topaquinone (TPQ) is generated by copper-dependent autoxidation of a specific tyrosyl residue.
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.
Belongs to the grh/CP2 family. CP2 subfamily.
Belongs to the VAMP-associated protein (VAP) (TC 9.B.17) family.
Belongs to the cytochrome c oxidase subunit 6c family.
Belongs to the eukaryotic RPC7 RNA polymerase subunit family.
Functions as a component of the nuclear pore complex (NPC).
Catalyzes the synthesis of dihydrouridine, a modified base found in the D-loop of most tRNAs.
Belongs to the small membrane AKAP family.
The glycine cleavage system catalyzes the degradation of glycine.
The glycine cleavage system is composed of four proteins: P, T, L and H.
UTP--glucose-1-phosphate uridylyltransferase catalyzing the conversion of glucose-1-phosphate into UDP-glucose, a crucial precursor for the production of glycogen.
Belongs to the glutaminyl-peptide cyclotransferase family.
Expressed preferentially in neutrophils.
Phosphorylated upon ligand binding; which is required for desensitization.
Receptor for interleukin-8 which is a powerful neutrophil chemotactic factor. Binding of IL-8 to the receptor causes activation of neutrophils. This response is mediated via a G-protein that activates a phosphatidylinositol-calcium second messenger system. Binds to IL-8 with high affinity. Also binds with high affinity to CXCL3, GRO/MGSA and NAP-2.
Belongs to the phosphohexose mutase family.
Belongs to the PtdIns transfer protein family. PI transfer class I subfamily.
Catalyzes the transfer of phosphatidylinositol (PI) and phosphatidylcholine (PC) between membranes (By similarity). Shows a preference for PI and PC containing shorter saturated or monosaturated acyl chains at the sn-1 and sn-2 positions (By similarity). Preference order for PC is C16:1 > C16:0 > C18:1 > C18:0 > C20:4 and for PI is C16:1 > C16:0 > C18:1 > C18:0 > C20:4 > C20:3 (By similarity).
Phosphorylated by PKC in a calcium and phosphatidylserine-dependent manner.
Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-mediated signals are transmitted across the cell membrane by the CD3 chains CD3D, CD3E, CD3G and CD3Z. All CD3 chains contain immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic domain. Upon TCR engagement, these motifs become phosphorylated by Src family protein tyrosine kinases LCK and FYN, resulting in the activation of downstream signaling pathways. CD3Z ITAMs phosphorylation creates multiple docking sites for the protein kinase ZAP70 leading to ZAP70 phosphorylation and its conversion into a catalytically active enzyme. Plays an important role in intrathymic T-cell differentiation. Additionally, participates in the activity-dependent synapse formation of retinal ganglion cells (RGCs) in both the retina and dorsal lateral geniculate nucleus (dLGN).
Phosphorylated on Tyr residues after T-cell receptor triggering by LCK in association with CD4/CD8.
The ITAM domains mediate interaction with SHB.
The TCR-CD3 complex is composed of a CD3D/CD3E and a CD3G/CD3E heterodimers that preferentially associate with TCRalpha and TCRbeta, respectively, to form TCRalpha/CD3E/CD3G and TCRbeta/CD3G/CD3E trimers. In turn, the hexamer interacts with CD3Z homodimer to form the TCR-CD3 complex. Alternatively, TCRalpha and TCRbeta can be replaced by TCRgamma and TCRdelta. Interacts with SLA. Interacts with TRAT1. Interacts with DOCK2. Interacts with SLA2. Interacts with SHB. Interacts with ZAP70. Interacts (tyrosine phosphorylated) with SHC1 (via SH2 domain). Interacts with PTPRC. Interacts with CRK; this interaction regulates CD3Z phosphorylation. Interacts (on T cell side) with CD81, ICAM1 and CD9 at immunological synapses between antigen-presenting cells and T cells. Interacts with CD160. Interacts with LY6E. Interacts with LY6E (By similarity). The signaling subunit of immunoglobulin gamma (IgG) Fc receptor complex. As a homodimer or a heterodimer with FCER1G, associates with the ligand binding subunit FCGR3A (via transmembrane domain); this interaction is a prerequisite for Fc receptor complex expression on the cell surface.
Belongs to the alpha-carbonic anhydrase family.
Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. EngB GTPase family.
Activated by reversible S-nitrosylation (PubMed:22036948). Repeated very high-level exercise increases S-nitrosylation (By similarity).
Belongs to the ryanodine receptor (TC 1.A.3.1) family. RYR1 subfamily.
Channel activity is modulated by phosphorylation. Phosphorylation at Ser-2843 may increase channel activity. Repeated very high-level exercise increases phosphorylation at Ser-2843.
Coexpression of normal and mutant Thr-4897 RYR1 in a 1:1 ratio produces RYR1 channels with normal halothane and caffeine sensitivities, but maximal levels of Ca(2+) release are reduced by 67%. Binding of [3H]ryanodine indicates that the heterozygous channel is activated by Ca(2+) concentrations 4-fold lower than normal. Single-cell analysis of cotransfected cells shows a significantly increased resting cytoplasmic Ca(2+) level and a significantly reduced luminal Ca(2+) level. These data indicated a leaky channel, possibly caused by a reduction in the Ca(2+) concentration required for channel activation.
Cytosolic calcium-activated calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytosol and thereby plays a key role in triggering muscle contraction following depolarization of T-tubules (PubMed:3722165, PubMed:10388749, PubMed:10097181, PubMed:12732639, PubMed:22036948, PubMed:26245150, PubMed:27662087). Repeated very high-level exercise increases the open probability of the channel and leads to Ca(2+) leaking into the cytoplasm (By similarity). Can also mediate the release of Ca(2+) from intracellular stores in neurons, and may thereby promote prolonged Ca(2+) signaling in the brain. Required for normal embryonic development of muscle fibers and skeletal muscle. Required for normal heart morphogenesis, skin development and ossification during embryogenesis (By similarity).
Detected in skeletal muscle (at protein level) (PubMed:2725677, PubMed:3722165, PubMed:25470059, PubMed:25517095, PubMed:27573175, PubMed:27468892). Fast- or slow-twitch skeletal muscle.
Homotetramer (PubMed:10097181, PubMed:15908964, PubMed:17027503, PubMed:18621707, PubMed:25470059, PubMed:25517095, PubMed:27662087, PubMed:27573175, PubMed:27468892). Can also form heterotetramers with RYR2 (PubMed:12213830). Identified in a complex composed of RYR1, PDE4D, PKA, FKBP1A and protein phosphatase 1 (PP1). Repeated very high-level exercise decreases interaction with PDE4D and protein phosphatase 1 (PP1) (By similarity). Interacts with CALM; CALM with bound calcium inhibits the RYR1 channel activity (PubMed:10601232, PubMed:11562475, PubMed:17027503). Interacts with S100A1 (By similarity). Interacts with FKBP1A; this stabilizes the closed conformation of the channel (PubMed:7669046, PubMed:10603943, PubMed:26245150, PubMed:25517095, PubMed:27468892). Interacts with CACNA1S; interaction with CACNA1S is important for activation of the RYR1 channel (PubMed:10388749). Interacts with CACNB1 (PubMed:21320436). Interacts with TRDN and ASPH; these interactions stimulate RYR1 channel activity (PubMed:9737879, PubMed:19398037). Interacts with SELENON (PubMed:18713863). Interacts with scorpion calcins (AC P0DPT1; AC P0DM30; AC A0A1L4BJ42; AC P59868; AC P60254; AC B8QG00; AC L0GBR1; AC P60252; AC P60253) (PubMed:27114612).
The calcium release channel activity resides in the C-terminal region while the remaining part of the protein constitutes the 'foot' structure spanning the junctional gap between the sarcoplasmic reticulum (SR) and the T-tubule (PubMed:2725677, PubMed:25517095, PubMed:27662087, PubMed:27573175, PubMed:27468892). Pore opening is mediated via the cytoplasmic calcium-binding domains that mediate a small rotation of the channel-forming transmembrane regions that then leads to channel opening (PubMed:27468892).
The calcium release is activated by increased cytosolic calcium levels, by nitric oxyde (NO), caffeine and ATP (PubMed:12732639, PubMed:22036948, PubMed:26245150, PubMed:27662087). Channel activity is modulated by the alkaloid ryanodine that binds to the open Ca-release channel with high affinity (PubMed:27662087). At low concentrations, ryanodine maintains the channel in an open conformation (PubMed:27662087). High ryanodine concentrations inhibit channel activity (PubMed:27662087). Channel activity is regulated by calmodulin (CALM). Channel activity is inhibited by magnesium ions, possibly by competition for calcium binding sites (PubMed:12732639).
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.
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.
Belongs to the prefoldin subunit beta family.
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.
Component of intercellular desmosome junctions. Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion.
In the kidney cortex and medulla, adrenal gland and stomach. In kidney, expression is higher in tubules in the outer medulla, with lower levels in cortex. In kidney cortex, expression is restricted to distal tubules.
Receptor for prostaglandin E2 (PGE2) (PubMed:8119961). Required for normal development of fever in response to pyrinogens, including IL1B, prostaglandin E2 and bacterial lipopolysaccharide (LPS). Required for normal potentiation of platelet aggregation by prostaglandin E2, and thus plays a role in the regulation of blood coagulation. Required for increased HCO3(-) secretion in the duodenum in response to mucosal acidification, and thereby contributes to the protection of the mucosa against acid-induced ulceration. Not required for normal kidney function, normal urine volume and osmolality (By similarity).
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.
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. The mature dimeric form interacts with PPP1R16B (via its fourth ankyrin repeat). Interacts with PPP1CA only in the presence of PPP1R16B.
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. Also acts as a receptor for several other ligands, including the pathogenic prion protein, viruses, and bacteria. Acts as a PPP1R16B-dependent substrate of PPP1CA.
This protein appears to have acquired a second function as a laminin receptor specifically in the vertebrate lineage.
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily.
Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily.
Belongs to the DNA polymerase type-X family.
Template-independent DNA polymerase which catalyzes the random addition of deoxynucleoside 5'-triphosphate to the 3'-end of a DNA initiator.
Endogenous F(1)F(o)-ATPase inhibitor limiting ATP depletion when the mitochondrial membrane potential falls below a threshold and the F(1)F(o)-ATP synthase starts hydrolyzing ATP to pump protons out of the mitochondrial matrix. Required to avoid the consumption of cellular ATP when the F(1)F(o)-ATP synthase enzyme acts as an ATP hydrolase.
Forms an alpha-helical dimer with monomers associated via an antiparallel alpha-helical coiled coil, leaving each N-terminal inhibitory region accessible for interaction with an F1 catalytic domain. The inhibitory N-terminal region binds the alpha(ADP-bound)-beta(ADP-bound) (ATP5F1A-ATP5F1B) interface of F1-ATPase, and also contact the central gamma subunit (ATP5F1C). This dimeric state is favored by pH values below 7.0, and at higher values the dimers associate to form inactive homotetramer, where the inhibitory region is occluded, masking its inhibitory activity.
Homodimer; represents the active form and is present at a pH value below 6.5. Homotetramer; represents the inactive form and is present at a pH value above 7.0.
Indirectly acts as a regulator of heme synthesis in erythroid tissues: regulates heme synthesis by modulating the mitochondrial pH and redox potential, allowing fech to efficiently catalyze the incorporation of iron into protoporphyrin IX to produce heme.
Multiubiquitin chain receptor involved in modulation of proteasomal degradation. Involved in nucleotide excision repair.
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.
Belongs to the metallo-dependent hydrolases superfamily. Peptidase M19 family.
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. Down-regulates IFNG-mediated STAT1 signaling and subsequent activation of JAK. Down-regulates SRC activity and signaling through MAP kinases.
FK506- and rapamycin-binding proteins (FKBPs) constitute a family of receptors for the two immunosuppressants which inhibit T-cell proliferation by arresting two distinct cytoplasmic signal transmission pathways. PPIases accelerate the folding of proteins (By similarity).
Inhibited preferentially by rapamycin over FK506.
Belongs to the TTC30/dfy-1/fleer family.
Required for polyglutamylation of axonemal tubulin. Plays a role in anterograde intraflagellar transport (IFT), the process by which cilia precursors are transported from the base of the cilium to the site of their incorporation at the tip.
Glycosylated. The nature of the carbohydrate chain varies between cell types (By similarity).
May have a role in immune function. Probably involved in the processing of antigenic peptides during MHC class II-mediated antigen presentation. May play a role in activation-induced lymphocyte depletion in the thymus, and in neuronal degeneration and glial cell activation in the brain (By similarity).
Belongs to the universal ribosomal protein uL23 family.
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 WD repeat WDR12/YTM1 family.
Component of the PeBoW complex, composed of BOP1, PES1 and WDR12. Within the PeBoW complex BOP1 interacts directly with PES1 and WDR12. The PeBoW complex also associates with the 66S pre-ribosome.
Component of the PeBoW complex, which is required for maturation of 28S and 5.8S ribosomal RNAs and formation of the 60S ribosome.
Has low activity towards the organophosphate paraxon and aromatic carboxylic acid esters (By similarity). Rapidly hydrolyzes lactones such as statin prodrugs (e.g. lovastatin). Hydrolyzes aromatic lactones and 5- or 6-member ring lactones with aliphatic substituents but not simple lactones or those with polar substituents.
Belongs to the Clp1 family. Clp1 subfamily.
Component of the tRNA splicing endonuclease complex, composed of CLP1, TSEN2, TSEN15, TSEN34 and TSEN54. Component of pre-mRNA cleavage complex II (CF-II). Also associates with numerous components of the pre-mRNA cleavage complex I (CF-I/CFIm), including NUDT21, CPSF2, CPSF3, CPSF6 and CPSF7. Interacts with CSTF2 and SYMPK.
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. Appears to have roles 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. 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.
Dual cyclooxygenase and peroxidase that plays an important role in the biosynthesis pathway of prostanoids, a class of C20 oxylipins mainly derived from arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate, AA, C20:4(n-6)), with a particular role in the inflammatory response. The cyclooxygenase activity oxygenates AA to the hydroperoxy endoperoxide prostaglandin G2 (PGG2), and the peroxidase activity reduces PGG2 to the hydroxy endoperoxide prostaglandin H2 (PGH2), the precursor of all 2-series prostaglandins and thromboxanes. This complex transformation is initiated by abstraction of hydrogen at carbon 13 (with S-stereochemistry), followed by insertion of molecular O2 to form the endoperoxide bridge between carbon 9 and 11 that defines prostaglandins. The insertion of a second molecule of O2 (bis-oxygenase activity) yields a hydroperoxy group in PGG2 that is then reduced to PGH2 by two electrons. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gastric epithelial cells, it is a key step in the generation of prostaglandins, such as prostaglandin E2 (PGE2), which plays an important role in cytoprotection. In platelets, it is involved in the generation of thromboxane A2 (TXA2), which promotes platelet activation and aggregation, vasoconstriction and proliferation of vascular smooth muscle cells. Can also use linoleate (LA, (9Z,12Z)-octadecadienoate, C18:2(n-6)) as substrate and produce hydroxyoctadecadienoates (HODEs) in a regio- and stereospecific manner, being (9R)-HODE ((9R)-hydroxy-(10E,12Z)-octadecadienoate) and (13S)-HODE ((13S)-hydroxy-(9Z,11E)-octadecadienoate) its major products.
The cyclooxygenase activity is inhibited by nonsteroidal anti-inflammatory drugs (NSAIDs) including ibuprofen, flurbiprofen, ketoprofen, naproxen, flurbiprofen, anirolac, fenclofenac and diclofenac.
Interacts with CFAP53, ODAD1 and ODAD3; the interactions link the outer dynein arms docking complex (ODA-DC) to the internal microtubule inner proteins (MIP) in cilium axoneme.
Belongs to the glycosyltransferase 2 family. GalNAc-T subfamily.
Belongs to the NADP-dependent oxidoreductase L4BD family.
NAD(P)H-dependent oxidoreductase involved in metabolic inactivation of pro- and anti-inflammatory eicosanoids: prostaglandins (PG), leukotrienes (LT) and lipoxins (LX). Catalyzes with high efficiency the reduction of the 13,14 double bond of 15-oxoPGs, including 15-oxo-PGE1, 15-oxo-PGE2, 15-oxo-PGF1-alpha and 15-oxo-PGF2-alpha (By similarity). Catalyzes with lower efficiency the oxidation of the hydroxyl group at C12 of LTB4 and its derivatives, converting them into biologically less active 12-oxo-LTB4 metabolites (By similarity). Reduces 15-oxo-LXA4 to 13,14 dihydro-15-oxo-LXA4, enhancing neutrophil recruitment at the inflammatory site (By similarity). Plays a role in metabolic detoxification of alkenals and ketones. Reduces alpha,beta-unsaturated alkenals and ketones, particularly those with medium-chain length, showing highest affinity toward (2E)-decenal and (3E)-3-nonen-2-one (By similarity). May inactivate 4-hydroxy-2-nonenal, a cytotoxic lipid constituent of oxidized low-density lipoprotein particles (By similarity).
Belongs to the eIF4E-binding protein family.
Belongs to the universal ribosomal protein uL13 family.
Belongs to the complex I LYR family. LYRM9 subfamily.
Buffers cytosolic calcium. May stimulate a membrane Ca(2+)-ATPase and a 3',5'-cyclic nucleotide phosphodiesterase.
Belongs to the cyclic nucleotide phosphodiesterase family. PDE1 subfamily.
Involved in an early step of the mitochondrial complex IV assembly process.
Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain.
Acts as Baeyer-Villiger monooxygenase on a broad range of substrates. Catalyzes the insertion of an oxygen atom into a carbon-carbon bond adjacent to a carbonyl, which converts ketones to esters (By similarity). Active on diverse carbonyl compounds, whereas soft nucleophiles are mostly non- or poorly reactive. In contrast with other forms of FMO it is non- or poorly active on 'classical' substrates such as drugs, pesticides, and dietary components containing soft nucleophilic heteroatoms (PubMed:7872795). Able to oxidize drug molecules bearing a carbonyl group on an aliphatic chain, such as nabumetone and pentoxifylline. Also, in the absence of substrates, shows slow but yet significant NADPH oxidase activity (By similarity). Acts as a positive modulator of cholesterol biosynthesis as well as glucose homeostasis, promoting metabolic aging via pleiotropic effects (By similarity).
Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.
Homodimerization via the leucine zipper domains is required for autophosphorylation.
The RING-type zinc finger domain is responsible for E3 ligase activity.
Belongs to the distal-less homeobox family.
Belongs to the type I cytokine receptor family. Type 1 subfamily.
Belongs to the aldehyde dehydrogenase family.
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, often at the interface between subunits. Can bind around 80 Ca(2+) ions. Regulates the release of lumenal Ca(2+) via the calcium release channel RYR1; this plays an important role in triggering muscle contraction. Negatively regulates store-operated Ca(2+) entry (SOCE) activity (By similarity).
Detected in skeletal muscle (at protein level). Detected in skeletal muscle.
Monomer; increases in response to a depletion of intracellular calcium. Homodimer. Homotetramer and homopolymer. Can form linear homooligomers. Ca(2+) ions promote oligomerization. Interacts (via C-terminal end and preferentially with the monomeric form) with STIM1; this interaction increases in response to a depletion of intracellular calcium, decreases both STIM1 aggregation and clustering, interaction of STIM1 with ORAI1 and store-operated Ca(2+) entry (SOCE) activity (By similarity). Interacts with ASPH and TRDN (PubMed:15731387, PubMed:19230141, PubMed:19398037).
Phosphorylated at very low, substoichiometric levels when isolated from skeletal muscle sarcoplasmic reticulum (PubMed:1985907). Can be phosphorylated by CK2 at Thr-381 (in vitro), albeit with low efficiency, suggesting this is not a physiological CK2 substrate (PubMed:1985907). Not phosphorylated at Thr-381 (PubMed:22170046).
Contributes to the regulation of the Wnt signaling pathway. Down-regulates CTNNB1-mediated transcriptional activation of target genes. May be involved in neuron differentiation.
Part of the tectonic-like complex (also named B9 complex).
Heterodimer of a B chain and an A chain linked by two disulfide bonds.
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.
The inhibitory site contains regions very similar to the hinge regions (sites that directly interact with the enzyme active site) and 'pseudosubstrate site' of the regulatory chains; but, unlike these chains, PKI does not contain cAMP-binding sites. The arginine residues within the inhibitory site are essential for inhibition and recognition of the enzyme active site.
Belongs to the protein phosphatase inhibitor 1 family.
Belongs to the snRNP Sm proteins family. SmF/LSm6 subfamily.
Belongs to the FKBP-type PPIase family. FKBP1 subfamily.
Has the potential to contribute to the immunosuppressive and toxic effects of FK506 and rapamycin. PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides (By similarity).
Identified in a complex composed of RYR2, FKBP1B, PKA catalytic subunit, PRKAR2A, AKAP6, and the protein phosphatases PP2A and PP1. Interacts directly with RYR2 (By similarity).
Asn-16 and Asn-72 undergo deamidation which gives rise to four extra negative charges. These are expected to decrease subunit-subunit interactions and so expose the hydrophobic interface to the aqueous environment.
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.
Belongs to the anion channel-forming bestrophin (TC 1.A.46) family. Calcium-sensitive chloride channel subfamily.
Forms calcium-sensitive chloride channels. Permeable to bicarbonate.
According to the authors the mRNA described in PubMed:9600854 may be encoded by a gene different from ALOX15.
Detected in reticulocytes (at protein level).
Interacts with PEBP1; in response to IL13/interleukin-13, prevents the interaction of PEBP1 with RAF1 to activate the ERK signaling cascade.
Non-heme iron-containing dioxygenase that catalyzes the stereo-specific peroxidation of free and esterified polyunsaturated fatty acids generating a spectrum of bioactive lipid mediators (PubMed:9600854, PubMed:9414270, PubMed:15123652, PubMed:17493578, PubMed:18311922). It inserts peroxyl groups at C12 or C15 of arachidonate ((5Z,8Z,11Z,14Z)-eicosatetraenoate) producing both 12-hydroperoxyeicosatetraenoate/12-HPETE and 15-hydroperoxyeicosatetraenoate/15-HPETE (PubMed:9600854, PubMed:9414270, PubMed:15123652, PubMed:17493578). It may then act on 12-HPETE to produce hepoxilins, which may show pro-inflammatory properties (PubMed:15123652). Can also peroxidize linoleate ((9Z,12Z)-octadecadienoate) to 13-hydroperoxyoctadecadienoate. May participate in the sequential oxidations of DHA ((4Z,7Z,10Z,13Z,16Z,19Z)-docosahexaenoate) to generate specialized pro-resolving mediators (SPMs)like resolvin D5 ((7S,17S)-diHPDHA) and (7S,14S)-diHPDHA, that actively down-regulate the immune response and have anti-aggregation properties with platelets. Can convert epoxy fatty acids to hydroperoxy-epoxides derivatives followed by an intramolecular nucleophilic substitution leading to the formation of monocyclic endoperoxides (By similarity). Plays an important role during the maintenance of self-tolerance by peroxidizing membrane-bound phosphatidylethanolamine which can then signal the sorting process for clearance of apoptotic cells during inflammation and prevent an autoimmune response. In addition to its role in the immune and inflammatory responses, this enzyme may play a role in epithelial wound healing in the cornea through production of lipoxin A4 (LXA(4)) and docosahexaenoic acid-derived neuroprotectin D1 (NPD1; 10R,17S-HDHA), both lipid autacoids exhibit anti-inflammatory and neuroprotective properties. Furthermore, it may regulate actin polymerization which is crucial for several biological processes such as the phagocytosis of apoptotic cells. It is also implicated in the generation of endogenous ligands for peroxisome proliferator activated receptor (PPAR-gamma), hence modulating macrophage development and function. It may also exert a negative effect on skeletal development by regulating bone mass through this pathway. As well as participates in ER stress and downstream inflammation in adipocytes, pancreatic islets, and liver (By similarity). Finally, it is also involved in the cellular response to IL13/interleukin-13 (By similarity).
The PLAT domain can bind calcium ions; this promotes association with membranes.
Belongs to the TRAFAC class dynamin-like GTPase superfamily. IRG family.
Associates with IL23A to form the IL-23 interleukin, a heterodimeric cytokine which functions in innate and adaptive immunity. IL-23 may constitute with IL-17 an acute response to infection in peripheral tissues. IL-23 binds to a heterodimeric receptor complex composed of IL12RB1 and IL23R, activates the Jak-Stat signaling cascade, stimulates memory rather than naive T-cells and promotes production of pro-inflammatory cytokines. IL-23 induces autoimmune inflammation and thus may be responsible for autoimmune inflammatory diseases and may be important for tumorigenesis.
Cytokine that can act as a growth factor for activated T and NK cells, enhance the lytic activity of NK/lymphokine-activated killer cells, and stimulate the production of IFN-gamma by resting PBMC.
Heterodimer with IL12A; disulfide-linked. The heterodimer is known as interleukin IL-12.
Belongs to the glycosyl hydrolase 13 family.
Mediates feedback control of cholesterol synthesis.
Belongs to the eukaryotic ribosomal protein eS27 family.
Belongs to the DEAD box helicase family.
Functional P2XRs are organized as homomeric and heteromeric trimers.
Involved in the lipid remodeling steps of GPI-anchor maturation. Required for stable expression of GPI-anchored proteins at the cell surface.
Multifunctional protein that is involved in the regulation of many processes.
Belongs to the 2'-deoxynucleoside 5'-phosphate N-hydrolase 1 family.
Catalyzes the cleavage of the N-glycosidic bond of deoxyribonucleoside 5'-monophosphates to yield deoxyribose 5-phosphate and a purine or pyrimidine base. Deoxyribonucleoside 5'-monophosphates containing purine bases are preferred to those containing pyrimidine bases.
Belongs to the Golgi pH regulator (TC 1.A.38) family.
Belongs to the potassium channel family. B (Shab) (TC 1.A.1.2) subfamily. Kv2.2/KCNB2 sub-subfamily.
Homotetramer or heterotetramer with KCNB1. Heterotetramer with KCNS1 and KCNS2 (By similarity). Interacts (via phosphorylated FFAT motif) with VAPA and VAPB (By similarity).
Inhibited by quinine at micromolar levels. Modestly sensitive to millimolar levels of tetraethylammonium (TEA) and 4-aminopyridine (4-AP).
Phosphorylated (By similarity). Phosphorylation at Ser-608 of the FFAT motif activates interaction with MOSPD2, VAPA and VAPB (By similarity).
The transmembrane segment S4 functions as voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Channel opening and closing is effected by a conformation change that affects the position and orientation of the voltage-sensor paddle formed by S3 and S4 within the membrane. A transmembrane electric field that is positive inside would push the positively charged S4 segment outwards, thereby opening the pore, while a field that is negative inside would pull the S4 segment inwards and close the pore. Changes in the position and orientation of S4 are then transmitted to the activation gate formed by the inner helix bundle via the S4-S5 linker region.
Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and smooth muscle cells. Channels open or close in response to the voltage difference across the membrane, letting potassium ions pass in accordance with their electrochemical gradient. Homotetrameric channels mediate a delayed-rectifier voltage-dependent outward potassium current that display rapid activation and slow inactivation in response to membrane depolarization. Can form functional homotetrameric and heterotetrameric channels that contain variable proportions of KCNB1; channel properties depend on the type of alpha subunits that are part of the channel. Can also form functional heterotetrameric channels with other alpha subunits that are non-conducting when expressed alone, such as KCNS1 and KCNS2, creating a functionally diverse range of channel complexes. In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Contributes to the delayed-rectifier voltage-gated potassium current in cortical pyramidal neurons and smooth muscle cells.
Belongs to the glutamine synthetase family.
Dodecamer. Interacts with BFSP2 and VIM.
May act as a component of the cytoskeleton or as a chaperone for the reorganization of intermediate filament proteins during terminal differentiation in the lens. Does not seem to have enzymatic activity (By similarity).
Belongs to the glycosyltransferase 10 family.
Predominantly fucosylates the innermost N-acetyl glucosamine (GlcNAc) residue in biantennary N-glycan acceptors.
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. 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. Acts as a lipid sensor that regulates mitochondrial fusion by regulating activation of the JNK pathway.
Required for recruitment of CENPA to centromeres and normal chromosome segregation during mitosis.
Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family. CACNA1C subfamily.
Binding of intracellular calcium through the EF-hand motif inhibits the opening of the channel.
Component of a calcium channel complex consisting of a pore-forming alpha subunit (CACNA1C) and ancillary beta, gamma and delta subunits (PubMed:17525370, PubMed:21127204). The channel complex contains alpha, beta, gamma and delta subunits in a 1:1:1:1 ratio, i.e. it contains only one of each type of subunit (Probable). CACNA1C channel activity is modulated by ancillary subunits, such as CACNB1, CACNB2, CACNB3, CACNA2D1 and CACNA2D4 (PubMed:9278523, PubMed:15615847, PubMed:17525370, PubMed:21127204). Interacts with CACNB1 (PubMed:7509046, PubMed:15615847, PubMed:21127204). Interacts with CACNB2 (PubMed:17525370, PubMed:21127204, PubMed:22649239). Identified in a complex with CACNA2D4 and CACNB3. Interacts with CACNB3 (By similarity). Interacts with CACNA2D1 (PubMed:9278523, PubMed:21127204). Interacts with the gamma subunits CACNG4, CACNG6, CACNG7 and CACNG8 (PubMed:21127204). Interacts with CACNA2D4 (By similarity). Interacts with CALM1 (PubMed:29363593). Interacts (via the N-terminus and the C-terminal C and IQ motifs) with CABP1; this inhibits Ca(2+)-dependent channel inactivation. The binding via the C motif is calcium independent whereas the binding via IQ requires the presence of calcium and is mutually exclusive with calmodulin binding (By similarity). The binding to the cytoplasmic N-terminal domain is calcium independent but is essential for the channel modulation. Interacts (via C-terminal CDB motif) with CABP5; in a calcium-dependent manner. Interacts with CIB1; the interaction increases upon cardiomyocytes hypertrophy (By similarity). Interacts with STAC1, STAC2 and STAC3; this inhibits channel inactivation, probably by hindering CALM1 binding (PubMed:25548159, PubMed:29363593).
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.
Expression in cardiac muscle. In lung, expressed in airway and vascular smooth muscle cells.
Inhibited by dihydropyridines (DHP), such as isradipine (PubMed:2474130, PubMed:9278523). Inhibited by nifedipine (PubMed:23145875). Channel activity is regulated by Ca(2+) and calmodulin (PubMed:7491499, PubMed:29363593). Binding of STAC1, STAC2 or STAC3 to a region that overlaps with the calmodulin binding site inhibits channel inactivation by Ca(2+) and calmodulin (PubMed:29363593). Binding of calmodulin or CABP1 at the same regulatory sites results in opposite effects on the channel function (By similarity). Shear stress and pressure increases calcium channel activity (By similarity).
Phosphorylation by PKA at Ser-1928 activates the channel (PubMed:1325377). Elevated levels of blood glucose lead to increased phosphorylation by PKA (By similarity).
Pore-forming, alpha-1C subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents (PubMed:2474130, PubMed:2169433, PubMed:8232554, PubMed:9502794, PubMed:9278523, PubMed:15615847, PubMed:17525370, PubMed:21127204, PubMed:22928916, PubMed:23145875, PubMed:29363593, PubMed:22649239). Mediates influx of calcium ions into the cytoplasm, and thereby triggers calcium release from the sarcoplasm (PubMed:23145875). Plays an important role in excitation-contraction coupling in the heart (PubMed:17525370, PubMed:22928916, PubMed:23145875). Required for normal heart development and normal regulation of heart rhythm (By similarity). Required for normal contraction of smooth muscle cells in blood vessels and in the intestine. Essential for normal blood pressure regulation via its role in the contraction of arterial smooth muscle cells (By similarity). Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group (Probable).
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.
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.
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.
Involved in the detoxification of xenobiotics and in the activation of ester and amide prodrugs.
Belongs to the exonuclease superfamily. TREX family.
Belongs to the carotenoid oxygenase family.
May be involved in the intracellular transport of sterols or other lipids. May bind cholesterol or other sterols.
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.
Belongs to the eukaryotic release factor 1 family.
Component of the eRF1-eRF3-GTP ternary complex, a ternary complex that mediates translation termination in response to the termination codons. The eRF1-eRF3-GTP complex binds to a stop codon in the ribosomal A-site. ETF1/ERF1 is responsible for stop codon recognition and inducing hydrolysis of peptidyl-tRNA. Following GTP hydrolysis, eRF3 (GSPT1/ERF3A or GSPT2/ERF3B) dissociates, permitting ETF1/eRF1 to accommodate fully in the A-site, followed by hydrolysis of peptidyl-tRNA. Component of the transient SURF complex which recruits UPF1 to stalled ribosomes in the context of nonsense-mediated decay (NMD) of mRNAs containing premature stop codons. Required for SHFL-mediated translation termination which inhibits programmed ribosomal frameshifting (-1PRF) of mRNA from viruses and cellular genes.
Component of the eRF1-eRF3-GTP ternary complex, composed of ETF1/ERF1 and eRF3 (GSPT1/ERF3A or GSPT2/ERF3B) and GTP. Component of the transient SURF (SMG1-UPF1-eRF1-eRF3) complex. Interacts with JMJD4. The ETF1-GSPT1 complex interacts with JMJD4.
Hydroxylation at Lys-63 by JMJD4 promotes its translational termination efficiency.
Ubiquitinated via 'Lys-6'-linked polyubiquitin chains by RNF14 and RNF25 in response to ribosome collisions (ribosome stalling), leading to its degradation by the proteasome and rescue of stalled ribosomes.
Acetylation at Lys-125 markedly inhibits catalysis of cis to trans isomerization (By similarity). PPIA acetylation also antagonizes the immunosuppressive effects of cyclosporine by inhibiting the sequential steps of cyclosporine binding and calcineurin inhibition (By similarity). Acetylation at Lys-125 favors the interaction with TARDBP (By similarity).
Belongs to the cyclophilin-type PPIase family. PPIase A subfamily.
Binds cyclosporin A (CsA). CsA mediates some of its effects via an inhibitory action on PPIase.
Catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides (By similarity). Exerts a strong chemotactic effect on leukocytes partly through activation of one of its membrane receptors BSG/CD147, initiating a signaling cascade that culminates in MAPK/ERK activation (By similarity). Activates endothelial cells (ECs) in a proinflammatory manner by stimulating activation of NF-kappa-B and ERK, JNK and p38 MAP-kinases and by inducing expression of adhesion molecules including SELE and VCAM1 (By similarity). Induces apoptosis in ECs by promoting the FOXO1-dependent expression of CCL2 and BCL2L11 which are involved in EC chemotaxis and apoptosis (By similarity). In response to oxidative stress, initiates proapoptotic and antiapoptotic signaling in ECs via activation of NF-kappa-B and AKT1 and up-regulation of antiapoptotic protein BCL2 (By similarity). Negatively regulates MAP3K5/ASK1 kinase activity, autophosphorylation and oxidative stress-induced apoptosis mediated by MAP3K5/ASK1 (By similarity). Necessary for the assembly of TARDBP in heterogeneous nuclear ribonucleoprotein (hnRNP) complexes and regulates TARDBP binding to RNA UG repeats and TARDBP-dependent expression of HDAC6, ATG7 and VCP which are involved in clearance of protein aggregates (By similarity). Plays an important role in platelet activation and aggregation (By similarity). Regulates calcium mobilization and integrin ITGA2B:ITGB3 bidirectional signaling via increased ROS production as well as by facilitating the interaction between integrin and the cell cytoskeleton (By similarity). Binds heparan sulfate glycosaminoglycans (By similarity).
Interacts with protein phosphatase PPP3CA/calcineurin A (By similarity). Interacts with isoform 2 of BSG/CD147 (By similarity). Interacts with FOXO1; the interaction promotes FOXO1 dephosphorylation, nuclear accumulation and transcriptional activity (By similarity). Interacts with integrin ITGA2B:ITGB3; the interaction is ROS and peptidyl-prolyl cis-trans isomerase (PPIase) activity-dependent and is increased in the presence of thrombin (By similarity). Interacts with MAP3K5 (By similarity). Interacts with TARDBP; the interaction is dependent on the RNA-binding activity of TARDBP and the PPIase activity of PPIA/CYPA and the acetylation of PPIA/CYPA at Lys-125 favors the interaction (By similarity). Interacts with HNRNPA1, HNRNPA2B1, HNRNPC, RBMX, HNRNPK and HNRNPM (By similarity).
Belongs to the thiolase-like superfamily. Thiolase 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.
Inhibits factor X (X(a)) directly and, in a Xa-dependent way, inhibits VIIa/tissue factor activity, presumably by forming a quaternary Xa/LACI/VIIa/TF complex. It possesses an antithrombotic action and also the ability to associate with lipoproteins in plasma.
This inhibitor contains three inhibitory domains. The first domain interacts with VIIa and TF, the second one with Xa (By similarity).
Potential NADPH-dependent oxidoreductase. May be involved in the regulation of neuronal survival, differentiation and axonal outgrowth.
Belongs to the GLI C2H2-type zinc-finger protein family.
Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.
Belongs to the ubiquitin-conjugating enzyme family.
Belongs to the Mediator complex subunit 21 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.
Belongs to the type I cytokine receptor family. Type 4 subfamily.
Receptor for both interleukin 4 and interleukin 13. Couples to the JAK1/2/3-STAT6 pathway. The IL4 response is involved in promoting Th2 differentiation. The IL4/IL13 responses are involved in regulating IgE production and, chemokine and mucus production at sites of allergic inflammation. In certain cell types, can signal through activation of insulin receptor substrates, IRS1/IRS2.
Homodimer; disulfide-linked. Seems to also exist as monomers.
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 small GTPase superfamily. Rab 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 phosphatidylserine decarboxylase family. PSD-B subfamily. Eukaryotic type I sub-subfamily.
Binds 1 pyruvoyl group covalently per subunit.
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.
Belongs to the protein kinase superfamily. Tyr protein kinase family.
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.
In the N-terminal section; belongs to the MoaB/Mog family.
Found in the skin, kidney, distal colon and brain. In the kidney it is found in the connecting tubule, cortical collecting duct and outer medullary collecting duct while in the brain it is specific to choroid plexus and cortex.
The X(+)/K(+) ATPase pump is composed of a catalytic alpha subunit and an auxiliary non-catalytic beta subunit. The alpha subunit pairs with the beta subunit of gastric H(+)/K(+) ATPase ATP4B or the beta subunit of Na(+)/K(+) ATPases ATP1B1 and ATP1B3; this interaction is required for the formation of a functionally active pump and its targeting at the plasma membrane.
The catalytic subunit of a H(+)/K(+) ATPase and/or Na(+)/K(+) ATPase pump which transports K(+) ions in exchange for Na(+) and/or H(+) ions across the apical membrane of epithelial cells. Uses ATP as an energy source to pump K(+) ions into the cell while transporting Na(+) and/or H(+) ions to the extracellular compartment (By similarity). Involved in the maintenance of electrolyte homeostasis through K(+) ion absorption in kidney and colon (By similarity). In the airway epithelium, may play a primary role in mucus acidification regulating its viscosity and clearance (By similarity).
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 (By similarity). Interacts with NXN; the interaction is direct (By similarity). Interacts with KCTD20 (By similarity). Interacts with BTBD10 (By similarity). Interacts with SGO1 and SGO2. Interacts with TP53. Interacts with AXIN1; the interaction dephosphorylates AXIN1. Interacts with PIM3; this interaction promotes dephosphorylation, ubiquitination and proteasomal degradation of PIM3. Interacts with RAF1. Interaction with IGBP1 protects unassembled PPP2CA from degradative ubiquitination. Interacts with GSK3B (via C2 domain). Interacts with MFHAS1; retains PPP2CA into the cytoplasm and excludes it from the nucleus. Interacts with PABIR1/FAM122A. Interacts with ADCY8; interaction is phosphatase activity-dependent; antagonizes interaction between ADCY8 and calmodulin. Interacts with CRTC3 (when phosphorylated at 'Ser-391'). Interacts with SPRY2; the interaction is inhibited by TESK1 interaction with SPRY2, possibly by vesicular sequestration of SPRY2. Interacts with TRAF3IP3. Interacts with AMBRA1 (via PxP motifs); enhancing interaction between PPP2CA and MYC or FOXO3 (By similarity). Forms a complex with AMBRA1 and BECN1; AMBRA1 and BECN1 components of the complex regulate MYC stability via different pathways (By similarity).
PP2A is the major phosphatase for microtubule-associated proteins (MAPs) (By similarity). PP2A can modulate the activity of phosphorylase B kinase casein kinase 2, mitogen-stimulated S6 kinase, and MAP-2 kinase (By similarity). Cooperates with SGO2 to protect centromeric cohesin from separase-mediated cleavage in oocytes specifically during meiosis I (By similarity). Can dephosphorylate p53/TP53 (By similarity). Activates RAF1 by dephosphorylating it at 'Ser-259' (By similarity). Mediates dephosphorylation of WEE1, preventing its ubiquitin-mediated proteolysis, increasing WEE1 protein levels, and promoting the G2/M checkpoint (By similarity). Mediates dephosphorylation of MYC; promoting its ubiquitin-mediated proteolysis: interaction with AMBRA1 enhances interaction between PPP2CA and MYC (By similarity). Mediates dephosphorylation of FOXO3; promoting its stabilization: interaction with AMBRA1 enhances interaction between PPP2CA and FOXO3 (By similarity). Catalyzes dephosphorylation of the pyrin domain of NLRP3, promoting assembly of the NLRP3 inflammasome (By similarity).
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).
Polyubiquitinated, leading to its degradation by the proteasome.
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).
Binds specifically to the 3'-terminal U-tract of U6 snRNA.
Belongs to the GPI inositol-deacylase family.
Involved in inositol deacylation of GPI-anchored proteins. GPI inositol deacylation may important for efficient transport of GPI-anchored proteins from the endoplasmic reticulum to the Golgi.
Belongs to the ubiquitin family. SUMO subfamily.
Belongs to the FMN-dependent alpha-hydroxy acid dehydrogenase family.
Belongs to the cytidylyltransferase family.
Catalyzes the key rate-limiting step in the CDP-choline pathway for phosphatidylcholine biosynthesis.
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 SIMIBI class G3E GTPase family. ArgK/MeaB subfamily.
GTPase, binds and hydrolyzes GTP (By similarity). Involved in intracellular vitamin B12 metabolism, mediates the transport of cobalamin (Cbl) into mitochondria for the final steps of adenosylcobalamin (AdoCbl) synthesis (By similarity). Functions as a G-protein chaperone that assists AdoCbl cofactor delivery from MMAB to the methylmalonyl-CoA mutase (MMUT) (By similarity). Plays a dual role as both a protectase and a reactivase for MMUT (By similarity). Protects MMUT from progressive inactivation by oxidation by decreasing the rate of the formation of the oxidized inactive cofactor hydroxocobalamin (OH2Cbl) (By similarity). Additionally acts a reactivase by promoting the replacement of OH2Cbl by the active cofactor AdoCbl, restoring the activity of MMUT in the presence and hydrolysis of GTP (By similarity).
Homodimer. Interacts with MMUT (the apoenzyme form); the interaction is GTP dependent.
Functions as a voltage-gated monoatomic cation channel permeable to both potassium and calcium (PubMed:21381722). Plays a role in the cellular response to DNA damage (By similarity).
Homooligomer (PubMed:21381722). Interacts with CRYAB; in the cellular response to DNA damage (By similarity).
Widely expressed. Expressed in skeletal, cardiac and smooth muscle cells, in brain, including neuroglial cells, cerebral cortex neurons and cerebellum, but not Purkinje cells. Also detected in Paneth and Goblet cells of the small intestine (but not in the epithelium), duodenal gland, pancreas, parotid gland, testis, thyroid gland and adrenal gland, as well as in epidermis, choroid plexus, ductus epididymidis, lymphocytes, fibroblasts, endothelial cells and seminiferous epithelial cells (at protein level). Not detected in mucous cells of the duodenal gland, in hepatocytes nor in uriniferous tubules.
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).
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 anti-Muellerian hormone.
Phosphorylated; lowers poly(rC)-binding activity.
Single-stranded nucleic acid binding protein that binds preferentially to oligo dC (By similarity). Together with PCBP2, required for erythropoiesis, possibly by regulating mRNA splicing (By similarity).
Belongs to the glycosyl hydrolase 47 family.
Belongs to the V-ATPase F 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.
V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex.
Belongs to the glycosyltransferase 22 family.
Belongs to the sphingomyelin synthase 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.
Expressed in hippocampus, striatum, hypothalamus, cerebellum, small intestine, colon and adrenal gland.
Receptor for neuropeptide Y and peptide YY. The activity of this receptor is mediated by G proteins that inhibit adenylate cyclase activity.
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.
Belongs to the eukaryotic/archaeal PrmC-related family.
Milk-specific; major protein component of milk whey.
Belongs to the immunoglobulin superfamily. Contactin family.
Belongs to the class-V pyridoxal-phosphate-dependent aminotransferase family.
Belongs to the class-V pyridoxal-phosphate-dependent aminotransferase family. NifS/IscS subfamily.
Stimulates the secretion of gonadotropins; it stimulates the secretion of both luteinizing and follicle-stimulating hormones.
Belongs to the sodium:solute symporter (SSF) (TC 2.A.21) family.
Belongs to the protein-tyrosine phosphatase family. Receptor class 5 subfamily.
Homodimer; binds DNA as homodimer. Heterodimer; heterodimerizes with other members of ATF family and with JUN family members.
Stress-responsive chromatin regulator that plays a role in various biological processes including innate immunological memory, adipocyte differentiation or telomerase regulation. In absence of stress, contributes to the formation of heterochromatin and heterochromatin-like structure by recruiting histone H3K9 tri- and di-methyltransferases thus silencing the transcription of target genes such as STAT1 in adipocytes, or genes involved in innate immunity in macrophages and adipocytes. Stress induces ATF7 phosphorylation that disrupts interactions with histone methyltransferase and enhances the association with coactivators containing histone acetyltransferase and/or histone demethylase, leading to disruption of the heterochromatin-like structure and subsequently transcriptional activation. In response to TNF-alpha, which is induced by various stresses, phosphorylated ATF7 and telomerase are released from telomeres leading to telomere shortening.
Belongs to the FIT family. FIT1 subfamily.
Plays an important role in the formation of lipid droplets (LDs), which are storage organelles at the center of lipid and energy homeostasis. Directly binds to diacylglycerol (DAGs) and triacylglycerol.
Belongs to the UbiA prenyltransferase family.
Catalyzes the prenylation of para-hydroxybenzoate (PHB) with an all-trans polyprenyl group. Mediates the second step in the final reaction sequence of coenzyme Q (CoQ) biosynthesis, which is the condensation of the polyisoprenoid side chain with PHB, generating the first membrane-bound Q intermediate.
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.
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.
Belongs to the class I-like SAM-binding methyltransferase superfamily. rRNA adenine N(6)-methyltransferase family.
Belongs to the adaptor complexes small subunit family.
A cytochrome P450 monooxygenase involved in primary bile acid biosynthesis. Catalyzes the 12alpha-hydroxylation of 7alpha-hydroxy-4-cholesten-3-one, an intermediate metabolite in cholic acid biosynthesis (PubMed:1400444, PubMed:8943286). Controls biliary balance of cholic acid and chenodeoxycholic acid, ultimately regulating the intestinal absorption of dietary lipids (By similarity). 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--hemoprotein reductase) (PubMed:1400444, PubMed:8943286).
Up-regulated upon treatment with streptozotocin.
Belongs to the protein-tyrosine phosphatase family. Non-receptor class myotubularin subfamily.
Belongs to the class I-like SAM-binding methyltransferase superfamily. Glycine N-methyltransferase family.
Catalyzes the methylation of glycine by using S-adenosylmethionine (AdoMet) to form N-methylglycine (sarcosine) with the concomitant production of S-adenosylhomocysteine (AdoHcy), a reaction regulated by the binding of 5-methyltetrahydrofolate (PubMed:4692843, PubMed:8281755). Plays an important role in the regulation of methyl group metabolism by regulating the ratio between S-adenosyl-L-methionine and S-adenosyl-L-homocysteine (By similarity).
Inhibited by 5-methyltetrahydrofolate monoglutamate and by 5-methyltetrahydrofolate pentaglutamate, inhibition is much more effective by the pentaglutamate form than by the monoglutamate form. Two molecules of 5-methyltetrahydrofolate are bound per tetramer. The binding sites are localized between subunits. Inhibitor binding may preclude movements of the polypeptide chain that are necessary for enzyme activity.
Belongs to the G-protein coupled receptor Fz/Smo family.
Belongs to the dynein light chain Tctex-type family.
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.
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 by FAM20C in the extracellular medium at multiple sites within the S-x-E/pS motif (By similarity). The phosphorylated form inhibits hydroxyapatite crystallization. Dephosphorylation via a mechanism involving ALPL/TNAP promotes hydroxyapatite crystallization (By similarity).
Forms covalent cross-links mediated by transglutaminase TGM2, between a glutamine and the epsilon-amino group of a lysine residue, forming homopolymers and heteropolymers, increasing its collagen binding properties.
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 clathrin heavy chain family.
Clathrin is the major protein of the polyhedral coat of coated pits and vesicles.
Hormone involved in the regulation of erythrocyte proliferation and differentiation and the maintenance of a physiological level of circulating erythrocyte mass. Binds to EPOR leading to EPOR dimerization and JAK2 activation thereby activating specific downstream effectors, including STAT1 and STAT3.
Belongs to the glycosyl hydrolase 79 family.
Involved in the initiation of DNA replication. Also participates in checkpoint controls that ensure DNA replication is completed before mitosis is initiated.
Belongs to the multicopper oxidase family.
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.
Autoacetylation strongly increases tubulin acetylation.
Belongs to the acetyltransferase ATAT1 family.
Component of the BBSome complex. Interacts with AP2 alpha-adaptins, including AP2A2, but not with AP1 gamma-adaptin (AP1G1/AP1G2); this interaction is required for efficient alpha-tubulin acetylation, hence clathrin-coated pits are sites of microtubule acetylation.
Specifically acetylates 'Lys-40' in alpha-tubulin on the lumenal side of microtubules. Promotes microtubule destabilization and accelerates microtubule dynamics; this activity may be independent of acetylation activity. Acetylates alpha-tubulin with a slow enzymatic rate, due to a catalytic site that is not optimized for acetyl transfer. Enters the microtubule through each end and diffuses quickly throughout the lumen of microtubules. Acetylates only long/old microtubules because of its slow acetylation rate since it does not have time to act on dynamically unstable microtubules before the enzyme is released. Required for normal sperm flagellar function. Promotes directional cell locomotion and chemotaxis, through AP2A2-dependent acetylation of alpha-tubulin at clathrin-coated pits that are concentrated at the leading edge of migrating cells. May facilitate primary cilium assembly.
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 SLC26A/SulP transporter (TC 2.A.53) family.
Mediates chloride-bicarbonate exchange with a chloride bicarbonate stoichiometry of 2:1 in the intestinal epithelia. Plays a role in the chloride and bicarbonate homeostasis during sperm epididymal maturation and capacitation.
Belongs to the small GTPase superfamily. Arf family.
Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth. Could also have a single-stranded nucleic acid-binding activity and could play a role in RNA and/or DNA metabolism. It may also have a role in the development of malignancy and the growth progression of some tumors.
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 oligoribonuclease family.
Belongs to the eukaryotic ribosomal protein eL22 family.
Belongs to the G-protein coupled receptor 1 family. Vasopressin/oxytocin receptor subfamily.
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.
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.
4 consecutive G-P-P tripeptides are present at the C-terminus of the triple-helical region. These may provide high thermal stability of this region.
Homotrimers, or heterotrimers in association with alpha 2(VIII) type collagens. Four homotrimers can form a tetrahedron stabilized by central interacting C-terminal NC1 trimers (By similarity).
Macromolecular component of the subendothelium. Major component of the Descemet's membrane (basement membrane) of corneal endothelial cells. Also a component of the endothelia of blood vessels. Necessary for migration and proliferation of vascular smooth muscle cells and thus, has a potential role in the maintenance of vessel wall integrity and structure, in particular in atherogenesis (By similarity).
Prolines at the third position of the tripeptide repeating unit (G-X-Y) are hydroxylated in some or all of the chains.
Proteolytically cleaved by neutrophil elastase, in vitro. Proteolytic processing produces the C-terminal NC1 domain fragment, vastatin (By similarity).
Vastatin, the C-terminal fragment comprising the NC1 domain, inhibits aortic endothelial cell proliferation and causes cell apoptosis.
Belongs to the WD repeat G protein beta family.
Acetylated. Acetylation occurs in pancreatic beta cells in response to stimulation by incretin hormones in a histone acetyltransferase (HAT)/histone deacetylase (HDAC)-dependent signaling pathway, promoting beta cell survival.
Belongs to the potassium channel family. B (Shab) (TC 1.A.1.2) subfamily. Kv2.1/KCNB1 sub-subfamily.
Homotetramer or heterotetramer with KCNB2. Heterotetramer with non-conducting channel-forming alpha subunits such as KCNF1, KCNG1, KCNG3, KCNG4, KCNH1, KCNH2, KCNS1, KCNS2, KCNS3 and KCNV1. Channel activity is regulated by association with ancillary beta subunits such as AMIGO1, KCNE1, KCNE2 and KCNE3. Interacts with KCNV2 (By similarity). Self-associates (via N-terminus and C-terminus); self-association is required to regulate trafficking, gating and C-terminal phosphorylation-dependent modulation of the channel. Interacts (via C-terminus) with STX1A (via C-terminus); this decreases the rate of channel activation and increases the rate of channel inactivation in pancreatic beta cells, induces also neuronal apoptosis in response to oxidative injury as well as pore-independent enhancement of exocytosis in neuroendocrine cells, chromaffin cells, pancreatic beta cells and from the soma of dorsal root ganglia (DRG) neurons. Interacts (via N-terminus) with SNAP25; this decreases the rate of channel inactivation in pancreatic beta cells and also increases interaction during neuronal apoptosis in a N-methyl-D-aspartate receptor (NMDAR)-dependent manner. Interacts (via N-terminus and C-terminus) with VAMP2 (via N-terminus); stimulates channel inactivation rate. Interacts with CREB1; this promotes channel acetylation in response to stimulation by incretin hormones. Interacts (via N-terminus and C-terminus) with MYL12B. Interacts (via N-terminus) with PIAS3; this increases the number of functional channels at the cell surface. Interacts with SUMO1. Interacts (via phosphorylated form) with PTPRE; this reduces phosphorylation and channel activity in heterologous cells. Interacts (via phosphorylated FFAT motif) with VAPA and VAPB (By similarity).
Inhibited by 12.7 nM stromatoxin 1 (ScTx1), a spider venom toxin of the tarantula S.calceata. Inhibited by 42 nM hanatoxin 1 (HaTx1), a spider venom toxin of the tarantula G.spatulata. Modestly sensitive to millimolar levels of tetraethylammonium (TEA). Modestly sensitive to millimolar levels of 4-aminopyridine (4-AP). Completely insensitive to toxins such as dendrotoxin (DTX) and charybdotoxin (CTX).
Phosphorylated. Differential C-terminal phosphorylation on a subset of serines allows graded activity-dependent regulation of channel gating in hippocampal neurons. Ser-607 and Tyr-128 are significant sites of voltage-gated regulation through phosphorylation/dephosphorylation activities. Tyr-128 can be phosphorylated by Src and dephosphorylated by cytoplasmic form of the phosphatase PTPRE. CDK5-induced Ser-607 phosphorylation increases in response to acute blockade of neuronal activity. Phosphorylated on Tyr-128 by Src and on Ser-805 by MAPK14/P38MAPK; phosphorylations are necessary and sufficient for an increase in plasma membrane insertion, apoptotic potassium current surge and completion of the neuronal cell death program. Phosphorylated on Ser-520, Ser-607, Ser-656 and Ser-805 by CDK5; phosphorylation is necessary for KCNB1 channel clustering formation. The Ser-607 phosphorylation state differs between KCNB1-containing clusters on the proximal and distal portions of the axon initial segment (AIS). Highly phosphorylated on serine residues in the C-terminal cytoplasmic tail in resting neurons. Phosphorylated in pancreatic beta cells in response to incretin hormones stimulation in a PKA- and RPS6KA5/MSK1-dependent signaling pathway, promoting beta cell survival. Phosphorylation on Ser-567 is reduced during postnatal development with low levels at P2 and P5; levels then increase to reach adult levels by P14. Phosphorylation on Ser-457, Ser-541, Ser-567, Ser-607, Ser-656 and Ser-720 as well as the N-terminal Ser-15 are sensitive to calcineurin-mediated dephosphorylation contributing to the modulation of the voltage-dependent gating properties. Dephosphorylation by phosphatase PTPRE confers neuroprotection by its inhibitory influence on the neuronal apoptotic potassium current surge in a Zn(2+)-dependent manner. Dephosphorylated at Ser-607 by protein phosphatase PPP1CA. Hypoxia-, seizure- or glutamate-induced neuronal activity promote calcium/calcineurin-dependent dephosphorylation resulting in a loss of KCNB1-containing clustering and enhanced channel activity. In response to brain ischemia, Ser-567 and Ser-607 are strongly dephosphorylated while Ser-457 and Ser-720 are less dephosphorylated. In response to brain seizures, phosphorylation levels on Ser-567 and Ser-607 are greatly reduced. Phosphorylated/dephosphorylated by Src or FYN tyrosine-protein kinases and tyrosine phosphatase PTPRE in primary Schwann cells and sciatic nerve tissue. Phosphorylation at Ser-593 of the FFAT motif activates interaction with MOSPD2, VAPA and VAPB (By similarity).
Sumoylated on Lys-474, preferentially with SUMO1; sumoylation induces a positive shift in the voltage-dependence of activation and inhibits channel activity. Sumoylation increases the frequency of repetitive action potential firing at the cell surface of hippocampal neurons and decreases its frequency in pancreatic beta cells. Desumoylated by SENP1.
The FFAT motif is involved in the interaction with VAPA and VAPB and its phosphorylation regulates these interactions.
The N-terminal and C-terminal cytoplasmic regions mediate homooligomerization; self-association is required to regulate trafficking, gating and C-terminal phosphorylation-dependent modulation of the channel. The N-terminal cytoplasmic region is important for interaction with other channel-forming alpha subunits and with ancillary beta subunits. The C-terminus is necessary and sufficient for the restricted localization to, and clustering within, both in soma and proximal portions of dendrite of neurons and in lateral membrane of non-neuronal polarized cells. The C-terminus is both necessary and sufficient as a mediator of cholinergic and calcium-stimulated modulation of channel cell membrane clustering localization and activity in hippocampal neurons.
Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain, but also in the pancreas and cardiovascular system. Contributes to the regulation of the action potential (AP) repolarization, duration and frequency of repetitive AP firing in neurons, muscle cells and endocrine cells and plays a role in homeostatic attenuation of electrical excitability throughout the brain. Also plays a role in the regulation of exocytosis independently of its electrical function. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane. Homotetrameric channels mediate a delayed-rectifier voltage-dependent outward potassium current that display rapid activation and slow inactivation in response to membrane depolarization. Can form functional homotetrameric and heterotetrameric channels that contain variable proportions of KCNB2; channel properties depend on the type of alpha subunits that are part of the channel. Can also form functional heterotetrameric channels with other alpha subunits that are non-conducting when expressed alone, such as KCNF1, KCNG1, KCNG3, KCNG4, KCNH1, KCNH2, KCNS1, KCNS2, KCNS3 and KCNV1, creating a functionally diverse range of channel complexes (By similarity). Heterotetrameric channel activity formed with KCNS3 show increased current amplitude with the threshold for action potential activation shifted towards more negative values in hypoxic-treated pulmonary artery smooth muscle cells. Channel properties are also modulated by cytoplasmic ancillary beta subunits, such as AMIGO1, KCNE1, KCNE2 and KCNE3, slowing activation and inactivation rate of the delayed rectifier potassium channels. In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Major contributor to the delayed-rectifier voltage-gated potassium current in neurons of the central nervous system, sympathetic ganglion neurons, neuroendocrine cells, pancreatic beta cells, cardiomyocytes and smooth muscle. Mediates the major part of the somatodendritic delayed-rectifier potassium current in hippocampal and cortical pyramidal neurons and sympathetic superior cervical ganglion (CGC) neurons that acts to slow down periods of firing, especially during high frequency stimulation. Plays a role in the induction of long-term potentiation (LTP) of neuron excitability in the CA3 layer of the hippocampus. Contributes to the regulation of the glucose-induced amplitude and duration of action potentials in pancreatic beta-cells, hence limiting calcium influx and insulin secretion. Plays a role in the regulation of resting membrane potential and contraction in hypoxia-treated pulmonary artery smooth muscle cells. May contribute to the regulation of the duration of both the action potential of cardiomyocytes and the heart ventricular repolarization QT interval. Contributes to the pronounced pro-apoptotic potassium current surge during neuronal apoptotic cell death in response to oxidative injury. May confer neuroprotection in response to hypoxia/ischemic insults by suppressing pyramidal neurons hyperexcitability in hippocampal and cortical regions. Promotes trafficking of KCNG3, KCNH1 and KCNH2 to the cell surface membrane, presumably by forming heterotetrameric channels with these subunits. Plays a role in the calcium-dependent recruitment and release of fusion-competent vesicles from the soma of neurons, neuroendocrine and glucose-induced pancreatic beta cells by binding key components of the fusion machinery in a pore-independent manner.
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, and PPP1R12C mediate binding to myosin. PPP1R3A (in skeletal muscle), PPP1R3B (in liver), PPP1R3C, PPP1R3D and PPP1R3F (in brain) mediate binding to glycogen. PPP1R15A and PPP1R15B mediate binding to EIF2S1. Part of a complex containing PPP1R15B, PP1 and NCK1/2. Interacts with PPP1R7 and PPP1R12C. Interacts with PPP1R16B. Component of the PTW/PP1 phosphatase complex, composed of PPP1R10/PNUTS, TOX4, WDR82, and PPP1CA or PPP1CB or PPP1CC. Interacts with PPP1R8. Interacts with PPP1R12A and NUAK1; the interaction is direct. Interacts with TRIM28; the interaction dephosphorylates TRIM28 on 'Ser-824' and forms a complex at the p21 promoter site (By similarity). Interacts with PPP1R12B (PubMed:9827534). Interacts with FOXP3 (By similarity). Interacts with RRP1B (By similarity). Interacts with SERPINE1. Interacts with LZTR1 (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. Component of the PTW/PP1 phosphatase complex, which plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase. In balance with CSNK1D and CSNK1E, determines the circadian period length, through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation. May dephosphorylate CSNK1D and CSNK1E (By similarity).
The phosphatase activity of the PPP1R15A-PP1 complex toward EIF2S1 is specifically inhibited by Salubrinal, a drug that protects cells from endoplasmic reticulum stress (By similarity). Inhibited by the toxins okadaic acid, tautomycin and microcystin Leu-Arg.
Belongs to the eukaryotic ribosomal protein eL39 family.
Belongs to the sodium channel (TC 1.A.1.10) family.
Belongs to the sodium channel (TC 1.A.1.10) family. Nav1.7/SCN9A subfamily.
Expressed in the sciatic nerve, spinal cord, brainstem, cerebellum and cortex, but not expressed in the lung, skeletal and cardiac muscles, kidney and liver.
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.
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. It is a tetrodotoxin-sensitive Na(+) channel isoform. Plays a role in pain mechanisms, especially in the development of inflammatory pain.
Phosphorylation at Ser-1487 by PKC in a highly conserved cytoplasmic loop increases peak sodium currents.
The sequence contains 4 internal repeats, each with 5 hydrophobic segments (S1, S2, S3, S5, S6) and one positively charged segment (S4). Segments S4 are probably the voltage-sensors and are characterized by a series of positively charged amino acids at every third position.
The sodium channel complex consists of a large, channel-forming alpha subunit (SCN9A) regulated by one or more beta subunits (SCN1B, SCN2B, SCN3B and SCN4B) (By similarity). SCN1B and SCN3B are non-covalently associated with SCN2A. SCN2B and SCN4B are disulfide-linked to SCN2A (By similarity). Interacts with NEDD4 and NEDD4L (By similarity). Interacts with the conotoxin GVIIJ (By similarity).
Ubiquitinated by NEDD4L; which may promote its endocytosis. Does not seem to be ubiquitinated by NEDD4.
Neuropeptides that play a significant role in the regulation of food intake and sleep-wakefulness, possibly by coordinating the complex behavioral and physiologic responses of these complementary homeostatic functions. A broader role in the homeostatic regulation of energy metabolism, autonomic function, hormonal balance and the regulation of body fluids, is also suggested.
Electrogenic sodium/bicarbonate cotransporter with a Na(+):HCO3(-) stoichiometry varying from 1:2 to 1:3. May regulate bicarbonate influx/efflux at the basolateral membrane of cells and regulate intracellular pH.
Expressed in colonic mucosa, kidney cortex and to gastric mucosa.
Homodimer. Interacts with CA2/carbonic anhydrase 2 and CA4/carbonic anhydrase 4 which may regulate transporter activity. Isoform 1 but not isoform 2 interacts with AHCYL1 (via PEST domain when phosphorylated); the interaction increases SLC4A4 isoform 1 activity. Interacts with AHCYL2.
N-glycosylated. May not be necessary for the transporter basic functions.
Phosphorylation of Ser-1026 by PKA increases the binding of CA2 and changes the Na(+):HCO3(-) stoichiometry of the transporter from 3:1 to 2:1. Phosphorylated in presence of STK39 and dephosphorylated in presence of PP1 phosphatase; phosphorylation seems to inhibit SLC4A4 activity.
Belongs to the potassium channel family. D (Shal) (TC 1.A.1.2) subfamily. Kv4.2/KCND2 sub-subfamily.
Homotetramer or heterotetramer with KCND1 or KCND3. Associates with the regulatory subunits KCNIP1, KCNIP2, KCNIP3 and KCNIP4. Interacts with DPP6, DPP10, DLG4 and DLG1. In vivo, probably exists as heteromeric complex containing variable proportions of KCND1, KCND2, KCND3, KCNIP1, KCNIP2, KCNIP3, KCNIP4, DPP6 and DPP10 (By similarity). The tetrameric channel can associate with up to four regulatory subunits, such as KCNIP2 or KCNIP4 (By similarity). Interaction with KCNIP3 promotes tetramerization and formation of a functional potassium channel (By similarity). Interaction with four KCNIP4 chains does not reduce interaction with DPP10 (By similarity). Probably part of a complex consisting of KCNIP1, KCNIP2 isoform 3 and KCND2 (By similarity). Interacts with FLNA and FLNC (By similarity). Interacts with NCS1/FREQ (By similarity). Identified in a complex with cAMP-dependent protein kinase (PKA), CAV3, AKAP6 and KCND3 in cardiac myocytes (By similarity).
Is specifically and reversibly inhibited by the scorpion toxin Ts8 (AC P69940).
Phosphorylation at Ser-438 in response to MAPK activation is increased in stimulated dendrites. Interaction with KCNIP2 and DPP6 propomtes phosphorylation by PKA at Ser-552. Phosphorylation at Ser-552 has no effect on interaction with KCNIP3, but is required for the regulation of channel activity by KCNIP3. Phosphorylation at Ser-552 leads to KCND2 internalization (By similarity). Phosphorylated by MAPK in response to signaling via the metabotropic glutamate receptor GRM5 (By similarity). Phosphorylation at Ser-616 is required for the down-regulation of neuronal A-type currents in response to signaling via GRM5 (By similarity).
The C-terminal cytoplasmic region is important for normal expression at the cell membrane and modulates the voltage-dependence of channel activation and inactivation. It is required for interaction with KCNIP2, and probably other family members as well.
The N-terminal cytoplasmic region can mediate N-type inactivation by physically blocking the channel (By similarity). This probably does not happen in vivo, where the N-terminal region mediates interaction with regulatory subunits, such as KCNIP1 and KCNIP2 (By similarity). The zinc binding sites in the N-terminal domain are important for tetramerization and assembly of a functional channel complex (By similarity). Most likely, the channel undergoes closed-state inactivation, where a subtle conformation change would render the protein less sensitive to activation.
The transient neuronal A-type potassium current called I(SA) is triggered at membrane potentials that are below the threshold for action potentials. It inactivates rapidly and recovers rapidly from inactivation. It regulates the firing of action potentials and plays a role in synaptic integration and plasticity. Potassium channels containing KCND2 account for about 80% of the neuronal A-type potassium current. In contrast, the potassium channel responsible for the cardiac I(to) current differs between species; it is mediated by KCND2 in rodents. In human and other non-rodents KCND3 may play an equivalent role.
Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain, but also in rodent heart. Mediates the major part of the dendritic A-type current I(SA) in brain neurons (By similarity). This current is activated at membrane potentials that are below the threshold for action potentials. It regulates neuronal excitability, prolongs the latency before the first spike in a series of action potentials, regulates the frequency of repetitive action potential firing, shortens the duration of action potentials and regulates the back-propagation of action potentials from the neuronal cell body to the dendrites. Contributes to the regulation of the circadian rhythm of action potential firing in suprachiasmatic nucleus neurons, which regulates the circadian rhythm of locomotor activity (By similarity). Functions downstream of the metabotropic glutamate receptor GRM5 and plays a role in neuronal excitability and in nociception mediated by activation of GRM5 (By similarity). Mediates the transient outward current I(to) in rodent heart left ventricle apex cells, but not in human heart, where this current is mediated by another family member. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane. Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCND2 and KCND3; channel properties depend on the type of pore-forming alpha subunits that are part of the channel. In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes. Interaction with specific isoforms of the regulatory subunits KCNIP1, KCNIP2, KCNIP3 or KCNIP4 strongly increases expression at the cell surface and thereby increases channel activity; it modulates the kinetics of channel activation and inactivation, shifts the threshold for channel activation to more negative voltage values, shifts the threshold for inactivation to less negative voltages and accelerates recovery after inactivation. Likewise, interaction with DPP6 or DPP10 promotes expression at the cell membrane and regulates both channel characteristics and activity (By similarity).
Contributes to the regulation of lumenal Ca2+ release via the sarcoplasmic reticulum calcium release channels RYR1 and RYR2, a key step in triggering skeletal and heart muscle contraction (PubMed:19398037, PubMed:17846166, PubMed:7721813). Required for normal organization of the triad junction, where T-tubules and the sarcoplasmic reticulum terminal cisternae are in close contact. Required for normal skeletal muscle strength. Plays a role in excitation-contraction coupling in the heart and in regulating the rate of heart beats (By similarity).
Detected in skeletal muscle and in heart (at protein level). Detected in skeletal muscle and in heart.
Interacts with CASQ2 (By similarity). Homooligomer of variable subunit number; disulfide-linked. Interacts with CASQ1 and RYR1 in skeletal muscle.
Belongs to the eukaryotic ribosomal protein eL42 family.
Belongs to the bacterial ribosomal protein bL35 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.
Kidney specific. Limited to the basolateral membranes of renal tubular epithelial cells.
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.
Belongs to the class-II aminoacyl-tRNA synthetase family. Type-1 seryl-tRNA synthetase subfamily.
Catalyzes the attachment of serine to tRNA(Ser) in a two-step reaction: serine is first activated by ATP to form Ser-AMP and then transferred to the acceptor end of tRNA(Ser). Is probably also able to aminoacylate tRNA(Sec) with serine, to form the misacylated tRNA L-seryl-tRNA(Sec), which will be further converted into selenocysteinyl-tRNA(Sec). In the nucleus, binds to the VEGFA core promoter and prevents MYC binding and transcriptional activation by MYC. Recruits SIRT2 to the VEGFA promoter, promoting deacetylation of histone H4 at 'Lys-16' (H4K16). Thereby, inhibits the production of VEGFA and sprouting angiogenesis mediated by VEGFA.
Consists of two distinct domains, a catalytic core and a N-terminal extension that is involved in tRNA binding.
Homodimer. The tRNA molecule may bind across the dimer. Interacts with SIRT2. Interacts with METTL6; interaction is required for the tRNA N(3)-methylcytidine methyltransferase activity of METTL6.
Was originally thought to function in mRNA expression.
Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A12 subfamily.
Transporter that mediates cellular uptake of betaine and GABA in a sodium- and chloride-dependent process. May have a role in regulation of GABAergic transmission in the brain through the reuptake of GABA into presynaptic terminals, as well as in osmotic regulation (By similarity). Probably also involved in renal and hepatic osmotic regulation (By similarity).
