Belongs to the dynactin subunit 2 family.
Part of the dynactin complex that activates the molecular motor dynein for ultra-processive transport along microtubules. In the dynactin soulder domain, binds the ACTR1A filament and acts as a molecular ruler to determine the length (By similarity). Modulates cytoplasmic dynein binding to an organelle, and plays a role in prometaphase chromosome alignment and spindle organization during mitosis. Involved in anchoring microtubules to centrosomes (By similarity).
Subunit of dynactin, a multiprotein complex part of a tripartite complex with dynein and a adapter, such as BICDL1, BICD2 or HOOK3. The dynactin complex is built around ACTR1A/ACTB filament and consists of an actin-related filament composed of a shoulder domain, a pointed end and a barbed end. Its length is defined by its flexible shoulder domain. The soulder is composed of 2 DCTN1 subunits, 4 DCTN2 and 2 DCTN3.
Belongs to the transglutaminase superfamily. Transglutaminase family.
Lacks conserved residue(s) required for the propagation of feature annotation.
Belongs to the G-protein coupled receptor 1 family.
Transcription factor involved in anterior and eye development. Promotes the differentiation of both rod and cone photoreceptors cells in the retina. Together with other retinal homeobox proteins, acts as an effector of a cellular clock which, depending on cell cycle progression, establishes the generation of distinct retinal neuronal cell types. Acts synergistically with nrl to activate the rhodopsin promoter. Promotes the formation of anterior regions and represses the formation of posterior structures during development (By similarity).
Belongs to the poly(ADP-ribose) glycohydrolase family.
Component of the EDM complex, at least composed of e2f4, e2f5, mcidas and tfdp1.
The TIRT domain mediates interaction with e2f4 and tfdp1.
Transcription regulator specifically required for multiciliate cell differentiation. Acts in a multiprotein complex containing e2f4 and e2f5 that binds and activate genes required for centriole biogenesis. Activates genes required for centriole assembly (plk4, cep152) and genes specifically required for motile cilia formation (foxj1). Also promotes the deuterosome pathway of centriole biogenesis by activating expression of deup1, but not its paralog cep63.
Belongs to the inositol monophosphatase superfamily.
Belongs to the SLC26A/SulP transporter (TC 2.A.53) family.
Can bind about 5 Ca(2+) ions per subunit.
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily.
Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family.
Belongs to the apolipoprotein C1 family.
Shares weak sequence similarity with the cyclin family, hence its name. However, it has no cyclin-like function in vivo.
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 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.
The C-terminal di-lysine motif may confer endoplasmic reticulum localization.
Heterotetramer of two alpha chains and two beta chains.
Involved in oxygen transport from the lung to the various peripheral tissues.
Belongs to the nuclear hormone receptor family. NR3 subfamily.
May play a pivotal role in the transcriptional cascade that specifies primary neurons in embryos. Stabilizes the higher neural potential of selected progenitor cells that express neurog2/X-ngnr-1 by maintaining Delta-Notch signaling. Thus ensures the transition between neural competence and irreversible commitment to a neural fate. Also promotes neuronal differentiation by activating neurod1 expression, directly or indirectly (By similarity).
Belongs to the class I-like SAM-binding methyltransferase superfamily. TrmB family.
Catalytic component of METTL1-WDR4 methyltransferase complex that mediates the formation of N(7)-methylguanine in a subset of RNA species, such as tRNAs, mRNAs and microRNAs (miRNAs). Catalyzes the formation of N(7)-methylguanine at position 46 (m7G46) in a large subset of tRNAs that contain the 5'-RAGGU-3' motif within the variable loop. M7G46 interacts with C13-G22 in the D-loop to stabilize tRNA tertiary structure and protect tRNAs from decay. Also acts as a methyltransferase for a subset of internal N(7)-methylguanine in mRNAs. Internal N(7)-methylguanine methylation of mRNAs in response to stress promotes their relocalization to stress granules, thereby suppressing their translation. Also methylates a specific subset of miRNAs.
Catalytic component of the METTL1-WDR4 complex, composed of mettl1 and wdr4.
Required for G1/S transition. Recruits and stabilizes the origin recognition complex (ORC) onto chromatin during G1 to establish pre-replication complex (preRC) and to heterochromatic sites in post-replicated cells. Binds a combination of DNA and histone methylation repressive marks on heterochromatin. Required for silencing of major satellite repeats. May be important ORC2, ORC3 and ORC4 stability (By similarity).
The entire WD repeat region is required for the interaction with ORC complex components, as well as for association with chromatin and for binding to histone methylation marks.
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 cation transport ATPase (P-type) (TC 3.A.3) family. Type V subfamily.
Monomer. Homodecamer; composed of 2 back to back homopentamers. The protein may exist as monomer in solution and oiligomerizes upon ligand binding.
Putative nucleotidyltransferase required for several aspects of embryonic development including normal development of the eye (By similarity). It is unclear whether it displays nucleotidyltransferase activity in vivo. Binds single-stranded RNA (ssRNA) (By similarity).
Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner.
Belongs to the short-chain dehydrogenases/reductases (SDR) family.
Belongs to the protein kinase superfamily.
Belongs to the aldolase class II family. Adducin subfamily.
Belongs to the JHDM3 histone demethylase family.
Belongs to the ubiquitin-conjugating enzyme family.
Expressed ventrally in early gastrulae (stage 10.5) and is expressed most strongly in the outer layer of ectodermal cells. At the late gastrula stage (stage 12), expression appears to be up-regulated consistently in a small group of cells clustered around the ventral edge of the closing blastopore. At the early neurula stage (stage 13), four regions of ectodermal expression are clearly detected. At stage 19 (late neurula), expression persists in the cement gland, the ventral epidermis, the proctodeal region, the lens placodes, and in a broad placodal area caudal to the eye anlagen. In addition, expression also detected in the dorsal root ganglia of the future spinal cord. At stage 21/22, expression seen in a wishbone-shaped group of cells situated dorsal and caudal to each developing optic vesicle corresponding to the cranial (profundal and trigeminal) ganglia. Expression persists in these cells through tail bud and into early tadpole stages. From stage 21/22 onward, the bilateral expression in the ectodermal placodes becomes restricted primarily to the otic placode and the developing otic vesicles. At stage 24, also observed in the precursors of the hypaxial muscles and the pronephric duct in the trunk, in the developing branchial arches and in the primordium of the heart. In stage 29 embryos, expression detected in the frontonasal process and continues to be expressed in the same regions of the embryo at stage 33, although its expression becomes clearly regionalized in the looping heart. A higher level of expression seen in the ventricle as compared with the atrium.
Transcription factor which acts as a transcriptional repressor (By similarity). May also function as a transcriptional activator (By similarity). Binds to the palindromic T site 5'-TTCACACCTAGGTGTGAA-3' DNA sequence, or a half-site, which are present in the regulatory region of several genes (By similarity).
Belongs to the glutathione peroxidase family.
Belongs to the glycosyltransferase group 1 family. Glycosyltransferase 4 subfamily.
In the C-terminal section; belongs to the phosphoglycerate mutase family.
Belongs to the protein kinase superfamily. Tyr protein kinase family. EGF receptor subfamily.
Belongs to the class I-like SAM-binding methyltransferase superfamily. rRNA adenine N(6)-methyltransferase 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.
Acts as a glycogen-targeting subunit for PP1 and regulates its activity. Activates glycogen synthase, reduces glycogen phosphorylase activity and limits glycogen breakdown.
Interacts with PPP1CC catalytic subunit of PP1 and associates with glycogen. Forms complexes with glycogen phosphorylase, glycogen synthase and phosphorylase kinase which is necessary for its regulation of PP1 activity.
The N-terminal region is required for binding to PP1, the central region is required for binding to glycogen and the C-terminal region is required for binding to glycogen phosphorylase glycogen synthase and phosphorylase kinase.
Regulates NF-kappa-B transcription factor activity. Promotes growth of cardiomyocytes, but not cardiomyocyte proliferation. Promotes cardiac muscle hypertrophy. Plays a role in the regulation of the growth of actin filaments. Inhibits the activity of the F-actin-capping protein complex (By similarity).
Belongs to the glycosyltransferase 10 family.
Belongs to the type-B carboxylesterase/lipase family.
Dimer of alpha and beta chains. A typical microtubule is a hollow water-filled tube with an outer diameter of 25 nm and an inner diameter of 15 nM. Alpha-beta heterodimers associate head-to-tail to form protofilaments running lengthwise along the microtubule wall with the beta-tubulin subunit facing the microtubule plus end conferring a structural polarity. Microtubules usually have 13 protofilaments but different protofilament numbers can be found in some organisms and specialized cells.
Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers. Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms. Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin.
Belongs to the nucleotide-sugar transporter family. SLC35A subfamily.
Belongs to the DNA repair metallo-beta-lactamase (DRMBL) family.
Activated by magnesium and inorganic phosphate. Competitively or non-competitively inhibited by ADP, 2,3-bisphosphoglyceride or GDP (By similarity).
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 (By similarity).
Belongs to the class-II pyridoxal-phosphate-dependent aminotransferase family.
Belongs to the class I-like SAM-binding methyltransferase superfamily. NNMT/PNMT/TEMT family.
Belongs to the ubiquitin family. SUMO subfamily.
Cleavage of precursor form by a sentrin-specific protease is necessary for function.
Interacts with sae2 and ube2i. Covalently attached to a number of proteins (By similarity).
Polymeric chains can be formed through Lys-11 cross-linking.
Ubiquitin-like protein which can be covalently attached to target lysines either as a monomer or as a lysine-linked polymer. Does not seem to be involved in protein degradation and may function as an antagonist of ubiquitin in the degradation process. Plays a role in a number of cellular processes such as nuclear transport, DNA replication and repair, mitosis and signal transduction. Covalent attachment to its substrates requires prior activation by the E1 complex sae1-sae2 and linkage to the E2 enzyme ube2i (By similarity).
Belongs to the ammonium transporter (TC 2.A.49) family. Rh subfamily.
Functions as a specific ammonium transporter.
Belongs to the universal ribosomal protein uL13 family.
Cysteine protease that plays a key role in autophagy by mediating both proteolytic activation and delipidation of ATG8 family proteins.
Belongs to the RBR family. RNF144 subfamily.
E3 ubiquitin-protein ligase which accepts ubiquitin from E2 ubiquitin-conjugating enzymes ube2l3 and ube2l6 in the form of a thioester and then directly transfers the ubiquitin to targeted substrates.
Lacks the His residue in the RING-type domain 2 that is one of the conserved features of the family.
Members of the RBR family are atypical E3 ligases. They interact with the E2 conjugating enzyme UBE2L3 and function like HECT-type E3 enzymes: they bind E2s via the first RING domain, but require an obligate trans-thiolation step during the ubiquitin transfer, requiring a conserved cysteine residue in the second RING domain.
Belongs to the sphingomyelin synthase family.
Belongs to the metallo-beta-lactamase superfamily. Glyoxalase II family.
Belongs to the glycosyltransferase 29 family.
Ligand for members of the frizzled family of seven transmembrane receptors.
Belongs to the eukaryotic diacylglycerol kinase family.
Regulatory subunit of the mRNA-capping methyltransferase RNMT:RAMAC complex that methylates the N7 position of the added guanosine to the 5'-cap structure of mRNAs. Promotes the recruitment of the methyl donor, S-adenosyl-L-methionine, to RNMT. Regulates RNMT expression by a post-transcriptional stabilizing mechanism. Binds RNA.
Essential for mitochondrial network organization, mitochondrial metabolism and cell growth at organism and cellular level. May play an important role in mitochondrial protein synthesis. May also participate in mitochondrial DNA replication. May bind to mitochondrial DNA D-loops and contribute to nucleoid stability. Required for enhanced channeling of cholesterol for hormone-dependent steroidogenesis (By similarity).
May be signaling molecules that resemble neuropeptides.
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 DHHC palmitoyltransferase family.
The DHHC domain is required for palmitoyltransferase activity.
Responsible for the release of ribosomes from messenger RNA at the termination of protein biosynthesis. May increase the efficiency of translation by recycling ribosomes from one round of translation to another.
Belongs to the Arg-specific ADP-ribosyltransferase family.
Associated component of the Ragulator complex. Associated component of the Rag GTPases heterodimers.
Belongs to the amino acid/polyamine transporter 2 family. SLC38A9 subfamily.
Lysosomal amino acid transporter involved in the activation of mTORC1 in response to amino acid levels. Probably acts as an amino acid sensor of the Rag GTPases and Ragulator complexes, 2 complexes involved in amino acid sensing and activation of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids. Following activation by amino acids, the Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes where it is in turn activated. SLC38A9 mediates transport of amino acids with low capacity and specificity with a slight preference for polar amino acids. Acts as an arginine sensor. Following activation by arginine binding, mediates transport of L-glutamine, leucine and tyrosine with high efficiency, and is required for the efficient utilization of these amino acids after lysosomal protein degradation. However, the transport mechanism is not well defined and the role of sodium is not clear. Guanine exchange factor (GEF) that, upon arginine binding, stimulates GDP release from RRAGA and therefore activates the Rag GTPase heterodimer and the mTORC1 pathway in response to nutrient sufficiency.
The cytosolic N-terminus part of the protein mediates interaction with the Ragulator complex. The cytosolic N-terminus part of the protein mediates interaction with the Rag GTPase heterodimer in a RRAGA GDP-loaded state dependent and upon arginine binding, leading to the GDP release and SLC38A9 dissociation from the activated Rag GTPase heterodimer (By similarity). The cytosolic N-terminus part of the protein exists at least in two distinct conformations; The first is when the N-terminus is bound snugly in the arginine binding site (in the absence of arginine, low luminal arginine state) and the second is where the N-terminus is released and the substrate-binding site is occupied by arginine (in the presence of arginine, high luminal arginine state) (By similarity).
the CARC and CRAC motifs mediate binding to cholesterol.
Belongs to the tetraspanin (TM4SF) family.
Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits thereby driving them into their inactive GDP-bound form. Binds to G(i)-alpha and G(o)-alpha, but not to G(s)-alpha.
Belongs to the transferase hexapeptide repeat family.
GMPPA is a close homolog of GMPPB, that has been shown to catalyze the formation of GDP-mannose, an essential precursor of glycan moieties of glycoproteins and glycolipids. It has been hypothesized that GMPPA might serve as a regulatory subunit and allow allosteric feedback inhibition of GMPPB by GDP-mannose. Alignment of GMPPAs and GMPPBs from various species shows that GMPPAs are characterized by a 2 amino acid-insertion (residues 11-12) in a highly conserved motif that borders the catalytic pocket and binds the nucleotide substrate in homologous enzymes. This insertion might inactivate the ancestral catalytic site, converting it to an allosteric site.
May serve as a regulatory subunit and allow allosteric feedback inhibition of GMPPB by GDP-mannose.
Belongs to the HIBADH-related family. 3-hydroxyisobutyrate dehydrogenase subfamily.
Component of the cleavage and polyadenylation specificity factor (CPSF) complex that play a key role in pre-mRNA 3'-end formation, recognizing the AAUAAA signal sequence and interacting with poly(A) polymerase and other factors to bring about cleavage and poly(A) addition. CPSF4 binds RNA polymers with a preference for poly(U).
Component of the cleavage and polyadenylation specificity factor (CPSF) complex.
Belongs to the intermediate filament family.
Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IV subfamily.
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 protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.
Interacts with ccny; ccny mediates its recruitment to the plasma membrane and promotes phosphorylation of lrp6.
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, leading to the activation of the Wnt signaling pathway (By similarity).
Belongs to the eukaryotic ribosomal protein eL18 family.
Acts as component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity.
Acts as component of the mcm2-7 complex (mcm complex) which is the putative 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. The existence of maternal and zygotic forms of mcm3 and mcm6 suggests that specific forms of mcm2-7 complexes may be used during different stages of development (By similarity).
Acts as component of the mcm2-7 complex (mcm complex) which is the putative 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. The existence of maternal and zygotic forms of mcm3 and mcm6 suggests that specific forms of mcm2-7 complexes may be used during different stages of development.
Component of the mcm2-7 complex (RLF-M). The complex forms a toroidal hexameric ring with the proposed subunit order mcm2-mcm6-mcm4-mcm7-mcm3-mcm5. The heterodimer of mmcm3/mcm5 interacts with mcm4, mmcm6, mcm7 and weakly with mcm2. The N-terminus is required for interaction with mmcm3, though this interaction may not be direct, and remains in a complex with mmcm3 throughout the cell cycle. Begins to associate with zmcm6 at the neurula stage (By similarity). Component of the replisome complex (By similarity). Component of the CMG helicase complex, composed of the mcm2-7 complex, the GINS complex and cdc45 (By similarity).
Early fractionation of eukaryotic MCM proteins yielded a variety of dimeric, trimeric and tetrameric complexes with unclear biological significance. Specifically a MCM467 subcomplex is shown to have in vitro helicase activity which is inhibited by the MCM2 subunit. The MCM2-7 hexamer is the proposed physiological active complex.
Ubiquitinated by traip when forks converge following formation of DNA interstrand cross-links. Short ubiquitin chains on mcm7 promote recruitment of DNA glycosylase neil3. If the interstrand cross-link cannot be cleaved by neil3, the ubiquitin chains continue to grow on mcm7, promoting the unloading of the CMG helicase complex by the vcp/p97 ATPase.
Belongs to the TAF9 family. CENP-S/MHF1 subfamily.
Belongs to the protease inhibitor I39 (alpha-2-macroglobulin) family.
Belongs to the cyclic nucleotide phosphodiesterase family. PDE8 subfamily.
Binds 2 divalent metal cations per subunit. Site 1 may preferentially bind zinc ions, while site 2 has a preference for magnesium and/or manganese ions.
Belongs to the chloride channel (TC 2.A.49) family. ClC-2/CLCN2 subfamily.
Belongs to the chemokine-like receptor (CMKLR) family.
Belongs to the metallo-beta-lactamase superfamily. RNA-metabolizing metallo-beta-lactamase-like family. CPSF2/YSH1 subfamily.
Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. AIG1/Toc34/Toc159-like paraseptin GTPase family. IAN subfamily.
Belongs to the syndecan proteoglycan family.
ATP-specific succinyl-CoA synthetase functions in the citric acid cycle (TCA), coupling the hydrolysis of succinyl-CoA to the synthesis of ATP and thus represents the only step of substrate-level phosphorylation in the TCA. The beta subunit provides nucleotide specificity of the enzyme and binds the substrate succinate, while the binding sites for coenzyme A and phosphate are found in the alpha subunit.
Belongs to the succinate/malate CoA ligase beta subunit family. ATP-specific subunit beta subfamily.
Heterodimer of an alpha and a beta subunit. The beta subunit determines specificity for ATP.
Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CaMK subfamily.
Belongs to the complex I NDUFA12 subunit family.
May act as a scaffolding protein within caveolar membranes. Interacts directly with G-protein alpha subunits and can functionally regulate their activity.
Belongs to the anion exchanger (TC 2.A.31) family.
May play a role in endosome to Golgi protein trafficking.
Probably involved in the regulation of pre-mRNA splicing.
Belongs to the ligand-gated ion channel (TC 1.A.9) family.
Catalyzes the synthesis of dihydrouridine, a modified base found in the D-loop of most tRNAs.
Belongs to the G-protein coupled receptor T2R family.
Acts as a scaffolding protein at cell-cell junctions, thereby regulating various cellular and signaling processes.
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 protein kinase superfamily. Ser/Thr protein kinase family.
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 2 family.
Component of the replication protein A complex (RPA/RP-A), a heterotrimeric complex composed of RPA1, RPA2 and RPA3.
Differentially phosphorylated throughout the cell cycle, becoming phosphorylated at the G1-S transition and dephosphorylated in late mitosis. Phosphorylation increases upon replication fork stalling (By similarity).
Interacts (via RRM3) with cirbp. Unable to form oligomers. Part of a ribonucleoprotein (RNP) complex, at least composed of elavl1/elrA and/or elavl2/elrB, igf2bp3/vg1RBP, ddx6/Xp54, ybx2/frgy2, lsm14b/rap55b and, in a subset of RNP complexes, stau1/staufen (By similarity).
RNA-binding protein that binds to the 3'-UTR region of mRNAs and increases their stability. Involved in embryonic stem cells (ESCs) differentiation: preferentially binds mRNAs that are not methylated by N6-methyladenosine (m6A), stabilizing them, promoting ESCs differentiation (By similarity). Binds to poly-U elements and AU-rich elements (AREs) in the 3'-UTR of target mRNAs. Acts cooperatively with cribp to stabilize AU-rich sequence (ARE)-containing mRNAs. May play a role during gastrulation. Required for the vegetal localization of vg1 mRNA (By similarity).
Belongs to the TRAFAC class dynamin-like GTPase superfamily. Very large inducible GTPase (VLIG) family.
Tetramer of heterotrimers consisting of exclusion domain, heavy- and light chains.
Belongs to the tumor necrosis factor family.
Cytoplasmic form induces gene transcription inhibition.
Belongs to the WD repeat IPI3/WDR18 family.
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 VPS10-related sortilin family. SORL1 subfamily.
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.
Involved in the mineralization and structural organization of enamel.
A pair of annexin repeats may form one binding site for calcium and phospholipid.
May bind and stabilize microtubules during myotubes formation.
Phosphatidylinositol-4-phosphate-binding protein that may play a role in the process of vesicle budding at the Golgi and anterograde transport to the plasma membrane.
Belongs to the potassium channel HCN family.
Efficient DNA binding requires dimerization with another bHLH protein. Binds DNA as a heterodimer with MAX (By similarity).
Transcriptional repressor. MAD binds with MAX to form a sequence-specific DNA-binding protein complex which recognizes the core sequence 5'-CAC[GA]TG-3'. MAD thus antagonizes MYC transcriptional activity by competing for MAX (By similarity).
May be involved in ciliary biogenesis or function.
Plays an important role in membrane trafficking through the secretory apparatus.
May be involved in 20S pre-rRNA processing.
Involved in transport of proteins from the cis/medial-Golgi to the trans-Golgi network.
Belongs to the two pore domain potassium channel (TC 1.A.1.8) family.
Belongs to the prickle / espinas / testin family.
Scaffold protein that may play a role in cell adhesion, cell spreading and in the reorganization of the actin cytoskeleton. May inhibit cell growth (By similarity). Regulates cranial neural crest migration. Acts together with prickle1 to control axial elongation (By similarity).
The N-terminal and the C-terminal halves of the protein can associate with each other, thereby hindering interactions with other proteins.
Plays a role in nonsense-mediated mRNA decay.
Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family. CACNA1C subfamily.
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death.
Belongs to the beta type-B retroviral polymerase family. HERV class-II K(HML-2) pol subfamily.
Component of the IFT complex A (IFT-A) complex.
Required for cilia formation during embryonal development. Acts as a negative regulator of Shh signaling.
Belongs to the tRNA-intron endonuclease family.
Constitutes one of the two catalytic subunit of the tRNA-splicing endonuclease complex, a complex responsible for identification and cleavage of the splice sites in pre-tRNA. It cleaves pre-tRNA at the 5'- and 3'-splice sites to release the intron. The products are an intron and two tRNA half-molecules bearing 2',3'-cyclic phosphate and 5'-OH termini. There are no conserved sequences at the splice sites, but the intron is invariably located at the same site in the gene, placing the splice sites an invariant distance from the constant structural features of the tRNA body.
Belongs to the universal ribosomal protein uS19 family.
Component of the small ribosomal subunit.
Belongs to the acid sphingomyelinase family.
Belongs to the dynein heavy chain family.
Belongs to the major facilitator superfamily.
Belongs to the DEAD box helicase family. DEAH subfamily.
Belongs to the PtdIns transfer protein family. PI transfer class IIA subfamily.
Belongs to the small GTPase superfamily. Arf family.
GTP-binding protein involved in protein trafficking; modulates vesicle budding and uncoating within the Golgi apparatus.
Belongs to the monovalent cation:proton antiporter 1 (CPA1) transporter (TC 2.A.36) family.
Belongs to the LU7TM family. TMEM87 subfamily.
May be involved in retrograde transport from endosomes to the trans-Golgi network (TGN) (By similarity). In one study, shown to be a component of a novel mechanoelectrical transduction pathway which is involved in cell adhesion and migration, and is thought to act either as a mechanically activated ion channel or as an accessory protein which modulates an unidentified mechanically activated ion channel (By similarity). In another study, neither basal nor mechanically activated channel activity has been observed and, based on structural similarity with WLS, has been suggested to function as a trafficking chaperone for membrane-associated cargo (By similarity).
Belongs to the sodium:solute symporter (SSF) (TC 2.A.21) family.
Belongs to the XRCC4-XLF family. XRCC4 subfamily.
As part of the Ragulator complex it is involved in amino acid sensing and activation of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids. Activated by amino acids through a mechanism involving the lysosomal V-ATPase, the Ragulator plays a dual role for the small GTPases Rag (RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and/or RagD/RRAGD): it (1) acts as a guanine nucleotide exchange factor (GEF), activating the small GTPases Rag and (2) mediates recruitment of Rag GTPases to the lysosome membrane. Activated Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes where it is in turn activated.
Part of the Ragulator complex composed of lamtor1, lamtor2, lamtor3, lamtor4 and lamtor5. The Ragulator complex interacts with slc38a9; the probable amino acid sensor. Component of the lysosomal folliculin complex (LFC).
Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. TGFB receptor subfamily.
Belongs to the aldehyde dehydrogenase family.
RNA-binding protein that inhibits processing of pre-let-7 miRNAs and regulates translation of mRNAs that control developmental timing, pluripotency and metabolism. Seems to recognize a common structural G-quartet (G4) feature in its miRNA and mRNA targets (By similarity). 'Translational enhancer' that drives specific mRNAs to polysomes and increases the efficiency of protein synthesis. Its association with the translational machinery and target mRNAs results in an increased number of initiation events per molecule of mRNA and, indirectly, in mRNA stabilization. Suppressor of microRNA (miRNA) biogenesis, including that of let-7. Binds specific target miRNA precursors (pre-miRNAs), recognizing an 5'-GGAG-3' motif found in their terminal loop, and recruits uridylyltransferase. This results in the terminal uridylation of target pre-miRNAs. Uridylated pre-miRNAs fail to be processed by Dicer and undergo degradation (By similarity). Localized to the periendoplasmic reticulum area, binds to a large number of spliced mRNAs and inhibits the translation of mRNAs destined for the ER, reducing the synthesis of transmembrane proteins, ER or Golgi lumen proteins, and secretory proteins. Binds to and enhances the translation of mRNAs for several metabolic enzymes, increasing glycolysis and oxidative phosphorylation. Which, with the let-7 repression may enhance tissue repair in adult tissue (By similarity).
The CCHC zinc fingers interact with the GGAG motif at the 3' end of let-7 miRNAs precursors, more generally they bind the 5'-NGNNG-3' consensus motif with micromolar affinity. The CSD domain recognizes the loop at the 5' end. The flexible linker allows accommodating variable sequences and lengths among let-7 family members (By similarity).
Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family.
DNA-binding transcription regulator that regulates endothelial cell proliferation and G1/S cell-cycle progression. Specifically binds the 5'-[AT]NTNN[GT]GGCA[AGT]-3' core DNA sequence and acts by modulating expression of pRB-E2F cell-cycle target genes.
Belongs to the galactose-3-O-sulfotransferase family.
Potent stimulator of insulin secretion and relatively poor inhibitor of gastric acid secretion.
Belongs to the inorganic phosphate transporter (PiT) (TC 2.A.20) family.
Sodium-phosphate symporter which preferentially transports the monovalent form of phosphate with a stoichiometry of two sodium ions per phosphate ion.
Transcription factor required for ciliogenesis and islet cell differentiation during endocrine pancreas development.
Belongs to the multicopper oxidase family.
Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.
Probably involved in cement gland formation.
Belongs to the steroid 5-alpha reductase family.
Belongs to the sulfotransferase 1 family.
Belongs to the DNA2/NAM7 helicase family.
Belongs to the major facilitator superfamily. Proton-dependent oligopeptide transporter (POT/PTR) (TC 2.A.17) family.
Interacts (via extracellular domain region) with trypsin.
Belongs to the Toll-like receptor 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.
Belongs to the glycosyltransferase 32 family.
Belongs to the cytidylyltransferase family.
Catalyzes the key rate-limiting step in the CDP-choline pathway for phosphatidylcholine biosynthesis.