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).
Belongs to the chemokine-like receptor (CMKLR) family.
Belongs to the dermatan-sulfate isomerase family.
Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity.
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.
Component of the 7-subunit TFIIH core complex.
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.
Belongs to the complex I NDUFB4 subunit family.
A pair of annexin repeats may form one binding site for calcium and phospholipid.
This protein is an anticoagulant protein that acts as an indirect inhibitor of the thromboplastin-specific complex, which is involved in the blood coagulation cascade.
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.
Plays a role in apoptosis. Suppression of the anti-apoptotic members or activation of the pro-apoptotic members of the Bcl-2 family leads to altered mitochondrial membrane permeability resulting in release of cytochrome c into the cytosol. Binding of cytochrome c to Apaf-1 triggers the activation of caspase-9, which then accelerates apoptosis by activating other caspases.
Probable subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors.
The PAL motif is required for normal active site conformation.
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.
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 (By similarity).
N-terminal cleavage of acetylated cysteine of intermediate muscle actin by ACTMAP.
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.
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).
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 class-II aminoacyl-tRNA synthetase family.
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. GPRK subfamily.
As part of the NSL complex it is involved in acetylation of nucleosomal histone H4 on several lysine residues and therefore may be involved in the regulation of transcription.
Component of the NSL complex at least composed of MOF/KAT8, KANSL1, KANSL2, KANSL3, MCRS1, PHF20, OGT1/OGT, WDR5 and HCFC1.
Belongs to the eukaryotic ribosomal protein eS4 family.
Plays an important role in the organization of the cytoskeleton. Binds to and sequesters actin monomers (G actin) and therefore inhibits actin polymerization.
Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.
Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily.
Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Binding of extracellular ligands such as growth factors, cytokines and hormones to their cell-surface receptors activates RAS and this initiates RAF1 activation. RAF1 then further activates the dual-specificity protein kinases MAP2K1/MEK1 and MAP2K2/MEK2. Both MAP2K1/MEK1 and MAP2K2/MEK2 function specifically in the MAPK/ERK cascade, and catalyze the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in the extracellular signal-regulated kinases MAPK3/ERK1 and MAPK1/ERK2, leading to their activation and further transduction of the signal within the MAPK/ERK cascade. Activates BRAF in a KSR1 or KSR2-dependent manner; by binding to KSR1 or KSR2 releases the inhibitory intramolecular interaction between KSR1 or KSR2 protein kinase and N-terminal domains which promotes KSR1 or KSR2-BRAF dimerization and BRAF activation (By similarity). Depending on the cellular context, this pathway mediates diverse biological functions such as cell growth, adhesion, survival and differentiation, predominantly through the regulation of transcription, metabolism and cytoskeletal rearrangements. One target of the MAPK/ERK cascade is peroxisome proliferator-activated receptor gamma (PPARG), a nuclear receptor that promotes differentiation and apoptosis. MAP2K1/MEK1 has been shown to export PPARG from the nucleus. The MAPK/ERK cascade is also involved in the regulation of endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC), as well as in the fragmentation of the Golgi apparatus during mitosis (By similarity).
Found in a complex with at least BRAF, HRAS, MAP2K1, MAPK3/ERK1 and RGS14 (By similarity). Forms a heterodimer with MAP2K2/MEK2 (By similarity). Forms heterodimers with KSR2 which further dimerize to form tetramers (PubMed:21441910). Interacts with KSR1 or KSR2 and BRAF; the interaction with KSR1 or KSR2 mediates KSR1-BRAF or KSR2-BRAF dimerization (By similarity). Interacts with ARBB2, LAMTOR3, MAPK1/ERK2 and RAF1 (By similarity). Interacts with MAPK1/ERK2 (By similarity). Interacts with MORG1 (By similarity). Interacts with PPARG (By similarity). Interacts with SGK1 (By similarity). Interacts with BIRC6/bruce (By similarity). Interacts with KAT7; the interaction promotes KAT7 phosphorylation (By similarity). Interacts with RAF1 and NEK10; the interaction is required for ERK1/2-signaling pathway activation in response to UV irradiation (By similarity). Interacts with TRAF3IP3 (By similarity).
Phosphorylation at Ser-218 and Ser-222 by MAP kinase kinase kinases (RAF or MEKK1) regulates positively the kinase activity (By similarity). Also phosphorylated at Thr-292 by MAPK1/ERK2 and at Ser-298 by PAK (By similarity). MAPK1/ERK2 phosphorylation of Thr-292 occurs in response to cellular adhesion and leads to inhibition of Ser-298 phosphorylation by PAK (By similarity). Autophosphorylated at Ser-218 and Ser-222, autophosphosphorylation is promoted by NEK10 following UV irradiation (By similarity).
Ras proteins such as HRAS mediate the activation of RAF proteins such as RAF1 or BRAF which in turn activate extracellular signal-regulated kinases (ERK) through MAPK (mitogen-activated protein kinases) and ERK kinases MAP2K1/MEK1 and MAP2K2/MEK2. Activation occurs through phosphorylation of Ser-218 and Ser-222 (By similarity). MAP2K1/MEK1 binds KSR1 or KSR2 releasing the inhibitory intramolecular interaction between KSR1 or KSR2 protein kinase and N-terminal domains (By similarity). This allows KSR1 or KSR2 dimerization with BRAF leading to BRAF activation and phosphorylation of MAP2K1 (By similarity). MAP2K1/MEK1 is also the target of negative feed-back regulation by its substrate kinases, such as MAPK1/ERK2. These phosphorylate MAP2K1/MEK1 on Thr-292, thereby facilitating dephosphorylation of the activating residues Ser-218 and Ser-222. Inhibited by serine/threonine phosphatase 2A (By similarity).
The proline-rich region localized between residues 270 and 307 is important for the binding to RAF1 and activation of MAP2K1/MEK1.
Belongs to the intercrine beta (chemokine CC) family.
Monokine with inflammatory and chemokinetic properties.
Occurs in almost all aerobically respiring organisms and serves to protect cells from the toxic effects of hydrogen peroxide.
Belongs to the complex I 49 kDa subunit family.
Belongs to the MMS22 family. MMS22L subfamily.
In the C-terminal section; belongs to the Cu-Zn superoxide dismutase family.
Cardiac muscle Tn-C can bind 3 calcium ions per molecule. Domain I does not bind calcium.
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.
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.
Belongs to the LAPTM4/LAPTM5 transporter family.
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 dicarboxylate/amino acid:cation symporter (DAACS) (TC 2.A.23) family. SLC1A1 subfamily.
Brain, but also small intestine, kidney, liver and heart.
Contains eight transmembrane regions plus two helical hairpins that dip into the membrane. These helical hairpin structures play an important role in the transport process. The first enters the membrane from the cytoplasmic side, the second one from the extracellular side. During the transport cycle, the regions involved in amino acid transport, and especially the helical hairpins, move vertically by about 15-18 Angstroms, alternating between exposure to the aqueous phase and reinsertion in the lipid bilayer. In contrast, the regions involved in trimerization do not move.
Homotrimer (Probable). Interacts with ARL6IP5. Interacts with RTN2 (via N-terminus); the interaction promotes cell surface expression of SLC1A1. Interacts with SORCS2; this interaction is important for normal expression at the cell membrane (By similarity).
Sodium-dependent, high-affinity amino acid transporter that mediates the uptake of L-glutamate and also L-aspartate and D-aspartate (PubMed:1280334). Can also transport L-cysteine (By similarity). Functions as a symporter that transports one amino acid molecule together with two or three Na(+) ions and one proton, in parallel with the counter-transport of one K(+) ion (PubMed:1280334). Mediates Cl(-) flux that is not coupled to amino acid transport; this avoids the accumulation of negative charges due to aspartate and Na(+) symport. Plays an important role in L-glutamate and L-aspartate reabsorption in renal tubuli (By similarity). Plays a redundant role in the rapid removal of released glutamate from the synaptic cleft, which is essential for terminating the postsynaptic action of glutamate (By similarity). Contributes to glutathione biosynthesis and protection against oxidative stress via its role in L-glutamate and L-cysteine transport (By similarity). Negatively regulated by ARL6IP5 (By similarity).
Belongs to the ubiquitin-activating E1 family.
Catalyzes the first step in ubiquitin conjugation to mark cellular proteins for degradation through the ubiquitin-proteasome system. Activates ubiquitin by first adenylating its C-terminal glycine residue with ATP, and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding a ubiquitin-E1 thioester and free AMP (PubMed:9322736). Essential for the formation of radiation-induced foci, timely DNA repair and for response to replication stress. Promotes the recruitment of TP53BP1 and BRCA1 at DNA damage sites (By similarity).
There are two active sites within the E1 molecule, allowing it to accommodate two ubiquitin moieties at a time, with a new ubiquitin forming an adenylate intermediate as the previous one is transferred to the thiol site.
Belongs to the pseudouridine synthase TruB family.
Forms protease inhibiting heterodimer with TMPRSS7.
Belongs to the eukaryotic diacylglycerol kinase family.
Identified in a complex containing FGFR4, NCAM1, CDH2, PLCG1, FRS2, SRC, SHC1, GAP43 and CTTN. Interacts (via IQ domain) with calmodulin. Binds calmodulin with a greater affinity in the absence of Ca(2+) than in its presence.
Palmitoylated. Palmitoylation is essential for plasma membrane association.
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.
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.
Heavy chains are linked to bikunin via chondroitin 4-sulfate esterified to the alpha-carboxyl of the C-terminal aspartate after propeptide cleavage.
I-alpha-I plasma protease inhibitors are assembled from one or two heavy chains (HC) and one light chain, bikunin. Pre-alpha-inhibitor (P-alpha-I) is composed of ITIH3/HC3 and bikunin.
May act as a carrier of hyaluronan in serum or as a binding protein between hyaluronan and other matrix protein, including those on cell surfaces in tissues to regulate the localization, synthesis and degradation of hyaluronan which are essential to cells undergoing biological processes.
Consists of three domains, a large central CORE domain and two small peripheral domains, NMPbind and LID, which undergo movements during catalysis. The LID domain closes over the site of phosphoryl transfer upon GTP/ATP binding. Assembling and dissambling the active center during each catalytic cycle provides an effective means to prevent GTP/ATP hydrolysis.
Involved in maintaining the homeostasis of cellular nucleotides by catalyzing the interconversion of nucleoside phosphates. Efficiently phosphorylates AMP and dAMP using ATP as phosphate donor, but phosphorylates only AMP when using GTP as phosphate donor. Also displays broad nucleoside diphosphate kinase activity.
Belongs to the nucleotide-sugar transporter family. SLC35A subfamily.
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.
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.
The C-terminal helices form a flat, hydrophobic surface that is probably tightly associated with the cytosolic surface of the endoplasmic reticulum membrane.
Growth factor of the TGF-beta superfamily that plays essential roles in many developmental processes, including cardiogenesis, neurogenesis, and osteogenesis. Induces cartilage and bone formation. Initiates the canonical BMP signaling cascade by associating with type I receptor BMPR1A and type II receptor BMPR2. Once all three components are bound together in a complex at the cell surface, BMPR2 phosphorylates and activates BMPR1A. In turn, BMPR1A propagates signal by phosphorylating SMAD1/5/8 that travel to the nucleus and act as activators and repressors of transcription of target genes. Also acts to promote expression of HAMP, via the interaction with its receptor BMPR1A/ALK3 (By similarity). Can also signal through non-canonical pathways such as ERK/MAP kinase signaling cascade that regulates osteoblast differentiation. Also stimulates the differentiation of myoblasts into osteoblasts via the EIF2AK3-EIF2A-ATF4 pathway by stimulating EIF2A phosphorylation which leads to increased expression of ATF4 which plays a central role in osteoblast differentiation. Acts as a positive regulator of odontoblast differentiation during mesenchymal tooth germ formation, expression is repressed during the bell stage by MSX1-mediated inhibition of CTNNB1 signaling (By similarity).
Homodimer; disulfide-linked. Interacts with SOSTDC1 (By similarity). Interacts with GREM2, RGMA, RGMB and RGMC. Interacts with ASPN (By similarity). Interacts with MAFP5 (By similarity). Interacts with FBN1 (via N-terminal domain) and FBN2. Interacts with type I receptor BMPR1A. Interacts with type II receptor BMPR2 (By similarity). Interacts with SCUBE3 (By similarity). Interacts with TNFAIP6 (primarily via Link domain); this interaction is inhibited by hyaluronan. Interacts with ERFE (By similarity). Interacts with BMPR1A/ALK3; the interaction may induce HAMP expression (By similarity). Forms heterodimers with BMP6 in vitro; the heterodimer then binds to its receptor BMPR1A /ALK3 and may induce HAMP expression (By similarity).
Belongs to the TALE/MEIS homeobox family.
Belongs to the calycin superfamily. Fatty-acid binding protein (FABP) family.
Associates with the cytoplasmic domain of a variety of cadherins. The association of catenins to cadherins produces a complex which is linked to the actin filament network, and which seems to be of primary importance for cadherins cell-adhesion properties. Can associate with both E- and N-cadherins. Originally believed to be a stable component of E-cadherin/catenin adhesion complexes and to mediate the linkage of cadherins to the actin cytoskeleton at adherens junctions. In contrast, cortical actin was found to be much more dynamic than E-cadherin/catenin complexes and CTNNA1 was shown not to bind to F-actin when assembled in the complex suggesting a different linkage between actin and adherens junctions components. The homodimeric form may regulate actin filament assembly and inhibit actin branching by competing with the Arp2/3 complex for binding to actin filaments. Involved in the regulation of WWTR1/TAZ, YAP1 and TGFB1-dependent SMAD2 and SMAD3 nuclear accumulation (By similarity). May play a crucial role in cell differentiation (By similarity).
Belongs to the vinculin/alpha-catenin family.
Monomer and homodimer; the monomer preferentially binds to CTNNB1 and the homodimer to actin (By similarity). Component of an cadherin:catenin adhesion complex composed of at least of CDH26, beta-catenin/CTNNB1, alpha-catenin/CTNNA1 and p120 catenin/CTNND1 (By similarity). Possible component of an E-cadherin/ catenin adhesion complex together with E-cadherin/CDH1 and beta-catenin/CTNNB1 or gamma-catenin/JUP; the complex is located to adherens junctions (By similarity). The stable association of CTNNA1 is controversial as CTNNA1 was shown not to bind to F-actin when assembled in the complex (By similarity). Alternatively, the CTNNA1-containing complex may be linked to F-actin by other proteins such as LIMA1 (By similarity). Binds AFDN and F-actin (By similarity). Interacts with ARHGAP21 (By similarity). Interacts with AJUBA (By similarity). Interacts with LIMA1 (By similarity). Interacts with vinculin/VCL (By similarity). Interacts with TJP2/ZO2 (via N-terminus) (By similarity). Interacts with TJP1/ZO1 (via N-terminus) (By similarity).
Phosphorylation seems to contribute to the strength of cell-cell adhesion rather than to the basic capacity for cell-cell adhesion.
Belongs to the eukaryotic ribosomal protein eL28 family.
Belongs to the DDOST 48 kDa subunit 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).
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.
Binds the telomeric double-stranded 5'-TTAGGG-3' repeat.
Belongs to the ankyrin SOCS box (ASB) family.
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 2-oxoacid dehydrogenase family.
Belongs to the phytoene/squalene synthase family.
Catalyzes the condensation of 2 farnesyl pyrophosphate (FPP) moieties to form squalene.
Belongs to the RecA family. DMC1 subfamily.
May participate in meiotic recombination, specifically in homologous strand assimilation, which is required for the resolution of meiotic double-strand breaks.
Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family.
Belongs to the universal ribosomal protein uS12 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. Does not translocate ADP-bound HSP70 proteins into the nucleus.
Forms an asymmetric homodimer; required for binding and nuclear import of HSP70 proteins. Interacts with ATP-bound HSP70 proteins.
Belongs to the protein-tyrosine phosphatase family. Receptor class 4 subfamily.
A cytochrome P450 monooxygenase involved in the metabolism of endogenous cholesterol and its oxygenated derivatives (oxysterols) (By similarity). 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) (By similarity). Functions as a critical regulatory enzyme of bile acid biosynthesis and cholesterol homeostasis (Probable). Catalyzes the hydroxylation of carbon hydrogen bond at 7-alpha position of cholesterol, a rate-limiting step in cholesterol catabolism and bile acid biosynthesis (Probable). 7-alpha hydroxylates several oxysterols, including 4beta-hydroxycholesterol and 24-hydroxycholesterol (By similarity). Catalyzes the oxidation of the 7,8 double bond of 7-dehydrocholesterol and lathosterol with direct and predominant formation of the 7-keto derivatives (By similarity).
Belongs to the acetyltransferase family. ARD1 subfamily.
Belongs to the intercrine alpha (chemokine CxC) family.
Homodimer. May interact with ROPN1 (By similarity).
Sperm surface zona pellucida binding protein. Helps to bind spermatozoa to the zona pellucida with high affinity. Might function in binding zona pellucida and carbohydrates.
Dual specificity phosphatase able to dephosphorylate phosphotyrosine, phosphoserine and phosphothreonine residues, with a preference for phosphotyrosine as a substrate.
Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A9 subfamily.
Tachykinins are active peptides which excite neurons, evoke behavioral responses, are potent vasodilators and secretagogues, and contract (directly or indirectly) many smooth muscles.
The substance P form is cleaved at Pro-59 by the prolyl endopeptidase FAP (seprase) activity (in vitro). Substance P is also cleaved and degraded by Angiotensin-converting enzyme (ACE) and neprilysin (MME).
Calcium-dependent lectin that mediates cell adhesion by binding to glycoproteins on neighboring cells. Mediates the adherence of lymphocytes to endothelial cells of high endothelial venules in peripheral lymph nodes. Promotes initial tethering and rolling of leukocytes in endothelia.
Interaction with SELPLG/PSGL1 and PODXL2 is required for promoting recruitment and rolling of leukocytes. This interaction is dependent on the sialyl Lewis X glycan modification of SELPLG and PODXL2, and tyrosine sulfation modifications of SELPLG. Sulfation on 'Tyr-51' of SELPLG is important for L-selectin binding.
Pro-inflammatory cytokine primarily involved in epithelial barrier repair, polarized T-helper 1 (Th1) cell and natural killer (NK) cell immune responses. Upon binding to IL18R1 and IL18RAP, forms a signaling ternary complex which activates NF-kappa-B, triggering synthesis of inflammatory mediators. Synergizes with IL12/interleukin-12 to induce IFNG synthesis from T-helper 1 (Th1) cells and natural killer (NK) cells. Involved in transduction of inflammation downstream of pyroptosis: its mature form is specifically released in the extracellular milieu by passing through the gasdermin-D (GSDMD) pore.
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.
Belongs to the DEAD box helicase family. DDX1 subfamily.
The helicase domain is involved in the stimulation of RELA transcriptional activity.
Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. KIN-5/BimC subfamily.
Component of the Arp2/3 complex composed of ARP2, ARP3, ARPC1B/p41-ARC, ARPC2/p34-ARC, ARPC3/p21-ARC, ARPC4/p20-ARC and ARPC5/p16-ARC. Interacts with SHANK3; the interaction probably mediates the association of SHANK3 with the Arp2/3 complex.
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.
Component of the small nucleolar ribonucleoprotein particles containing H/ACA-type snoRNAs (H/ACA snoRNPs).
Required for ribosome biogenesis. Part of a 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. Pseudouridine ("psi") residues may serve to stabilize the conformation of rRNAs.
PP1 comprises a catalytic subunit, PPP1CA, PPP1CB or PPP1CC, which is folded into its native form by inhibitor 2 and glycogen synthetase kinase 3, and then complexed to one or several targeting or regulatory subunits. PPP1R12A, PPP1R12B and PPP1R12C mediate binding to myosin. PPP1R3A (in skeletal muscle), PPP1R3B (in liver), PPP1R3C, PPP1R3D and PPP1R3F (in brain) mediate binding to glycogen. Interacts with PPP1R15A and PPP1R15B; the interactions mediate binding to EIF2S1. Part of a complex containing PPP1R15B, PP1 and NCK1/2. Interacts with PPP1R9A, PPP1R9B and PPP1R7. Interacts with YLPM1. Forms a complex with ILF2, ILF3, YLPM1, KHDRBS1, RBMX and NCOA5. Interacts with NOM1 and PPP1R8. Interacts with PPP1R16B. Interacts with RPSA only in the presence of PPP1R16B. Component of the PTW/PP1 phosphatase complex, composed of PPP1R10/PNUTS, TOX4, WDR82, and PPP1CA or PPP1CB or PPP1CC. Interacts with PPP1R10/PNUTS and PPP1R8. Interacts with WDR82 in the presence of PPP1R10/PNUTS. Interacts with TRIM28; the interaction dephosphorylates TRIM28 on 'Ser-824' and forms a complex at the p21 promoter site (By similarity). Interacts with PPP1R39. Interacts with NEK2. Interacts with PHACTR4; which acts as an activator of PP1 activity. Interacts with FER; this promotes phosphorylation at Thr-320 (By similarity). Interacts with BTBD10 (By similarity). Interacts with KCTD20 (By similarity). Interacts with FOXP3 (By similarity). Interacts with CENPA (By similarity). Interacts with ATG16L1 (By similarity). Found in a complex with PPP1CA, PPP1CC, SHC1 and PEAK1 (By similarity). Interacts with tensin TNS1 (By similarity). Interacts with SAXO4, PPP1R21, PPP1R26, PPP1R27, PPP1R35, PPP1R36, PPP1R37, SH3RF2, ELFN1 and ELFN2 (By similarity).
Phosphorylated. Dephosphorylated at Thr-320 in the presence of ionizing radiation (By similarity).
Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets. Protein phosphatase 1 (PP1) is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Involved in regulation of ionic conductances and long-term synaptic plasticity. May play an important role in dephosphorylating substrates such as the postsynaptic density-associated Ca(2+)/calmodulin dependent protein kinase II. Component of the PTW/PP1 phosphatase complex, which plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase. Regulates NEK2 function in terms of kinase activity and centrosome number and splitting, both in the presence and absence of radiation-induced DNA damage. Regulator of neural tube and optic fissure closure, and enteric neural crest cell (ENCCs) migration during development. In balance with CSNK1D and CSNK1E, determines the circadian period length, through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation. May dephosphorylate CSNK1D and CSNK1E (By similarity). Dephosphorylates CENPA (By similarity). Dephosphorylates the 'Ser-139' residue of ATG16L1 causing dissociation of ATG12-ATG5-ATG16L1 complex, thereby inhibiting autophagy (By similarity).
Belongs to the universal ribosomal protein uL24 family.
Belongs to the glycerophosphoryl diester phosphodiesterase family.
Belongs to the connexin family. Beta-type (group I) subfamily.
Belongs to the organo anion transporter (TC 2.A.60) family.
Belongs to the G-protein coupled receptor 1 family. FSH/LSH/TSH subfamily.
Receptor for lutropin-choriogonadotropic hormone. The activity of this receptor is mediated by G proteins which activate adenylate cyclase.
Belongs to the CDP-alcohol phosphatidyltransferase class-I family.
Belongs to the major facilitator superfamily.
Mediates high-affinity intracellular uptake of the rare oligo-element molybdenum.
May be an activator of the JNK/SAPK pathway.
Belongs to the SRC/p160 nuclear receptor coactivator family.
Belongs to the G-protein coupled receptor 1 family. Muscarinic acetylcholine receptor 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 Pi turnover.
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.
Inhibited by sarcolipin (SLN) and myoregulin (MRLN) (PubMed:10551848, PubMed:8428955, PubMed:29081402). Inhibited by phospholamban (PLN) (PubMed:10551848, PubMed:8428955, PubMed:29081402, PubMed:23996003). Reversibly inhibited by phospholamban (PLN) at low calcium concentrations (PubMed:10551848, PubMed:8428955, PubMed:29081402, PubMed:23996003). Dephosphorylated PLN decreases the apparent affinity of the ATPase for calcium (PubMed:10551848, PubMed:8428955). This inhibition is regulated by the phosphorylation of PLN (PubMed:10551848, PubMed:8428955). Enhanced by DWORF; DWORF increases activity by displacing sarcolipin (SLN), phospholamban (PLN) and myoregulin (MRLN) (By similarity).
Interacts with sarcolipin (SLN) (PubMed:29081402, PubMed:23455422, PubMed:23455424). Interacts with phospholamban (PLN) (PubMed:8428955, PubMed:10551848, PubMed:29081402, PubMed:23996003). Interacts with myoregulin (MRLN) (By similarity). Interacts with DWORF (By similarity). Interacts with VMP1 (By similarity).
Isoform SERCA1A and isoform SERCA1B are predominantly found in adult and neonatal skeletal muscle respectively.
Key regulator of striated muscle performance by acting as the major Ca(2+) ATPase responsible for the reuptake of cytosolic Ca(2+) into the sarcoplasmic reticulum. Catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen (PubMed:10914677, PubMed:11438520, PubMed:15189864, PubMed:29081402, PubMed:18075584, PubMed:24270570, PubMed:23996003). Contributes to calcium sequestration involved in muscular excitation/contraction.
PLN and SLN both have a single transmembrane helix; both occupy a similar binding site on ATP2A1 that is situated between the ATP2A1 transmembrane helices.
Skeletal muscle (at protein level) (PubMed:11438520, PubMed:15189864, PubMed:29081402, PubMed:10864315, PubMed:18075584, PubMed:23996003, PubMed:23455422). Skeletal muscle, fast twitch muscle (type II) fibers (PubMed:2936465, PubMed:3029125).
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. cAMP subfamily.
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.
Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. Aurora subfamily.
Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IV subfamily.
Ligand for members of the frizzled family of seven transmembrane receptors.
Belongs to the LDH/MDH superfamily. LDH family.
Binds 3 Ca(2+) ions per subunit. The calcium ions probably have a structural role.
Cleaved into a large and a small subunit.
Heterodimer of the large and small subunits; disulfide-linked.
Removes the secondary (acyloxyacyl-linked) fatty acyl chains from the lipid A region of bacterial lipopolysaccharides (LPS). By breaking down LPS, terminates the host response to bacterial infection and prevents prolonged and damaging inflammatory responses. In peritoneal macrophages, seems to be important for recovery from a state of immune tolerance following infection by Gram-negative bacteria.
Belongs to the ABC transporter superfamily. ABCC family. Conjugate transporter (TC 3.A.1.208) subfamily.
Belongs to the SLC41A transporter family.
Belongs to the major facilitator superfamily. Sugar transporter (TC 2.A.1.1) family. Glucose transporter subfamily.
Belongs to the secreted frizzled-related protein (sFRP) family.
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.
Expressed at low levels in heart, hypothalamus, liver, lung, spleen and stomach. Expressed at higher levels in testis and brain. Within the brain, expressed in cerebellum, cerebral stem, cortex and striatum.
Palmitoylation at Cys-273 reduces affinity for dynein.
Phosphorylated in mitosis. Can be phosphorylated by CDK1, CDK5 and MAPK1. Phosphorylation by CDK5 promotes interaction with KATNA1 and YWHAE (By similarity).
Required for organization of the cellular microtubule array and microtubule anchoring at the centrosome. May regulate microtubule organization at least in part by targeting the microtubule severing protein KATNA1 to the centrosome. Also positively regulates the activity of the minus-end directed microtubule motor protein dynein. May enhance dynein-mediated microtubule sliding by targeting dynein to the microtubule plus ends. Required for several dynein- and microtubule-dependent processes such as the maintenance of Golgi integrity, the centripetal motion of secretory vesicles and the coupling of the nucleus and centrosome. Also required during brain development for the migration of newly formed neurons from the ventricular/subventricular zone toward the cortical plate. Plays a role, together with DISC1, in the regulation of neurite outgrowth. Required for mitosis in some cell types but appears to be dispensible for mitosis in cortical neuronal progenitors, which instead requires NDE1. Facilitates the polymerization of neurofilaments from the individual subunits NEFH and NEFL. Positively regulates lysosome peripheral distribution and ruffled border formation in osteoclasts (By similarity).
Self-associates. Interacts with DISC1, dynein, dynactin, tubulin gamma, KATNA1, KATNB1, microtubules, PAFAH1B1, PCM1, PCNT, and YWHAE. Interacts directly with NEFL and indirectly with NEFH. Interacts (via C-terminus) with CENPF. Interacts with ZNF365. Interacts with PLEKHM1 (via N- and C-terminus).
Was originally thought to function as an oligopeptidase (NUDEL-oligopeptidase or endooligopeptidase A) which could regulate peptide levels relevant to brain function.
Belongs to the eukaryotic ribosomal protein eS17 family.
Belongs to the class V-like SAM-binding methyltransferase superfamily.
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.
During periods of oxidative stress, Sec-46 may react with a superoxide radical, irreversibly lose hydroselenide and be converted to dehydroalanine.
Homotetramer. Interacts with MIEN1 (By similarity).
Protects the hemoglobin in erythrocytes from oxidative breakdown. In platelets, plays a crucial role of glutathione peroxidase in the arachidonic acid metabolism.
Part of the SNARE core complex containing SNAP25, VAMP2 and STX1A; this complex binds CPLX1. Found in a complex containing SYT1, SV2B and syntaxin-1. Found in a ternary complex with STX1A and VAMP8. Interacts with HSC70 and with SYT9, forming a complex with DNAJC5. The interaction with SYT9 is inhibited in presence of calcium. Isoform 1 and isoform 2 interact with BLOC1S6. Interacts with CENPF. Interacts with EQTN. Interacts with HGS. Interacts with KCNB1 (via N-terminus); reduces the voltage-dependent potassium channel KCNB1 activity in pancreatic beta cells. Interacts with OTOF. Interacts with RIMS1. Interacts with SNAPIN. Interacts with STXBP6. Interacts with TRIM9. Interacts with ZDHHC13 (via ANK repeats). Interacts with ZDHHC17 (via ANK repeats). Associates with the BLOC-1 complex. Interacts with PLCL1 (via C2 domain). Interacts with PRRT2; this interaction may impair the formation of the SNARE complex. Interacts with alpha-synuclein/SNCA. Interacts with PRPH2. Interacts with ROM1. Interacts with STX3.
t-SNARE involved in the molecular regulation of neurotransmitter release. Plays an important role in the synaptic function of specific neuronal systems. Associates with proteins involved in vesicle docking and membrane fusion. Regulates plasma membrane recycling through its interaction with CENPF. Modulates the gating characteristics of the delayed rectifier voltage-dependent potassium channel KCNB1 in pancreatic beta cells.
Belongs to the universal ribosomal protein uL30 family.
Belongs to the thiolase-like superfamily. Beta-ketoacyl-ACP synthases family.
May play a role in the biosynthesis of lipoic acid as well as longer chain fatty acids required for optimal mitochondrial function.
Belongs to the WD repeat striatin family.
Binds calmodulin in a calcium dependent manner. May function as scaffolding or signaling protein.
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.
Belongs to the Antp homeobox family. Labial subfamily.
Belongs to the ammonium transporter (TC 2.A.49) family. Rh subfamily.
Belongs to the protein phosphatase inhibitor 2 family.
Phosphorylation on Ser-44 by ATM activates PP1 by dissociating the PP1-PPP1R2 complex (By similarity). Phosphorylation on Thr-73 by GSK3 activates PP1 by dissociating the PP1-PPP1R2 complex.
May participate in suppression of cell proliferation and induces apoptotic cell death through activation of interleukin-1-beta converting enzyme (ICE)-like proteases.
Belongs to the aldo/keto reductase family. Glutamate--cysteine ligase light chain subfamily.
Heterodimer of a catalytic heavy chain and a regulatory light chain.
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. Interacts with beta subunits KCNMB1, KCNMB2, KCNMB3 and KCNMB4. Interacts with gamma subunits LRRC26, LRRC38, LRRC52 and LRRC55. Beta and gamma subunits are accessory, and modulate its activity. Interacts with RAB11B (By similarity).
Palmitoylation by ZDHHC22 and ZDHHC23 within the intracellular linker between the S0 and S1 transmembrane domains regulates localization to the plasma membrane. Depalmitoylated by LYPLA1 and LYPLAL1, leading to retard exit from the trans-Golgi network (By similarity).
Phosphorylated (Probable). Phosphorylation by kinases such as PKA and/or PKG. In smooth muscles, phosphorylation affects its activity (By similarity).
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. Kinetics of KCNMA1 channels are determined by alternative splicing, phosphorylation status and its combination with modulating beta subunits. Highly sensitive to both iberiotoxin (IbTx) and charybdotoxin (CTX) (By similarity).
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 KCNMB1, KCNMB2, KCNMB3 and KCNMB4.
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+) sensor regions required for activation of the channel.
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 nucleobase:cation symporter-2 (NCS2) (TC 2.A.40) family.
Cleaved by a 20S proteasomal protease in response to agents that damage DNA (PubMed:16193061). Cleavage takes place in the absence of ubiquitination and ATP. The resulting N-terminal fragment accumulates in the nucleus (PubMed:16193061).
DNA- and RNA-binding protein involved in various processes, such as translational repression, RNA stabilization, mRNA splicing, DNA repair and transcription regulation (PubMed:11574481, PubMed:16354698, PubMed:7852402). Predominantly acts as a RNA-binding protein: binds preferentially to the 5'-[CU]CUGCG-3' RNA motif and specifically recognizes mRNA transcripts modified by C5-methylcytosine (m5C) (By similarity). Promotes mRNA stabilization: acts by binding to m5C-containing mRNAs and recruiting the mRNA stability maintainer ELAVL1, thereby preventing mRNA decay (By similarity). Component of the CRD-mediated complex that promotes MYC mRNA stability (By similarity). Contributes to the regulation of translation by modulating the interaction between the mRNA and eukaryotic initiation factors (PubMed:12582179). Plays a key role in RNA composition of extracellular exosomes by defining the sorting of small non-coding RNAs, such as tRNAs, Y RNAs, Vault RNAs and miRNAs (By similarity). Probably sorts RNAs in exosomes by recognizing and binding C5-methylcytosine (m5C)-containing RNAs (By similarity). Acts as a key effector of epidermal progenitors by preventing epidermal progenitor senescence: acts by regulating the translation of a senescence-associated subset of cytokine mRNAs, possibly by binding to m5C-containing mRNAs (By similarity). Also involved in pre-mRNA alternative splicing regulation: binds to splice sites in pre-mRNA and regulates splice site selection (By similarity). Binds to TSC22D1 transcripts, thereby inhibiting their translation and negatively regulating TGF-beta-mediated transcription of COL1A2 (By similarity). Also able to bind DNA: regulates transcription of the multidrug resistance gene MDR1 is enhanced in presence of the APEX1 acetylated form at 'Lys-6' and 'Lys-7' (By similarity). Binds to promoters that contain a Y-box (5'-CTGATTGGCCAA-3'), such as MDR1 and HLA class II genes (By similarity). Promotes separation of DNA strands that contain mismatches or are modified by cisplatin (By similarity). Has endonucleolytic activity and can introduce nicks or breaks into double-stranded DNA, suggesting a role in DNA repair (By similarity). The secreted form acts as an extracellular mitogen and stimulates cell migration and proliferation (By similarity).
Homodimer in the presence of ATP (PubMed:12582179). Component of the coding region determinant (CRD)-mediated complex, composed of DHX9, HNRNPU, IGF2BP1, SYNCRIP and YBX1 (By similarity). Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs (By similarity). Component of the U11/U12 snRNPs that are part of the U12-type spliceosome (By similarity). Identified in a histone pre-mRNA complex, at least composed of ERI1, LSM11, SLBP, SNRPB, SYNCRIP and YBX1 (By similarity). Interacts with IGF2BP1 and RBBP6 (PubMed:16354698). Component of cytoplasmic messenger ribonucleoprotein particles (mRNPs) (PubMed:16354698). Interacts with AKT1, MBNL1, SFRS9, SFRS12, ALYREF/THOC4, MSH2, XRCC5, WRN and NCL (PubMed:16354698). Interacts (via C-terminus) with APEX1 (via N-terminus); the interaction is increased with APEX1 acetylated at 'Lys-6' and 'Lys-7' (By similarity). Interacts with AGO1 and AGO2 (By similarity). Interacts with ANKRD2 (By similarity). Interacts with DERA (By similarity). Interacts with FMR1; this interaction occurs in association with polyribosome (By similarity). Interacts with ZBTB7B (By similarity). Interacts with HDGF (By similarity). Interacts with ELAVL1; leading to ELAVL1 recruitment on C5-methylcytosine (m5C)-containing mRNAs and subsequent mRNA stability (By similarity).
In the CSD domain, Trp-65 specifically recognizes C5-methylcytosine (m5C) modification through its indole ring.
Phosphorylated; increased by TGFB1 treatment (By similarity). Phosphorylation by PKB/AKT1 reduces interaction with cytoplasmic mRNA (PubMed:16354698). In the absence of phosphorylation the protein is retained in the cytoplasm (By similarity).
Ubiquitinated by RBBP6; leading to a decrease of YBX1 transactivational ability.
Homodimer; disulfide-linked. Forms a trimeric complex with FBXW7 and NOTCH1. Interacts with MAPK3/ERK1, MAPK1/ERK2, MAP2K1/MEK1, MAP2K2/MEK2, NEDD4, NEDD4L, MAPT/TAU, MAPK7, CREB1, SLC9A3R2/NHERF2 and KCNJ1/ROMK1. Associates with the mammalian target of rapamycin complex 2 (mTORC2) via an interaction with MAPKAP1/SIN1 (By similarity).
Regulated by phosphorylation. Activated by phosphorylation on Ser-422 by mTORC2, transforming it into a substrate for PDPK1 which phosphorylates it on Thr-256. Phosphorylation on Ser-397 and Ser-401 are also essential for its activity. Phosphorylation on Ser-78 by MAPK7 is required for growth factor-induced cell cycle progression (By similarity).
Serine/threonine-protein kinase which is involved in the regulation of a wide variety of ion channels, membrane transporters, cellular enzymes, transcription factors, neuronal excitability, cell growth, proliferation, survival, migration and apoptosis. Plays an important role in cellular stress response. Contributes to regulation of renal Na(+) retention, renal K(+) elimination, salt appetite, gastric acid secretion, intestinal Na(+)/H(+) exchange and nutrient transport, insulin-dependent salt sensitivity of blood pressure, salt sensitivity of peripheral glucose uptake, cardiac repolarization and memory consolidation. Up-regulates Na(+) channels: SCNN1A/ENAC, SCN5A and ASIC1/ACCN2, K(+) channels: KCNJ1/ROMK1, KCNA1-5, KCNQ1-5 and KCNE1, epithelial Ca(2+) channels: TRPV5 and TRPV6, chloride channels: BSND, CLCN2 and CFTR, glutamate transporters: SLC1A3/EAAT1, SLC1A2 /EAAT2, SLC1A1/EAAT3, SLC1A6/EAAT4 and SLC1A7/EAAT5, amino acid transporters: SLC1A5/ASCT2, SLC38A1/SN1 and SLC6A19, creatine transporter: SLC6A8, Na(+)/dicarboxylate cotransporter: SLC13A2/NADC1, Na(+)-dependent phosphate cotransporter: SLC34A2/NAPI-2B, glutamate receptor: GRIK2/GLUR6. Up-regulates carriers: SLC9A3/NHE3, SLC12A1/NKCC2, SLC12A3/NCC, SLC5A3/SMIT, SLC2A1/GLUT1, SLC5A1/SGLT1 and SLC15A2/PEPT2. Regulates enzymes: GSK3A/B, PMM2 and Na(+)/K(+) ATPase, and transcription factors: CTNNB1 and nuclear factor NF-kappa-B. Stimulates sodium transport into epithelial cells by enhancing the stability and expression of SCNN1A/ENAC. This is achieved by phosphorylating the NEDD4L ubiquitin E3 ligase, promoting its interaction with 14-3-3 proteins, thereby preventing it from binding to SCNN1A/ENAC and targeting it for degradation. Regulates store-operated Ca(+2) entry (SOCE) by stimulating ORAI1 and STIM1. Regulates KCNJ1/ROMK1 directly via its phosphorylation or indirectly via increased interaction with SLC9A3R2/NHERF2. Phosphorylates MDM2 and activates MDM2-dependent ubiquitination of p53/TP53. Phosphorylates MAPT/TAU and mediates microtubule depolymerization and neurite formation in hippocampal neurons. Phosphorylates SLC2A4/GLUT4 and up-regulates its activity. Phosphorylates APBB1/FE65 and promotes its localization to the nucleus. Phosphorylates MAPK1/ERK2 and activates it by enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2. Phosphorylates FBXW7 and plays an inhibitory role in the NOTCH1 signaling. Phosphorylates FOXO1 resulting in its relocalization from the nucleus to the cytoplasm. Phosphorylates FOXO3, promoting its exit from the nucleus and interference with FOXO3-dependent transcription. Phosphorylates BRAF and MAP3K3/MEKK3 and inhibits their activity. Phosphorylates SLC9A3/NHE3 in response to dexamethasone, resulting in its activation and increased localization at the cell membrane. Phosphorylates CREB1. Necessary for vascular remodeling during angiogenesis (By similarity).
Two specific sites, one in the kinase domain (Thr-256) and the other in the C-terminal regulatory region (Ser-422), need to be phosphorylated for its full activation (By similarity). Phosphorylation at Ser-397 and Ser-401 are also essential for its activity (By similarity). Activated by WNK1, WNK2, WNK3 and WNK4; which promote phosphorylation by mTORC2 (By similarity).
Ubiquitinated by NEDD4L; which promotes proteasomal degradation. Ubiquitinated by SYVN1 at the endoplasmic reticulum; which promotes rapid proteasomal degradation and maintains a high turnover rate in resting cells (By similarity).
Interacts with DIAPH1. Forms a nuclear ternary complex with MRTFA and SRF.
Tumor suppressor which functions to suppress MRTFA-induced SRF transcriptional activity.
Belongs to the cyclic nucleotide phosphodiesterase family. PDE4 subfamily.
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.
Catalyzes the conversion of phosphatidic acid (PA) to CDP-diacylglycerol (CDP-DAG), an essential intermediate in the synthesis of phosphatidylglycerol, cardiolipin and phosphatidylinositol.
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.
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 phosphatidylethanolamine-binding protein family.
Binds ATP, opioids and phosphatidylethanolamine. Has lower affinity for phosphatidylinositol and phosphatidylcholine. Serine protease inhibitor which inhibits thrombin, neuropsin and chymotrypsin but not trypsin, tissue type plasminogen activator and elastase (By similarity). Inhibits the kinase activity of RAF1 by inhibiting its activation and by dissociating the RAF1/MEK complex and acting as a competitive inhibitor of MEK phosphorylation (By similarity).
HCNP may be involved in the function of the presynaptic cholinergic neurons of the central nervous system. HCNP increases the production of choline acetyltransferase but not acetylcholinesterase. Seems to be mediated by a specific receptor (By similarity).
Has a tendency to form dimers by disulfide cross-linking. Interacts with RAF1 and this interaction is enhanced if RAF1 is phosphorylated on residues 'Ser-338', 'Ser-339', 'Tyr-340' and 'Tyr-341'. Interacts with ALOX15; in response to IL13/interleukin-13, prevents the interaction of PEBP1 with RAF1 to activate the ERK signaling cascade (By similarity).
Belongs to the immunoglobulin superfamily. BTN/MOG family.
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.
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.
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. The eIF-3 complex appears to include 3 stable modules: module A is composed of EIF3A, EIF3B, EIF3G and EIF3I; module B is composed of EIF3F, EIF3H, and EIF3M; and module C is composed of EIF3C, EIF3D, EIF3E, EIF3K and EIF3L. EIF3C of module C binds EIF3B of module A and EIF3H of module B, thereby linking the three modules. EIF3J is a labile subunit that binds to the eIF-3 complex via EIF3B. The eIF-3 complex interacts with RPS6KB1 under conditions of nutrient depletion. Mitogenic stimulation leads to binding and activation of a complex composed of MTOR and RPTOR, leading to phosphorylation and release of RPS6KB1 and binding of EIF4B to eIF-3.
Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis. The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation. The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression.
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.
The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO2.
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.
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 nuclear hormone receptor family. NR1 subfamily.
Cornea specific. Expressed in the basal cells of corneal epithelium and stroma. Also expressed in esophageal epithelium.
Heterotetramer of two type I and two type II keratins. Keratin-3 associates with keratin-12.
There are two types of cytoskeletal and microfibrillar keratin: I (acidic; 40-55 kDa) and II (neutral to basic; 56-70 kDa).
Belongs to the PI3/PI4-kinase family. ATM subfamily.
Serine/threonine protein kinase which activates checkpoint signaling upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionizing ultraviolet A light (UVA), thereby acting as a DNA damage sensor. Recognizes the substrate consensus sequence [ST]-Q. Phosphorylates 'Ser-139' of histone variant H2AX at double strand breaks (DSBs), thereby regulating DNA damage response mechanism. Also plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and monospecific recognition by the B-cell antigen receptor (BCR) expressed on individual B-lymphocytes. After the introduction of DNA breaks by the RAG complex on one immunoglobulin allele, acts by mediating a repositioning of the second allele to pericentromeric heterochromatin, preventing accessibility to the RAG complex and recombination of the second allele. Also involved in signal transduction and cell cycle control. May function as a tumor suppressor. Necessary for activation of ABL1 and SAPK. Phosphorylates DYRK2, CHEK2, p53/TP53, FANCD2, NFKBIA, BRCA1, CTIP, nibrin (NBN), TERF1, RAD9, UBQLN4 and DCLRE1C. May play a role in vesicle and/or protein transport. Could play a role in T-cell development, gonad and neurological function. Binds DNA ends. Plays a role in replication-dependent histone mRNA degradation. Phosphorylation of DYRK2 in nucleus in response to genotoxic stress prevents its MDM2-mediated ubiquitination and subsequent proteasome degradation. Phosphorylates ATF2 which stimulates its function in DNA damage response. Phosphorylates ERCC6 which is essential for its chromatin remodeling activity at DNA double-strand breaks.
Belongs to the class IV-like SAM-binding methyltransferase superfamily. RNA methyltransferase NEP1 family.
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.
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.
Plays a role in transport between endoplasmic reticulum and Golgi.
Belongs to the LanC-like protein family.
Interacts (via C-terminus) with ARHGEF5.
Tooth-associated epithelia protein that probably plays a role in odontogenesis, the complex process that results in the initiation and generation of the tooth. May be incorporated in the enamel matrix at the end of mineralization process. Involved in the induction of RHOA activity via interaction with ARHGEF and expression of downstream factors such as ROCK. Plays a role in attachment of the junctional epithelium to the tooth surface.
Belongs to the eukaryotic ribosomal protein eS19 family.
Belongs to the chloride channel (TC 2.A.49) family. ClC-2/CLCN2 subfamily.
Phosphorylated. Activated by dephosphorylation.
The CLC channel family contains both chloride channels and proton-coupled anion transporters that exchange chloride or another anion for protons. The absence of conserved gating glutamate residues is typical for family members that function as channels (By similarity).
Voltage-gated chloride channel. Chloride channels have several functions including the regulation of cell volume, membrane potential stabilization, signal transduction and transepithelial transport (By similarity). Involved in the regulation of aldosterone production. The opening of CLCN2 channels at hyperpolarized membrane potentials in the glomerulosa causes cell membrane depolarization, activation of voltage-gated Ca2+ channels and increased expression of aldosterone synthase, the rate-limiting enzyme for aldosterone biosynthesis (By similarity).
Electrogenic proton-coupled amino-acid transporter that transports oligopeptides of 2 to 4 amino acids with a preference for dipeptides. Transports neutral and monovalently charged peptides with a proton to peptide stoichiometry of 1:1 or 2:1 (PubMed:8139693, PubMed:9051570, PubMed:12082113). Primarily responsible for the absorption of dietary di- and tripeptides from the small intestinal lumen (PubMed:8139693). Mediates transepithelial transport of muramyl and N-formylated bacterial dipeptides contributing to recognition of pathogenic bacteria by the mucosal immune system.
Intestine, kidney, liver and low in brain.
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 CND2 (condensin subunit 2) family.
Regulatory subunit of the condensin complex, a complex required for conversion of interphase chromatin into mitotic-like condense chromosomes.
Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MNB/DYRK subfamily.
Belongs to the glycosyl hydrolase 56 family.
According to some authors, ADP-ribosyltransferase activity of sirtuins may be an inefficient side reaction of the deacetylase activity and may not be physiologically relevant.
Acts as NAD-dependent protein lipoamidase, biotinylase, deacetylase and ADP-ribosyl transferase. Catalyzes more efficiently removal of lipoyl- and biotinyl- than acetyl-lysine modifications. Inhibits the pyruvate dehydrogenase complex (PDH) activity via the enzymatic hydrolysis of the lipoamide cofactor from the E2 component, DLAT, in a phosphorylation-independent manner. Catalyzes the transfer of ADP-ribosyl groups onto target proteins, including mitochondrial GLUD1, inhibiting GLUD1 enzyme activity. Acts as a negative regulator of mitochondrial glutamine metabolism by mediating mono ADP-ribosylation of GLUD1: expressed in response to DNA damage and negatively regulates anaplerosis by inhibiting GLUD1, leading to block metabolism of glutamine into tricarboxylic acid cycle and promoting cell cycle arrest. In response to mTORC1 signal, SIRT4 expression is repressed, promoting anaplerosis and cell proliferation. Acts as a tumor suppressor. Also acts as a NAD-dependent protein deacetylase: mediates deacetylation of 'Lys-471' of MLYCD, inhibiting its activity, thereby acting as a regulator of lipid homeostasis. Does not seem to deacetylate PC. Controls fatty acid oxidation by inhibiting PPARA transcriptional activation. Impairs SIRT1-PPARA interaction probably through the regulation of NAD(+) levels. Down-regulates insulin secretion.
Belongs to the sirtuin family. Class II subfamily.
Interacts with GLUD1, IDE and SLC25A5. Interacts with DLAT and PDHX.
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.
May be involved in MAP kinase activation, epithelial sodium channel (ENaC) down-regulation and cell cycling.
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.
Forms a heterooligomeric complex with ITAM-containing signaling subunits FCER1G. Interacts (via transmembrane domain) with signaling subunits; this interaction is a prerequisite for receptor complex expression on the cell surface and intracellular signal transduction. Binds the Fc region of antigen-complexed IgG.
Receptor for the invariable Fc fragment of immunoglobulin gamma (IgG) (By similarity). Optimally activated upon binding of clustered antigen-IgG complexes displayed on cell surfaces, triggers lysis of antibody-coated cells, a process known as antibody-dependent cellular cytotoxicity (ADCC). Does not bind free monomeric IgG, thus avoiding inappropriate effector cell activation in the absence of antigenic trigger. Mediates IgG effector functions on natural killer (NK) cells. Binds antigen-IgG complexes generated upon infection and triggers NK cell-dependent cytokine production and degranulation to limit viral load and propagation (By similarity). Fc-binding subunit that associates with FCER1G adapter to form functional signaling complexes. Following the engagement of antigen-IgG complexes, triggers phosphorylation of immunoreceptor tyrosine-based activation motif (ITAM)-containing adapters with subsequent activation of phosphatidylinositol 3-kinase signaling and sustained elevation of intracellular calcium that ultimately drive NK cell activation (By similarity). Mediates enhanced ADCC in response to afucosylated IgGs (PubMed:34485821).
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 eukaryotic ribosomal protein eS26 family.
Belongs to the phospholipase B-like family.
Belongs to the universal ribosomal protein uL16 family.
Belongs to the RNA polymerase beta chain family.
DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.
Component of the ribosome quality control complex (RQC).
E3 ubiquitin-protein ligase. Component of the ribosome quality control complex (RQC), a ribosome-associated complex that mediates ubiquitination and extraction of incompletely synthesized nascent chains for proteasomal degradation.
Belongs to the eukaryotic ribosomal protein eL15 family.
Chemotactic factor that mediates inflammatory response by attracting neutrophils, basophils, and T-cells to clear pathogens and protect the host from infection. Also plays an important role in neutrophil activation. Released in response to an inflammatory stimulus, exerts its effect by binding to the G-protein-coupled receptors CXCR1 and CXCR2, primarily found in neutrophils, monocytes and endothelial cells. G-protein heterotrimer (alpha, beta, gamma subunits) constitutively binds to CXCR1/CXCR2 receptor and activation by IL8 leads to beta and gamma subunits release from Galpha (GNAI2 in neutrophils) and activation of several downstream signaling pathways including PI3K and MAPK pathways.
Citrullination at Arg-27 prevents proteolysis, and dampens tissue inflammation, it also enhances leukocytosis, possibly through impaired chemokine clearance from the blood circulation.
Homodimer. Interacts with TNFAIP6 (via Link domain); this interaction interferes with chemokine binding to glycosaminoglycans.
Belongs to the glycosyl hydrolase 31 family.
Plays an important role in the final stage of carbohydrate digestion. Isomaltase activity is specific for both alpha-1,4- and alpha-1,6-oligosaccharides.
The precursor is proteolytically cleaved when exposed to pancreatic proteases in the intestinal lumen.
The resulting sucrase and isomaltase subunits stay associated with one another in a complex by non-covalent linkages.
There is a high degree of homology between the isomaltase and sucrase portions (41% of amino acid identity) indicating that this protein is evolved by partial gene duplication.
Interacts (via lumenal domain) with lysosomal protein MFSD1; the interaction starts while both proteins are still in the endoplasmic reticulum and is required for stability and lysosomal localization of MFSD1.
Required to protect lysosomal transporter MFSD1 from lysosomal proteolysis and for MFSD1 lysosomal localization.
Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia and flagellar axoneme. Forms filamentous polymers in the walls of ciliary and flagellar microtubules. Required for normal sperm mobility.
Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family.
Functions as a Na(+)-independent bidirectional multispecific transporter. Contributes to the renal and hepatic elimination of endogenous organic compounds from the systemic circulation into the urine and bile, respectively. Capable of transporting a wide range of purine and pyrimidine nucleobases, nucleosides and nucleotides, with cGMP, 2'deoxyguanosine and GMP being the preferred substrates. Functions as a pH- and chloride-independent cGMP bidirectional facilitative transporter that can regulate both intracellular and extracellular levels of cGMP and may be involved in cGMP signaling pathways. Mediates orotate/glutamate bidirectional exchange and most likely display a physiological role in hepatic release of glutamate into the blood. Involved in renal secretion and possible reabsorption of creatinine. Able to uptake prostaglandin E2 (PGE2) and may contribute to PGE2 renal excretion. Also transports alpha-ketoglutarate and urate. Apart from the orotate/glutamate exchange, the counterions for the uptake of other SLC22A7/OAT2 substrates remain to be identified.
Belongs to the heat shock protein 70 family.
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.
Activates the JUN N-terminal pathway through activation of the MAP kinase kinase MAP2K7.
Belongs to the bacterial ribosomal protein bS18 family. Mitochondrion-specific ribosomal protein mS40 subfamily.
Belongs to the DHHC palmitoyltransferase family.
The DHHC domain is required for palmitoyltransferase activity.
Belongs to the adenosylhomocysteinase family.
Belongs to the major facilitator superfamily. Sodium/anion cotransporter family.
Important for the resorption of phosphate by the kidney. May be involved in actively transporting phosphate into cells via Na(+) cotransport in the renal brush border membrane. Plays a role in urate transport in the kidney.
Belongs to the TRAFAC class dynamin-like GTPase superfamily. Dynamin/Fzo/YdjA family.
Interacts with unphosphorylated ITGA4. Interacts with AR and SRF (By similarity). Interacts with PTK2B/PYK2, PTPN22 and PTPN12. Interacts (via LD motif 3) with LYN and the interaction is induced upon B-cell antigen receptor (BCR) activation. Interacts (via LD motif 3) with PTK2/FAK (By similarity).
Phosphorylated on tyrosine residues. Phosphorylation on Tyr-72 is important for its inhibitory function. Bombesin stimulates phosphorylation on Tyr-22, Tyr-62 and Tyr-72 (By similarity).
The LIM domain 3 is critical for focal adhesion targeting and the suppression of paxillin (PXN) tyrosine phosphorylation. The LIM domain 3 alone or both LIM domains 3 and 4 can mediate interaction with AR (By similarity).
Transcriptional coactivator for androgen receptor (AR) and serum response factor (SRF). Contributes to the regulation of cell adhesion, spreading and cell migration and acts as a negative regulator in integrin-mediated cell adhesion events. Suppresses the integrin-induced tyrosine phosphorylation of paxillin (PXN). May play a critical role as an adapter protein in the formation of the adhesion zone in osteoclasts. Negatively regulates B-cell antigen receptor (BCR) signaling (By similarity).
Although homologous to serine proteases, it has lost all essential catalytic residues and has no enzymatic activity.
As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of heme iron and to prevent kidney damage. Haptoglobin also acts as an antioxidant, has antibacterial activity and plays a role in modulating many aspects of the acute phase response. Hemoglobin/haptoglobin complexes are rapidly cleared by the macrophage CD163 scavenger receptor expressed on the surface of liver Kupfer cells through an endocytic lysosomal degradation pathway (By similarity).
Expressed by the liver and secreted in plasma.
Tetramer of two alpha and two beta chains; disulfide-linked (By similarity). The hemoglobin/haptoglobin complex is composed of a haptoglobin dimer bound to two hemoglobin alpha-beta dimers (By similarity). Interacts with CD163 (By similarity). Interacts with ERGIC3 (By similarity).
The beta chain mediates most of the interactions with both subunits of hemoglobin, while the alpha chain forms the homodimeric interface.
Belongs to the peptidase C19 family. USP14/UBP6 subfamily.
Homodimer (Potential). Associates with the 26S proteasome. Interacts with FANCC, CXCR4 and ERN1. Interacts with TRIM14; this interaction recruits USP14 to cleave ubiquitin chains of CGAS (By similarity).
Proteasome-associated deubiquitinase which releases ubiquitin from the proteasome targeted ubiquitinated proteins. Ensures the regeneration of ubiquitin at the proteasome. Is a reversibly associated subunit of the proteasome and a large fraction of proteasome-free protein exists within the cell. Required for the degradation of the chemokine receptor CXCR4 which is critical for CXCL12-induced cell chemotaxis. Serves also as a physiological inhibitor of endoplasmic reticulum-associated degradation (ERAD) under the non-stressed condition by inhibiting the degradation of unfolded endoplasmic reticulum proteins via interaction with ERN1 (By similarity). Indispensable for synaptic development and function at neuromuscular junctions (NMJs) (By similarity). Plays a role in the innate immune defense against viruses by stabilizing the viral DNA sensor CGAS and thus inhibiting its autophagic degradation (By similarity).
Was originally thought to be a guanine tRNA-ribosyltransferase.
Gamma-tubulin complex is necessary for microtubule nucleation at the centrosome.
Belongs to the ribonucleoside diphosphate reductase small chain family.
Belongs to the eukaryotic ribosomal protein eL38 family.
Exhibits ester hydrolase activity on the substrate p-nitrophenyl acetate.
Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ2 subfamily.
Highly expressed in the ventricle and skeletal muscle, moderately in cerebrum and cerebellum. Only low levels are detected in kidney or lung.
Homomultimeric and heteromultimeric association with KCNJ4/Kir2.3. 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 extracellular barium and cesium.
S-nitrosylation increases the open probability and inward rectifying currents.
pH-dependent, voltage-insensitive, background potassium channel protein.
Interacts with SERPINE1/PAI1 and C1QBP (By similarity). Monomer.
It has been suggested that the active SMB domain may be permitted considerable disulfide bond heterogeneity or variability, thus two alternate disulfide patterns based on 3D structures are described with 1 disulfide bond conserved in both.
The SMB domain mediates interaction with SERPINE1/PAI1.
Vitronectin is a cell adhesion and spreading factor found in serum and tissues. Vitronectin interact with glycosaminoglycans and proteoglycans. Is recognized by certain members of the integrin family and serves as a cell-to-substrate adhesion molecule. Inhibitor of the membrane-damaging effect of the terminal cytolytic complement pathway.
Ferritin receptor that mediates non-transferrin-dependent delivery of iron. Mediates cellular uptake of ferritin-bound iron by stimulating ferritin endocytosis from the cell surface with consequent iron delivery within the cell. Delivery of iron to cells by ferritin is required for the development of specific cell types, suggesting the existence of cell type-specific mechanisms of iron traffic in organogenesis, which alternatively utilize transferrin or non-transferrin iron delivery pathways. Ferritin mediates iron uptake in capsule cells of the developing kidney. Binds preferrentially ferritin light chain (FTL) compared to heavy chain (FTH1).
Belongs to the metallo-dependent hydrolases superfamily. ATZ/TRZ family.
Catalyzes the hydrolytic deamination of guanine, producing xanthine and ammonia.
Translation initiation factor that is able to deliver tRNA to the P-site of the eukaryotic ribosome in a GTP-independent manner. The binding of Met-tRNA(I) occurs after the AUG codon finds its position in the P-site of 40S ribosomes, the situation that takes place during initiation complex formation on some specific RNAs. Its activity in tRNA binding with 40S subunits does not require the presence of the aminoacyl moiety. Possesses the unique ability to deliver non-Met (elongator) tRNAs into the P-site of the 40S subunit. In addition to its role in initiation, can promote release of deacylated tRNA and mRNA from recycled 40S subunits following ABCE1-mediated dissociation of post-termination ribosomal complexes into subunits.
Belongs to the nucleotide pyrophosphatase/phosphodiesterase family.
Isoform MLC3 is acetylated at position 2.
Myosin is a hexamer of 2 heavy chains and 4 light chains. Does not bind calcium.
Non-regulatory myosin light chain required for proper formation and/or maintenance of myofibers, and thus appropriate muscle function.
Belongs to the chondroitin N-acetylgalactosaminyltransferase family.
Interacts with PPIF; the interaction is impaired by CsA.
Belongs to the apolipoprotein A2 family.
Belongs to the class I-like SAM-binding methyltransferase superfamily. C5-methyltransferase family.
Belongs to the protein-tyrosine phosphatase family. Non-receptor class subfamily.
May act at junctions between the membrane and the cytoskeleton.
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.
Belongs to the protein disulfide isomerase family.
Belongs to the aerobic coproporphyrinogen-III oxidase family.
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 TAF9 family. CENP-S/MHF1 subfamily.
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.
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.
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 class I-like SAM-binding methyltransferase superfamily. Cation-dependent O-methyltransferase family.
Belongs to the glycosyltransferase 39 family.
Transfers mannose from Dol-P-mannose to Ser or Thr residues on proteins.
Binds to actin and to fibronectin. Identified in a complex composed of ACTA1, COBL, GSN and TMSB4X. Interacts with the inactive form of EIF2AK2/PKR.
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. Plays a role in ciliogenesis.
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.
Belongs to the V-ATPase 116 kDa subunit family.
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.
Belongs to the ALG10 glucosyltransferase family.
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.
Acts as a negative regulator of innate and adaptive immunity by maintaining immune homeostasis. Plays a regulatory role in the Toll-like signaling pathway by determining the strength of LPS-induced signaling and gene expression (By similarity). Inhibits TCR-mediated T-cell activation and negatively regulate T-cell function to prevent hyperresponsiveness (By similarity). Inhibits also autolysosome formation via negatively modulating MTOR activation by interacting with RAC1 and promoting the disassociation of the RAC1-MTOR complex (By similarity). Plays an essential role in NK-cell biology by acting as a checkpoint and displaying an expression pattern correlating with NK-cell maturation process and by negatively regulating NK-cell maturation and antitumor immunity (By similarity). Mechanistically, suppresses IL-15-triggered mTOR activity in NK-cells (By similarity).
Belongs to the TNFAIP8 family. TNFAIP8L2 subfamily.
May interact with CASP8; however, such result is unclear since could not reproduce the interaction with CASP8. Interacts with RAC1.
Phosphorylated by TAK1/MAP3K7; this phosphorylation triggers association with BTRC and subsequent ubiquitination and degradation.
The central region was initially thought to constitute a DED (death effector) domain. However, 3D-structure data reveal a previously uncharacterized fold that is different from the predicted fold of a DED (death effector) domain. It consists of a large, hydrophobic central cavity that is poised for cofactor binding (By similarity).
Ubiquitinated in a BTRC-depdent manner; leading to degradation mediated through the proteasome pathway.
Belongs to the amiloride-sensitive sodium channel (TC 1.A.6) family. SCNN1A subfamily.
ENaC cleavage by furin, and subsequently by prostasin (PRSS8), leads to a stepwise increase in the open probability of the channel as a result of release of the alpha and gamma subunit inhibitory tracts, respectively. Interaction of ENaC subunit SCNN1B with BPIFA1 protects ENaC against proteolytic activation.
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. Interacts with NEDD4 (via WW domains). Interacts with NEDD4L (via WW domains). Interacts with WWP1 (via WW domains). Interacts with WWP2 (via WW domains). Interacts with the full-length immature form of PCSK9 (pro-PCSK9).
Sodium permeable non-voltage-sensitive ion channel inhibited by the diuretic amiloride. Mediates the electrodiffusion of the luminal sodium (and water, which follows osmotically) through the apical membrane of epithelial cells. Plays an essential role in electrolyte and blood pressure homeostasis, but also in airway surface liquid homeostasis, which is important for proper clearance of mucus. Controls the reabsorption of sodium in kidney, colon, lung and eccrine sweat glands. Also plays a role in taste perception.
Ubiquitinated; this targets individual subunits for endocytosis and proteasome-mediated degradation.
Belongs to the mitochondrion-specific ribosomal protein mL50 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.
May modify the assembly dynamics of microtubules, such that microtubules are slightly longer, but more dynamic.
Catalyzes the oxidative metabolism of numerous xenobiotics, including mainly therapeutic drugs and insecticides that contain a soft nucleophile, most commonly nitrogen and sulfur and participates to their bioactivation (PubMed:3785145, PubMed:10950853, PubMed:16620765, PubMed:11302936, PubMed:15144220, PubMed:15294458). Most drug substrates are tertiary amines such as prochlorperazine and trifluoperazine which are N-oxygenated to form the N-oxide, or sulfides such as thiourea and ethionamide, which are S-oxygenated to the sulfoxide (PubMed:3785145, PubMed:15144220, PubMed:16620765). Others include primary alkylamines such as N-dodecylamine and octan-1-amine that are sequentially monooxygenated to oximes through intermediate hydroxylamines and both steps are NADPH- and oxygen-dependent (PubMed:3785145). Also metabolized N-Deacetyl ketoconazole (DAK) to N-hydroxy-DAK and appears to further metabolizes N-hydroxy-DAK to two others metabolites (PubMed:10950853). Also catalyzes S-oxygenation of the thioether-containing organophosphate insecticides, phorate and disulfoton (PubMed:15294458).
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).
Endoplasmic reticulum-Golgi intermediate compartment
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.
Belongs to the short-chain dehydrogenases/reductases (SDR) family.
May be involved in ciliary biogenesis or function.
Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A4 subfamily.
Belongs to the universal ribosomal protein uS10 family.
Belongs to the formin homology family. Cappuccino subfamily.
Belongs to the chloride channel (TC 2.A.49) family. ClC-5/CLCN5 subfamily.
Proton-coupled chloride transporter. Functions as antiport system and exchanges chloride ions against protons. Important for normal acidification of the endosome lumen. May play an important role in renal tubular function (By similarity). The CLC channel family contains both chloride channels and proton-coupled anion transporters that exchange chloride or another anion for protons. The absence of conserved gating glutamate residues is typical for family members that function as channels (Probable).
Ubiquitinated by NEDD4L in the presence of albumin; which promotes endocytosis and proteasomal degradation.
Belongs to the type I cytokine receptor family. Type 2 subfamily.
Belongs to the glycosyltransferase 47 family.
Belongs to the phosphatase 2A regulatory subunit B56 family.
The B regulatory subunit might modulate substrate selectivity and catalytic activity, and also might direct the localization of the catalytic enzyme to a particular subcellular compartment.
Catalyzes the reversible hydration of carbon dioxide into bicarbonate and protons and thus is essential to maintaining intracellular and extracellular pH. May stimulate the sodium/bicarbonate transporter activity of SLC4A4 that acts in pH homeostasis. It is essential for acid overload removal from the retina and retina epithelium, and acid release in the choriocapillaris in the choroid.
Belongs to the DEAD box helicase family. eIF4A subfamily.
Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIB subfamily.
Catalyzes the hydrolysis of ATP coupled with the transport of calcium from the cytoplasm to the extracellular space thereby maintaining intracellular calcium homeostasis. Plays a role in blood pressure regulation through regulation of intracellular calcium concentration and nitric oxide production leading to regulation of vascular smooth muscle cells vasoconstriction. Positively regulates bone mineralization through absorption of calcium from the intestine. Plays dual roles in osteoclast differentiation and survival by regulating RANKL-induced calcium oscillations in preosteoclasts and mediating calcium extrusion in mature osteoclasts (By similarity). Regulates insulin sensitivity through calcium/calmodulin signaling pathway by regulating AKT1 activation and NOS3 activation in endothelial cells (By similarity). May play a role in synaptic transmission by modulating calcium and proton dynamics at the synaptic vesicles.
Isoform B is ubiquitously expressed and is the most predominant isoform. Isoform C is expressed at much lower levels in all tissues tested, but liver, while isoform A is found only in aorta, brain and stomach.
Isoforms A and C contain and additional calmodulin-binding subdomain B which is different in the different splice variants and shows pH dependent calmodulin binding properties.
Monomer. Dimer. Oligomer. Calmodulin binding. Interacts with PDZD11. Interacts with SLC35G1 and STIM1. Interacts with YWHAE; interacts with the monomeric and dimeric forms of the YWHAE but prefer the monomer form; this interaction inhibits calcium-transporting ATPase activity (By similarity). Interacts with NPTN; this interaction stabilizes ATP2B1 and increases ATPase activity; this interaction controls T cell calcium homeostasis following T cell activation. Interacts with EPB41; regulates small intestinal calcium absorption through regulation of membrane expression of ATP2B1 (By similarity).
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.
Belongs to the connexin family. Alpha-type (group II) subfamily.
Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. PKD subfamily.
Involved in transport of proteins from the cis/medial-Golgi to the trans-Golgi network.
Catalyzes the hydrolysis of ATP coupled with the transport of calcium.
Belongs to the G-protein coupled receptor 1 family. Opsin subfamily.
Contains one covalently linked retinal chromophore.
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.
Homodimer (By similarity). May form a complex composed of RHO, GRK1 and RCVRN in a Ca(2+)-dependent manner; RCVRN prevents the interaction between GRK1 and RHO (By similarity). Interacts with GRK1 (By similarity). Interacts (phosphorylated form) with SAG. Interacts with GNAT1. Interacts with GNAT3. SAG and G-proteins compete for a common binding site (By similarity). Interacts with PRCD; the interaction promotes PRCD stability. Forms a complex with ASAP1 and ARF4. Forms a complex with ASAP1, RAB11A, Rabin8/RAB3IP, ARF4 and RAB11FIP3; the complex regulates Golgi-to-cilia rhodopsin/RHO transport in photoreceptors (By similarity).
Phosphorylated on some or all of the serine and threonine residues present in the C-terminal region.
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 the arrestin SAG and terminates signaling (By similarity).
Belongs to the nuclear hormone receptor family.
Phosphorylated on Ser and Thr residues at the cytoplasmic C-terminus by G protein-coupled receptor kinases (GRKs).
Receptor for secretin (SCT), which is involved in different processes such as regulation of the pH of the duodenal content, food intake and water homeostasis. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase (By similarity). Upon binding to secretin, regulates the pH of the duodenum by (1) inhibiting the secretion of gastric acid from the parietal cells of the stomach and (2) stimulating the production of bicarbonate (NaHCO(3)) from the ductal cells of the pancreas (By similarity). In addition to regulating the pH of the duodenal content, plays a central role in diet induced thermogenesis: acts as a non-sympathetic brown fat (BAT) activator mediating prandial thermogenesis, which consequentially induces satiation. Mechanistically, secretin released by the gut after a meal binds to secretin receptor (SCTR) in brown adipocytes, activating brown fat thermogenesis by stimulating lipolysis, which is sensed in the brain and promotes satiation. Also able to stimulate lipolysis in white adipocytes. Also plays an important role in cellular osmoregulation by regulating renal water reabsorption. Also plays a role in the central nervous system: required for synaptic plasticity (By similarity).
Belongs to the eIF-2B alpha/beta/delta subunits family.