Expressed broadly prior to stage 23, after which expression becomes restricted to dorsal tissues. By stage 28, restricted to the notochord and floorplate. Expressed almost exclusively in the most ventral part of the neural tube in anterior regions of the embryo. In posterior regions, expressed more dorsally in the neural tube. At stage 35, expression remains in the notochord, neural tube and brain.
Belongs to the mitochondrion-specific ribosomal protein mL46 family.
GTPase-activating protein for rhoa and cdc42.
Belongs to the calcium channel subunit alpha-2/delta family.
Belongs to the protein-tyrosine phosphatase family. Non-receptor class myotubularin subfamily.
Although it shares weak sequence similarity with GTF2B/TFIIB, displays a similar subdomain organization as GTF2B/TFIIB, with a N-terminal zinc finger, a connecting region (composed of B-reader and B-linker regions), followed by 2 cyclin folds. The RRN7-type zinc finger plays an essential postrecruitment role in Pol I transcription at a step preceding synthesis of the first 40 nucleotides (By similarity).
Component of RNA polymerase I core factor complex that acts as a GTF2B/TFIIB-like factor and plays a key role in multiple steps during transcription initiation such as pre-initiation complex (PIC) assembly and postpolymerase recruitment events in polymerase I (Pol I) transcription. Binds rDNA promoters and plays a role in Pol I recruitment (By similarity).
Belongs to the nuclear hormone receptor family.
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.
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.
Belongs to the complement C6/C7/C8/C9 family.
Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily.
Belongs to the centaurin gamma-like family.
Belongs to the mitochondrial carrier (TC 2.A.29) family.
Catalyzes the exchange of ADP and ATP across the membrane.
Belongs to the glutamate--cysteine ligase type 3 family.
Belongs to the SLC12A transporter family.
Belongs to the immunoglobulin superfamily. L1/neurofascin/NgCAM family.
The branched-chain alpha-keto dehydrogenase complex catalyzes the overall conversion of alpha-keto acids to acyl-CoA and CO(2). It contains multiple copies of three enzymatic components: branched-chain alpha-keto acid decarboxylase (E1), lipoamide acyltransferase (E2) and lipoamide dehydrogenase (E3).
Actin filament (F-actin)-binding protein involved in cell-matrix adhesion and cell-cell adhesion. Regulates cell-surface E-cadherin expression and potentiates mechanosensing by the E-cadherin complex. May also play important roles in cell morphology and locomotion.
Belongs to the vinculin/alpha-catenin family.
May function as a substrate receptor for CUL4-DDB1 E3 ubiquitin-protein ligase complex.
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 PPP phosphatase family. PP-4 (PP-X) subfamily.
Protein phosphatase that regulates many processes such as microtubule organization at centrosomes.
Serine/threonine-protein phosphatase 4 (PP4) occurs in different assemblies of the catalytic and one or more regulatory subunits.
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. Can bind NADP (in vitro).
Belongs to the beta/gamma-crystallin family.
Belongs to the Mediator complex subunit 4 family.
Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors (By similarity).
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 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.
Belongs to the mitochondrial Rho GTPase family.
Mitochondrial GTPase involved in mitochondrial trafficking.
Mitochondrial GTPase involved in mitochondrial trafficking. Probably involved in control of anterograde transport of mitochondria and their subcellular distribution (By similarity).
Ubiquitinated by PRKN in a PINK1-dependent manner, leading to its degradation.
May be involved in transcriptional regulation.
Belongs to the glycosyl hydrolase 33 family.
Receptor for the neuromedin-U and neuromedin-S neuropeptides.
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.
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, gabarapl1-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, gabarapl1-II. During non-canonical autophagy, the processed form is conjugated to phosphatidylserine (PS) phospholipid. Atg4 proteins also mediate the delipidation of PE-conjugated forms required for gabarapl1 recycling when autophagosomes fuse with lysosomes. In addition, some atg4 proteins mediate delipidation of ATG8 proteins conjugated to PS during non-canonical autophagy.
Ubiquitin-like modifier that increases cell-surface expression of kappa-type opioid receptor through facilitating anterograde intracellular trafficking of the receptor. Involved in formation of autophagosomal vacuoles. While LC3s are involved in elongation of the phagophore membrane, the GABARAP/GATE-16 subfamily is essential for a later stage in autophagosome maturation.
TFIIA is a component of the transcription machinery of RNA polymerase II and plays an important role in transcriptional activation.
E3 ubiquitin-protein ligase that is essential for proper development of the forebrain, the eye, and the face (By similarity). Negatively regulates nitric oxide production by inducing nitric oxide synthase translocation to actin cytoskeleton and inhibiting its enzymatic activity (By similarity).
Belongs to the small GTPase superfamily. Rab family.
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 neutral sphingomyelinase family.
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 (By similarity).
Key regulator of the exon junction complex (EJC), a multiprotein complex that associates immediately upstream of the exon-exon junction on mRNAs and serves as a positional landmark for the intron exon structure of genes and directs post-transcriptional processes in the cytoplasm such as mRNA export, nonsense-mediated mRNA decay (NMD) or translation. Acts as an EJC disassembly factor, allowing translation-dependent EJC removal and recycling by disrupting mature EJC from spliced mRNAs. Its association with the 40S ribosomal subunit probably prevents a translation-independent disassembly of the EJC from spliced mRNAs, by restricting its activity to mRNAs that have been translated. Interferes with NMD and enhances translation of spliced mRNAs, probably by antagonizing EJC functions (By similarity).
Belongs to the glycosyltransferase 31 family.
Belongs to the somatotropin/prolactin family.
Acts as a transcriptional activator or repressor. Implicated in the regulation of cell-type specific gene expression and play a role in inductive events during lens development (By similarity).
Belongs to the bZIP family. Maf subfamily.
Expressed in the somites at stage 19 onwards. Expressed in the developing hindbrain between neural plate at stage 32. Expressed in the ventral blood islands from stage 22 until stage 28. Expressed in the condensing pronephros at stage 24. Expressed in the pronephric tubules at stage 33. Expressed in the presumptive lens-forming ectoderm (PLE) at stage 22 and during lens formation. Expressed in the invaginating placode at stage 28. Expressed in lens epithelia at stage 33. Expressed in the rhombencephalon at least until stage 40. Expressed in the olfactory bulb and the thalamus at stage 43. Expressed in the neural crest cells.
Homodimer or heterodimer with other bHLH-Zip transcription factors. Binds DNA as a homodimer or a heterodimer (By similarity).
May play a role in the structure and strength of both muscle and bone.
Belongs to the dynein light chain Tctex-type family.
Protein transport. Probably involved in vesicular traffic.
Component of the mcm2-7 complex (RLF-M). The complex forms a toroidal hexameric ring with the proposed subunit order mcm2-mcm6-mcm4-mcm7-mcm3-mcm5. Component of the CMG helicase complex, composed of the mcm2-7 complex, the GINS complex and cdc45.
Belongs to the eukaryotic ribosomal protein eS4 family.
Component of the small ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell.
Belongs to the class I-like SAM-binding methyltransferase superfamily. RsmB/NOP family.
Cooperation and regulatory loops of multiple nodals are essential for mesendoderm patterning in early embryos. Essential for mesoderm formation and axial patterning during embryonic development. Activates the activin-like signaling pathway to induce dorsal and ventral mesoderm in animal cap ectoderm. In addition, also dorsalizes ventral marginal zone (VMZ) tissues during gastrulation. Acts in a downstream signaling cascade via cripto and cer1 to mediate cardiogenesis in embryonic mesoderm. Directs the orientation of the left-right axis by driving the left-specific gene cascade in the left lateral plate mesoderm (By similarity).
Homodimer; disulfide-linked. Interacts with, and is inhibited by cer1 and gdf10/bmp3b.
Probably involved in the organization of the actin cytoskeleton by acting downstream of CDC42, inducing actin filament assembly.
Belongs to the PI3/PI4-kinase family. ATM subfamily.
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.
Heterodimer of an alpha and a beta subunit.
Catalyzes one step in the degradation of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA).
Belongs to the protein-tyrosine phosphatase family. Non-receptor class 2 subfamily.
Belongs to the peptidase C65 family. Otulin subfamily.
Belongs to the ADP-ribosyl cyclase family.
Binds specifically to collagen. Could be involved as a chaperone in the biosynthetic pathway of collagen.
Plays a key role in steroid hormone synthesis by enhancing the metabolism of cholesterol into pregnenolone. Mediates the transfer of cholesterol from the outer mitochondrial membrane to the inner mitochondrial membrane where it is cleaved to pregnenolone.
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.
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.
Belongs to the SMC family. SMC1 subfamily.
Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity.
Belongs to the bacterial ribosomal protein bL19 family.
Belongs to the acyl-CoA dehydrogenase family.
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 Ca(2+):cation antiporter (CaCA) (TC 2.A.19) family. SLC8 subfamily.
Belongs to the TRAFAC class dynamin-like GTPase superfamily. IRG family.
Mitochondrial carrier mediating the transport of coenzyme A (CoA) in mitochondria in exchange for intramitochondrial (deoxy)adenine nucleotides and adenosine 3',5'-diphosphate.
Belongs to the WD repeat G protein beta family.
Belongs to the bacterial ribosomal protein bS21 family.
Belongs to the pancreatic ribonuclease family.
Component of a multi-subunit COQ enzyme complex, composed of at least COQ3, COQ4, COQ5, COQ6, COQ7 and COQ9.
Component of the coenzyme Q biosynthetic pathway. May play a role in organizing a multi-subunit COQ enzyme complex required for coenzyme Q biosynthesis. Required for steady-state levels of other COQ polypeptides.
Belongs to the nuclear hormone receptor family. NR1 subfamily.
Belongs to the universal ribosomal protein uL2 family.
Transcription factor that plays a key role in several developmental processes, including neurogenesis, chondrocytes differentiation and cartilage formation. Specifically binds the 5'-AACAAT-3' DNA motif present in enhancers and super-enhancers and promotes expression of genes important for chondrogenesis. Required for overt chondrogenesis when condensed prechondrocytes differentiate into early stage chondrocytes: sox5 and sox6 cooperatively bind with sox9 on active enhancers and super-enhancers associated with cartilage-specific genes, and thereby potentiate sox9's ability to transactivate. Not involved in precartilaginous condensation, the first step in chondrogenesis, during which skeletal progenitors differentiate into prechondrocytes. Binds to the proximal promoter region of the myelin protein MPZ gene, and is thereby involved in the differentiation of oligodendroglia in the developing spinal tube.
Belongs to the Cu-Zn superoxide dismutase family.
Destroys radicals which are normally produced within the cells and which are toxic to biological systems.
Belongs to the SLC35F solute transporter family.
May play a role as a nucleotide-sugar transporter.
Functions as a GC-rich promoter-specific transactivating transcription factor.
Dioxygenase that demethylates RNA by oxidative demethylation: specifically demethylates N(6)-methyladenosine (m6A) RNA, the most prevalent internal modification of messenger RNA (mRNA) in higher eukaryotes. Can also demethylate N(6)-methyladenosine in single-stranded DNA (in vitro) (By similarity). Requires molecular oxygen, alpha-ketoglutarate and iron (By similarity). Demethylation of m6A mRNA affects mRNA processing and export (By similarity).
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 eukaryotic mitochondrial porin family.
Component of the oligosaccharyltransferase (OST) complex.
Subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophosphate to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains, the first step in protein N-glycosylation. N-glycosylation occurs cotranslationally and the complex associates with the Sec61 complex at the channel-forming translocon complex that mediates protein translocation across the endoplasmic reticulum (ER). All subunits are required for a maximal enzyme activity.
Belongs to the cation diffusion facilitator (CDF) transporter (TC 2.A.4) family. SLC30A subfamily.
Probable component of a SCF(NIPA) E3 complex.
Probable component of a SCF-type E3 ligase complex, SCF(NIPA), a complex that controls mitotic entry by mediating ubiquitination and subsequent degradation of cyclin B1 (CCNB1).
Belongs to the carbon-nitrogen hydrolase superfamily. NIT1/NIT2 family.
Has omega-amidase activity. The role of omega-amidase is to remove potentially toxic intermediates by converting 2-oxoglutaramate and 2-oxosuccinamate to biologically useful 2-oxoglutarate and oxaloacetate, respectively.
Component of centromeric nucleosomes, where DNA is wrapped around a histone octamer core. The octamer contains two molecules each of H2A, H2B, CENPA and H4 assembled in one CENPA-H4 heterotetramer and two H2A-H2B heterodimers. CENPA modulates the DNA-binding characteristics of nucleosomes so that protruding DNA ends have higher flexibility than in nucleosomes containing conventional histone H3.
Histone H3-like nucleosomal protein that is specifically found in centromeric nucleosomes. Replaces conventional H3 in the nucleosome core of centromeric chromatin that serves as an assembly site for the inner kinetochore. The presence of CENPA subtly modifies the nucleosome structure and the way DNA is wrapped around the nucleosome and gives rise to protruding DNA ends that are less well-ordered and rigid compared to nucleosomes containing histone H3. May serve as an epigenetic mark that propagates centromere identity through replication and cell division. Required for recruitment and assembly of kinetochore proteins, and as a consequence required for progress through mitosis, chromosome segregation and cytokinesis.
Belongs to the cytidine and deoxycytidylate deaminase family.
This enzyme scavenges exogenous and endogenous cytidine and 2'-deoxycytidine for UMP synthesis.
It is uncertain whether Met-1 or Met-2 is the initiator.
Binds oxysterols in a pocket within their transmembrane domains and interacts with scap via transmembrane domains 3 and 4.
Interacts with scap; interaction is direct and only takes place in the presence of sterols; it prevents interaction between scap and the coat protein complex II (COPII). Associates with the SCAP-SREBP complex; association is mediated via its interaction with scap and only takes place in the presence of sterols.
Oxysterol-binding protein that mediates feedback control of cholesterol synthesis by controlling both endoplasmic reticulum to Golgi transport of scap and degradation of hmgcr. Acts as a negative regulator of cholesterol biosynthesis by mediating the retention of the SCAP-SREBP complex in the endoplasmic reticulum, thereby blocking the processing of sterol regulatory element-binding proteins (SREBPs). Binds oxysterol, including 22-hydroxycholesterol, 24-hydroxycholesterol, 25-hydroxycholesterol and 27-hydroxycholesterol, regulating interaction with scap and retention of the SCAP-SREBP complex in the endoplasmic reticulum. In presence of oxysterol, interacts with scap, retaining the SCAP-SREBP complex in the endoplasmic reticulum, thereby preventing scap from escorting SREBPs to the Golgi. Sterol deprivation reduce oxysterol-binding, disrupting the interaction between insig2 and scap, thereby promoting Golgi transport of the SCAP-SREBP complex, followed by processing and nuclear translocation of SREBPs. Also regulates cholesterol synthesis by regulating degradation of hmgcr.
The KxHxx motif mediates association with the coatomer complex.
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.
Probable C-mannosyltransferase that mediates C-mannosylation of tryptophan residues on target proteins.
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.
Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family.
May act as a specific coactivator for the mammalian TEFs.
Belongs to the repulsive guidance molecule (RGM) family.
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.
Functional P2XRs are organized as homomeric and heteromeric trimers.
Receptor for ATP that acts as a ligand-gated ion channel.
Belongs to the protein-tyrosine phosphatase family. Non-receptor class dual specificity subfamily.
Dual specificity phosphatase able to dephosphorylate phosphotyrosine, phosphoserine and phosphothreonine residues within the same substrate, with a preference for phosphotyrosine as a substrate (By similarity). Involved in the modulation of AMPK and MAPK1/2 signaling pathways (By similarity).
Dual specificity phosphatase able to dephosphorylate phosphotyrosine, phosphoserine and phosphothreonine residues, with a preference for phosphotyrosine as a substrate.
Belongs to the G-protein coupled receptor Fz/Smo family.
May be involved in DNA double-strand break (DBS) repair via homologous recombination (HR). May regulate osteoblast proliferation and differentiation (By similarity).
The N-terminus is necessary for its recruitment to DNA damage sites.
Acts as component of the retromer cargo-selective complex (CSC). The CSC is believed to be the core functional component of retromer or respective retromer complex variants acting to prevent missorting of selected transmembrane cargo proteins into the lysosomal degradation pathway. Retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) (By similarity).
Component of the heterotrimeric retromer cargo-selective complex (CSC) which is believed to associate with variable sorting nexins to form functionally distinct retromer complex variants (By similarity).
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.
May affect the rate of fibrils formation.
Belongs to the integrin alpha chain family.
Belongs to the VPS10-related sortilin family. SORCS subfamily.
Downstream effector of Notch signaling. Transcriptional repressor which binds preferentially to the canonical E box sequence 5'-CACGTG-3'. Acts as a suppressor of neurogenesis by antagonizing proneural gene function. Functions during floorplate development. Plays a role in pronephros formation in the inhibition of distal tubule and duct cell fates and the promotion of glomus and proximal tubule formation (By similarity).
Efficient DNA binding requires dimerization with another bHLH protein. Binds DNA in the form of homodimer or more strongly as a heterodimer with hes1/hairy1 or hes4/hairy2b. Also weakly interacts with the bHLH proteins hes2, neurod1 and neurod4/ath3. Interacts (via Orange domain) with ccdc89/boip (via C-terminus) (By similarity).
The C-terminal YRPW motif is not required for transcriptional repressor activity and is unable to recruit groucho.
The Orange domain, downstream sequence and the bHLH are required for efficient heterodimerization with hes/hairy proteins, and for transcriptional repressor activity.
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 bZIP family. CNC subfamily.
Belongs to the metallophosphoesterase superfamily. MPPE1 family.
Endoplasmic reticulum-Golgi intermediate compartment membrane
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.
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.
Belongs to the argininosuccinate synthase family.
One of the enzymes of the urea cycle, the metabolic pathway transforming neurotoxic amonia produced by protein catabolism into inocuous urea in the liver of ureotelic animals. Catalyzes the formation of arginosuccinate from aspartate, citrulline and ATP and together with ASL it is responsible for the biosynthesis of arginine in most body tissues.
Involved in the regulation of endocytosis and in several stages of intracellular trafficking. Together with snx4, involved in autophagosome assembly.
Belongs to the ubiA prenyltransferase family.
Converts protoheme IX and farnesyl diphosphate to heme O.
Belongs to the pyrimidine 5'-nucleotidase family.
Belongs to the dynein light chain 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 universal ribosomal protein uS10 family.
Component of the 40S small ribosomal subunit.
Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth.
Mycophenolic acid (MPA) is a non-competitive inhibitor that prevents formation of the closed enzyme conformation by binding to the same site as the amobile flap. In contrast, mizoribine monophosphate (MZP) is a competitive inhibitor that induces the closed conformation. MPA is a potent inhibitor of mammalian IMPDHs but a poor inhibitor of the bacterial enzymes. MZP is a more potent inhibitor of bacterial IMPDH.
Interacts with katna1. This interaction enhances the microtubule binding and severing activity of katna1 and also targets this activity to the centrosome.
Participates in a complex which severs microtubules in an ATP-dependent manner. May act to target the enzymatic subunit of this complex to sites of action such as the centrosome. Microtubule severing may promote rapid reorganization of cellular microtubule arrays and the release of microtubules from the centrosome following nucleation.
Belongs to the 2H phosphoesterase superfamily. CNPase family.
May participate in RNA metabolism in the myelinating cell, CNP is the third most abundant protein in central nervous system myelin.
Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is composed of 13 subunits: EIF3A, EIF3B, EIF3C, EIF3D, EIF3E, EIF3F, EIF3G, EIF3H, EIF3I, EIF3J, EIF3K, EIF3L and EIF3M.
Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is involved in protein synthesis of a specialized repertoire of mRNAs and, together with other initiation factors, stimulates binding of mRNA and methionyl-tRNAi to the 40S ribosome. The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation.
Facilitates ubiquitin-independent proteasomal degradation of polycomb protein CBX4. Plays a role in inhibiting the activity of glucokinase GCK and both glucose-induced and basal insulin secretion.
ATP-dependent annealing helicase that catalyzes the rewinding of the stably unwound DNA. Rewinds single-stranded DNA bubbles that are stably bound by replication protein A (RPA). Acts throughout the genome to reanneal stably unwound DNA, performing the opposite reaction of many enzymes, such as helicases and polymerases, that unwind DNA (By similarity).
Belongs to the SNF2/RAD54 helicase family. SMARCAL1 subfamily.
Acts as a positive cofactor of GATA transcription factors to establish the identity of the ventral mesoderm during gastrulation. Down-regulation in the dorsal mesoderm is necessary for the proper formation of this territory since, when present, lmo4 may bind ldb1 and restrict the availability of this cofactor for Spemman organizer transcription factors. At neurula stages, suppresses primary neuron differentiation and modulates gene expression at the Isthmic Organizer of the midbrain-hindbrain boundary (By similarity).
Belongs to the SMC family. RAD50 subfamily.
Belongs to the SOSS-B family. SOSS-B1 subfamily.
Component of the SOSS complex, a multiprotein complex that functions downstream of the MRN complex to promote DNA repair and G2/M checkpoint. In the SOSS complex, acts as a sensor of single-stranded DNA that binds to single-stranded DNA. The SOSS complex associates with DNA lesions and influences diverse endpoints in the cellular DNA damage response including cell-cycle checkpoint activation, recombinational repair and maintenance of genomic stability. Required for efficient homologous recombination-dependent repair of double-strand breaks (DSBs) (By similarity).
Component of the SOSS complex, composed of soss-b (soss-b1/nabp2 or soss-b2/nabp1), soss-a/ints3 and soss-c/inip. SOSS complexes containing soss-b1/nabp2 are more abundant than complexes containing soss-b2/nabp1 (By similarity).
Belongs to the glycosyltransferase 18 family.
Specific and highly efficient GDP-D-glucose phosphorylase regulating the levels of GDP-D-glucose in cells.
The ortholog in A.thaliana catalyzes the first reaction of the Smirnoff-Wheeler pathway, the major route to ascorbate biosynthesis in plants.
Belongs to the sulfotransferase 2 family.
Belongs to the Mediator complex subunit 24 family.
Acts as a transcriptional activator or repressor.
Expressed in the presumptive lens ectoderm at stage 24. Expressed in the pronephros from stage 28 onwards. Expressed in the forming tubules but also in the glomus of the pronephros from stage 33. Expressed in cells of the optic vesicle in a dorso-temporal location and in cells showing the expected dorsal location of Rohon-Beard neurons in the neural tube at stage 35.
Homodimer or heterodimer. Binds DNA as a homodimer or a heterodimer (By similarity).
Belongs to the beta-microseminoprotein family.
Belongs to the adaptor complexes small subunit family.
Belongs to the universal ribosomal protein uS4 family.
Belongs to the diacylglycerol acyltransferase family.
Belongs to the eukaryotic/archaeal RNase P protein component 2 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.
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.
Catalyzes the post-translational formation of 4-hydroxyproline in -Xaa-Pro-Gly- sequences in collagens and other proteins.
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.
Belongs to the dicarboxylate/amino acid:cation symporter (DAACS) (TC 2.A.23) family.
ATP-dependent chaperone, which plays an essential role in the cytoplasmic maturation steps of pre-60S ribosomal particles by promoting the release of shuttling protein RSL24D1/RLP24 from the pre-ribosomal particles.
Belongs to the AAA ATPase family. AFG2 subfamily.
Functions as guanine nucleotide exchange factor (GEF) for rab11a.
Belongs to the glycosyl hydrolase 22 family.
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 bacterial ribosomal protein bS16 family.
Belongs to the V-ATPase e1/e2 subunit family.
Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons. V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment.
V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex.
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.
Plays a role in the microtubule-dependent coupling of the nucleus and the centrosome.
Belongs to the ATP:guanido phosphotransferase family.
Belongs to the UDP-glycosyltransferase family.
Belongs to the TRAPP small subunits family.
Part of the multisubunit transport protein particle (TRAPP) complex.
Probable acetyltransferase, which acetylates the inositol ring of phosphatidylinositol during biosynthesis of GPI-anchor.
Belongs to the heat shock protein 90 family.
Functions as a component of the nuclear pore complex (NPC).
Functions as a component of the nuclear pore complex (NPC). NPC components, collectively referred to as nucleoporins (NUPs), can play the role of both NPC structural components and of docking or interaction partners for transiently associated nuclear transport factors (By similarity).
Belongs to the STXBP/unc-18/SEC1 family.
Belongs to the LDH/MDH superfamily. MDH type 1 family.
Belongs to the MPDU1 (TC 2.A.43.3) family.
Glycosylation is required for protein secretion.
Ligand for members of the frizzled family of seven transmembrane receptors (By similarity). Shares much functionality with wnt11b. Signals through a non-canonical Wnt pathway to activate Jun-N-terminal kinase (JNK) to regulate gastrulation movements. Acts in a non-cell-autonomous manner to control neural crest migration, probably acting as an extracellular signal from surrounding tissue, but is not required for neural crest induction. Acts redundantly with wnt11b during pronephros induction. Regulates cardiac morphogenesis through the activation of JNK, but is not required for cardiac differentiation. Essential for dorsal fin development; required for an epithelial to mesenchymal transformation event prior to migration of cells into the fin, and ultimately for maintenance of fin structure. Mediates dorsal fin development through a non-canonical pathway mediated by Ca(2+) (By similarity).
Palmitoleoylation is required for efficient binding to frizzled receptors. Depalmitoleoylation leads to Wnt signaling pathway inhibition.
Xenopus and other lower vertebrates contain duplicated wnt11 genes (wnt11 and wnt11b) resulting from an ancient gene duplication event, but the second copy has since been lost in mammals.
Associates with GIRK2, GIRK3 or GIRK4 to form a G-protein activated heteromultimer pore-forming unit. The resulting inward current is much larger.
Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ3 subfamily.
This potassium channel is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. This receptor plays a crucial role in regulating the heartbeat.
Plays a role in phosphate homeostasis. Mediates phosphate export from the cell. Binds inositol hexakisphosphate (Ins6P) and similar inositol polyphosphates, such as 5-diphospho-inositol pentakisphosphate (5-InsP7); these are important intracellular signaling molecules.
The SPX domain has high affinity for inositol polyphosphates, such as myo-inositol hexakisphosphate and 5-diphospho-myo-inositol pentakisphosphate (5-InsP7). Its affinity for inorganic phosphate is tow to three orders of magnitude lower.
Forms protease inhibiting heterodimer with TMPRSS7.
Associates with the 60S ribosomal subunit of the 80S translational complex.
Belongs to the peptidase M24A family. Methionine aminopeptidase type 1 subfamily.
Binds 2 divalent metal cations per subunit. Has a high-affinity and a low affinity metal-binding site. The true nature of the physiological cofactor is under debate. The enzyme is active with cobalt, zinc, manganese or divalent iron ions. Most likely, methionine aminopeptidases function as mononuclear Fe(2+)-metalloproteases under physiological conditions, and the catalytically relevant metal-binding site has been assigned to the histidine-containing high-affinity site.
Binds 2 divalent metal cations per subunit. Has a high-affinity and a low affinity metal-binding site. The true nature of the physiological cofactor is under debate. The enzyme is active with zinc, cobalt, manganese or divalent iron ions. Has high activity with zinc; zinc cofactor is transferred into the active site region by the ZNG1 zinc chaperone.
Cotranslationally removes the N-terminal methionine from nascent proteins. The N-terminal methionine is often cleaved when the second residue in the primary sequence is small and uncharged (Met-Ala-, Cys, Gly, Pro, Ser, Thr, or Val).
Belongs to the CDP-alcohol phosphatidyltransferase class-I family.
Belongs to the 2-oxoacid dehydrogenase family.
Belongs to the cyclic nucleotide phosphodiesterase family.
Acetylation at Lys-6 (H4K5ac), Lys-9 (H4K8ac), Lys-13 (H4K12ac) and Lys-17 (H4K16ac) occurs in coding regions of the genome but not in heterochromatin.
Butyrylation of histones marks active promoters and competes with histone acetylation.
Citrullination at Arg-4 (H4R3ci) by PADI4 impairs methylation.
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 (By similarity).
Glutarylation at Lys-92 (H4K91glu) destabilizes nucleosomes by promoting dissociation of the H2A-H2B dimers from nucleosomes.
Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.
Monomethylated, dimethylated or trimethylated at Lys-21 (H4K20me1, H4K20me2, H4K20me3). Monomethylation is performed by KMT5A/SET8. Trimethylation is performed by KMT5B and KMT5C and induces gene silencing. Monomethylated at Lys-13 (H4K12me1) by N6AMT1; H4K12me1 modification is present at the promoters of numerous genes encoding cell cycle regulators.