Catalyzes the exchange of eukaryotic initiation factor 2-bound GDP for GTP.
Complex of five different subunits; alpha, beta, gamma, delta and epsilon.
Belongs to the ATP-dependent DNA ligase family.
Belongs to the G-protein coupled receptor 3 family.
Belongs to the FARP (FMRFamide related peptide) family.
Belongs to the ATPase alpha/beta chains family.
Produces ATP from ADP in the presence of a proton gradient across the membrane.
Involved in intracellular signal transduction mediated by cytokines and growth factors. Upon IL-2 and GM-CSL stimulation, it plays a role in signaling leading to DNA synthesis and MYC induction. May also play a role in T-cell development. Involved in down-regulation of receptor tyrosine kinase via multivesicular body (MVBs) when complexed with HGS (ESCRT-0 complex). 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.
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 KCNMB (TC 8.A.14.1) family.
Interacts with KCNMA1 tetramer. There are probably 4 molecules of KCMNB per KCNMA1 tetramer.
Regulatory subunit of the calcium activated potassium KCNMA1 (maxiK) channel. Modulates the calcium sensitivity and gating kinetics of KCNMA1, thereby contributing to KCNMA1 channel diversity.
Belongs to the fatty acyl-CoA reductase family.
Catalyzes the reduction of fatty acyl-CoA to fatty alcohols.
Belongs to the BPI/LBP/Plunc superfamily. BPI/LBP family.
Plays a role in the innate immune response. Binds to the lipid A moiety of bacterial lipopolysaccharides (LPS), a glycolipid present in the outer membrane of all Gram-negative bacteria. Acts as an affinity enhancer for CD14, facilitating its association with LPS. Promotes the release of cytokines in response to bacterial lipopolysaccharide.
When bound to LPS, interacts (via C-terminus) with soluble and membrane-bound CD14.
Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.
Belongs to the peptidase C78 family. ZUFSP subfamily.
Belongs to the DEAD box helicase family. DDX59 subfamily.
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.
Belongs to the group II decarboxylase family.
Belongs to the PI3/PI4-kinase family. Type III PI4K subfamily.
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. The eIF-3 complex appears to include 3 stable modules: module A is composed of EIF3A, EIF3B, EIF3G and EIF3I; module B is composed of EIF3F, EIF3H, and EIF3M; and module C is composed of EIF3C, EIF3D, EIF3E, EIF3L and EIF3K. EIF3C of module C binds EIF3B of module A and EIF3H of module B, thereby linking the three modules. EIF3J is a labile subunit that binds to the eIF-3 complex via EIF3B. The eIF-3 complex interacts with RPS6KB1 under conditions of nutrient depletion. Mitogenic stimulation leads to binding and activation of a complex composed of MTOR and RPTOR, leading to phosphorylation and release of RPS6KB1 and binding of EIF4B to eIF-3. Interacts with EIF4G1. Also interacts with KRT7 and PIWIL2.
Phosphorylated. Phosphorylation is enhanced upon serum stimulation.
RNA-binding component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis. The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation. The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression.
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.
Belongs to the complex I 30 kDa subunit family.
Part of BBSome complex, that contains BBS1, BBS2, BBS4, BBS5, BBS7, BBS8/TTC8, BBS9 and BBIP10.
The BBSome complex is thought to function as a coat complex required for sorting of specific membrane proteins to the primary cilia. The BBSome complex is required for ciliogenesis but is dispensable for centriolar satellite function. This ciliogenic function is mediated in part by the Rab8 GDP/GTP exchange factor, which localizes to the basal body and contacts the BBSome. Rab8(GTP) enters the primary cilium and promotes extension of the ciliary membrane. Firstly the BBSome associates with the ciliary membrane and binds to RAB3IP/Rabin8, the guanosyl exchange factor (GEF) for Rab8 and then the Rab8-GTP localizes to the cilium and promotes docking and fusion of carrier vesicles to the base of the ciliary membrane. The BBSome complex, together with the LTZL1, controls SMO ciliary trafficking and contributes to the sonic hedgehog (SHH) pathway regulation. Required for BBSome complex ciliary localization but not for the proper complex assembly.
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.
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.
Heterodimer of an alpha chain and a beta chain (beta-2-microglobulin).
Involved in the presentation of foreign antigens to the immune system.
Belongs to the small heat shock protein (HSP20) family.
Belongs to the integrin alpha chain family.
Belongs to the JHDM3 histone demethylase family.
Belongs to the Mediator complex subunit 18 family.
Belongs to the phosphatase and actin regulator family.
Component of the Mediator complex, which is composed of MED1, MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L, MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct module termed the CDK8 module. Mediator containing the CDK8 module is less active than Mediator lacking this module in supporting transcriptional activation. Individual preparations of the Mediator complex lacking one or more distinct subunits have been variously termed ARC, CRSP, DRIP, PC2, SMCC and TRAP.
Regulator of protein phosphatase 1 (PP1) required for neural tube and optic fissure closure, and enteric neural crest cell (ENCCs) migration during development. Acts as an activator of PP1. During neural tube closure, localizes to the ventral neural tube and activates PP1, leading to down-regulate cell proliferation within cranial neural tissue and the neural retina. Also acts as a regulator of migration of enteric neural crest cells (ENCCs) by activating PP1, leading to repression of the integrin signaling through the rho/rock pathway.
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.
Belongs to the eukaryotic cobalamin transport proteins family.
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.
Belongs to the lipopolysaccharide (LPS) receptor, a multi-protein complex containing at least CD14, LY96 and TLR4. Interacts with LPS-bound LPB. Interacts with LPAR1. Interacts with the TLR2:TLR6 or TLR2:TLR1 heterodimers; upon interaction with ligands such as diacylated lipopeptides and triacylated lipopeptides, respectively. Interacts with MYO18A. Interacts with FSTL1.
Coreceptor for bacterial lipopolysaccharide. In concert with LBP, binds to monomeric lipopolysaccharide and delivers it to the LY96/TLR4 complex, thereby mediating the innate immune response to bacterial lipopolysaccharide (LPS) (PubMed:1375269). Acts via MyD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Acts as a coreceptor for TLR2:TLR6 heterodimer in response to diacylated lipopeptides and for TLR2:TLR1 heterodimer in response to triacylated lipopeptides, these clusters trigger signaling from the cell surface and subsequently are targeted to the Golgi in a lipid-raft dependent pathway (By similarity). Binds electronegative LDL (LDL(-)) and mediates the cytokine release induced by LDL(-) (By similarity).
The C-terminal leucine-rich repeat (LRR) region is required for responses to smooth LPS.
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. Required for protein transport from the endoplasmic reticulum to the Golgi complex. Regulates the compacted morphology of the Golgi.
Belongs to the opioid neuropeptide precursor family.
Dynorphin peptides differentially regulate the kappa opioid receptor. Dynorphin A(1-13) has a typical opioid activity, it is 700 times more potent than Leu-enkephalin.
Leu-enkephalins compete with and mimic the effects of opiate drugs. They play a role in a number of physiologic functions, including pain perception and responses to stress.
Leumorphin has a typical opioid activity and may have anti-apoptotic effect.
Acetylation of Lys-380 by CREBBP enhances transcriptional activity. Acetylation of Lys-380 by EP300. Deacetylation of Lys-380 by SIRT1 impairs its ability to induce proapoptotic program and modulate cell senescence. Deacetylation by SIRT2 impairs its ability to induce transcription activation in a AKT-dependent manner. Acetylation at Lys-379 increases stability. Deacetylation at Lys-379 by SIRT6 decreases its stability, thereby regulating cell senescence.
Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type. Involved in cell cycle regulation as a trans-activator that acts to negatively regulate cell division by controlling a set of genes required for this process. One of the activated genes is an inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. Its pro-apoptotic activity is activated via its interaction with PPP1R13B/ASPP1 or TP53BP2/ASPP2 (By similarity). However, this activity is inhibited when the interaction with PPP1R13B/ASPP1 or TP53BP2/ASPP2 is displaced by PPP1R13L/iASPP (By similarity). In cooperation with mitochondrial PPIF is involved in activating oxidative stress-induced necrosis; the function is largely independent of transcription. Prevents CDK7 kinase activity when associated to CAK complex in response to DNA damage, thus stopping cell cycle progression. Induces the transcription of long intergenic non-coding RNA p21 (lincRNA-p21) and lincRNA-Mkln1. LincRNA-p21 participates in TP53-dependent transcriptional repression leading to apoptosis and seems to have an effect on cell-cycle regulation. Regulates the circadian clock by repressing CLOCK-ARNTL/BMAL1-mediated transcriptional activation of PER2.
Forms homodimers and homotetramers (By similarity). Binds DNA as a homotetramer. Interacts with AXIN1. Probably part of a complex consisting of TP53, HIPK2 and AXIN1. Interacts with histone acetyltransferases EP300 and methyltransferases HRMT1L2 and CARM1, and recruits them to promoters. Interacts (via C-terminus) with TAF1; when TAF1 is part of the TFIID complex. Interacts with ING4; this interaction may be indirect. Found in a complex with CABLES1 and TP73. Interacts with HIPK1, HIPK2, and TP53INP1. Interacts with WWOX. Interacts with USP7 and SYVN1. Interacts with HSP90AB1. Interacts with CHD8; leading to recruit histone H1 and prevent transactivation activity. Interacts with ARMC10, BANP, CDKN2AIP, NUAK1, STK11/LKB1, UHRF2 and E4F1. Interacts with YWHAZ; the interaction enhances TP53 transcriptional activity. Phosphorylation of YWHAZ inhibits this interaction. Interacts (via DNA-binding domain) with MAML1 (via N-terminus). Interacts with MKRN1. Interacts with PML (via C-terminus). Interacts with MDM2; leading to ubiquitination and proteasomal degradation of TP53. Directly interacts with FBXO42; leading to ubiquitination and degradation of TP53. Interacts (phosphorylated at Ser-15 by ATM) with the phosphatase PP2A-PPP2R5C holoenzyme; regulates stress-induced TP53-dependent inhibition of cell proliferation. Interacts with PPP2R2A. Interacts with AURKA, DAXX, BRD7 and TRIM24. Interacts (when monomethylated at Lys-380) with L3MBTL1. Interacts with GRK5. Binds to the CAK complex (CDK7, cyclin H and MAT1) in response to DNA damage. Interacts with CDK5 in neurons. Interacts with AURKB, SETD2, UHRF2 and NOC2L. Interacts (via N-terminus) with PTK2/FAK1; this promotes ubiquitination by MDM2. Interacts with PTK2B/PYK2; this promotes ubiquitination by MDM2. Interacts with PRKCG. Interacts with PPIF; the association implicates preferentially tetrameric TP53, is induced by oxidative stress and is impaired by cyclosporin A (CsA). Interacts with SNAI1; the interaction induces SNAI1 degradation via MDM2-mediated ubiquitination and inhibits SNAI1-induced cell invasion. Interacts with KAT6A. Interacts with UBC9. Interacts with ZNF385B; the interaction is direct. Interacts (via DNA-binding domain) with ZNF385A; the interaction is direct and enhances p53/TP53 transactivation functions on cell-cycle arrest target genes, resulting in growth arrest. Interacts with ANKRD2. Interacts with RFFL and RNF34; involved in p53/TP53 ubiquitination. Interacts with MTA1 and COP1. Interacts with CCAR2 (via N-terminus). Interacts with MORC3. Interacts (via C-terminus) with POU4F2 (via C-terminus). Interacts (via oligomerization region) with NOP53; the interaction is direct and may prevent the MDM2-mediated proteasomal degradation of TP53. Interacts with AFG1L; mediates mitochondrial translocation of TP53. Interacts with UBD. Interacts with TAF6. Interacts with C10orf90/FATS; the interaction inhibits binding of TP53 and MDM2 (By similarity). Interacts with NUPR1; interaction is stress-dependent. Forms a complex with EP300 and NUPR1; this complex binds CDKN1A promoter leading to transcriptional induction of CDKN1A (By similarity). Interacts with PRMT5 in response to DNA damage; the interaction is TTC5/STRAP dependent (By similarity). Interacts with PPP1R13L (via SH3 domain and ANK repeats); the interaction inhibits pro-apoptotic activity of p53/TP53 (By similarity). Interacts with PPP1R13B/ASPP1 and TP53BP2/ASPP2; the interactions promotes pro-apoptotic activity (By similarity). When phosphorylated at Ser-15, interacts with DDX3X and gamma-tubulin (By similarity). Interacts with KAT7/HBO1; leading to inhibit histone acetyltransferase activity of KAT7/HBO1 (By similarity). Interacts (via N-terminus) with E3 ubiquitin-protein ligase MUL1; the interaction results in ubiquitination of cytoplasmic TP53 at Lys-24 and subsequent proteasomal degradation (By similarity). Interacts with S100A4; this interaction promotes TP53 degradation (By similarity). Interacts with TTC5/STRAP; the interaction may result in increased mitochondrial-dependent apoptosis (By similarity). Interacts with NQO1; this interaction is NADH-dependent, stabilizes TP53 in response to oxidative stress and protects it from ubiquitin-independent degradation by the 20S proteasome (By similarity). Interacts with DAZAP2 at TP53 target gene promoters; the interaction is triggered by DNA damage and leads to modulation of the expression of a subset of TP53 target genes, reducing DNA damage-induced cell death by limiting the expression of cell death-mediating TP53 target genes (By similarity). Interacts (via N-terminus) with ZNF768 (via zinc-finger domains); interaction might be facilitated by TP53 oligomerization state (By similarity). Forms a ternary complex with ALDOB and G6PD; this interaction is direct. ALDOB stabilizes the complex inhibiting G6PD activity and keeping oxidative pentose phosphate metabolism in check. Interacts with MORN3; the interactions mediate post-transcriptional modifications of TP53 by MDM2 and SIRT1 (By similarity).
Monomethylated at Lys-370 by SETD7, leading to stabilization and increased transcriptional activation. Monomethylated at Lys-368 by SMYD2, leading to decreased DNA-binding activity and subsequent transcriptional regulation activity. Lys-370 monomethylation prevents interaction with SMYD2 and subsequent monomethylation at Lys-368. Dimethylated at Lys-371 by EHMT1 and EHMT2. Monomethylated at Lys-380 by KMT5A, promoting interaction with L3MBTL1 and leading to repress transcriptional activity. Demethylation of dimethylated Lys-368 by KDM1A prevents interaction with TP53BP1 and represses TP53-mediated transcriptional activation (By similarity). Monomethylated at Arg-331 and dimethylated at Arg-333 and Arg-335 by PRMT5; methylation is increased after DNA damage and might possibly affect TP53 target gene specificity (By similarity). Polyubiquitinated by MUL1 at Lys-24 which leads to proteasomal degradation (By similarity).
Phosphorylation on Ser residues mediates transcriptional activation. Phosphorylation at Ser-9 by HIPK4 increases repression activity on BIRC5 promoter (By similarity). Phosphorylated on Thr-18 by VRK1, which may prevent the interaction with MDM2. Phosphorylated on Ser-20 by CHEK2 in response to DNA damage, which prevents ubiquitination by MDM2. Phosphorylated on Ser-20 by PLK3 in response to reactive oxygen species (ROS), promoting p53/TP53-mediated apoptosis. Probably phosphorylated on by CDK7 in a CAK complex in response to DNA damage. Phosphorylated by HIPK1. Phosphorylated on Ser-390 following UV but not gamma irradiation. Stabilized by CDK5-mediated phosphorylation in response to genotoxic and oxidative stresses at Ser-15, leading to accumulation of p53/TP53, particularly in the nucleus, thus inducing the transactivation of p53/TP53 target genes. Phosphorylated at Ser-313 and Ser-390 by CDK2 in response to DNA-damage (By similarity). Phosphorylation at Ser-15 is required for interaction with DDX3X and gamma-tubulin (By similarity).
Sumoylated with SUMO1. Sumoylated at Lys-384 by UBC9 (By similarity).
The [KR]-[STA]-K motif is specifically recognized by the SETD7 methyltransferase.
Ubiquitinated by MDM2 and SYVN1, which leads to proteasomal degradation. Ubiquitinated by RFWD3, which works in cooperation with MDM2 and may catalyze the formation of short polyubiquitin chains on p53/TP53 that are not targeted to the proteasome. Ubiquitinated by MKRN1, which leads to proteasomal degradation. Deubiquitinated by USP10, leading to stabilize it. Ubiquitinated by TRIM24, RFFL, RNF34 and RNF125, which leads to proteasomal degradation. Ubiquitination by TOPORS induces degradation. Deubiquitination by USP7, leading to stabilize it. Ubiquitinated by COP1, which leads to proteasomal degradation (By similarity). Ubiquitination and subsequent proteasomal degradation is negatively regulated by CCAR2 (By similarity). Polyubiquitinated by C10orf90/FATS, polyubiquitination is 'Lys-48'-linkage independent and non-proteolytic, leading to TP53 stabilization (By similarity).
p53 is found in increased amounts in a wide variety of transformed cells. p53 is frequently mutated or inactivated in many types of cancer.
Initiates complex N-linked carbohydrate formation. Essential for the conversion of high-mannose to hybrid and complex N-glycans.
Interacts with MGAT4D. Interacts with BRI3 (By similarity).
The cofactor is mostly bound to the substrate.
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 sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A15 subfamily.
Important role in the capacity of milk to transport calcium phosphate.
Mammary gland specific. Secreted in milk.
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.
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.
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 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.
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 (By similarity).
Belongs to the metallo-dependent hydrolases superfamily. TatD-type hydrolase family.
Involved in nucleolar processing of pre-18S ribosomal RNA.
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 syndecan proteoglycan 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.
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.
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.
Detected in heart muscle (at protein level).
Monomer, homodimer and homooligomer. Mostly monomeric in the absence of calcium. Forms higher oligomers in a calcium-dependent manner. Dimers associate to form tetramers, that then form linear homomer chains. Interacts with ASPH and TRDN (By similarity).
Phosphorylation in the C-terminus, probably by CK2, moderately increases calcium buffering capacity.
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 histone-like Alba family.
Component of nuclear RNase P and RNase MRP complexes. RNase P consists of a catalytic RNA moiety and 10 different protein chains; POP1, POP4, POP5, POP7, RPP14, RPP21, RPP25, RPP30, RPP38 and RPP40. Within the RNase P complex, POP1, POP7 and RPP25 form the 'finger' subcomplex, POP5, RPP14, RPP40 and homodimeric RPP30 form the 'palm' subcomplex, and RPP21, POP4 and RPP38 form the 'wrist' subcomplex. All subunits of the RNase P complex interact with the catalytic RNA. Several subunits of RNase P are also part of the RNase MRP complex. RNase MRP consists of a catalytic RNA moiety and about 8 protein subunits; POP1, POP7, RPP25, RPP30, RPP38, RPP40 and possibly also POP4 and POP5. Interacts with SMN1. POP7 forms a heterodimer with RPP25 that binds to the P3 stem loop of the catalytic RNA.
Component of ribonuclease P, a ribonucleoprotein complex that generates mature tRNA molecules by cleaving their 5'-ends. Also a component of the MRP ribonuclease complex, which cleaves pre-rRNA sequences.
Belongs to the ATP:guanido phosphotransferase family.
Belongs to the GTR/RAG GTP-binding protein family.
Guanine nucleotide-binding protein that plays a crucial role in the cellular response to amino acid availability through regulation of the mTORC1 signaling cascade.
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). Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Binds with high affinity to IPO4. Interacts with DDIT3.
May play a role during erythropoiesis through regulation of transcription factor DDIT3.
Belongs to the cytochrome c oxidase subunit 6A family.
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 unsing 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix.
Pseudokinase which, in complex with CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta), binds to and activates STK11/LKB1. Adopts a closed conformation typical of active protein kinases and binds STK11/LKB1 as a pseudosubstrate, promoting conformational change of STK11/LKB1 in an active conformation.
Sodium-independent transporter of chloride and iodide.
Belongs to the universal ribosomal protein uL14 family.
Component of the ribosomal small subunit (SSU) processome.
Required for 40S ribosome biogenesis. Involved in nucleolar processing of pre-18S ribosomal RNA and ribosome assembly.
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. The cytoplasmic C-terminus PDZ-binding motif (DTHL) is essential for interaction with NHERF1 and for targeting NHERF1 to the apical cell membrane. The extracellular domain is necessary for microvillus formation (By similarity).
Glomerular epithelium cell (podocyte) and endothelial cells.
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. Induces the formation of apical actin-dependent microvilli. 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.
Monomer; when associated with the membrane raft. Oligomer; when integrated in the apical membrane. Found in a complex with EZR, PODXL and NHERF2. Associates with the actin cytoskeleton through complex formation with EZR and NHERF2. Interacts (via the C-terminal PDZ-binding motif DTHL) with NHERF1 (via the PDZ domains); interaction is not detected in glomerular epithelium cells, take place early in the secretory pathway and is necessary for its apical membrane sorting. Interacts (via the C-terminal PDZ-binding motif DTHL) with NHERF2 (via the PDZ 1 domain); interaction is detected in glomerular epithelium cells. Interacts with EZR (By similarity).
N- and O-linked glycosylated. Sialoglycoprotein (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.
Belongs to the G-protein coupled receptor 2 family. Adhesion G-protein coupled receptor (ADGR) subfamily.
Belongs to the complexin/synaphin family.
Belongs to the G-protein coupled receptor 3 family. GABA-B receptor subfamily.
Central nervous system-specific myelin protein that increase myelin genes expression during oligodendrocyte differentiation. Promotes oligodendrocyte terminal differentiation.
Activation of PRKCA induces phosphorylation of TRPC1 and subsequent Ca2+ entry into cells.
Belongs to the transient receptor (TC 1.A.4) family. STrpC subfamily. TRPC1 sub-subfamily.
Homotetramer and heterotetramer with TRPC4 and/or TRPC5 (By similarity). Interacts with TRPC4 and TRPC5 (By similarity). Interacts with ITPR3 (By similarity). Interacts with MX1 and RNF24 (By similarity). Interacts with FKBP4 (By similarity). Interacts with TRPC4AP (By similarity). Interacts with PLSCR1 (By similarity).
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.
Important in the maintenance of hemostasis, it promotes adhesion of platelets to the sites of vascular injury by forming a molecular bridge between sub-endothelial collagen matrix and platelet-surface receptor complex GPIb-IX-V. Also acts as a chaperone for coagulation factor VIII, delivering it to the site of injury, stabilizing its heterodimeric structure and protecting it from premature clearance from plasma.
Directs RNA polymerase II nuclear import.
In the C-terminal section; belongs to the phosphoglycerate mutase family.
Belongs to the methyltransferase superfamily. Arsenite methyltransferase family.
Component of the RNF20/40 complex (also known as BRE1 complex) probably composed of 2 copies of RNF20/BRE1A and 2 copies of RNF40/BRE1B. Interacts with UBE2E1/UBCH6.
Belongs to the nuclear hormone receptor family. NR0 subfamily.
Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.
Belongs to the universal ribosomal protein uS5 family.
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 (By similarity).
Heterodimer of an alpha and a beta subunit. Component of the WASH complex, composed of F-actin-capping protein subunit alpha (CAPZA1, CAPZA2 or CAPZA3), F-actin-capping protein subunit beta (CAPZB), WASHC1, WASHC2, WASHC3, WASHC4 and WASHC5. Interacts with RCSD1/CAPZIP (By similarity).
Found in gastrointestinal tract tissues, liver and kidney.
Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation. Sulfonates p-nitrophenol, a small phenolic compond. Does not sulfonate steroids, dopamine, acetaminophen, or alpha-naphthol.
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.
Belongs to the peroxisomal targeting signal receptor family.
Belongs to the iodothyronine deiodinase family.
Responsible for the deiodination of T4 (3,5,3',5'-tetraiodothyronine).
Heterotetramer of two alpha chains and two beta chains.
Involved in oxygen transport from the lung to the various peripheral tissues.
There are two alleles. The sequence shown is that of beta-1; the most frequent of the two common alleles.
Belongs to the V-ATPase H 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.
Heterodimer of an alpha and a beta subunit.
Acts as a positive regulator of apoptosis. May also act as a regulator of cellular reactive oxygen species.
Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. DAP kinase subfamily.
Highly expressed in bone marrow. Lower levels in brain, heart, lung, liver and kidney.
Inhibited by thiazolidinedione-type compounds: inhibited by furan- and pyridone- thiazolidinediones.
Functions at least in part by activating the formyl peptide receptors and downstream signaling cascades. Promotes chemotaxis of granulocytes and monocytes via activation of the formyl peptide receptors. Promotes rearrangement of the actin cytoskeleton, cell polarization and cell migration. Promotes resolution of inflammation and wound healing. Acts via neutrophil N-formyl peptide receptors to enhance the release of CXCL2.
Homodimer; non-covalently linked (By similarity). Homodimer; linked by transglutamylation. Homodimers linked by transglutamylation are observed in placenta, but not in other tissues. Interacts with S100A11. Heterotetramer, formed by two molecules each of S100A11 and ANXA1 (By similarity). Interacts with DYSF (By similarity). Interacts with EGFR (By similarity).
In the lung, expressed in the ciliated cells of the tracheal endothelium, but not in the goblet cells. Expressed in type II pneumocytes and alveolar macrophages.
Phosphorylated by protein kinase C, EGFR and TRPM7. Phosphorylated in response to EGF treatment.
Plays important roles in the innate immune response as effector of glucocorticoid-mediated responses and regulator of the inflammatory process. Has anti-inflammatory activity. Plays a role in glucocorticoid-mediated down-regulation of the early phase of the inflammatory response. Contributes to the adaptive immune response by enhancing signaling cascades that are triggered by T-cell activation, regulates differentiation and proliferation of activated T-cells. Promotes the differentiation of T-cells into Th1 cells and negatively regulates differentiation into Th2 cells (By similarity). Has no effect on unstimulated T-cells. Negatively regulates hormone exocytosis via activation ofthe formyl peptide receptors and reorganization of the actin cytoskeleton (By similarity). Has high affinity for Ca(2+) and can bind up to eight Ca(2+) ions (By similarity). Displays Ca(2+)-dependent binding to phospholipid membranes (By similarity). Plays a role in the formation of phagocytic cups and phagosomes. Plays a role in phagocytosis by mediating the Ca(2+)-dependent interaction between phagosomes and the actin cytoskeleton (By similarity).
Proteolytically cleaved by cathepsin CTSG to release the active N-terminal peptide Ac2-26.
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.
Was originally identified as calcium and phospholipid binding protein that displays Ca(2+)-dependent binding to phospholipid membranes and can promote membrane aggregation in vitro. Was initially identified as inhibitor of phospholipase A2 activity (in vitro). Inhibition of phospholipase activity is mediated via its phospholipid binding activity that limits the access of phospholipase to its substrates.
Belongs to the protein-tyrosine phosphatase family. Non-receptor class 2 subfamily.
Belongs to the TNF receptor-associated factor family.
Thrombomodulin is a specific endothelial cell receptor that forms a 1:1 stoichiometric complex with thrombin. This complex is responsible for the conversion of protein C to the activated protein C (protein Ca). Once evolved, protein Ca scissions the activated cofactors of the coagulation mechanism, factor Va and factor VIIIa, and thereby reduces the amount of thrombin generated.
Cysteine protease that plays a key role in autophagy by mediating both proteolytic activation and delipidation of ATG8 family proteins.
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. The complex is involved in double-strand break (DSB) repair, DNA recombination, maintenance of telomere integrity, cell cycle checkpoint control and meiosis.
Belongs to the peptidase M67A family. CSN6 subfamily.
Component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes.
Lymphotoxin beta-activated kinase which seems to be exclusively involved in the activation of NF-kappa-B and its transcriptional activity.
Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family.
Belongs to the DOK family. Type B subfamily.
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.
UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Acts on small phenolic agents such as 2-beta-naphthol and 4-methylumbelliferone as well as bulky phenolic compounds like 2-hydroxy- and 4-hydroxybiphenyl. In contrast to 2B16 it is active toward octylgallate.
Belongs to the monovalent cation:proton antiporter 1 (CPA1) transporter (TC 2.A.36) family.
Belongs to the small GTPase superfamily. SAR1 family.
Belongs to the histone deacetylase family. HD Type 1 subfamily.
Histone deacetylase that catalyzes 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. Also involved in the deacetylation of cohesin complex protein SMC3 regulating release of cohesin complexes from chromatin. May play a role in smooth muscle cell contractility. In addition to protein deacetylase activity, also has protein-lysine deacylase activity: acts as a protein decrotonylase by mediating decrotonylation ((2E)-butenoyl) of histones.
Belongs to the protein prenyltransferase subunit alpha family.
Catalyzes the transfer of a geranyl-geranyl moiety from geranyl-geranyl pyrophosphate to cysteines occuring in specific C-terminal amino acid sequences.
Catalyzes the transfer of a geranylgeranyl moiety from geranylgeranyl diphosphate to both cysteines of Rab proteins with the C-terminal sequence -XXCC, -XCXC and -CCXX, such as RAB1A, RAB3A, RAB5A and RAB7A.
Interacts with GPHN and NSF (By similarity). Interacts with ATG3, ATG7 and ATG13. Interacts with alpha-tubulin (By similarity). Interacts with beta-tubulin (By similarity). Interacts with GABRG2. Interacts with RB1CC1. Interacts with ULK1. Interacts with CALR. Interacts with DDX47. Interacts with TP53INP1 and TP53INP2. Interacts with TBC1D5 (By similarity). Interacts with TBC1D25 (By similarity). Directly interacts with SQSTM1. Interacts with MAPK15. Interacts with TECPR2. Interacts with PCM1. Interacts with TRIM5 and TRIM21. Interacts with MEFV (By similarity). Interacts with KIF21B (By similarity). Interacts with WDFY3; this interaction is required for WDFY3 recruitment to MAP1LC3B-positive p62/SQSTM1 bodies. Interacts with FLCN; interaction regulates autophagy (By similarity). Interacts with UBA5 (By similarity). Interacts with KBTBD6 and KBTBD7; the interaction is direct and required for the ubiquitination of TIAM1 (By similarity). Interacts with reticulophagy regulators RETREG1, RETREG2 and RETREG3 (By similarity). Interacts with IRGM (By similarity). Interacts with STX17 (By similarity). Interacts with CT55; this interaction may be important for GABARAP protein stability (By similarity).
The precursor molecule is cleaved by ATG4 (ATG4A, ATG4B, ATG4C or ATG4D) to expose the glycine at the C-terminus and form the cytosolic form, GABARAP-I. The processed form is then activated by APG7L/ATG7, transferred to ATG3 and conjugated to phosphatidylethanolamine (PE) phospholipid to form the membrane-bound form, GABARAP-II. During non-canonical autophagy, the processed form is conjugated to phosphatidylserine (PS) phospholipid. ATG4 proteins also mediate the delipidation of PE-conjugated forms. In addition, ATG4B and ATG4D mediate delipidation of ATG8 proteins conjugated to PS during non-canonical autophagy. ATG4B constitutes the major protein for proteolytic activation (By similarity). ATG4D is the main enzyme for delipidation activity (By similarity).
Ubiquitin-like modifier that plays a role in intracellular transport of GABA(A) receptors and its interaction with the cytoskeleton. Involved in autophagy: while LC3s are involved in elongation of the phagophore membrane, the GABARAP/GATE-16 subfamily is essential for a later stage in autophagosome maturation. Through its interaction with the reticulophagy receptor TEX264, participates in the remodeling of subdomains of the endoplasmic reticulum into autophagosomes upon nutrient stress, which then fuse with lysosomes for endoplasmic reticulum turnover. Also required for the local activation of the CUL3(KBTBD6/7) E3 ubiquitin ligase complex, regulating ubiquitination and degradation of TIAM1, a guanyl-nucleotide exchange factor (GEF) that activates RAC1 and downstream signal transduction. Thereby, regulates different biological processes including the organization of the cytoskeleton, cell migration and proliferation. Involved in apoptosis.
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 CTL (choline transporter-like) 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 glycosyltransferase 6 family.
Mediates the post-translational oxidative deamination of lysine residues on target proteins leading to the formation of deaminated lysine (allysine).
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.
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 HAD-like hydrolase superfamily. EYA family.
Belongs to the beta-2-microglobulin family.
Belongs to the metallophosphoesterase superfamily. MPPE1 family.
Interacts with GPI-anchor proteins. Interacts with TMED10.
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.
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.
Belongs to the nucleoporin interacting component (NIC) family.
Plays a role in the nuclear pore complex (NPC) assembly and/or maintenance.
Hydrolyzes oligopeptides such as neurotensin, bradykinin and dynorphin A. Acts as a regulator of cannabinoid signaling pathway by mediating degradation of hemopressin, an antagonist peptide of the cannabinoid receptor CNR1.
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.
Belongs to the DNA mismatch repair MutL/HexB family.
Belongs to the RIN (Ras interaction/interference) family.
Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.
Belongs to the bacterial ribosomal protein bL33 family.
Homomultimers may associate with EGR1 bound to DNA.
Belongs to the small leucine-rich proteoglycan (SLRP) family. SLRP class III subfamily.
Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IB subfamily.
Belongs to the VEFS (VRN2-EMF2-FIS2-SU(Z)12) family.
May regulate a number of protein-protein interactions by competing for PDZ domain binding sites.
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 integrin beta chain family.
Substrate-binding subunit of tRNA (adenine-N1-)-methyltransferase, which catalyzes the formation of N1-methyladenine at position 58 (m1A58) in initiator methionyl-tRNA.
Activated by a monovalent cation that binds near, but not in, the active site. The most likely occupant of the site in vivo is potassium. Ion binding induces a conformational change that may alter substrate affinity.
Belongs to the carbohydrate kinase PfkB family. Ribokinase subfamily.
Catalyzes the phosphorylation of ribose at O-5 in a reaction requiring ATP and magnesium. The resulting D-ribose-5-phosphate can then be used either for sythesis of nucleotides, histidine, and tryptophan, or as a component of the pentose phosphate pathway.
Requires a divalent cation, most likely magnesium in vivo, as an electrophilic catalyst to aid phosphoryl group transfer. It is the chelate of the metal and the nucleotide that is the actual substrate.
Inactivates histamine by N-methylation. Plays an important role in degrading histamine and in regulating the airway response to histamine.
Belongs to the synaptophysin/synaptobrevin family.
Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis.
N-APP binds TNFRSF21 triggering caspase activation and degeneration of both neuronal cell bodies (via caspase-3) and axons (via caspase-6).
The gamma-CTF peptides as well as the caspase-cleaved peptides, including C31, are potent enhancers of neuronal apoptosis.
Belongs to the glycosyl hydrolase 1 family.
Broad specificity glycosidase of the intestinal brush border membrane that hydrolyzes lactose, the main sugar in mammalian milk, to produce D-glucose and D-galactose (PubMed:1388157). The mature protein is composed of two domains that catalyze the hydrolysis of beta-glucopyranosides and beta-galactopyranosides, with a preference for hydrophilic aglycones (in lactose and cellobiose) for one domain and hydrophobic aglycones (in phlorizin and glycosylceramides) for the other (PubMed:1388157).
Specifically expressed in small intestine.
The glycosyl hydrolase-1 3/region III carries the phlorizin hydrolase/glycosylceramidase activities (By similarity). The initial assignment of the activities to different regions was revised by the authors using alternative approaches (PubMed:1388157, PubMed:9762914).
The glycosyl hydrolase-1 4/region IV carries the lactase activity (By similarity). The initial assignment of the activities to different regions was revised by the authors using alternative approaches (PubMed:1388157, PubMed:9762914).
Broad spectrum monooxygenase that catalyzes the oxygenation of a wide variety of nitrogen- and sulfur-containing compounds including xenobiotics (By similarity). Catalyzes the S-oxygenation of hypotaurine to produce taurine, an organic osmolyte involved in cell volume regulation as well as a variety of cytoprotective and developmental processes (By similarity). In vitro, catalyzes the N-oxygenation of trimethylamine (TMA) to produce trimethylamine N-oxide (TMAO) and could therefore participate to the detoxification of this compound that is generated by the action of gut microbiota from dietary precursors such as choline, choline containing compounds, betaine or L-carnitine (By similarity).
Belongs to the X(+)/potassium ATPases subunit beta family.
Mediates cell adhesion of neurons and astrocytes, and promotes neurite outgrowth.
The C-terminal lobe folds into an immunoglobulin-like domain and mediates cell adhesion properties.
The sodium/potassium-transporting ATPase is composed of a catalytic alpha subunit, an auxiliary non-catalytic beta subunit and an additional regulatory subunit. Interacts with BSG (By similarity).
This is the non-catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of Na(+) and K(+) ions across the plasma membrane. The exact function of the beta-2 subunit is not known (By similarity).
Belongs to the DEAD box helicase family. DEAH subfamily. DDX15/PRP43 sub-subfamily.
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.
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 bacterial ribosomal protein bL32 family.
Component of multiple SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complexes formed of CUL1, SKP1, RBX1 and a variable F-box domain-containing protein as substrate-specific subunit.
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.
The functional specificity of the SCF complex depends on the F-box protein as substrate recognition component.
Acetylation by CLOCK reduces its binding to glucocorticoid response elements and its transcriptional activity.
Belongs to the nuclear hormone receptor family. NR3 subfamily.
Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain. The ligand-binding domain is required for correct chromosome segregation during mitosis although ligand binding is not required.
Heteromultimeric cytoplasmic complex with HSP90AA1, HSPA1A/HSPA1B, and FKBP5 or another immunophilin such as PPID, STIP1, or the immunophilin homolog PPP5C (PubMed:9195923). Upon ligand binding FKBP5 dissociates from the complex and FKBP4 takes its place, thereby linking the complex to dynein and mediating transport to the nucleus, where the complex dissociates (PubMed:9195923). Probably forms a complex composed of chaperones HSP90 and HSP70, co-chaperones CDC37, PPP5C, TSC1 and client protein TSC2, CDK4, AKT, RAF1 and NR3C1; this complex does not contain co-chaperones STIP1/HOP and PTGES3/p23 (By similarity). Directly interacts with UNC45A (By similarity). Binds to DNA as a homodimer, and as heterodimer with NR3C2 or the retinoid X receptor (By similarity). Binds STAT5A and STAT5B homodimers and heterodimers (By similarity). Interacts with NRIP1, POU2F1, POU2F2 and TRIM28 (By similarity). Interacts with several coactivator complexes, including the SMARCA4 complex, CREBBP/EP300, TADA2L (Ada complex) and p160 coactivators such as NCOA2 and NCOA6 (By similarity). Interaction with BAG1 inhibits transactivation (By similarity). Interacts with HEXIM1 and TGFB1I1 (By similarity). Interacts with NCOA1 (By similarity). Interacts with NCOA3, SMARCA4, SMARCC1, SMARCD1, and SMARCE1 (By similarity). Interacts with CLOCK, CRY1 and CRY2 in a ligand-dependent fashion (By similarity). Interacts with CIART (By similarity). Interacts with RWDD3 (By similarity). Interacts with UBE2I/UBC9 and this interaction is enhanced in the presence of RWDD3 (By similarity). Interacts with GRIP1 (By similarity). Interacts with NR4A3 (via nuclear receptor DNA-binding domain), represses transcription activity of NR4A3 on the POMC promoter Nur response element (NurRE) (By similarity). Directly interacts with PNRC2 to attract and form a complex with UPF1 and DCP1A; the interaction leads to rapid mRNA degradation (By similarity). Interacts with GSK3B (By similarity). Interacts with FNIP1 and FNIP2 (By similarity). Interacts (via C-terminus) with HNRNPU (via C-terminus) (By similarity). Interacts with MCM3AP (By similarity). Interacts (via domain NR LBD) with HSP90AA1 and HSP90AB1 (By similarity). In the absence of hormonal ligand, interacts with TACC1 (By similarity). Interacts (via NR LBD domain) with ZNF764 (via KRAB domain); the interaction regulates transcription factor activity of NR3C1 by directing its actions toward certain biologic pathways (By similarity).
Increased proteasome-mediated degradation in response to glucocorticoids.
Phosphorylated in the absence of hormone; becomes hyperphosphorylated in the presence of glucocorticoid. The Ser-203, Ser-226 and Ser-399-phosphorylated forms are mainly cytoplasmic, and the Ser-211-phosphorylated form is nuclear. Phosphorylation at Ser-211 increases transcriptional activity. Phosphorylation at Ser-203, Ser-226 and Ser-399 decreases signaling capacity. Phosphorylation at Ser-399 may protect from glucocorticoid-induced apoptosis. Phosphorylation at Ser-203 and Ser-211 is not required in regulation of chromosome segregation. May be dephosphorylated by PPP5C, attenuates NR3C1 action.
Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors. Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Involved in chromatin remodeling. Plays a role in rapid mRNA degradation by binding to the 5' UTR of target mRNAs and interacting with PNRC2 in a ligand-dependent manner which recruits the RNA helicase UPF1 and the mRNA-decapping enzyme DCP1A, leading to RNA decay. Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth. Mediates glucocorticoid-induced apoptosis. Promotes accurate chromosome segregation during mitosis. May act as a tumor suppressor. May play a negative role in adipogenesis through the regulation of lipolytic and antilipogenic gene expression.
Sumoylation at Lys-277 and Lys-293 negatively regulates its transcriptional activity. Sumoylation at Lys-698 positively regulates its transcriptional activity in the presence of RWDD3. Sumoylation at Lys-277 and Lys-293 is dispensable whereas sumoylation at Lys-698 is critical for the stimulatory effect of RWDD3 on its transcriptional activity. Heat shock increases sumoylation in a RWDD3-dependent manner.
Ubiquitinated; restricts glucocorticoid-mediated transcriptional signaling.
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.
DNA polymerase that functions in several pathways of DNA repair. Involved in base excision repair (BER) responsible for repair of lesions that give rise to abasic (AP) sites in DNA. Also contributes to DNA double-strand break repair by non-homologous end joining and homologous recombination. Has both template-dependent and template-independent (terminal transferase) DNA polymerase activities. Has also a 5'-deoxyribose-5-phosphate lyase (dRP lyase) activity.
Belongs to the universal ribosomal protein uS13 family.
Component of the small ribosomal subunit.
Belongs to the WD repeat DDB2/WDR76 family.
Interacts with the core-glycosylated, but not the fully glycosylated form of KCNH2/HERG. Interacts with DNAJA1 and HSPA8. Interacts (via the C-terminus) with HSPA1A; this interaction additively increases KCNH2 expression.
Plays a role in cardiac repolarization possibly by stabilizing membrane expression of the potassium channel KCNH2/HERG, or by assisting its synthesis, folding or export from the endoplasmic reticulum, in a heat shock protein-dependent manner.
Belongs to the transcription factor STAT family.
Belongs to the 1-acyl-sn-glycerol-3-phosphate acyltransferase family.
Belongs to the PDGF/VEGF growth factor 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 (PubMed:7902354, PubMed:8171037). 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 (PubMed:7902354). 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). Acts as a regulator of synaptic plasticity in the nucleus accumbens of the brain by mediating cleavage of Met-enkephalin-Arg-Phe, a strong ligand of Mu-type opioid receptor OPRM1, into Met-enkephalin (By similarity). Met-enkephalin-Arg-Phe cleavage by ACE decreases activation of OPRM1, leading to long-term synaptic potentiation of glutamate release (By similarity). Also acts as a regulator of hematopoietic stem cell differentiation by mediating degradation of hemoregulatory peptide N-acetyl-SDKP (AcSDKP) (By similarity). Acts as a regulator of cannabinoid signaling pathway by mediating degradation of hemopressin, an antagonist peptide of the cannabinoid receptor CNR1 (By similarity). Involved in amyloid-beta metabolism by catalyzing degradation of Amyloid-beta protein 40 and Amyloid-beta protein 42 peptides, thereby preventing plaque formation (By similarity). Catalyzes cleavage of cholecystokinin (maturation of Cholecystokinin-8 and Cholecystokinin-5) and Gonadoliberin-1 (both maturation and degradation) hormones (PubMed:2554881). Degradation of hemoregulatory peptide N-acetyl-SDKP (AcSDKP) and amyloid-beta proteins is mediated by the N-terminal catalytic domain, while angiotensin I and cholecystokinin cleavage is mediated by the C-terminal catalytic region (By similarity).
Isoform Testis-specific only binds 1 Zn(2+) ion per subunit.
Isoform produced by alternative promoter usage that is specifically expressed in spermatocytes and adult testis, and which is required for male fertility (By similarity). In contrast to somatic isoforms, only contains one catalytic domain (By similarity). Acts as a dipeptidyl carboxypeptidase that removes dipeptides from the C-terminus of substrates (PubMed:7902354). The identity of substrates that are needed for male fertility is unknown (By similarity). May also have a glycosidase activity which releases GPI-anchored proteins from the membrane by cleaving the mannose linkage in the GPI moiety (By similarity). The GPIase activity was reported to be essential for the egg-binding ability of the sperm (By similarity). This activity is however unclear and has been challenged by other groups, suggesting that it may be indirect (PubMed:16270062).
Monomer and homodimer; homodimerizes following binding to an inhibitor (By similarity). Interacts with calmodulin (CALM1, CALM2 or CALM3); interaction takes place in the cytoplasmic region and regulates phosphorylation and proteolytic cleavage (PubMed:16096279).
Phosphorylated by CK2 on Ser-1303; which allows membrane retention (By similarity). Phosphorylated on tyrosine residues on its extracellular part, promoting cleavage by secretase enzymes and formation of the soluble form (Angiotensin-converting enzyme, soluble form) (PubMed:15252021).
Produced following proteolytic cleavage by secretase enzymes that cleave the transmembrane form in the juxtamembrane stalk region upstream of the transmembrane region (PubMed:15252021, PubMed:16096279). Cleavage can take place at different sites of the juxtamembrane stalk region (By similarity).
Soluble form that is released in blood plasma and other body fluids following proteolytic cleavage in the juxtamembrane stalk region.
Strongly inhibited by lisinopril and captopril.
Testis-specific isoform is expressed in spermatocytes, adult testis.
The dipeptidyl carboxypeptidase activity is strongly activated by chloride (By similarity). Specifically inhibited by lisinopril (PubMed:7902354). Inhibited by mixanpril, an orally-active drug used for the treatment of hypertension (PubMed:8171037).
Binds to the 60S ribosomal subunit and prevents its association with the 40S ribosomal subunit to form the 80S initiation complex in the cytoplasm. Behaves as a stimulatory translation initiation factor downstream insulin/growth factors. Is also involved in ribosome biogenesis. Associates with pre-60S subunits in the nucleus and is involved in its nuclear export. Cytoplasmic release of TIF6 from 60S subunits and nuclear relocalization is promoted by a RACK1 (RACK1)-dependent protein kinase C activity. In tissues responsive to insulin, controls fatty acid synthesis and glycolysis by exerting translational control of adipogenic transcription factors such as CEBPB, CEBPD and ATF4 that have G/C rich or uORF in their 5'UTR. Required for ROS-dependent megakaryocyte maturation and platelets formation, controls the expression of mitochondrial respiratory chain genes involved in reactive oxygen species (ROS) synthesis. Involved in 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. Modulates cell cycle progression and global translation of pre-B cells, its activation seems to be rate-limiting in tumorigenesis and tumor growth.
Monomer. Associates with the 60S ribosomal subunit. Interacts with RACK1. Interacts with DICER1, AGO2, TARBP2, MOV10 and RPL7A; they form a large RNA-induced silencing complex (RISC).
Phosphorylation at Ser-174 and Ser-175 promotes nuclear export.
A prominent expression is seen in gastric parietal cells.
Interacts with RAB11FIP1, RAB11FIP2, RAB11FIP3 (via its C-terminus) and RAB11FIP4 (By similarity). Forms a complex with RAB11FIP3 and dynein intermediate chain DYNC1LI1; the interaction between RAB11A1 and RAB11FIP3 is direct; the complex regulates endocytic trafficking (By similarity). Interacts with EVI5; EVI5 and RAB11FIP3 may be mutually exclusive and compete for binding RAB11A (By similarity). Interacts with SGSM1, SGSM2, SGSM3 and VIPAS39 (By similarity). Interacts with EXOC6 in a GTP-dependent manner. Interacts with RAB11FIP5. Interacts with STXBP6. Interacts (GDP-bound form) with ZFYVE27 (By similarity). Interacts with BIRC6/bruce (By similarity). May interact with TBC1D14 (By similarity). Interacts with UNC119; in a cell cycle-dependent manner (By similarity). GDP-bound and nucleotide-free forms interact with SH3BP5 (By similarity). Interacts (GDP-bound form) with KIF5A in a ZFYVE27-dependent manner (By similarity). Interacts (GDP-bound form) with RELCH (By similarity). Found in a complex composed of RELCH, OSBP1 and RAB11A (By similarity). Interacts with TBC1D12 (By similarity). Interacts with DEF6 (By similarity). Interacts with ATP9A (By similarity). Forms a heterotetramer with RAB11FIP3; the GTP-bound form is preferred for binding. Forms a complex with Rabin8/RAB3IP and RAB11FIP3, probably a heterohexamer with two of each protein subunit, where Rabin8/RAB3IP and RAB11FIP3 simultaneously bind to RAB11A; the complex promotes preciliary trafficking and cilia growth. Forms a complex containing RAB11A, ASAP1, Rabin8/RAB3IP, RAP11FIP3 and ARF4; the complex promotes preciliary trafficking; the complex binds to RHO in photoreceptor cells and promotes RHO ciliary transport. Interacts (GTP-bound form) with WDR44; the interaction prevents RAB11A-RAB3IP-RAB11FIP3 complex formation (By similarity).
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 set of downstream effectors directly responsible for vesicle formation, movement, tethering and fusion (By similarity). The small Rab GTPase RAB11A regulates endocytic recycling (By similarity). Forms a functional Rab11/FIP3/dynein complex that regulates the movement of peripheral sorting endosomes (SE) along microtubule tracks toward the microtubule organizing center/centrosome, generating the endosomal recycling compartment (ERC) (By similarity). Acts as a major regulator of membrane delivery during cytokinesis. Together with MYO5B and RAB8A participates in epithelial cell polarization. Together with RAB3IP, RAB8A, the exocyst complex, PARD3, PRKCI, ANXA2, CDC42 and DNMBP promotes transcytosis of PODXL to the apical membrane initiation sites (AMIS), apical surface formation and lumenogenesis. Together with MYO5B participates in CFTR trafficking to the plasma membrane and TF (Transferrin) recycling in nonpolarized cells. Required in a complex with MYO5B and RAB11FIP2 for the transport of NPC1L1 to the plasma membrane. Participates in the sorting and basolateral transport of CDH1 from the Golgi apparatus to the plasma membrane. Regulates the recycling of FCGRT (receptor of Fc region of monomeric Ig G) to basolateral membranes (By similarity). May also play a role in melanosome transport and release from melanocytes (By similarity). Promotes Rabin8/RAB3IP preciliary vesicular trafficking to mother centriole by forming a ciliary targeting complex containing Rab11, ASAP1, Rabin8/RAB3IP, RAB11FIP3 and ARF4, thereby regulating ciliogenesis initiation. On the contrary, upon LPAR1 receptor signaling pathway activation, interaction with phosphorylated WDR44 prevents Rab11-RAB3IP-RAB11FIP3 complex formation and cilia growth (By similarity). Participates in the export of a subset of neosynthesized proteins through a Rab8-Rab10-Rab11-endososomal dependent export route via interaction with WDR44 (By similarity).
Detected in eye aqueous humor (at protein level).
Homodimer (via N-terminus). Can also form higher oligomers. Interacts with OLFM3, FN1, NRCAM, GLDN and NFASC. Interacts (via N-terminus) with MYL2. Interacts with SFRP1, FRZB, FZD7, FZD10, FZD1 and WIF1; regulates Wnt signaling (By similarity). Interacts with SNTA1; regulates muscle hypertrophy. Interacts with ERBB2 and ERBB3; activates ERBB2-ERBB3 signaling pathway. Interacts with SNCG; affects its secretion and its aggregation (By similarity).
Secreted glycoprotein regulating the activation of different signaling pathways in adjacent cells to control different processes including cell adhesion, cell-matrix adhesion, cytoskeleton organization and cell migration. Promotes substrate adhesion, spreading and formation of focal contacts. Negatively regulates cell-matrix adhesion and stress fiber assembly through Rho protein signal transduction. Modulates the organization of actin cytoskeleton by stimulating the formation of stress fibers through interactions with components of Wnt signaling pathways. Promotes cell migration through activation of PTK2 and the downstream phosphatidylinositol 3-kinase signaling. Plays a role in bone formation and promotes osteoblast differentiation in a dose-dependent manner through mitogen-activated protein kinase signaling. Mediates myelination in the peripheral nervous system through ERBB2/ERBB3 signaling. Plays a role as a regulator of muscle hypertrophy through the components of dystrophin-associated protein complex. Involved in positive regulation of mitochondrial depolarization. Plays a role in neurite outgrowth. May participate in the obstruction of fluid outflow in the trabecular meshwork.
Undergoes a calcium-dependent proteolytic cleavage at Arg-212 by CAPN2 in the endoplasmic reticulum. The result is the production of two fragments, one of 35 kDa containing the C-terminal olfactomedin-like domain, and another of 20 kDa containing the N-terminal leucine zipper-like domain (By similarity).
Belongs to the eukaryotic-type N-acetylglucosamine kinase family.
Belongs to the glycine N-acyltransferase family.
Homodimer (By similarity). Interacts with STEAP3 (By similarity). Interacts with TSC22D1; interaction results in the destabilization of TSC22D1 protein (By similarity).
Involved in calcium binding and microtubule stabilization (By similarity). Acts as a negative regulator of TSC22D1-mediated apoptosis, via interaction with and destabilization of TSC22D1 protein (By similarity).
Undergoes developmental regulation during mammary gland development.
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 zinc-containing alcohol dehydrogenase family. Quinone oxidoreductase subfamily.
Exhibits progesterone 6 beta-hydroxylase activity.
Interacts with TRPC3 (By similarity). Interacts with BAG5 and HSPA8; the interaction with HSPA8 is increased in the presence of BAG5 (By similarity). Junctophilin-2 N-terminal fragment: Interacts with MEF2C (By similarity).
Membrane-binding protein that provides a structural bridge between the plasma membrane and the sarcoplasmic reticulum and is required for normal excitation-contraction coupling in cardiomyocytes. Provides a structural foundation for functional cross-talk between the cell surface and intracellular Ca(2+) release channels by maintaining the 12-15 nm gap between the sarcolemma and the sarcoplasmic reticulum membranes in the cardiac dyads. Necessary for proper intracellular Ca(2+) signaling in cardiac myocytes via its involvement in ryanodine receptor-mediated calcium ion release. Contributes to the construction of skeletal muscle triad junctions.
Phosphorylation on Ser-165, probably by PKC, affects RYR1-mediated calcium ion release, interaction with TRPC3, and skeletal muscle myotubule development.
Proteolytically cleaved by calpain in response to cardiac stress. The major cleavage site takes place at the C-terminus and leads to the release of the Junctophilin-2 N-terminal fragment chain (JP2NT).
The MORN (membrane occupation and recognition nexus) repeats contribute to the plasma membrane binding, by interacting with phospholipids. Has affinity for phosphatidylserine, and phosphorylated phosphatidylinositols including PtdIns3P, PtdIns4P, PtdIns5P, PtdIns(3,5)P2 and PtdIns(3,4,5)P3.
The bipartite nuclear localization signal (bNLS) and Ala-rich (alanine-rich; ARR) regions are involved in DNA-binding.
Transcription repressor required to safeguard against the deleterious effects of cardiac stress. Generated following cleavage of the Junctophilin-2 chain by calpain in response to cardiac stress in cardiomyocytes. Following cleavage and release from the membrane, translocates to the nucleus, binds DNA and represses expression of genes implicated in cell growth and differentiation, hypertrophy, inflammation and fibrosis. Modifies the transcription profile and thereby attenuates pathological remodeling in response to cardiac stress. Probably acts by competing with MEF2 transcription factors and TATA-binding proteins.
Glutathionylated (By similarity). N-glycosylated (By similarity).
Involved in cell adhesion and establishing epithelial cell polarity.
The sodium/potassium-transporting ATPase is composed of a catalytic alpha subunit, an auxiliary non-catalytic beta subunit and an additional regulatory subunit. Interacts with catalytic subunit ATP12A. Interacts with regulatory subunit FXYD1 (By similarity). Interacts with regulatory subunit FXYD3 (PubMed:21454534). Interacts with NKAIN1, NKAIN2 and NKAIN4 (By similarity). Interacts with MLC1 (By similarity). Part of a complex containing MLC1, TRPV4, AQP4 and HEPACAM (By similarity). Interacts with KIRREL3 (By similarity). Interacts with OBSCN (via protein kinase domain 1) (By similarity).
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 (By similarity).
May bind and stabilize microtubules during myotubes formation.
As part of the MCIA complex, involved in the assembly of the mitochondrial complex I.
Bifunctional enzyme localized in the lumen of the endoplasmic reticulum that catalyzes the first two steps of the oxidative branch of the pentose phosphate pathway/shunt, an alternative to glycolysis and a major source of reducing power and metabolic intermediates for biosynthetic processes. Has a hexose-6-phosphate dehydrogenase activity, with broad substrate specificity compared to glucose-6-phosphate 1-dehydrogenase/G6PD, and catalyzes the first step of the pentose phosphate pathway. In addition, acts as a 6-phosphogluconolactonase and catalyzes the second step of the pentose phosphate pathway. May have a dehydrogenase activity for alternative substrates including glucosamine 6-phosphate and glucose 6-sulfate. The main function of this enzyme is to provide reducing equivalents such as NADPH to maintain the adequate levels of reductive cofactors in the oxidizing environment of the endoplasmic reticulum. By producing NADPH that is needed by reductases of the lumen of the endoplasmic reticulum like corticosteroid 11-beta-dehydrogenase isozyme 1/HSD11B1, indirectly regulates their activity.
In the C-terminal section; belongs to the glucosamine/galactosamine-6-phosphate isomerase family. 6-phosphogluconolactonase subfamily.
In the N-terminal section; belongs to the glucose-6-phosphate dehydrogenase family.
Belongs to the methyltransferase superfamily. RRP8 family.
Essential component of the eNoSC (energy-dependent nucleolar silencing) complex, a complex that mediates silencing of rDNA in response to intracellular energy status and acts by recruiting histone-modifying enzymes. The eNoSC complex is able to sense the energy status of cell: upon glucose starvation, elevation of NAD(+)/NADP(+) ratio activates SIRT1, leading to histone H3 deacetylation followed by dimethylation of H3 at 'Lys-9' (H3K9me2) by SUV39H1 and the formation of silent chromatin in the rDNA locus. In the complex, RRP8 binds to H3K9me2 and probably acts as a methyltransferase.
The kidney P-450 system is rather specialized for the omega-hydroxylation of fatty acids. Both P450-KA1 and P450-KA2 catalyze the omega- and (omega-1)-hydroxylation of various fatty acids with no drug-metabolizing activity, and hydroxylate prostaglandin A1 and A2 solely at the omega-position.
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.
Belongs to the biopterin-dependent aromatic amino acid hydroxylase family.
Homodimer; disulfide-linked. Binds to CD80/B7-1 and CD86/B7.2. Interacts with ICOSLG.
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.
N-glycosylation is important for dimerization.
Phosphorylation at Tyr-201 prevents binding to the AP-2 adapter complex, blocks endocytosis, and leads to retention of CTLA4 on the cell surface.
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.
Plays a role in the recruitment of the exosome to pre-rRNA to mediate the 3'-5' end processing of the 5.8S rRNA.
Acts as a dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins. Also acts as a lipid phosphatase, removing the phosphate in the D3 position of the inositol ring from phosphatidylinositol 3,4,5-trisphosphate, phosphatidylinositol 3,4-diphosphate, phosphatidylinositol 3-phosphate and inositol 1,3,4,5-tetrakisphosphate with order of substrate preference in vitro PtdIns(3,4,5)P3 > PtdIns(3,4)P2 > PtdIns3P > Ins(1,3,4,5)P4.
Belongs to the PTEN phosphatase protein family.
Belongs to the eukaryotic ribosomal protein eL30 family.
Belongs to the arylamine N-acetyltransferase family.
Acts in the cytoplasm to initiate and regulate protein synthesis and is required in the nucleus for export of a subset of mRNAs from the nucleus to the cytoplasm which promotes processes such as RNA capping, processing and splicing (By similarity). Component of the protein complex eIF4F, which is involved in the recognition of the mRNA cap, ATP-dependent unwinding of 5'-terminal secondary structure and recruitment of mRNA to the ribosome (By similarity). This protein recognizes and binds the 7-methylguanosine (m7G)-containing mRNA cap during an early step in the initiation of protein synthesis and facilitates ribosome binding by inducing the unwinding of the mRNAs secondary structures (By similarity). Together with EIF4G1, antagonizes the scanning promoted by EIF1-EIF4G1 and is required for TISU translation, a process where the TISU element recognition makes scanning unnecessary (By similarity). In addition to its role in translation initiation, also acts as a regulator of translation and stability in the cytoplasm (By similarity). Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression: in the complex, EIF4E mediates the binding to the mRNA cap. Component of a multiprotein complex that sequesters and represses translation of proneurogenic factors during neurogenesis (By similarity). In P-bodies, component of a complex that mediates the storage of translationally inactive mRNAs in the cytoplasm and prevents their degradation (By similarity). May play an important role in spermatogenesis through translational regulation of stage-specific mRNAs during germ cell development (By similarity). As well as its roles in translation, also involved in mRNA nucleocytoplasmic transport (By similarity). Its role in mRNA export from the nucleus to the cytoplasm relies on its ability to bind the m7G cap of RNAs and on the presence of the 50-nucleotide EIF4E sensitivity element (4ESE) in the 3'UTR of sensitive transcripts (By similarity). Interaction with the 4ESE is mediated by LRPPRC which binds simultaneously to both EIF4E and the 4ESE, thereby acting as a platform for assembly for the RNA export complex (By similarity). EIF4E-dependent mRNA export is independent of ongoing protein or RNA synthesis and is also NFX1-independent but is XPO1-dependent with LRPPRC interacting with XPO1 to form an EIF4E-dependent mRNA export complex (By similarity). Alters the composition of the cytoplasmic face of the nuclear pore to promote RNA export by reducing RANBP2 expression, relocalizing nucleoporin NUP214 and increasing expression of RANBP1 and RNA export factors DDX19 and GLE1. Promotes the nuclear export of cyclin CCND1 mRNA (By similarity). Promotes the nuclear export of NOS2/iNOS mRNA (By similarity). Promotes the nuclear export of MDM2 mRNA (By similarity). Also promotes the export of additional mRNAs, including others involved in the cell cycle (By similarity). In the nucleus, binds to capped splice factor-encoding mRNAs and stimulates their nuclear export to enhance splice factor production by increasing their cytoplasmic availability to the translation machinery (By similarity). May also regulate splicing through interaction with the spliceosome in an RNA and m7G cap-dependent manner (By similarity). Also binds to some pre-mRNAs and may play a role in their recruitment to the spliceosome (By similarity). Promotes steady-state capping of a subset of coding and non-coding RNAs by mediating nuclear export of capping machinery mRNAs including RNMT, RNGTT and RAMAC to enhance their translation (By similarity). Stimulates mRNA 3'-end processing by promoting the expression of several core cleavage complex factors required for mRNA cleavage and polyadenylation, and may also have a direct effect through its interaction with the CPSF3 cleavage enzyme (By similarity). Rescues cells from apoptosis by promoting activation of serine/threonine-protein kinase AKT1 through mRNA export of NBS1 which potentiates AKT1 phosphorylation and also through mRNA export of AKT1 effectors, allowing for increased production of these proteins (By similarity).
Belongs to the eukaryotic initiation factor 4E family.
Phosphorylation increases the ability of the protein to bind to mRNA caps and to form the eIF4F complex (By similarity). Phosphorylation also enhances its mRNA transport function (By similarity). Phosphorylation at Ser-209 is not essential for protein synthesis (By similarity).
eIF4F is a multi-subunit complex, the composition of which varies with external and internal environmental conditions (By similarity). It is composed of at least EIF4A, EIF4E and EIF4G1/EIF4G3 (PubMed:6853548). EIF4E is also known to interact with other partners. Interacts with EIF4ENIF1/4E-T; promotes recruitment to P-bodies and import into the nucleus. Hypophosphorylated EIF4EBP1, EIF4EBP2 and EIF4EBP3 compete with EIF4G1/EIF4G3 to interact with EIF4E; insulin stimulated MAP-kinase (MAPK1 and MAPK3) phosphorylation of EIF4EBP1 causes dissociation of the complex allowing EIF4G1/EIF4G3 to bind and consequent initiation of translation. Interacts mutually exclusive with EIF4A1 or EIF4A2 (By similarity). Interacts with NGDN and PIWIL2. Component of the CYFIP1-EIF4E-FMR1 complex composed of CYFIP, EIF4E and FMR1. Interacts directly with CYFIP1. Interacts with CLOCK (By similarity). Binds to MKNK2 in nucleus. Interacts with LIMD1, WTIP and AJUBA. Interacts with APOBEC3G in an RNA-dependent manner. Interacts with LARP1. Interacts with METTL3. Interacts with RBM24; this interaction prevents EIF4E from binding to p53/TP53 mRNA and inhibits the assembly of translation initiation complex. Interacts with DDX3X; interaction is direct and in an RNA-independent manner; this interaction enhances EIF4E cap-binding ability and is required for the repression of cap-dependent translation and the increase of IRES-mediated translation. DDX3X competes with EIF4G1 for interaction with EIF4E (By similarity). Interacts with EIF4G1; which in a mutual exclusive interaction associates either with EIF1 or with EIF4E on a common binding site (By similarity). Interacts with BTG4 and CNOT7 (By similarity). Interacts with LRPPRC (via N-terminus); the interaction promotes association of EIF4E with 4ESE-containing mRNAs (By similarity). Interacts with mRNA cleavage enzyme CPSF3 and its cofactor CPSF1 (By similarity). Interacts (via RING-type zinc finger) with PML; the interaction results in conformational changes of both interacting proteins and reduces EIF4E affinity for the 5' m7G cap of mRNA, thus reducing EIF4E-mediated mRNA nuclear export (By similarity). Interacts with homeobox protein HHEX/PRH; the interaction inhibits EIF4E-mediated mRNA nuclear export (By similarity). Interacts with homeobox protein HOXA9; the interaction positively regulates EIF4E-mediated mRNA nuclear export (By similarity). Interacts with homeobox protein EMX2 (By similarity).
Belongs to the SMC family. RAD50 subfamily.
Belongs to the DNA repair enzymes AP/ExoA family.
Initiates repair of AP sites in DNA by catalyzing hydrolytic incision of the phosphodiester backbone immediately adjacent to the damage, generating a single-strand break with 5'-deoxyribose phosphate and 3'-hydroxyl ends.
Probably binds two magnesium or manganese ions per subunit.
Acts as decoy receptor for TNFSF11/RANKL and thereby neutralizes its function in osteoclastogenesis.
Acts as guanine nucleotide exchange factor (GEF) for RhoA and RhoB GTPases.
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 adaptor complexes large subunit family.
Associates with MYD88 and IRAK2 to form a ternary complex called the Myddosome.
Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. Pelle subfamily.
Serine/threonine-protein kinase that plays a critical role in initiating innate immune response against foreign pathogens.
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).
Belongs to the amidase family. GatA subfamily.
Catalyzes the exchange of ADP and ATP across the membrane.
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).
Belongs to the amiloride-sensitive sodium channel (TC 1.A.6) family.
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.
This is a receptor for the tachykinin neuropeptide neuromedin-K (neurokinin B). It is associated with G proteins that activate a phosphatidylinositol-calcium second messenger system (By similarity).
Calretinin is a calcium-binding protein which is abundant in auditory neurons.
Belongs to the endoribonuclease YbeY family.
Belongs to the ABC transporter superfamily. ABCD family. Peroxisomal fatty acyl CoA transporter (TC 3.A.1.203) subfamily.
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-102 and Arg-105) that bind to malonylated and succinylated substrates and define the specificity.
Monomer. Homodimer. Interacts with CPS1.
NAD-dependent lysine demalonylase, desuccinylase and deglutarylase that specifically removes malonyl, succinyl and glutaryl groups on target proteins. Activates CPS1 and contributes to the regulation of blood ammonia levels during prolonged fasting: acts by mediating desuccinylation and deglutarylation of CPS1, thereby increasing CPS1 activity in response to elevated NAD levels during fasting. Activates SOD1 by mediating its desuccinylation, leading to reduced reactive oxygen species. Modulates ketogenesis through the desuccinylation and activation of HMGCS2. Has weak NAD-dependent protein deacetylase activity; however this activity may not be physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) and a number of other proteins in vitro such as Uox.
Belongs to the ZIP transporter (TC 2.A.5) family.
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.
Associates with SLC3A2 to form a functional heterodimeric complex that translocates small and large neutral amino acids with broad specificity and a stoichiometry of 1:1 (PubMed:10631289). Functions as amino acid antiporter mediating the influx of extracellular essential amino acids mainly in exchange with the efflux of highly concentrated intracellular amino acids. Has relatively symmetrical selectivities but strongly asymmetrical substrate affinities at both the intracellular and extracellular sides of the transporter. This asymmetry allows SLC7A8 to regulate intracellular amino acid pools (mM concentrations) by exchange with external amino acids (uM concentration range), equilibrating the relative concentrations of different amino acids across the plasma membrane instead of mediating their net uptake. May play an essential role in the reabsorption of neutral amino acids from the epithelial cells to the bloodstream in the kidney. Involved in the uptake of methylmercury (MeHg) when administered as the L-cysteine or D,L-homocysteine complexes, and hence plays a role in metal ion homeostasis and toxicity. Involved in the cellular activity of small molecular weight nitrosothiols, via the stereoselective transport of L-nitrosocysteine (L-CNSO) across the transmembrane (By similarity). Imports the thyroid hormone diiodothyronine (T2) and to a smaller extent triiodothyronine (T3) but not rT 3 or thyroxine (T4) (By similarity). Mediates the uptake of L-DOPA (By similarity). May participate in auditory function (By similarity).
Belongs to the amino acid-polyamine-organocation (APC) superfamily. L-type amino acid transporter (LAT) (TC 2.A.3.8) family.
Disulfide-linked heterodimer composed of the catalytic light chain subunit SLC7A8 and the heavy chain subunit SLC3A2 (PubMed:10631289). SLC3A2 acts as chaperones for correct plasma membrane trafficking and stabilization of SLC7A8 and modulates the substrate affinity and specificity of SLC7A8. ICAM-1 associates with the heterodimer SLC3A2/SLC7A8; facilitates leucine uptake (By similarity).
Mainly expressed in kidney and small intestine.
The transporter activity is inhibited by 2-aminobicyclo-(2,2,1)heptane-2-carboxylic acid (BCH) (a specific inhibitor of system L transport).
Belongs to the eukaryotic ribosomal protein eS6 family.
Belongs to the eukaryotic ATPase B chain family.
F-type ATPases have 2 components, CF(1) - the catalytic core - and CF(0) - the membrane proton channel. 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. 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 eIF-2B gamma/epsilon subunits family.
Complex of five different subunits; alpha, beta, gamma, delta and epsilon. Interacts with RGS2 (By similarity).
Phosphorylated at Ser-544 by DYRK2; this is required for subsequent phosphorylation by GSK3B. Phosphorylated on serine and threonine residues by GSK3B; phosphorylation inhibits its function (By similarity).
Expressed in endothelial and smooth muscle cells of collateral arteries as well as in satellite cells.
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 (By similarity). May play a role in the initiation of arteriogenesis.
The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin-protein ligase complexes.
Up-regulated in growing collateral arteries.
Functions as cell surface receptor for TIMP1 and plays a role in the activation of cellular signaling cascades. Plays a role in the activation of ITGB1 and integrin signaling, leading to the activation of AKT, FAK/PTK2 and MAP kinases. Promotes cell survival, reorganization of the actin cytoskeleton, cell adhesion, spreading and migration, via its role in the activation of AKT and FAK/PTK2. Plays a role in VEGFA signaling via its role in regulating the internalization of KDR/VEGFR2. Plays a role in intracellular vesicular transport processes, and is required for normal trafficking of the PMEL luminal domain that is essential for the development and maturation of melanocytes. Plays a role in the adhesion of leukocytes onto endothelial cells via its role in the regulation of SELP trafficking. May play a role in mast cell degranulation in response to Ms4a2/FceRI stimulation, but not in mast cell degranulation in response to other stimuli (By similarity).