Monomethylation and asymmetric dimethylation at Arg-4 (H4R3me1 and H4R3me2a, respectively) by PRMT1 favors acetylation at Lys-9 (H4K8ac) and Lys-13 (H4K12ac). Demethylation is performed by JMJD6. Symmetric dimethylation on Arg-4 (H4R3me2s) by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage (By similarity).
Phosphorylated by pak2 at Ser-48 (H4S47ph). This phosphorylation increases the association of H3.3-H4 with the histone chaperone HIRA, thus promoting nucleosome assembly of H3.3-H4 and inhibiting nucleosome assembly of H3.1-H4 (By similarity).
Sumoylated, which is associated with transcriptional repression.
The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA (By similarity).
Ubiquitinated by the CUL4-DDB-RBX1 complex in response to ultraviolet irradiation. This may weaken the interaction between histones and DNA and facilitate DNA accessibility to repair proteins. Monoubiquitinated at Lys-92 of histone H4 (H4K91ub1) in response to DNA damage. The exact role of H4K91ub1 in DNA damage response is still unclear but it may function as a licensing signal for additional histone H4 post-translational modifications such as H4 Lys-21 methylation (H4K20me) (By similarity).
Ufmylated; monofmylated by UFL1 at Lys-32 (H4K31Ufm1) in response to DNA damage.
Regulates intra- and extracellular levels of inorganic pyrophosphate (PPi), probably functioning as PPi transporter.
Belongs to the ribulose-phosphate 3-epimerase family.
Binds 1 divalent metal cation per subunit.
Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IB subfamily.
Endoplasmic reticulum (ER)-anchored autophagy regulator which exists in an inactive state under basal conditions but is activated following cellular stress. When activated, induces ER fragmentation and mediates ER delivery into lysosomes through sequestration into autophagosomes via interaction with ATG8 family proteins. Promotes ER membrane curvature and ER tubulation required for subsequent ER fragmentation and engulfment into autophagosomes.
Interacts with ATG8 family modifier proteins.
The LIR motif interacts with ATG8 family proteins.
Belongs to the glycosyl hydrolase 2 family.
Exoglycosidase that cleaves the single beta-linked mannose residue from the non-reducing end of all N-linked glycoprotein oligosaccharides.
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family.
Belongs to the glycosyl hydrolase 47 family.
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.
Stimulates the secretion of gonadotropins.
Bifunctional DNA N-glycosylase with associated apurinic/apyrimidinic (AP) lyase function that catalyzes the first step in base excision repair (BER), the primary repair pathway for the repair of oxidative DNA damage. The DNA N-glycosylase activity releases the damaged DNA base from DNA by cleaving the N-glycosidic bond, leaving an AP site. The AP lyase activity cleaves the phosphodiester bond 3' to the AP site by a beta-elimination. Primarily recognizes and repairs oxidative base damage of pyrimidines.
Binds 1 [4Fe-4S] cluster. The cluster does not appear to play a role in catalysis, but is probably involved in the proper positioning of the enzyme along the DNA strand.
Contains Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs, a motif known to be important for the association with nuclear receptors.
Scaffolding component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. Its scaffolding function implies its interaction with the catalytic complex module and diverse RNA-binding proteins mediating the complex recruitment to selected mRNA 3'UTRs. Acts as a transcriptional repressor. Represses the ligand-dependent transcriptional activation by nuclear receptors (By similarity).
Receptor for netrin required for axon guidance. Mediates axon repulsion of neuronal growth cones in the developing nervous system upon ligand binding.
Binds to the 60S ribosomal subunit and prevents its association with the 40S ribosomal subunit to form the 80S initiation complex in the cytoplasm. May also be involved in ribosome biogenesis.
Monomer. Associates with the 60S ribosomal subunit.
Belongs to the 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 F-actin-capping protein beta subunit 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.
RNA-binding protein that may be implicated in the regulation of pre-mRNA alternative splicing.
Heterohexamer. Oligomerizes with other LRRC8 proteins (lrrc8a, lrrc8c, lrrc8d and/or lrrc8b) to form a heterohexamer. Detected in a channel complex that contains lrrc8a, lrrc8c and lrrc8e. In vivo, the subunit composition may depend primarily on expression levels, and heterooligomeric channels containing various proportions of the different LRRC8 proteins may coexist.
Non-essential component of the volume-regulated anion channel (VRAC, also named VSOAC channel), an anion channel required to maintain a constant cell volume in response to extracellular or intracellular osmotic changes. The VRAC channel conducts iodide better than chloride and can also conduct organic osmolytes like taurine. Mediates efflux of amino acids, such as aspartate, in response to osmotic stress. The VRAC channel also mediates transport of immunoreactive cyclic dinucleotide GMP-AMP (2'-3'-cGAMP), an immune messenger produced in response to DNA virus in the cytosol. Channel activity requires lrrc8a plus at least one other family member (lrrc8b, lrrc8c, lrrc8d or lrrc8e); channel characteristics depend on the precise subunit composition. Also plays a role in lysosome homeostasis by forming functional lysosomal VRAC channels in response to low cytoplasmic ionic strength condition: lysosomal VRAC channels are necessary for the formation of large lysosome-derived vacuoles, which store and then expel excess water to maintain cytosolic water homeostasis.
The volume-regulated anion channel (VRAC) channel forms a trimer of dimers, with symmetry mismatch between the pore-forming domain and the cytosolic LRR repeats, a topology similar to gap junction proteins.
Belongs to the mitochondrion-specific ribosomal protein mL52 family.
Belongs to the acetyltransferase family. MAK3 subfamily.
Prenyltransferase that mediates the formation of menaquinone-4 (MK-4) and coenzyme Q10. MK-4 is a vitamin K2 isoform required for endothelial cell development. Mediates the conversion of phylloquinone (PK) into MK-4, probably by cleaving the side chain of phylloquinone (PK) to release 2-methyl-1,4-naphthoquinone (menadione; K3) and then prenylating it with geranylgeranyl pyrophosphate (GGPP) to form MK-4. Also plays a role in cardiovascular development independently of MK-4 biosynthesis, by acting as a coenzyme Q10 biosynthetic enzyme: coenzyme Q10, also named ubiquinone, plays an important antioxidant role in the cardiovascular system. Mediates biosynthesis of coenzyme Q10 in the Golgi membrane, leading to protect cardiovascular tissues from NOS3/eNOS-dependent oxidative stress.
Belongs to the G-protein coupled receptor 1 family. Opsin 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.
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.
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 multi antimicrobial extrusion (MATE) (TC 2.A.66.1) family.
Belongs to the glycosyltransferase 43 family.
Belongs to the class-I aminoacyl-tRNA synthetase family.
Catalyzes the attachment of tyrosine to tRNA(Tyr) in a two-step reaction: tyrosine is first activated by ATP to form Tyr-AMP and then transferred to the acceptor end of tRNA(Tyr).
The nuclear localization signal, which mediates localization to the nucleus, is also important for interacting with tRNA(Tyr), suggesting that it is sterically blocked when tRNA(Tyr) is bound.
Belongs to the heparin-binding growth factors family.
Belongs to the ALG10 glucosyltransferase family.
Belongs to the bacterial ribosomal protein bS6 family.
Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.
Belongs to the phosphorylase b kinase regulatory chain family.
Phosphorylase b kinase catalyzes the phosphorylation of serine in certain substrates, including troponin I.
Belongs to the class-I pyridine nucleotide-disulfide oxidoreductase family.
Maintains high levels of reduced glutathione in the cytosol.
Belongs to the glycosyltransferase 39 family.
Transfers mannose from Dol-P-mannose to Ser or Thr residues on proteins.
Belongs to the succinate dehydrogenase/fumarate reductase iron-sulfur protein family.
Component of complex II composed of four subunits: the flavoprotein (FP) sdha, iron-sulfur protein (IP) sdhb, and a cytochrome b composed of sdhc and sdhd.
Iron-sulfur protein (IP) subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q).
Belongs to the thiolase-like superfamily. Thiolase family.
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.
Belongs to the carbohydrate kinase pfkB family.
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.
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 universal ribosomal protein uL11 family.
Belongs to the major facilitator superfamily. Spinster (TC 2.A.1.49) family.
In cyliated cells, dynein axonemal particle-specific protein required for deployment of ODA to the axoneme. Interacts with outer dynein arm (ODA) subunits.
Required for centrosome duplication and formation and function of the mitotic spindle.
Self-associates. Interacts with pafah1b1 (By similarity).
Belongs to the PA-phosphatase related phosphoesterase family.
Has no 2-lysophosphatidate/LPA phosphatase activity. This is supported by the fact that the phosphatase sequence motifs as well as the His residue acting as a nucleophile in active phosphatases of the PA-phosphatase related phosphoesterase family are not conserved.
May play a role in neurite outgrowth and neurogenesis.
Belongs to the major facilitator superfamily. Sugar transporter (TC 2.A.1.1) family.
Belongs to the short-chain dehydrogenases/reductases (SDR) family. 17-beta-HSD 3 subfamily.
Catalyzes the second 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 has a 3-ketoacyl-CoA reductase activity, reducing 3-ketoacyl-CoA to 3-hydroxyacyl-CoA, within each cycle of fatty acid elongation. Thereby, it may participate in the production of VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators. May also catalyze the transformation of estrone (E1) into estradiol (E2) and play a role in estrogen formation.
Belongs to the class VI-like SAM-binding methyltransferase superfamily. Isoprenylcysteine carboxyl methyltransferase family.
Catalyzes the post-translational methylation of isoprenylated C-terminal cysteine residues.
Belongs to the peroxiredoxin-like PRXL2 family. PRXL2A subfamily.
Involved in redox regulation of the cell. Acts as an antioxidant (By similarity).
Belongs to the poly(A) polymerase family.
Binds 2 magnesium ions. Also active with manganese.
Polymerase that creates the 3'-poly(A) tail of mRNA's.
Belongs to the Mediator complex subunit 1 family.
Endoplasmic reticulum disulfide reductase involved both in the correct folding of proteins and degradation of misfolded proteins.
Oligomeric complex of 4 set of homotrimers.
Belongs to the xanthine dehydrogenase family.
Binds 1 Mo-molybdopterin (Mo-MPT) cofactor per subunit.
Belongs to the V-ATPase V0D/AC39 subunit family.
Belongs to the AB hydrolase superfamily.
Composed of three domains: a modulating N-terminal domain, a DNA-binding domain and a C-terminal ligand-binding domain.
Steroid hormone receptor involved in the regulation of eukaryotic gene expression which affects cellular proliferation and differentiation in target tissues.
Belongs to the dynactin 150 kDa subunit family.
Belongs to the glycosyltransferase 6 family.
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. S6 kinase subfamily.
Belongs to the N-acylglucosamine 2-epimerase family.
Belongs to the membrane-bound acyltransferase family. Sterol o-acyltransferase subfamily.
Belongs to the calycin superfamily. Fatty-acid binding protein (FABP) 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 (By similarity).
Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC/C complex acts by mediating ubiquitination and subsequent degradation of target proteins: it mainly mediates the formation of 'Lys-11'-linked polyubiquitin chains and, to a lower extent, the formation of 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains.
The APC/C is composed of at least 12 subunits. ANAPC16 associates with the rest of the complex independently of ANAPC2 and ANAPC11 (By similarity).
Belongs to the metallo-beta-lactamase superfamily. RNA-metabolizing metallo-beta-lactamase-like family. INTS9 subfamily.
Arginine methyltransferase that can both catalyze the formation of omega-N monomethylarginine (MMA) and symmetrical dimethylarginine (sDMA), with a preference for the formation of MMA. Specifically mediates the symmetrical dimethylation of arginine residues in the small nuclear ribonucleoproteins Sm D1 (SNRPD1) and Sm D3 (SNRPD3); such methylation being required for the assembly and biogenesis of snRNP core particles. Specifically mediates the symmetric dimethylation of histone H4 'Arg-3' to form H4R3me2s. Plays a role in gene imprinting by being recruited by CTCFL at the H19 imprinted control region (ICR) and methylating histone H4 to form H4R3me2s, possibly leading to recruit DNA methyltransferases at these sites. May also play a role in embryonic stem cell (ESC) pluripotency. Also able to mediate the arginine methylation of histone H2A and myelin basic protein (MBP) in vitro; the relevance of such results is however unclear in vivo.
Belongs to the class I-like SAM-binding methyltransferase superfamily. Protein arginine N-methyltransferase family. PRMT7 subfamily.
Kinase that can phosphorylate various inositol polyphosphate such as Ins(3,4,5,6)P4 or Ins(1,3,4)P3.
Belongs to the ZIP transporter (TC 2.A.5) family.
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 AAA ATPase family. Katanin p60 subunit A1 subfamily. A-like 2 sub-subfamily.
Severs microtubules in vitro in an ATP-dependent manner. This activity may promote rapid reorganization of cellular microtubule arrays.
Binds the telomeric double-stranded 5'-TTAGGG-3' repeat.
Belongs to the WD repeat BOP1/ERB1 family.
Component of the PeBoW complex, composed of bop1, pes1 and wdr12. The complex is held together by bop1, which interacts with pes1 via its N-terminal domain and with wdr12 via a high-affinity interaction between the seven-bladed beta-propeller domains of the 2 proteins. The PeBoW complex 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.
Cadherins are calcium-dependent cell adhesion proteins.
Belongs to the SEC23/SEC24 family. SEC24 subfamily.
Binds acetylated histones H3 and H4. Binds butyrylated histone H4.
Plays a role in chromatin remodeling and regulation of transcription. Acts as a chromatin reader that recognizes and binds acylated histones: binds histones that are acetylated and/or butyrylated.
The Bromo domain mediates interaction with histones that have acetylated lysine residues at specific positions. Also recognizes and binds histones that are butyrylated.
Belongs to the cytochrome c oxidase subunit 3 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 using 4 electrons from cytochrome c in the IMS and 4 protons from the mitochondrial matrix.
Belongs to the archaeal Rpo10/eukaryotic RPB10 RNA polymerase subunit family.
Regulates the earliest stages of development of the anterior neural plate. Plays a role in forebrain development by inhibiting the expression of otx2 and pax6 in the rostral region of the anterior neural plate. Necessary for both neural differentiation and neural patterning. Controls Spemann organizer development. May act as a transcriptional repressor (By similarity).
Belongs to the TRAFAC class dynamin-like GTPase superfamily. GB1/RHD3 GTPase family.