Interacts with TIMP1 and ITGB1 and recruits TIMP1 to ITGB1. Interacts with CD9. Identified in a complex with CD9 and ITGB3. Interacts with PMEL. Interacts with KDR/VEGFR2; identified in a complex with ITGB1 and KDR/VEGFR2 and is required to recruit KDR to ITGB1 complexes. Interacts with SYT7 (By similarity).
Palmitoylated at a low, basal level in unstimulated platelets. The level of palmitoylation increases when platelets are activated by thrombin (in vitro) (By similarity).
Belongs to the methyltransferase superfamily. METTL16/RlmF family.
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.
Belongs to the DEAD box helicase family. DDX21/DDX50 subfamily.
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.
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.
Belongs to the alpha-ketoglutarate dehydrogenase family.
Belongs to the nucleotide-sugar transporter family. SLC35B subfamily.
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 class-III pyridoxal-phosphate-dependent aminotransferase family.
Belongs to the glycosyl hydrolase 30 family.
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 Nudix hydrolase family. DIPP subfamily.
Belongs to the methyltransferase superfamily. METL family.
S-adenosyl-L-methionine-dependent methyltransferase.
Acts as an essential factor in bone homeostasis and on vessels directly or indirectly by induction of VEGF, resulting in increased angiogenesis activity and vascular permeability. Induces, through 'trans-signaling' and synergistically with IL1B and TNF, the production of VEGF. Involved in metabolic controls, is discharged into the bloodstream after muscle contraction increasing lipolysis and improving insulin resistance (By similarity). 'Trans-signaling' in central nervous system also regulates energy and glucose homeostasis. Mediates, through GLP-1, crosstalk between insulin-sensitive tissues, intestinal L cells and pancreatic islets to adapt to changes in insulin demand (By similarity). Also acts as a myokine (By similarity). Plays a protective role during liver injury, being required for maintenance of tissue regeneration (By similarity). Also has a pivotal role in iron metabolism by regulating HAMP/hepcidin expression upon inflammation or bacterial infection (By similarity). Through activation of IL6ST-YAP-NOTCH pathway, induces inflammation-induced epithelial regeneration (By similarity).
Component of a hexamer of two molecules each of IL6, IL6R and IL6ST; first binds to IL6R to associate with the signaling subunit IL6ST. Interacts with IL6R (via the N-terminal ectodomain); this interaction may be affected by IL6R-binding with SORL1, hence decreasing IL6 cis signaling. Interacts with SORL1 (via the N-terminal ectodomain); this interaction leads to IL6 internalization and lysosomal degradation. May form a trimeric complex with the soluble SORL1 ectodomain and soluble IL6R receptor; this interaction might stabilize circulating IL6, hence promoting IL6 trans signaling.
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.
IL6 is a potent inducer of the acute phase response. Rapid production of IL6 contributes to host defense during infection and tissue injury, but excessive IL6 synthesis is involved in disease pathology. In the innate immune response, is synthesized by myeloid cells, such as macrophages and dendritic cells, upon recognition of pathogens through toll-like receptors (TLRs) at the site of infection or tissue injury (By similarity). In the adaptive immune response, is required for the differentiation of B cells into immunoglobulin-secreting cells. Plays a major role in the differentiation of CD4(+) T cell subsets. Essential factor for the development of T follicular helper (Tfh) cells that are required for the induction of germinal-center formation. Required to drive naive CD4(+) T cells to the Th17 lineage. Also required for proliferation of myeloma cells and the survival of plasmablast cells (By similarity).
Belongs to the protein kinase superfamily. Tyr protein kinase family. Fibroblast growth factor receptor subfamily.
Belongs to the dynein light intermediate chain family.
Probably part of the adaptor protein complex 5 (AP-5) a tetramer composed of AP5B1, AP5M1, AP5S1 and AP5Z1.
Belongs to the 'GDSL' lipolytic enzyme family. Phospholipase B1 subfamily.
Calcium-independent membrane-associated phospholipase that catalyzes complete diacylation of phospholipids by hydrolyzing both sn-1 and sn-2 fatty acyl chains attached to the glycerol backbone (phospholipase B activity) (PubMed:8509424). Has dual phospholipase and lysophospholipase activities toward diacylphospholipids. Preferentially cleaves sn-2 ester bonds over sn-1 bonds. Acts as a lipase toward glycerolipid substrates (PubMed:8509424). Hydrolyzes fatty acyl chains of diacylglycerols with preference for the sn-2 position and of triacylglycerols with not positional selectivity (PubMed:8509424). May also hydrolyze long chain retinyl esters such as retinyl palmitate (Probable). May contribute to digestion of dietary phospholipids, glycerolipids and retinoids, facilitating lipid absorption at the brush border (Probable).
Expressed in the intestine of adult but not baby rabbits.
Undergoes proteolytic cleavage in the ileum.
Component C2 which is part of the classical pathway of the complement system is cleaved by activated factor C1 into two fragments: C2b and C2a. C2a, a serine protease, then combines with complement factor C4b to generate the C3 or C5 convertase.
Belongs to the retinoblastoma protein (RB) family.
A large substrate binding region with partially overlapping binding domains for structurally different substrates is formed by several transmembrane helix domains (TMH) including TMH 2, 4, 10 and 11, and it is alternatingly exposed to the extracellular or intracellular side during substrate transport.
Cellular localization of OCT1 in the intestine and the kidney remains to be finally defined. While most authors have deduced a localization at the basolateral side of enterocytes consistent with a physiological role in organic anions uptake from the blood flow and intestinal excretion (By similarity), other studies demonstrated an apical localization (By similarity), supporting a function in intestinal absorption of organic anions and drugs (By similarity). Similarly, contradictory findings have shown a localization to the basolateral side (By similarity) or to the apical side (By similarity) of proximal tubules (By similarity). Affinity and capacity of the transporter for endogenous substrates vary among orthologs (By similarity).
Contains one proline-rich sequence (Pro-Glu-Ser-Pro-Arg) that is required for transport activity.
Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics (PubMed:9528667, PubMed:12060594). Functions as a pH- and Na(+)-independent, bidirectional transporter (By similarity). Cation cellular uptake or release is driven by the electrochemical potential (i.e. membrane potential and concentration gradient) and substrate selectivity (By similarity). Hydrophobicity is a major requirement for recognition in polyvalent substrates and inhibitors (By similarity). Primarily expressed in the basolateral membrane of hepatocytes and proximal tubules and involved in the uptake and disposition of cationic compounds from the blood by hepatic and renal clearance (By similarity). Most likely functions as an uptake carrier in enterocytes contributing to the intestinal elimination of organic cations from the systemic circulation. Transports endogenous monoamines such as N-1-methylnicotinamide (NMN), guanidine, neurotransmitters dopamine, serotonin, noradrenaline, adrenaline and histamine, and quaternary ammonium compound such as choline. Also transports natural polyamines such as spermidine, agmatine and putrescine at low affinity, but relatively high turnover. Involved in the hepatic and intestinal uptake of the vitamin B1/thiamine, hence regulating hepatic lipid and energy metabolism. Contributes to the influx and efflux of fatty acid carriers carnitines and acylcarnitines across the basolateral membrane of hepatocytes, from the liver to the systemic circulation and inversely and may be involved in regulating the systemic availability of hepatic acylcarnitines (By similarity). Also capable of transporting non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) (By similarity). May contribute to the transport of cationic compounds in testes across the blood-testis-barrier (By similarity). Also mediates the uptake of xenobiotics tributylmethylammonium (TBuMA), quinidine, N-methyl-quinine (NMQ), N-methyl-quinidine (NMQD) N-(4,4-azo-n-pentyl)-quinuclidine (APQ), azidoprocainamide methoiodide (AMP), N-(4,4-azo-n-pentyl)-21-deoxyajmalinium (APDA) and 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP) (PubMed:12060594).
Expressed in kidney, liver and intestine.
Involved in the uptake of clinically used drugs including diabete treatment medicine metformin, neurotoxins 1-methyl-4-phenylpyridinium (MPP(+)) and iobenguane and platinum-based drug cisplatin (PubMed:9528667). Also involved in metformin efflux transport (By similarity). Metformin competitively inhibits OCT1-mediated thiamine uptake, leading to a decrease in hepatic steatosis (By similarity). Plays a role in the anticancer activity of cisplatin and may contribute to antitumor specificity (By similarity).
Phosphorylation of the transporter leads to changes in its substrate affinity, resulting in a regulation of the transport activity. In contrast with rat ortholog, ASP uptake is inhibited by protein kinase A (PKA) and C (PKC) activation. ASP uptake is also endogenously activated by calmodulin, the calmodulin-dependent kinase II and LCK tyrosine kinase (By similarity). Inhibited by cGMP, most likely through a cGMP-binding protein that interacts with OCT1 (By similarity).
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 JARID1 histone demethylase family.
Belongs to the P-Pant transferase superfamily. AcpS family.
Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In association with the E3 enzyme BRE1 (RNF20 and/or RNF40), it plays a role in transcription regulation by catalyzing the monoubiquitination of histone H2B at 'Lys-120' to form H2BK120ub1. H2BK120ub1 gives a specific tag for epigenetic transcriptional activation, elongation by RNA polymerase II, telomeric silencing, and is also a prerequisite for H3K4me and H3K79me formation. In vitro catalyzes 'Lys-11'-, as well as 'Lys-48'- and 'Lys-63'-linked polyubiquitination. Required for postreplication repair of UV-damaged DNA. Associates to the E3 ligase RAD18 to form the UBE2B-RAD18 ubiquitin ligase complex involved in mono-ubiquitination of DNA-associated PCNA on 'Lys-164'. May be involved in neurite outgrowth.
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 ribulose-phosphate 3-epimerase family.
Binds 1 divalent metal cation per subunit.
In the hair cortex, hair keratin intermediate filaments are embedded in an interfilamentous matrix, consisting of hair keratin-associated proteins (KRTAP), which are essential for the formation of a rigid and resistant hair shaft through their extensive disulfide bond cross-linking with abundant cysteine residues of hair keratins. The matrix proteins include the high-sulfur and high-glycine-tyrosine keratins.
KAP6 proteins are first expressed in differentiating hair shaft keratinocytes a considerable distance above the proliferative zone of the follicle bulb.
Efficient DNA binding requires dimerization with another bHLH protein. Binds DNA as a homodimer or a heterodimer (USF1/USF2).
Transcription factor that binds to a symmetrical DNA sequence (E-boxes) (5'-CACGTG-3') that is found in a variety of viral and cellular promoters. Regulates the expression of the surfactant protein-A (SP-A) gene.
Belongs to the nucleosome assembly protein (NAP) family.
Belongs to the sauvagine/corticotropin-releasing factor/urotensin I family.
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 TFIIE alpha 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.
Belongs to the peptidase C69 family. Secernin subfamily.
The N-terminal C2 domain associates with lipid membranes upon calcium binding.
The zeta subunit may be involved in regulating the coat assembly and, hence, the rate of biosynthetic protein transport due to its association-dissociation properties with the coatomer complex.
Belongs to the aconitase/IPM isomerase family.
Bifunctional iron sensor that switches between 2 activities depending on iron availability (By similarity). Iron deprivation, promotes its mRNA binding activity through which it regulates the expression of genes involved in iron uptake, sequestration and utilization (PubMed:17185597). 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 (PubMed:17185597).
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.
Interacts (when associated with the 4Fe-4S) with FBXL5. Interacts with frataxin(81-210).
Belongs to the WD repeat PRL1/PRL2 family.
Hydrolase highly specific for thiamine triphosphate (ThTP).
Kappa-casein stabilizes micelle formation, preventing casein precipitation in milk.
Belongs to the SIX/Sine oculis homeobox family.
Exhibits adenosine 5'-monophosphoramidase activity, hydrolyzing purine nucleotide phosphoramidates with a single phosphate group such as adenosine 5'monophosphoramidate (AMP-NH2) to yield AMP and NH2 (PubMed:11805111, PubMed:15703176). Hydrolyzes adenosine 5'monophosphomorpholidate (AMP-morpholidate) and guanosine 5'monophosphomorpholidate (GMP-morpholidate) (PubMed:15703176). Hydrolyzes lysyl-AMP (AMP-N-epsilon-(N-alpha-acetyl lysine methyl ester)) generated by lysine tRNA ligase (PubMed:20940308). Hydrolyzes Met-AMP, His-AMP, Asp-AMP, lysyl-GMP (GMP-N-epsilon-(N-alpha-acetyl lysine methyl ester)) and AMP-N-alanine methyl ester (By similarity). Can also convert adenosine 5'-O-phosphorothioate and guanosine 5'-O-phosphorothioate to the corresponding nucleoside 5'-O-phosphates with concomitant release of hydrogen sulfide (PubMed:20940308). In addition, functions as scaffolding protein that modulates transcriptional activation by the LEF1/TCF1-CTNNB1 complex and by the complex formed with MITF and CTNNB1 (By similarity). Modulates p53/TP53 levels and p53/TP53-mediated apoptosis. Modulates proteasomal degradation of target proteins by the SCF (SKP2-CUL1-F-box protein) E3 ubiquitin-protein ligase complex (By similarity). Also exhibits SUMO-specific isopeptidase activity, deconjugating SUMO1 from RANGAP1 and RGS17 (By similarity).
Homodimer (By similarity). Interacts with CDK7 (By similarity). Interacts with RUVBL1 and RUVBL2 and is associated with the LEF1/TCF1-CTNNB1 complex and with a KAT5 histone acetyltransferase complex (By similarity). Identified in a complex with MITF and CTNNB1 (By similarity). Interacts with CDC34 and RBX1, and is part of a SCF (SKP2-CUL1-F-box protein) E3 ubiquitin-protein ligase complex (By similarity). Interacts with SUMO1, SUMO2 and RGS17 (By similarity). Interacts with the Ten-1 ICD form of TENM1 (By similarity). Interacts with CALM1; interaction increases in the presence of calcium ions (By similarity).
Was originally thought to be a protein kinase C inhibitor and to bind zinc in solution. Both seem to be incorrect.
Component of the ARISC complex. Component of the BRCA1-A complex. Component of the BRISC complex. Binds polyubiquitin.
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.
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.
Belongs to the cysteine dioxygenase family.
Catalyzes the oxidation of cysteine to cysteine sulfinic acid with addition of molecular dioxygen.
Splice factor required for alternative splicing of TRA2B/SFRS10 transcripts. May interfere with constitutive 5'-splice site selection.
Auxillary component of the N-terminal acetyltransferase C (NatC) complex which catalyzes acetylation of N-terminal methionine residues.
Acetylated within its nuclear localization sequence, which impacts subcellular localization.
Cytokine constitutively present intracellularly in nearly all resting non-hematopoietic cells that plays an important role in inflammation and bridges the innate and adaptive immune systems. After binding to its receptor IL1R1 together with its accessory protein IL1RAP, forms the high affinity interleukin-1 receptor complex. Signaling involves the recruitment of adapter molecules such as MYD88, IRAK1 or IRAK4. In turn, mediates the activation of NF-kappa-B and the three MAPK pathways p38, p42/p44 and JNK pathways. Within the cell, acts as an alarmin and cell death results in its liberation in the extracellular space after disruption of the cell membrane to induce inflammation and alert the host to injury or damage. In addition to its role as a danger signal, which occurs when the cytokine is passively released by cell necrosis, directly senses DNA damage and acts as signal for genotoxic stress without loss of cell integrity.
Monomer. Interacts with TMED10; the interaction mediates the translocation from the cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) and thereby secretion. Interacts with IL1R1. Interacts with S100A13; this interaction is the first step in the export of IL1A, followed by direct translocation of this complex across the plasma membrane.
Phosphorylated. Phosphorylation greatly enhances susceptibility to digestion and promotes the conversion of pre-IL1A alpha to the biologically active IL1A.
Proteolytic processed by CAPN1 in a calcium-dependent manner. Cleavage from 31 kDa precursor to 18 kDa biologically active molecules.
The similarity among the IL-1 precursors suggests that the amino ends of these proteins serve some as yet undefined function.
Belongs to the xanthine dehydrogenase family.
Binds 1 Mo-molybdopterin (Mo-MPT) cofactor per subunit.
Involved in nucleotide metabolism via production of dUMP, the immediate precursor of thymidine nucleotides, and decreases the intracellular concentration of dUTP so that uracil cannot be incorporated into DNA.
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs 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. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling inhibits adenylate cyclase activity and activates a phosphatidylinositol-calcium second messenger system that regulates the release of Ca(2+) ions from intracellular stores. Plays a role in the regulation of 5-hydroxytryptamine release and in the regulation of dopamine and 5-hydroxytryptamine metabolism. Plays a role in the regulation of dopamine and 5-hydroxytryptamine levels in the brain, and thereby affects neural activity, mood and behavior. Plays a role in the response to anxiogenic stimuli.
Belongs to the SNF2/RAD54 helicase family.
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.
Homodimer. The cytoplasmic dynein 1 complex consists of two catalytic heavy chains (HCs) and a number of non-catalytic subunits presented by intermediate chains (ICs), light intermediate chains (LICs) and light chains (LCs); the composition seems to vary in respect to the IC, LIC and LC composition. The heavy chain homodimer serves as a scaffold for the probable homodimeric assembly of the respective non-catalytic subunits. The ICs and LICs bind directly to the HC dimer and the LCs assemble on the IC dimer.
Belongs to the complex I subunit 6 family.
Core subunit of respiratory chain NADH dehydrogenase (Complex I) which is composed of 45 different subunits.
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.
Can be activated without removal of the activation peptide.
Cleaves collagens of types I, II, and III at one site in the helical domain. Also cleaves collagens of types VII and X.
Tyrosine phosphorylated in platelets by PKDCC/VLK.
CNTF is a survival factor for various neuronal cell types. Seems to prevent the degeneration of motor axons after axotomy.
Metalloproteinase with a rather broad substrate specificity that can degrade fibronectin, laminin, gelatins of type I, III, IV, and V; collagens III, IV, X, and IX, and cartilage proteoglycans. Activates different molecules including growth factors, plasminogen or other matrix metalloproteinases such as MMP9. Once released into the extracellular matrix (ECM), the inactive pro-enzyme is activated by the plasmin cascade signaling pathway. Acts also intracellularly. For example, in dopaminergic neurons, gets activated by the serine protease HTRA2 upon stress and plays a pivotal role in DA neuronal degeneration by mediating microglial activation and alpha-synuclein/SNCA cleavage. In addition, plays a role in immune response and possesses antiviral activity against various viruses. Mechanistically, translocates from the cytoplasm into the cell nucleus upon virus infection to influence NF-kappa-B activities.
Belongs to the transglutaminase superfamily. Transglutaminase family.
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.
Binds heme and transports it to the liver for breakdown and iron recovery, after which the free hemopexin returns to the circulation.
The isolated N-terminal domain binds one heme. The full-length protein also binds one heme, but at a different site. The physiological significance of this is not clear.
Belongs to the potassium channel HCN family.
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. 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.
Acts as a component of the essential kinetochore-associated NDC80 complex, which is required for chromosome segregation and spindle checkpoint activity.
A connexon is composed of a hexamer of connexins. Interacts with SGSM3 (By similarity). Interacts with RIC1/CIP150 (By similarity). Interacts with CNST and CSNK1D (By similarity). Interacts (via C-terminus) with TJP1. Interacts (via C-terminus) with SRC (via SH3 domain). Interacts (not ubiquitinated) with UBQLN4 (via UBA domain) (By similarity). Interacts with NOV. Interacts with TMEM65 (By similarity).
Acetylated in the developing cortex; leading to delocalization from the cell membrane.
Gap junction protein that acts as a regulator of bladder capacity. A gap junction consists of a cluster of closely packed pairs of transmembrane channels, the connexons, through which materials of low MW diffuse from one cell to a neighboring cell. May play a critical role in the physiology of hearing by participating in the recycling of potassium to the cochlear endolymph. Negative regulator of bladder functional capacity: acts by enhancing intercellular electrical and chemical transmission, thus sensitizing bladder muscles to cholinergic neural stimuli and causing them to contract. May play a role in cell growth inhibition through the regulation of NOV expression and localization. Plays an essential role in gap junction communication in the ventricles (By similarity).
Phosphorylation at Ser-325, Ser-328 and Ser-330 by CK1 modulates gap junction assembly (By similarity). Phosphorylated at Ser-368 by PRKCG; phosphorylation induces disassembly of gap junction plaques and inhibition of gap junction activity. Phosphorylation at Ser-368 by PRKCD triggers its internalization into small vesicles leading to proteasome-mediated degradation (By similarity).
S-nitrosylation at Cys-271 is enriched at the muscle endothelial gap junction in arteries, it augments channel permeability and may regulate of smooth muscle cell to endothelial cell communication.
Sumoylated with SUMO1, SUMO2 and SUMO3, which may regulate the level of functional Cx43 gap junctions at the plasma membrane. May be desumoylated by SENP1 or SENP2 (By similarity).
Catalyzes the transfer of a dimethylallyl group onto the adenine at position 37.
Belongs to the sarcoglycan alpha/epsilon 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 (By similarity). Interacts with the syntrophin SNTA1.
Highly expressed in gastric parietal cells.
Interacts with the regulatory region of protein kinase N (PKN), protein phosphatase 2A (PP2A), protein phosphatase 1 (PP1) and the immature non-phosphorylated form of PKC epsilon. Interacts with CIP4 and FNBP1. Interacts with chloride intracellular channel proteins CLIC1, CLIC4 and CLIC5. CSNK1D binding promotes its centrosomal subcellular location. Interacts with GM130/GOLGA2; leading to recruitment to the Golgi apparatus. Interacts with KCNQ1; targets protein kinase A (PKA) catalytic and regulatory subunits and protein phosphatase 1 (PP1), to the heterodimer KCNQ1-KCNE1. Interacts with PDE4DIP; this interaction stabilizes both proteins. In complex with PDE4DIP, recruits CAMSAP2 to the Golgi apparatus. Forms a pericentrosomal complex with CDK5RAP2, EB1/MAPRE1 and PDE4DIP; within this complex, MAPRE1 binding to CDK5RAP2 may be mediated by PDE4DIP. The interaction with PDE4DIP is isoform-specific. Interacts with MAPRE1 and MAPRE3. Interacts (via C-terminus) with CAMSAP2; this interaction is much stronger in the presence of PDE4DIP. Interacts with CAMSAP3. Interacts (via C-terminus) with the gamma-tubulin ring complex (gamma-TuRC), composed of gamma-tubulin, TUBGCP2, TUBGCP3, TUBGCP4, TUBGCP5 and TUBGCP6.
RII-binding site, predicted to form an amphipathic helix, could participate in protein-protein interactions with a complementary surface on the R-subunit dimer.
Scaffolding protein that assembles several protein kinases and phosphatases on the centrosome and Golgi apparatus. Required to maintain the integrity of the Golgi apparatus. Required for microtubule nucleation at the cis-side of the Golgi apparatus. Required for association of the centrosomes with the poles of the bipolar mitotic spindle during metaphase. In complex with PDE4DIP, recruits CAMSAP2 to the Golgi apparatus and tethers non-centrosomal minus-end microtubules to the Golgi, an important step for polarized cell movement. In complex with PDE4DIP, EB1/MAPRE1 and CDK5RAP2, contributes to microtubules nucleation and extension also from the centrosome to the cell periphery. The interaction with PDE4DIP is isoform-specific.
G protein-coupled receptor for follitropin, the follicle-stimulating hormone. Through cAMP production activates the downstream PI3K-AKT and ERK1/ERK2 signaling pathways.
Belongs to the metallo-beta-lactamase superfamily. RNA-metabolizing metallo-beta-lactamase-like family. INTS9 subfamily.
Belongs to the type II (or gamma) interferon family.
Homodimer. Interacts with IFNGR1 (via extracellular domain); this interaction promotes IFNGR1 dimerization.
Released primarily from activated T lymphocytes.
Type II interferon produced by immune cells such as T-cells and NK cells that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing antigen presentation. Primarily signals through the JAK-STAT pathway after interaction with its receptor IFNGR1 to affect gene regulation. Upon IFNG binding, IFNGR1 intracellular domain opens out to allow association of downstream signaling components JAK2, JAK1 and STAT1, leading to STAT1 activation, nuclear translocation and transcription of IFNG-regulated genes. Many of the induced genes are transcription factors such as IRF1 that are able to further drive regulation of a next wave of transcription. Plays a role in class I antigen presentation pathway by inducing a replacement of catalytic proteasome subunits with immunoproteasome subunits. In turn, increases the quantity, quality, and repertoire of peptides for class I MHC loading. Increases the efficiency of peptide generation also by inducing the expression of activator PA28 that associates with the proteasome and alters its proteolytic cleavage preference. Up-regulates as well MHC II complexes on the cell surface by promoting expression of several key molecules such as cathepsins B/CTSB, H/CTSH, and L/CTSL (By similarity). Participates in the regulation of hematopoietic stem cells during development and under homeostatic conditions by affecting their development, quiescence, and differentiation (By similarity).
Type II interferon produced by immune cells such as T-cells and NK cells that plays crucial roles in antimicrobial, antiviral, and antitumor responses by activating effector immune cells and enhancing antigen presentation. Primarily signals through the JAK-STAT pathway after interaction with its receptor IFNGR1 to affect gene regulation. Upon IFNG binding, IFNGR1 intracellular domain opens out to allow association of downstream signaling components JAK2, JAK1 and STAT1, leading to STAT1 activation, nuclear translocation and transcription of IFNG-regulated genes. Many of the induced genes are transcription factors such as IRF1 that are able to further drive regulation of a next wave of transcription. Plays a role in class I antigen presentation pathway by inducing a replacement of catalytic proteasome subunits with immunoproteasome subunits. In turn, increases the quantity, quality, and repertoire of peptides for class I MHC loading. Increases the efficiency of peptide generation also by inducing the expression of activator PA28 that associates with the proteasome and alters its proteolytic cleavage preference. Up-regulates as well MHC II complexes on the cell surface by promoting expression of several key molecules such as cathepsins B/CTSB, H/CTSH, and L/CTSL. Participates in the regulation of hematopoietic stem cells during development and under homeostatic conditions by affecting their development, quiescence, and differentiation.
Forms a beta-barrel structure that accommodates hydrophobic ligands in its interior.
May play a role in lipid transport protein in Schwann cells. May bind cholesterol (By similarity).
P2 protein and myelin basic protein together constitute a major fraction of peripheral nervous system myelin protein.
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.
Component of the RNA polymerase III (Pol III) complex.
Cytokine produced by activated CD4-positive helper T-cells and to a lesser extend activated CD8-positive T-cells and natural killer (NK) cells that plays pivotal roles in the immune response and tolerance. Binds to a receptor complex composed of either the high-affinity trimeric IL-2R (IL2RA/CD25, IL2RB/CD122 and IL2RG/CD132) or the low-affinity dimeric IL-2R (IL2RB and IL2RG). Interaction with the receptor leads to oligomerization and conformation changes in the IL-2R subunits resulting in downstream signaling starting with phosphorylation of JAK1 and JAK3. In turn, JAK1 and JAK3 phosphorylate the receptor to form a docking site leading to the phosphorylation of several substrates including STAT5. This process leads to activation of several pathways including STAT, phosphoinositide-3-kinase/PI3K and mitogen-activated protein kinase/MAPK pathways. Functions as a T-cell growth factor and can increase NK-cell cytolytic activity as well. Promotes strong proliferation of activated B-cells and subsequently immunoglobulin production. Plays a pivotal role in regulating the adaptive immune system by controlling the survival and proliferation of regulatory T-cells, which are required for the maintenance of immune tolerance. Moreover, participates in the differentiation and homeostasis of effector T-cell subsets, including Th1, Th2, Th17 as well as memory CD8-positive T-cells.
Belongs to the cAMP-dependent kinase regulatory chain family.
Functions as an androgen transport protein, but may also be involved in receptor mediated processes. Each dimer binds one molecule of steroid. Specific for 5-alpha-dihydrotestosterone, testosterone, and 17-beta-estradiol. Regulates the plasma metabolic clearance rate of steroid hormones by controlling their plasma concentration (By similarity).
Belongs to the POU transcription factor family.
IL1B production occurs in 2 steps, each being controlled by different stimuli. First, inflammatory signals, such as LPS, stimulate the synthesis and promote the accumulation of cytosolic stores of pro-IL1B (priming). Then additional signals are required for inflammasome assembly, leading to CASP1 activation, pro-IL1B processing and eventually secretion of the active cytokine. IL1B processing and secretion are temporarily associated.
Monomer. In its precursor form, weakly interacts with full-length MEFV; the mature cytokine does not interact at all. Interacts with integrins ITGAV:ITGBV and ITGA5:ITGB1; integrin-binding is required for IL1B signaling. Interacts with cargo receptor TMED10; the interaction is direct and is required for the secretion of IL1B mature form. Interacts with HSP90AB1; the interaction facilitates cargo translocation into the ERGIC. Interacts with HSP90B1; the interaction facilitates cargo translocation into the ERGIC.
Potent pro-inflammatory cytokine. Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil influx and activation, T-cell activation and cytokine production, B-cell activation and antibody production, and fibroblast proliferation and collagen production. Promotes Th17 differentiation of T-cells. Synergizes with IL12/interleukin-12 to induce IFNG synthesis from T-helper 1 (Th1) cells. Plays a role in angiogenesis by inducing VEGF production synergistically with TNF and IL6. Involved in transduction of inflammation downstream of pyroptosis: its mature form is specifically released in the extracellular milieu by passing through the gasdermin-D (GSDMD) pore.
Belongs to the cyclophilin-type PPIase family. PPIase E subfamily.
Catalyzes the cis-trans isomerization of proline imidic peptide bonds in proteins.
Belongs to the tyrosyl-DNA phosphodiesterase family.
Required for proper homologous chromosome pairing and efficient cross-over and intragenic recombination during meiosis.
Belongs to the ABC transporter superfamily. ABCC family. CFTR transporter (TC 3.A.1.202) subfamily.
Binds and hydrolyzes ATP via the two cytoplasmic ABC transporter nucleotide-binding domains. The two ATP-binding domains interact with each other, forming a head-to-tail dimer. Normal ATPase activity requires interaction between the two domains. The first ABC transporter nucleotide-binding domain has no ATPase activity by itself.
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 (By similarity). 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. Modulates the activity of the epithelial sodium channel (ENaC) complex, in part by regulating the cell surface expression of the ENaC complex. May regulate bicarbonate secretion and salvage in epithelial cells by regulating the transporter SLC4A7. Can inhibit the chloride channel activity of ANO1 (By similarity). Plays a role in the chloride and bicarbonate homeostasis during sperm epididymal maturation and capacitation (By similarity).
Isoform 1 is expressed in the pancreas. Isoform 2 is specifically expressed in the ventricle.
Monomer; does not require oligomerization for channel activity. May form oligomers in the membrane (By similarity). Interacts with SLC26A3, SLC26A6 and NHERF1 (By similarity). Interacts with SHANK2 (By similarity). Interacts with MYO6 (By similarity). Interacts (via C-terminus) with GOPC (via PDZ domain); this promotes CFTR internalization and thereby decreases channel activity. Interacts with SLC4A7 through NHERF1. Found in a complex with MYO5B and RAB11A. Interacts with ANO1. Interacts with SLC26A8 (By similarity). Interacts with AHCYL1; the interaction increases CFTR activity (By similarity). Interacts with CSE1L (By similarity). The core-glycosylated form interacts with GORASP2 (via PDZ GRASP-type 1 domain) in respone to ER stress (By similarity). Interacts with MARCHF2; the interaction leads to CFTR ubiqtuitination and degradation (By similarity).
Phosphorylated; cAMP treatment promotes phosphorylation and activates the channel. Dephosphorylation decreases the ATPase activity (in vitro). Phosphorylation at PKA sites activates the channel. Phosphorylation at PKC sites enhances the response to phosphorylation by PKA. Phosphorylated by AMPK; this inhibits channel activity.
The PDZ-binding motif mediates interactions with GOPC and with the SLC4A7, NHERF1/EBP50 complex.
The disordered R region mediates channel activation when it is phosphorylated, but not in the absence of phosphorylation.
Ubiquitinated, leading to its degradation in the lysosome. Deubiquitination by USP10 in early endosomes enhances its endocytic recycling to the cell membrane. Ubiquitinated by RNF185 during ER stress. Ubiquitinated by MARCHF2 (By similarity).
Belongs to the KCNMB (TC 8.A.14.1) family. KCNMB1 subfamily.
Interacts with KCNMA1 tetramer. There are probably 4 molecules of KCMNB1 per KCNMA1 tetramer (By similarity).
Regulatory subunit of the calcium activated potassium KCNMA1 (maxiK) channel. Modulates the calcium sensitivity and gating kinetics of KCNMA1, thereby contributing to KCNMA1 channel diversity. Increases the apparent Ca(2+)/voltage sensitivity of the KCNMA1 channel. It also modifies KCNMA1 channel kinetics and alters its pharmacological properties. It slows down the activation and the deactivation kinetics of the channel. Acts as a negative regulator of smooth muscle contraction by enhancing the calcium sensitivity to KCNMA1. Its presence is also a requirement for internal binding of the KCNMA1 channel opener dehydrosoyasaponin I (DHS-1) triterpene glycoside and for external binding of the agonist hormone 17-beta-estradiol (E2). Increases the binding activity of charybdotoxin (CTX) toxin to KCNMA1 peptide blocker by increasing the CTX association rate and decreasing the dissociation rate (By similarity).
Belongs to the universal ribosomal protein uL11 family.
Acts both as a chaperone in the cytosol and as a chromatin regulator in the nucleus. When cytosolic, acts as a molecular chaperone: component of the ribosome-associated complex (RAC), a complex involved in folding or maintaining nascent polypeptides in a folding-competent state. In the RAC complex, stimulates the ATPase activity of the ribosome-associated pool of Hsp70-type chaperones HSPA14 that bind to the nascent polypeptide chain. When nuclear, mediates the switching from polycomb-repressed genes to an active state: specifically recruited at histone H2A ubiquitinated at 'Lys-119' (H2AK119ub), and promotes the displacement of the polycomb PRC1 complex from chromatin, thereby facilitating transcription activation.
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).
Belongs to the WD repeat coronin family.
Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.
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. May play a role in the metabolism of endogenous lipids such as epoxide-containing fatty acids. Metabolizes the abundant endocannabinoid 2-arachidonoylglycerol (2-AG) to free arachidonic acid (AA) and glycerol (By similarity).
Inhibited by 10-hydroxystearamide and methoxy-arachidonyl fluorophosphate.
Belongs to the SNF2/RAD54 helicase family. RAD16 subfamily.
Has both helicase and E3 ubiquitin ligase activities. Possesses intrinsic ATP-dependent nucleosome-remodeling activity. This activity may be required for transcriptional activation or repression of specific target promoters (By similarity). These may include the SERPINE1, to which this protein can bind directly. Mediates repression by c-Rel through a DNA-looping mechanism. Plays a role in error-free postreplication repair (PRR) of damaged DNA and maintains genomic stability through acting as a ubiquitin ligase for 'Lys-63'-linked polyubiquitination of chromatin-bound PCNA (By similarity). Transcriptional regulator that mediates the ability of prolactin to augment progesterone-dependent transcription of the SCGB1A1/uteroglobin gene through a bipartite progesterone receptor half-site/overlapping Y-box combination (-38/-26) where progesterone activation is attenuated by nuclear factor Y binding. Regulation also involves two GC-rich sequences in the proximal promoter (positions -162/+90) and a RUSH/SMARCA3 site (positions -616/-611) in the 5'-untranslated region.
Interacts with SP1 and SP3 independently of DNA; the interaction with these transcriptional factors may be required for basal transcription of target genes (By similarity). Interacts (via the RING-finger) with isoform RFBP of ATP11B. Progesterone-dependent isoform 1 interacts with EGR1; the interaction requires prior binding to DNA and represses c-Rel via a DNA looping mechanism. Interacts with GATA4. Interacts with PCNA; the interaction promotes polyubiquitination of PCNA through association with the UBE2B-RAD18 and UBE2V2-UBE2N ubiquitin ligase complexes. Interacts with RAD18, SHPRH, UBE2V2 and UBE2N (By similarity).
Isoform 1 is expressed preferentially in bladder, cervix, diaphragm, duodenum, epididymis, heart, kidney, liver, lung, ovary (granulosa cells), prostate, spleen, testis (predominantly in the Sertoli cells of the seminiferous tubules) and vagina. Isoform 2 is expressed preferentially in lactating mammary gland and uterine endometrium.
Isoform RUSH 1-alpha expression is increased by progesterone and decreased by estradiol. Progesterone induction is increased in the presence of prolactin. Isoform RUSH 1-beta/RFBP expression is increased by estrogen and decreased by progesterone.
Major isoform in progesterone-dominant endometrium.
Phosphorylated on serine, threonine, and tyrosine residues. Tyr-195 phosphorylation is catalyzed by JAK2 in response to prolactin treatment. It is required for DNA binding.
Belongs to the zinc-containing alcohol dehydrogenase family. Class-III subfamily.
Catalyzes the oxidation of long-chain primary alcohols and the oxidation of S-(hydroxymethyl) glutathione. Also oxidizes long chain omega-hydroxy fatty acids, such as 20-HETE, producing both the intermediate aldehyde, 20-oxoarachidonate and the end product, a dicarboxylic acid, (5Z,8Z,11Z,14Z)-eicosatetraenedioate. Class-III ADH is remarkably ineffective in oxidizing ethanol. Required for clearance of cellular formaldehyde, a cytotoxic and carcinogenic metabolite that induces DNA damage.
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 glycosyltransferase 43 family.
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. Has a preference for the L-3-hydroxy form. Also has cysteine-conjugate-beta-lyase activity.
This is a receptor for the tachykinin neuropeptide substance K (neurokinin A). It is associated with G proteins that activate a phosphatidylinositol-calcium second messenger system.
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.
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 constitutive coactivator of PPAR-gamma family.
Belongs to the SLC29A/ENT transporter (TC 2.A.57) family.
Belongs to the GHMP kinase family. GalK subfamily.
The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription.
Component of the dystrophin-glycoprotein complex (DGC), a complex that spans the muscle plasma membrane and forms a link between the F-actin cytoskeleton and the extracellular matrix. Preferentially associates with the sarcoglycan subcomplex of the DGC.
Belongs to the actin-binding proteins ADF family.
Plays a role in establishing and maintaining the asymmetric distribution of channels and receptors at the plasma membrane of polarized cells.
Belongs to the sulfotransferase 3 family.
Belongs to the glycosyl hydrolase 35 family.
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.
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 DNA2/NAM7 helicase family. SDE3 subfamily.
Belongs to the galactose-3-O-sulfotransferase 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.
PP1 comprises a catalytic subunit, and one or several targeting or regulatory subunits.
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.
Belongs to the sulfotransferase 6 family.
Membrane glycoproteins implicated in the pathologic deposition of cholesterol in arterial walls during atherogenesis. Two types of receptor subunits exist. These receptors mediate the endocytosis of a diverse group of macromolecules, including modified low density lipoproteins (LDL).
Heterotetramer of two alpha chains and two gamma chains.
This protein functions as an embryonic globin, but the gene structure and chromosomal location resemble more closely the human gamma chain gene, which codes for a fetal globin.
Belongs to the class-I pyridoxal-phosphate-dependent aminotransferase family.
Catalyzes the irreversible transamination of the L-tryptophan metabolite L-kynurenine to form kynurenic acid (KA). As a member of the malate-aspartate shuttle, it has a key role in the intracellular NAD(H) redox balance. Is important for metabolite exchange between mitochondria and cytosol, and for amino acid metabolism. Facilitates cellular uptake of long-chain free fatty acids.
In eukaryotes there are cytoplasmic, mitochondrial and chloroplastic isozymes.
Component of the PAQosome complex which is responsible for the biogenesis of several protein complexes and which consists of R2TP complex members RUVBL1, RUVBL2, RPAP3 and PIH1D1, URI complex members PFDN2, PFDN6, PDRG1, UXT and URI1 as well as ASDURF, POLR2E and DNAAF10/WDR92.
May play a role in chaperone-mediated protein folding.
Belongs to the Integrator subunit 7 family.
Belongs to the RRM HNRPC family. RALY subfamily.
Belongs to the eukaryotic ribosomal protein eL19 family.
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.
May play a role in the regulation of extra-urea cycle arginine metabolism and also in down-regulation of nitric oxide synthesis. Extrahepatic arginase functions to regulate L-arginine bioavailability to nitric oxid synthase (NOS). Arginine metabolism is a critical regulator of innate and adaptive immune responses. Seems to be involved in negative regulation of the survival capacity of activated T cells. May suppress inflammation-related signaling in asthmatic airway epithelium. May play a role in promoting prenatal immune suppression. Regulates RPS6KB1 signaling, which promotes endothelial cell senescence and inflammation and implicates NOS3/eNOS dysfunction. Can inhibit endothelial autophagy independently of its enzymatic activity implicating mTORC2 signaling. Involved in vascular smooth muscle cell senescence and apoptosis independently of its enzymatic activity.
Plays a role in cytokinesis. Displays serine/threonine protein kinase activity.
Belongs to the ZP domain family. ZPB subfamily.
Component of the zona pellucida, an extracellular matrix surrounding oocytes which mediates sperm binding, induction of the acrosome reaction and prevents post-fertilization polyspermy. The zona pellucida is composed of 3 to 4 glycoproteins, ZP1, ZP2, ZP3, and ZP4. ZP1 ensures the structural integrity of the zona pellucida (By similarity).
Expressed in oocytes (at protein level).
Polymers of ZP2 and ZP3 organized into long filaments cross-linked by ZP1 homodimers. Interacts with ZP3.
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.
Belongs to the somatotropin/prolactin family.
Prolactin acts primarily on the mammary gland by promoting lactation.
Activated by threonine and tyrosine phosphorylation.
Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. MAP kinase subfamily.
Anti-inflammatory antagonist of interleukin-1 family of proinflammatory cytokines such as interleukin-1beta/IL1B and interleukin-1alpha/IL1A. Protects from immune dysregulation and uncontrolled systemic inflammation triggered by IL1 for a range of innate stimulatory agents such as pathogens.
Belongs to the bacterial ribosomal protein bS21 family.
Belongs to the non-repetitive/WGA-negative nucleoporin family.
Plays a role in mitochondrial aerobic respiration. Regulates mitochondrial organization and fission.
Belongs to the acetyltransferase family. GNA1 subfamily.
Efficient DNA binding requires dimerization with another bHLH protein.
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.
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.
Expressed in brain, lung and kidney. In the kidney, strongly expressed in the cortex, at the luminal side of proximal convoluted tubules and in BBMVs. Weaker expression observed in the medulla (at protein level).
Involved in the sodium-dependent cotransport of myo-inositol (MI) with a Na(+):MI stoichiometry of 2:1. Exclusively responsible for apical MI transport and absorption in intestine. Can also transport D-chiro-inositol (DCI) but not L-fucose (PubMed:12133831, PubMed:15181167, PubMed:17932225, PubMed:15613375). Exhibits stereospecific cotransport of both D-glucose and D-xylose (PubMed:12133831). May induce apoptosis through the TNF-alpha, PDCD1 pathway (By similarity). May play a role in the regulation of MI concentration in serum, involving reabsorption in at least the proximal tubule of the kidney (PubMed:17306760).
MI transport activity stimulated five-fold under 24 hour hypertonic shock conditions. MI inward currents were gradually inhibited as increasing amounts of phlorizin were added to the superfusion medium. When sodium is replaced by potassium, MI uptake is dramatically reduced and in the presence of L-fucose or D-chiro-inositol (DCI), the specific accumulation of tracer amounts of MI is also reduced.
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 gamma-glutamyltransferase family.
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.
Belongs to the glycogen debranching enzyme family.
Monomer. Interacts with NHLRC1/malin (By similarity).
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.
Calcium-independent and membrane-bound phospholipase, that catalyzes the esterolytic cleavage of fatty acids from glycerophospholipids to yield free fatty acids and lysophospholipids, hence regulating membrane physical properties and the release of lipid second messengers and growth factors. Hydrolyzes phosphatidylethanolamine, phosphatidylcholine and probably phosphatidylinositol with a possible preference for the former. Has also a broad substrate specificity in terms of fatty acid moieties, hydrolyzing saturated and mono-unsaturated fatty acids at nearly equal rates from either the sn-1 or sn-2 position in diacyl phosphatidylcholine. However, has a weak activity toward polyunsaturated fatty acids at the sn-2 position, and thereby favors the production of 2-arachidonoyl lysophosphatidylcholine, a key branch point metabolite in eicosanoid signaling. On the other hand, can produce arachidonic acid from the sn-1 position of diacyl phospholipid and from the sn-2 position of arachidonate-containing plasmalogen substrates. Therefore, plays an important role in the mobilization of arachidonic acid in response to cellular stimuli and the generation of lipid second messengers. Can also hydrolyze lysophosphatidylcholine. In the mitochondrial compartment, catalyzes the hydrolysis and release of oxidized aliphatic chains from cardiolipin and integrates mitochondrial bioenergetics and signaling. It is essential for maintaining efficient bioenergetic mitochondrial function through tailoring mitochondrial membrane lipid metabolism and composition.
Belongs to the protease inhibitor I35 (TIMP) family.
Interacts with MMP1, MMP3, MMP10 and MMP13, but has only very low affinity for MMP14. Interacts with CD63; identified in a complex with CD63 and ITGB1 (By similarity).
Metalloproteinase inhibitor that functions by forming one to one complexes with target metalloproteinases, such as collagenases, and irreversibly inactivates them by binding to their catalytic zinc cofactor. Acts on MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP10, MMP11, MMP12, MMP13 and MMP16. Does not act on MMP14. Also functions as a growth factor that regulates cell differentiation, migration and cell death and activates cellular signaling cascades via CD63 and ITGB1. Plays a role in integrin signaling (By similarity).
The activity of TIMP1 is dependent on the presence of disulfide bonds.
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) (By similarity).
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.
Has no constitutive proton transporter activity and has to be activated by long-chain fatty acids/LCFAs. Inhibited by purine nucleotides. Both purine nucleotides and LCFAs bind the cytosolic side of the transporter and directly compete to activate or inhibit it. Activated by noradrenaline and reactive oxygen species. Despite lacking canonical translational encoding for selenocysteine, a small pool of the protein has been observed to selectively incorporate selenocysteine at 'Cys-253'. Selenocysteine-modified protein is highly sensitive to redox modification and may constitute a pool of protein highly sensitive to activation by elevated levels of reactive oxygen species (ROS).
May undergo sulfenylation upon cold exposure. May increase the sensitivity of UCP1 thermogenic function to the activation by noradrenaline probably through structural effects.
May undergo ubiquitin-mediated proteasomal degradation.
Mitochondrial protein responsible for thermogenic respiration, a specialized capacity of brown adipose tissue and beige fat that participates in non-shivering adaptive thermogenesis to temperature and diet variations and more generally to the regulation of energy balance. Functions as a long-chain fatty acid/LCFA and proton symporter, simultaneously transporting one LCFA and one proton through the inner mitochondrial membrane. However, LCFAs remaining associated with the transporter via their hydrophobic tails, it results in an apparent transport of protons activated by LCFAs. Thereby, dissipates the mitochondrial proton gradient and converts the energy of substrate oxydation into heat instead of ATP. Regulates the production of reactive oxygen species/ROS by mitochondria.
Most probably functions as a monomer. Binds one purine nucleotide per monomer. However, has also been suggested to function as a homodimer or a homotetramer. Tightly associates with cardiolipin in the mitochondrion inner membrane; may stabilize and regulate its activity.
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.
N-glycosylated; different glycan composition appears to lead to two forms of this protein (56 and 60 kDa).
The N-terminal acidic repeat region mediates, in part, the glycosaminoglycan-accelerated thrombin inhibition.
Thrombin inhibitor activated by the glycosaminoglycans, heparin or dermatan sulfate. In the presence of the latter, HC-II becomes the predominant thrombin inhibitor in place of antithrombin III (AT).
Acts as a ligand for C-C chemokine receptor CCR2 (By similarity). Signals through binding and activation of CCR2 and induces a strong chemotactic response and mobilization of intracellular calcium ions (By similarity). Exhibits a chemotactic activity for monocytes and basophils but not neutrophils or eosinophils (By similarity). Plays an important role in mediating peripheral nerve injury-induced neuropathic pain (By similarity). Increases NMDA-mediated synaptic transmission in both dopamine D1 and D2 receptor-containing neurons, which may be caused by MAPK/ERK-dependent phosphorylation of GRIN2B/NMDAR2B (By similarity).
Monomer or homodimer; in equilibrium. Is tethered on endothelial cells by glycosaminoglycan (GAG) side chains of proteoglycans. Interacts with TNFAIP6 (via Link domain).
Processing at the N-terminus can regulate receptor and target cell selectivity (By similarity). Deletion of the N-terminal residue converts it from an activator of basophil to an eosinophil chemoattractant (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 protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily.
Belongs to the eukaryotic ribosomal protein eS24 family.
Regulates negatively FAS-induced apoptosis and NGFR-mediated pro-apoptotic signaling.
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). Catalyzes the hydrolysis of 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (platelet-activating factor or PAF) to 1-O-alkyl-sn-glycero-3-phosphocholine (lyso-PAF) (By similarity). Also catalyzes the transfer of the acetate group from PAF to 1-hexadecanoyl-sn-glycero-3-phosphocholine forming lyso-PAF (By similarity). Catalyzes the esterification of (24S)-hydroxycholesterol (24(S)OH-C), also known as cerebrosterol to produce 24(S)OH-C monoesters (By similarity).
Detected in blood plasma (at protein level) (PubMed:8820107). Highly expressed in liver.
Levels increase up to 3-fold on a 6-week cholesterol-enriched diet.
Essential factor for the assembly of mitochondrial NADH:ubiquinone oxidoreductase complex (complex I).
Belongs to the MINDY deubiquitinase family. FAM188 subfamily.
Hydrolase that can remove 'Lys-48'-linked conjugated ubiquitin from proteins.
Belongs to the potassium channel family. A (Shaker) (TC 1.A.1.2) subfamily. Kv1.2/KCNA2 sub-subfamily.
Detected in portal vein myocytes (at protein level) (PubMed:11717160). Detected in portal vein (PubMed:11717160). Brain, liver and kidney.
Homotetramer and heterotetramer with other channel-forming alpha subunits, such as KCNA1, KCNA4, KCNA5, KCNA6 and KCNA7. Channel activity is regulated by interaction with the beta subunits, including KCNAB1 and KCNAB2. Identified in a complex with KCNA1 and KCNAB2 (By similarity). Identified in a complex with KCNA4 and FYN (PubMed:11149959). Identified in a complex with KCNA5 and KCNAB1 (PubMed:11717160). Interacts with the beta subunit KCNAB1 (PubMed:11717160). Interacts with PTK2B (By similarity). Interacts (via C-terminus) with CTTN (By similarity). Interacts (via N-terminal cytoplasmic domain) with RHOA (GTP-bound form); this regulates channel activity by reducing location at the cell surface in response to CHRM1 activation (By similarity). Interacts with DRD2 (By similarity). Interacts with SIGMAR1; cocaine consumption leads to increased interaction (By similarity). Interacts with ADAM22 (By similarity). Interacts with CNTNAP2 (By similarity). Interacts (via C-terminus) with the PDZ domains of DLG1, DLG2 and DLG4 (By similarity). Interacts with ADAM11 (By similarity).
Inhibited by 4-aminopyridine (4-AP) (PubMed:11717161). Inhibited by dendrotoxin (DTX) and charybdotoxin (CTX), but not by tetraethylammonium (TEA) (By similarity). Inhibited by tityustoxin-K alpha (TsTX-Kalpha), a toxin that is highly specific for KCNA2 (By similarity). Inhibited by maurotoxin (By similarity). Inhibited by kappaM conotoxins kappaM-RIIIJ and kappaM-RIIIK (By similarity).
N-glycosylated, with complex, sialylated N-glycans.
Phosphorylated on tyrosine residues; phosphorylation increases in response to ischemia (By similarity). Phosphorylated on tyrosine residues by activated PTK2B/PYK2 (By similarity). Phosphorylation on tyrosine residues suppresses ion channel activity (By similarity). Phosphorylated on tyrosine residues in response to CHRM1 activation; this abolishes interaction with CTTN. This is probably due to endocytosis of the phosphorylated channel subunits (By similarity). Phosphorylated on serine residues in response to increased cAMP levels; phosphorylation is apparently not catalyzed by PKA (By similarity).
The cytoplasmic N-terminus is important for tetramerization. Interactions between the different subunits modulate the gating characteristics (By similarity). Besides, the cytoplasmic N-terminal domain mediates interaction with RHOA and thus is required for RHOA-mediated endocytosis (By similarity).
The delay or D-type current observed in hippocampus pyramidal neurons is probably mediated by potassium channels containing KCNA2 plus KCNA1 or other family members. It is activated at about -50 mV, i.e. below the action potential threshold, and is characterized by slow inactivation, extremely slow recovery from inactivation, sensitivity to dendrotoxin (DTX) and to 4-aminopyridine (4-AP).
Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes, primarily in the brain and the central nervous system, but also in the cardiovascular system. Prevents aberrant action potential firing and regulates neuronal output. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:11717161). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, KCNA6, KCNA7, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (PubMed:11717161). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation of delayed rectifier potassium channels (By similarity). In vivo, membranes probably contain a mixture of heteromeric potassium channel complexes, making it difficult to assign currents observed in intact tissues to any particular potassium channel family member. Homotetrameric KCNA2 forms a delayed-rectifier potassium channel that opens in response to membrane depolarization, followed by slow spontaneous channel closure (PubMed:11717161, PubMed:19389710). In contrast, a heteromultimer formed by KCNA2 and KCNA4 shows rapid inactivation (By similarity). Regulates neuronal excitability and plays a role as pacemaker in the regulation of neuronal action potentials (By similarity). KCNA2-containing channels play a presynaptic role and prevent hyperexcitability and aberrant action potential firing (By similarity). Response to toxins that are selective for KCNA2-containing potassium channels suggests that in Purkinje cells, dendritic subthreshold KCNA2-containing potassium channels prevent random spontaneous calcium spikes, suppressing dendritic hyperexcitability without hindering the generation of somatic action potentials, and thereby play an important role in motor coordination (By similarity). Plays a role in the induction of long-term potentiation of neuron excitability in the CA3 layer of the hippocampus (By similarity). May function as down-stream effector for G protein-coupled receptors and inhibit GABAergic inputs to basolateral amygdala neurons (By similarity). May contribute to the regulation of neurotransmitter release, such as gamma-aminobutyric acid (GABA) (By similarity). Contributes to the regulation of the axonal release of the neurotransmitter dopamine (By similarity). Reduced KCNA2 expression plays a role in the perception of neuropathic pain after peripheral nerve injury, but not acute pain (By similarity). Plays a role in the regulation of the time spent in non-rapid eye movement (NREM) sleep (By similarity).
Belongs to the protein kinase superfamily. RIO-type Ser/Thr kinase family.
Involved in regulation of type I interferon (IFN)-dependent immune response which plays a critical role in the innate immune response against DNA and RNA viruses.
According to a well-established model, RNF168 cannot initiate H2A 'Lys-63'-linked ubiquitination and is recruited following RNF8-dependent histone ubiquitination to amplify H2A 'Lys-63'-linked ubiquitination. However, other data suggest that RNF168 is the priming ubiquitin ligase by mediating monoubiquitination of 'Lys-13' and 'Lys-15' of nucleosomal histone H2A (H2AK13Ub and H2AK15Ub respectively). These data suggest that RNF168 might be recruited to DSBs sites in a RNF8-dependent manner by binding to non-histone proteins ubiquitinated via 'Lys-63'-linked and initiates monoubiquitination of H2A, which is then amplified by RNF8. Additional evidences are however required to confirm these data.
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 H2AX and amplifies the RNF8-dependent H2A ubiquitination, 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. Also recruited at DNA interstrand cross-links (ICLs) sites and promotes accumulation of 'Lys-63'-linked ubiquitination of histones H2A and H2AX, leading to recruitment of FAAP20 and Fanconi anemia (FA) complex, followed by interstrand cross-link repair. H2A ubiquitination also mediates the ATM-dependent transcriptional silencing at regions flanking DSBs in cis, a mechanism to avoid collision between transcription and repair intermediates. Also involved in class switch recombination in immune system, via its role in regulation of DSBs repair. Following DNA damage, promotes the ubiquitination and degradation of JMJD2A/KDM4A in collaboration with RNF8, leading to unmask H4K20me2 mark and promote the recruitment of TP53BP1 at DNA damage sites. Not able to initiate 'Lys-63'-linked ubiquitination in vitro; possibly due to partial occlusion of the UBE2N/UBC13-binding region. Catalyzes monoubiquitination of 'Lys-13' and 'Lys-15' of nucleosomal histone H2A (H2AK13Ub and H2AK15Ub, respectively).
Sumoylated with SUMO1 by PIAS4 in response to double-strand breaks (DSBs).
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).
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.
A phosphorylation cycle of C-terminal serine cluster (Ser-805-Ser-815) regulates the release of target mRNAs. Target-binding leads to phosphorylation of these residues by CSNK1A1, which reduces the affinity of AGO2 for mRNA and enables target release. The ANKRD52-PPP6C phosphatase complex dephosphorylates the residues, which primes AGO2 for binding a new target.
Belongs to the argonaute family. Ago subfamily.
Hydroxylated. 4-hydroxylation appears to enhance protein stability but is not required for miRNA-binding or endonuclease activity.
Interacts with DICER1 through its Piwi domain and with TARBP2 during assembly of the RNA-induced silencing complex (RISC). Together, DICER1, AGO2 and TARBP2 constitute the trimeric RISC loading complex (RLC), or micro-RNA (miRNA) loading complex (miRLC). Within the RLC/miRLC, DICER1 and TARBP2 are required to process precursor miRNAs (pre-miRNAs) to mature miRNAs and then load them onto AGO2. AGO2 bound to the mature miRNA constitutes the minimal RISC and may subsequently dissociate from DICER1 and TARBP2. Note however that the term RISC has also been used to describe the trimeric RLC/miRLC. The formation of RISC complexes containing siRNAs rather than miRNAs appears to occur independently of DICER1. Interacts with AGO1. Also interacts with DDB1, DDX5, DDX6, DDX20, DHX30, DHX36, DDX47, DHX9, ELAVL, FXR1, GEMIN4, HNRNPF, IGF2BP1, ILF3, IMP8, MATR3, PABPC1, PRMT5, P4HA1, P4HB, RBM4, SART3, TNRC6A, TNRC6B, UPF1 and YBX1. Interacts with the P-body components DCP1A and XRN1. Associates with polysomes and messenger ribonucleoproteins (mNRPs). Interacts with RBM4; the interaction is modulated under stress-induced conditions, occurs under both cell proliferation and differentiation conditions and in an RNA- and phosphorylation-independent manner. Interacts with LIMD1, WTIP and AJUBA. Interacts with TRIM71; the interaction increases in presence of RNA. Interacts with APOBEC3G in an RNA-dependent manner. Interacts with APOBEC3A, APOBEC3C, APOBEC3F and APOBEC3H. Interacts with DICER1, TARBP2, EIF6, MOV10 and RPL7A (60S ribosome subunit); they form a large RNA-induced silencing complex (RISC). Interacts with FMR1. Interacts with ZFP36. Interacts with RC3H1; the interaction is RNA independent (By similarity). Found in a complex composed of AGO2, CHD7 and FAM172A (By similarity). Interacts with SND1 and SYT11 (By similarity). Interacts with CLNK (By similarity). Interacts with GARRE1 (By similarity).
Phosphorylation at Ser-368 by AKT3; leads to up-regulate translational repression of microRNA target and down-regulate endonucleolytic cleavage.
Required for RNA-mediated gene silencing (RNAi) by the RNA-induced silencing complex (RISC). The 'minimal RISC' appears to include AGO2 bound to a short guide RNA such as a microRNA (miRNA) or short interfering RNA (siRNA). These guide RNAs direct RISC to complementary mRNAs that are targets for RISC-mediated gene silencing. The precise mechanism of gene silencing depends on the degree of complementarity between the miRNA or siRNA and its target. Binding of RISC to a perfectly complementary mRNA generally results in silencing due to endonucleolytic cleavage of the mRNA specifically by AGO2. Binding of RISC to a partially complementary mRNA results in silencing through inhibition of translation, and this is independent of endonuclease activity. May inhibit translation initiation by binding to the 7-methylguanosine cap, thereby preventing the recruitment of the translation initiation factor eIF4-E. May also inhibit translation initiation via interaction with EIF6, which itself binds to the 60S ribosomal subunit and prevents its association with the 40S ribosomal subunit. The inhibition of translational initiation leads to the accumulation of the affected mRNA in cytoplasmic processing bodies (P-bodies), where mRNA degradation may subsequently occur. In some cases RISC-mediated translational repression is also observed for miRNAs that perfectly match the 3' untranslated region (3'-UTR). Can also up-regulate the translation of specific mRNAs under certain growth conditions. Binds to the AU element of the 3'-UTR of the TNF (TNF-alpha) mRNA and up-regulates translation under conditions of serum starvation. Also required for transcriptional gene silencing (TGS), in which short RNAs known as antigene RNAs or agRNAs direct the transcriptional repression of complementary promoter regions.
The Piwi domain may perform RNA cleavage by a mechanism similar to that of RNase H. However, while RNase H utilizes a triad of Asp-Asp-Glu (DDE) for metal ion coordination, this protein appears to utilize a triad of Asp-Asp-His (DDH).
Ubiquitinated on surface-exposed lysines by a SCF-like E3 ubiquitin-protein ligase complex containing ZSWIM8 during target-directed microRNA degradation (TDMD), a process that mediates degradation of microRNAs (miRNAs). Ubiquitination by the SCF-like E3 ubiquitin-protein ligase complex containing ZSWIM8 leads to its subsequent degradation, thereby exposing miRNAs for degradation. ZSWIM8 recognizes and binds AGO2 when it is engaged with a TDMD target.
Belongs to the Tim17/Tim22/Tim23 family.
Essential core component of the TIM22 complex, a complex that mediates the import and insertion of multi-pass transmembrane proteins into the mitochondrial inner membrane. In the TIM22 complex, it constitutes the voltage-activated and signal-gated channel. Forms a twin-pore translocase that uses the membrane potential as external driving force in 2 voltage-dependent steps.
Belongs to the pyridoxamine 5'-phosphate oxidase family.
Catalyzes the oxidation of either pyridoxine 5'-phosphate (PNP) or pyridoxamine 5'-phosphate (PMP) into pyridoxal 5'-phosphate (PLP).
Belongs to the protein-tyrosine phosphatase family. Receptor class 8 subfamily.
Belongs to the complex I NDUFB3 subunit family.
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.
At alkaline pH BPGM favors the synthase reaction; however, at lower pH the phosphatase reaction is dominant. Inhibited by citrate.
Belongs to the phosphoglycerate mutase family. BPG-dependent PGAM subfamily.
Plays a major role in regulating hemoglobin oxygen affinity by controlling the levels of its allosteric effector 2,3-bisphosphoglycerate (2,3-BPG). Also exhibits mutase (EC 5.4.2.11) activity.
Found in a ternary complex with CX3CL1 and ITGAV:ITGB3 or ITGA4:ITGB1.
Receptor for the C-X3-C chemokine fractalkine (CX3CL1) present on many early leukocyte cells; CX3CR1-CX3CL1 signaling exerts distinct functions in different tissue compartments, such as immune response, inflammation, cell adhesion and chemotaxis. CX3CR1-CX3CL1 signaling mediates cell migratory functions. Responsible for the recruitment of natural killer (NK) cells to inflamed tissues. Acts as a regulator of inflammation process leading to atherogenesis by mediating macrophage and monocyte recruitment to inflamed atherosclerotic plaques, promoting cell survival. Involved in airway inflammation by promoting interleukin 2-producing T helper (Th2) cell survival in inflamed lung. Involved in the migration of circulating monocytes to non-inflamed tissues, where they differentiate into macrophages and dendritic cells. Acts as a negative regulator of angiogenesis, probably by promoting macrophage chemotaxis. Plays a key role in brain microglia by regulating inflammatory response in the central nervous system (CNS) and regulating synapse maturation. Required to restrain the microglial inflammatory response in the CNS and the resulting parenchymal damage in response to pathological stimuli. Involved in brain development by participating in synaptic pruning, a natural process during which brain microglia eliminates extra synapses during postnatal development. Synaptic pruning by microglia is required to promote the maturation of circuit connectivity during brain development. Acts as an important regulator of the gut microbiota by controlling immunity to intestinal bacteria and fungi. Expressed in lamina propria dendritic cells in the small intestine, which form transepithelial dendrites capable of taking up bacteria in order to provide defense against pathogenic bacteria. Required to initiate innate and adaptive immune responses against dissemination of commensal fungi (mycobiota) component of the gut: expressed in mononuclear phagocytes (MNPs) and acts by promoting induction of antifungal IgG antibodies response to confer protection against disseminated C.albicans or C.auris infection (By similarity). Also acts as a receptor for C-C motif chemokine CCL26, inducing cell chemotaxis (By similarity).
This protein is not N-glycosylated which is unusual for G-protein-coupled receptors.
Belongs to the TRAPP small subunits family. BET3 subfamily.
May play a role in vesicular transport from endoplasmic reticulum to Golgi.
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.
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.
Contains a putative mitochondrial transit peptide at positions 1-20.
In the N-terminal section; belongs to the thiolase-like superfamily. Thiolase family.
Interacts with PEX5; the interaction is essential for peroxisomal import.
Mediates the transfer of all common phospholipids, cholesterol and gangliosides from the endoplasmic reticulum to the plasma membrane (PubMed:9711242). 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.
Belongs to the diacylglycerol acyltransferase family.
Belongs to the small GTPase superfamily. RGK family.
Non-catalytic component of the proteasome.
Highly expressed in intestine, duodenal epithelium, uterus, thymus and adrenal cortex. Lower but significant expression in whole adrenal, lung, spleen, stomach, and kidney. In this latter organ, the receptor is localized in the glomeruli and the transitional epithelium of the renal calyx.
Phosphorylation mediates agonist-mediated desensitization by promoting cytoplasmic retention.
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.
Belongs to the Integrator subunit 3 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 major facilitator superfamily. Organophosphate:Pi antiporter (OPA) (TC 2.A.1.4) family.
Inorganic phosphate and glucose-6-phosphate antiporter. May transport cytoplasmic glucose-6-phosphate into the lumen of the endoplasmic reticulum and translocate inorganic phosphate into the opposite direction. Independent of a lumenal glucose-6-phosphatase. May not play a role in homeostatic regulation of blood glucose levels.
Involved in the synthesis of the GDP-mannose and dolichol-phosphate-mannose required for a number of critical mannosyl transfer reactions.
Belongs to the universal ribosomal protein uL22 family.
Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2 domain.
Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase involved in various cellular processes such as regulation of the B-cell receptor (BCR) signalosome, oxidative stress-induced apoptosis, androgen receptor-dependent transcription regulation, insulin signaling and endothelial cells proliferation. Plays a key role in B-cell activation by regulating BCR-induced NF-kappa-B activation. Mediates the activation of the canonical NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11/CARMA1 at 'Ser-559', 'Ser-644' and 'Ser-652'. Phosphorylation induces CARD11/CARMA1 association with lipid rafts and recruitment of the BCL10-MALT1 complex as well as MAP3K7/TAK1, which then activates IKK complex, resulting in nuclear translocation and activation of NFKB1. Plays a direct role in the negative feedback regulation of the BCR signaling, by down-modulating BTK function via direct phosphorylation of BTK at 'Ser-180', which results in the alteration of BTK plasma membrane localization and in turn inhibition of BTK activity. Involved in apoptosis following oxidative damage: in case of oxidative conditions, specifically phosphorylates 'Ser-36' of isoform p66Shc of SHC1, leading to mitochondrial accumulation of p66Shc, where p66Shc acts as a reactive oxygen species producer. Acts as a coactivator of androgen receptor (ANDR)-dependent transcription, by being recruited to ANDR target genes and specifically mediating phosphorylation of 'Thr-6' of histone H3 (H3T6ph), a specific tag for epigenetic transcriptional activation that prevents demethylation of histone H3 'Lys-4' (H3K4me) by LSD1/KDM1A. In insulin signaling, may function downstream of IRS1 in muscle cells and mediate insulin-dependent DNA synthesis through the RAF1-MAPK/ERK signaling cascade. Participates in the regulation of glucose transport in adipocytes by negatively modulating the insulin-stimulated translocation of the glucose transporter SLC2A4/GLUT4. Phosphorylates SLC2A1/GLUT1, promoting glucose uptake by SLC2A1/GLUT1. Under high glucose in pancreatic beta-cells, is probably involved in the inhibition of the insulin gene transcription, via regulation of MYC expression. In endothelial cells, activation of PRKCB induces increased phosphorylation of RB1, increased VEGFA-induced cell proliferation, and inhibits PI3K/AKT-dependent nitric oxide synthase (NOS3/eNOS) regulation by insulin, which causes endothelial dysfunction. Also involved in triglyceride homeostasis. Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription. Phosphorylates KLHL3 in response to angiotensin II signaling, decreasing the interaction between KLHL3 and WNK4 (By similarity).
Classical (or conventional) PKCs (PRKCA, PRKCB and PRKCG) are activated by calcium and diacylglycerol (DAG) in the presence of phosphatidylserine. Three specific sites; Thr-500 (activation loop of the kinase domain), Thr-642 (turn motif) and Ser-661 (hydrophobic region), need to be phosphorylated for its full activation. Specifically inhibited by enzastaurin (LY317615) (By similarity).
Interacts with PDK1. Interacts in vitro with PRKCBP1. Interacts with PHLPP1 and PHLPP2; both proteins mediate its dephosphorylation. Interacts with KDM1A/LSD1, PKN1 and ANDR (By similarity).
Phosphorylation on 'Thr-499' of isoform beta-I, within the activation loop, renders it competent to autophosphorylate. Subsequent autophosphorylation of Thr-642 maintains catalytic competence, and autophosphorylation on Ser-661 appears to release the kinase into the cytosol. Similarly, isoform beta-II is autophosphorylated on 'Thr-640' and 'Ser-659', subsequent to phosphorylation on Thr-500. Autophosphorylated on other sites i.e. in the N-terminal and hinge regions have no effect on enzyme activity. Phosphorylation at Tyr-662 by SYK induces binding with GRB2 and contributes to the activation of MAPK/ERK signaling cascade (By similarity).
Belongs to the peptidase S1 family. Plasminogen subfamily.
Belongs to the SNF2/RAD54 helicase family. SMARCAL1 subfamily.
Interacts with PPP1CC catalytic subunit of PP1, and associates with glycogen.
Phosphorylation at Ser-48 by ISPK stimulates the dephosphorylation of glycogen synthase and phosphorylase kinase.
Seems to act as a glycogen-targeting subunit for PP1. PP1 is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Plays an important role in glycogen synthesis but is not essential for insulin activation of glycogen synthase (By similarity).
Skeletal muscle, diaphragm and cardiac muscle.
The CBM21 domain is known to be involved in the localization to glycogen and is characteristic of some regulatory subunit of phosphatase complexes.
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.
Heterotetramer containing 2 light chains of S100A10/p11 and 2 heavy chains of ANXA2/p36 (By similarity). Interacts with SCN10A (By similarity). Interacts with TASOR (By similarity).
Involved in pre-mRNA splicing as a component of the spliceosome.
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.
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.
Binds 2 magnesium or manganese ions per subunit.
Enzyme with a broad specificity. Negatively regulates TGF-beta signaling through dephosphorylating SMAD2 and SMAD3, resulting in their dissociation from SMAD4, nuclear export of the SMADs and termination of the TGF-beta-mediated signaling (By similarity). Dephosphorylates PRKAA1 and PRKAA2. Plays an important role in the termination of TNF-alpha-mediated NF-kappa-B activation through dephosphorylating and inactivating IKBKB/IKKB (By similarity).
Monomer (By similarity). Interacts with SMAD2; the interaction dephosphorylates SMAD2 in its C-terminal SXS motif resulting in disruption of the SMAD2/SMAD4 complex, SMAD2 nuclear export and termination of the TGF-beta-mediated signaling. Interacts with SMAD2; the interaction dephosphorylates SMAD2 in its C-terminal SXS motif resulting in disruption of the SMAD2/SMAD4 complex, SMAD2 nuclear export and termination of the TGF-beta-mediated signaling (By similarity). Interacts with the phosphorylated form of IKBKB/IKKB (By similarity).