Belongs to the protein prenyltransferase subunit alpha family.
Interacts with the GATOR1 complex; interaction is disrupted when BMT2/SAMTOR binds S-adenosyl-L-methionine. Interacts with the KICSTOR complex; interaction is disrupted when BMT2/SAMTOR binds S-adenosyl-L-methionine.
S-adenosyl-L-methionine-binding protein that acts as an inhibitor of mTORC1 signaling via interaction with the GATOR1 and KICSTOR complexes. Acts as a sensor of S-adenosyl-L-methionine to signal methionine sufficiency to mTORC1: in presence of methionine, binds S-adenosyl-L-methionine, leading to disrupt interaction with the GATOR1 and KICSTOR complexes and promote mTORC1 signaling. Upon methionine starvation, S-adenosyl-L-methionine levels are reduced, thereby promoting the association with GATOR1 and KICSTOR, leading to inhibit mTORC1 signaling. Probably also acts as a S-adenosyl-L-methionine-dependent methyltransferase.
Belongs to the universal ribosomal protein uL16 family.
Belongs to the cyclin family. Cyclin Y subfamily.
May play a role in lysosomes motility. Alternatively, may play a role in chromosome segregation (By similarity).
Belongs to the PNRC family. PNRC2 subfamily.
Involved in nonsense-mediated mRNA decay (NMD) by acting as a bridge between the mRNA decapping complex and the NMD machinery. May act by targeting the NMD machinery to the P-body and recruiting the decapping machinery to aberrant mRNAs. Required for upf1/rent1 localization to the P-body. Also acts as a nuclear receptor coactivator (By similarity).
Belongs to the Tim17/Tim22/Tim23 family.
Component of the TIM23 complex at least composed of timm23, timm17 and timm50. The complex interacts with the timm44 component of the PAM complex (By similarity).
Essential component of the TIM23 complex, a complex that mediates the translocation of transit peptide-containing proteins across the mitochondrial inner membrane.
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 copper transporter (Ctr) (TC 1.A.56) family. SLC31A subfamily.
Belongs to the glucose-6-phosphatase family.
Belongs to the MIP/aquaporin (TC 1.A.8) family.
Belongs to the SCAMP family. SCAMP5 subfamily.
Required for the calcium-dependent exocytosis of signal sequence-containing cytokines. Probably acts in cooperation with the SNARE machinery (By similarity).
Belongs to the enoyl-CoA hydratase/isomerase family.
Belongs to the snRNP core protein family.
Belongs to the TALE/IRO homeobox 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 Integrator subunit 3 family.
Identified in the spliceosome B complex. Component of the U4/U6-U5 tri-snRNP complex. Component of some MLL1/MLL complex.
Interacts with the snRNP via the Nop domain.
Involved in pre-mRNA splicing as component of the spliceosome. Required for the assembly of the U4/U5/U6 tri-snRNP complex, one of the building blocks of the spliceosome.
The coiled coil domain is formed by two non-contiguous helices.
Belongs to the small heat shock protein (HSP20) family.
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 (By similarity). Acts as a 3'-untranslated region (UTR) ARE mRNA-binding adapter protein to communicate signaling events to the mRNA decay machinery (By similarity). 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 (By similarity). Binds to 3'-UTR ARE of numerous mRNAs (By similarity). Induces also the degradation of ARE-containing mRNAs even in absence of poly(A) tail (By similarity). Required for tubulogenesis during pronephros development (By similarity).
Belongs to the glycosyltransferase 22 family.
Belongs to the shaker potassium channel beta subunit family.
Belongs to the glycosyl hydrolase 23 family.
Belongs to the AAA ATPase family. BCS1 subfamily.
Belongs to the ubiquitin conjugation factor E4 family.
Belongs to the heat shock protein 70 family.
Belongs to the POU transcription factor family.
Belongs to the Mediator complex subunit 10 family.
Activated by autophosphorylation of the T-loop at Thr-169 and Ser-173: in contrast to other members of the SNF1 subfamily, phosphorylation at Thr-169 is not mediated by STK11/LKB1 but via autophosphorylation instead.
Autophosphorylated: autophosphorylation of the T-loop at Thr-169 and Ser-173 is required for activation. Phosphorylated by the maturation promoting factor (MPF), composed of cdk1 and a cyclin-B. Also phosphorylated by some MAPK. Phosphorylated during oocyte maturation. Dephosphorylation destabilizes the protein (By similarity).
Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.
Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, self-renewal of stem cells, apoptosis and splicing regulation. Also plays a role in primitive hematopoiesis, possibly by affecting the expression of genes critical for hematopoiesis. Plays a role in cytokinesis during early development (By similarity).
The KA1 domain mediates binding to phospholipids and targeting to membranes.
Belongs to the universal ribosomal protein uS3 family.
Although the SET domain contains the active site of enzymatic activity, both pre-SET and post-SET domains are required for methyltransferase activity. The SET domain also participates in stable binding to heterochromatin (By similarity).
Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. Suvar3-9 subfamily.
Histone methyltransferase that specifically trimethylates 'Lys-9' of histone H3 using monomethylated H3 'Lys-9' as substrate. H3 'Lys-9' trimethylation represents a specific tag for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated histones. Mainly functions in heterochromatin regions, thereby playing a central role in the establishment of constitutive heterochromatin at pericentric and telomere regions. H3 'Lys-9' trimethylation is also required to direct DNA methylation at pericentric repeats. SUV39H1 is targeted to histone H3 via its interaction with RB1 and is involved in many processes (By similarity).
In the pre-SET domain, Cys residues bind 3 zinc ions that are arranged in a triangular cluster; some of these Cys residues contribute to the binding of two zinc ions within the cluster.
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.
Plays a role in endosomal protein trafficking and in targeting proteins for lysosomal degradation. May also contribute to the regulation of gene expression in the nucleus. Binds DNA (in vitro) and may play a synergistic role in the nucleus in regulating the expression of numerous cytokines.
The LITAF domain is stabilized by a bound zinc ion. The LITAF domain contains an amphipathic helix that mediates interaction with lipid membranes.
Acts as chaperone and promotes the dimerization of transcription factors containing basic leucine zipper (bZIP) domains and thereby promotes transcriptional activation.
Component of the transcription/export (TREX) complex; TREX seems to have a dynamic structure involving ATP-dependent remodeling (By similarity).
Export adapter involved in nuclear export of spliced and unspliced mRNA. Binds mRNA which is thought to be transferred to the NXF1-NXT1 heterodimer for export (TAP/NFX1 pathway). Component of the TREX complex which is thought to couple mRNA transcription, processing and nuclear export, and specifically associates with spliced mRNA and not with unspliced pre-mRNA. TREX is recruited to spliced mRNAs by a transcription-independent mechanism, binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5' end of the mRNA where it functions in mRNA export to the cytoplasm. Involved in the nuclear export of intronless mRNA. Involved in transcription elongation and genome stability (By similarity).
Belongs to the reduced folate carrier (RFC) transporter (TC 2.A.48) family.
Mediates high affinity thiamine uptake, probably via a proton anti-port mechanism. Has no folate transport activity.
Belongs to the PDK/BCKDK protein kinase family.
Tyrosine kinase substrate that inhibits growth-factor-mediated activation of MAP kinase.
Major role in the synthesis of nucleoside triphosphates other than ATP. The ATP gamma phosphate is transferred to the NDP beta phosphate via a ping-pong mechanism, using a phosphorylated active-site intermediate.
Part of the E2F6.com-1 complex in G0 phase composed of E2F6, MGA, MAX, TFDP1, CBX3, BAT8, EUHMTASE1, RING1, RNF2, MBLR, BAT8 and YAF2.
Putative Polycomb group (PcG) protein. PcG proteins maintain the transcriptionally repressive state of genes, probably via a modification of chromatin, rendering it heritably changed in its expressibility. Its association with a chromatin-remodeling complex suggests that it may contribute to prevent expression of genes that trigger the cell into mitosis. Binds to monomethylated and dimethylated 'Lys-20' on histone H4. Binds histone H3 peptides that are monomethylated or dimethylated on 'Lys-4', 'Lys-9' or 'Lys-27'.
Belongs to the FIT family. FIT1 subfamily.
May play a role in the formation of lipid droplets (LDs), which are storage organelles at the center of lipid and energy homeostasis. May directly bind to diacylglycerol (DAGs) and triacylglycerol.
Belongs to the peroxisomal membrane protein PXMP2/4 family.
Interacts with the large mitochondrial ribosomal subunit.
Required for the assembly and stability of the mitochondrial ribosome (By similarity). Is a positive regulator of mitochondrial protein synthesis (By similarity).
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.
Calcium-selective channel required to prevent calcium stores from overfilling.
Belongs to the proteasome subunit S11 family.
Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits including PSMD13, a base containing 6 ATPases and few additional components.
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.
Belongs to the amino acid-polyamine-organocation (APC) superfamily. Cationic amino acid transporter (CAT) (TC 2.A.3.3) family.
Belongs to the adaptor complexes large subunit family.
Belongs to the AVIT (prokineticin) family.
Belongs to the eukaryotic ribosomal protein P1/P2 family.
Plays an important role in the elongation step of protein synthesis.
Belongs to the class I-like SAM-binding methyltransferase superfamily. C5-methyltransferase family.
Belongs to the dihydroorotate dehydrogenase family. Type 2 subfamily.
Catalyzes the conversion of dihydroorotate to orotate with quinone as electron acceptor. Required for UMP biosynthesis via de novo pathway.
Hydrolyzes ADP-ribose, IDP-ribose, CDP-glycerol, CDP-choline and CDP-ethanolamine, but not other non-reducing ADP-sugars or CDP-glucose.
Required for correct functioning of the GINS complex, a complex that plays an essential role in the initiation of DNA replication, and progression of DNA replication forks. GINS complex seems to bind preferentially to single-stranded DNA.
Belongs to the POU transcription factor family. Class-3 subfamily.
Belongs to the natural cytotoxicity receptor (NCR) family.
Homodimer in the unliganted form. Interacts with CD3Z. Interacts with and is activated by binding to NCR3LG1. Interacts with and is activated by binding to BAG6.
Belongs to the LDH/MDH superfamily. MDH type 2 family.
Catalyzes the reduction of aromatic alpha-keto acids in the presence of NADH. Plays essential roles in the malate-aspartate shuttle and the tricarboxylic acid cycle, important in mitochondrial NADH supply for oxidative phosphorylation. Catalyzes the reduction of 2-oxoglutarate to 2-hydroxyglutarate, leading to elevated reactive oxygen species (ROS).
Component of the CPC at least composed of survivin/birc5, incenp, cdca8/borealin and/or cdca9/dasra-A, and aurkb/aurora-B. Interacts (via C-terminus) with aurkb (via N-terminus and kinase domain). Interacts (via N-terminus) with birc5.1, birc5.2, cdca8 and cdca9. Interacts with mtus1 (By similarity).
Component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly. Acts as a scaffold regulating CPC localization and activity. The C-terminus associates with aurkb/aurora-B, the N-terminus associated with cdca8/borealin and/or cdca9/dasra-A tethers the CPC to the inner centromere, and the microtubule binding activity within the central SAH domain directs aurkb/aurora-B toward substrates near microtubules. Activates aurkb.
Originally predicted to contain a coiled coil domain but shown to contain a stable SAH domain instead.
The IN box mediates interaction with aurkb/aurora-B.
The SAH (single alpha-helix) region is characterized by a high content of charged residues which are predicted to stabilize the alpha-helical structure by ionic bonds. It can refold after extension suggesting an in vivo force-dependent function. The isolated SAH domain is monomeric.
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.
High affinity receptor for urotensin-2 and urotensin-2B. The activity of this receptor is mediated by a G-protein that activate a phosphatidylinositol-calcium second messenger system.
Component of clathrin-coated vesicles (By similarity). Plays a role in protein trafficking (By similarity).
Belongs to the sulfotransferase 1 family. NDST subfamily.
Belongs to the potassium channel family. H (Eag) (TC 1.A.1.20) subfamily. Kv11.1/KCNH2 sub-subfamily.
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 PI3/PI4-kinase family. Type III PI4K subfamily.
May function as a transcriptional repressor.
Belongs to the protein disulfide isomerase family.
Acts as component of the retromer cargo-selective complex (CSC). The CSC is believed to be the core functional component of retromer or respective retromer complex variants acting to prevent missorting of selected transmembrane cargo proteins into the lysosomal degradation pathway.
Acts as component of the retromer cargo-selective complex (CSC). The CSC is believed to be the core functional component of retromer or respective retromer complex variants acting to prevent missorting of selected transmembrane cargo proteins into the lysosomal degradation pathway. Retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) (By similarity). Acts also as component of the retriever complex. The retriever complex is an heterotrimeric complex related to retromer cargo-selective complex (CSC) and essential for retromer-independent retrieval and recycling of numerous cargos such as integrins. In the endosomes, retriever complex drives the retrieval and recycling of NxxY-motif-containing cargo proteins by coupling to SNX17, a cargo essential for the homeostatic maintenance of numerous cell surface proteins associated with processes that include cell migration, cell adhesion, nutrient supply and cell signaling (By similarity).
Component of the heterotrimeric retromer cargo-selective complex (CSC) which is believed to associate with variable sorting nexins to form functionally distinct retromer complex variants (By similarity). Component of the heterotrimeric retriever complex (By similarity).
Belongs to the mitochondrion-specific ribosomal protein mS31 family.
Potential calcium-dependent cell-adhesion protein. May be involved in the establishment and maintenance of specific neuronal connections in the brain.
Belongs to the actin-binding proteins ADF family.
Cytochromes P450 are a group of heme-thiolate monooxygenases. They oxidize a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
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 X(+)/potassium ATPases subunit beta family.
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.
Belongs to the metallo-dependent hydrolases superfamily. Adenosine and AMP deaminases family.
Belongs to the LanC-like protein family.
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.
Plays a role in the assembly/stability of the mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V).
Enzyme activity is tightly regulated to prevent the accumulation of reactive oxygen species in the endoplasmic reticulum. Reversibly down-regulated by the formation of disulfide bonds between the active site Cys-99 and Cys-138, and between Cys-104 and Cys-109. Glutathione may be required to regulate its activity in the endoplasmic reticulum (By similarity).