N-myristoylation is essential for the recognition of its substrates for dephosphorylation.
Belongs to the polyribonucleotide nucleotidyltransferase family.
Interacts (via the C-terminal hemopexin-like domains-containing region) with the integrin alpha-V/beta-3; the interaction promotes vascular invasion in angiogenic vessels and melamoma cells. Interacts (via the C-terminal PEX domain) with TIMP2 (via the C-terminal); the interaction inhibits the degradation activity. Interacts with GSK3B (By similarity).
PEX, the C-terminal non-catalytic fragment of MMP2, posseses anti-angiogenic and anti-tumor properties and inhibits cell migration and cell adhesion to FGF2 and vitronectin. Ligand for integrin alpha-v/beta-3 on the surface of blood vessels (By similarity).
Phosphorylation on multiple sites modulates enzymatic activity. Phosphorylated by PKC in vitro (By similarity).
The propeptide is processed by MMP14 (MT-MMP1) and MMP16 (MT-MMP3) (By similarity). Autocatalytic cleavage in the C-terminal produces the anti-angiogenic peptide, PEX. This processing appears to be facilitated by binding integrinv/beta3 (By similarity).
Ubiquitinous metalloproteinase that is involved in diverse functions such as remodeling of the vasculature, angiogenesis, tissue repair, tumor invasion, inflammation, and atherosclerotic plaque rupture. As well as degrading extracellular matrix proteins, can also act on several nonmatrix proteins such as big endothelial 1 and beta-type CGRP promoting vasoconstriction. Also cleaves KISS at a Gly-|-Leu bond. Appears to have a role in myocardial cell death pathways. Contributes to myocardial oxidative stress by regulating the activity of GSK3beta. Cleaves GSK3beta in vitro. Involved in the formation of the fibrovascular tissues (By similarity).
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.
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.
Belongs to the cyclin family. Cyclin C subfamily.
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.
Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane.
Belongs to the mitochondrion-specific ribosomal protein mL42 family.
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).
Catalyzes the epimerization of the S- and R-forms of NAD(P)HX, a damaged form of NAD(P)H that is a result of enzymatic or heat-dependent hydration. This is a prerequisite for the S-specific NAD(P)H-hydrate dehydratase to allow the repair of both epimers of NAD(P)HX. Accelerates cholesterol efflux from endothelial cells to high-density lipoprotein (HDL) and thereby regulates angiogenesis.
Homodimer. Interacts with APOA1 and APOA2.
Undergoes physiological phosphorylation during sperm capacitation, downstream to PKA activation.
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 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.
Released extracellularly via exosomes, it is a ligand of the natural killer/NK cells receptor NCR3 and stimulates NK cells cytotoxicity. It may thereby trigger NK cells cytotoxicity against neighboring tumor cells and immature myeloid dendritic cells (DC).
Required for the processing of the 27S pre-rRNA.
Belongs to the mitochondrion-specific ribosomal protein mL52 family.
Catalyzes the removal of transit peptides required for the targeting of proteins from the mitochondrial matrix, across the inner membrane, into the inter-membrane space. Known to process the nuclear encoded protein DIABLO.
Heterodimer of 2 subunits, IMMPL1 and IMMPL2.
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 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.
Sulfate transporter which mediates sulfate uptake into chondrocytes in order to maintain adequate sulfation of proteoglycans which is needed for cartilage development. Mediates electroneutral anion exchange of sulfate ions for oxalate ions, sulfate and oxalate ions for chloride and/or hydroxyl ions and chloride ions for bromide, iodide and nitrate ions. The coupling of sulfate transport to both hydroxyl and chloride ions likely serves to ensure transport at both acidic pH when most sulfate uptake is mediated by sulfate-hydroxide exchange and alkaline pH when most sulfate uptake is mediated by sulfate-chloride exchange. Essential for chondrocyte proliferation, differentiation and cell size expansion.
Belongs to the cytochrome c oxidase VIIb family.
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.
Belongs to the phosphoglycerate kinase family.
Belongs to the GTP cyclohydrolase I family.
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.
Belongs to the eukaryotic initiation factor 4G family.
Lactose synthase (LS) is a heterodimer of a catalytic component, beta1,4-galactosyltransferase (beta4Gal-T1) and a regulatory component, alpha-lactalbumin (LA).
Regulatory subunit of lactose synthase, changes the substrate specificity of galactosyltransferase in the mammary gland making glucose a good acceptor substrate for this enzyme. This enables LS to synthesize lactose, the major carbohydrate component of milk. In other tissues, galactosyltransferase transfers galactose onto the N-acetylglucosamine of the oligosaccharide chains in glycoproteins.
Belongs to the glycerate kinase type-2 family.
Belongs to the calcium channel beta subunit family.
Beta subunit of voltage-dependent calcium channels which contributes to the function of the calcium channel by increasing peak calcium current (By similarity). Plays a role in shifting voltage dependencies of activation and inactivation of the channel. May modulate G protein inhibition (By similarity). May contribute to beta-adrenergic augmentation of Ca(2+) influx in cardiomyocytes, thereby regulating increases in heart rate and contractile force (By similarity). Involved in membrane targeting of the alpha-1 subunit CACNA1C (By similarity).
Component of a calcium channel complex consisting of a pore-forming alpha subunit (CACNA1S) and the ancillary subunits CACNB1 or CACNB2, CACNG1 and CACNA2D1 (PubMed:15134636). The channel complex contains alpha, beta, gamma and delta subunits in a 1:1:1:1 ratio, i.e. it contains either CACNB1 or CACNB2 (By similarity). Interacts with CACNA1C (PubMed:22649239). Interacts with RRAD; interaction may be involved in beta-adrenergic regulation of heart rate and contractile force (By similarity). Interaction with RRAD regulates the trafficking of CACNA1C to the cell membrane. Interacts with TMIGD2 (By similarity). Interacts with CAMK2D. Interacts with CBARP (By similarity). Interacts with CAMK2A (By similarity).
Predominantly expressed in heart, aorta and brain.
Regulated through phosphorylation at Thr-526 by CaMK2D.
Cytokine that binds to TNFRSF4. Co-stimulates T-cell proliferation and cytokine production.
Belongs to the metallo-beta-lactamase superfamily. RNA-metabolizing metallo-beta-lactamase-like family. CPSF2/YSH1 subfamily.
Belongs to the DNA mismatch repair MutS family.
Component of the post-replicative DNA mismatch repair system (MMR).
Required for S phase entry of the cell cycle.
Involved in the early part of the secretory pathway.
Positive regulator of amino acid starvation-induced autophagy.
Belongs to the teashirt C2H2-type zinc-finger protein family.
Identified in the spliceosome C complex. Found in the Intron Large (IL) complex, a post-mRNA release spliceosomal complex containing the excised intron, U2, U5 and U6 snRNPs, and splicing factors. Interacts with TUFT1. Interacts with DHX15; indicative for a recruitment of DHX15 to the IL complex. Interacts with GCFC2 (By similarity).
Involved in pre-mRNA splicing, specifically in spliceosome disassembly during late-stage splicing events. Intron turnover seems to proceed through reactions in two lariat-intron associated complexes termed Intron Large (IL) and Intron Small (IS). In cooperation with DHX15 seems to mediate the transition of the U2, U5 and U6 snRNP-containing IL complex to the snRNP-free IS complex leading to efficient debranching and turnover of excised introns. May play a role in the differentiation of ameloblasts and odontoblasts or in the forming of the enamel extracellular matrix (By similarity).
Belongs to the KIF-binding protein family.
Belongs to the G-alpha family. G(i/o/t/z) subfamily.
Interacts with KNTC1 and ZW10. These interactions appear weak and may be transient or indirect.
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. Also required for correct spindle orientation. Does not appear to be required for the removal of spindle assembly checkpoint (SAC) proteins from the kinetochore upon bipolar spindle attachment.
Belongs to the bacterial ribosomal protein bL19 family.
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.
Induces fibroblasts to differentiate into myoblasts. Acts as a transcriptional activator that promotes transcription of muscle-specific target genes and plays a role in muscle differentiation.
Homodimer. Interacts with APOC2; the interaction activates LPL activity in the presence of lipids.
Key enzyme in triglyceride metabolism. Catalyzes the hydrolysis of triglycerides from circulating chylomicrons and very low density lipoproteins (VLDL), and thereby plays an important role in lipid clearance from the blood stream, lipid utilization and storage. Mediates margination of triglyceride-rich lipoprotein particles in capillaries. Recruited to its site of action on the luminal surface of vascular endothelium by binding to GPIHBP1 and cell surface heparan sulfate proteoglycans.
Tyrosine nitration after lipopolysaccharide (LPS) challenge down-regulates the lipase activity.
Negative regulator of sphingolipid synthesis.
Monomer. Interacts with AZGP1 (By similarity).
Although the final Cys may be farnesylated, the terminal tripeptide is probably not removed, and the C-terminus is not methylated.
Belongs to the phosphorylase b kinase regulatory chain family.
By phosphorylation of various serine residues and by calcium.
Cys-1234 is farnesylated, but the C-terminal tripeptide is not removed and the cysteine carboxyl is not methylated.
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.
Isoform 1 predominates in muscle, heart, brain and testis. Isoforms 1 and 2 are expressed in similar quantities in the other tissues. Isoform 3 is highly expressed in slow muscle and heart.
Phosphorylase b kinase catalyzes the phosphorylation of serine in certain substrates, including troponin I. The alpha chain may bind calmodulin.
Phosphorylation of Ser-1018 by PKA stimulates the dephosphorylation of the beta subunit and, thus, reverses the initial stimulation of PHK by the faster beta-subunit phosphorylation by PKA, that occurs in muscle in response to adrenaline.
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 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).
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.
Involved in communication between the T-tubular and junctional sarcoplasmic reticulum (SR) membranes.
Was named 'Mitsugumin' which means 'triad junction' in Japanese as it was identified in the triad junctions in skeletal muscle.
Belongs to the calcium channel subunit alpha-2/delta family.
Binds gabapentin, an antiepileptic drug.
Dimer formed of alpha-2-1 and delta-1 chains; disulfide-linked. Voltage-dependent calcium channels are multisubunit complexes, consisting of alpha-1 (CACNA1), alpha-2 (CACNA2D), beta (CACNB) and delta (CACNA2D) subunits in a 1:1:1:1 ratio.
Proteolytically processed into subunits alpha-2-1 and delta-1 that are disulfide-linked.
The MIDAS-like motif in the VWFA domain binds divalent metal cations and is required to promote trafficking of the alpha-1 (CACNA1) subunit to the plasma membrane by an integrin-like switch.
The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel (By similarity). Plays an important role in excitation-contraction coupling (By similarity).
Expressed at high level in spleen. Expressed at lower level in thymus, heart, lung, liver, kidney, ileum, blood and adherent alveolar macrophage cells.
Receptor for bile acid. Bile-acid binding induces its internalization, activation of extracellular signal-regulated kinase and intracellular cAMP production. May be involved in the suppression of macrophage functions by bile acids. Involved in bile acid promoted GLP1R secretion (By similarity).
Belongs to the Mediator complex subunit 6 family.
Found in a complex with LRP6, CCNY and CAPRIN2 during G2/M stage; CAPRIN2 functions as a scaffold for the complex by binding to CCNY via its N terminus and to CDK14 via its C terminus. Interacts with CCNY; CCNY mediates its recruitment to the plasma membrane and promotes phosphorylation of LRP6. Interacts with CCDN3 and CDKN1A. Interacts with SEPT8. Interacts with 14-3-3 proteina YWHAB, YWHAE, YWHAH and YWHAQ.
Serine/threonine-protein kinase activity is promoted by associated cyclins CCDN3 and CCNY and repressed by CDKN1A.
Serine/threonine-protein kinase involved in the control of the eukaryotic cell cycle, whose activity is controlled by an associated cyclin. Acts as a cell-cycle regulator of Wnt signaling pathway during G2/M phase by mediating the phosphorylation of LRP6 at 'Ser-1490', leading to the activation of the Wnt signaling pathway. Acts as a regulator of cell cycle progression and cell proliferation via its interaction with CCDN3. Phosphorylates RB1 in vitro, however the relevance of such result remains to be confirmed in vivo. May also play a role in meiosis, neuron differentiation and may indirectly act as a negative regulator of insulin-responsive glucose transport (By similarity).
Belongs to the ALG6/ALG8 glucosyltransferase family.
Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. Suvar3-9 subfamily.
Does not seem to be a disulfide isomerase.
Mediates the endoplasmic reticulum-associated degradation (ERAD) of inositol 1,4,5-trisphosphate receptors (IP3Rs). Involved in regulation of cellular cholesterol homeostasis by regulation the SREBP signaling pathway.
A scaffold protein that connects plasma membrane proteins and regulatory components, regulating their surface expression in epithelial cells apical domains. May be involved in the coordination of a diverse range of regulatory processes for ion transport and second messenger cascades. In complex with NHERF1, may cluster proteins that are functionally dependent in a mutual fashion and modulate the trafficking and the activity of the associated membrane proteins. May play a role in the cellular mechanisms associated with multidrug resistance through its interaction with ABCC2 and PDZK1IP1. May potentiate the CFTR chloride channel activity. Required for normal cell-surface expression of SCARB1. Plays a role in maintaining normal plasma cholesterol levels via its effects on SCARB1. Plays a role in the normal localization and function of the chloride-anion exchanger SLC26A6 to the plasma membrane in the brush border of the proximal tubule of the kidney. May be involved in the regulation of proximal tubular Na(+)-dependent inorganic phosphate cotransport therefore playing an important role in tubule function (By similarity).
Highly expressed in the brush border membrane of duodenal and ileal mucosa.
Interaction with the C-terminus of CFTR could be mediated through independent binding of PDZ 1, 3 and 4 domains.
Interacts with PDZK1IP1 and ABCC2. Interacts (via PDZ domains 1 and 3) with SCARB1 (C-terminal domain). Forms a heterodimeric complex with NHERF1. Interacts with AKAP2, BCR, CFTR, SLCO1A1, SLC22A12, SLC22A4, SLC22A5, NHERF2 and SLC17A1. Component of a complex, composed of PDZK1, SYNGAP1, KLHL17 and NMDA receptors. Interacts (via PDZ1 domain) directly with KLHL17; the interaction is important for integrity of actin cytoskeleton structures in neurons. Interacts (via C-terminal PDZ domain) with SLC9A3 (via C-terminal domain). Interacts (via the first PDZ domain) with PTGIR (via non-isoprenylated C-terminus) (By similarity). Binds to the C-terminal region of SLC26A3. Interacts (via C-terminal PDZ domain) with SLC26A6 (via C-terminal domain). Interacts (via PDZ domains 1 and 3) with SLC5A8 (via PDZ-binding motif); interaction increases nicotinate transport activity of SLC5A8 (By similarity).
The PDZ 1 and 3 domains seem to be involved in the interaction with SLCO1A1.
The PDZ 2 and 3 domains seem to be involved in the interaction with SLC26A3.
The PDZ 2 and 4 domains do not interact with the C-terminal region of SCARB1.
Stabilizes the cyclin H-CDK7 complex to form a functional CDK-activating kinase (CAK) enzymatic complex.
Belongs to the potassium channel family. A (Shaker) (TC 1.A.1.2) subfamily. Kv1.4/KCNA4 sub-subfamily.
Seems to promote the survival of visceral and proprioceptive sensory neurons.
Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. May play a role in changing or maintaining the spatial distribution of cytoskeletal structures (By similarity).
Belongs to the dynein light chain family.
Binds and inhibits the catalytic activity of neuronal nitric oxide synthase/NOS1.
Homodimer. Monomer; the monomeric form is incapable of binding to target proteins. The cytoplasmic dynein 1 complex consists of two catalytic heavy chains (HCs) and a number of non-catalytic subunits presented by intermediate chains (ICs), light intermediate chains (LICs) and light chains (LCs); the composition seems to vary in respect to the IC, LIC and LC composition. The heavy chain homodimer serves as a scaffold for the probable homodimeric assembly of the respective non-catalytic subunits. The ICs and LICs bind directly to the HC dimer and the LCs assemble on the IC dimer. Interacts with TXNDC17. Interacts with WWC1 and ESR1. The interaction with WWC1 is mandatory for the recruitment and transactivation functions of ESR1 or DYNLL1 to the target chromatin. Interacts with BCL2L11 isoform 1 and isoform 2. Interacts with BCL2; the interaction is greatly enhanced in the nucleus and in mitochondria upon induction of apoptosis. Interacts with PAK1; the interaction requires dimeric DYNLL1. Interacts with MYZAP. Part of an astrin (SPAG5)-kinastrin (SKAP) complex containing KNSTRN, SPAG5, PLK1, DYNLL1 and SGO2. Interacts with ATMIN; this interaction inhibits ATMIN transcriptional activity and hence may play a role in a feedback loop whereby DYNLL1 inhibits transactivation of its own promoter by ATMIN. Interacts with NEK9 (not phosphorylated at 'Ser-944'). Interacts with BICD2. Interacts with BCAS1. Interacts with Bassoon/BSN (By similarity). Interacts with HDAC6 (By similarity). Interacts with TPPP (By similarity). Interacts with AMBRA1 (via TQT motifs); tethering AMBRA1 to the cytoskeleton (By similarity). Interacts with FAM83D/CHICA (via C-terminus) (By similarity). Interacts with HMMR, SPAG5/Astrin and KNSTRN/Kinastrin (By similarity). Interacts with TLK2 (By similarity). Interacts with NOS1 (By similarity).
Phosphorylation at Ser-88 appears to control the dimer-monomer transition.
Promotes transactivation functions of ESR1 and plays a role in the nuclear localization of ESR1.
Regulates apoptotic activities of BCL2L11 by sequestering it to microtubules. Upon apoptotic stimuli the BCL2L11-DYNLL1 complex dissociates from cytoplasmic dynein and translocates to mitochondria and sequesters BCL2 thus neutralizing its antiapoptotic activity (By similarity).
Binds to various kinds of negatively charged substances such as heparin, phospholipids, and dextran sulfate. May prevent activation of the intrinsic blood coagulation cascade by binding to phospholipids on the surface of damaged cells.
Belongs to the complex I 75 kDa subunit family.
Component of the STAGA transcription coactivator-HAT complex, at least composed of SUPT3H, GCN5L2, TAF5L, TAF6L, SUPT7L, TADA3L, TAD1L, TAF10, TAF12, TRRAP and TAF9.
Probably involved in transcriptional regulation.
Belongs to the clathrin light chain family.
Interacts with PTBP2; the interaction is direct.
Expressed in renal distal tubules, especially in cortical collecting duct and cortical thick ascending limb, with lower levels in the connecting tubule.
Homodimer; disulfide-linked (By similarity). Heterodimer with KCNK2; disulfide-linked (By similarity). In astrocytes, forms mostly heterodimeric potassium channels with KCNK2, with only a minor proportion of functional channels containing homodimeric KCNK1 (By similarity). Interacts with KCNK3 and KCNK9, forming functional heterodimeric channels (By similarity). Interacts with GNG4 (By similarity). Identified in a complex with PSD and ARF6; interacts only with PSD that is bound to ARF6 (By similarity). Interacts with UBE2I (By similarity).
Ion channel that contributes to passive transmembrane potassium transport and to the regulation of the resting membrane potential in brain astrocytes, but also in kidney and in other tissues. Forms dimeric channels through which potassium ions pass in accordance with their electrochemical gradient. The channel is selective for K(+) ions at physiological potassium concentrations and at neutral pH, but becomes permeable to Na(+) at subphysiological K(+) levels and upon acidification of the extracellular medium. The homodimer has very low potassium channel activity, when expressed in heterologous systems, and can function as weakly inward rectifying potassium channel (By similarity). Channel activity is modulated by activation of serotonin receptors (By similarity). Heterodimeric channels containing KCNK1 and KCNK2 have much higher activity, and may represent the predominant form in astrocytes (By similarity). Heterodimeric channels containing KCNK1 and KCNK3 or KCNK9 have much higher activity. Heterodimeric channels formed by KCNK1 and KCNK9 may contribute to halothane-sensitive currents (By similarity). Mediates outward rectifying potassium currents in dentate gyrus granule cells and contributes to the regulation of their resting membrane potential (By similarity). Contributes to the regulation of action potential firing in dentate gyrus granule cells and down-regulates their intrinsic excitability (By similarity). In astrocytes, the heterodimer formed by KCNK1 and KCNK2 is required for rapid glutamate release in response to activation of G-protein coupled receptors, such as F2R and CNR1 (By similarity). Required for normal ion and water transport in the kidney (By similarity). Contributes to the regulation of the resting membrane potential of pancreatic beta cells (By similarity). The low channel activity of homodimeric KCNK1 may be due to sumoylation. The low channel activity may be due to rapid internalization from the cell membrane and retention in recycling endosomes (By similarity).
Sumoylation is controversial. Sumoylated by UBE2I. Not sumoylated when expressed in xenopus oocytes or mammalian cells. Sumoylation inactivates the channel, but does not interfere with expression at the cell membrane. Sumoylation of a single subunit is sufficient to silence the dimeric channel. Sumoylation of KCNK1 is sufficient to silence heterodimeric channels formed by KCNK1 and KCNK3 or KCNK9. Desumoylated by SENP1; this activates the channel. Desumoylated by SENP1; this strongly increases halothane-mediated activation of heterodimeric channels formed with KCNK9. SENP1 treatment has no effect.
Belongs to the complex I subunit 4L 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.
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. Important for saturated C24:0 and monounsaturated C24:1 sphingolipid synthesis. Indirectly inhibits RPE65 via production of VLCFAs.
Interacts with LASS2, TECR and HSD17B12.
The C-terminal di-lysine motif may confer endoplasmic reticulum localization.
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.
Associates with the RNA polymerase II complex.
Interacts with phosphorylated C-terminal heptapeptide repeat domain (CTD) of the largest RNA polymerase II subunit POLR2A, and participates in dephosphorylation of the CTD.
Cytochrome P450 monooxygenase that catalyzes regio- and stereospecific hydroxylation of cholesterol and its derivatives. Hydroxylates (with R stereochemistry) the terminal methyl group of cholesterol side-chain in a three step reaction to yield at first a C26 alcohol, then a C26 aldehyde and finally a C26 acid (By similarity). Regulates cholesterol homeostasis by catalyzing the conversion of excess cholesterol to bile acids via both the 'neutral' (classic) and the 'acid' (alternative) pathways (PubMed:2722778). May also regulate cholesterol homeostasis via generation of active oxysterols, which act as ligands for NR1H2 and NR1H3 nuclear receptors, modulating the transcription of genes involved in lipid metabolism. Plays a role in cholestanol metabolism in the cerebellum. Similarly to cholesterol, hydroxylates cholestanol and may facilitate sterol diffusion through the blood-brain barrier to the systemic circulation for further degradation. Also hydroxylates retinal 7-ketocholesterol, a noxious oxysterol with pro-inflammatory and pro-apoptotic effects, and may play a role in its elimination from the retinal pigment epithelium. May play a redundant role in vitamin D biosynthesis. Catalyzes 25-hydroxylation of vitamin D3 that is required for its conversion to a functionally active form (By similarity).
Expressed in all tissues tested. Highest expression in liver and duodenum, followed by adrenal gland and lung. Low expression in kidney and spleen.
Interacts with HSP70; this interaction is required for initial targeting to mitochondria.
Specifically recognizes and binds N6-methyladenosine (m6A)-containing RNAs, and regulates mRNA stability. M6A is a modification present at internal sites of mRNAs and some non-coding RNAs and plays a role in mRNA stability and processing.
Adapter protein in a cytoplasmic complex linking beta-integrins to the actin cytoskeleton, bridges the complex to cell surface receptor tyrosine kinases and growth factor receptors.
Part of the heterotrimeric IPP complex composed of integrin-linked kinase (ILK), LIMS1 or LIMS2, and PARVA.
Belongs to the complex I 24 kDa subunit family.
Core subunit of respiratory chain NADH dehydrogenase (Complex I) which is composed of 45 different subunits. This is a component of the flavoprotein-sulfur (FP) fragment of the enzyme.
Centrosomal protein involved in regulation of centriole duplication. Required to limit centriole duplication to once per cell cycle by preventing centriole reduplication.
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.
Component of the membrane attack complex (MAC). MAC assembly is initiated by proteolytic cleavage of C5 into C5a and C5b. C5b binds sequentially C6, C7, C8 and multiple copies of the pore-forming subunit C9. About 20 C9 chains oligomerize to give rise to a huge beta-barrel that forms a 100 Angstrom diameter pore in target membranes.
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. C9 is the pore-forming subunit of the MAC.
The structure of the human polymeric form indicates the existence of an additional disulfide bond compared to the mouse monomeric form.
Thrombin cleaves factor C9 to produce C9a and C9b.
Binds pre-mRNA and nucleates the assembly of 40S hnRNP particles. Interacts with poly-U tracts in the 3'-UTR or 5'-UTR of mRNA and modulates the stability and the level of translation of bound mRNA molecules. Single HNRNPC tetramers bind 230-240 nucleotides. Trimers of HNRNPC tetramers bind 700 nucleotides. May play a role in the early steps of spliceosome assembly and pre-mRNA splicing. N6-methyladenosine (m6A) has been shown to alter the local structure in mRNAs and long non-coding RNAs (lncRNAs) via a mechanism named 'm(6)A-switch', facilitating binding of HNRNPC, leading to regulation of mRNA splicing.
Phosphorylated on Ser-260 and Ser-299 in resting cells.
Sumoylated. Sumoylation reduces affinity for mRNA.
Tetramer composed of 3 copies of isoform C1 and 1 copy of isoform C2. Assembly of 3 tetramers with bound pre-mRNA gives rise to a 19S complex that interacts with HNRNPA2B1 tetramers. Component of the 40S hnRNP particle. Identified in the spliceosome C complex. Interacts with IGF2BP1 (By similarity). Interacts with PPIA/CYPA (By similarity).
Belongs to the transient receptor (TC 1.A.4) family. STrpC subfamily. TRPC5 sub-subfamily.
Calcium channel activity is enhanced by MYLK, that promotes its subcellular localization at the plasma membrane.
Homotetramer and heterotetramer with TRPC1 and/or TRPC4 (By similarity). Interacts with NHERF1 (By similarity). Interacts with MX1 and RNF24 (By similarity). Interacts (via C-terminus) with CABP1 (By similarity). Interacts with SESTD1 (via the spectrin 1 repeat) (By similarity). Interacts with TRPC4AP (By similarity). Interacts with PLSCR1 (By similarity).
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. Has also been shown to be calcium-selective. May also be activated by intracellular calcium store depletion (By similarity). Mediates calcium-dependent phosphatidylserine externalization and apoptosis in neurons via its association with PLSCR1 (By similarity).
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.
APOD occurs in the macromolecular complex with lecithin-transport and binding of bilin. Appears to be able to transport a variety of ligands in a number of different contexts.
Most heavily expressed in adrenal gland, lung, brain, testis and spleen.
Belongs to the bile acid:sodium symporter (BASS) (TC 2.A.28) family.
Receptor for the neuromedin-U and neuromedin-S neuropeptides.
Belongs to the archaeal Rpo3/eukaryotic RPB3 RNA polymerase subunit family.
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.
Belongs to the eukaryotic ribosomal protein eL8 family.
Common component of the spliceosome and rRNA processing machinery.
Belongs to the poly(ADP-ribose) glycohydrolase family.
Involved in the second step of GPI biosynthesis. De-N-acetylation of N-acetylglucosaminyl-phosphatidylinositol.
May regulate cell proliferation and coordinate apoptosis and cell cycle progression via a novel mechanism independent of both p53/TP53 and NF-kappa-B.
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.
Component of the ER membrane protein complex (EMC).
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 dynein intermediate chain family.
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 metallo-dependent hydrolases superfamily. ACMSD family.
Converts alpha-amino-beta-carboxymuconate-epsilon-semialdehyde (ACMS) to alpha-aminomuconate semialdehyde (AMS). ACMS can be converted non-enzymatically to quinolate (QA), a key precursor of NAD, and a potent endogenous excitotoxin of neuronal cells which is implicated in the pathogenesis of various neurodegenerative disorders. In the presence of ACMSD, ACMS is converted to AMS, a benign catabolite. ACMSD ultimately controls the metabolic fate of tryptophan catabolism along the kynurenine pathway.
Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.
Belongs to the protein kinase superfamily. ADCK protein kinase family.
Belongs to the eukaryotic ribosomal protein eL27 family.
Belongs to the universal ribosomal protein uS19 family.
Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type V subfamily.
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.
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 glycosyl hydrolase 18 family. Chitinase class II subfamily.
Belongs to the casein kinase 2 subunit beta family.
Casein kinase II/CK2 is a tetramer composed of an alpha subunit, an alpha' subunit and two beta subunits. The beta subunit dimerization is mediated by zinc ions. Interacts with DYNLT2 (By similarity). Interacts with CD163. Also a component of a CK2-SPT16-SSRP1 complex composed of SSRP1, SUPT16H, CSNK2A1, CSNK2A2 and CSNK2B, the complex associating following UV irradiation. Interacts with MUSK; mediates phosphorylation of MUSK by CK2. Interacts with FGF1; this interaction is increased in the presence of FIBP, suggesting a possible cooperative interaction between CSNKB and FIBP in binding to FGF1 (By similarity). Interacts (via KSSR motif) with ARK2N. Interacts with JUN and ARK2N; mediates the interaction between ARK2N and JUN (By similarity).
Phosphorylated by alpha subunit. Also a component of a CK2-SPT16-SSRP1 complex composed of SSRP1, SUPT16H, CSNK2A1, CSNK2A2 and CSNK2B, the complex associating following UV irradiation (By similarity).
Regulatory subunit of casein kinase II/CK2. As part of the kinase complex regulates the basal catalytic activity of the alpha subunit a constitutively active serine/threonine-protein kinase that phosphorylates a large number of substrates containing acidic residues C-terminal to the phosphorylated serine or threonine (By similarity). Participates in Wnt signaling (By similarity).
The KSSR motif is part of a protein interaction pocket that mediates interaction with cellular and viral proteins.
Belongs to the prickle / espinas / testin family.
Belongs to the potassium channel family. A (Shaker) (TC 1.A.1.2) subfamily. Kv1.5/KCNA5 sub-subfamily.
Homotetramer and heterotetramer of potassium channel proteins. Interacts with DLG1, which enhances channel currents. Forms a ternary complex with DLG1 and CAV3 (By similarity). Interacts with KCNAB1 (By similarity). Interacts with UBE2I (By similarity).
The amino terminus may be important in determining the rate of inactivation of the channel while the C-terminal PDZ-binding motif may play a role in modulation of channel activity and/or targeting of the channel to specific subcellular compartments. Interacts with UBE2I.
Voltage-gated potassium channel that mediates transmembrane potassium transport in excitable membranes. Forms tetrameric potassium-selective channels through which potassium ions pass in accordance with their electrochemical gradient. The channel alternates between opened and closed conformations in response to the voltage difference across the membrane (PubMed:7556635). Can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA5, and possibly other family members as well; channel properties depend on the type of alpha subunits that are part of the channel (By similarity). Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation (PubMed:7556635). Homotetrameric channels display rapid activation and slow inactivation (PubMed:7556635). May play a role in regulating the secretion of insulin in normal pancreatic islets (By similarity).
Belongs to the pyrroline-5-carboxylate reductase family.
Homotetramer. Dimer of dimers. In the homotetramer, subunits assemble around a central channel that can accommodate two ligand molecules. Interacts with RBP4.
Thyroid hormone-binding protein. Probably transports thyroxine from the bloodstream to the brain.
Acts as a molecular chaperone for PCSK2/PC2, preventing its premature activation in the regulated secretory pathway. Binds to inactive PCSK2 in the endoplasmic reticulum and facilitates its transport from there to later compartments of the secretory pathway where it is proteolytically matured and activated. Also required for cleavage of PCSK2 but does not appear to be involved in its folding. Plays a role in regulating pituitary hormone secretion. The C-terminal peptide inhibits PCSK2 in vitro.
Interacts with PCSK2/PC2 early in the secretory pathway. Dissociation occurs at later stages.
Belongs to the HAD-like hydrolase superfamily. PHOSPHO family.
Belongs to the cytidine and deoxycytidylate deaminase family.
Cytidine deaminase catalyzing the cytidine to uridine postranscriptional editing of a variety of mRNAs (PubMed:8063816). Form complexes with cofactors that confer differential editing activity and selectivity. Responsible for the postranscriptional editing of a CAA codon for Gln to a UAA codon for stop in the apolipoprotein B mRNA. Also involved in CGA (Arg) to UGA (Stop) editing in the NF1 mRNA (By similarity). May also play a role in the epigenetic regulation of gene expression by participating in DNA demethylation (By similarity).
Homodimer. Interacts with A1CF; form an mRNA editing complex. Interacts with RBM47; form an mRNA editing complex. Found in a complex with CELF2/CUGBP2 and A1CF. Interacts with HNRPAB. Interacts with SYNCRIP.
Belongs to the DNA repair metallo-beta-lactamase (DRMBL) family.
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.
Intestine, and to a lesser extent in kidney.
Belongs to the protein-tyrosine phosphatase family. Non-receptor class 4 subfamily.
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 actin-binding proteins ADF family. GMF subfamily.
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.
Component of the outer dense fibers (ODF) of spermatozoa. ODF are filamentous structures located on the outside of the axoneme in the midpiece and principal piece of the mammalian sperm tail and may help to maintain the passive elastic structures and elastic recoil of the sperm tail.
Belongs to the universal ribosomal protein uL29 family.
Belongs to the acid sphingomyelinase family.
Belongs to the serpin family. Ov-serpin subfamily.
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.
In the C-terminal section; belongs to the saccharopine dehydrogenase family.
In the N-terminal section; belongs to the AlaDH/PNT family.
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.
Belongs to the PIGG/PIGN/PIGO family. PIGO subfamily.
Belongs to the thiolase-like superfamily. HMG-CoA synthase family.
Catalyzes the condensation of acetyl-CoA with acetoacetyl-CoA to form HMG-CoA.
Inhibitor of bone morphogenetic proteins (BMP) signaling which is required for growth and patterning of the neural tube and somite.
Belongs to the helicase family. RAD25/XPB subfamily.
Belongs to the aspartate/ornithine carbamoyltransferase superfamily.
Activated by cAMP, and at 10-100 times higher concentrations, also by cGMP. cAMP binding promotes tetramerization and formation of an active channel. Compared to other family members, cAMP has less stimulatory effect on HCN1 because part of the molecules already contain bound cAMP and form homotetramers when cAMP levels are low.
Detected in myocytes in heart sinoatrial node (SAN) and in brain, in particular in the granule cell layer and in Purkinje neuron bodies in the cerebellum.
Homotetramer. Heterotetramer with HCN2. The potassium channel is composed of a homo- or heterotetrameric complex of pore-forming subunits. Interacts with KCNE2. Interacts with the SH3 domain of CSK.
Hyperpolarization-activated ion channel exhibiting weak selectivity for potassium over sodium ions. Contributes to the native pacemaker currents in heart (If) and in neurons (Ih). May mediate responses to sour stimuli.
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 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.
Belongs to the bacterial ribosomal protein bL17 family.
Belongs to the 5'(3')-deoxyribonucleotidase family.
Maximally expressed at the beginning of gastrulation.
May play a role in cell differentiation in the intestinal epithelium.
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).
Belongs to the class I-like SAM-binding methyltransferase superfamily. NNMT/PNMT/TEMT family.
Catalyzes the N-methylation of tryptamine and structurally related compounds (By similarity). Functions as thioether S-methyltransferase and is active with a variety of thioethers and the corresponding selenium and tellurium compounds, including 3-methylthiopropionaldehyde, dimethyl selenide, dimethyl telluride, 2-methylthioethylamine, 2-methylthioethanol, methyl-n-propyl sulfide and diethyl sulfide. Plays an important role in the detoxification of selenium compounds (By similarity).
Highly expressed in lung, also detected in liver and at very low levels in brain.
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 bZIP family. ATF subfamily.
Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes monoubiquitination and 'Lys-48'-linked polyubiquitination. May be involved in degradation of katenin.
Was originally thought to be UBE2R1/CDC34.
When phosphorylated, interacts with beta-TrCP (BTRC).
Belongs to the complex I NDUFB11 subunit family.
Belongs to the cytidine and deoxycytidylate deaminase family. ADAT2 subfamily.
Probably participates in deamination of adenosine-34 to inosine in many tRNAs.
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.
Activated by pro-inflammatory cytokines and in response to physical and chemical stresses, including osmotic stress, oxidative stress, arsenic and ultraviolet light irradiation. Activated by 'Lys-63'-linked polyubiquitination and by autophosphorylation.
Belongs to the ABC transporter superfamily. ABCB family. Multidrug resistance exporter (TC 3.A.1.201) subfamily.
Catalyzes the transport of the major hydrophobic bile salts, such as taurine and glycine-conjugated cholic acid across the canalicular membrane of hepatocytes in an ATP-dependent manner, therefore participates in hepatic bile acid homeostasis and consequently to lipid homeostasis through regulation of biliary lipid secretion in a bile salts dependent manner. Transports taurine-conjugated bile salts more rapidly than glycine-conjugated bile salts. Also transports non-bile acid compounds, such as pravastatin and fexofenadine in an ATP-dependent manner and may be involved in their biliary excretion.
Expressed predominantly, if not exclusively in the liver, where it was further localized to the canalicular microvilli and to subcanalicular vesicles of the hepatocytes by in situ.
Interacts with HAX1 (By similarity). Interacts with the adapter protein complex 2 (AP-2) throught AP2A2 or AP2A1; this interaction regulates cell membrane expression of ABCB11 through its internalization in a clathrin-dependent manner and its subsequent degradation (By similarity).
Multifunctional polypeptide with two homologous halves, each containing a hydrophobic membrane-anchoring domain and an ATP binding cassette (ABC) domain.
The uptake of taurocholate is inhibited by taurolithocholate sulfate with an IC(50) of 9 uM. Pravastatin competitively inhibits the transport of taurocholic acid. Cyclosporin A, glibenclamide, rifampicin and troglitazonestrongly competitively inhibit the transport activity of taurocholate. The canalicular transport activity of taurocholate is strongly dependent on canalicular membrane cholesterol content. The uptake of taurocholate is increased by short- and medium-chain fatty acids. Cholesterol increases transport capacity of taurocholate without affecting the affinity for the substrate.
Ubiquitinated; short-chain ubiquitination regulates cell-Surface expression of ABCB11.
Endothelins are endothelium-derived vasoconstrictor peptides.
Belongs to the potassium channel family. D (Shal) (TC 1.A.1.2) subfamily. Kv4.3/KCND3 sub-subfamily.
Detected in carotid body chemoreceptor cells and in frontal cortex.
Homotetramer or heterotetramer with KCND1 and/or KCND2. Associates with the regulatory subunits KCNIP1, KCNIP2, KCNIP3 and KCNIP4. Interacts with DLG1, KCNE1, KCNE2, SCN1B and KCNAB1 (By similarity).
Pore-forming (alpha) subunit of voltage-gated rapidly inactivating A-type potassium channels. May contribute to I(To) current in heart and I(Sa) current in neurons. Channel properties are modulated by interactions with other alpha subunits and with regulatory subunits.
Regulated through phosphorylation at Ser-569 by CaMK2D.
Arginine methyltransferase involved in the assembly or stability of mitochondrial NADH:ubiquinone oxidoreductase complex (complex I).
Belongs to the SLC35F solute transporter family.
Involved in oxygen transport in the brain. Hexacoordinate globin, displaying competitive binding of oxygen or the distal His residue to the iron atom. Not capable of penetrating cell membranes (By similarity).
Monomer. Homodimer and homotetramer; disulfide-linked.
Has peptide-independent ATPase activity.
Belongs to the acyl carrier protein (ACP) family.
Carrier of the growing fatty acid chain in fatty acid biosynthesis.
Homodimer; disulfide-linked. May form a hexamer composed of 3 homodimers. Interacts with HSP70 (By similarity).
Overexpressed in atherosclerotic lesions.
Receptor that mediates the recognition, internalization and degradation of oxidatively modified low density lipoprotein (oxLDL) by vascular endothelial cells. OxLDL is a marker of atherosclerosis that induces vascular endothelial cell activation and dysfunction, resulting in pro-inflammatory responses, pro-oxidative conditions and apoptosis. Its association with oxLDL induces the activation of NF-kappa-B through an increased production of intracellular reactive oxygen and a variety of pro-atherogenic cellular responses including a reduction of nitric oxide (NO) release, monocyte adhesion and apoptosis. In addition to binding oxLDL, it acts as a receptor for the HSP70 protein involved in antigen cross-presentation to naive T-cells in dendritic cells, thereby participating in cell-mediated antigen cross-presentation. Also involved in inflammatory process, by acting as a leukocyte-adhesion molecule at the vascular interface in endotoxin-induced inflammation. Also acts as a receptor for advanced glycation end (AGE) products, activated platelets, monocytes, apoptotic cells and both Gram-negative and Gram-positive bacteria (By similarity).
The C-type lectin domain mediates the recognition and binding of oxLDL.
The cytoplasmic region is required for subcellular sorting on the cell surface.
Cleavage by granzyme B, caspase-6, caspase-8 and caspase-10 generates the two active subunits. Additional processing of the propeptides is likely due to the autocatalytic activity of the activated protease. Active heterodimers between the small subunit of caspase-7 protease and the large subunit of caspase-3 also occur and vice versa.
Heterotetramer that consists of two anti-parallel arranged heterodimers, each one formed by a 17 kDa (p17) and a 12 kDa (p12) subunit. Interacts with BIRC6/bruce.
Involved in the activation cascade of caspases responsible for apoptosis execution. At the onset of apoptosis, it proteolytically cleaves poly(ADP-ribose) polymerase PARP1 at a '216-Asp-|-Gly-217' bond. Cleaves and activates sterol regulatory element binding proteins (SREBPs) between the basic helix-loop-helix leucine zipper domain and the membrane attachment domain. Cleaves and activates caspase-6, -7 and -9. Triggers cell adhesion in sympathetic neurons through RET cleavage (By similarity). Cleaves IL-1 beta between an Asp and an Ala, releasing the mature cytokine which is involved in a variety of inflammatory processes (By similarity). Cleaves and inhibits serine/threonine-protein kinase AKT1 in response to oxidative stress. Acts as an inhibitor of type I interferon production during virus-induced apoptosis by mediating cleavage of antiviral proteins CGAS, IRF3 and MAVS, thereby preventing cytokine overproduction. Also involved in pyroptosis by mediating cleavage and activation of gasdermin-E (GSDME) (By similarity). Cleaves XRCC4 and phospholipid scramblase proteins XKR4, XKR8 and XKR9, leading to promote phosphatidylserine exposure on apoptotic cell surface (By similarity).
S-nitrosylated on its catalytic site cysteine in unstimulated cell lines and denitrosylated upon activation of the Fas apoptotic pathway, associated with an increase in intracellular caspase activity. Fas therefore activates caspase-3 not only by inducing the cleavage of the caspase zymogen to its active subunits, but also by stimulating the denitrosylation of its active site thiol.
Belongs to the helicase family. RecQ 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.
Receptor for Dickkopf proteins. Cooperates with DKK1/2 to inhibit Wnt/beta-catenin signaling by promoting the endocytosis of Wnt receptors LRP5 and LRP6.
Glycosylation at Asn-628 is necessary both for surface expression and neutral endopeptidase activity.
Inhibited by mixanpril, an orally-active drug used for the treatment of hypertension.
Myristoylation is a determinant of membrane targeting.
Thermolysin-like specificity, but is almost confined on acting on polypeptides of up to 30 amino acids (PubMed:3162886). Biologically important in the destruction of opioid peptides such as Met- and Leu-enkephalins by cleavage of a Gly-Phe bond. Catalyzes cleavage of bradykinin, substance P and neurotensin peptides (By similarity). Able to cleave angiotensin-1, angiotensin-2 and angiotensin 1-9. Involved in the degradation of atrial natriuretic factor (ANF) and brain natriuretic factor (BNP(1-32)) (By similarity). Displays UV-inducible elastase activity toward skin preelastic and elastic fibers (By similarity).
Pulmonary surfactant consists of 90% lipid and 10% protein. There are 4 surfactant-associated proteins: 2 collagenous, carbohydrate-binding glycoproteins (SP-A and SP-D) and 2 small hydrophobic proteins (SP-B and SP-C).
Pulmonary surfactant-associated proteins promote alveolar stability by lowering the surface tension at the air-liquid interface in the peripheral air spaces. SP-B increases the collapse pressure of palmitic acid to nearly 70 millinewtons per meter.
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.
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.
Cytoplasmic adapter regulating receptors of the signaling lymphocytic activation molecule (SLAM) family such as SLAMF1, CD244, LY9, CD84, SLAMF6 and SLAMF7. In SLAM signaling seems to cooperate with SH2D1B/EAT-2.
Identified in the spliceosome C complex. Component of the XAB2 complex, a multimeric protein complex composed of XAB2, PRPF19, AQR, ZNF830, ISY1, and PPIE.
Intron-binding spliceosomal protein required to link pre-mRNA splicing and snoRNP (small nucleolar ribonucleoprotein) biogenesis. Plays a key role in position-dependent assembly of intron-encoded box C/D small snoRNP, splicing being required for snoRNP assembly. May act by helping the folding of the snoRNA sequence. Binds to intron of pre-mRNAs in a sequence-independent manner, contacting the region between snoRNA and the branchpoint of introns (40 nucleotides upstream of the branchpoint) during the late stages of splicing.
Belongs to the damage-control phosphatase family. Sugar phosphate phosphatase III subfamily.
Metal-dependent phosphatase that shows phosphatase activity against several substrates, including fructose-1-phosphate and fructose-6-phosphate. Its preference for fructose-1-phosphate, a strong glycating agent that causes DNA damage rather than a canonical yeast metabolite, suggests a damage-control function in hexose phosphate metabolism. Has also been shown to have O-methyltransferase activity that methylates glutamate residues of target proteins to form gamma-glutamyl methyl ester residues. Possibly methylates PCNA, suggesting it is involved in the DNA damage response.
Subfamily III proteins have a conserved RTxK motif about 40-50 residues from the C-terminus; the threonine may be replaced by serine or cysteine.
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.
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.
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.
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.
Mutarotase that catalyzes the interconversion of beta-D-galactose and alpha-D-galactose during galactose metabolism.
This protein differs from other forms of cytochrome P450 in that it catalyzes the 21-hydroxylation of progesterone, resulting in the formation of deoxycorticosterone.
A cytochrome P450 monooxygenase involved in the metabolism of fatty acids. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates fatty acids specifically at the omega-1 position displaying the highest catalytic activity for saturated fatty acids. May be involved in the oxidative metabolism of xenobiotics.
Interacts with chaperones HSP70 and HSP90; this interaction is required for initial targeting to mitochondria.
The omega-1 hydroxylase activity is stimulated by cytochrome b5.
Part of the multisubunit TRAPP (transport protein particle) complex.
Binds DNA as a homodimer or as a heterodimer with JUN or ATF2/CREBP1.
Binds to the cAMP response element and activates transcription.
Belongs to the DOK family. Type A subfamily.
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.
Protein phosphatase inhibitor that specifically inhibits protein phosphatase 2A (PP2A) during mitosis.
Acetylated on Lys-5, Lys-8 and Lys-12 during interphase. Acetylation disappears at mitosis (By similarity).
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 H2AZ2 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 glucose-6-phosphatase family.
Belongs to the 5'-3' exonuclease family.
Involved in the mineralization and structural organization of enamel.
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).
Putative Notch ligand involved in the mediation of Notch signaling.
Important role in determination of the surface properties of the casein micelles.
Interacts with CTTN/cortactin SH3 domain. Interacts with STRN, STRN4/zinedin and MOB4/phocein; this interaction may regulate dendritic spine distribution of STRN and STRN4 in hippocampal neurons. Activation of glutamate receptors weakens the interaction with STRN and STRN4.
Regulates the dendritic spine distribution of CTTN/cortactin in hippocampal neurons, thus controls dendritic spinogenesis and dendritic spine maintenance.
Belongs to the methyltransferase superfamily. RsmH 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.
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 metallo-dependent hydrolases superfamily. Phosphotriesterase family.
Binds 2 divalent metal cations per subunit.
Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers beta-catenin signaling through inducing aggregation of receptor-ligand complexes into ribosome-sized signalosomes.
Homodimer; disulfide-linked. Forms phosphorylated oligomer aggregates on Wnt-signaling.
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.
In the C-terminal section; belongs to the formate--tetrahydrofolate ligase family.
In the N-terminal section; belongs to the tetrahydrofolate dehydrogenase/cyclohydrolase family.
Belongs to the Ca(2+):cation antiporter (CaCA) (TC 2.A.19) family. SLC24A subfamily.
GTP-binding protein involved in protein trafficking; modulates vesicle budding and uncoating within the Golgi apparatus.
Alkylation of Arg-43 inactivates the enzyme.
Asn-361 in form alpha is deaminated to Asp in form beta.
Homotetramer. Interacts with SNX9 and WAS. Interacts with FBP2; the interaction blocks FBP2 inhibition by physiological concentrations of AMP and reduces inhibition by Ca(2+).
In vertebrates, three forms of this ubiquitous glycolytic enzyme are found, aldolase A in muscle, aldolase B in liver and aldolase C in brain.
Plays a key role in glycolysis and gluconeogenesis. In addition, may also function as scaffolding protein.
Belongs to the protoporphyrinogen/coproporphyrinogen oxidase family. Protoporphyrinogen oxidase subfamily.
Catalyzes the 6-electron oxidation of protoporphyrinogen-IX to form protoporphyrin-IX.
Belongs to the UTP23/FCF1 family. FCF1 subfamily.
Predominantly expressed in osteclasts (bones).
Thiol protease involved in osteoclastic bone resorption and may participate partially in the disorder of bone remodeling. Displays potent endoprotease activity against fibrinogen at acid pH. May play an important role in extracellular matrix degradation. Involved in the release of thyroid hormone thyroxine (T4) by limited proteolysis of TG/thyroglobulin in the thyroid follicle lumen.
Belongs to the AVIT (prokineticin) family.
Subunit of ATP-sensitive potassium channels (KATP). Can form cardiac and smooth muscle-type KATP channels with KCNJ11. KCNJ11 forms the channel pore while ABCC9 is required for activation and regulation.
Homodimer or heterodimer (Potential). But, in contrast to other members of this family, cannot be disulfide-linked.
Belongs to the sulfotransferase 1 family. Gal/GlcNAc/GalNAc subfamily.
Belongs to the carnitine/choline acetyltransferase family.
Belongs to the proteasome subunit S3 family.
Has different conformational states with differential Ca2+ affinity. The E1 conformational state (active form) shows high Ca(2+) affinity, while the E2 state exhibits low Ca(2+) affinity. Reversibly inhibited by phospholamban (PLN) at low calcium concentrations. Inhibited by sarcolipin (SLN) and myoregulin (MRLN). The inhibition is blocked by VMP1 (By similarity). Enhanced by DWORF; DWORF increases activity by displacing sarcolipin (SLN), phospholamban (PLN) and myoregulin (MRLN) (By similarity). Stabilizes SERCA2 in its E2 state (By similarity).
Interacts with sarcolipin (SLN); the interaction inhibits ATP2A2 Ca(2+) affinity. Interacts with phospholamban (PLN); the interaction inhibits ATP2A2 Ca(2+) affinity (By similarity). Interacts with myoregulin (MRLN) (By similarity). Interacts with DWORF (By similarity). Interacts with HAX1 (By similarity). Interacts with S100A8 and S100A9 (By similarity). Interacts with SLC35G1 and STIM1. Interacts with TMEM203 (By similarity). Interacts with TMEM64 and PDIA3 (By similarity). Interacts with TMX2 (By similarity). Interacts with VMP1; VMP1 competes with PLN and SLN to prevent them from forming an inhibitory complex with ATP2A2. Interacts with ULK1 (By similarity). Interacts with TUNAR (By similarity). Interacts with FLVCR2; this interaction occurs in the absence of heme and promotes ATP2A2 proteasomal degradation; this complex is dissociated upon heme binding. Interacts with FNIP1.
Involved in the regulation of the contraction/relaxation cycle. Acts as a regulator of TNFSF11-mediated Ca(2+) signaling pathways via its interaction with TMEM64 which is critical for the TNFSF11-induced CREB1 activation and mitochondrial ROS generation necessary for proper osteoclast generation. Association between TMEM64 and SERCA2 in the ER leads to cytosolic Ca(2+) spiking for activation of NFATC1 and production of mitochondrial ROS, thereby triggering Ca(2+) signaling cascades that promote osteoclast differentiation and activation.
Isoform 2 is highly expressed in heart and slow twitch skeletal muscle. Isoform 1 is widely expressed.
Nitrated under oxidative stress. Nitration on the two tyrosine residues inhibits catalytic activity.
Serotonylated on Gln residues by TGM2 in response to hypoxia, leading to its inactivation.
This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen. Involved in autophagy in response to starvation. Upon interaction with VMP1 and activation, controls ER-isolation membrane contacts for autophagosome formation. Also modulates ER contacts with lipid droplets, mitochondria and endosomes (By similarity). In coordination with FLVCR2 mediates heme-stimulated switching from mitochondrial ATP synthesis to thermogenesis (By similarity).
Involved in protein trafficking. May serve as a receptor for ARFRP1.
Galactose-specific lectin which binds IgE. May mediate with the alpha-3, beta-1 integrin the stimulation by CSPG4 of endothelial cells migration. Together with DMBT1, required for terminal differentiation of columnar epithelial cells during early embryogenesis. In the nucleus: acts as a pre-mRNA splicing factor. Involved in acute inflammatory responses including neutrophil activation and adhesion, chemoattraction of monocytes macrophages, opsonization of apoptotic neutrophils, and activation of mast cells. Together with TRIM16, coordinates the recognition of membrane damage with mobilization of the core autophagy regulators ATG16L1 and BECN1 in response to damaged endomembranes.
Probably forms homo- or heterodimers. Interacts with DMBT1 (By similarity). Interacts with CD6 and ALCAM. Forms a complex with the ITGA3, ITGB1 and CSPG4. Interacts with LGALS3BP, LYPD3, ZFTRAF1 and UACA. Interacts with TRIM16; this interaction mediates autophagy of damage endomembranes (By similarity).
Component of multiple ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes formed of CUL5, Elongin BC (ELOB and ELOC), RBX2 and a variable SOCS box domain-containing protein as substrate-specific recognition component. Component of the probable ECS(LRRC41) complex with the substrate recognition component LRRC41. Component of the probable ECS(SOCS1) complex with the substrate recognition component SOCS1. Component of the probable ECS(WSB1) complex with the substrate recognition subunit WSB1. Component of the probable ECS(SOCS3) complex with the substrate recognition component SOCS3. Component of the probable ECS(SPSB1) complex with the substrate recognition component SPSB1. Component of the probable ECS(SPSB2) complex with the substrate recognition component SPSB2. Component of the probable ECS(SPSB4) complex with the substrate recognition component SPSB4. Component of the probable ECS(RAB40C) complex with the substrate recognition subunit RAB40C. Component of the probable ECS(KLHDC1) complex with the substrate recognition component KLHDC1. May also form complexes containing CUL5, elongin BC complex (ELOB and ELOC), RBX1 and ELOA. May also form complexes containing CUL5, Elongin BC (ELOB and ELOC), RBX1 and VHL. Interacts with RNF7/RBX2, LRRC41, SOCS3, SPSB1, SPSB2, SPSB4 and RAB40C. Interacts with ASB1, ASB2, ASB6, ASB7 and ASB12. Interacts (when neddylated) with ARIH2; leading to activate the E3 ligase activity of ARIH1. Interacts with NOS2 in the presence of SPSB1 or SPSB2 or SPSB4. Interacts with ERCC6; the interaction is induced by DNA damaging agents or inhibitors of RNA polymerase II elongation. Interacts with ELOA (via the BC-box). Interacts (unneddylated form) with DCUN1D1, DCUN1D2, DCUN1D3, DCUN1D4 and DCUN1D5; these interactions promote the cullin neddylation. Component of the probable ECS(PCMTD1) complex with the substrate recognition subunit PCMTD1.
Core component of multiple SCF-like ECS (Elongin-Cullin 2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The functional specificity of the E3 ubiquitin-protein ligase complex depends on the variable substrate recognition component. ECS(SOCS1) seems to direct ubiquitination of JAK2. ECS(KLHDC1) complex is part of the DesCEND (destruction via C-end degrons) pathway and mediates ubiquitination and degradation of truncated SELENOS selenoprotein produced by failed UGA/Sec decoding, which ends with a glycine. As part of a multisubunit complex composed of elongin BC complex (ELOB and ELOC), elongin A/ELOA, RBX1 and CUL5; polyubiquitinates monoubiquitinated POLR2A. May form a cell surface vasopressin receptor.
Neddylated; which enhances the ubiquitination activity of SCF and prevents binding of the inhibitor CAND1. Deneddylated via its interaction with the COP9 signalosome (CSN).
May be involved in the endocytic machinery.
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.
GAP activity stimulated by phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidic acid.
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.
Activated by binding small G proteins. Binding of GTP-bound CDC42 or RAC1 to the autoregulatory region releases monomers from the autoinhibited dimer, enables phosphorylation of Thr-402 and allows the kinase domain to adopt an active structure. Following caspase cleavage, autophosphorylated PAK-2p34 is constitutively active (By similarity).
During apoptosis proteolytically cleaved by caspase-3 or caspase-3-like proteases to yield active PAK-2p34.
Full-length PAK2 is autophosphorylated when activated by CDC42/p21. Following cleavage, both peptides, PAK-2p27 and PAK-2p34, become highly autophosphorylated. Autophosphorylation of PAK-2p27 can occur in the absence of any effectors and is dependent on phosphorylation of Thr-402, because PAK-2p27 is acting as an exogenous substrate (By similarity).
Interacts tightly with GTP-bound but not GDP-bound CDC42/p21 and RAC1. Interacts with SH3MD4. Interacts with SCRIB. Interacts with ARHGEF7 and GIT1. PAK-2p34 interacts with ARHGAP10. Interacts with RAC1 (By similarity).
Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell motility, cell cycle progression, apoptosis or proliferation. Acts as downstream effector of the small GTPases CDC42 and RAC1. Activation by the binding of active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Full-length PAK2 stimulates cell survival and cell growth. Phosphorylates MAPK4 and MAPK6 and activates the downstream target MAPKAPK5, a regulator of F-actin polymerization and cell migration. Phosphorylates JUN and plays an important role in EGF-induced cell proliferation. Phosphorylates many other substrates including histone H4 to promote assembly of H3.3 and H4 into nucleosomes, BAD, ribosomal protein S6, or MBP. Phosphorylates CASP7, thereby preventing its activity. Additionally, associates with ARHGEF7 and GIT1 to perform kinase-independent functions such as spindle orientation control during mitosis. On the other hand, apoptotic stimuli such as DNA damage lead to caspase-mediated cleavage of PAK2, generating PAK-2p34, an active p34 fragment that translocates to the nucleus and promotes cellular apoptosis involving the JNK signaling pathway. Caspase-activated PAK2 phosphorylates MKNK1 and reduces cellular translation (By similarity).
Ubiquitinated, leading to its proteasomal degradation.
Specifically binds 5-hydroxymethylcytosine (5hmC), suggesting that it acts as a specific reader of 5hmC.
Belongs to the glycoprotein hormones subunit alpha family.
Heterodimer. The active hormones thyrotropin, lutropin and follitropin are heterodimers composed of CGA, a common alpha chain described here and a unique beta chain which confers their biological specificity to the hormones: TSHB for thyrotropin, LHB for lutropin and FSHB for follitropin.
Shared alpha chain of the active heterodimeric glycoprotein hormones thyrotropin/thyroid stimulating hormone/TSH, lutropin/luteinizing hormone/LH and follitropin/follicle stimulating hormone/FSH. These hormones bind specific receptors on target cells that in turn activate downstream signaling pathways.
Belongs to the PPP phosphatase family. PP-2B 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 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.
Exists as monomer or homodimer; disulfide-linked. Exists also as heterodimer with LCN2. Macrophages and transformed cell lines produce only the monomeric form. Interacts with ECM1.
Matrix metalloproteinase that plays an essential role in local proteolysis of the extracellular matrix and in leukocyte migration (By similarity). Could play a role in bone osteoclastic resorption (By similarity). Cleaves KiSS1 at a Gly-|-Leu bond (By similarity). Cleaves NINJ1 to generate the Secreted ninjurin-1 form (By similarity). Cleaves type IV and type V collagen into large C-terminal three quarter fragments and shorter N-terminal one quarter fragments. Degrades fibronectin but not laminin or Pz-peptide (By similarity).
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.
Catalyzes the post-translational formation of 4-hydroxyproline in -Xaa-Pro-Gly- sequences in collagens and other proteins.
Belongs to the G-protein coupled receptor 1 family. Endothelin receptor subfamily. EDNRB sub-subfamily.
Non-specific receptor for endothelin 1, 2, and 3. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system (By similarity).
Belongs to the small GTPase superfamily. Ras family.
Small GTP-binding protein which cycles between a GDP-bound inactive and a GTP-bound active form.
Interacts with TNPO3; the interaction mediates nuclear import of the protein and is disrupted by nuclear Ran bound to GTP. Interacts with EIF4G1 and WT1. Interacts with EIF4A1; the interaction is modulated under stress-induced conditions. Interacts with AGO1. Interacts with AGO2; the interaction occurs under both cell proliferation and differentiation conditions and in an RNA- and phosphorylation-independent manner. Interacts with DDX5; the interaction occurs in an RNA-independent manner (By similarity).
Phosphorylated. Phosphorylated in vitro on Ser-304 by SRPK1. Phosphorylation on Ser-304 is induced upon cell stress signaling, which alters its subcellular localization and may modulate its activity on IRES-mediated mRNA translation. Phosphorylation on Ser-304 is induced upon cell muscle differentiation (By similarity).
RNA-binding factor involved in multiple aspects of cellular processes like alternative splicing of pre-mRNA and translation regulation. Modulates alternative 5'-splice site and exon selection. Acts as a muscle cell differentiation-promoting factor. Activates exon skipping of the PTB pre-mRNA during muscle cell differentiation. Antagonizes the activity of the splicing factor PTBP1 to modulate muscle cell-specific exon selection of alpha tropomyosin. Binds to intronic pyrimidine-rich sequence of the TPM1 and MAPT pre-mRNAs. Required for the translational activation of PER1 mRNA in response to circadian clock. Binds directly to the 3'-UTR of the PER1 mRNA. Exerts a suppressive activity on Cap-dependent translation via binding to CU-rich responsive elements within the 3'UTR of mRNAs, a process increased under stress conditions or during myocytes differentiation. Recruits EIF4A1 to stimulate IRES-dependent translation initiation in respons to cellular stress. Associates to internal ribosome entry segment (IRES) in target mRNA species under stress conditions. Plays a role for miRNA-guided RNA cleavage and translation suppression by promoting association of AGO2-containing miRNPs with their cognate target mRNAs. Associates with miRNAs during muscle cell differentiation. Binds preferentially to 5'-CGCGCG[GCA]-3' motif in vitro (By similarity).
Interacts (via N-terminus) with magoh and rbm8a; the interaction is direct. Associates (eIF2A-like region) with the 40S ribosomal subunit and the 48S preinitiation complex.
Activated at acidic pHs (Probable). Inhibited by cariporide and eniporide. Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) bind and differentially regulate SLC9A1 activity (By similarity).
Electroneutral Na(+) /H(+) antiporter that extrudes Na(+) in exchange for external protons driven by the inward sodium ion chemical gradient, protecting cells from acidification that occurs from metabolism (PubMed:8244988) (Probable). Exchanges intracellular H(+) ions for extracellular Na(+) in 1:1 stoichiometry (By similarity). Plays a key role in maintening intracellular pH neutral and cell volume, and thus is important for cell growth, proliferation, migration and survival. In addition, can transport lithium Li(+) and functions also as a Na(+)/Li(+) antiporter. SLC9A1 also functions in membrane anchoring and organization of scaffolding complexes that coordinate signaling inputs (By similarity).
Homodimer; dimerization is crucial for its function (By similarity). Oligomer (By similarity). Interacts with CALM in a calcium-dependent manner (By similarity). Interacts with TESC (By similarity). Interacts (via the juxtamembrane region of the cytoplasmic C-terminal domain) with CHP1; the interaction occurs at the plasma membrane in a calcium-dependent manner (By similarity). Interacts with CHP2; the interaction occurs in a calcium-dependent manner (By similarity). Interacts with EZR; regulates the cytoskeletal interactions of SLC9A1 and promotes stress fiber formation (By similarity).
Palmitoylated; may play a major role in SLC9A1 regulation.
Phosphorylation at Ser-648 by AKT1 reduces SLC9A1 binding to CALM1.
Predicted models used for more than 20 years predicted 10-12 transmembrane segments. Recently, the stucture of SLC9A1 has been solved and reveals that SLC9A1 posseses 13 transmembranes.
The interacting region with TESC is conflicting: In human, it has been reported that SLC9A1 interacts with TESC via the juxtamembrane region of the cytoplasmic C-terminal domain, including residues 503-545. However, another publication has reported interaction with TESC via residues 633-816, the region of the cytoplasmic C-terminus more distal to the membrane.
Ubiquitinated, leading to its degradation by the proteasome. Ubiquitination is reduced by CHP1.
Catalyzes the formation of L-carnitine from gamma-butyrobetaine.
Belongs to the GST superfamily. Alpha family.
Belongs to the class-V pyridoxal-phosphate-dependent aminotransferase family. SerC subfamily.
Binds 1 pyridoxal phosphate per subunit.
Catalyzes the reversible conversion of 3-phosphohydroxypyruvate to phosphoserine and of 3-hydroxy-2-oxo-4-phosphonooxybutanoate to phosphohydroxythreonine.
Plays a critical role in the sodium-dependent reabsorption of bile acids from the lumen of the small intestine (PubMed:10484607). Transports various bile acids, unconjugated or conjugated, such as cholate and taurocholate (PubMed:10484607). Also responsible for bile acid transport in the renal proximal tubules, a salvage mechanism that helps conserve bile acids. Works collaboratively with the Na(+)-taurocholate cotransporting polypeptide (NTCP), the organic solute transporter (OST), and the bile salt export pump (BSEP), to ensure efficacious biological recycling of bile acids during enterohepatic circulation (By similarity).
Molecular adapter which is involved in cilium biogenesis. Part of a functional complex including OFD1 a centriolar protein involved in cilium assembly. Could regulate the cAMP-dependent phosphorylation of OFD1, and its subsequent ubiquitination by PJA2 which ultimately leads to its proteasomal degradation.
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 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.
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.
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.
Homodimer; disulfide-linked. Interacts with DUSP14. Binds to CD80/B7-1 and CD86/B7-2/B70. Interacts with GRB2 (By similarity).
Involved in T-cell activation, the induction of cell proliferation and cytokine production and promotion of T-cell survival. Enhances the production of IL4 and IL10 in T-cells in conjunction with TCR/CD3 ligation and CD40L costimulation.
Belongs to the FAM175 family. Abraxas subfamily.
Associates with the organic matrix of bone and cartilage. Thought to act as an inhibitor of bone formation.
Belongs to the osteocalcin/matrix Gla protein family.
Requires vitamin K-dependent gamma-carboxylation for its function.
Receptor for platelet activating factor, a chemotactic phospholipid mediator that possesses potent inflammatory, smooth-muscle contractile and hypotensive activity. Seems to mediate its action via a G protein that activates a phosphatidylinositol-calcium second messenger system.
Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays essential roles in the regulation of multiple cellular processes linked to cytoskeletal proteins, such as cell adhesion, motility, migration and cell cycle, functions in neuron growth and ion channel regulation, and is involved in immune response, cancer cell invasion and regulation of apoptosis. Mediates cell adhesion to the extracellular matrix via integrin-dependent signaling, by mediating angiotensin-2-induced activation of integrin beta-1 (ITGB1) in cardiac fibroblasts. Phosphorylates MARCKS, which phosphorylates and activates PTK2/FAK, leading to the spread of cardiomyocytes. Involved in the control of the directional transport of ITGB1 in mesenchymal cells by phosphorylating vimentin (VIM), an intermediate filament (IF) protein. In epithelial cells, associates with and phosphorylates keratin-8 (KRT8), which induces targeting of desmoplakin at desmosomes and regulates cell-cell contact. Phosphorylates IQGAP1, which binds to CDC42, mediating epithelial cell-cell detachment prior to migration. During cytokinesis, forms a complex with YWHAB, which is crucial for daughter cell separation, and facilitates abscission by a mechanism which may implicate the regulation of RHOA. In cardiac myocytes, regulates myofilament function and excitation coupling at the Z-lines, where it is indirectly associated with F-actin via interaction with COPB1. During endothelin-induced cardiomyocyte hypertrophy, mediates activation of PTK2/FAK, which is critical for cardiomyocyte survival and regulation of sarcomere length. Plays a role in the pathogenesis of dilated cardiomyopathy via persistent phosphorylation of troponin I (TNNI3). Involved in nerve growth factor (NFG)-induced neurite outgrowth and neuron morphological change independently of its kinase activity, by inhibition of RHOA pathway, activation of CDC42 and cytoskeletal rearrangement. May be involved in presynaptic facilitation by mediating phorbol ester-induced synaptic potentiation. Phosphorylates gamma-aminobutyric acid receptor subunit gamma-2 (GABRG2), which reduces the response of GABA receptors to ethanol and benzodiazepines and may mediate acute tolerance to the intoxicating effects of ethanol. Upon PMA treatment, phosphorylates the capsaicin- and heat-activated cation channel TRPV1, which is required for bradykinin-induced sensitization of the heat response in nociceptive neurons. Is able to form a complex with PDLIM5 and N-type calcium channel, and may enhance channel activities and potentiates fast synaptic transmission by phosphorylating the pore-forming alpha subunit CACNA1B (CaV2.2). Downstream of TLR4, plays an important role in the lipopolysaccharide (LPS)-induced immune response by phosphorylating and activating TICAM2/TRAM, which in turn activates the transcription factor IRF3 and subsequent cytokines production. In differentiating erythroid progenitors, is regulated by EPO and controls the protection against the TNFSF10/TRAIL-mediated apoptosis, via BCL2. May be involved in the regulation of the insulin-induced phosphorylation and activation of AKT1 (By similarity). Phosphorylates NLRP5/MATER and may thereby modulate AKT pathway activation in cumulus cells (By similarity).
Forms a ternary complex with TRIM63 and RACK1/GN2BL1 (By similarity). Can form a complex with PDLIM5 and N-type calcium channel (By similarity). Interacts with COPB1 (By similarity). Interacts with DGKQ (By similarity). Interacts with STAT3 (By similarity). Interacts with YWHAB (By similarity). Interacts with HSP90AB1; promotes functional activation in a heat shock-dependent manner (By similarity). Interacts (via phorbol-ester/DAG-type 2 domain) with PRPH and VIM (By similarity). Interacts with NLRP5/MATER (By similarity).
Novel PKCs (PRKCD, PRKCE, PRKCH and PRKCQ) are calcium-insensitive, but activated by diacylglycerol (DAG) and phosphatidylserine. Three specific sites; Thr-565 (activation loop of the kinase domain), Thr-709 (turn motif) and Ser-728 (hydrophobic region), need to be phosphorylated for its full activation.
Phosphorylation on Thr-565 by PDPK1 triggers autophosphorylation on Ser-728. Phosphorylation in the hinge domain at Ser-350 by MAPK11 or MAPK14, Ser-346 by GSK3B and Ser-368 by autophosphorylation is required for interaction with YWHAB (By similarity).
The C1 domain, containing the phorbol ester/DAG-type region 1 (C1A) and 2 (C1B), is the diacylglycerol sensor and the C2 domain is a non-calcium binding domain.
May function as a negative regulator of endoplasmic reticulum-stress induced autophagy.
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). Homooligomer; disulfide-linked, leading to inactivation (in vitro). Interacts with PORCN. Interacts with WLS (By similarity). Interacts with glypican GCP3 (By similarity). Interacts with PKD1 (via extracellular domain) (By similarity). Interacts with TMEM67 (By similarity).
Glycosylation is necessary for secretion but not for activity.
In cartilage and cultured chondrocytes, induced by interleukin IL1B.