Oxidoreductase involved in disulfide bond formation in the endoplasmic reticulum. Efficiently reoxidizes P4HB/PDI, the enzyme catalyzing protein disulfide formation, in order to allow P4HB to sustain additional rounds of disulfide formation. Following P4HB reoxidation, passes its electrons to molecular oxygen via FAD, leading to the production of reactive oxygen species (ROS) in the cell. Required for the folding of immunoglobulins (By similarity).
Predominantly monomer. May function both as a monomer and a homodimer (By similarity).
The Cys-99/Cys-104 and Cys-401/Cys-404 disulfide bonds constitute the redox-active center. The Cys-99/Cys-104 disulfide bond may accept electron from protein disulfide isomerase (PDI) and funnel them to the active site disulfide Cys-401/Cys-404 (By similarity).
Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.
Belongs to the class I fructose-bisphosphate aldolase family.
Belongs to the peptidase S1 family. Plasminogen subfamily.
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 eukaryotic cobalamin transport proteins family.
Belongs to the RRM HNRPC family. RALY subfamily.
Belongs to the proteasome subunit S3 family.
Belongs to the HAD-like hydrolase superfamily. PHOSPHO family.
Belongs to the C/M/P thioester hydrolase family.
Belongs to the amidinotransferase family.
Catalyzes the biosynthesis of guanidinoacetate, the immediate precursor of creatine. Creatine plays a vital role in energy metabolism in muscle tissues. May play a role in embryonic and central nervous system development (By similarity).
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.
Transcriptional regulator (lacking a basic DNA binding domain) which negatively regulates the basic helix-loop-helix (bHLH) transcription factors by forming heterodimers and inhibiting their DNA binding and transcriptional activity. Inhibits the activity of both neurogenic (neurog1/neurogenin, neurod1/neuroD) and myogenic (myod1/myoD) bHLH factors (By similarity).
Positive regulator of amino acid starvation-induced autophagy.
Allosterically activated by various compounds including ATP, 2,3-BPG/2,3-Bisphosphoglyceric acid and Ap4A/P1,P4-bis(5'-adenosyl) tetraphosphate. Binding of an allosteric activator is a prerequisiste to magnesium and substrate binding. Inhibited by inorganic phosphate.
Belongs to the 5'(3')-deoxyribonucleotidase family.
Broad specificity cytosolic 5'-nucleotidase that catalyzes the dephosphorylation of 6-hydroxypurine nucleoside 5'-monophosphates. In addition, possesses a phosphotransferase activity by which it can transfer a phosphate from a donor nucleoside monophosphate to an acceptor nucleoside, preferably inosine, deoxyinosine and guanosine. Has the highest activities for IMP and GMP followed by dIMP, dGMP and XMP. Could also catalyze the transfer of phosphates from pyrimidine monophosphates but with lower efficiency. Through these activities regulates the purine nucleoside/nucleotide pools within the cell.
Component of the nuclear pore complex (NPC), a complex required for the trafficking across the nuclear envelope. Required for proper protein transport into the nucleus.
Expressed in the developing kidney at stages 26-29 and 33-36, and in the branchial arches at stage 33-36.
Morpholino knockdown of the protein causes abnormal heart and gut looping.
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. DMPK subfamily.
Belongs to the SLC29A/ENT transporter (TC 2.A.57) family.
Belongs to the methylmalonyl-CoA epimerase family.
Belongs to the queuine tRNA-ribosyltransferase family. QTRT2 subfamily.
Heterodimer of a catalytic subunit QTRT1 and an accessory subunit QTRT2.
Non-catalytic subunit of the queuine tRNA-ribosyltransferase (TGT) that catalyzes the base-exchange of a guanine (G) residue with queuine (Q) at position 34 (anticodon wobble position) in tRNAs with GU(N) anticodons (tRNA-Asp, -Asn, -His and -Tyr), resulting in the hypermodified nucleoside queuosine (7-(((4,5-cis-dihydroxy-2-cyclopenten-1-yl)amino)methyl)-7-deazaguanosine).
Endoribonuclease; cleaves preferentially 3' to purine-pyrimidine dinucleotide motifs in single-stranded RNA. The cleavage product contains a free 3' -OH group. Has no activity with double-stranded RNA or DNA. Required for normal mitochondrial function and cell viability.
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 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.
Belongs to the calcium channel alpha-1 subunit (TC 1.A.1.11) family.
DNA-binding transcriptional factor that plays a role in a broad range of cellular and developmental processes such as eye, bones, cardiovascular, kidney and skin development. Acts either as a transcriptional activator or repressor. Binds to the consensus binding site 5'-[G/C][A/T]AAA[T/C]AA[A/C]-3' in promoter of target genes. Upon DNA-binding, promotes DNA bending. Required for cell viability and resistance to oxidative stress in the eye. Promotes cell growth inhibition by stopping the cell cycle in the G1 phase through TGFB1-mediated signals. Involved in epithelial-mesenchymal transition (EMT) induction by increasing cell proliferation, migration and invasion. Involved in chemokine-induced endothelial cell migration. Plays a role in epidermal keratinocyte terminal differentiation. Essential developmental transcriptional factor required for mesoderm-derived tissues formation, such as the somites, skin, bone and cartilage. Plays a role in the development and maintenance of mesenchymal niches for haematopoietic stem and progenitor cells (HSPC). Plays a role in corneal transparency by preventing both blood vessel and lymphatic vessel growth during embryonic development in a VEGF-dependent manner. Plays a role at the gastrula stage for expression of several mesodermal and endodermal genes. At the late neurula stage, regulates expression of adhesion genes to maintain cell adhesion in the mesodermal germ layer.
Component of the elongator complex which is required for multiple tRNA modifications, including mcm5U (5-methoxycarbonylmethyl uridine), mcm5s2U (5-methoxycarbonylmethyl-2-thiouridine), and ncm5U (5-carbamoylmethyl uridine). The elongator complex catalyzes formation of carboxymethyluridine in the wobble base at position 34 in tRNAs.
Belongs to the type I cytokine receptor family. Type 2 subfamily.
Belongs to the DEAD box helicase family.
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.
Catalytic component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids from the outer to the inner leaflet of various membranes and ensures the maintenance of asymmetric distribution of phospholipids (By similarity). Phospholipid translocation seems also to be implicated in vesicle formation and in uptake of lipid signaling molecules. May also participate in the establishment of the canalicular membrane integrity by ensuring asymmetric distribution of phospholipids in the canicular membrane (By similarity).
Component of a P4-ATPase flippase complex which consists of a catalytic alpha subunit and an accessory beta subunit. The flippase ATP8B1:TMEM30A complex can form an intermediate phosphoenzyme in vitro. Also interacts with beta subunit TMEM30B.
Belongs to the eukaryotic ribosomal protein eL43 family.
May play a role in cell adhesion and cell migration.
Belongs to the 1-acyl-sn-glycerol-3-phosphate acyltransferase family.
Belongs to the TRAPP small subunits family. BET3 subfamily.
May play a role in vesicular transport from endoplasmic reticulum to Golgi.
Belongs to the biopterin-dependent aromatic amino acid hydroxylase family.
Belongs to the major facilitator superfamily. Vesicular transporter family.
Contributes to the maintenance of intracerebral BDNF levels within the normal range. May enhance growth factor-induced ERK1 and ERK2 phosphorylation. May attenuate growth factor-promoted ELK1 phosphorylation in a microtubule-dependent manner (By similarity).
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 rod/cone cGMP-PDE gamma subunit family.
Participates in processes of transmission and amplification of the visual signal. cGMP-PDEs are the effector molecules in G-protein-mediated phototransduction in vertebrate rods and cones.
Belongs to the protein arginine deiminase 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.
Ubiquitin-protein ligase which is mainly involved pre-mRNA splicing and DNA repair. Required for pre-mRNA splicing as component of the spliceosome.
Belongs to the protein kinase superfamily. Tyr protein kinase family.
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.
Belongs to the Integrator subunit 8 family.
Pulmonary surfactant associated proteins promote alveolar stability by lowering the surface tension at the air-liquid interface in the peripheral air spaces.
Belongs to the Mediator complex subunit 21 family.
Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.
Belongs to the mitochondrion-specific ribosomal protein mL54 family.
Belongs to the iodothyronine deiodinase family.
Responsible for the deiodination of T4 (3,5,3',5'-tetraiodothyronine).
Belongs to the G-protein coupled receptor 2 family. Adhesion G-protein coupled receptor (ADGR) subfamily.
Belongs to the G-protein coupled receptor 2 family. LN-TM7 subfamily.
Receptor that may have an important role in cell/cell signaling during nervous system formation.
Belongs to the HAD-like hydrolase superfamily.
Belongs to the BPI/LBP/Plunc superfamily. BPI/LBP family.
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.
Single-stranded DNA (ssDNA) metal-dependent exonuclease involved in mitochondrial genome maintenance. Has preference for 5'-3' exonuclease activity. Necessary for maintenance of proper 7S DNA levels. Probably involved in mitochondrial DNA (mtDNA) repair. Specifically binds 5-hydroxymethylcytosine (5hmC)-containing DNA in stem cells (By similarity).
This protein may be expected to contain an N-terminal transit peptide but none has been predicted.
Belongs to the ATP-dependent AMP-binding enzyme family.
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.
Degraded in a 2-step mechanism; a caspase-independent first step and a caspase-dependent second step. Stabilized indirectly by MAPK, which acts to delay caspase activation, rather than directly phosphorylating xiap.
Multi-functional protein which regulates not only caspases and apoptosis, but also acts as an E3 ubiquitin-protein ligase mediating ubiquitination and subsequent proteasomal degradation of its target proteins. Acts as a direct caspase inhibitor. E3 ubiquitin-protein ligase that acts as an important regulator of innate immunity by mediating 'Lys-63'-linked polyubiquitination of ripk2 downstream of NOD1 and NOD2, thereby transforming ripk2 into a scaffolding protein for downstream effectors, ultimately leading to activation of the NF-kappa-B and MAP kinases signaling (By similarity). A key apoptotic suppressor in eggs. Acts as a positive regulator of Wnt signaling (By similarity).
The BIR and RING-type domains are dispensable for anti-apoptotic function.
Interacts with mus81 to form a DNA structure-specific endonuclease which cleaves substrates such as 3'-flap structures.
Tautomerization of D-dopachrome with decarboxylation to give 5,6-dihydroxyindole (DHI).
Belongs to the protein kinase superfamily. BUD32 family.
Belongs to the ABC transporter superfamily. ABCG family. Eye pigment precursor importer (TC 3.A.1.204) subfamily.
Belongs to the LIMR family. LMBRD1 subfamily.
Lysosomal membrane chaperone required to export cobalamin (vitamin B12) from the lysosome to the cytosol, allowing its conversion to cofactors. Targets ABCD4 transporter from the endoplasmic reticulum to the lysosome. Then forms a complex with lysosomal ABCD4 and cytoplasmic MMACHC to transport cobalamin across the lysosomal membrane (By similarity). May play a role in mediating and regulating the internalization of the insulin receptor (By similarity).
Belongs to the complex I 24 kDa subunit family.
Belongs to the PTEN phosphatase protein family.
Belongs to the SMC family. SMC5 subfamily.
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 Rab3-GAP catalytic subunit family.
Efficient DNA binding requires dimerization with another bHLH protein.
Belongs to the AB hydrolase superfamily. AB hydrolase 2 family.
Belongs to the CTL (choline transporter-like) family.
Belongs to the protein-tyrosine phosphatase family. Receptor class 2B subfamily.
Belongs to the TNF receptor-associated factor family.
Belongs to the potassium channel family. B (Shab) (TC 1.A.1.2) subfamily. Kv2.1/KCNB1 sub-subfamily.
Catalyzes the addition of GlcNAc or GlcUA monosaccharides to the nascent hyaluronan polymer. Therefore, it is essential to hyaluronan synthesis a major component of most extracellular matrices that has a structural role in tissues architectures and regulates cell adhesion, migration and differentiation. Also able to catalyze the synthesis of chito-oligosaccharide depending on the substrate (By similarity).
Belongs to the eukaryotic ribosomal protein eL14 family.
Endosome-associated protein that plays a role in membrane receptor sorting, cytokinesis and ciliogenesis.
Belongs to the class I-like SAM-binding methyltransferase superfamily. TPMT family.
Plays a central role in 2-thiolation of mcm(5)S(2)U at tRNA wobble positions of tRNA(Lys), tRNA(Glu) and tRNA(Gln). May act by forming a heterodimer with CTU1/ATPBD3 that ligates sulfur from thiocarboxylated URM1 onto the uridine of tRNAs at wobble position.
Belongs to the class-II aminoacyl-tRNA synthetase family. Type 1 subfamily.
Belongs to the PPP phosphatase family. PP-2B subfamily.
Belongs to the TRAFAC class OBG-HflX-like GTPase superfamily. OBG GTPase family. YchF/OLA1 subfamily.
Hydrolyzes ATP, and can also hydrolyze GTP with lower efficiency. Has lower affinity for GTP.
Detected in blastula and gastrula, in dorsal mesoderm.
Functions in cell-cell adhesion, cell migration and axon guidance, exerting an attractive or repulsive role depending on its interaction partners (By similarity). Modulates cadherin-dependent cell-cell adhesion and cell sorting (By similarity). Plays a role in the spatial organization of brain neurons. Plays a role in vascular development. Plays a role in cell-cell adhesion via its interaction with latrophilins that are expressed at the surface of adjacent cells. Mediates axon attraction towards cells expressing ntn1. mediates axon growth cone collapse and plays a repulsive role in neuron guidance via its interaction with unc-5 family members. Plays a role in the regulation of the density of glutamaergic synapses (By similarity). Plays a role in signaling cascades downstream of fgfr1, and possibly also other fgfr family members (By similarity). Plays a role in embryonic morphogenesis, but not in embryonic patterning (PubMed:19492039).
Interacts with fgfr1 and fgfr4. Interacts with rnd1, cdh1 and pcdh8. Interacts (via extracellular domain) with unc5b and unc5d (via extracellular domain) (By similarity).
Proteolytic cleavage in the juxtamembrane region gives rise to a soluble ectodomain. Cleavage is probably effected by a metalloprotease.
Required to protect lysosomal transporter MFSD1 from lysosomal proteolysis and for MFSD1 lysosomal localization.
Belongs to the U2 small nuclear ribonucleoprotein A family.
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.
Guanine nucleotide exchange factor (GEF) with specificity for rap2a and other Ras family proteins (in vitro). Plays a role in cell migration (By similarity).
Belongs to the complex I NDUFA13 subunit family.