Ligand for members of the frizzled family of seven transmembrane receptors. Can activate or inhibit canonical Wnt signaling, depending on receptor context. In the presence of FZD4, activates beta-catenin signaling. In the presence of ROR2, inhibits the canonical Wnt pathway by promoting beta-catenin degradation through a GSK3-independent pathway which involves down-regulation of beta-catenin-induced reporter gene expression (By similarity). Suppression of the canonical pathway allows chondrogenesis to occur (PubMed:16754689). Inhibits tumor formation. Stimulates cell migration. Decreases proliferation, migration, invasiveness and clonogenicity of carcinoma cells and may act as a tumor suppressor. Mediates motility of melanoma cells (By similarity). Required during embryogenesis for extension of the primary anterior-posterior axis and for outgrowth of limbs and the genital tubercle (By similarity). Inhibits type II collagen expression in chondrocytes (PubMed:16754689).
Palmitoleoylation is required for efficient binding to frizzled receptors. Depalmitoleoylation leads to Wnt signaling pathway inhibition.
Proteolytic processing by TIKI1 and TIKI2 promotes oxidation and formation of large disulfide-bond oligomers, leading to inactivation of WNT5A.
After maturation cleavage, interacts (via N-terminus) with its own propeptide; this interaction prevents interaction with other ligands, including CRLF1, GDNF, GFRA1, IL6 and IL6R. Interacts (via N-terminal ectodomain) with APP, forming a 1:1 stoichiometric complex; this interaction retains APP in the trans-Golgi network and reduces processing into soluble APP-alpha and amyloid-beta peptides. Also interacts with APP C-terminal fragment C99 and with Abeta40. Interacts with beta-secretase BACE1/BACE; this interaction may affect BACE1-binding to APP and hence reduce BACE1-dependent APP cleavage. Interacts with LRPAP1/RAP. Interacts (via C-terminal cytosolic domain) with GGA1 and GGA2 (via N-terminal VHS domain). Interacts with PACS1. May interact (via the N-terminal ectodomain) with the morphogenetic neuropeptide, also called head activator or HA; this interaction is impaired in the presence of propeptide. Interacts with neurotensin/NTS. Interacts (via the N-terminal ectodomain) with PDGFB homodimer. Interacts (via N-terminal ectodomain) with the uPA receptor PLAUR. Interacts with uPA/PLAU and PAI1/SERPINE1, either individually or in complex with each other, leading to endocytosis. Also interacts with PAI1/SERPINE1 in complex with tPA/PLAT. Interacts (via C-terminus) with AP-1 and AP-2 complexes (By similarity). Interacts with BMPR1A and BMPR1B (By similarity). Interacts with lipoprotein lipase LPL; this interaction is optimal in slightly acidic conditions. Interacts (via N-terminal ectodomain) with GDNF (via propeptide) and GDNF receptor alpha-1/GFRA1, either individually or in complex with each other. The interaction with GDNF occurs mostly intracellularly. Also interacts with other GDNF receptor alpha family members, including GFRA2, GFRA3 and GFRA4. Interacts with the insulin receptor INSR; this interaction strongly increases the surface exposure of INSR. Interacts (via cytosolic C-terminus) with STK39/SPAK. Interacts (via N-terminal ectodomain) with the heterodimeric complex CRLF1-CLC; within this complex, the interaction is mediated predominantly by the CRLF1 moiety. Interacts with CNTFR, as well as with the tripartite signaling complex formed by CRLF1, CLC and CNTFR. Interacts (via N-terminal ectodomain) with IL6; this interaction leads to IL6 internalization and lysosomal degradation. Binding of SOLRL1 secreted N-terminal ectodomain to IL6 may increase IL6 trans signaling. Interacts with secreted IL6R; this interaction leads to IL6R internalization. Also interacts with transmembrane IL6R; this interaction does not affect subcellular location. Interacts with APOE (By similarity). Interacts with apolipoprotein E-rich beta-VLDL (PubMed:8798746). Interacts with APOA5; this interaction leads to APOA5 internalization and is abolished by heparin. Interaction with APOA5 results in enhanced binding to chylomicrons. Interacts with ROCK2 (By similarity). Interacts (via cytosolic C-terminus) with PPP3CB/calcineurin A beta. Interacts with NTRK2/TRKB; this interaction facilitates NTRK2 trafficking between synaptic plasma membranes, postsynaptic densities and cell soma, hence positively regulates BDNF signaling (By similarity). Interacts (via cytosolic C-terminus) with HSPA12A in an ADP-dependent manner; this interaction affects SORL1 internalization and subcellular localization (By similarity). Interacts (via N-terminal ectodomain) with ERBB2/HER2 (By similarity).
Belongs to the VPS10-related sortilin family. SORL1 subfamily.
Expressed in brain, in particular the hippocampus, dentate gyrus, and cerebral cortex (at protein level) (PubMed:8798746). Also detected in liver, adrenal glands, pancreas and testis (PubMed:8798746). Expressed in smooth muscle cells, predominantly during proliferation (PubMed:14764453).
Phosphorylation at Ser-2205 facilitates the interaction with GGA1.
Sorting receptor that directs several proteins to their correct location within the cell. Along with AP-1 complex, involved Golgi apparatus - endosome sorting. Sorting receptor for APP, regulating its intracellular trafficking and processing into amyloidogenic-beta peptides. Retains APP in the trans-Golgi network, hence preventing its transit through late endosomes where amyloid beta peptides Abeta40 and Abeta42 are generated. May also sort newly produced amyloid-beta peptides to lysosomes for catabolism. Does not affect APP trafficking from the endoplasmic reticulum to Golgi compartments. Sorting receptor for the BDNF receptor NTRK2/TRKB that facilitates NTRK2 trafficking between synaptic plasma membranes, postsynaptic densities and cell soma, hence positively regulates BDNF signaling by controlling the intracellular location of its receptor. Sorting receptor for GDNF that promotes GDNF regulated, but not constitutive secretion. Sorting receptor for the GDNF-GFRA1 complex, directing it from the cell surface to endosomes. GDNF is then targeted to lysosomes and degraded, while its receptor GFRA1 recycles back to the cell membrane, resulting in a GDNF clearance pathway. The SORL1-GFRA1 complex further targets RET for endocytosis, but not for degradation, affecting GDNF-induced neurotrophic activities. Sorting receptor for ERBB2/HER2. Regulates ERBB2 subcellular distribution by promoting its recycling after internalization from endosomes back to the plasma membrane, hence stimulating phosphoinositide 3-kinase (PI3K)-dependent ERBB2 signaling. Sorting receptor for lipoprotein lipase LPL. Promotes LPL localization to endosomes and later to the lysosomes, leading to degradation of newly synthesized LPL. Potential sorting receptor for APOA5, inducing APOA5 internalization to early endosomes, then to late endosomes, wherefrom a portion is sent to lysosomes and degradation, another portion is sorted to the trans-Golgi network. Sorting receptor for the insulin receptor INSR. Promotes recycling of internalized INSR via the Golgi apparatus back to the cell surface, thereby preventing lysosomal INSR catabolism, increasing INSR cell surface expression and strengthening insulin signal reception in adipose tissue. Does not affect INSR internalization (By similarity). Plays a role in renal ion homeostasis, controlling the phospho-regulation of SLC12A1/NKCC2 by STK39/SPAK kinase and PPP3CB/calcineurin A beta phosphatase, possibly through intracellular sorting of STK39 and PPP3CB (By similarity). Stimulates, via the N-terminal ectodomain, the proliferation and migration of smooth muscle cells, possibly by increasing cell surface expression of the urokinase receptor uPAR/PLAUR. This may promote extracellular matrix proteolysis and hence facilitate cell migration. By acting on the migration of intimal smooth muscle cells, may accelerate intimal thickening following vascular injury (PubMed:14764453, PubMed:17332490). Promotes adhesion of monocytes (By similarity). Stimulates proliferation and migration of monocytes/macrophages (PubMed:17332490). Through its action on intimal smooth muscle cells and macrophages, may accelerate intimal thickening and macrophage foam cell formation in the process of atherosclerosis (By similarity). Regulates hypoxia-enhanced adhesion of hematopoietic stem and progenitor cells to the bone marrow stromal cells via a PLAUR-mediated pathway. This function is mediated by the N-terminal ectodomain (By similarity). Metabolic regulator, which functions to maintain the adequate balance between lipid storage and oxidation in response to changing environmental conditions, such as temperature and diet. The N-terminal ectodomain negatively regulates adipose tissue energy expenditure, acting through the inhibition the BMP/Smad pathway (By similarity). May regulate signaling by the heterodimeric neurotrophic cytokine CLCF1-CRLF1 bound to the CNTFR receptor by promoting the endocytosis of the tripartite complex CLCF1-CRLF1-CNTFR and lysosomal degradation. May regulate IL6 signaling, decreasing cis signaling, possibly by interfering with IL6-binding to membrane-bound IL6R, while up-regulating trans signaling via soluble IL6R (By similarity).
Within the Golgi apparatus, the propeptide may be cleaved off by FURIN or a furin-like protease. After cleavage, the propeptide interacts with the mature protein N-terminus, preventing the association with other ligands. At the cell surface, partially subjected to proteolytic shedding that releases the ectodomain in the extracellular milieu. The shedding may be catalyzed by ADAM17/TACE. Following shedding, PSEN1/presenilin-1 cleaves the remaining transmembrane fragment and catalyzes the release of a C-terminal fragment in the cytosol and of a soluble N-terminal beta fragment in the extracellular milieu. The C-terminal cytosolic fragment localizes to the nucleus.
Acts as guanine nucleotide exchange factor (GEF) for CDC42. Promotes formation of GPHN clusters.
Component of the DRB sensitivity-inducing factor complex (DSIF complex), which regulates transcription elongation by RNA polymerase II.
Belongs to the Rab3-GAP catalytic subunit 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. Interacts with HSPBAP1 and TTN/titin. Interacts with TMEM109; in the cellular response to DNA damage. Interacts with DES; binds rapidly during early stages of DES filament assembly and a reduced binding seen in the later stages. Interacts with TMED10; the interaction mediates the translocation from the cytoplasm into the ERGIC (endoplasmic reticulum-Golgi intermediate compartment) and thereby secretion. Interacts with ATP6V1A and with MTOR, forming a ternary complex (By similarity).
May contribute to the transparency and refractive index of the lens. Has chaperone-like activity, preventing aggregation of various proteins under a wide range of stress conditions. In lens epithelial cells, stabilizes the ATP6V1A protein, preventing its degradation by the proteasome (By similarity).
Belongs to the snRNP core protein family.
Core component of the spliceosomal U1, U2, U4 and U5 small nuclear ribonucleoproteins (snRNPs), the building blocks of the spliceosome. 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. 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, and at least three U1 snRNP-specific proteins SNRNP70/U1-70K, SNRPA/U1-A and SNRPC/U1-C. 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. Component of the minor spliceosome, which splices U12-type introns. 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. 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. Interacts (via C-terminus) with SMN1 (via Tudor domain); the interaction is direct. Interacts with GEMIN2; the interaction is direct. Interacts with SNRPD2; the interaction is direct.
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. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs. May act as a charged protein scaffold to promote snRNP assembly or strengthen snRNP-snRNP interactions through non-specific electrostatic contacts with RNA.
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).
Belongs to the importin beta family. Importin beta-1 subfamily.
Belongs to the class-II aminoacyl-tRNA synthetase family. Type 1 subfamily.
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.
Highly expressed in cardiac right ventricle, cardiac left ventricle, uterus and lung (at protein level). Detected at low levels in skeletal muscle, uterus, small intestine and liver (at protein level). Detected in blood vessels of kidney, pancreas, spleen and brain (at protein level). Detected in aorta and skeletal muscle.
Induces bone formation in conjunction with TGF-beta-1 or TGF-beta-2.
Component of a multi-subunit COQ enzyme complex, composed of at least COQ3, COQ4, COQ5, COQ6, COQ7 and COQ9. Interacts with ADCK4 and COQ7.
FAD-dependent monooxygenase required for the C5-ring hydroxylation during ubiquinone biosynthesis. Catalyzes the hydroxylation of 3-polyprenyl-4-hydroxybenzoic acid to 3-polyprenyl-4,5-dihydroxybenzoic acid. The electrons required for the hydroxylation reaction may be funneled indirectly from NADPH via a ferredoxin/ferredoxin reductase system to COQ6.
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. Implicated in the regulation of centrosome duplication.
Heterotetramer of 2 NUBP1 and 2 NUBP2 chains. Interacts with KIFC1.
Belongs to the eukaryotic mitochondrial porin family.
Consists mainly of a membrane-spanning beta-barrel formed by 19 beta-strands.
Forms a channel through the mitochondrial outer membrane that allows diffusion of small hydrophilic molecules (By similarity). The channel adopts an open conformation at low or zero membrane potential and a closed conformation at potentials above 30-40 mV (By similarity). The open state has a weak anion selectivity whereas the closed state is cation-selective (By similarity). Binds various lipids, including the sphingolipid ceramide, the phospholipid phosphatidylcholine, and the sterol cholesterol (By similarity). Binding of ceramide promotes the Binding of ceramide promotes the mitochondrial outer membrane permeabilization (MOMP) apoptotic pathway (By similarity).
Interacts with hexokinases (By similarity). Interacts with ARMC12 in a TBC1D21-dependent manner (By similarity). Interacts with KLC3 (By similarity). Interacts with SPATA33 (By similarity). Interacts with PPP3CC in a SPATA33-dependent manner (By similarity).
Ubiquitinated by PRKN during mitophagy, leading to its degradation and enhancement of mitophagy. Deubiquitinated by USP30.
Belongs to the immunoglobulin superfamily. AMIGO family.
Important for the epidermal barrier integrity.
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.
As a component of the IFT complex A (IFT-A), a complex required for retrograde ciliary transport and entry into cilia of G protein-coupled receptors (GPCRs), it is involved in ciliogenesis and ciliary protein trafficking.
Interacts with a broad range of peroxisomal membrane proteins, including PEX3, PEX10, PEX11A, PEX11B, PEX12, PEX13, PEX14 and PEX16, PXMP2/PMP22, PXMP4/PMP24, SLC25A17/PMP34, ABCD1/ALDP, ABCD2/ALDRP, and ABCD3/PMP70. Also interacts with the tumor suppressor CDKN2A/p19ARF.
Necessary for early peroxisomal biogenesis. Acts both as a cytosolic chaperone and as an import receptor for peroxisomal membrane proteins (PMPs). Binds and stabilizes newly synthesized PMPs in the cytoplasm by interacting with their hydrophobic membrane-spanning domains, and targets them to the peroxisome membrane by binding to the integral membrane protein PEX3. Excludes CDKN2A from the nucleus and prevents its interaction with MDM2, which results in active degradation of TP53.
The potassium channel is probably composed of a homo- or heterotetrameric complex of pore-forming alpha subunits that can associate with modulating beta subunits.
Belongs to the acyl-CoA dehydrogenase family.
Associates with mature 80S ribosomes (PubMed:30355441). Interacts with EEF2/eEF2; interaction sequesters EEF2/eEF2 at the A-site of the ribosome, thereby blocking the interaction sites of the mRNA-tRNA complex, promoting ribosome stabilization and hibernation (PubMed:30355441). Interacts with SPIN1 (By similarity). Interacts with CHD3 and TDRD3 (By similarity). Interacts with ZDHHC17 (via ANK repeats) (By similarity).
Phosphorylation by MTOR inhibits SERBP1 and relieves ribosome hibernation.
Ribosome-binding protein that promotes ribosome hibernation, a process during which ribosomes are stabilized in an inactive state and preserved from proteasomal degradation (PubMed:30355441). Acts via its association with EEF2/eEF2 factor, sequestering EEF2/eEF2 at the A-site of the ribosome and promoting ribosome stabilization and storage in an inactive state (PubMed:30355441). May also play a role in the regulation of mRNA stability: binds to the 3'-most 134 nt of the SERPINE1/PAI1 mRNA, a region which confers cyclic nucleotide regulation of message decay. Seems to play a role in PML-nuclear bodies formation (By similarity).
Belongs to the uracil-DNA glycosylase (UDG) superfamily. SMUG1 family.
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.
Belongs to the DNA photolyase class-1 family.
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. Cleaves both polyubiquitin and di-ubiquitin.
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. May play a critical role in early brain and skin development.
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). Promotes the closure of KCNA1, KCNA2 and KCNA5 channels (By similarity). Accelerates KCNA4 channel closure (By similarity). Accelerates the closure of heteromeric channels formed by KCNA1 and KCNA4 (By similarity). Accelerates the closure of heteromeric channels formed by KCNA2, KCNA5 and KCNA6 (By similarity). Enhances KCNB1 and KCNB2 channel activity (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).
Detected in portal vein myocytes (at protein level) (PubMed:11717160).
Homotetramer (By similarity). Interaction with tetrameric potassium channel alpha subunits gives rise to a heterooctamer (Probable). Identified in potassium channel complexes containing KCNA1, KCNA2, KCNA4, KCNA5, KCNA6, KCNAB1 and KCNAB2 (By similarity). Interacts with KCNA1 (PubMed:11717160). Interacts with the dimer formed by GNB1 and GNG2; this enhances KCNA1 binding (By similarity). Interacts with KCNA4 (By similarity). Interacts with KCNA5 (PubMed:11717160). Interacts with KCNB2 (By similarity). Interacts with SQSTM1 (By similarity). Part of a complex containing KCNA1, KCNA4 and LGI1; interaction with LGI1 inhibits down-regulation of KCNA1 channel activity (By similarity).
The N-terminal domain of the beta subunit mediates closure of delayed rectifier potassium channels by physically obstructing the pore.
Belongs to the NAD(P)H dehydrogenase (quinone) family.
Belongs to the cytochrome c oxidase VIIa family.
Acetylated by EP300, leading to impair phosphoenolpyruvate substrate-binding and promote its homodimerization and subsequent translocation to the nucleus. Deacetylation by SIRT6 promotes its nuclear export into the cytoplasm, leading to suppress its nuclear localization and oncogenic function.
Acetylation at Lys-305 is stimulated by high glucose concentration, it decreases enzyme activity and promotes its lysosomal-dependent degradation via chaperone-mediated autophagy.
Catalyzes the final rate-limiting step of glycolysis by mediating the transfer of a phosphoryl group from phosphoenolpyruvate (PEP) to ADP, generating ATP. The ratio between the highly active tetrameric form and nearly inactive dimeric form determines whether glucose carbons are channeled to biosynthetic processes or used for glycolytic ATP production. The transition between the 2 forms contributes to the control of glycolysis and is important for tumor cell proliferation and survival.
FGFR1-dependent tyrosine phosphorylation is reduced by interaction with TRIM35.
Has high pyruvate kinase activity by itself and does not require allosteric activation by D-fructose 1,6-bisphosphate (FBP) for activity.
Isoform M2 is allosterically activated by D-fructose 1,6-bisphosphate (FBP). Inhibited by oxalate and 3,3',5-triiodo-L-thyronine (T3). The activity of the tetrameric form is inhibited by PML. Selective binding to tyrosine-phosphorylated peptides releases the allosteric activator FBP, leading to inhibition of PKM enzymatic activity, this diverts glucose metabolites from energy production to anabolic processes when cells are stimulated by certain growth factors. Glycolytic flux are highly dependent on de novo biosynthesis of serine and glycine, and serine is a natural ligand and allosteric activator of isoform M2.
Isoform specifically expressed during embryogenesis that has low pyruvate kinase activity by itself and requires allosteric activation by D-fructose 1,6-bisphosphate (FBP) for pyruvate kinase activity. In addition to its pyruvate kinase activity in the cytoplasm, also acts as a regulator of transcription in the nucleus by acting as a protein kinase. Translocates into the nucleus in response to various signals, such as EGF receptor activation, and homodimerizes, leading to its conversion into a protein threonine- and tyrosine-protein kinase. Catalyzes phosphorylation of STAT3 at 'Tyr-705' and histone H3 at 'Thr-11' (H3T11ph), leading to activate transcription. Its ability to activate transcription plays a role in cancer cells by promoting cell proliferation and promote tumorigenesis (By similarity). Promotes the expression of the immune checkpoint protein CD274 in BMAL1-deficient macrophages. May also act as a translation regulator for a subset of mRNAs, independently of its pyruvate kinase activity: associates with subpools of endoplasmic reticulum-associated ribosomes, binds directly to the mRNAs translated at the endoplasmic reticulum and promotes translation of these endoplasmic reticulum-destined mRNAs (By similarity). Plays a role in caspase independent cell death of tumor cells (By similarity).
Monomer and homotetramer; exists as a monomer in the absence of D-fructose 1,6-bisphosphate (FBP), and reversibly associates to form a homotetramer in the presence of FBP. The monomeric form binds 3,3',5-triiodo-L-thyronine (T3). Tetramer formation induces pyruvate kinase activity. The tetrameric form has high affinity for the substrate and is associated within the glycolytic enzyme complex. FBP stimulates the formation of tetramers from dimers. Homodimer; exists in a dimeric form in tumor cells and the dimeric form has less affinity for the phosphoenolpyruvate substrate. The homodimer converts into a protein kinase. Interacts with HERC1, POU5F1 and PML. Interacts with EGLN3; the interaction hydroxylates PKM under hypoxia and enhances binding to HIF1A. Interacts with HIF1A; the interaction is enhanced by binding of EGLN3, promoting enhanced transcription activity under hypoxia. Interacts with TRIM35; this interaction prevents FGFR1-dependent tyrosine phosphorylation. Interacts with JMJD8. Interacts with TRAF4. Interacts with (phosphorylated) CTNNB1; leading to activate transcription. Interacts with TSC22D2; the interaction results in reduced nuclear levels of PKM isoform M2, leading to repression of cyclin CCND1 transcription and reduced cell growth (By similarity).
Pyruvate kinase isoform expressed in adult tissues, which replaces isoform M2 after birth. In contrast to isoform M2, has high pyruvate kinase activity by itself and does not require allosteric activation by D-fructose 1,6-bisphosphate (FBP) for activity.
There are 4 isozymes of pyruvate kinase in mammals (L, R, M1, M2) encoded by 2 different genes: PKLR and PKM. The L and R isozymes are generated from the PKLR by differential splicing of RNA; the M1 and M2 forms are produced from the PKM gene by differential splicing. L type is major isozyme in the liver, R is found in red cells, M1 is the main form in muscle, heart and brain, and M2 is found in early fetal tissues as well as in most cancer cells.
Belongs to the eukaryotic ribosomal protein eL33 family.
Expressed in endocardial endothelial cells.
Phosphorylation on Tyr-10 modulates pumping activity. Phosphorylation of Ser-943 by PKA modulates the response of ATP1A1 to PKC. Dephosphorylation by protein phosphatase 2A (PP2A) following increases in intracellular sodium, leading to increase catalytic activity (By similarity).
The sodium/potassium-transporting ATPase is composed of a catalytic alpha subunit, an auxiliary non-catalytic beta subunit and an additional regulatory subunit. Interacts with regulatory subunit FXYD1. Interacts with regulatory subunit FXYD3. Interacts with SIK1. Interacts with SLC35G1 and STIM1. Interacts with CLN3; this interaction regulates the sodium/potassium-transporting ATPase complex localization at the plasma membrane (By similarity).
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 (By similarity). May contribute to blood-heart barrier properties of endocardial endothelium and may control cardiac performance via endothelial Na(+)/H(+) exchange (PubMed:11738066).
Belongs to the glucosamine/galactosamine-6-phosphate isomerase family.
Belongs to the ryanodine receptor (TC 1.A.3.1) family. RYR3 subfamily.
Channel activity is modulated by the alkaloid ryanodine that binds to the open calcium-release channel with high affinity. At low concentrations, ryanodine maintains the channel in an open conformation. High ryanodine concentrations inhibit channel activity. Channel activity is regulated by calmodulin (CALM). The calcium release is activated by elevated cytoplasmic calcium levels in the micromolar range, by caffeine and adenine nucleotides, such as AMP and ATP. Inhibited by Mg(2+) and ruthenium red.
Cytosolic calcium-activated calcium channel that mediates the release of Ca(2+) from the sarcoplasmic reticulum into the cytosol in muscle and thereby plays a role in triggering muscle contraction. May regulate Ca(2+) release by other calcium channels. Calcium channel that mediates Ca(2+)-induced Ca(2+) release from the endoplasmic reticulum in non-muscle cells. Plays a role in cellular calcium signaling. Contributes to cellular calcium ion homeostasis.
Detected in skeletal muscle from young rabbits and in adult diaphragm muscle (at protein level). Detected in brain, especially in corpus striatum, thalamus and hippocampus. Detected in taenia coli, uterus, vas deferens, aorta, stomach, small intestine, heart, diaphragm and ureter. Isoform 2 is highly expressed in uterus and aorta, and at much lower levels in heart, brain and diaphragm.
Homotetramer. Isoform 2 can form tetramers with isoform 1. Heterotetramer with RYR2. Interacts with FKBP1A. Interacts with CALM. Interacts with SELENON (PubMed:18713863).
Lacks a predicted transmembrane segment and does not form functional calcium channels by itself; however, it can form tetramers with isoforms that contain the full complement of transmembrane segments and modulate their activity.
Lacks a predicted transmembrane segment and does not form functional calcium channels.
The calcium release channel activity resides in the C-terminal region while the remaining part of the protein resides in the cytoplasm.
Ubiquitous in skeletal muscle in neonates and in 15 day old rabbits. In adult, detected in diaphragm muscle, and in a subset of skeletal muscles including digastricus, pterygoideus, tongue and masseter.
Forms disulfide-linked homodimers at the cell surface. Interacts with LCK. Interacts with PTK2/FAK1. Binds to P4HB/PDI. Interacts with IL16; this interaction induces a CD4-dependent signaling in lymphocytes. Interacts (via Ig-like V-type domain) with MHCII alpha chain (via alpha-2 domain) and beta chain (via beta-2 domain); this interaction increases the affinity of TCR for peptide-MHCII. CD4 oligomerization via Ig-like C2-type 2 and 3 domains appears to be required for stable binding to MHCII and adhesion between T cells and APCs.
Integral membrane glycoprotein that plays an essential role in the immune response and serves multiple functions in responses against both external and internal offenses. In T-cells, functions primarily as a coreceptor for MHC class II molecule:peptide complex. The antigens presented by class II peptides are derived from extracellular proteins while class I peptides are derived from cytosolic proteins. Interacts simultaneously with the T-cell receptor (TCR) and the MHC class II presented by antigen presenting cells (APCs). In turn, recruits the Src kinase LCK to the vicinity of the TCR-CD3 complex. LCK then initiates different intracellular signaling pathways by phosphorylating various substrates ultimately leading to lymphokine production, motility, adhesion and activation of T-helper cells. In other cells such as macrophages or NK cells, plays a role in differentiation/activation, cytokine expression and cell migration in a TCR/LCK-independent pathway. Participates in the development of T-helper cells in the thymus and triggers the differentiation of monocytes into functional mature macrophages.
Palmitoylation and association with LCK contribute to the enrichment of CD4 in lipid rafts.
Phosphorylated by PKC; phosphorylation plays an important role for CD4 internalization.
The Ig-like V-type domain mediates the interaction with MHCII.
Key player in the regulation of energy balance and body weight control. Once released into the circulation, has central and peripheral effects by binding LEPR, found in many tissues, which results in the activation of several major signaling pathways. In the hypothalamus, acts as an appetite-regulating factor that induces a decrease in food intake and an increase in energy consumption by inducing anorexinogenic factors and suppressing orexigenic neuropeptides, also regulates bone mass and secretion of hypothalamo-pituitary-adrenal hormones. In the periphery, increases basal metabolism, influences reproductive function, regulates pancreatic beta-cell function and insulin secretion, is pro-angiogenic for endothelial cell and affects innate and adaptive immunity. In the arcuate nucleus of the hypothalamus, activates by depolarization POMC neurons inducing FOS and SOCS3 expression to release anorexigenic peptides and inhibits by hyperpolarization NPY neurons inducing SOCS3 with a consequent reduction on release of orexigenic peptides. In addition to its known satiety inducing effect, has a modulatory role in nutrient absorption. In the intestine, reduces glucose absorption by enterocytes by activating PKC and leading to a sequential activation of p38, PI3K and ERK signaling pathways which exerts an inhibitory effect on glucose absorption. Acts as a growth factor on certain tissues, through the activation of different signaling pathways increases expression of genes involved in cell cycle regulation such as CCND1, via JAK2-STAT3 pathway, or VEGFA, via MAPK1/3 and PI3K-AKT1 pathways. May also play an apoptotic role via JAK2-STAT3 pathway and up-regulation of BIRC5 expression. Pro-angiogenic, has mitogenic activity on vascular endothelial cells and plays a role in matrix remodeling by regulating the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). In innate immunity, modulates the activity and function of neutrophils by increasing chemotaxis and the secretion of oxygen radicals. Increases phagocytosis by macrophages and enhances secretion of pro-inflammatory mediators. Increases cytotoxic ability of NK cells. Plays a pro-inflammatory role, in synergy with IL1B, by inducing NOS2 wich promotes the production of IL6, IL8 and Prostaglandin E2, through a signaling pathway that involves JAK2, PI3K, MAP2K1/MEK1 and MAPK14/p38. In adaptive immunity, promotes the switch of memory T-cells towards T helper-1 cell immune responses. Increases CD4(+)CD25(-) T-cell proliferation and reduces autophagy during TCR (T-cell receptor) stimulation, through MTOR signaling pathway activation and BCL2 up-regulation.
DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Second largest core component of RNA polymerase I which synthesizes ribosomal RNA precursors. Proposed to contribute to the polymerase catalytic activity and forms the polymerase active center together with the largest subunit. Pol I is composed of mobile elements and RPA2 is part of the core element with the central large cleft and probably a clamp element that moves to open and close the cleft.
Dynein-attachment factor required for cilia motility.
Belongs to the inositol 1,4,5-trisphosphate 5-phosphatase type II family.
Belongs to the phenylalanyl-tRNA synthetase beta subunit family. Type 2 subfamily.
Cleavage of precursor form by UCHL3 or SENP8 is necessary for function.
Interacts with AHR; interaction is direct. Interacts with NUB1; interaction is direct.
Ubiquitin-like protein which plays an important role in cell cycle control and embryogenesis via its conjugation to a limited number of cellular proteins, such as cullins or p53/TP53. Attachment of NEDD8 to cullins is critical for the recruitment of E2 to the cullin-RING-based E3 ubiquitin-protein ligase complex, thus facilitating polyubiquitination and proteasomal degradation of cyclins and other regulatory proteins. Attachment of NEDD8 to p53/TP53 inhibits p53/TP53 transcriptional activity. Covalent attachment to its substrates requires prior activation by the E1 complex UBE1C-APPBP1 and linkage to the E2 enzyme UBE2M.
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.
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.
Homodimer. Interacts with MARCH8 (By similarity). Interacts (via cytoplasmic domain) with PHB1 and PHB2; the interactions increases after priming with CD40 (By similarity).
Polyubiquitinated; which is promoted by MARCH8 and results in endocytosis and lysosomal degradation.
Receptor involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4. May play a critical role in the early events of T-cell activation and costimulation of naive T-cells, such as deciding between immunity and anergy that is made by T-cells within 24 hours after activation. Also involved in the regulation of B cells function, plays a role in regulating the level of IgG(1) produced. Upon CD40 engagement, activates NF-kappa-B signaling pathway via phospholipase C and protein kinase C activation (By similarity).
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).
Belongs to the CorA metal ion transporter (MIT) (TC 1.A.35) family.
Belongs to the MsrA Met sulfoxide reductase family.
Involved in the costimulatory signal essential for T lymphocytes activation. T-cell proliferation and cytokine production is induced by the binding of CD28 or CTLA-4 to this receptor.
Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. CK2 subfamily.
Can use both ATP and GTP as phosphoryl donors. Phosphorylation by casein kinase 2 has been estimated to represent up to one quarter of the eukaryotic phosphoproteome.
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. Also required for p53/TP53-mediated apoptosis, phosphorylating 'Ser-392' of p53/TP53 following UV irradiation. 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. Phosphorylates YY1, protecting YY1 from cleavage by CASP7 during apoptosis. Regulates transcription by direct phosphorylation of RNA polymerases I, II, III and IV. Also phosphorylates and regulates numerous transcription factors including NF-kappa-B, STAT1, CREB1, IRF1, IRF2, ATF1, ATF4, SRF, MAX, JUN, FOS, MYC and MYB. Phosphorylates Hsp90 and its co-chaperones FKBP4 and CDC37, which is essential for chaperone function. Mediates sequential phosphorylation of FNIP1, promoting its gradual interaction with Hsp90, leading to activate both kinase and non-kinase client proteins of Hsp90. Regulates Wnt signaling by phosphorylating CTNNB1 and the transcription factor LEF1. Acts as an ectokinase that phosphorylates several extracellular proteins. During viral infection, phosphorylates various proteins involved in the viral life cycles of EBV, HSV, HBV, HCV, HIV, CMV and HPV. Phosphorylates PML at 'Ser-565' and primes it for ubiquitin-mediated degradation (By similarity). Plays an important role in the circadian clock function by phosphorylating BMAL1 at 'Ser-90' which is pivotal for its interaction with CLOCK and which controls CLOCK nuclear entry (By similarity). Phosphorylates FMR1, promoting FMR1-dependent formation of a membraneless compartment (By similarity).
Constitutively active protein kinase whose activity is not directly affected by phosphorylation. Seems to be regulated by level of expression and localization (By similarity).
Heterotetramer composed of two catalytic subunits (alpha chain and/or alpha' chain) and two regulatory subunits (beta chains). The tetramer can exist as a combination of 2 alpha/2 beta, 2 alpha'/2 beta or 1 alpha/1 alpha'/2 beta subunits. Also part of a CK2-SPT16-SSRP1 complex composed of SSRP1, SUPT16H, CSNK2A1, CSNK2A2 and CSNK2B, which forms following UV irradiation. Interacts with RNPS1, SNAI1, PML and CCAR2 (By similarity).
Phosphorylated at Thr-344, Thr-360, Ser-362 and Ser-370 by CDK1 in prophase and metaphase and dephosphorylated during anaphase. Phosphorylation does not directly affect casein kinase 2 activity, but may contribute to its regulation by forming binding sites for interacting proteins and/or targeting it to different compartments (By similarity).
Belongs to the glycosyl hydrolase 20 family.
Plays role in pre-mRNA splicing as core component of the SMN-Sm complex that mediates spliceosomal snRNP assembly and as 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.
A tripeptide motif (VGE) within disintegrin-like domain could be involved in the binding to egg integrin receptor and thus could mediate sperm/egg binding.
Heterodimer with ADAM1/fertilin subunit alpha.
Sperm surface membrane protein that may be involved in sperm-egg plasma membrane adhesion and fusion during fertilization. Could have a direct role in sperm-zona binding or migration of sperm from the uterus into the oviduct. Interactions with egg membrane could be mediated via binding between its disintegrin-like domain to one or more integrins receptors on the egg. This is a non catalytic metalloprotease-like protein (By similarity).
The signal and the metalloprotease domain are cleaved during the epididymal maturation of the spermatozoa.
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.
Required for vesicular transport between the endoplasmic reticulum and the Golgi apparatus.
Belongs to the complex I NDUFC2 subunit family.
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.
Belongs to the ABC transporter superfamily. ABCB family. MHC peptide exporter (TC 3.A.1.209) 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.
Belongs to the glycosyltransferase 41 family. O-GlcNAc transferase subfamily.
Catalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine or threonine residue (PubMed:2137449). Acts on cytoplasmic and nuclear proteins resulting in their modification with a beta-linked N-acetylglucosamine (O-GlcNAc). Glycosylates a large and diverse number of proteins including histone H2B, AKT1, ATG4B, EZH2, PFKL, KMT2E/MLL5, MAPT/TAU, NOD2 and HCFC1. Can regulate their cellular processes via cross-talk between glycosylation and phosphorylation or by affecting proteolytic processing. Probably by glycosylating KMT2E/MLL5, stabilizes KMT2E/MLL5 by preventing its ubiquitination (By similarity). Involved in insulin resistance in muscle and adipocyte cells via glycosylating insulin signaling components and inhibiting the 'Thr-308' phosphorylation of AKT1, enhancing IRS1 phosphorylation and attenuating insulin signaling (By similarity). Involved in glycolysis regulation by mediating glycosylation of 6-phosphofructokinase PFKL, inhibiting its activity. Component of a THAP1/THAP3-HCFC1-OGT complex that is required for the regulation of the transcriptional activity of RRM1. Plays a key role in chromatin structure by mediating O-GlcNAcylation of 'Ser-112' of histone H2B: recruited to CpG-rich transcription start sites of active genes via its interaction with TET proteins (TET1, TET2 or TET3). As part of the NSL complex indirectly involved in acetylation of nucleosomal histone H4 on several lysine residues. O-GlcNAcylation of 'Ser-75' of EZH2 increases its stability, and facilitating the formation of H3K27me3 by the PRC2/EED-EZH2 complex. Regulates circadian oscillation of the clock genes and glucose homeostasis in the liver. Stabilizes clock proteins BMAL1 and CLOCK through O-glycosylation, which prevents their ubiquitination and subsequent degradation. Promotes the CLOCK-BMAL1-mediated transcription of genes in the negative loop of the circadian clock such as PER1/2 and CRY1/2. O-glycosylates HCFC1 and regulates its proteolytic processing and transcriptional activity (By similarity). Regulates mitochondrial motility in neurons by mediating glycosylation of TRAK1 (By similarity). Glycosylates HOXA1 (By similarity). O-glycosylates FNIP1 (By similarity). Promotes autophagy by mediating O-glycosylation of ATG4B (By similarity).
Homotrimer, oligomerizes via TPR repeats 6 and 7. Trimerization is not necessary for activity in vitro, however it increases affinity for UDP-GlcNAc (By similarity). Component of a THAP1/THAP3-HCFC1-OGT complex. Component of the NSL complex at least composed of MOF/KAT8, KANSL1, KANSL2, KANSL3, MCRS1, PHF20, OGT1/OGT, WDR5 and HCFC1. Interacts directly with HCFC1; the interaction O-glycosylates HCFC1, regulates its proteolytic processing and transcriptional activity and, in turn, stabilizes OGT in the nucleus. Interacts (via TPRs 1-6) with SIN3A; the interaction mediates transcriptional repression in parallel with histone deacetylase. Interacts (via TPR 5-6) with TET1, TET2 and TET3 (By similarity). Interacts (via TPR repeats 6 and 7) with ATXN10 (By similarity). Interacts with histone H2B (By similarity). Interacts with BMAL1. Found in a complex composed of at least SINHCAF, SIN3A, HDAC1, SAP30, RBBP4, OGT and TET1. Interacts with SINHCAF (By similarity). Component of a complex composed of KMT2E/MLL5, OGT and USP7; the complex stabilizes KMT2E/MLL5, preventing KMT2E/MLL5 ubiquitination and proteasomal-mediated degradation. Interacts (via TRP repeats) with KMT2E/MLL5 (via N-terminus). Interacts with USP7. Interacts with TRAK1; this interaction is not required for glycosylation of TRAK1 by this protein. Found in a complex with KIF5B, RHOT1, RHOT2 and TRAK1 (By similarity). Interacts (via TPR repeats domain) with HOXA1; the interaction takes place mainly in the nucleus (By similarity). Interacts with NSD2 (By similarity). Interacts with PROSER1; this interaction mediates TET2 O-GlcNAcylation and stability by promoting the interaction between OGT and TET2 (By similarity).
Phosphorylation on Ser-3 or Ser-4 by GSK3-beta positively regulates its activity.
The TPR repeat domain is required for substrate binding and oligomerization.
Belongs to the eukaryotic RPA49/POLR1E RNA polymerase subunit family.
Belongs to the PUR DNA-binding protein family.
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) that contains at least Met-tRNA, EIF1, EIF1A (EIF1AX or EIF1AY), EIF2S1, EIF2S2, EIF2S3, EIF3A, EIF3B, EIF3C, EIF3D, EIF3E, EIF3F, EIF3G, EIF3H, EIF3I, EIF3J, EIF3K, EIF3L, EIF3M, DHX29 and the 40S ribosomal subunit.
Belongs to the class I-like SAM-binding methyltransferase superfamily. UbiG/COQ3 family.
O-methyltransferase that catalyzes the 2 O-methylation steps in the ubiquinone biosynthetic pathway.
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.
Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.
Interacts with SMARD1 and UNC45A. Interacts with CUEDC2; the interaction promotes ubiquitination, decreases sumoylation, and represses transcriptional activity. Interacts with PIAS3; the interaction promotes sumoylation of PR in a hormone-dependent manner, inhibits DNA-binding, and alters nuclear export. Interacts with SP1; the interaction requires ligand-induced phosphorylation on Ser-344 by ERK1/2-MAPK. Interacts with PRMT2. Interacts with NCOA2 and NCOA1. Interacts with KLF9. Interacts with GTF2B (By similarity).
Palmitoylated by ZDHHC7 and ZDHHC21. Palmitoylation is required for plasma membrane targeting and for rapid intracellular signaling via ERK and AKT kinases and cAMP generation (By similarity).
Phosphorylated on multiple serine sites. Several of these sites are hormone-dependent. Phosphorylation on Ser-293 is highly hormone-dependent and modulates ubiquitination and sumoylation on Lys-387. Phosphorylation on Ser-102 and Ser-344 also requires induction by hormone. Basal phosphorylation on Ser-82, Ser-191 and Ser-399 is increased in response to progesterone and can be phosphorylated in vitro by the CDK2-A1 complex. Increased levels of phosphorylation on Ser-399 also in the presence of EGF, heregulin, IGF, PMA and FBS. Phosphorylation at this site by CDK2 is ligand-independent, and increases nuclear translocation and transcriptional activity. Phosphorylation at Ser-293, but not at Ser-191, is impaired during the G(2)/M phase of the cell cycle. Phosphorylation on Ser-344 by ERK1/2 MAPK is required for interaction with SP1 (By similarity).
Sumoylation is hormone-dependent and represses transcriptional activity. Sumoylation on all three sites is enhanced by PIAS3. Desumoylated by SENP1. Sumoylation on Lys-387, the main site of sumoylation, is repressed by ubiquitination on the same site, and modulated by phosphorylation at Ser-293 (By similarity).
The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcriptional activator of several progesteron-dependent promoters in a variety of cell types. Involved in activation of SRC-dependent MAPK signaling on hormone stimulation.
Ubiquitination is hormone-dependent and represses sumoylation on the same site. Promoted by MAPK-mediated phosphorylation on Ser-293 (By similarity).
Catalyzes an early step in the biosynthesis of tetrapyrroles. Binds two molecules of 5-aminolevulinate per subunit, each at a distinct site, and catalyzes their condensation to form porphobilinogen.
Homooctamer; active form. Homohexamer; low activity form.
Does not show transport activity towards bile acids or steroid sulfates.
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 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.
Belongs to the uroporphyrinogen decarboxylase family.
Belongs to the neutral sphingomyelinase family.
Acts as a transcriptional repressor. May be involved in DNA damage-inducible cell cycle arrests (checkpoints).
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.
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).
A head-to-tail association, of the N-terminal and C-terminal halves results in a closed conformation (inactive form) which is incapable of actin or membrane-binding.
Has three main structural domains: an N-terminal FERM domain, a central alpha-helical domain and a C-terminal actin-binding domain.
Interacts with PALS1 (PubMed:15677456). Found in a complex with EZR, PODXL and NHERF2. Interacts with MCC, PLEKHG6, PODXL, SCYL3/PACE1, NHERF1, NHERF2 and TMEM8B. Interacts (when phosphorylated) with FES/FPS. Interacts with dimeric S100P, the interaction may be activating through unmasking of F-actin binding sites. Identified in complexes that contain VIM, EZR, AHNAK, BFSP1, BFSP2, ANK2, PLEC, PRX and spectrin. Detected in a complex composed of at least EZR, AHNAK, PPL and PRX. Interacts with PDPN (via cytoplasmic domain); activates RHOA and promotes epithelial-mesenchymal transition. Interacts with SPN/CD43 cytoplasmic tail, CD44 and ICAM2 (By similarity). Interacts with SLC9A3; interaction targets SLC9A3 to the apical membrane (PubMed:16540524). Interacts with SLC9A1; regulates interactions of SLC9A1 with cytoskeletal and promotes stress fiber formation (By similarity).
Phosphorylated by tyrosine-protein kinases. Phosphorylation by ROCK2 suppresses the head-to-tail association of the N-terminal and C-terminal halves resulting in an opened conformation which is capable of actin and membrane-binding (By similarity).
Probably involved in connections of major cytoskeletal structures to the plasma membrane (By similarity). In epithelial cells, required for the formation of microvilli and membrane ruffles on the apical pole. Along with PLEKHG6, required for normal macropinocytosis (By similarity).
S-nitrosylation is induced by interferon-gamma and oxidatively-modified low-densitity lipoprotein (LDL(ox)) possibly implicating the iNOS-S100A8/9 transnitrosylase complex.
The FERM domain is organized in a clover-shaped structure that comprises three subdomains identified as F1 (residues 2-82), F2 (residues 96-198), and F3 (residues 204-296). In the active form, the subdomain F3 adopts two mutually exclusive conformational isomers where a row of four phenylalanine side chains (Phe250, Phe255, Phe267 and Phe269) must point in the same direction. In the autoinhibited form, the F3 subdomain interacts with the C-terminal domain (residues 516-586) and stabilizes the structure, selecting only one possible arrangement of phenylalanine side chains. The FERM domain mediates binding to membrane lipids and signaling molecules.
The [IL]-x-C-x-x-[DE] motif is a proposed target motif for cysteine S-nitrosylation mediated by the iNOS-S100A8/A9 transnitrosylase complex.
The central alpha-helical domain is composed of two alpha helices (residues 326-406 and 417-466) connected by a linker. It protrudes from the FERM domain forming a coiled coil structure where the linker can have either a loop or a helix conformation. The monomer is predicted to form an intra-molecular helix-loop-helix coiled coil structure. Whereas the dimer adopts an elongated dumbbell-shaped configuration where continuous alpha helices from each protomer are organized in a antiparallel coiled coil structure that connect FERM:C-terminal domain swapped complex at each end. The dimer is predicted to link actin filaments parallel to the plasma membrane.
Component of a complex composed of RGS9 (isoform RGS9-1), GNB5 and RGS9BP; within this complex, the presence of GNB5 stabilizes both itself and RGS9 and increases RGS9 GTPase-activating protein (GAP) activity. Interacts with RGS7, forming the RGS7-GNB5 complex; within this complex, the presence of GNB5 increases RGS7 GTPase-activating protein (GAP) activity. Interacts with GPR158; promotes the GTPase activator activity of the RGS7-GNB5 complex in absence of glycine, in contrast GTPase activator activity of the RGS7-GNB5 complex is inhibited in presence of glycine. Interacts with RGS6.
Enhances GTPase-activating protein (GAP) activity of regulator of G protein signaling (RGS) proteins, such as RGS7 and RGS9, hence involved in the termination of the signaling initiated by the G protein coupled receptors (GPCRs) by accelerating the GTP hydrolysis on the G-alpha subunits, thereby promoting their inactivation (By similarity). Increases RGS7 GTPase-activating protein (GAP) activity, thereby regulating mood and cognition (By similarity). Increases RGS9 GTPase-activating protein (GAP) activity, hence contributes to the deactivation of G protein signaling initiated by D(2) dopamine receptors (By similarity). May play an important role in neuronal signaling, including in the parasympathetic, but not sympathetic, control of heart rate (By similarity).
Interacts via LIM domain 1 with ZYX. Interacts (via LIM domain 3) with ENAH and VASP. Interacts with ALKBH4, talin, actin, alpha-actinin, GRIP1 and PXN (By similarity). Interacts (via LIM domain 2) with ACTL7A (via N-terminus). Heterodimer with ACTL7A; the heterodimer interacts with ENAH to form a heterotrimer (By similarity).
Scaffold protein that may play a role in cell adhesion, cell spreading and in the reorganization of the actin cytoskeleton. Plays a role in the regulation of cell proliferation. May act as a tumor suppressor (By similarity).
The N-terminal and the C-terminal halves of the protein can associate with each other, thereby hindering interactions with ZYX.
Belongs to the CISD protein family. CISD2 subfamily.
Regulator of autophagy that contributes to antagonize BECN1-mediated cellular autophagy at the endoplasmic reticulum. Participates in the interaction of BCL2 with BECN1 and is required for BCL2-mediated depression of endoplasmic reticulum Ca(2+) stores during autophagy.
Activation requires multiple phosphorylation events on serine/threonine residues. Activation appears to be first mediated by phosphorylation of multiple sites in the autoinhibitory domain, which facilitates phosphorylation at Thr-412, disrupting the autoinhibitory mechanism and allowing phosphorylation of Thr-252 by PDPK1. The active conformation of the kinase is believed to be stabilized by a mechanism involving three conserved phosphorylation sites located in the kinase domain activation loop (Thr-252) and in the AGC-kinase C-terminal domain (Ser-394 in the middle of the tail/linker region and Thr-412 within a hydrophobic motif at its end). Activated by mTORC1; isoform Alpha I and isoform Alpha II are sensitive to rapamycin, which inhibits activating phosphorylation at Thr-412. Activated by PDPK1 (By similarity).
Interacts with PPP1R9A/neurabin-1. Interacts with RPTOR. Interacts with IRS1. Interacts with EIF3B and EIF3C. Interacts with TRAF4. Interacts with POLDIP3. Interacts (via N-terminus) with IER5.
Phosphorylation at Thr-412 is regulated by mTORC1. The phosphorylation at this site is maintained by an agonist-dependent autophosphorylation mechanism. Activated by phosphorylation at Thr-252 by PDPK1. Dephosphorylation by PPP1CC at Thr-412 in mitochondrion (By similarity).
Serine/threonine-protein kinase that acts downstream of mTOR signaling in response to growth factors and nutrients to promote cell proliferation, cell growth and cell cycle progression. Regulates protein synthesis through phosphorylation of EIF4B, RPS6 and EEF2K, and contributes to cell survival by repressing the pro-apoptotic function of BAD. Under conditions of nutrient depletion, the inactive form associates with the EIF3 translation initiation complex. Upon mitogenic stimulation, phosphorylation by the mechanistic target of rapamycin complex 1 (mTORC1) leads to dissociation from the EIF3 complex and activation. The active form then phosphorylates and activates several substrates in the pre-initiation complex, including the EIF2B complex and the cap-binding complex component EIF4B. Also controls translation initiation by phosphorylating a negative regulator of EIF4A, PDCD4, targeting it for ubiquitination and subsequent proteolysis. Promotes initiation of the pioneer round of protein synthesis by phosphorylating POLDIP3/SKAR. In response to IGF1, activates translation elongation by phosphorylating EEF2 kinase (EEF2K), which leads to its inhibition and thus activation of EEF2. Also plays a role in feedback regulation of mTORC2 by mTORC1 by phosphorylating RICTOR, resulting in the inhibition of mTORC2 and AKT1 signaling. Also involved in feedback regulation of mTORC1 and mTORC2 by phosphorylating DEPTOR (By similarity). Mediates cell survival by phosphorylating the pro-apoptotic protein BAD and suppressing its pro-apoptotic function (By similarity). Phosphorylates mitochondrial URI1 leading to dissociation of a URI1-PPP1CC complex. The free mitochondrial PPP1CC can then dephosphorylate RPS6KB1 at Thr-412, which is proposed to be a negative feedback mechanism for the RPS6KB1 anti-apoptotic function. Mediates TNF-alpha-induced insulin resistance by phosphorylating IRS1 at multiple serine residues, resulting in accelerated degradation of IRS1. In cells lacking functional TSC1-2 complex, constitutively phosphorylates and inhibits GSK3B (By similarity). May be involved in cytoskeletal rearrangement through binding to neurabin (By similarity). Phosphorylates and activates the pyrimidine biosynthesis enzyme CAD, downstream of MTOR. Following activation by mTORC1, phosphorylates EPRS and thereby plays a key role in fatty acid uptake by adipocytes and also most probably in interferon-gamma-induced translation inhibition (By similarity).
The TOS (TOR signaling) motif is essential for activation by mTORC1.
The autoinhibitory domain is believed to block phosphorylation within the AGC-kinase C-terminal domain and the activation loop.
Belongs to the cytochrome c oxidase VIIc 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, encoded in the mitochondrial DNA, and 11 supernumerary subunits, 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)).
CAP18 binds to the lipid A moiety of bacterial lipopolysaccharides (LPS), a glycolipid present in the outer membrane of all Gram-negative bacteria. Has antibiotic activity.
Belongs to the complex I NDUFB5 subunit family.
Heterodimer with IL12B; disulfide-linked. The heterodimer is known as interleukin IL-12.
Heterodimerizes with IL12B to form the IL-12 cytokine or with EBI3/IL27B to form the IL-35 cytokine. IL-12 is primarily produced by professional antigen-presenting cells (APCs) such as B-cells and dendritic cells (DCs) as well as macrophages and granulocytes and regulates T-cell and natural killer-cell responses, induces the production of interferon-gamma (IFN-gamma), favors the differentiation of T-helper 1 (Th1) cells and is an important link between innate resistance and adaptive immunity. Mechanistically, exerts its biological effects through a receptor composed of IL12R1 and IL12R2 subunits. Binding to the receptor results in the rapid tyrosine phosphorylation of a number of cellular substrates including the JAK family kinases TYK2 and JAK2. In turn, recruited STAT4 gets phosphorylated and translocates to the nucleus where it regulates cytokine/growth factor responsive genes. As part of IL-35, plays essential roles in maintaining the immune homeostasis of the liver microenvironment and functions also as an immune-suppressive cytokine. Mediates biological events through unconventional receptors composed of IL12RB2 and gp130/IL6ST heterodimers or homodimers. Signaling requires the transcription factors STAT1 and STAT4, which form a unique heterodimer that binds to distinct DNA sites.
Belongs to the dynein heavy chain family.
Belongs to the protein-tyrosine phosphatase 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.
Homodimer in the catalytically active form, monomer in the secreted form.
In the cytoplasm, catalyzes the conversion of glucose-6-phosphate to fructose-6-phosphate, the second step in glycolysis, and the reverse reaction during gluconeogenesis (By similarity). Besides it's role as a glycolytic enzyme, also acts as a secreted cytokine: acts as an angiogenic factor (AMF) that stimulates endothelial cell motility. Acts as a neurotrophic factor, neuroleukin, for spinal and sensory neurons. It is secreted by lectin-stimulated T-cells and induces immunoglobulin secretion (By similarity).
Phosphorylation at Ser-185 by CK2 has been shown to decrease enzymatic activity and may contribute to secretion by a non-classical secretory pathway.
Component of the U11/U12 snRNPs that are part of the U12-type spliceosome. Found in a complex with m(7)G-capped U12 snRNA. Interacts with PDCD7.
Participates in pre-mRNA U12-dependent splicing, performed by the minor spliceosome which removes U12-type introns. U12-type introns comprises less than 1% of all non-coding sequences. Binds to the 3'-stem-loop of m(7)G-capped U12 snRNA.
Belongs to the complex I subunit 3 family.
Core subunit of respiratory chain NADH dehydrogenase (Complex I) which is composed of 45 different subunits. Interacts with TMEM186. Interacts with TMEM242 (By similarity).
Core subunit of respiratory chain NADH dehydrogenase (Complex I) which is composed of 45 different subunits. Interacts with TMEM186. Interacts with TMEM242.
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 of complex I.
Asp-61, Arg-76, Arg-77, and Glu-81 may be involved in the calcium-dependent binding of phosphorylcholine, a property that may be important for the biological function of this protein.
Displays several functions associated with host defense: it promotes agglutination, bacterial capsular swelling, phagocytosis and complement fixation through its calcium-dependent binding to phosphorylcholine. Can interact with DNA and histones and may scavenge nuclear material released from damaged circulating cells (By similarity).
Homopentamer. Pentraxin (or pentaxin) have a discoid arrangement of 5 non-covalently bound subunits. Interacts with FCN1; may regulate monocyte activation by FCN1 (By similarity).
The concentration of CRP in plasma increases greatly during acute phase response to tissue injury, infection or other inflammatory stimuli.
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) (By similarity). The elongator complex catalyzes the formation of carboxymethyluridine in the wobble base at position 34 in tRNAs (By similarity). Regulates the migration and branching of projection neurons in the developing cerebral cortex, through a process depending on alpha-tubulin acetylation (By similarity). ELP1 binds to tRNA, mediating interaction of the elongator complex with tRNA (By similarity). May act as a scaffold protein that assembles active IKK-MAP3K14 complexes (IKKA, IKKB and MAP3K14/NIK) (By similarity).
Homodimer; dimerization promotes ELP1 stability and elongator complex formation. Component of the elongator complex which consists of ELP1, ELP2, ELP3, ELP4, ELP5 and ELP6. Interacts preferentially with MAP3K14/NIK followed by IKK-alpha and IKK-beta.
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 vacuolar ATPase subunit S1 family.
Essential component of the renin-angiotensin system (RAS), a potent regulator of blood pressure, body fluid and electrolyte homeostasis.
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.
During squamous cell differentiation. Repressed by retinoic acid.
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.
Belongs to the aldolase class II family. Adducin subfamily.
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, which plays a key role in cancer, apoptosis, microbial proliferation and inflammation. May inhibit the CASP1-related inflammatory response (pyroptosis), the CASP9-dependent apoptotic pathway and the cytochrome c-dependent and APAF1-mediated cell death.
Homotetramer. Interacts with APAF1. May interact with CASP1.
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)). Interacts with UQCC6.
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.
Belongs to the alkaline ceramidase family.
Hydrolyzes the sphingolipid ceramide into sphingosine and free fatty acid.
Required for formation of the RNA induced silencing complex (RISC). Component of the RISC loading complex (RLC), also known as the micro-RNA (miRNA) loading complex (miRLC), which is composed of DICER1, AGO2 and TARBP2. Within the RLC/miRLC, DICER1 and TARBP2 are required to process precursor miRNAs (pre-miRNAs) to mature miRNAs and then load them onto AGO2. AGO2 bound to the mature miRNA constitutes the minimal RISC and may subsequently dissociate from DICER1 and TARBP2. May also play a role in the production of short interfering RNAs (siRNAs) from double-stranded RNA (dsRNA) by DICER1.
Self-associates. Component of the RISC loading complex (RLC), or micro-RNA (miRNA) loading complex (miRLC), which is composed of DICER1, AGO2 and TARBP2. Note that the trimeric RLC/miRLC is also referred to as RISC. Interacts with EIF2AK2/PKR and inhibits its protein kinase activity. Interacts with DHX9 and PRKRA. Interacts with DICER1, AGO2, MOV10, EIF6 and RPL7A (60S ribosome subunit); they form a large RNA-induced silencing complex (RISC).
Decapping enzyme for NAD-capped RNAs: specifically hydrolyzes the nicotinamide adenine dinucleotide (NAD) cap from a subset of RNAs by removing the entire NAD moiety from the 5'-end of an NAD-capped RNA.
Belongs to the myelin proteolipid protein family.
Defects in PLP1 are the cause of paralytic tremor (pt); a sex-linked mutation in rabbit that affects myelination of the CNS.
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.
Can serve as a substrate in transglutaminase-catalyzed cross linking reactions and can function as a cross-linked envelope precursor.
Suppressed by retinoic acid. RAR-selective retinoid is more effective than RXR-selective retinoid.
Suprabasal layers of the squamous epithelia of esophagus, tongue and oral mucosa.
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.
Converts inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5).
Detected in kidney, intestine, liver and heart.
Was first identified because of its ability to stimulate Na(+)-dependent phosphate cotransport.
C-terminal Ser or Thr residues may be phosphorylated.
Interacts with MAS1 (By similarity). Interacts with ARRB1 (By similarity). Interacts with FLNA (via filamin repeat 21); increases PKA-mediated phosphorylation of FLNA (By similarity).
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.
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) 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.
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 complex I NDUFA12 subunit family.
Belongs to the complex I subunit 4 family.
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.
Catalytic subunit of protein phosphatase 2A (PP2A), a serine/threonine phosphatase involved in the regulation of a wide variety of enzymes, signal transduction pathways, and cellular events. PP2A can modulate the activity of phosphorylase B kinase, casein kinase 2, mitogen-stimulated S6 kinase, and MAP-2 kinase.
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. Binds PPME1. May indirectly interact with SGO1, most probably through regulatory B56 subunits. Found in a complex with at least ARL2, PPP2CB, PPP2R1A, PPP2R2A, PPP2R5E and TBCD. Interacts with TBCD. Interacts with CTTNBP2NL. Interacts with PTPA.
Exerts its effect at some terminal stage of cytochrome c oxidase synthesis, probably by being involved in the insertion of the copper B into subunit I.
Required for proper 34S pre-rRNA processing and 60S ribosome subunit assembly.
Displays temperature-dependent chaperone activity.
Belongs to the Mediator complex subunit 1 family.
Involved in endoplasmic reticulum to Golgi apparatus trafficking at a very early stage.
TFIIA is a component of the transcription machinery of RNA polymerase II and plays an important role in transcriptional activation.
Belongs to the type II cytokine receptor family.
Belongs to the nucleoporin Nup84/Nup107 family.
Belongs to the ubiquitin conjugation factor E4 family.
The U-box domain is required for the ubiquitin protein ligase activity.
Ubiquitin-protein ligase that probably functions as an E3 ligase in conjunction with specific E1 and E2 ligases. Also functions as an E4 ligase mediating the assembly of polyubiquitin chains on substrates ubiquitinated by another E3 ubiquitin ligase. Mediates 'Lys-48'-linked polyubiquitination of substrates.
Belongs to the bacterial ribosomal protein bL9 family.
Abundant in liver, vas deferens, brain, and aorta, but not in heart.
Belongs to the G-protein coupled receptor 1 family. Adrenergic receptor subfamily. ADRA1A sub-subfamily.
Homo- and heterooligomer. Heterooligomerizes with ADRA1B homooligomers in cardiac myocytes. Interacts with CAVIN4.
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 (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.
Plays a role as pro-apoptotic protein that induces caspase-dependent apoptosis.
Plays a role in valine and pyrimidine metabolism. Binds fatty acyl-CoA.
Belongs to the class-IV pyridoxal-phosphate-dependent aminotransferase family.
Belongs to the eutherian X-chromosome-specific Armcx family.
May be required for cellular fusion during osteoclastogenesis.
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 RNA polymerase beta' chain family.
Belongs to the pyrimidine 5'-nucleotidase family.
Receptor for the invariable Fc fragment of immunoglobulin gamma (IgG) (By similarity). Optimally activated upon binding of clustered antigen-IgG complexes displayed on cell surfaces, triggers lysis of antibody-coated cells, a process known as antibody-dependent cellular cytotoxicity (ADCC). Does not bind free monomeric IgG, thus avoiding inappropriate effector cell activation in the absence of antigenic trigger. Mediates IgG effector functions on natural killer (NK) cells. Binds antigen-IgG complexes generated upon infection and triggers NK cell-dependent cytokine production and degranulation to limit viral load and propagation (By similarity). Fc-binding subunit that associates with FCER1G adapters to form functional signaling complexes. Following the engagement of antigen-IgG complexes, triggers phosphorylation of immunoreceptor tyrosine-based activation motif (ITAM)-containing adapters with subsequent activation of phosphatidylinositol 3-kinase signaling and sustained elevation of intracellular calcium that ultimately drive NK cell activation (By similarity). Mediates enhanced ADCC in response to afucosylated IgGs (PubMed:34485821).
Belongs to the ribose 5-phosphate isomerase family.
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.
May act as a scaffolding protein within caveolar membranes. Interacts directly with G-protein alpha subunits and can functionally regulate their activity. Acts as an accessory protein in conjunction with CAV1 in targeting to lipid rafts and driving caveolae formation. Positive regulator of cellular mitogenesis of the MAPK signaling pathway. Required for the insulin-stimulated nuclear translocation and activation of MAPK1 and STAT3, and the subsequent regulation of cell cycle progression (By similarity).
Monomer or homodimer. Interacts with CAV1; the interaction forms a stable heterooligomeric complex that is required for targeting to lipid rafts and for caveolae formation. Tyrosine phosphorylated forms do not form heterooligomers with the Tyr-19-phosphorylated form existing as a monomer or dimer. Interacts (tyrosine phosphorylated form) with the SH2 domain-containing proteins, RASA1, NCK1 and SRC. Interacts (tyrosine phosphorylated form) with INSR. Interacts (Tyr-19 phosphorylated form) with MAPK1 (phosphorylated form); the interaction, promoted by insulin, leads to nuclear location and MAPK1 activation. Interacts with STAT3; the interaction is increased on insulin-induced tyrosine phosphorylation leading to STAT activation (By similarity).
Phosphorylated on serine and tyrosine residues. CAV1 promotes phosphorylation on Ser-23 which then targets the complex to the plasma membrane, lipid rafts and caveolae. Phosphorylation on Tyr-19 is required for insulin-induced phosphorylation of MAPK1 and DNA binding of STAT3. Tyrosine phosphorylation is induced by both EGF and insulin (By similarity).
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.
65 kDa monomer is produced by proteolytic cleavage.
Autophosphorylation increases kinase activity.
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. cGMP subfamily.
Composed of an N-terminal leucine-zipper domain followed by an autoinhibitory domain, which mediate homodimer formation and inhibit kinase activity, respectively. Next, two cGMP-binding domains are followed by the catalytic domain at the C-terminus. Binding of cGMP to cGMP-binding domains results in a conformational change that activates kinase activity by removing the autoinhibitory domain from the catalytic cleft leaving the catalytic domain free to phosphorylate downstream substrates. Isoforms alpha and beta have identical cGMP-binding and catalytic domains but differ in their leucine zipper and autoinhibitory sequences and therefore differ in their dimerization substrates and kinase enzyme activity (By similarity).
Heterotetramerization is mediated by the interaction between a coiled-coil of PRKG1 and the leucine/isoleucine zipper of PPP1R12A/MBS, the myosin-binding subunit of the myosin phosphatase.
In the absence of cGMP, PRKG1 activity is suppressed by autoinhibitory contacts.
Isoform alpha: parallel homodimer or heterodimer and also heterotetramer. Interacts directly with PPP1R12A. Non-covalent dimer of dimer of PRKG1-PRKG1 and PPP1R12A-PPP1R12A. This interaction targets PRKG1 to stress fibers to mediate smooth muscle cell relaxation and vasodilation in responses to rises in cGMP (By similarity). Isoform beta: antiparallel homodimer. Part of cGMP kinase signaling complex at least composed of ACTA2/alpha-actin, CNN1/calponin H1, PLN/phospholamban, PRKG1 and ITPR1. Interacts with IRAG1 (By similarity). Forms a stable complex with ITPR1, IRAG1, and isoform beta of PRKG1 (By similarity). Interacts with TRPC7 (via ankyrin repeat domain) (By similarity). Isoform alpha interacts with RGS2 (By similarity). Interacts with GTF2I (By similarity).
Serine/threonine protein kinase that acts as key mediator of the nitric oxide (NO)/cGMP signaling pathway. GMP binding activates PRKG1, which phosphorylates serines and threonines on many cellular proteins. Numerous protein targets for PRKG1 phosphorylation are implicated in modulating cellular calcium, but the contribution of each of these targets may vary substantially among cell types. Proteins that are phosphorylated by PRKG1 regulate platelet activation and adhesion, smooth muscle contraction, cardiac function, gene expression, feedback of the NO-signaling pathway, and other processes involved in several aspects of the CNS like axon guidance, hippocampal and cerebellar learning, circadian rhythm and nociception. Smooth muscle relaxation is mediated through lowering of intracellular free calcium, by desensitization of contractile proteins to calcium, and by decrease in the contractile state of smooth muscle or in platelet activation. Regulates intracellular calcium levels via several pathways: phosphorylates IRAG1 and inhibits IP3-induced Ca(2+) release from intracellular stores, phosphorylation of KCNMA1 (BKCa) channels decreases intracellular Ca(2+) levels, which leads to increased opening of this channel. PRKG1 phosphorylates the canonical transient receptor potential channel (TRPC) family which inactivates the associated inward calcium current. Another mode of action of NO/cGMP/PKGI signaling involves PKGI-mediated inactivation of the Ras homolog gene family member A (RhoA). Phosphorylation of RHOA by PRKG1 blocks the action of this protein in myriad processes: regulation of RHOA translocation; decreasing contraction; controlling vesicle trafficking, reduction of myosin light chain phosphorylation resulting in vasorelaxation. Activation of PRKG1 by NO signaling alters also gene expression in a number of tissues. In smooth muscle cells, increased cGMP and PRKG1 activity influence expression of smooth muscle-specific contractile proteins, levels of proteins in the NO/cGMP signaling pathway, down-regulation of the matrix proteins osteopontin and thrombospondin-1 to limit smooth muscle cell migration and phenotype. Regulates vasodilator-stimulated phosphoprotein (VASP) functions in platelets and smooth muscle (By similarity).
Implicated in the level of global muscle contraction and cardiac function (By similarity). Phosphorylates a specific serine in the N-terminus of a myosin light chain.
Belongs to the GTP-binding elongation factor family. EF-G/EF-2 subfamily.
Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase 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.
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. Inhibits the activity of the calcium channel CACNA1H. Required for normal embryonic development of the adrenal gland and for normal hormonal responses to stress. Plays a role in the response to anxiogenic stimuli.
Belongs to the peptidase M24 family. SPT16 subfamily.
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.
Belongs to the palmitoyl-protein thioesterase family.
Activated by cAMP. cAMP binding causes a conformation change that leads to the assembly of an active tetramer and channel opening.
Highly expressed in the heart sinoatrial node (SAN). Not detected in atrium, ventricle, forebrain or cerebellum. Detected at very low levels in total brain.
Homotetramer. The potassium channel is composed of a homo- or heterotetrameric complex of pore-forming subunits (By similarity).
Hyperpolarization-activated ion channel with very slow activation and inactivation exhibiting weak selectivity for potassium over sodium ions. May contribute to the native pacemaker currents in heart (If) that regulate the rhythm of heart beat. May contribute to the native pacemaker currents in neurons (Ih). May mediate responses to sour stimuli.
Belongs to the repulsive guidance molecule (RGM) family.
This protein is involved in the oxidative metabolism of a variety of xenobiotics such as drugs and pesticides.
Interacts with CD4. Interacts with ALDH16A1.
May play a role as a negative regulatory factor in CD4-dependent T-cell activation.
Belongs to the universal ribosomal protein uL5 family.
Belongs to the universal ribosomal protein uL3 family.
Belongs to the extended synaptotagmin family.
Belongs to the methyltransferase superfamily.
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.
Interacts with F-actin (By similarity). Interacts with ANKRD54. Interacts with KBTBD10 (By similarity).
Phosphorylated on serine residues after stimulation with histamine.
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 (By similarity).
Widely expressed with highest levels in mucosal tissues throughout the gastrointestinal tract as well as in heart, lung, liver, kidney, adrenal and smooth muscle. Lowest level is observed in skeletal muscle.
Belongs to the potassium channel family. S (TC 1.A.1.2) subfamily. Kv9.3/KCNS3 sub-subfamily.
Heterotetramer with KCNB1. Does not form homomultimers.
Potassium channel subunit that does not form functional channels by itself. Can form functional heterotetrameric channels with KCNB1; modulates the delayed rectifier voltage-gated potassium channel activation and deactivation rates of KCNB1. Heterotetrameric channel activity formed with KCNB1 show increased current amplitude with the threshold for action potential activation shifted towards more negative values in hypoxic-treated pulmonary artery smooth muscle cells.
Predominantly expressed in liver and other non-muscle tissues.
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. ZP4 may act as a sperm receptor.
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.
Belongs to the SOS response-associated peptidase family.
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.
Belongs to the Mediator complex subunit 31 family.
Nomenclature used in PubMed:8576224 refers to PP2A B subunit B' gamma isoform, which is cited as PP2A B subunit delta-PR61 isoform in later publications.
PP2A consists of a common heterodimeric core enzyme, composed of a 36 kDa catalytic subunit (subunit C) and a 65 kDa constant regulatory subunit (PR65 or subunit A), that associates with a variety of regulatory subunits. Proteins that associate with the core dimer include three families of regulatory subunits B (the R2/B/PR55/B55, R3/B''/PR72/PR130/PR59 and R5/B'/B56 families), the 48 kDa variable regulatory subunit, viral proteins, and cell signaling molecules. Interacts with SGO1 (By similarity). Interacts with ADCY8 (By similarity).
Belongs to the ADP-ribosyl cyclase family.
Synthesizes cyclic ADP-ribose (cADPR), a second messenger for glucose-induced insulin secretion (Probable). Synthesizes the Ca(2+) mobilizer nicotinate-adenine dinucleotide phosphate, NAADP(+), from 2'-phospho-cADPR and nicotinic acid, as well as from NADP(+) and nicotinic acid. Also has cADPR hydrolase activity (By similarity).
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 (By similarity). Required for mesendoderm differentiation (By similarity).
Found in a complex with ADD2, DMTN and SLC2A1. Interacts (via C-terminus cytoplasmic region) with DMTN. Interacts with SNX27; the interaction is required when endocytosed to prevent degradation in lysosomes and promote recycling to the plasma membrane. Interacts with GIPC (via PDZ domain). Interacts with STOM. Interacts with SGTA (via Gln-rich region) (By similarity). Interacts with BSG (By similarity). Interacts with SMIM43; the interaction may promote SLC2A1-mediated glucose transport to meet the energy needs of mesendoderm differentiation (By similarity).
Phosphorylation at Ser-226 by PKC promotes glucose uptake by increasing cell membrane localization.
The uptake of glucose is inhibited by cytochalasin B. Glucose uptake is increased in response to phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment: TPA-induced glucose uptake requires phosphorylation at Ser-226.
Involved in maintaining Golgi structure. Stimulates the formation of Golgi stacks and ribbons. Involved in intra-Golgi retrograde transport.
Belongs to the acetyltransferase family. MAK3 subfamily.
Participates in at least several B-cell activation processes as well as of other cell types. It is a costimulator of DNA-synthesis. It induces the expression of class II MHC molecules on resting B-cells. It enhances both secretion and cell surface expression of IgE and IgG1. It also regulates the expression of the low affinity Fc receptor for IgE (CD23) on both lymphocytes and monocytes.
Participates in at least several B-cell activation processes as well as of other cell types. It is a costimulator of DNA-synthesis. It induces the expression of class II MHC molecules on resting B-cells. It enhances both secretion and cell surface expression of IgE and IgG1. It also regulates the expression of the low affinity Fc receptor for IgE (CD23) on both lymphocytes and monocytes. Positively regulates IL31RA expression in macrophages. Stimulates autophagy in dendritic cells by interfering with mTORC1 signaling and through the induction of RUFY4.
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.
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).
Li(+) decreases succinate transport in the presence of Na(+), by competing at one of the three cation binding sites.
Low-affinity sodium-dicarboxylate cotransporter, that mediates the entry of citric acid cycle intermediates, such as succinate, citrate, fumarate and alpha-ketoglutarate (2-oxoglutarate) into the small intestine and renal proximal tubule (By similarity) (PubMed:7890707, PubMed:28731330). Transports the dicarboxylate into the cell with a probable stoichiometry of 3 Na(+) for 1 divalent dicarboxylate, rendering the process electrogenic (PubMed:7890707, PubMed:28731330). Citrate is transported in protonated form as a divalent anion, rather than the trivalent form which is normally found in blood (PubMed:28731330). Has a critical role in renal dicarboxylate transport (By similarity).
The C-terminal lobe folds into an immunoglobulin-like domain and may mediate cell adhesion properties.
The sodium/potassium-transporting ATPase is composed of a catalytic alpha subunit, an auxiliary non-catalytic beta subunit and an additional regulatory subunit. Interacts with catalytic alpha subunit ATP12A.
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 (By similarity).
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.
Belongs to the carbon-nitrogen hydrolase superfamily. NIT1/NIT2 family.
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).
Ligand for members of the frizzled family of seven transmembrane receptors. Probable developmental protein. May be a signaling molecule which affects the development of discrete regions of tissues. Is likely to signal over only few cell diameters (By similarity).
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. Component of an ATP synthase complex composed of ATP5PB, ATP5MC1, ATP5F1E, ATP5PD, ATP5ME, ATP5PF, ATP5MF, MT-ATP6, MT-ATP8, ATP5F1A, ATP5F1B, ATP5F1D, ATP5F1C, ATP5PO, ATP5MG, ATP5MK and ATP5MJ (By similarity). Interacts with DNAJC30; interaction is direct (By similarity).
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. Key component of the proton channel; it may play a direct role in the translocation of protons across the membrane.
Belongs to the liprin family. Liprin-beta subfamily.
Metallothioneins have a high content of cysteine residues that bind various heavy metals.
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.
Belongs to the replication factor A protein 3 family.
Calcium-regulated non-lysosomal thiol-protease.
Belongs to the glycosyltransferase 2 family.
Belongs to the thymidylate synthase family.
Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO).
Belongs to the MICOS complex subunit Mic19 family. Metazoan Mic25 subfamily.
Belongs to the major facilitator superfamily. Vesicular transporter family.
Belongs to the glyceraldehyde-3-phosphate dehydrogenase family.
Glyceraldehyde-3-phosphate dehydrogenase activity is inhibited by fumarate, via the formation of S-(2-succinyl)cysteine residues.
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). Modulates the organization and assembly of the cytoskeleton. Facilitates the CHP1-dependent microtubule and membrane associations through its ability to stimulate the binding of CHP1 to microtubules (By similarity). Component of the GAIT (gamma interferon-activated inhibitor of translation) complex which mediates interferon-gamma-induced transcript-selective translation inhibition in inflammation processes. Upon interferon-gamma treatment assembles into the GAIT complex which binds to stem loop-containing GAIT elements in the 3'-UTR of diverse inflammatory mRNAs (such as ceruplasmin) and suppresses their translation. Also plays a role in innate immunity by promoting TNF-induced NF-kappa-B activation and type I interferon production, via interaction with TRAF2 and TRAF3, respectively (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).
Homotetramer (By similarity). Interacts with TPPP; the interaction is direct (By similarity). Interacts (when S-nitrosylated) with SIAH1; leading to nuclear translocation. Interacts with RILPL1/GOSPEL, leading to prevent the interaction between GAPDH and SIAH1 and prevent nuclear translocation. Interacts with CHP1; the interaction increases the binding of CHP1 with microtubules. Associates with microtubules (By similarity). Interacts with EIF1AD, USP25, PRKCI and WARS1. Interacts with phosphorylated RPL13A; inhibited by oxidatively-modified low-densitity lipoprotein (LDL(ox)). Component of the GAIT complex. Interacts with FKBP6; leading to inhibit GAPDH catalytic activity. Interacts with TRAF2, promoting TRAF2 ubiquitination. Interacts with TRAF3, promoting TRAF3 ubiquitination (By similarity).
Oxidative stress can promote the formation of high molecular weight disulfide-linked GAPDH aggregates, through a process called nucleocytoplasmic coagulation.
S-nitrosylation of Cys-150 leads to interaction with SIAH1, followed by translocation to the nucleus S-nitrosylation of Cys-245 is induced by interferon-gamma and LDL(ox) implicating the iNOS-S100A8/9 transnitrosylase complex and seems to prevent interaction with phosphorylated RPL13A and to interfere with GAIT complex activity (By similarity).
Sulfhydration at Cys-150 increases catalytic activity.
Belongs to the dynactin subunits 5/6 family. Dynactin subunit 5 subfamily.
Adapter protein that binds to and probably organizes the subcellular localization of a variety of membrane proteins. May link various receptors to the actin cytoskeleton and the extracellular matrix via dystrophin glycoprotein complex. Plays an important role in synapse formation and in the organization of UTRN and acetylcholine receptors at the neuromuscular synapse. Binds to phosphatidylinositol 4,5-bisphosphate (By similarity).
Highly expressed in skeletal and cardiac muscle and is also detected in brain.
Monomer and homodimer. Interacts with the dystrophin related protein DTNA; SGCG of the dystrophin glycoprotein complex; NOS1; GRB2; GA; TGFA; MAPK12 and the sodium channel proteins SCN4A and SCN5A (By similarity). Interacts with the dystrophin protein DMD in a calmodulin dependent manner and with related protein UTRN; SGCA of the dystrophin glycoprotein complex; F-actin; calmodulin and with the other members of the syntrophin family SNTB1 and SNTB2. Interacts with MYOC; regulates muscle hypertrophy (By similarity). Interacts with DTNB (By similarity).
Phosphorylated by CaM-kinase II. Phosphorylation may inhibit the interaction with DMD (By similarity).
The PDZ domain binds to the last three or four amino acids of ion channels and receptor proteins. The association with dystrophin or related proteins probably leaves the PDZ domain available to recruit proteins to the membrane (By similarity).
The PH 1 domain mediates the oligomerization in a calcium dependent manner, and the association with the phosphatidylinositol 4,5-bisphosphate.
The SU domain binds calmodulin in a calcium-dependent manner (By similarity). It contains actin-binding sites.
Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. CDC5/Polo subfamily.
Belongs to the glycosyl hydrolase 23 family.
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 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.
Belongs to the isocitrate and isopropylmalate dehydrogenases family.
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.
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.
May be involved in photoreceptor outer segment disk morphogenesis.
Homotetramer. Directly interacts with ATP7A; this interaction is copper-dependent and is required for SOD3 activity.
Protect the extracellular space from toxic effect of reactive oxygen intermediates by converting superoxide radicals into hydrogen peroxide and oxygen.
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 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).
Represents a conventional myosin. This protein should not be confused with the unconventional myosin-4 (MYO4).
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 prokaryotic/mitochondrial release factor family.
Belongs to the inorganic phosphate transporter (PiT) (TC 2.A.20) family.
Belongs to the complex I subunit 1 family.
Cytokine that in its homotrimeric form binds to TNFRSF1A/TNFR1, TNFRSF1B/TNFBR and TNFRSF14/HVEM (By similarity). In its heterotrimeric form with LTB binds to TNFRSF3/LTBR. Lymphotoxin is produced by lymphocytes and is cytotoxic for a wide range of tumor cells in vitro and in vivo.
Cytokine that in its homotrimeric form binds to TNFRSF1A/TNFR1, TNFRSF1B/TNFBR and TNFRSF14/HVEM. In its heterotrimeric form with LTB binds to TNFRSF3/LTBR. Lymphotoxin is produced by lymphocytes and is cytotoxic for a wide range of tumor cells in vitro and in vivo.
Homotrimer, and heterotrimer of either two LTB and one LTA subunits or (less prevalent) two LTA and one LTB subunits. Interacts with TNFRSF14.
Forms homooligomers, but does not form complexes with the other coronins. Interacts with Arp2/3 complex components, including ACTR2, ARPC1B and ARPC2 (By similarity). Binds actin.
Phosphorylated in vivo by PKC in response to cholinergic stimulation. Phosphorylation on Ser-2 regulates the interaction with the Arp2/3 complex and cell motility in fibroblasts. Phosphorylation does not seem to affect subcellular location (By similarity).
Regulates leading edge dynamics and cell motility in fibroblasts. May be involved in cytokinesis and signal transduction (By similarity).
May be involved in 20S pre-rRNA processing.
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.
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.
Forms a ternary complex with IGFR1 and ITGAV:ITGB3. Forms a ternary complex with IGFR1 and ITGA6:ITGB4.
The insulin-like growth factors, isolated from plasma, are structurally and functionally related to insulin but have a much higher growth-promoting activity. May be a physiological regulator of [1-14C]-2-deoxy-D-glucose (2DG) transport and glycogen synthesis in osteoblasts. Stimulates glucose transport in bone-derived osteoblastic (PyMS) cells and is effective at much lower concentrations than insulin, not only regarding glycogen and DNA synthesis but also with regard to enhancing glucose uptake. May play a role in synapse maturation. Ca(2+)-dependent exocytosis of IGF1 is required for sensory perception of smell in the olfactory bulb. 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 ITGAV:ITGB3 and ITGA6:ITGB4. Its binding to integrins and subsequent ternary complex formation with integrins and IGFR1 are essential for IGF1 signaling. Induces the phosphorylation and activation of IGFR1, MAPK3/ERK1, MAPK1/ERK2 and AKT1 (By similarity).
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). 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.
Belongs to the peptidase M67A family. CSN5 subfamily.
Belongs to the glycosyltransferase 16 (GT16) protein family.
Involved in sperm-egg adhesion. Upon fertilization sperm must first penetrate a layer of cumulus cells that surrounds the egg before reaching the zona pellucida. The cumulus cells are embedded in a matrix containing hyaluronic acid which is formed prior to ovulation. This protein aids in penetrating the layer of cumulus cells by digesting hyaluronic acid.
Deubiquitination at Lys-191 and Lys-194 by USP32.
Interacts with NTRK1/TRKA (By similarity). Interacts with RILP (By similarity). Interacts with PSMA7 (By similarity). Interacts with RNF115 (By similarity). Interacts with FYCO1 (By similarity). Interacts with the PIK3C3/VPS34-PIK3R4 complex (By similarity). The GTP-bound form interacts with OSBPL1A (By similarity). The GTP-bound form interacts with RAC1 (By similarity). Interacts with CLN3 (By similarity). Interacts with CHM, the substrate-binding subunit of the Rab geranylgeranyltransferase complex (By similarity). Interacts with C9orf72. Does not interact with HPS4 and the BLOC-3 complex (heterodimer of HPS1 and HPS4). Interacts with CLN5 (By similarity). Interacts with PLEKHM1 (via N- and C-terminus) (By similarity). Interacts with RUFY4 (By similarity). Interacts with PRPH; the interaction is direct (By similarity). Interacts with VPS13A (By similarity). The GDP-bound form interacts with RIMOC1 (By similarity). Interacts with the MON1A-CCZ1B complex and this interaction is enhanced in the presence of RIMOC1 (By similarity).
Small GTPase which cycles between active GTP-bound and inactive GDP-bound states. In its active state, binds to a variety of effector proteins playing a key role in the regulation of endo-lysosomal trafficking. Governs early-to-late endosomal maturation, microtubule minus-end as well as plus-end directed endosomal migration and positioning, and endosome-lysosome transport through different protein-protein interaction cascades (By similarity). Plays a central role, not only in endosomal traffic, but also in many other cellular and physiological events, such as growth-factor-mediated cell signaling, nutrient-transporter-mediated nutrient uptake, neurotrophin transport in the axons of neurons and lipid metabolism (By similarity). Also involved in regulation of some specialized endosomal membrane trafficking, such as maturation of melanosomes, pathogen-induced phagosomes (or vacuoles) and autophagosomes (By similarity). Plays a role in the maturation and acidification of phagosomes that engulf pathogens, such as S.aureus and Mycobacteria (By similarity). Plays a role in the fusion of phagosomes with lysosomes (By similarity). Plays important roles in microbial pathogen infection and survival, as well as in participating in the life cycle of viruses (By similarity). Microbial pathogens possess survival strategies governed by RAB7A, sometimes by employing RAB7A function (e.g. Salmonella) and sometimes by excluding RAB7A function (e.g. Mycobacterium) (By similarity). In concert with RAC1, plays a role in regulating the formation of RBs (ruffled borders) in osteoclasts (By similarity). Controls the endosomal trafficking and neurite outgrowth signaling of NTRK1/TRKA (By similarity). Regulates the endocytic trafficking of the EGF-EGFR complex by regulating its lysosomal degradation (By similarity). Involved in the ADRB2-stimulated lipolysis through lipophagy, a cytosolic lipase-independent autophagic pathway.Required for the exosomal release of SDCBP, CD63 and syndecan (By similarity). Required for vesicular trafficking and cell surface expression of ACE2 (By similarity). May play a role in PRPH neuronal intermediate filament assembly (By similarity).
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.
Belongs to the RecA family. RAD51 subfamily.
Forms linear homooligomers, giving rise to a RAD51 nucleoprotein filament, which is essential for strand-pairing reactions during DNA recombination. Interacts with BRCA1 and either directly or indirectly with p53. Interacts with XRCC3, RAD54L and RAD54B. Interacts with the BCDX2 subcomplex RAD51C:RAD51B. Component of the homologous recombination repair (HR) complex composed of ERCC5/XPG, BRCA2, PALB2, DSS1 and RAD51. Interacts directly with PALB2 which may serve as a scaffold for a HR complex containing PALB2, BRCA2, RAD51C, RAD51 and XRCC3. Interacts with RAD51AP1 and RAD51AP2. Interacts with CHEK1, and this may require prior phosphorylation of CHEK1. Interacts with the MND1-PSMC3IP heterodimer. Found in a complex, at least composed of BLM, RAD51 and SPIDR; the complex formation is mediated by SPIDR. Interacts with SPIDR; the interaction is direct and recruits RAD51 to DNA damage sites. Interacts with FIGNL1 (via N-terminal one-half region); the interaction is direct. Interacts with RAD51AP1 (via C-terminal region); the interaction is direct. Interacts with NABP2, RPA1, PALB2 and RAD51. Interacts with SWI5/C9orf119, and at lower level with SFR1/MEIR5. Interacts with hyperphosphorylated RPA2; this interaction is necessary for efficient recruitment to chromatin in response to DNA damage. Interacts with SWSAP1; involved in homologous recombination repair. Interacts with PARPBP, BRCA2 and RECQL5; these interactions interfere with the formation of the RAD51-DNA homologous recombination structure. Interacts with POLQ; POLQ acts as an inhibitor of homology-recombination repair (HR) pathway by limiting RAD51 accumulation at resected ends. Interacts with FBH1. Interacts with POLN. Interacts with RFWD3. Interacts with the MCM8-MCM9 complex; the interaction recruits RAD51 to DNA damage sites (By similarity). Component of a multiprotein complex with MEIOB and SPATA22. Interacts with the complex BRME1:HSF2BP:BRCA2 (By similarity). Interacts with HELQ; stimulating HELQ DNA helicase activity and ability to unwing DNA. Interacts with MMS22L; the interaction is direct and promotes recruitment of RAD51 to sites of DNA damage. Interacts with the ATAD5 RFC-like complex. Within the ATAD5 RFC-like complex, interacts with ATAD5 (via N-terminus); the interaction is direct and enhanced under replication stress. Interacts with WDR48; the interaction is enhanced under replication stress (By similarity).
Phosphorylated. Phosphorylation of Thr-309 by CHEK1 may enhance association with chromatin at sites of DNA damage and promote DNA repair by homologous recombination. Phosphorylation by ABL1 inhibits function.
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.
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. Part of a PALB2-scaffolded HR complex containing BRCA2 and RAD51C and which is thought to play a role in DNA repair by HR. Plays a role in regulating mitochondrial DNA copy number under conditions of oxidative stress in the presence of RAD51C and XRCC3. Also involved in interstrand cross-link repair.
Ubiquitinated by the SCF(FBH1) E3 ubiquitin ligase complex, regulating RAD51 subcellular location and preventing its association with DNA. Ubiquitinated by RFWD3 in response to DNA damage: ubiquitination leads to degradation by the proteasome, promoting homologous recombination.
Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXO9) composed of CUL1, SKP1, RBX1 and FBXO9. Interacts with TTI1 and TELO2; when TTI1 and TELO2 are phosphorylated by CK2.
Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins and plays a role in several biological processes such as cell cycle, cell proliferation, or maintenance of chromosome stability. Ubiquitinates mTORC1-bound TTI1 and TELO2 when they are phosphorylated by CK2 following growth factor deprivation, leading to their degradation. In contrast, does not mediate ubiquitination of TTI1 and TELO2 when they are part of the mTORC2 complex. As a consequence, mTORC1 is inactivated to restrain cell growth and protein translation, while mTORC2 is the activated due to the relief of feedback inhibition by mTORC1. Plays a role in maintaining epithelial cell survival by regulating the turn-over of chromatin modulator PRMT4 through ubiquitination and degradation by the proteasomal pathway. Regulates also PPARgamma stability by facilitating PPARgamma/PPARG ubiquitination and thereby plays a role in adipocyte differentiation.
Activated by forskolin. Activated by GNAS. Activity is further increased by interaction with the G protein beta and gamma subunit complex formed by GNB1 and GNG2 (By similarity). Is not activated by calmodulin. Inhibited by adenosine and ATP analogs. Inhibited by calcium ions, already at micromolar concentrations (By similarity). Phosphorylation by RAF1 results in its activation (By similarity).
Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling. Mediates signaling downstream of ADRB1. Regulates the increase of free cytosolic Ca(2+) in response to increased blood glucose levels and contributes to the regulation of Ca(2+)-dependent insulin secretion.
Interacts with GNAS, GNB1 and GNG2 (By similarity). Part of a complex containing AKAP5, ADCY6, PDE4C and PKD2 (By similarity). Interacts with RAF1 (By similarity).
The protein contains two modules with six transmembrane helices each; both are required for catalytic activity. Isolated N-terminal or C-terminal guanylate cyclase domains have no catalytic activity, but when they are brought together, enzyme activity is restored. The active site is at the interface of the two domains. Both contribute substrate-binding residues, but the catalytic metal ions are bound exclusively via the N-terminal guanylate cyclase domain.
ADP:ATP antiporter that mediates import of ADP into the mitochondrial matrix for ATP synthesis, and export of ATP out to fuel the cell (By similarity). Cycles between the cytoplasmic-open state (c-state) and the matrix-open state (m-state): operates by the alternating access mechanism with a single substrate-binding site intermittently exposed to either the cytosolic (c-state) or matrix (m-state) side of the inner mitochondrial membrane (By similarity). In addition to its ADP:ATP antiporter activity, also involved in mitochondrial uncoupling and mitochondrial permeability transition pore (mPTP) activity. Plays a role in mitochondrial uncoupling by acting as a proton transporter: proton transport uncouples the proton flows via the electron transport chain and ATP synthase to reduce the efficiency of ATP production and cause mitochondrial thermogenesis. Proton transporter activity is inhibited by ADP:ATP antiporter activity, suggesting that SLC25A4/ANT1 acts as a master regulator of mitochondrial energy output by maintaining a delicate balance between ATP production (ADP:ATP antiporter activity) and thermogenesis (proton transporter activity). Proton transporter activity requires free fatty acids as cofactor, but does not transport it. Probably mediates mitochondrial uncoupling in tissues that do not express UCP1. Also plays a key role in mPTP opening, a non-specific pore that enables free passage of the mitochondrial membranes to solutes of up to 1.5 kDa, and which contributes to cell death. It is however unclear if SLC25A4/ANT1 constitutes a pore-forming component of mPTP or regulates it (By similarity). Acts as a regulator of mitophagy independently of ADP:ATP antiporter activity: promotes mitophagy via interaction with TIMM44, leading to inhibit the presequence translocase TIMM23, thereby promoting stabilization of PINK1 (By similarity).
Monomer (By similarity). Found in a complex with ARL2, ARL2BP and SLC25A4/ANT1. Interacts with ARL2BP. Interacts with TIMM44; leading to inhibit the presequence translocase TIMM23, thereby promoting stabilization of PINK1 (By similarity).
The matrix-open state (m-state) is inhibited by the membrane-permeable bongkrekic acid (BKA). The cytoplasmic-open state (c-state) is inhibited by the membrane-impermeable toxic inhibitor carboxyatractyloside (CATR) (By similarity). Proton transporter activity is inhibited by ADP:ATP antiporter activity (By similarity).
The transmembrane helices are not perpendicular to the plane of the membrane, but cross the membrane at an angle. Odd-numbered transmembrane helices exhibit a sharp kink, due to the presence of a conserved proline residue.
Under cell death induction, transglutaminated by TGM2. Transglutamination leads to formation of covalent cross-links between a glutamine and the epsilon-amino group of a lysine residue, forming polymers.
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.
May function as a transcription factor involved in cell differentiation.
Essential hepatic enzyme that catalyzes the oxygenation of a wide variety of nitrogen- and sulfur-containing compounds including drugs as well as dietary compounds. Plays an important role in the metabolism of trimethylamine (TMA), via the production of trimethylamine N-oxide (TMAO) metabolite. TMA is generated by the action of gut microbiota using dietary precursors such as choline, choline containing compounds, betaine or L-carnitine. By regulating TMAO concentration, FMO3 directly impacts both platelet responsiveness and rate of thrombus formation.
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).
Belongs to the 5'-3' exonuclease family. XRN2/RAT1 subfamily.
Possesses 5'->3' exoribonuclease activity. May promote termination of transcription by RNA polymerase II.
Belongs to the major facilitator superfamily. Spinster (TC 2.A.1.49) family.
Component of the origin recognition complex (ORC) that binds origins of replication.
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.
Potent inhibitor of the complement membrane attack complex (MAC) action. Acts by binding to the C8 and/or C9 complements of the assembling MAC, thereby preventing incorporation of the multiple copies of C9 required for complete formation of the osmolytic pore.
The mature form of this CD59 contains an additional serine residue before the conserved N-terminal leucine residue found in all other CD59 homologs sequenced to date.
Catalyzes the reversible hydration of carbon dioxide. Can also hydrate cyanamide to urea (By similarity). Involved in the regulation of fluid secretion into the anterior chamber of the eye. Essential for bone resorption and osteoclast differentiation. Contributes to intracellular pH regulation in the duodenal upper villous epithelium during proton-coupled peptide absorption. Stimulates the chloride-bicarbonate exchange activity of SLC26A6.
Interacts with SLC4A4 and SLC26A6. Interaction with SLC4A7 regulates SLC4A7 transporter activity (By similarity).
Belongs to the Nudix hydrolase family. NudC subfamily.
Skeletal muscle troponin C binds four calcium ions.
Belongs to the proteasome subunit S5A family.
Receptor for gastrin and cholecystokinin. The CCK-B receptors occur throughout the central nervous system where they modulate anxiety, analgesia, arousal, and neuroleptic activity. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system.
May be involved in the negative control of osteogenic differentiation of osteochondrogenic precursor cells in peripheral zones of fetal cartilage and at the cartilage-bone interface.
Belongs to the reduced folate carrier (RFC) transporter (TC 2.A.48) family.
Interacts with SRF. Forms complexes with SRF and SRF cofactors ARID2, MYOCD and NKX2-5. Interacts with the N-terminus of SLC2A4.
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.
Cytokine that plays a major role in the development of inflammatory and protective immune responses to microbial invaders and parasites by modulating immune cells of both the innate and adaptive immune systems. Stimulates the proliferation of natural killer cells, T-cells and B-cells and promotes the secretion of several cytokines. In monocytes, induces the production of IL8 and monocyte chemotactic protein 1/CCL2, two chemokines that attract neutrophils and monocytes respectively to sites of infection. Unlike most cytokines, which are secreted in soluble form, IL15 is expressed in association with its high affinity IL15RA on the surface of IL15-producing cells and delivers signals to target cells that express IL2RB and IL2RG receptor subunits. Binding to its receptor triggers the phosphorylation of JAK1 and JAK3 and the recruitment and subsequent phosphorylation of signal transducer and activator of transcription-3/STAT3 and STAT5 (By similarity). In mast cells, induces the rapid tyrosine phosphorylation of STAT6 and thereby controls mast cell survival and release of cytokines such as IL4 (By similarity).
Expressed in many tissues including heart, spleen, lung, liver, muscle and kidney (at mRNA level). Expressed in many tissues including heart, spleen, lung, liver, muscle and kidney (at protein level).
Belongs to the ZP domain family. ZPC subfamily.
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.
Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating.
Belongs to the protein kinase superfamily. Tyr protein kinase family. SYK/ZAP-70 subfamily.
Adapter involved in the TLR2 and TLR4 signaling pathways in the innate immune response.
Belongs to the pseudouridine synthase TruD family.
On GH binding, phosphorylated on tyrosine residues in the cytoplasmic domain by JAK2.
On growth hormone (GH) binding, forms homodimers and binds JAK2 via a box 1-containing domain (By similarity). Binding to SOCS3 inhibits JAK2 activation, binding to CIS and SOCS2 inhibits STAT5 activation (By similarity). Interacts with ADAM17.
On ligand binding, ubiquitinated on lysine residues in the cytoplasmic domain. This ubiquitination is not sufficient for GHR internalization.
Receptor for pituitary gland growth hormone involved in regulating postnatal body growth. On ligand binding, couples to, and activates the JAK2/STAT5 pathway (By similarity).
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 soluble form (GHBP) is produced by phorbol ester-promoted proteolytic cleavage at the cell surface (shedding) by ADAM17/TACE. Shedding is inhibited by growth hormone (GH) binding to the receptor probably due to a conformational change in GHR rendering the receptor inaccessible to ADAM17.
The ubiquitination-dependent endocytosis motif (UbE) is required for recruitment of the ubiquitin conjugation system on to the receptor and for its internalization.
Belongs to the vasopressin/oxytocin family.
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.
Tetramer of heterotrimers consisting of exclusion domain, heavy- and light chains.
Ribosomal protein P0 is the functional equivalent of E.coli protein L10.
Interacts with KATNA1. This interaction enhances the microtubule binding and severing activity of KATNA1 and also targets this activity to the centrosome. This interaction is weakly competed by KATNBL1 which has a lower affinity for it. Interacts with ASPM; the katanin complex formation KATNA1:KATNB1 is required for the association of ASPM. Interacts with dynein, microtubules, NDEL1 and PAFAH1B1. Interacts with KATNAL1; this interaction is weakly competed by KATNBL1 which has a lower affinity for it. Interacts with CAMSAP2 and CAMSAP3; leading to regulate the length of CAMSAP-decorated microtubule stretches.
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. Microtubule release from the mitotic spindle poles may allow depolymerization of the microtubule end proximal to the spindle pole, leading to poleward microtubule flux and poleward motion of chromosome. Microtubule release within the cell body of neurons may be required for their transport into neuronal processes by microtubule-dependent motor proteins. This transport is required for axonal growth.
The C-terminal part of the hedgehog protein precursor displays an autoproteolysis activity that results in the cleavage of the full-length protein into two parts (N-product and C-product). In addition, the C-terminal part displays a cholesterol transferase activity that results by the covalent attachment of a cholesterol moiety to the C-terminal of the newly generated N-product.
The dually lipidated hedgehog protein N-product is a morphogen which is essential for a variety of patterning events during development.
Belongs to the class-I pyridine nucleotide-disulfide oxidoreductase family. PYROXD1 subfamily.
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-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in positive and negative regulation of cell proliferation, apoptosis, differentiation, migration and adhesion, cardiac hypertrophy, angiogenesis, platelet function and inflammation, by directly phosphorylating targets such as RAF1, BCL2, CSPG4, TNNT2/CTNT, or activating signaling cascades involving MAPK1/3 (ERK1/2) and RAP1GAP. Depending on the cell type, is involved in cell proliferation and cell growth arrest by positive and negative regulation of the cell cycle. Can promote cell growth by phosphorylating and activating RAF1, which mediates the activation of the MAPK/ERK signaling cascade, and/or by up-regulating CDKN1A, which facilitates active cyclin-dependent kinase (CDK) complex formation. In cells stimulated by the phorbol ester PMA, can trigger a cell cycle arrest program which is associated with the accumulation of the hyper-phosphorylated growth-suppressive form of RB1 and induction of the CDK inhibitors CDKN1A and CDKN1B. Depending on the cell type, exhibits anti-apoptotic function and protects cells from apoptosis by suppressing the p53/TP53-mediated activation of IGFBP3, or mediates anti-apoptotic action by phosphorylating BCL2. During macrophage differentiation induced by macrophage colony-stimulating factor (CSF1), is translocated to the nucleus and is associated with macrophage development. After wounding, translocates from focal contacts to lamellipodia and participates in the modulation of desmosomal adhesion. Plays a role in cell motility by phosphorylating CSPG4, which induces association of CSPG4 with extensive lamellipodia at the cell periphery and polarization of the cell accompanied by increases in cell motility. During chemokine-induced CD4(+) T cell migration, phosphorylates CDC42-guanine exchange factor DOCK8 resulting in its dissociation from LRCH1 and the activation of GTPase CDC42. Negatively regulates myocardial contractility and positively regulates angiogenesis, platelet aggregation and thrombus formation in arteries. Mediates hypertrophic growth of neonatal cardiomyocytes, in part through a MAPK1/3 (ERK1/2)-dependent signaling pathway, and upon PMA treatment, is required to induce cardiomyocyte hypertrophy up to heart failure and death, by increasing protein synthesis, protein-DNA ratio and cell surface area. Regulates cardiomyocyte function by phosphorylating cardiac troponin T (TNNT2/CTNT), which induces significant reduction in actomyosin ATPase activity, myofilament calcium sensitivity and myocardial contractility. In angiogenesis, is required for full endothelial cell migration, adhesion to vitronectin (VTN), and vascular endothelial growth factor A (VEGFA)-dependent regulation of kinase activation and vascular tube formation. Involved in the stabilization of VEGFA mRNA at post-transcriptional level and mediates VEGFA-induced cell proliferation. In the regulation of calcium-induced platelet aggregation, mediates signals from the CD36/GP4 receptor for granule release, and activates the integrin heterodimer ITGA2B-ITGB3 through the RAP1GAP pathway for adhesion. During response to lipopolysaccharides (LPS), may regulate selective LPS-induced macrophage functions involved in host defense and inflammation. But in some inflammatory responses, may negatively regulate NF-kappa-B-induced genes, through IL1A-dependent induction of NF-kappa-B inhibitor alpha (NFKBIA/IKBA). Upon stimulation with 12-O-tetradecanoylphorbol-13-acetate (TPA), phosphorylates EIF4G1, which modulates EIF4G1 binding to MKNK1 and may be involved in the regulation of EIF4E phosphorylation. Phosphorylates KIT, leading to inhibition of KIT activity. Phosphorylates ATF2 which promotes cooperation between ATF2 and JUN, activating transcription. Phosphorylates SOCS2 at 'Ser-52' facilitating its ubiquitination and proteasomal degradation (By similarity). Phosphorylates KLHL3 in response to angiotensin II signaling, decreasing the interaction between KLHL3 and WNK4 (By similarity).
Classical (or conventional) PKCs (PRKCA, PRKCB and PRKCG) are activated by calcium and diacylglycerol (DAG) in the presence of phosphatidylserine. Three specific sites; Thr-497 (activation loop of the kinase domain), Thr-638 (turn motif) and Ser-657 (hydrophobic region), need to be phosphorylated for its full activation.
Interacts with ADAP1/CENTA1, CSPG4 and PRKCABP. Binds to CAVIN2 in the presence of phosphatidylserine. Interacts with PICK1 (via PDZ domain). Interacts with TRIM41. Recruited in a circadian manner into a nuclear complex which also includes BMAL1 and RACK1. Interacts with PARD3 (By similarity). Interacts with SOCS2 (By similarity).
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 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.
Heterodimer of an alpha and a beta subunit. Beta-8 (ITGB8) associates with alpha-V (ITGAV) to form ITGAV:ITGB8. ITGAV:ITGB8 interacts with TGFB1.
Integrin alpha-V:beta-8 (ITGAV:ITGB8) is a receptor for fibronectin (By similarity). It recognizes the sequence R-G-D in its ligands (By similarity). Integrin alpha-V:beta-6 (ITGAV:ITGB6) 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 on the surface of activated regulatory T-cells (Tregs) (By similarity). Required during vasculogenesis (By similarity).
Placenta, kidney, brain, ovary, uterus and in several transformed cells.
The VWFA domain (or beta I domain) contains two cation-binding sites: the ligand-associated metal ion-binding site (LIMBS or SyMBS) and the metal ion-dependent adhesion site (MIDAS). Unlike in the other beta integrins, the cation-binding site adjacent MIDAS site (ADMIDAS) in ITGB8 is not functional due to the presence of two Asn residues instead of 2 Asp residues. This domain is also part of the ligand-binding site.
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.
Belongs to the hcp beta-lactamase family.
Required for assembly of mitochondrial respiratory chain complexes.
Forms a 1:1 stoichiometric complex with (pro)colipase/CLPS.
Inhibited by bile salts, is reactivated by (pro)colipase/CLPS.
Plays an important role in fat metabolism. It preferentially splits the esters of long-chain fatty acids at positions 1 and 3, producing mainly 2-monoacylglycerol and free fatty acids, and shows considerably higher activity against insoluble emulsified substrates than against soluble ones.
Plays a role in the process of neurogenesis.
May activate the NF-kappa-B signaling pathway.
Belongs to the universal ribosomal protein uL2 family.
Necessary for protein translocation in the endoplasmic reticulum.
Translation factor that promotes translation elongation and termination, particularly upon ribosome stalling at specific amino acid sequence contexts. Binds between the exit (E) and peptidyl (P) site of the ribosome and promotes rescue of stalled ribosome: specifically required for efficient translation of polyproline-containing peptides as well as other motifs that stall the ribosome. Acts as ribosome quality control (RQC) cofactor by joining the RQC complex to facilitate peptidyl transfer during CAT tailing step.
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.
May play a role as a nucleotide-sugar transporter.
Functions as a dosage-dependent inducer in mitotic control. Tyrosine protein phosphatase required for progression of the cell cycle.
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.
Component of the CIA complex. Component of the MMXD complex, which includes CIAO1, ERCC2, FAM96B, MMS19 and SLC25A5. Interacts with WT1. Interacts with FAM96A.
Key component of the cytosolic iron-sulfur protein assembly (CIA) complex, a multiprotein complex that mediates the incorporation of iron-sulfur cluster into extramitochondrial Fe/S proteins. Seems to specifically modulate the transactivation activity of WT1. As part of the mitotic spindle-associated MMXD complex it may play a role in chromosome segregation.
Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively.
Interacts with PRAF2. Efficient ligand binding to CCL3/MIP-1alpha and CCL4/MIP-1beta requires sulfation, O-glycosylation and sialic acid modifications. Glycosylation on Ser-6 is required for efficient binding of CCL4. Interacts with GRK2. Interacts with ARRB1 and ARRB2. Interacts with CNIH4. Interacts with S100A4; this interaction stimulates T-lymphocyte chemotaxis.
O-glycosylated, but not N-glycosylated. Ser-6 appears to be the major site. Also sialylated glycans present which contribute to chemokine binding. Ser-17 may also be glycosylated and, if so, with small moieties such as a T-antigen (By similarity).
Palmitoylation in the C-terminal is important for cell surface expression.
Phosphorylation on serine residues in the C-terminal is stimulated by binding CC chemokines especially by APO-RANTES.
Receptor for a number of inflammatory CC-chemokines including CCL3/MIP-1-alpha, CCL4/MIP-1-beta and RANTES and subsequently transduces a signal by increasing the intracellular calcium ion level. May play a role in the control of granulocytic lineage proliferation or differentiation. Participates in T-lymphocyte migration to the infection site by acting as a chemotactic receptor.
Sulfated on at least 2 of the N-terminal tyrosines. Sulfation is required for efficient binding of the chemokines, CCL3 and CCL4 (By similarity).
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.
Exists as an octamer composed of four CKMT2 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 (By similarity).
Homodimer; head to tail assembly of 2 subunits. Interacts with CACYBP in a calcium-dependent manner. Interacts with ANXA2 and ANXA11 (via N-terminus). Interacts with SUGT1. Interacts with TP53; has higher affinity for TP53 that is phosphorylated on its N-terminal domain, and lower affinity for TP53 that is phosphorylated on its C-terminal domain. Interacts with tropomyosin. Interacts with FKBP4. Interacts with PPP5C (via TPR repeats); the interaction is calcium-dependent and modulates PPP5C activity. Interacts with TPPP; this interaction inhibits TPPP dimerization (By similarity).
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).
Binds to bacterial lipopolysaccharides (LPS), potentiates strongly the early antibacterial effects of BPI. Inhibits the late lethal action of BPI.
Belongs to the PMP-22/EMP/MP20 family. CACNG subfamily.
Belongs to the glycosyltransferase 28 family.
Activated by RHOA binding. Inhibited by Y-27632 (By similarity).
Autophosphorylated on serine and threonine residues.
Cleaved by caspase-3 during apoptosis. This leads to constitutive activation of the kinase and membrane blebbing (By similarity).
Homodimer. Interacts with RHOA (activated by GTP), RHOB, RHOC, GEM, MYLC2B, RHOE, PPP1R12A, LIMK1, LIMK2, TSG101, CHORDC1, DAPK3, PFN1, PTEN and JIP3. Interacts with FHOD1 in a Src-dependent manner. Interacts with ITGB1BP1 (via N-terminus and PTB domain). Interacts with SHROOM3 (By similarity).
Protein kinase which is a key regulator of the actin cytoskeleton and cell polarity (By similarity). Involved in regulation of smooth muscle contraction, actin cytoskeleton organization, stress fiber and focal adhesion formation, neurite retraction, cell adhesion and motility via phosphorylation of DAPK3, GFAP, LIMK1, LIMK2, MYL9/MLC2, TPPP, PFN1 and PPP1R12A (By similarity) (PubMed:9139666). Phosphorylates FHOD1 and acts synergistically with it to promote SRC-dependent non-apoptotic plasma membrane blebbing. Phosphorylates JIP3 and regulates the recruitment of JNK to JIP3 upon UVB-induced stress (By similarity). Acts as a suppressor of inflammatory cell migration by regulating PTEN phosphorylation and stability (By similarity). Acts as a negative regulator of VEGF-induced angiogenic endothelial cell activation. Required for centrosome positioning and centrosome-dependent exit from mitosis (By similarity). Plays a role in terminal erythroid differentiation (By similarity). Inhibits podocyte motility via regulation of actin cytoskeletal dynamics and phosphorylation of CFL1 (By similarity). Promotes keratinocyte terminal differentiation (By similarity). Involved in osteoblast compaction through the fibronectin fibrillogenesis cell-mediated matrix assembly process, essential for osteoblast mineralization (By similarity). May regulate closure of the eyelids and ventral body wall by inducing the assembly of actomyosin bundles (By similarity).
The C-terminal auto-inhibitory domain interferes with kinase activity. RHOA binding leads to a conformation change and activation of the kinase. Truncated ROCK1 is constitutively activated.
Belongs to the chloride channel (TC 2.A.49) family. ClC-3/CLCN3 subfamily.
Strongly outwardly rectifying, electrogenic H(+)/Cl(-)exchanger which mediates the exchange of chloride ions against protons (By similarity). The CLC channel family contains both chloride channels and proton-coupled anion transporters that exchange chloride or another anion for protons (By similarity). The presence of conserved gating glutamate residues is typical for family members that function as antiporters (By similarity).
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.
Forms a homodimer or heterodimer with other members of the family.
Phosphorylated in a calcium/calmodulin-dependent manner.
In the central section; belongs to the inositol 1,4,5-trisphosphate 5-phosphatase family.
Belongs to the peroxisomal membrane protein PXMP2/4 family.
Homodimer or homotrimer. Interacts (via FFAT motif) with VAPA. Interacts (via C-terminus) with RELCH (via the third HEAT repeat) (By similarity). Found in a complex composed of RELCH, OSBP1 and RAB11A (By similarity).
Lipid transporter involved in lipid countertransport between the Golgi complex and membranes of the endoplasmic reticulum: specifically exchanges sterol with phosphatidylinositol 4-phosphate (PI4P), delivering sterol to the Golgi in exchange for PI4P, which is degraded by the SAC1/SACM1L phosphatase in the endoplasmic reticulum (By similarity). Binds cholesterol and a range of oxysterols including 25-hydroxycholesterol (PubMed:18165705). Cholesterol binding promotes the formation of a complex with PP2A and a tyrosine phosphatase which dephosphorylates ERK1/2, whereas 25-hydroxycholesterol causes its disassembly (By similarity). Regulates cholesterol efflux by decreasing ABCA1 stability (By similarity).
The FFAT motif is required for interaction with VATA and proper localization of the protein.
The PH and the Ala/Gly-rich domains control cholesterol binding without affecting 25-hydroxycholesterol binding.
The second coiled-coil domain is required for interaction with the tyrosine phosphatase.
Encoded on a bicistronic transcript that code for two proteins, SNRPN and SNURF.
In the N-terminal section; belongs to the enoyl-CoA hydratase/isomerase family.
Belongs to the PDK/BCKDK protein kinase family.
Belongs to the TALE/PBX homeobox family.
Belongs to the HAD-like hydrolase superfamily.
High-affinity transporter for the intake of thiamine.
Decapping scavenger enzyme that catalyzes the cleavage of a residual cap structure following the degradation of mRNAs by the 3'->5' exosome-mediated mRNA decay pathway.
Homodimer. Associates with components of the exosome multienzyme ribonuclease complex, such as EXOSC3 and EXOSC4. Interacts with NDOR1.
In muscle, parvalbumin is thought to be involved in relaxation after contraction. It binds two calcium ions.
This parvalbumin has an isoelectric point of 5.50.
Belongs to the AB hydrolase superfamily. AB hydrolase 4 family.
Belongs to the TRAPP small subunits family.
Part of the multisubunit transport protein particle (TRAPP) complex.
Has a glutathione-disulfide oxidoreductase activity in the presence of NADPH and glutathione reductase. Reduces low molecular weight disulfides and proteins.
Catalyzes the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PtdIns-4,5-P2) to phosphatidylinositol-4-phosphate (PtdIns-4-P).
Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. NIM1 subfamily.
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. The eIF-3 complex appears to include 3 stable modules: module A is composed of EIF3A, EIF3B, EIF3G and EIF3I; module B is composed of EIF3F, EIF3H, and EIF3M; and module C is composed of EIF3C, EIF3D, EIF3E, EIF3K and EIF3L. EIF3C of module C binds EIF3B of module A and EIF3H of module B, thereby linking the three modules. EIF3J is a labile subunit that binds to the eIF-3 complex via EIF3B. The eIF-3 complex interacts with RPS6KB1 under conditions of nutrient depletion. Mitogenic stimulation leads to binding and activation of a complex composed of MTOR and RPTOR, leading to phosphorylation and release of RPS6KB1 and binding of EIF4B to eIF-3. Interacts with CCND3, but not with CCND1 and CCND2.
Required for gamma-tubulin complex recruitment to the centrosome.
In the C-terminal section; belongs to the sulfate adenylyltransferase family.
In the N-terminal section; belongs to the APS kinase family.
Contains one proline-rich sequence (Pro-Glu-Ser-Pro-Arg) that may be involved in tyrosine-protein kinase YES1 binding and is requirered for the induction of transport activity.
Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics. Functions as a Na(+)-independent, bidirectional uniporter. Cation cellular uptake or release is driven by the electrochemical potential, i.e. membrane potential and concentration gradient (By similarity). However, may also engage electroneutral cation exchange when saturating concentrations of cation substrates are reached (By similarity). Predominantly expressed at the basolateral membrane of hepatocytes and proximal tubules and involved in the uptake and disposition of cationic compounds by hepatic and renal clearance from the blood flow. Implicated in monoamine neurotransmitters uptake such as histamine, dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, serotonin and tyramine, thereby supporting a physiological role in the central nervous system by regulating interstitial concentrations of neurotransmitters. Also capable of transporting dopaminergic neuromodulators cyclo(his-pro), salsolinol and N-methyl-salsolinol, thereby involved in the maintenance of dopaminergic cell integrity in the central nervous system. Mediates the bidirectional transport of acetylcholine (ACh) at the apical membrane of ciliated cell in airway epithelium, thereby playing a role in luminal release of ACh from bronchial epithelium. Also transports guanidine and endogenous monoamines such as vitamin B1/thiamine, creatinine and N-1-methylnicotinamide (NMN). Mediates the uptake and efflux of quaternary ammonium compound choline. Mediates the bidirectional transport of polyamine agmatine and the uptake of polyamines putrescine and spermidine. Able to transport non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha). Also involved in the uptake of xenobiotic 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP). May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (By similarity).
May be down-regulated in diabetic patients.
Mediates the renal secretion of many clinically used cationic drugs. Transports drugs such as diabetes treatment medicine metformin and neurotoxins 1-methyl-4-phenylpyridinium (MPP(+)), famotidine, ranitidine, amantadine, acriflavine, amiloride, memantine, cimetidine, cisplatin, oxaliplatin, platinum-based drugs cisplatin and oxaliplatin, 3'-azido-3'-deoxythymidine (AZT) and tetraethylammonium (TEA). Mediates the bidirectional transport of MPP(+). Metformin competitively inhibits OCT1-mediated thiamine uptake, leading to a decrease in hepatic steatosis. Plays a predominant role in the anticancer activity of cisplatin and oxaliplatin and may contribute to antitumor specificity (By similarity). Involved in cisplatin-induced nephrotoxicity (By similarity).
Tyrosine phosphorylation of the transporter leads to activation of the transport activity. Inhibited by cGMP, most likely through a cGMP-binding protein that interacts with OCT2.
While most authors have deduced a localization at the basolateral membrane of proximal tubules, other studies demonstrated a localization to the luminal membrane in the distal tubule.
Catalyzes the final step in the metabolic pathway of hydroxyproline.
Belongs to the proteasome subunit S5B/HSM3 family.
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.
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.
Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase (By similarity).
Component of the ubiquinol-cytochrome c reductase complex (complex III or cytochrome b-c1 complex) that is part of the mitochondrial respiratory chain. The b-c1 complex mediates electron transfer from ubiquinol to cytochrome c. Contributes to the generation of a proton gradient across the mitochondrial membrane that is then used for ATP synthesis.
Heme 1 (or BL or b562) is low-potential and absorbs at about 562 nm, and heme 2 (or BH or b566) is high-potential and absorbs at about 566 nm.
The cytochrome bc1 complex contains 11 subunits: 3 respiratory subunits (MT-CYB, CYC1 and UQCRFS1), 2 core proteins (UQCRC1 and UQCRC2) and 6 low-molecular weight proteins (UQCRH/QCR6, UQCRB/QCR7, UQCRQ/QCR8, UQCR10/QCR9, UQCR11/QCR10 and a cleavage product of UQCRFS1). This cytochrome bc1 complex then forms a dimer.
The full-length protein contains only eight transmembrane helices, not nine as predicted by bioinformatics tools.
The [NKR]KIAxRE motif seems to be a cyclin-binding region.
Belongs to the Mediator complex subunit 28 family.
Down-regulated by doxorubicin (adriamycin), in vitro.
May play an important role in endothelial cell activation. May act as a nuclear transcription factor that negatively regulates the expression of cardiac genes (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.
Acts specifically as a negative regulator of skeletal muscle growth.
Homodimer; disulfide-linked. Interacts with WFIKKN2, leading to inhibit its activity. Interacts with FSTL3.
Belongs to the peroxiredoxin family. Prx6 subfamily.
Together with ARL2, plays a role in the nuclear translocation, retention and transcriptional activity of STAT3. May play a role as an effector of ARL2.
After cleavage, the post-translationally modified ChM-I is secreted as a glycoprotein.
Bifunctional growth regulator that stimulates the growth of cultured chondrocytes in the presence of basic fibroblast growth factor (FGF) but inhibits the growth of cultured vascular endothelial cells. May contribute to the rapid growth of cartilage and vascular invasion prior to the replacement of cartilage by bone during endochondral bone development. Inhibits in vitro tube formation and mobilization of endothelial cells. Plays a role as antiangiogenic factor in cardiac valves to suppress neovascularization (By similarity).
Belongs to the DPH1/DPH2 family. DPH2 subfamily.
Required for the first step of diphthamide biosynthesis, a post-translational modification of histidine which occurs in elongation factor 2. 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. Facilitates the reduction of the catalytic iron-sulfur cluster found in the DPH1 subunit.
Belongs to the non-lysosomal glucosylceramidase family.
Non-lysosomal glucosylceramidase that catalyzes the hydrolysis of glucosylceramide (GlcCer) to free glucose and ceramide.
Catalyzes the hydrolysis of triglycerides and phospholipids present in circulating plasma lipoproteins, including chylomicrons, intermediate density lipoproteins (IDL), low density lipoproteins (LDL) of large size and high density lipoproteins (HDL), releasing free fatty acids (FFA) and smaller lipoprotein particles (PubMed:1770315). Also exhibits lysophospholipase activity (By similarity). Can hydrolyze both neutral lipid and phospholipid substrates but shows a greater binding affinity for neutral lipid substrates than phospholipid substrates (By similarity). In native LDL, preferentially hydrolyzes the phosphatidylcholine species containing polyunsaturated fatty acids at sn-2 position (By similarity).
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.
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.
Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type. Involved in cell cycle regulation as a trans-activator that acts to negatively regulate cell division by controlling a set of genes required for this process. One of the activated genes is an inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression.
Binds DNA as a homotetramer. Isoform composition of the tetramer may determine transactivation activity.
Appears to play a role in the switch from cap-dependent to IRES-mediated translation during mitosis, apoptosis and viral infection. Cleaved by some caspases and viral proteases.
Interacts with the serine/threonine protein kinases MKNK1 and MKNK2. Binds EIF4A and EIF3. Interacts with MIF4GD (By similarity). Interacts with DAZAP2 (By similarity).
Phosphorylation; hyperphosphorylated during mitosis.
This gene has been shown to be extensively edited in the liver of APOBEC1 transgenic animals. Its aberrant editing could contribute to the potent oncogenesis induced by overexpression of APOBEC1. The aberrant edited sequence, called NAT1, is likely to be a fundamental translational repressor.
Guanine nucleotide exchange factor that specifically activates the small GTPase SAR1B. Mediates the recruitment of SAR1B and other COPII coat components to endoplasmic reticulum membranes and is therefore required for the formation of COPII transport vesicles from the ER.
Interacts with SAR1B (GDP-bound form). Interacts with MIA2; recruits PREB to endoplasmic reticulum exit sites.
Was first identified based on its probable role in the regulation of pituitary gene transcription. Binds to the prolactin gene (PRL) promoter and seems to activate transcription.
A connexon is composed of a hexamer of connexins. Interacts with CNST.
Belongs to the connexin family. Gamma-type subfamily.
Component of a calcium channel complex consisting of a pore-forming alpha subunit (CACNA1S) and the ancillary subunits CACNB1 or CACNB2, CACNG1 and CACNA2D1 (PubMed:2158672, PubMed:12409298, PubMed:26680202, PubMed:27580036). 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 (PubMed:26680202, PubMed:27580036).
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 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.
According to a well-established model, RNF8 initiate H2A 'Lys-63'-linked ubiquitination leading to recruitment of RNF168 to amplify H2A 'Lys-63'-linked ubiquitination. However, other data suggest that RNF168 is the priming ubiquitin ligase by mediating monoubiquitination of 'Lys-13' and 'Lys-15' of nucleosomal histone H2A (H2AK13Ub and H2AK15Ub respectively). These data suggest that RNF168 might be recruited to DSBs sites in a RNF8-dependent manner by binding to non-histone proteins ubiquitinated via 'Lys-63'-linked and initiates monoubiquitination of H2A, which is then amplified by RNF8. Additional evidences are however required to confirm these data.
Autoubiquitinated through 'Lys-48' and 'Lys-63' of ubiquitin. 'Lys-63' polyubiquitination is mediated by UBE2N. 'Lys-29'-type polyubiquitination is also observed, but it doesn't require its own functional RING-type zinc finger.
E3 ubiquitin-protein ligase that plays a key role in DNA damage signaling via 2 distinct roles: by mediating the 'Lys-63'-linked ubiquitination of histones H2A and H2AX and promoting the recruitment of DNA repair proteins at double-strand breaks (DSBs) sites, and by catalyzing 'Lys-48'-linked ubiquitination to remove target proteins from DNA damage sites. Following DNA DSBs, it is recruited to the sites of damage by ATM-phosphorylated MDC1 and catalyzes the 'Lys-63'-linked ubiquitination of histones H2A and H2AX, thereby promoting the formation of TP53BP1 and BRCA1 ionizing radiation-induced foci (IRIF). Also controls the recruitment of UIMC1-BRCC3 (RAP80-BRCC36) and PAXIP1/PTIP to DNA damage sites. Also recruited at DNA interstrand cross-links (ICLs) sites and catalyzes 'Lys-63'-linked ubiquitination of histones H2A and H2AX, leading to recruitment of FAAP20 and Fanconi anemia (FA) complex, followed by interstrand cross-link repair. H2A ubiquitination also mediates the ATM-dependent transcriptional silencing at regions flanking DSBs in cis, a mechanism to avoid collision between transcription and repair intermediates. Promotes the formation of 'Lys-63'-linked polyubiquitin chains via interactions with the specific ubiquitin-conjugating UBE2N/UBC13 and ubiquitinates non-histone substrates such as PCNA. Substrates that are polyubiquitinated at 'Lys-63' are usually not targeted for degradation. Also catalyzes the formation of 'Lys-48'-linked polyubiquitin chains via interaction with the ubiquitin-conjugating UBE2L6/UBCH8, leading to degradation of substrate proteins such as CHEK2, JMJD2A/KDM4A and KU80/XRCC5: it is still unclear how the preference toward 'Lys-48'- versus 'Lys-63'-linked ubiquitination is regulated but it could be due to RNF8 ability to interact with specific E2 specific ligases. For instance, interaction with phosphorylated HERC2 promotes the association between RNF8 and UBE2N/UBC13 and favors the specific formation of 'Lys-63'-linked ubiquitin chains. Promotes non-homologous end joining (NHEJ) by promoting the 'Lys-48'-linked ubiquitination and degradation the of KU80/XRCC5. Following DNA damage, mediates the ubiquitination and degradation of JMJD2A/KDM4A in collaboration with RNF168, leading to unmask H4K20me2 mark and promote the recruitment of TP53BP1 at DNA damage sites. Following DNA damage, mediates the ubiquitination and degradation of POLD4/p12, a subunit of DNA polymerase delta. In the absence of POLD4, DNA polymerase delta complex exhibits higher proofreading activity. In addition to its function in damage signaling, also plays a role in higher-order chromatin structure by mediating extensive chromatin decondensation. Involved in the activation of ATM by promoting histone H2B ubiquitination, which indirectly triggers histone H4 'Lys-16' acetylation (H4K16ac), establishing a chromatin environment that promotes efficient activation of ATM kinase. Required in the testis, where it plays a role in the replacement of histones during spermatogenesis. At uncapped telomeres, promotes the joining of deprotected chromosome ends by inducing H2A ubiquitination and TP53BP1 recruitment, suggesting that it may enhance cancer development by aggravating telomere-induced genome instability in case of telomeric crisis. Promotes the assembly of RAD51 at DNA DSBs in the absence of BRCA1 and TP53BP1 Also involved in class switch recombination in immune system, via its role in regulation of DSBs repair. May be required for proper exit from mitosis after spindle checkpoint activation and may regulate cytokinesis. May play a role in the regulation of RXRA-mediated transcriptional activity. Not involved in RXRA ubiquitination by UBE2E2.
Homodimer. Forms a E2-E3 ubiquitin ligase complex composed of the RNF8 homodimer and a E2 heterodimer of UBE2N and UBE2V2. Interacts with class III E2s, including UBE2E1, UBE2E2, and UBE2E3 and with UBE2N. Interacts with RXRA. Interacts (via FHA domain) with phosphorylated HERC2 (via C-terminus). Interacts with PIWIL1; leading to sequester RNF8 in the cytoplasm.
The FHA domain specifically recognizes and binds ATM-phosphorylated MDC1 and phosphorylated HERC2.
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 pICln (TC 1.A.47) family.
Belongs to the tRNA pseudouridine synthase TruA family.
Belongs to the phosphoenolpyruvate carboxykinase [GTP] family.
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. DMPK subfamily.
Required for 60S pre-ribosomal subunits export to the cytoplasm.
Belongs to the class I-like SAM-binding methyltransferase superfamily. RNA methyltransferase RlmE family. TRM7 subfamily.
Methylates the 2'-O-ribose of nucleotides at positions 32 and 34 of the tRNA anticodon loop of substrate tRNAs.
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.
Gap-filling polymerase involved in repair of DNA double-strand breaks by non-homologous end joining (NHEJ).
Transports zinc ions across cell and organelle membranes into the cytoplasm and regulates intracellular zinc homeostasis. Participates in the zinc ions efflux out of the secretory compartments. Also functions as membrane androgen receptor that mediates, through a G protein, the non-classical androgen signaling pathway, characterized by the activation of MAPK3/MAPK1 (Erk1/2) and transcription factors CREB1 or ATF1. Moreover, has dual functions as membrane-bound androgen receptor and as an androgen-dependent zinc transporter both of which are mediated through an inhibitory G protein (Gi) that mediates both MAP kinase and zinc signaling leading to the androgen-dependent apoptotic process.
Belongs to the PPP phosphatase family. PP-4 (PP-X) subfamily.
Methylation at the C-terminal Leu-307 is critical for interactions with regulatory subunits and functions in DNA repair.
Protein phosphatase that is involved in many processes such as microtubule organization at centrosomes, maturation of spliceosomal snRNPs, apoptosis, DNA repair, tumor necrosis factor (TNF)-alpha signaling, activation of c-Jun N-terminal kinase MAPK8, regulation of histone acetylation, DNA damage checkpoint signaling, NF-kappa-B activation and cell migration. The PPP4C-PPP4R1 PP4 complex may play a role in dephosphorylation and regulation of HDAC3. The PPP4C-PPP4R2-PPP4R3A PP4 complex specifically dephosphorylates H2AX phosphorylated on Ser-140 (gamma-H2AX) generated during DNA replication and required for DNA DSB repair. Dephosphorylates NDEL1 at CDK1 phosphorylation sites and negatively regulates CDK1 activity in interphase (By similarity). In response to DNA damage, catalyzes RPA2 dephosphorylation, an essential step for DNA repair since it allows the efficient RPA2-mediated recruitment of RAD51 to chromatin (By similarity).
Serine/threonine-protein phosphatase 4 (PP4) occurs in different assemblies of the catalytic and one or more regulatory subunits. Component of the PP4 complexes PPP4C-PPP4R1, PPP4C-PPP4R2, PPP4C-PPP4R2-PPP4R3A, PPP4C-PPP4R2-PPP4R3B and PPP4C-PPP4R4. The PPP4C-PPP4R2 complex appears to be a tetramer composed of 2 molecules of PPP4C and 2 molecules of PPP4R2. Interacts with REL, NFKB1/p50 and RELA. Interacts with SMN1 and GEMIN4. Interacts with IRS4 (phosphorylated). Interacts with SMEK1/PPP4R3A; the interaction requires PP4R2. Interacts with HDAC3 (By similarity).
Belongs to the eukaryotic ribosomal protein eL34 family.
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.
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 trans-sulfuration enzymes family.
Ammonium transporter involved in the maintenance of acid-base homeostasis. Transports ammonium and its related derivative methylammonium across the basolateral plasma membrane of epithelial cells likely contributing to renal transepithelial ammonia transport and ammonia metabolism. May transport either NH4(+) or NH3 ammonia species predominantly mediating an electrogenic NH4(+) transport (By similarity). May act as a CO2 channel providing for renal acid secretion (By similarity).
Interacts (via C-terminus) with ANK2 and ANK3; required for targeting to the basolateral membrane.
Endoplasmic reticulum and mitochondria-associated protein that probably functions as a regulator of cellular redox state and thereby regulates protein post-translational modification, protein folding and mitochondrial activity. Indirectly regulates neuronal proliferation, migration, and organization in the developing brain.
Component of the eIF2 complex that 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 the 43S pre-initiation complex (43S PIC). Junction of the 60S ribosomal subunit to form the 80S initiation complex is preceded by hydrolysis of the GTP bound to eIF2 and release of an eIF2-GDP binary complex. In order for eIF2 to recycle and catalyze another round of initiation, the GDP bound to eIF2 must exchange with GTP by way of a reaction catalyzed by eIF-2B.
eIF2 is an heterotrimer composed of an alpha (EIF2S1), a beta (EIF2S2) and a gamma (EIF2S3) chain (By similarity). eIF2 is member of the 43S pre-initiation complex (43S PIC). eIF2 forms a complex with at least CELF1/CUGBP1, CALR, CALR3, EIF2S1, EIF2S2, HSP90B1 and HSPA5 (By similarity). Interacts with BZW2/5MP1 (By similarity). Interacts with EIF5 (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 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.
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.
Belongs to the eukaryotic ribosomal protein eS12 family.
Belongs to the zinc-containing alcohol dehydrogenase family. Class-II subfamily.
Component of 250-400 kDa complexes called cytochrome oxidase assembly intermediates or COA complexes.
Core component of the MITRAC (mitochondrial translation regulation assembly intermediate of cytochrome c oxidase complex) complex, that regulates cytochrome c oxidase assembly. MITRAC complexes regulate both translation of mitochondrial encoded components and assembly of nuclear-encoded components imported in mitochondrion. Required for efficient translation of MT-CO1 and mitochondrial respiratory chain complex IV assembly.
Required for assembly of cytochrome c oxidase (complex IV).
Detected in skeletal muscle (at protein level).
Interacts with GGCX (By similarity). Interacts with RYR1 in the presence of calcium ions, but not in the presence of EDTA.
Involved in regulation of vitamin K-dependent carboxylation of multiple N-terminal glutamate residues. Seems to inhibit gamma-carboxylase GGCX. Binds 7 calcium ions with a low affinity (By similarity). May modulate calcium release from the sarcoplasmic reticulum.
PubMed:16527250 attributed the differences between their clones to the existence of two separate genes. This seems rather unlikely, considering that the cDNAs are 100% identical outside of this clearly delimited zone.
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.
Binds GTP but lacks intrinsic GTPase activity and is resistant to Rho-specific GTPase-activating proteins.
Belongs to the Mediator complex subunit 30 family.
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. Enhances the enzymatic activity of SPC and facilitates the interactions between different components of the translocation site.
Associates with ribosomes; promoting ribosome inactivation.
Ribosome-binding protein that acts as an inhibitor of mRNA translation by promoting ribosome inactivation (PubMed:30355441). Associates with the P- and E-sites of the ribosome and inserts a C-terminal helix into the mRNA exit channel to preclude translation (PubMed:30355441).
Binds to bile acids and is involved in enterohepatic bile acid metabolism. Required for efficient apical to basolateral transport of conjugated bile acids in ileal enterocytes. Stimulates gastric acid and pepsinogen secretion (By similarity).
Forms a beta-barrel structure that accommodates hydrophobic ligands in its interior. Can bind at least two ligands per molecule, however, the stoichiometry is debated.
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 CTNNB1 at 'Ser-45' (By similarity). May phosphorylate PER1 and PER2 (By similarity). May play a role in segregating chromosomes during mitosis. May play a role in keratin cytoskeleton disassembly and thereby, it may regulate epithelial cell migration (By similarity). Acts as a positive regulator of mTORC1 and mTORC2 signaling in response to nutrients by mediating phosphorylation of DEPTOR inhibitor (By similarity). Acts as an inhibitor of NLRP3 inflammasome assembly by mediating phosphorylation of NLRP3 (By similarity).
Interacts with the Axin complex (By similarity). Interacts with TUT1, leading to TUT1 phosphorylation (By similarity). Interacts with FAM83H; recruits CSNK1A1 to keratin filaments (By similarity). Interacts with FAM83D (via N-terminus); in mitotic cells (By similarity).
Phosphorylated by MTOR in response to mitogenic stimulation, leading to its activation.
Regulates intra- and extracellular levels of inorganic pyrophosphate (PPi), probably functioning as PPi transporter.
Homodimer. Preferentially exists as a heterodimer or heterotetramer with S100A8 known as calprotectin (S100A8/A9) (By similarity). S100A9 interacts with ATP2A2 (By similarity). S100A9 interacts with AGER, and with the heterodimeric complex formed by TLR4 and LY96 in the presence of calcium and/or zinc ions. S100A9 binds quinoline-3-carboxamides in the presence of calcium and/or zinc ions. S100A9 interacts with amyloid-beta protein 40. Calprotectin (S100A8/9) interacts with CEACAM3 and tubulin filaments in a calcium-dependent manner. Heterotetrameric calprotectin (S100A8/A9) interacts with ANXA6 and associates with tubulin filaments in activated monocytes. Calprotectin (S100A8/9) interacts with NCF2/P67PHOX, RAC1, RAC2, CYBA and CYBB. Calprotectin (S100A8/9) interacts with NOS2 to form the iNOS-S100A8/A9 transnitrosylase complex; induced by LDL(ox) (By similarity).
Methylation at His-107 by METTL9 reduces zinc-binding without affecting heterodimerization with S100A8.
Phosphorylated. Phosphorylation inhibits activation of tubulin polymerization.
S100A9 is a calcium- and zinc-binding protein which plays a prominent role in the regulation of inflammatory processes and immune response. It can induce neutrophil chemotaxis, adhesion, can increase the bactericidal activity of neutrophils by promoting phagocytosis via activation of SYK, PI3K/AKT, and ERK1/2 and can induce degranulation of neutrophils by a MAPK-dependent mechanism. Predominantly found as calprotectin (S100A8/A9) which has a wide plethora of intra- and extracellular functions. The intracellular functions include: facilitating leukocyte arachidonic acid trafficking and metabolism, modulation of the tubulin-dependent cytoskeleton during migration of phagocytes and activation of the neutrophilic NADPH-oxidase. Activates NADPH-oxidase by facilitating the enzyme complex assembly at the cell membrane, transferring arachidonic acid, an essential cofactor, to the enzyme complex and S100A8 contributes to the enzyme assembly by directly binding to NCF2/P67PHOX. The extracellular functions involve pro-inflammatory, antimicrobial, oxidant-scavenging and apoptosis-inducing activities. Its pro-inflammatory activity includes recruitment of leukocytes, promotion of cytokine and chemokine production, and regulation of leukocyte adhesion and migration. Acts as an alarmin or a danger associated molecular pattern (DAMP) molecule and stimulates innate immune cells via binding to pattern recognition receptors such as Toll-like receptor 4 (TLR4) and receptor for advanced glycation endproducts (AGER). Binding to TLR4 and AGER activates the MAP-kinase and NF-kappa-B signaling pathways resulting in the amplification of the pro-inflammatory cascade. Has antimicrobial activity towards bacteria and fungi and exerts its antimicrobial activity probably via chelation of Zn(2+) which is essential for microbial growth. Can induce cell death via autophagy and apoptosis and this occurs through the cross-talk of mitochondria and lysosomes via reactive oxygen species (ROS) and the process involves BNIP3. Can regulate neutrophil number and apoptosis by an anti-apoptotic effect; regulates cell survival via ITGAM/ITGB and TLR4 and a signaling mechanism involving MEK-ERK. Its role as an oxidant scavenger has a protective role in preventing exaggerated tissue damage by scavenging oxidants. The iNOS-S100A8/A9 transnitrosylase complex is proposed to direct selective inflammatory stimulus-dependent S-nitrosylation of multiple targets such as GAPDH, NXA5, EZR, MSN and VIM by recognizing a [IL]-x-C-x-x-[DE] motif.
Interacts (when auto-poly-ADP-ribosylated) with AIFM1.
Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair.
This cleavage form irreversibly binds to DNA breaks and interferes with DNA repair, promoting DNA damage-induced apoptosis.
Adds a GMP to the 5'-end of tRNA(His) after transcription and RNase P cleavage.
Belongs to the tRNA(His) guanylyltransferase family.
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.
Required for biogenesis of the 60S ribosomal subunit.
Belongs to the nuclear transition protein 1 family.
Catalyzes the ATP-dependent amination of UTP to CTP with either L-glutamine or ammonia as the source of nitrogen.
Belongs to the eukaryotic GSH synthase family.
Belongs to the dicarboxylate/amino acid:cation symporter (DAACS) (TC 2.A.23) family.
Belongs to the eukaryotic ribosomal protein eS8 family.
Interacts with mitochondrial RNA polymerase POLRMT. Interacts with TFAM.
S-adenosyl-L-methionine-dependent methyltransferase which specifically dimethylates mitochondrial 12S rRNA at the conserved stem loop. Also required for basal transcription of mitochondrial DNA, probably via its interaction with POLRMT and TFAM. Stimulates transcription independently of the methyltransferase activity.
GTPase-activating protein (GAP) for ADP ribosylation factor 6 (ARF6).
Interacts with RAB35 (GTP-bound form); the interaction is direct and probably recruits ACAP2 to membranes. Interacts with MICALL1; the interaction is indirect through RAB35 (By similarity).
Catalyzes the oxidation of uric acid to 5-hydroxyisourate, which is further processed to form (S)-allantoin.
Belongs to the protein-tyrosine phosphatase family. Non-receptor class 1 subfamily.
Binds anionic lipids and gangliosides at acidic pH.
Belongs to the MINDY deubiquitinase family. FAM63 subfamily.
Hydrolase that can specifically remove 'Lys-48'-linked conjugated ubiquitin from proteins. Has exodeubiquitinase activity and has a preference for long polyubiquitin chains. May play a regulatory role at the level of protein turnover.
Homodimer (By similarity). Interacts with GLMN; rapamycin and FK506 abolish the interaction with GLMN in a dose dependent manner (PubMed:8955134). Associates with HSP90AA1 and HSP70 in steroid hormone receptor complexes. Also interacts with peroxisomal phytanoyl-CoA alpha-hydroxylase (PHYH) (PubMed:10051602). Interacts with NR3C1 and dynein. Interacts with HSF1 in the HSP90 complex. Associates with tubulin. Interacts with MAPT/TAU (By similarity). Interacts (via TPR domain) with S100A1, S100A2 and S100A6; the interaction is Ca(2+) dependent. Interaction with S100A1 and S100A2 (but not with S100A6) leads to inhibition of FKBP4-HSP90 interaction. Interacts with dynein; causes partially NR3C1 transport to the nucleus.
Immunophilin protein with PPIase and co-chaperone activities. Component of steroid receptors heterocomplexes through interaction with heat-shock protein 90 (HSP90). May play a role in the intracellular trafficking of heterooligomeric forms of steroid hormone receptors between cytoplasm and nuclear compartments. The isomerase activity controls neuronal growth cones via regulation of TRPC1 channel opening. Acts also as a regulator of microtubule dynamics by inhibiting MAPT/TAU ability to promote microtubule assembly. May have a protective role against oxidative stress in mitochondria (By similarity).
Phosphorylation by CK2 results in loss of HSP90 binding activity.
The C-terminal region (AA 375-458) is required to prevent tubulin polymerization.
The PPIase activity is mainly due to the first PPIase FKBP-type domain (1-138 AA).
The TPR repeats mediate mitochondrial localization.
The chaperone activity resides in the C-terminal region, mainly between amino acids 264 and 400.
Belongs to the small leucine-rich proteoglycan (SLRP) family. SLRP class I subfamily.
Binds to type I and type II collagen, fibronectin and TGF-beta. Forms a ternary complex with MFAP2 and ELN. Interacts with DPT (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 mitochondrion-specific ribosomal protein mL51 family.
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.
Electrogenic Na(+)-coupled sugar simporter that actively transports D-glucose or D-galactose at the plasma membrane, with a Na(+) to sugar coupling ratio of 2:1. Transporter activity is driven by a transmembrane Na(+) electrochemical gradient set by the Na(+)/K(+) pump (By similarity). Has a primary role in the transport of dietary monosaccharides from enterocytes to blood. Responsible for the absorption of D-glucose or D-galactose across the apical brush-border membrane of enterocytes, whereas basolateral exit is provided by GLUT2. Additionally, functions as a D-glucose sensor in enteroendocrine cells, triggering the secretion of the incretins GCG and GIP that control food intake and energy homeostasis (By similarity). Together with SGLT2, functions in reabsorption of D-glucose from glomerular filtrate, playing a nonredundant role in the S3 segment of the proximal tubules (By similarity). Transports D-glucose into endometrial epithelial cells, controlling glycogen synthesis and nutritional support for the embryo as well as the decidual transformation of endometrium prior to conception (By similarity). Acts as a water channel enabling passive water transport in response to the osmotic gradient created upon sugar and Na(+) uptake. Has high water conductivity comparable to aquaporins and therefore is expected to play an important role in transepithelial water permeability, especially in the small intestine.
Found predominantly in intestine, renal cortex and in outer renal medulla.
Mutation of Asp-28 is implicated in glucose/galactose malabsorption.
N-glycosylation is not necessary for the cotransporter function.
The cholesterol-binding site is formed by transmembrane helices TM1, TM7 and TM13.
Belongs to the membrane-bound acyltransferase family. Sterol o-acyltransferase subfamily.
May play a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier.
Belongs to the universal ribosomal protein uS9 family.
Junctophilins contribute to the formation of junctional membrane complexes (JMCs) which link the plasma membrane with the endoplasmic or sarcoplasmic reticulum in excitable cells. Provides a structural foundation for functional cross-talk between the cell surface and intracellular calcium release channels. JPH1 contributes to the construction of the skeletal muscle triad by linking the t-tubule (transverse-tubule) and SR (sarcoplasmic reticulum) membranes (By similarity).
The MORN (membrane occupation and recognition nexus) repeats contribute to the plasma membrane binding, possibly by interacting with phospholipids.
Component of the TIM23 complex at least composed of TIMM23, TIMM17 (TIMM17A or TIMM17B) and TIMM50.
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 sepiapterin reductase family.
Binds 1 Mg(2+) or Mn(2+) ion per subunit.
Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
May act as a physical homophilic interaction molecule between intestinal epithelial cells (IECs) and intraepithelial lymphocytes (IELs) at the mucosal epithelium for providing immunological barrier as a first line of defense against mucosal infection. Plays a role in embryonic stem cells proliferation and differentiation. Up-regulates the expression of FABP5, MYC and cyclins A and E.
Binds 2 zinc divalent cations per subunit.
Homodimer. Bile acids promote the assembly of inactive monomers into an active dimer and enable catalysis.
Interacts with DDX4, PIWIL1, RANBP9 and TDRD1.
Plays a central role during spermatogenesis by repressing transposable elements and preventing their mobilization, which is essential for the germline integrity. Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and governs the methylation and subsequent repression of transposons. Its association with pi-bodies suggests a participation in the primary piRNAs metabolic process. Required prior to the pachytene stage to facilitate the production of multiple types of piRNAs, including those associated with repeats involved in the regulation of retrotransposons. May act by mediating protein-protein interactions during germ cell maturation (By similarity).
Consists mainly of a membrane-spanning beta-barrel formed by 19 beta-strands. The helical N-terminus folds back into the pore opening and plays a role in voltage-gated channel activity.
Forms a channel through the mitochondrial outer membrane and also the plasma membrane. The channel at the outer mitochondrial membrane allows diffusion of small hydrophilic molecules; in the plasma membrane it is involved in cell volume regulation and apoptosis. It adopts an open conformation at low or zero membrane potential and a closed conformation at potentials above 30-40 mV. The open state has a weak anion selectivity whereas the closed state is cation-selective. Binds various signaling molecules, including the sphingolipid ceramide, the phospholipid phosphatidylcholine, and the sterol cholesterol. In depolarized mitochondria, acts downstream of PRKN and PINK1 to promote mitophagy or prevent apoptosis; polyubiquitination by PRKN promotes mitophagy, while monoubiquitination by PRKN decreases mitochondrial calcium influx which ultimately inhibits apoptosis. May participate in the formation of the permeability transition pore complex (PTPC) responsible for the release of mitochondrial products that triggers apoptosis. May mediate ATP export from cells.
Homodimer and homotrimer; in response to cyclic AMP or calcium. Interacts with hexokinases including HK1. The HK1-VDAC1 complex interacts with ATF2. Interacts with BCL2L1. Interacts with BAK1. Interacts with RTL10/BOP (via BH3 domain). Interacts with amyloid-beta and APP; induces VDAC1 dephosphorylation. Component of the mitochondrial permeability transition pore complex (mPTPC), at least composed of SPG7, VDAC1 and PPIF. Interacts with SPG7, NIPSNAP2 and SLC25A30. Interacts with TMEM41B. Interacts with BCAP31.
Phosphorylation at Ser-193 by NEK1 promotes the open conformational state preventing excessive mitochondrial membrane permeability and subsequent apoptotic cell death after injury. Phosphorylation by the AKT-GSK3B axis stabilizes the protein probably by preventing ubiquitin-mediated proteasomal degradation.
Ubiquitinated. Undergoes monoubiquitination and polyubiquitination by PRKN; monoubiquitination at Lys-274 inhibits apoptosis, whereas polyubiquitination leads to its degradation and promotes mitophagy. Deubiquitinated by USP30.
Belongs to the amiloride-sensitive sodium channel (TC 1.A.6) family. SCNN1G 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. Interacts with NEDD4; via the WW domains. Interacts with NEDD4L; via the WW domains. Interacts with WWP1; via the WW domains. Interacts with WWP2; via the WW domains. Interacts with the full length immature form of PCSK9 (pro-PCSK9).
Belongs to the protease inhibitor I47 (latexin) family.
Involved in the 5-carboxymethylaminomethyl modification (mnm(5)s(2)U34) of the wobble uridine base in mitochondrial tRNAs.
Ion transporter that can act both as an ion channel and anion exchanger. Mainly acts as a chloride channel, which mediate uncoupled chloride anion transport in an alternate-access mechanism where a saturable binding site is alternately exposed to either one or the other side of the membrane. Also acts as a DIDS- and thiosulfate- sensitive anion exchanger the exchange of chloride for bicarbonate ions across the cell membrane.
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 3' end-terminated with a 2',3'-cyclic phosphate.
Gamma-carboxyglutamate residues are formed by vitamin K dependent carboxylation. These residues are essential for the binding of calcium.
Belongs to the heat shock protein 90 family.
Cleaved following oxidative stress resulting in HSP90AB1 protein radicals formation; disrupts the chaperoning function and the degradation of its client proteins.
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.
Methylated by SMYD2; facilitates dimerization and chaperone complex formation; promotes cancer cell proliferation.
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. Apart from its chaperone activity, it also plays a role in the regulation of the transcription machinery. HSP90 and its co-chaperones modulate transcription at least at three different levels. They first alter the steady-state levels of certain transcription factors in response to various physiological cues. Second, they modulate the activity of certain epigenetic modifiers, such as histone deacetylases or DNA methyl transferases, and thereby respond to the change in the environment. Third, they participate in the eviction of histones from the promoter region of certain genes and thereby turn on gene expression. Antagonizes STUB1-mediated inhibition of TGF-beta signaling via inhibition of STUB1-mediated SMAD3 ubiquitination and degradation. Promotes cell differentiation by chaperoning BIRC2 and thereby protecting from auto-ubiquitination and degradation by the proteasomal machinery. Main chaperone involved in the phosphorylation/activation of the STAT1 by chaperoning both JAK2 and PRKCE under heat shock and in turn, activates its own transcription. Involved in the translocation into ERGIC (endoplasmic reticulum-Golgi intermediate compartment) of leaderless cargos (lacking the secretion signal sequence) such as the interleukin 1/IL-1; the translocation process is mediated by the cargo receptor TMED10.
Monomer. Homodimer (By similarity). Forms a complex with CDK6 and CDC37. Interacts with UNC45A; binding to UNC45A involves 2 UNC45A monomers per HSP90AB1 dimer (By similarity). Interacts with CHORDC1 (By similarity). Interacts with DNAJC7. Interacts with FKBP4. May interact with NWD1. Interacts with SGTA. Interacts with HSF1 in an ATP-dependent manner. Interacts with MET; the interaction suppresses MET kinase activity. Interacts with ERBB2 in an ATP-dependent manner; the interaction suppresses ERBB2 kinase activity. Interacts with HIF1A, KEAP1 and RHOBTB2. Interacts with STUB1 and SMAD3. Interacts with XPO1 and AHSA1. Interacts with BIRC2. Interacts with KCNQ4; promotes cell surface expression of KCNQ4. Interacts with BIRC2; prevents auto-ubiquitination and degradation of its client protein BIRC2. Interacts with NOS3. Interacts with AHR; interaction is inhibited by HSP90AB1 phosphorylation on Ser-226 and Ser-257. Interacts with STIP1 and CDC37; upon SMYD2-dependent methylation. Interacts with JAK2 and PRKCE; promotes functional activation in a heat shock-dependent manner. Interacts with HSP90AA1; interaction is constitutive. HSP90AB1-CDC37 chaperone complex interacts with inactive MAPK7 (via N-terminal half) in resting cells; the interaction is MAP2K5-independent and prevents from ubiquitination and proteasomal degradation. Interacts with CDC25A; prevents heat shock-mediated CDC25A degradation and contributes to cell cycle progression. Interacts with TP53 (via DNA binding domain); suppresses TP53 aggregation and prevents from irreversible thermal inactivation. Interacts with TGFB1 processed form (LAP); inhibits latent TGFB1 activation (By similarity). Interacts with TRIM8; prevents nucleus translocation of phosphorylated STAT3 and HSP90AB1 (By similarity). Interacts with NR3C1 (via domain NR LBD) and NR1D1 (via domain NR LBD) (By similarity). Interacts with PDCL3 (By similarity). Interacts with TTC4 (via TPR repeats) (By similarity). Interacts with IL1B; the interaction facilitates cargo translocation into the ERGIC (By similarity).
Phosphorylation at Tyr-303 by SRC is induced by lipopolysaccharide. Phosphorylation at Ser-226 and Ser-257 inhibits AHR interaction.
S-nitrosylated; negatively regulates the ATPase activity.
The TPR repeat-binding motif mediates interaction with TPR repeat-containing proteins.
Ubiquitinated in the presence of STUB1-UBE2D1 complex (in vitro).
Activated following phosphorylation by OXSR1/OSR1 and STK39/SPAK downstream of WNK kinases (WNK1, WNK2, WNK3 or WNK4).
Phosphorylated at Ser-90, Thr-99 and Thr-104 by OXSR1/OSR1 and STK39/SPAK downstream of WNK kinases (WNK1, WNK2, WNK3 or WNK4), promoting its activity.
Predominant in kidney. The 3 isoforms are differentially distributed within the kidney: B almost exclusively in cortex, F almost exclusively in medulla, and A about equally distributed.
Renal sodium, potassium and chloride ion cotransporter that mediates the transepithelial NaCl reabsorption in the thick ascending limb and plays an essential role in the urinary concentration and volume regulation. Electrically silent transporter system.
The RFXV motif mediates binding with OXSR1/OSR1 and STK39/SPAK.
When phosphorylated, interacts with PPP3CB.
A residue in the 7th transmembrane region ('Thr-355' in human, 'Asn-351' in mouse and rat) is important for species-specific sensitivity to various agonists.
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. Arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Regulates the release of 5-hydroxytryptamine, dopamine and acetylcholine in the brain, and thereby affects neural activity, nociceptive processing, pain perception, mood and behavior. Besides, plays a role in vasoconstriction of cerebral arteries.
Homodimer. Heterodimer with HTR1D (By similarity).
Ligands are bound in a hydrophobic pocket formed by the transmembrane helices.
Belongs to the ribonuclease III family. Mitochondrion-specific ribosomal protein mL44 subfamily.
Binds medium- and long-chain acyl-CoA esters with very high affinity and may function as an intracellular carrier of acyl-CoA esters. It is also able to displace diazepam from the benzodiazepine (BZD) recognition site located on the GABA type A receptor. It is therefore possible that this protein also acts as a neuropeptide to modulate the action of the GABA receptor (By similarity).
Voltage-sensitive motor protein that drives outer hair cell (OHC) electromotility (eM) and participates in sound amplification in the hearing organ. Converts changes in the transmembrane electric potential into mechanical displacements resulting in the coupling of its expansion to movement of a charged voltage sensor across the lipid membrane. The nature of the voltage sensor is not completely clear, and two models compete. In the first model, acts as an incomplete transporter where intracellular chloride anion acts as extrinsic voltage sensor that drives conformational change in the protein which is sufficient to produce a length change in the plane of the membrane and hence in the length of the OHC. The second model in which multiple charged amino acid residues are distributed at the intracellular and extracellular membrane interfaces that form an intrinsic voltage sensor, whose movement produces the non-linear capacitance (NLC). However, the effective voltage sensor may be the result of a hybrid voltage sensor, assembled from intrinsic charge (charged residues) and extrinsic charge (bound anion). Notably, binding of anions to the anion-binding pocket partially neutralizes the intrinsic positive charge rather than to form an electrically negative sensor, therefore remaining charge may serve as voltage sensor that, after depolarization, moves from down (expanded state) to up (contracted) conformation, which is accompanied by an eccentric contraction of the intermembrane cross-sectional area of the protein as well as a major increase in the hydrophobic thickness of the protein having as consequences the plasma membrane thickening and the cell contraction after membrane depolarization. The anion-binding pocket transits from the inward-open (Down) state, where it is exposed toward the intracellular solvent in the absence of anion, to the occluded (Up) state upon anion binding. Salicylate competes for the anion-binding site and inhibits the voltage-sensor movement, and therefore inhibits the charge transfer and electromotility by displacing Cl(-) from the anion-binding site and by preventing the structural transitions to the contracted state. In addition, can act as a weak Cl(-)/HCO3(-) antiporter across the cell membrane and so regulate the intracellular pH of the outer hair cells (OHCs), while firstly found as being unable to mediate electrogenic anion transport. Moreover, supports a role in cardiac mechanical amplification serving as an elastic element to enhance the actomyosin- based sarcomere contraction system.
Belongs to the apolipoprotein A1/A4/E family.
Homodimer (By similarity). Interacts with APOA1BP and CLU. Component of a sperm activating protein complex (SPAP), consisting of APOA1, an immunoglobulin heavy chain, an immunoglobulin light chain and albumin. Interacts with NDRG1. Interacts with SCGB3A2 (By similarity). Interacts with NAXE and YJEFN3 (By similarity).
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). As part of the SPAP complex, activates spermatozoa motility.
Phosphorylation sites are present in the extracellular medium.
Interacts with CDC42 (in GTP-bound form). Interacts weakly with RAC1 and not at all with RHOA.
Probably involved in the organization of the actin cytoskeleton by acting downstream of CDC42, inducing actin filament assembly. Alters CDC42-induced cell shape changes. In activated T-cells, may play a role in CDC42-mediated F-actin accumulation at the immunological synapse. May play a role in early contractile events in phagocytosis in macrophages.
Belongs to the protein kinase superfamily. NEK Ser/Thr protein kinase family. NIMA subfamily.
Belongs to the fibroblast growth factor-binding protein family.
Belongs to the calycin superfamily. Lipocalin family. Highly divergent.
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.
Minor component of the myelin sheath. May be involved in completion and/or maintenance of the myelin sheath and in cell-cell communication. Mediates homophilic cell-cell adhesion.
Belongs to the chloride channel MCLC family.
Associates with membrane-bound immunoglobulin on the surface of B-lymphocytes and with IgG Fc receptor on the membranes of T-lymphocytes. Interacts with LRP2; the interaction is required for renal uptake of GC in complex with 25-hydroxyvitamin D3.
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.
GTPase which can activate the MEK/ERK pathway and induce cell transformation when overexpressed. May act as a nuclear scaffold for MAPK1, probably by association with MAPK1 nuclear export signal leading to enhanced ERK1/ERK2 signaling.
Interacts directly with MAPK1 (wild-type and kinase-deficient forms). Interacts directly (in GTP-bound form) with MAP2K1 (wild-type and kinase-deficient forms).
Belongs to the protease inhibitor I27 (calpastatin) family.
Each of the four flexible inhibitory domains can inhibit one calcium-bound calpain molecule by occupying both sides of the active site.
In erythrocytes the protein lacks the N-terminal region of the liver inhibitor but retains three inhibitory units.
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.
Nucleolar protein that acts as a modulator of rRNA synthesis. Plays a central role during organogenesis.
Oxidizes the CoA esters of the bile acid intermediates di- and tri-hydroxycholestanoic acids (PubMed:9218493). Capable of oxidizing short as well as long chain 2-methyl branched fatty acids (By similarity).
Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. AIG1/Toc34/Toc159-like paraseptin GTPase family. IAN subfamily.
Component of the telomerase ribonucleoprotein (RNP) complex that is essential for the replication of chromosome termini.
Plays a role in nonsense-mediated mRNA decay.
The PINc domain confers endonuclease activity and is expected to bind the catalytic metal ion.
Protein transport. Probably involved in vesicular traffic.
Plays a role in vesicle-mediated protein trafficking to lysosomal compartments including the endocytic membrane transport pathways.
Belongs to the complex I subunit 2 family.
Core subunit of respiratory chain NADH dehydrogenase (Complex I) which is composed of 45 different subunits. Interacts with TMEM242 (By similarity).
Belongs to the sarcoglycan beta/delta/gamma/zeta family.
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 (By similarity).
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.
Belongs to the tRNA methyltransferase O family.
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. May recruit the E2 ubiquitin-conjugating enzymes to the complex.
In the C-terminal section; belongs to the purine/pyrimidine phosphoribosyltransferase family.
Plays an important role in growth control. Its major role in stimulating body growth is to stimulate the liver and other tissues to secrete IGF-1. It stimulates both the differentiation and proliferation of myoblasts. It also stimulates amino acid uptake and protein synthesis in muscle and other tissues.
Belongs to the Nudix hydrolase family. CPSF5 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.
Homodimer (via N- and C-terminus); binds RNA as homodimer. Component of the cleavage factor Im (CFIm) complex.
Belongs to the PNP/MTAP phosphorylase family.
The purine nucleoside phosphorylases catalyze the phosphorolytic breakdown of the N-glycosidic bond in the beta-(deoxy)ribonucleoside molecules, with the formation of the corresponding free purine bases and pentose-1-phosphate.
Identified in the spliceosome C complex.
Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family. CACNA1S subfamily.
Channel activity is blocked by dihydropyridines (DHP), phenylalkylamines, and by benzothiazepines.
Component of a calcium channel complex consisting of a pore-forming alpha subunit (CACNA1S) and the ancillary subunits CACNB1 or CACNB2, CACNG1 and CACNA2D1 (PubMed:3037387, PubMed:27621462, PubMed:15134636, PubMed:25667046, PubMed:26680202, PubMed:27580036). 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 (PubMed:15134636, PubMed:25667046, PubMed:26680202, PubMed:27580036). CACNA1S channel activity is modulated by the auxiliary subunits (CACNB1 or CACNB2, CACNG1 and CACNA2D1). Interacts with DYSF and JSRP1 (By similarity). Interacts with RYR1 (PubMed:10388749). Interacts with STAC, STAC2 and STAC3 (via their SH3 domains) (PubMed:28112192, PubMed:29078335, PubMed:29467163). Interaction with STAC3 promotes expression at the cell membrane (PubMed:25548159, PubMed:29467163). Interaction with STAC2 promotes expression at the cell membrane, but with much lower efficiency than STAC3. Interaction with STAC1 leads to very low levels expression at the cell membrane, much less than the levels observed upon interaction with STAC3 and STAC2 (PubMed:29467163). Interacts with CALM (By similarity).
Detected in skeletal muscle T-tubules (at protein level).
Phosphorylated. Phosphorylation by PKA activates the calcium channel. Both the minor and major forms are phosphorylated in vitro by PKA (PubMed:2549550, PubMed:2844809). Phosphorylation at Ser-1575 is involved in beta-adrenergic-mediated regulation of the channel (PubMed:20937870).
Pore-forming, alpha-1S subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents in skeletal muscle (PubMed:9465115, PubMed:15201141, PubMed:25548159, PubMed:27621462, PubMed:29078335, PubMed:29467163). Calcium channels containing the alpha-1S subunit play an important role in excitation-contraction coupling in skeletal muscle via their interaction with RYR1, which triggers Ca(2+) release from the sarcplasmic reticulum and ultimately results in muscle contraction (PubMed:9465115, PubMed:15201141, PubMed:27621462). Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group.
The alpha-1S subunit is found in two isoforms in the skeletal muscle: a minor form of 212 kDa containing the complete amino acid sequence, and a major form of 190 kDa derived from the full-length form by post-translational proteolysis close to Phe-1690.
The loop between repeats II and III interacts with the ryanodine receptor, and is therefore important for calcium release from the endoplasmic reticulum necessary for muscle contraction.
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. Costimulates T-cell proliferation and cytokine production. Involved in immunoglobulin class switching.
Plays a role in the degradation of extracellular matrix proteins including fibrillar collagen, fibronectin, TNC and ACAN. Cleaves triple helical collagens, including type I, type II and type III collagen, but has the highest activity with soluble type II collagen. Can also degrade collagen type IV, type XIV and type X. May also function by activating or degrading key regulatory proteins, such as TGFB1 and CCN2. Plays a role in wound healing, tissue remodeling, cartilage degradation, bone development, bone mineralization and ossification. Required for normal embryonic bone development and ossification. Plays a role in the healing of bone fractures via endochondral ossification. Plays a role in wound healing, probably by a mechanism that involves proteolytic activation of TGFB1 and degradation of CCN2. Plays a role in keratinocyte migration during wound healing. May play a role in cell migration and in tumor cell invasion (By similarity).
The C-terminal region binds to collagen.
The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme (By similarity).
The proenzyme is activated by removal of the propeptide; this cleavage can be effected by other matrix metalloproteinases, such as MMP2, MMP3 and MMP14 and may involve several cleavage steps. Cleavage can also be autocatalytic, after partial maturation by another protease or after treatment with 4-aminophenylmercuric acetate (APMA) (in vitro) (By similarity).
Belongs to the SIMIBI class G3E GTPase family. ZNG1 subfamily.
Plays a central role during spermatogenesis by repressing transposable elements and preventing their mobilization, which is essential for the germline integrity. Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and governs the methylation and subsequent repression of transposons. Its association with piP-bodies suggests a participation in the secondary piRNAs metabolic process. Required for the localization of germ-cell factors to the meiotic nuage.
Belongs to the eukaryotic ribosomal protein eL6 family.
Belongs to the galactose-1-phosphate uridylyltransferase type 1 family.
Acetylation is generally linked to gene activation. Acetylation on Lys-10 (H3K9ac) impairs methylation at Arg-9 (H3R8me2s). Acetylation on Lys-19 (H3K18ac) and Lys-24 (H3K24ac) favors methylation at Arg-18 (H3R17me). Acetylation at Lys-123 (H3K122ac) by EP300/p300 plays a central role in chromatin structure: localizes at the surface of the histone octamer and stimulates transcription, possibly by promoting nucleosome instability.
Asymmetric dimethylation at Arg-18 (H3R17me2a) by CARM1 is linked to gene activation. Symmetric dimethylation at Arg-9 (H3R8me2s) by PRMT5 is linked to gene repression. Asymmetric dimethylation at Arg-3 (H3R2me2a) by PRMT6 is linked to gene repression and is mutually exclusive with H3 Lys-5 methylation (H3K4me2 and H3K4me3). H3R2me2a is present at the 3' of genes regardless of their transcription state and is enriched on inactive promoters, while it is absent on active promoters.
Butyrylation of histones marks active promoters and competes with histone acetylation. It is present during late spermatogenesis.
Citrullination at Arg-9 (H3R8ci) and/or Arg-18 (H3R17ci) by PADI4 impairs methylation and represses transcription.
Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes.
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 throughout the cell cycle independently of DNA synthesis.
Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.
Lysine deamination at Lys-5 (H3K4all) to form allysine is mediated by LOXL2. Allysine formation by LOXL2 only takes place on H3K4me3 and results in gene repression.
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 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).
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 and Lys-80. 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), which are linked to gene repression, are underrepresented. Methylation at Lys-10 (H3K9me) is a specific target for HP1 proteins (CBX1, CBX3 and CBX5) and prevents subsequent phosphorylation at Ser-11 (H3S10ph) and acetylation of H3 and H4. Methylation at Lys-5 (H3K4me) and Lys-80 (H3K79me) require preliminary monoubiquitination of H2B at 'Lys-120'. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are enriched in inactive X chromosome chromatin. Monomethylation at Lys-57 (H3K56me1) by EHMT2/G9A in G1 phase promotes interaction with PCNA and is required for DNA replication.
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 HIRA, a chaperone required for its incorporation into nucleosomes. Interacts with ZMYND11; when trimethylated at 'Lys-36' (H3.3K36me3). Found in a co-chaperone complex with DNJC9, MCM2 and histone H3.3-H4 dimers (By similarity). Within the complex, interacts with DNJC9 (via C-terminus); the interaction is direct (By similarity). Interacts with ASF1A, MCM2, NASP and SPT2 (By similarity).
Ubiquitinated. Monoubiquitinated by RAG1 in lymphoid cells, monoubiquitination is required for V(D)J recombination (By similarity).
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.
Belongs to the universal ribosomal protein uS8 family.
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.
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 inositol 3,4-bisphosphate 4-phosphatase family.
Belongs to the transient receptor (TC 1.A.4) family. TrpV subfamily. TRPV1 sub-subfamily.
Interacts with PIRT (By similarity). Homotetramer. May also form a heteromeric channel with TRPV3. Interacts with CALM, PRKCM and CSK. Interacts with PRKCG and NTRK1, probably by forming a trimeric complex (By similarity). Interacts with the Scolopendra mutilans RhTx toxin (By similarity). Interacts with TMEM100 (By similarity). Interacts with PACS2 (By similarity).
Ligand-activated non-selective calcium permeant cation channel involved in detection of noxious chemical and thermal stimuli (PubMed:14996838, PubMed:11035011). Seems to mediate proton influx and may be involved in intracellular acidosis in nociceptive neurons. Involved in mediation of inflammatory pain and hyperalgesia. Sensitized by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases, which involves PKC isozymes and PCL. Can be activated by endogenous compounds, including 12-hydroperoxytetraenoic acid and bradykinin. Acts as ionotropic endocannabinoid receptor with central neuromodulatory effects. Triggers a form of long-term depression (TRPV1-LTD) mediated by the endocannabinoid anandamine in the hippocampus and nucleus accumbens by affecting AMPA receptors endocytosis (By similarity). Activation by vanilloids, like capsaicin, and temperatures higher than 42 degrees Celsius, exhibits a time- and Ca(2+)-dependent outward rectification, followed by a long-lasting refractory state. Mild extracellular acidic pH (6.5) potentiates channel activation by noxious heat and vanilloids, whereas acidic conditions (pH <6) directly activate the channel (By similarity).
Phosphorylation by PKA reverses capsaicin-induced dephosphorylation at multiple sites. Phosphorylation by CAMKII seems to regulate binding to vanilloids. Phosphorylated and modulated by PRKCE, PRKCM and probably PRKCZ. Dephosphorylation by calcineurin seems to lead to receptor desensitization and phosphorylation by CAMKII recovers activity.
The association domain (AD) is necessary for self-association.
The channel is sensitized by ATP binding. Repeated stimulation with capsaicin gives rise to progressively smaller responses, due to desensitization. This desensitization is triggered by the influx of calcium ions and is inhibited by elevated ATP levels. Ca(2+) and CALM displace ATP from its binding site and trigger a conformation change that leads to a closed, desensitized channel. The double-knot toxin (DkTx) from the Chinese earth tiger tarantula activates the channel and traps it in an open conformation (By similarity). The Scolopendra mutilans RhTx toxin potentiates the heat activation pathway mediated by this channel by binding to the charge-rich outer pore region (in an activated state) (By similarity). Channel activity is activated via the interaction with PIRT and phosphatidylinositol 4,5-bisphosphate (PIP2). Both PIRT and PIP2 are required to activate channel activity. Intracellular PIP2 inhibits desensitization (By similarity).
Belongs to the G-alpha family. G(q) subfamily.
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.
Deoxyglucose transport is inhibit by D-glucose, D-galactose and maltose. Galactose transport is inhibited by D-glucose and maltose.
Detected in stomach, placenta, lung and brain.
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.
Facilitative glucose transporter. 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. Required for mesendoderm differentiation (By similarity).
Interacts with SMIM43; the interaction may promote SLC2A3-mediated glucose transport to meet the energy needs of mesendoderm differentiation.
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.
Binds two calcium ions per molecule with an affinity similar to that of the S100 proteins.
Facilitates the differentiation and the cornification of keratinocytes.
Phosphorylation at Thr-7 significantly suppresses homodimerization and promotes association with NCL/nucleolin which induces nuclear translocation.
Autophagy factor required for autophagosome formation and mitophagy. Target of the TOR kinase signaling pathway that regulates autophagy through the control of the phosphorylation status of ATG13 and ULK1, and the regulation of the ATG13-ULK1-RB1CC1 complex. Through its regulation of ULK1 activity, plays a role in the regulation of the kinase activity of mTORC1 and cell proliferation.
Belongs to the ATG13 family. Metazoan subfamily.
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.
Belongs to the SEC23/SEC24 family. SEC24 subfamily.
Binds to linker H1 histones but not to core histones (By similarity). Interacts with histones H2A, H2B, H3 and H4 (By similarity). Interacts with histone H3.3 (By similarity). Also binds to HSP90 in the cytoplasm. This interaction stimulates binding of NASP to H1-6/H1T (By similarity).
Required for DNA replication, normal cell cycle progression and cell proliferation. Forms a cytoplasmic complex with HSP90 and H1 linker histones and stimulates HSP90 ATPase activity. NASP and H1 histone are subsequently released from the complex and translocate to the nucleus where the histone is released for binding to DNA.
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.
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 glycosyltransferase group 1 family. Glycosyltransferase 4 subfamily.
Autoubiquitinated in the presence of CDC34/UBCH3.
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. The chromatin structure plays an essential role in the V(D)J recombination reactions and the presence of histone H3 trimethylated at 'Lys-4' (H3K4me3) stimulates both the nicking and haipinning steps. The RAG complex also plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and monospecific recognition by the B-cell antigen receptor (BCR) expressed on individual B-lymphocytes. The introduction of DNA breaks by the RAG complex on one immunoglobulin allele induces ATM-dependent repositioning of the other allele to pericentromeric heterochromatin, preventing accessibility to the RAG complex and recombination of the second allele. In addition to its endonuclease activity, RAG1 also acts as an E3 ubiquitin-protein ligase that mediates monoubiquitination of histone H3. Histone H3 monoubiquitination is required for the joining step of V(D)J recombination. Mediates polyubiquitination of KPNA1 (By similarity).
Homodimer. Component of the RAG complex composed of core components RAG1 and RAG2, and associated component HMGB1 or HMGB2. Interacts with DCAF1, leading to recruitment of the CUL4A-RBX1-DDB1-DCAF1/VPRBP complex to ubiquitinate proteins and limit error-prone repair during V(D)J recombination (By similarity).
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.
Catalyzes one step in the degradation of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA).
Component of the RAG complex composed of core components RAG1 and RAG2, and associated component HMGB1 or HMGB2.
Core 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. DNA cleavage by the RAG complex occurs in 2 steps: a first nick is introduced in the top strand immediately upstream of the heptamer, generating a 3'-hydroxyl group that can attack the phosphodiester bond on the opposite strand in a direct transesterification reaction, thereby creating 4 DNA ends: 2 hairpin coding ends and 2 blunt, 5'-phosphorylated ends. The chromatin structure plays an essential role in the V(D)J recombination reactions and the presence of histone H3 trimethylated at 'Lys-4' (H3K4me3) stimulates both the nicking and haipinning steps. The RAG complex also plays a role in pre-B cell allelic exclusion, a process leading to expression of a single immunoglobulin heavy chain allele to enforce clonality and monospecific recognition by the B-cell antigen receptor (BCR) expressed on individual B-lymphocytes. The introduction of DNA breaks by the RAG complex on one immunoglobulin allele induces ATM-dependent repositioning of the other allele to pericentromeric heterochromatin, preventing accessibility to the RAG complex and recombination of the second allele. In the RAG complex, RAG2 is not the catalytic component but is required for all known catalytic activities mediated by RAG1. It probably acts as a sensor of chromatin state that recruits the RAG complex to H3K4me3 (By similarity).
The atypical PHD-type zinc finger recognizes and binds histone H3 trimethylated on 'Lys-4' (H3K4me3). The presence Tyr-445 instead of a carboxylate in classical PHD-type zinc fingers results in an enhanced binding to H3K4me3 in presence of dimethylated on 'Arg-2' (H3R2me2) rather than inhibited. The atypical PHD-type zinc finger also binds various phosphoinositides, such as phosphatidylinositol 3,4-bisphosphate binding (PtdIns(3,4)P2), phosphatidylinositol 3,5-bisphosphate binding (PtdIns(3,5)P2), phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and phosphatidylinositol 3,4,5-trisphosphate binding (PtdIns(3,4,5)P3) (By similarity).
Autophosphorylated in response to ligand binding on Tyr-1235 and Tyr-1236 in the kinase domain leading to further phosphorylation of Tyr-1350 and Tyr-1357 in the C-terminal multifunctional docking site. Dephosphorylated by PTPRJ at Tyr-1350 and Tyr-1366. Dephosphorylated by PTPN1 and PTPN2 (By similarity).
Heterodimer made of an alpha chain (50 kDa) and a beta chain (145 kDa) which are disulfide linked. Binds PLXNB1. Interacts when phosphorylated with downstream effectors including STAT3, PIK3R1, SRC, PCLG1, GRB2 and GAB1. Interacts with SPSB1, SPSB2 and SPSB4. Interacts with INPP5D/SHIP1. When phosphorylated at Tyr-1357, interacts with INPPL1/SHIP2. Interacts with RANBP9 and RANBP10, as well as SPSB1, SPSB2, SPSB3 and SPSB4. SPSB1 binding occurs in the presence and in the absence of HGF, however HGF treatment has a positive effect on this interaction. Interacts with MUC20; prevents interaction with GRB2 and suppresses hepatocyte growth factor-induced cell proliferation. Interacts with GRB10. Interacts with PTPN1 and PTPN2. Interacts with HSP90AA1 and HSP90AB1; the interaction suppresses MET kinase activity. Interacts with tensin TNS3 (By similarity). Interacts (when phosphorylated) with tensin TNS4 (via SH2 domain); the interaction increases MET protein stability by inhibiting MET endocytosis and subsequent lysosomal degradation (By similarity).
In its inactive state, the C-terminal tail interacts with the catalytic domain and inhibits the kinase activity. Upon ligand binding, the C-terminal tail is displaced and becomes phosphorylated, thus increasing the kinase activity (By similarity).
O-mannosylation of IPT/TIG domains by TMEM260 is required for protein maturation. O-mannosylated residues are composed of single mannose glycans that are not elongated or modified.
Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including proliferation, scattering, morphogenesis and survival. Ligand binding at the cell surface induces autophosphorylation of MET on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1, SRC, GRB2, STAT3 or the adapter GAB1. Recruitment of these downstream effectors by MET leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. The RAS-ERK activation is associated with the morphogenetic effects while PI3K/AKT coordinates prosurvival effects. During embryonic development, MET signaling plays a role in gastrulation, development and migration of muscles and neuronal precursors, angiogenesis and kidney formation. In adults, participates in wound healing as well as organ regeneration and tissue remodeling. Promotes also differentiation and proliferation of hematopoietic cells (By similarity).
The beta-propeller Sema domain mediates binding to HGF.
The kinase domain is involved in SPSB1 binding.
Ubiquitinated. Ubiquitination by CBL regulates the receptor stability and activity through proteasomal degradation (By similarity).
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.
SEC16A and SEC16B are each present in multiple copies in a heteromeric complex. Interacts with TFG. Interacts with SEC13.
Belongs to the eukaryotic ribosomal protein eL24 family.
Belongs to the metallo-dependent hydrolases superfamily. Adenosine and AMP deaminases family.
Interacts with SMARCA1. Interacts with NEK3 and VAV2 and this interaction is prolactin-dependent.
This is a receptor for the anterior pituitary hormone prolactin.
Belongs to the mitochondrion-specific ribosomal protein mS29 family.
Monomer. Homodimer only upon binding to a DNA (By similarity). Efficient DNA binding requires dimerization with another bHLH protein. Interacts with TACC3 (By similarity). Interacts with HIF1A, EPAS1, NPAS1 and NPAS3; forms a heterodimer that binds core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters (By similarity). Forms a heterodimer with AHRR, as well as with other bHLH proteins. Interacts with NOCA7 (By similarity). Interacts with TACC3 (By similarity). Interacts with AHR; the heterodimer ARNT:AHR binds to core DNA sequence 5'-TGCGTG-3' within the dioxin response element (DRE) of target gene promoters and activates their transcription (By similarity). Interacts with SIM1 and NPAS4 (By similarity).
Required for activity of the AHR. Upon ligand binding, AHR translocates into the nucleus, where it heterodimerizes with ARNT and induces transcription by binding to xenobiotic response elements (XRE). Not required for the ligand-binding subunit to translocate from the cytosol to the nucleus after ligand binding. The complex initiates transcription of genes involved in the regulation of a variety of biological processes, including angiogenesis, hematopoiesis, drug and lipid metabolism, cell motility and immune modulation (By similarity). The heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters and functions as a transcriptional regulator of the adaptive response to hypoxia (By similarity). The heterodimer ARNT:AHR binds to core DNA sequence 5'-TGCGTG-3' within the dioxin response element (DRE) of target gene promoters and activates their transcription (By similarity).
Was expressed at almost the same level in all tissues except for the heart, liver, and small intestine.
In the N-terminal section; belongs to the FGAMS family.
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.
Proposed core component of the chromatin remodeling INO80 complex which is involved in transcriptional regulation, DNA replication and probably DNA repair.
Belongs to the cyclin family. Cyclin AB subfamily.
Belongs to the type I cytokine receptor family. Type 3 subfamily.
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 mitochondrion-specific ribosomal protein mS26 family.
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.
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 methylthiotransferase family. MiaB subfamily.
Belongs to the 3-hydroxyacyl-CoA dehydrogenase family.
Homooligomer. Interacts (via the N-terminus) with DPP4; the interaction is direct. Forms a stable heterooligomeric complex with CAV2 that targets to lipid rafts and drives caveolae formation. Interacts with PACSIN2; this interaction induces membrane tubulation (By similarity). Interacts with BMX, BTK, CTNNB1, CDH1, GLIPR2, JUP, NOSTRIN, SNAP25 and STX1A. Interacts with SLC7A9. Interacts with TGFBR1. Interacts with CAVIN3 (via leucine-zipper domain) in a cholesterol-sensitive manner. Interacts with CAVIN1. Interacts with EHD2 in a cholesterol-dependent manner. Forms a ternary complex with UBXN6 and VCP; mediates CAV1 targeting to lysosomes for degradation. Interacts with ABCG1; this interaction regulates ABCG1-mediated cholesterol efflux (By similarity). Interacts with NEU3; this interaction enhances NEU3 sialidase activity within caveola. Interacts (via C-terminus) with SPRY1, SPRY2 (via C-terminus), SPRY3, and SPRY4 (By similarity).
May act as a scaffolding protein within caveolar membranes. Forms a stable heterooligomeric complex with CAV2 that targets to lipid rafts and drives caveolae formation. Mediates the recruitment of CAVIN proteins (CAVIN1/2/3/4) to the caveolae (By similarity). Interacts directly with G-protein alpha subunits and can functionally regulate their activity (By similarity). Involved in the costimulatory signal essential for T-cell receptor (TCR)-mediated T-cell activation. Its binding to DPP4 induces T-cell proliferation and NF-kappa-B activation in a T-cell receptor/CD3-dependent manner (By similarity). Recruits CTNNB1 to caveolar membranes and may regulate CTNNB1-mediated signaling through the Wnt pathway (By similarity). Negatively regulates TGFB1-mediated activation of SMAD2/3 by mediating the internalization of TGFBR1 from membrane rafts leading to its subsequent degradation (By similarity).
Phosphorylated at Tyr-14 by ABL1 in response to oxidative stress.
Ubiquitinated. Undergo monoubiquitination and multi- and/or polyubiquitination. Monoubiquitination of N-terminal lysines promotes integration in a ternary complex with UBXN6 and VCP which promotes oligomeric CAV1 targeting to lysosomes for degradation. Ubiquitinated by ZNRF1; leading to degradation and modulation of the TLR4-mediated immune response.
Component of the transcription factor SL1/TIF-IB complex, composed of TBP and at least TAF1A, TAF1B, TAF1C and TAF1D. In the complex interacts directly with TBP, TAF1A and TAF1B. Interaction of the SL1/TIF-IB subunits with TBP excludes interaction of TBP with the transcription factor IID (TFIID) subunits.
Component of the transcription factor SL1/TIF-IB complex, which is involved in the assembly of the PIC (pre-initiation 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.
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.
Activated by cytosolic calcium, which is necessary for binding to membrane lipids. Activated by phosphorylation in response to mitogenic stimuli.
Has primarily calcium-dependent phospholipase and lysophospholipase activities, with a major role in membrane lipid remodeling and biosynthesis of lipid mediators of the inflammatory response (By similarity). Plays an important role in embryo implantation and parturition through its ability to trigger prostanoid production (By similarity). Preferentially hydrolyzes the ester bond of the fatty acyl group attached at sn-2 position of phospholipids (phospholipase A2 activity). Selectively hydrolyzes sn-2 arachidonoyl group from membrane phospholipids, providing the precursor for eicosanoid biosynthesis via the cyclooxygenase pathway. In an alternative pathway of eicosanoid biosynthesis, hydrolyzes sn-2 fatty acyl chain of eicosanoid lysophopholipids to release free bioactive eicosanoids. Hydrolyzes the ester bond of the fatty acyl group attached at sn-1 position of phospholipids (phospholipase A1 activity) only if an ether linkage rather than an ester linkage is present at the sn-2 position. This hydrolysis is not stereospecific. Has calcium-independent phospholipase A2 and lysophospholipase activities in the presence of phosphoinositides. Has O-acyltransferase activity. Catalyzes the transfer of fatty acyl chains from phospholipids to a primary hydroxyl group of glycerol (sn-1 or sn-3), potentially contributing to monoacylglycerol synthesis (By similarity).
Phosphorylated at both Ser-505 and Ser-726 in response to mitogenic stimuli.
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 calcium. In the presence of phosphoinositides, regulates phospholipase A2 and lysophospholipase activities in a calcium-independent way.
Belongs to the CND3 (condensin subunit 3) family.
Belongs to the major facilitator superfamily. Sugar transporter (TC 2.A.1.1) family.
Autolytic cleavage produces the alpha and beta subunits. In cutaneous cells, as well as in certain pathological conditions, shedding of beta-dystroglycan can occur releasing a peptide of about 30 kDa (By similarity).
Detected in brain, cardiac muscle and skeletal muscle (at protein level) (PubMed:16709410). Expressed in lung, brain, liver, kidney, diaphragm and stomach (PubMed:1741056).
Extracellular peripheral glycoprotein that acts as a receptor for extracellular matrix proteins containing laminin-G domains. Receptor for laminin-2 (LAMA2) and agrin in peripheral nerve Schwann cells (By similarity). Also acts as a receptor for laminin LAMA5 (By similarity).
Monomer. Heterodimer of alpha- and beta-dystroglycan subunits which are the central components of the dystrophin-glycoprotein complex. This complex then can form a dystrophin-associated glycoprotein complex (DGC) which is composed of three subcomplexes: a cytoplasmic complex comprised of DMD (or UTRN), DTNA and a number of syntrophins, such as SNTB1, SNTB2, SNTG1 and SNTG2, the transmembrane dystroglycan complex, and the sarcoglycan-sarcospan complex. Interacts (via the N-terminal of alphaDAG1) with LARGE1; the interaction enhances laminin binding. Interacts with SGCD. Interacts with AGR2 and AGR3. Interacts (betaDAG1) with DMD; the interaction is inhibited by phosphorylation on the PPXY motif. Interacts (betaDAG1, via its PPXY motif) with UTRN (via its WWW and ZZ domains); the interaction is inhibited by phosphorylation on the PPXY motif. Interacts (betaDAG1, via its phosphorylated PPXY motif) with the SH2 domain-containing proteins, FYN, CSK, NCK and SHC. Interacts (betaDAG1) with CAV3 (via a central WW-like domain); the interaction disrupts the binding of DMD. BetaDAG1 directly interacts with ANK3, but not with ANK2; this interaction does not interfere with DMD-binding and is required for retention at costameres (By similarity). Identified in a dystroglycan complex that contains at least PRX, DRP2, UTRN, DMD and DAG1 (By similarity). Interacts with POMGNT1 (By similarity).
O-glycosylated (PubMed:9838223). POMGNT1 catalyzes the initial addition of N-acetylglucosamine, giving rise to the GlcNAc(beta1-2)Man(alpha1-)O-Ser/Thr moiety and thus providing the necessary basis for the addition of further carbohydrate moieties. Heavily O-glycosylated comprising of up to two thirds of its mass and the carbohydrate composition differs depending on tissue type. Mucin-type O-glycosylation is important for ligand binding activity. O-mannosylation is found in high abundance in both brain and muscle where the most abundant glycan is Sia-alpha-2-3-Gal-beta-1-4-Glc-NAc-beta-1-2-Man. In muscle, glycosylation on Thr-317, Thr-319 and Thr-379 by a phosphorylated O-mannosyl glycan with the structure 2-(N-acetylamido)-2-deoxygalactosyl-beta-1,3-2-(N-acetylamido)-2-deoxyglucosyl-beta-1,4-6-phosphomannose is mediated by like-acetylglucosaminyltransferase (LARGE1) protein amd is required for laminin binding. O-glycosylated in the N-terminal region with a core 1 or possibly core 8 glycan. The brain form displays a unique glycosylation pattern which is absent in other tissues; this form shows enhanced binding to laminin LAMA5 compared to the skeletal muscle form (By similarity).
SRC-mediated phosphorylation of the PPXY motif of the beta subunit recruits SH2 domain-containing proteins, but inhibits binding to WWW domain-containing proteins, DMD and UTRN. This phosphorylation also inhibits nuclear entry (By similarity).
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 (By similarity).
Activated by manganese or magnesium ions. In the presence of magnesium ions, the enzyme is activated by bicarbonate. Calcium mildly increases the enzyme activity, also in the presence of magnesium ions.
Catalyzes the formation of the signaling molecule cAMP. May function as sensor that mediates responses to changes in cellular bicarbonate and CO(2) levels (By similarity). Has a critical role in mammalian spermatogenesis by producing the cAMP which regulates cAMP-responsive nuclear factors indispensable for sperm maturation in the epididymis. Induces capacitation, the maturational process that sperm undergo prior to fertilization (By similarity). Involved in ciliary beat regulation (By similarity).
Catalyzes the formation of the signaling molecule cAMP. May function as sensor that mediates responses to changes in cellular bicarbonate and CO(2) levels. Has a critical role in mammalian spermatogenesis by producing the cAMP which regulates cAMP-responsive nuclear factors indispensable for sperm maturation in the epididymis. Induces capacitation, the maturational process that sperm undergo prior to fertilization. Involved in ciliary beat regulation.
The N-terminal guanylate cyclase domains are required for enzyme activity. Fragments containing the first 470 amino acid residues are fully active.
Belongs to the WD repeat peroxin-7 family.
Catalyzes the conversion of biologically active 11beta-hydroxyglucocorticoids (11beta-hydroxysteroid) such as corticosterone, to inactive 11-ketoglucocorticoids (11-oxosteroid) such as 11-dehydrocorticosterone, in the presence of NAD(+) (PubMed:7750480). Functions as a dehydrogenase (oxidase), thereby decreasing the concentration of active glucocorticoids, thus protecting the nonselective mineralocorticoid receptor from occupation by glucocorticoids (By similarity). Plays an important role in maintaining glucocorticoids balance during preimplantation and protects the fetus from excessive maternal corticosterone exposure (By similarity). Catalyzes the oxidation of 11beta-hydroxytestosterone (11beta,17beta-dihydroxyandrost-4-ene-3-one) to 11-ketotestosterone (17beta-hydroxyandrost-4-ene-3,11-dione), a major bioactive androgen. Catalyzes the conversion of 11beta-hydroxyandrostenedione (11beta-hydroxyandrost-4-ene-3,17-dione) to 11-ketoandrostenedione (androst-4-ene-3,11,17-trione), which can be further metabolized to 11-ketotestosterone. Converts 7-beta-25-dihydroxycholesterol to 7-oxo-25-hydroxycholesterol in vitro. 7-beta-25-dihydroxycholesterol (not 7-oxo-25-hydroxycholesterol) acts as ligand for the G-protein-coupled receptor (GPCR) Epstein-Barr virus-induced gene 2 (EBI2) and may thereby regulate immune cell migration (By similarity). May protect ovulating oocytes and fertilizing spermatozoa from the adverse effects of cortisol (By similarity).
Interacts with ligand-free cytoplasmic NR3C2.
Belongs to the complex I NDUFA2 subunit family.
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.
Binds 1 zinc ion per subunit. In the homodimer, two zinc ions are bound between subunits.
Catalyzes the conversion of hemimercaptal, formed from methylglyoxal and glutathione, to S-lactoylglutathione.
Detected in fast twitch skeletal muscle (at protein level).
Interacts with TGFBR1; prevents TGFBR1 phosphorylation by TGFBR2 and stabilizes it in the inactive conformation (By similarity). Interacts with ACVR1B and SMAD7. Identified in a complex composed of RYR1, PDE4D, PKA, FKBP1A and protein phosphatase 1 (PP1). Interacts directly with RYR2 and RYR3 (By similarity). Interacts directly with RYR1 (PubMed:1374404, PubMed:10603943, PubMed:25517095, PubMed:27468892). Interacts with GLMN; rapamycin and FK506 abolish the interaction with GLMN in a dose dependent manner (By similarity).
Keeps in an inactive conformation TGFBR1, the TGF-beta type I serine/threonine kinase receptor, preventing TGF-beta receptor activation in absence of ligand. Recruits SMAD7 to ACVR1B which prevents the association of SMAD2 and SMAD3 with the activin receptor complex, thereby blocking the activin signal. May modulate the RYR1 calcium channel activity. PPIases accelerate the folding of proteins. It catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides (By similarity).
Belongs to the nonaspanin (TM9SF) (TC 9.A.2) family.
Component of the transition zone in primary cilia. Required for ciliogenesis.
Inhibited by urea analogs and phloretin.
Mediates the transport of urea driven by a concentration gradient across the cell membrane of the renal inner medullary collecting duct which is critical to the urinary concentrating mechanism.
Belongs to the Mediator complex subunit 20 family.
Belongs to the U1 small nuclear ribonucleoprotein C family.
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.
Belongs to the class-II aminoacyl-tRNA synthetase family. Alax-L subfamily.
Cleaves the gamma-glutamyl peptide bond of glutathione and glutathione conjugates.
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.
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. Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis. Is a regulator of voltage-dependent L-type calcium channels. Mediates calcium-dependent inactivation of CACNA1C. Positively regulates calcium-activated potassium channel activity of KCNN2. Forms a potassium channel complex with KCNQ1 and regulates electrophysiological activity of the channel via calcium-binding. Acts as a sensor to modulate the endoplasmic reticulum contacts with other organelles mediated by VMP1:ATP2A2.
Interacts with CEP97, CCP110, TTN/titin and SRY. Interacts with MYO5A and RRAD (By similarity). Interacts with USP6; the interaction is calcium dependent (By similarity). Interacts with CDK5RAP2. Interacts with SCN5A. Interacts with RYR1 and RYR2 (By similarity). Interacts with FCHO1. Interacts with MIP in a 1:2 stoichiometry; the interaction with the cytoplasmic domains from two MIP subunits promotes MIP water channel closure. Interacts with ORAI1; this may play a role in the regulation of ORAI1-mediated calcium transport. Interacts with SYT7 (By similarity). Interacts with MYO10 and MYO1C (By similarity). Interacts with SLC9A1 in a calcium-dependent manner (By similarity). Interacts with HINT1; interaction increases in the presence of calcium ions (By similarity). Interacts with HINT3 (By similarity). Interacts with SLC26A5 (via STAS domain); this interaction is calcium-dependent and the STAS domain interacts with only one lobe of CALM which is an elongated conformation (By similarity).
Phosphorylation results in a decreased activity.
This protein has four functional calcium-binding sites.
Ubiquitination results in a strongly decreased activity.
Belongs to the complex I subunit 5 family.
Core component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junctions on mRNAs.
Heterodimer with MAGOH. Part of the mRNA splicing-dependent exon junction complex (EJC) complex; the core complex contains CASC3, EIF4A3, MAGOH and RBM8A.
Belongs to the dienelactone hydrolase family.
Involved in several stages of intracellular trafficking.
Belongs to the small GTPase superfamily. Ras family. KappaB-Ras subfamily.
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 protease inhibitor I39 (alpha-2-macroglobulin) family.
Belongs to the methyltransferase superfamily. Trimethylguanosine synthase family.
Involved in trafficking and recycling of synaptic vesicles.
The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2).
Sodium-dependent multivitamin transporter that mediates the electrogenic transport of pantothenate, biotin, lipoate and iodide. Functions as a Na(+)-coupled substrate symporter where the stoichiometry of Na(+):substrate is 2:1, creating an electrochemical Na(+) gradient used as driving force for substrate uptake. Required for biotin and pantothenate uptake in the intestine across the brush border membrane (By similarity). Plays a role in the maintenance of intestinal mucosa integrity, by providing the gut mucosa with biotin (By similarity). Contributes to the luminal uptake of biotin and pantothenate into the brain across the blood-brain barrier (By similarity).
The C-terminal tail is important for biotin uptake as well as apical localization in polarized cells.
Component of a calcium channel complex consisting of a pore-forming alpha subunit (CACNA1C) and the ancillary subunits CACNB3 and CACNA2D1 (PubMed:1312465). The channel complex contains alpha, beta, gamma and delta subunits in a 1:1:1:1 ratio. Interacts with CACNA2D4. Interacts with FASLG (By similarity). Interacts with CBARP; prevents the interaction of CACNB3 with the alpha subunit CACNA1C thereby negatively regulating the activity of the corresponding calcium channel (By similarity).
Most abundant in brain but also present in aorta, trachea and lung.
Regulatory subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents (PubMed:1312465). Increases CACNA1B peak calcium current and shifts the voltage dependencies of channel activation and inactivation (By similarity). Increases CACNA1C peak calcium current and shifts the voltage dependencies of channel activation and inactivation (By similarity).
Belongs to the aspartyl/asparaginyl beta-hydroxylase family.
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.
Interacts with ESR1. Interacts with UBE2I/UBC9. Interacts with SMAD3. Interacts with DDX20.
Sumoylated with SUMO1; sumoylation is required for transcriptional repression activity.
Transcriptional regulator. Critical factor essential for ovary differentiation and maintenance, and repression of the genetic program for somatic testis determination (By similarity). Prevents trans-differentiation of ovary to testis through transcriptional repression of the Sertoli cell-promoting gene SOX9 (By similarity). Has apoptotic activity in ovarian cells (By similarity). Suppresses ESR1-mediated transcription of PTGS2/COX2 stimulated by tamoxifen (By similarity). Activates SIRT1 transcription under cellular stress conditions (By similarity). Activates transcription of OSR2 (By similarity). Is a regulator of CYP19 expression (By similarity). Is a transcriptional repressor of STAR (By similarity). Participates in SMAD3-dependent transcription of FST via the intronic SMAD-binding element (By similarity).
Belongs to the sulfotransferase 1 family. NDST subfamily.
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.
Belongs to the cyclophilin-type PPIase family. PPIL2 subfamily.
Belongs to the ubiquitin-activating E1 family. UBA3 subfamily.
Catalytic subunit of the dimeric E1 enzyme, which activates NEDD8.
In the C-terminal section; belongs to the aldehyde dehydrogenase family. ALDH1L subfamily.
In the N-terminal section; belongs to the GART family.
Glucose-1,6-bisphosphate enhances phosphorylation of the active site Ser-117, and thereby increases enzyme activity.
Isoform 2 is the major calmodulin-dependent phosphoprotein in junctional skeletal sarcoplasmic reticulum vesicles.
Phosphorylation at Thr-467 by PAK1 significantly enhances enzymatic activity.
This enzyme participates in both the breakdown and synthesis of glucose.
Homopentamer. Interacts with HAX1. Interact with ATP2A2; the inhibition decreases ATP2A2 Ca(2+) affinity. Interacts with VMP1; VMP1 competes with PLN and SLN to prevent them from forming an inhibitory complex with ATP2A2. Interacts with S100A1 in a Ca(2+)-dependent manner.
In elongated spermatids, proteolytically cleaved by SPPL2C which modulates intracellular Ca(2+) homeostasis.
Palmitoylated by ZDHHC16, promoting formation of the homopentamer.
Phosphorylation by PKA abolishes the inhibition of ATP2A2-mediated calcium uptake. Phosphorylated at Thr-17 by CaMK2, and in response to beta-adrenergic stimulation. Phosphorylation by DMPK may stimulate sarcoplasmic reticulum calcium uptake in cardiomyocytes (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. Controls intracellular Ca(2+) levels in elongated spermatids. May play a role in germ cell differentiation.
Belongs to the nuclear hormone receptor family. NR2 subfamily.
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 bacterial ribosomal protein bL27 family.
Interacts with GCN1; prevents the interaction of GCN1 with EIF2AK4/GCN2 and inhibits EIF2AK4/GCN2 kinase activity. Interaction with RPL39; this interaction occurs in a GCN1-independent manner. Associates with ribosomes; this interaction occurs in a GCN1-independent manner. Associates with actin; this interaction occurs in a GCN1-independent manner.
The IMPACT locus is imprinted. Paternal inherited gene is expressed, while the maternal inherited gene is silenced.
Translational regulator that ensures constant high levels of translation upon a variety of stress conditions, such as amino acid starvation, UV-C irradiation, proteasome inhibitor treatment and glucose deprivation. Plays a role as a negative regulator of the EIF2AK4/GCN2 kinase activity; impairs GCN1-mediated EIF2AK4/GCN2 activation, and hence EIF2AK4/GCN2-mediated eIF-2-alpha phosphorylation and subsequent down-regulation of protein synthesis. May be required to regulate translation in specific neuronal cells under amino acid starvation conditions by preventing GCN2 activation and therefore ATF4 synthesis. Through its inhibitory action on EIF2AK4/GCN2, plays a role in differentiation of neuronal cells by stimulating neurite outgrowth.
ADP-binding promotes an inactive closed conformation.
Degraded via selective autophagy following interaction with IRGM. IRGM promotes NOD2-RIPK2 RIPosome recruitment to autophagosome membranes, promoting their SQSTM1/p62-dependent autophagic degradation.
Homooligomer: homooligomerizes following muramyl dipeptide (MDP)-binding, promoting RIPK2 recruitment. Interacts (via CARD domain) with RIPK2 (via CARD domain). Following RIPK2 recruitment, RIPK2 homooligomerizes via its CARD domain and forms long filaments named RIPosomes. Interacts (via CARD domain) with ubiquitin; inhibiting interaction with RIPK2. Component of a signaling complex consisting of ARHGEF2, NOD2 and RIPK2. Interacts with ANKRD17 (via N-terminus). Interacts with HSPA1A; the interaction enhances NOD2 stability. Interacts (via both CARD domains) with HSP90; the interaction enhances NOD2 stability. Interacts (via CARD domain) with SOCS3; the interaction promotes NOD2 degradation. Interacts (via CARD domain) with ERBIN; the interaction inhibits activation of NOD2. Interacts with MAPKBP1; the interaction is enhanced in the presence of muramyl dipeptide (MDP) and inhibits NOD2 homooligomerization and activation. Interacts with INAVA; the interaction takes place upon Pattern recognition receptor (PRR) stimulation. Interacts (via NACHT domain) with CARD9. Interacts (via CARD domain) with CASP1; this interaction leads to IL1B processing. Also interacts with CASP4. Interacts with NLRP1; this interaction is enhanced in the presence of muramyl dipeptide (MDP) and leads to increased IL1B release. Interacts with NLRP12; this interaction promotes degradation of NOD2 through the ubiquitin-proteasome pathway. Interacts with ANKHD1, C10orf67, CHMP5, DOCK7, ENTR1, KRT15, LDOC1, PPP1R12C, PPP2R3B, TRIM41 and VIM. Interacts with MAVS; interaction takes place following single-stranded RNA (ssRNA)-binding. Interacts with ATG16L1. Interacts with IRGM; promoting IRGM 'Lys-63'-linked polyubiquitination, which is required for interactions with the core autophagy factors.
Intramolecular interactions between the N-terminal moiety and the leucine-rich repeats (LRR) may be important for autoinhibition in the absence of activating signal.
O-glycosylated by OGT, O-GlcNAcylation increases protein stability.
Palmitoylated by ZDHHC5; palmitoylation is required for proper recruitment to the bacterial entry site and hence for proper signaling upon cognate peptidoglycan detection. Palmitoylation promotes localization to the cell membrane. Palmitoylation protects from SQSTM1/p62-dependent autophagic degradation.
Pattern recognition receptor (PRR) that detects bacterial peptidoglycan fragments and other danger signals and plays an important role in gastrointestinal immunity. Specifically activated by muramyl dipeptide (MDP), a fragment of bacterial peptidoglycan found in every bacterial peptidoglycan type. NOD2 specifically recognizes and binds 6-O-phospho-MDP, the phosphorylated form of MDP, which is generated by NAGK. 6-O-phospho-MDP-binding triggers oligomerization that facilitates the binding and subsequent activation of the proximal adapter receptor-interacting RIPK2. Following recruitment, RIPK2 undergoes 'Met-1'- (linear) and 'Lys-63'-linked polyubiquitination by E3 ubiquitin-protein ligases XIAP, BIRC2, BIRC3 and the LUBAC complex, becoming a scaffolding protein for downstream effectors, triggering activation of the NF-kappa-B and MAP kinases signaling. This in turn leads to the transcriptional activation of hundreds of genes involved in immune response (By similarity). Its ability to detect bacterial MDP plays a central role in maintaining the equilibrium between intestinal microbiota and host immune responses to control inflammation. An imbalance in this relationship results in dysbiosis, whereby pathogenic bacteria prevail on commensals, causing damage in the intestinal epithelial barrier as well as allowing bacterial invasion and inflammation. Acts as a regulator of appetite by sensing MDP in a subset of brain neurons: microbiota-derived MDP reach the brain, where they bind and activate NOD2 in inhibitory hypothalamic neurons, decreasing neuronal activity, thereby regulating satiety and body temperature. NOD2-dependent MDP-sensing of bacterial cell walls in the intestinal epithelial compartment contributes to sustained postnatal growth upon undernutrition (By similarity). Also plays a role in antiviral response by acting as a sensor of single-stranded RNA (ssRNA) from viruses: upon ssRNA-binding, interacts with MAVS, leading to activation of interferon regulatory factor-3/IRF3 and expression of type I interferon. Also acts as a regulator of autophagy in dendritic cells via its interaction with ATG16L1, possibly by recruiting ATG16L1 at the site of bacterial entry (By similarity). NOD2 activation in the small intestine crypt also contributes to intestinal stem cells survival and function: acts by promoting mitophagy via its association with ATG16L1. In addition to its main role in innate immunity, also regulates the adaptive immune system by acting as regulator of helper T-cell and regulatory T-cells (Tregs) (By similarity). Besides recognizing pathogens, also involved in the endoplasmic reticulum stress response: acts by sensing and binding to the cytosolic metabolite sphingosine-1-phosphate generated in response to endoplasmic reticulum stress, initiating an inflammation process that leads to activation of the NF-kappa-B and MAP kinases signaling. May also be involved in NLRP1 activation following activation by MDP, leading to CASP1 activation and IL1B release in macrophages (By similarity).
Polyubiquitinated by TRIM27, leading to proteasome-mediated degradation. Polyubiquitinated and degraded following muramyl dipeptide (MDP) stimulation, conferring MDP tolerance and preventing septic shock.
The ATG16L1-binding motif mediates interaction with ATG16L1.
The LRR repeats recognize and bind muramyl dipeptide (MDP).
The NACHT domain recognizes and binds sphingosine-1-phosphate in response to endoplasmic reticulum stress.
Endopeptidase that degrades various components of the extracellular matrix, such as collagen. Activates progelatinase A. Essential for pericellular collagenolysis and modeling of skeletal and extraskeletal connective tissues during development. May be involved in actin cytoskeleton reorganization by cleaving PTK7. Acts as a positive regulator of cell growth and migration via activation of MMP15 in association with pro-MMP2. Involved in the formation of the fibrovascular tissues in association with pro-MMP2. Cleaves ADGRB1 to release vasculostatin-40 which inhibits angiogenesis.
Interacts (via C-terminal cytoplasmic tail) with BST2. Interacts with DLL1; inhibits DLL1-induced Notch signaling.
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 V-ATPase V0D/AC39 subunit family.
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.
Regulatory subunit of L-type calcium channels (PubMed:7509046). Regulates the activity of L-type calcium channels that contain CACNA1A as pore-forming subunit (PubMed:7509046). Regulates the activity of L-type calcium channels that contain CACNA1C as pore-forming subunit and increases the presence of the channel complex at the cell membrane. Required for functional expression L-type calcium channels that contain CACNA1D as pore-forming subunit. Regulates the activity of L-type calcium channels that contain CACNA1B as pore-forming subunit (By similarity).
Regulatory subunit of L-type calcium channels that consist of a pore-forming alpha subunit and auxiliary beta, gamma and delta subunits (PubMed:7509046, PubMed:27580036). Interacts with CACNA1A, CACNA1B, CACNA1C and CACNA1S (PubMed:7509046). Component of a calcium channel complex consisting of a pore-forming alpha subunit (CACNA1S) and the ancillary subunits CACNB1 or CACNB2, CACNG1 and CACNA2D1 (PubMed:27580036). Identified in a complex with CACNA1C (PubMed:7509046, PubMed:21127204). Identified in a complex with the L-type calcium channel subunits CACNA1C, CACNA2D1, CACNB1 and one of the gamma subunits (CACNG4, CACNG6, CACNG7, or CACNG8) (PubMed:21127204). Part of a L-type calcium channel complex that contains CACNA1D, CACNA2D1 and CACNB1. Part of a L-type calcium channel complex that contains CACNA1B, CACNA2D1 and CACNB1 (By similarity). Interacts with JSRP1. Interacts with RYR1 (By similarity). Interacts with CBARP (By similarity).
Detected in eye lens, kidney, liver, heart, lung, brain and testis.
Functions as crystallin in the rabbit eye lens. Has high L-gulonate 3-dehydrogenase activity. It also exhibits low dehydrogenase activity toward L-3-hydroxybutyrate (HBA) and L-threonate.
Inhibited by malonate and by inorganic phosphate.
Belongs to the F-actin-capping protein beta subunit family.
Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation (By similarity). Induces insulin resistance in adipocytes via inhibition of insulin-induced IRS1 tyrosine phosphorylation and insulin-induced glucose uptake. Induces GKAP42 protein degradation in adipocytes which is partially responsible for TNF-induced insulin resistance (By similarity). Plays a role in angiogenesis by inducing VEGF production synergistically with IL1B and IL6 (By similarity). Promotes osteoclastogenesis and therefore mediates bone resorption (By similarity).
Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin-1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation. Induces insulin resistance in adipocytes via inhibition of insulin-induced IRS1 tyrosine phosphorylation and insulin-induced glucose uptake. Induces GKAP42 protein degradation in adipocytes which is partially responsible for TNF-induced insulin resistance. Plays a role in angiogenesis by inducing VEGF production synergistically with IL1B and IL6.
Homotrimer. Interacts with SPPL2B (By similarity).
O-glycosylated; glycans contain galactose, N-acetylgalactosamine and N-acetylneuraminic acid.
The TNF intracellular domain (ICD) form induces IL12 production in dendritic cells.
The membrane form, but not the soluble form, is phosphorylated on serine residues. Dephosphorylation of the membrane form occurs by binding to soluble TNFRSF1A/TNFR1 (By similarity).
The membrane form, but not the soluble form, is phosphorylated on serine residues. Dephosphorylation of the membrane form occurs by binding to soluble TNFRSF1A/TNFR1.
The soluble form derives from the membrane form by proteolytic processing. The membrane-bound form is further proteolytically processed by SPPL2A or SPPL2B through regulated intramembrane proteolysis producing TNF intracellular domains (ICD1 and ICD2) released in the cytosol and TNF C-domain 1 and C-domain 2 secreted into the extracellular space (By similarity).
The soluble form derives from the membrane form by proteolytic processing. The membrane-bound form is further proteolytically processed by SPPL2A or SPPL2B through regulated intramembrane proteolysis producing TNF intracellular domains (ICD1 and ICD2) released in the cytosol and TNF C-domain 1 and C-domain 2 secreted into the extracellular space.
The soluble form is demyristoylated by SIRT6, promoting its secretion.
Transferrins are iron binding transport proteins which can bind two Fe(3+) ions in association with the binding of an anion, usually bicarbonate. It is responsible for the transport of iron from sites of absorption and heme degradation to those of storage and utilization. Serum transferrin may also have a further role in stimulating cell proliferation.
Belongs to the DNA polymerase type-B family.
Belongs to the purine nucleoside phosphorylase YfiH/LACC1 family.
Belongs to the eukaryotic ribosomal protein eL31 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.
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 NHERF1. Interacts with GABARAPL1.
Belongs to the DNA polymerase type-B-like family.
Belongs to the prefoldin subunit alpha family.
Abundant in heart, muscle, and adipose tissue.
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).
Ubiquitinated at Lys-839 by MYLIP leading to degradation.
Belongs to the Integrator subunit 8 family.
Hydrolyzes specifically phosphatidic acid (PA) to produce 2-acyl lysophosphatidic acid (LPA; a potent bioactive lipid mediator) and fatty acid (By similarity). Does not hydrolyze other phospholipids, like phosphatidylserine (PS), phosphatidylcholine (PC) and phosphatidylethanolamine (PE) or triacylglycerol (TG) (By similarity).
Receptor for arginine vasopressin. The activity of this receptor is mediated by G proteins which activate a phosphatidyl-inositol-calcium second messenger system.
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.