Complex I functions in the transfer of electrons from NADH to the respiratory chain. Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis.
In the C-terminal section; belongs to the eukaryotic ribosomal protein eS31 family.
In the N-terminal section; belongs to the ubiquitin family.
Activated by threonine and tyrosine phosphorylation.
Activated by tyrosine and threonine phosphorylation.
Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. MAP kinase subfamily.
Interacts with sox11, hmgxb4/hmg2l1, rnf138/narf, stat3.1 and mef2a.
Negatively regulates Wnt/beta-catenin-signaling during development. Plays a role together with sox11 in neural induction during early embryogenesis. Involved in TGFbeta-mediated mesoderm induction in early embryos, acting downstream of map3k7/tak1 to phosphorylate stat3. Augments the rnf138/narf-directed ubiquitination and degradation of tcf/lef by enhancing the association of rnf138/narf and tcf/lef. Phosphorylates mef2a to play a role in anterior neural development, including eye formation (By similarity).
Receptor for adenosine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase.
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.
Belongs to the helicase family. SKI2 subfamily.
Required for crossover formation and complete synapsis of homologous chromosomes during meiosis.
Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.
Fatty acid synthetase is a multifunctional enzyme that catalyzes the de novo biosynthesis of long-chain saturated fatty acids starting from acetyl-CoA and malonyl-CoA in the presence of NADPH. This multifunctional protein contains 7 catalytic activities and a site for the binding of the prosthetic group 4'-phosphopantetheine of the acyl carrier protein ([ACP]) domain.
Histones H1 are necessary for the condensation of nucleosome chains into higher-order structures. The histones H1.0 are found in cells that are in terminal stages of differentiation or that have low rates of cell division (By similarity).
Belongs to the SPTSS family. SPTSSB subfamily.
Component of the serine palmitoyltransferase (SPT) complex, which is composed of SPTLC1, SPTLC2 or SPTLC3 and SPTSSA or SPTSSB. The heterodimer consisting of SPTLC1 and SPTLC2/SPTLC3 forms the catalytic core of the enzyme, while SPTSSA or SPTSSB subunits determine substrate specificity (By similarity). SPT also interacts with ORMDL proteins, especially ORMDL3, which negatively regulate SPT activity in the presence of ceramides (By similarity).
Component of the serine palmitoyltransferase multisubunit enzyme (SPT) that catalyzes the initial and rate-limiting step in sphingolipid biosynthesis by condensing L-serine and activated acyl-CoA (most commonly palmitoyl-CoA) to form long-chain bases. The SPT complex is composed of SPTLC1, SPTLC2 or SPTLC3 and SPTSSA or SPTSSB. Within this complex, the heterodimer consisting of SPTLC1 and SPTLC2/SPTLC3 forms the catalytic core. Within the SPT complex, SPTSSB stimulates the catalytic activity and plays a role in substrate specificity. SPT complexes with this subunit showing a preference for longer acyl-CoAs. The SPTLC1-SPTLC2-SPTSSB complex shows a strong preference for C18-CoA substrate, while the SPTLC1-SPTLC3-SPTSSB isozyme displays an ability to use a broader range of acyl-CoAs, without apparent preference.
Component of the nexin-dynein regulatory complex (N-DRC) a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes (By similarity). Involved in the regulation of flagellar motility (By similarity). Essential for male fertility, sperm head morphogenesis and sperm flagellum formation (By similarity).
Component of the nexin-dynein regulatory complex (N-DRC).
Belongs to the methyltransferase superfamily. L-isoaspartyl/D-aspartyl protein methyltransferase family.
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.
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.
Belongs to the Sp1 C2H2-type zinc-finger protein family.
The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. In SP9, the motif is inactive.
Transcription factor which plays a key role in limb development. Positively regulates FGF8 expression in the apical ectodermal ridge (AER) and contributes to limb outgrowth in embryos (By similarity).
In the C-terminal section; belongs to the purine/pyrimidine phosphoribosyltransferase family.
Belongs to the Mediator complex subunit 12 family.
Belongs to the inositol phosphokinase (IPK) family.
Phosphorylates phosphatidylinositol (PI) in the first committed step in the production of the second messenger inositol-1,4,5,-trisphosphate (PIP). May play an important role in the inner ear development.
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.
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.
Involved in maintaining Golgi structure. Stimulates the formation of Golgi stacks and ribbons. Involved in intra-Golgi retrograde transport.
Converts O-phosphoseryl-tRNA(Sec) to selenocysteinyl-tRNA(Sec) required for selenoprotein biosynthesis.
Homotetramer formed by a catalytic dimer and a non-catalytic dimer serving as a binding platform that orients tRNASec for catalysis. Each tetramer binds the CCA ends of two tRNAs which point to the active sites of the catalytic dimer.
Belongs to the glycosyltransferase 25 family.
Mediates the transport of CDP-ribitol (By similarity). Does not exhibit CMP-sialic acid, UDP-galactose and UDP-N-acetylglucosamine transport activity (By similarity).
Accessory subunit of the DNA polymerase alpha complex (also known as the alpha DNA polymerase-primase complex) which plays an essential role in the initiation of DNA synthesis.
Belongs to the DNA polymerase alpha subunit B family.
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.
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.
Belongs to the polyribonucleotide nucleotidyltransferase family.
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.
Component of the RZZ complex composed of kntc1/rod, zw10 and zwilch.
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 (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.
Regulator of the DNA damage response (DDR). Part of the TTT complex that is required to stabilize protein levels of the phosphatidylinositol 3-kinase-related protein kinase (PIKK) family proteins. Promotes assembly, stabilizes and maintains the activity of TORC complexes, which regulate cell growth and survival in response to nutrient and hormonal signals. May be involved in telomere length regulation (By similarity).
Belongs to the eukaryotic initiation factor 4G family.
Co-chaperone that binds to numerous proteins and promotes their interaction with Hsp70 and Hsp90.
In muscle, parvalbumin is thought to be involved in relaxation after contraction. It binds two calcium ions.
Belongs to the class-V pyridoxal-phosphate-dependent aminotransferase family. NifS/IscS subfamily.
During embryonic development, expressed in somites. First detected in stage 24 and remains excluded from the 2-3 caudal-most somites at all studied stages. First detectable in the developing hindbrain at stage 24. Expressed persists until stage 33. At stage 43, expressed in the olfactory bulb and thalamus.
Transcription factor, possibly involved in transcription regulation during lens development.
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.
Complex I is composed of 45 different subunits.
Acetylation is generally linked to gene activation. Acetylation on Lys-19 (H3K18ac) and Lys-24 (H3K24ac) favors methylation at Arg-18 (H3R17me). Acetylation at Lys-123 (H3K122ac) by EP300/p300 plays a central role in chromatin structure: localizes at the surface of the histone octamer and stimulates transcription, possibly by promoting nucleosome instability (By similarity).
Asymmetric dimethylation at Arg-18 (H3R17me2a) is linked to gene activation. Asymmetric dimethylation at Arg-3 (H3R2me2a) by prmt6 is linked to gene repression and is mutually exclusive with H3 Lys-5 methylation (H3K4me2 and H3K4me3). H3R2me2a is present at the 3' of genes regardless of their transcription state and is enriched on inactive promoters, while it is absent on active promoters (By similarity).
Butyrylation of histones marks active promoters and competes with histone acetylation. It is present during late spermatogenesis.
Dopaminylated by TGM2 at Gln-6 (H3Q5dop) in ventral tegmental area (VTA) neurons (By similarity). H3Q5dop mediates neurotransmission-independent role of nuclear dopamine by regulating relapse-related transcriptional plasticity in the reward system (By similarity).
Expressed during S phase, then expression strongly decreases as cell division slows down during the process of differentiation.
Lysine deamination at Lys-5 (H3K4all) to form allysine only takes place on H3K4me3 and results in gene repression.
Monoubiquitinated by rag1 in lymphoid cells, monoubiquitination is required for V(D)J recombination.
Phosphorylated at Thr-4 (H3T3ph) by HASPIN during prophase and dephosphorylated during anaphase. Phosphorylation at Ser-11 (H3S10ph) by aurkb is crucial for chromosome condensation and cell-cycle progression during mitosis and meiosis. In addition phosphorylation at Ser-11 (H3S10ph) by rps6ka4 and rps6ka5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or UV irradiation and result in the activation of genes, such as c-fos and c-jun. Phosphorylation at Ser-11 (H3S10ph), which is linked to gene activation, prevents methylation at Lys-10 (H3K9me) but facilitates acetylation of H3 and H4. Phosphorylation at Ser-11 (H3S10ph) by aurkb mediates the dissociation of HP1 proteins (cbx1, cbx3 and cbx5) from heterochromatin. Phosphorylation at Ser-11 (H3S10ph) is also an essential regulatory mechanism for neoplastic cell transformation. Phosphorylated at Ser-29 (H3S28ph) by map3k20 isoform 1, rps6ka5 or aurkb during mitosis or upon ultraviolet B irradiation. Phosphorylation at Thr-7 (H3T6ph) by prkcb is a specific tag for epigenetic transcriptional activation that prevents demethylation of Lys-5 (H3K4me) by lsd1/kdm1a. At centromeres, specifically phosphorylated at Thr-12 (H3T11ph) from prophase to early anaphase, by DAPK3 and PKN1. Phosphorylation at Thr-12 (H3T11ph) by PKN1 or isoform M2 of PKM (PKM2) is a specific tag for epigenetic transcriptional activation that promotes demethylation of Lys-10 (H3K9me) by kdm4c/jmjd2c. Phosphorylation at Tyr-42 (H3Y41ph) by jak2 promotes exclusion of cbx5 (HP1 alpha) from chromatin. Phosphorylation on Ser-32 (H3S31ph) is specific to regions bordering centromeres in metaphase chromosomes.
Serine ADP-ribosylation constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage. Serine ADP-ribosylation at Ser-11 (H3S10ADPr) is mutually exclusive with phosphorylation at Ser-11 (H3S10ph) and impairs acetylation at Lys-10 (H3K9ac).
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.
Specifically enriched in modifications associated with active chromatin such as methylation at Lys-5 (H3K4me), Lys-37 (H3K36me) and Lys-80 (H3K79me) are linked to gene activation. Methylation at Lys-5 (H3K4me) facilitates subsequent acetylation of H3 and H4. Methylation at Lys-80 (H3K79me) is associated with DNA double-strand break (DSB) responses and is a specific target for tp53bp1. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are linked to gene repression. Methylation at Lys-10 (H3K9me) is a specific target for HP1 proteins (cbx1, cbx3 and cbx5) and prevents subsequent phosphorylation at Ser-11 (H3S10ph) and acetylation of H3 and H4. Methylation at Lys-5 (H3K4me) and Lys-80 (H3K79me) require preliminary monoubiquitination of H2B at 'Lys-120' (By similarity).
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 zmynd11; when trimethylated at 'Lys-36' (H3.3K36me3).
Variant histone H3 which replaces conventional H3 in a wide range of nucleosomes in active genes. Constitutes the predominant form of histone H3 in non-dividing cells and is incorporated into chromatin independently of DNA synthesis. Deposited at sites of nucleosomal displacement throughout transcribed genes, suggesting that it represents an epigenetic imprint of transcriptionally active chromatin. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
E3 ubiquitin-protein ligase that plays a role in neuron cells differentiation. Plays a role in the establishment and maintenance of neuronal transmission and plasticity.
The RING-type zinc finger domain is required for E3 ligase activity.
Component of the conserved oligomeric Golgi complex which is composed of eight different subunits and is required for normal Golgi morphology and localization.
Belongs to the pseudouridine synthase RluA family.
Responsible for synthesis of pseudouridine from uracil.
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.
Belongs to the phosphatidyl serine synthase family.
Catalyzes a base-exchange reaction in which the polar head group of phosphatidylethanolamine (PE) or phosphatidylcholine (PC) is replaced by L-serine (By similarity). Catalyzes mainly the conversion of phosphatidylcholine but also converts, in vitro and to a lesser extent, phosphatidylethanolamine (By similarity).
Selectively hydrolyzes arachidonyl phospholipids in the sn-2 position releasing arachidonic acid. Together with its lysophospholipid activity, it is implicated in the initiation of the inflammatory response (By similarity).
Stimulated by agonists such as ATP, EGF, thrombin and bradykinin as well as by cytosolic Ca(2+).
The N-terminal C2 domain associates with lipid membranes upon calcium binding.
The N-terminal C2 domain associates with lipid membranes upon calcium binding. It modulates enzyme activity by presenting the active site to its substrate in response to elevations of cytosolic Ca(2+) (By similarity).
In the C-terminal section; belongs to the protein kinase superfamily. Alpha-type protein kinase family. ALPK subfamily.
Interacts with wnt11 and sdc4. The extracellular domain interacts with the extracellular domain of pcdh8/papc (By similarity).
Lys-Thr-X-X-X-Trp motif interacts with the PDZ domain of Dvl (Disheveled) family members and is involved in the activation of the Wnt/beta-catenin signaling pathway.
Receptor for Wnt proteins. Acts in both canonical and non-canonical Wnt pathways. Although different papers report differing Wnt preferences, wnt5a, wnt8b and wnt11 have been proposed as synergists. In the canonical Wnt pathway, acts via beta-catenin to promote the expression of the dorsal genes siamois, twin and nodal3 and to establish the dorsal axis of the embryo and induce dorsal mesoderm formation. In a non-canonical Wnt/planar cell polarity (PCP) pathway, acts with sdc4 and dvl2/dsh to regulate convergent extension movements in gastrulation. Triggers phosphorylation of dvl2/dsh and its translocation to the plasma membrane. In a third branch of Wnt signaling, acts in a non-canonical pathway via trimeric G proteins, and independently of dvl2/dsh, to recruit protein kinase C (PKC) to the membrane and thus activate PKC. PKC signaling controls cell sorting and tissue separation during gastrulation (By similarity).
The FZ domain is involved in binding with Wnt ligands.
The extracellular domain interacts with Wnt proteins and the intracellular C-terminus transmits the Wnt signal.
Belongs to the fructosamine kinase family.
Belongs to the AB hydrolase superfamily. Lipase family.
Homopentamer. Pentaxin (or pentraxin) have a discoid arrangement of 5 non-covalently bound subunits.
Displays acyl-CoA-dependent lysophospholipid acyltransferase activity with a subset of lysophospholipids as substrates. Prefers long chain acyl-CoAs (C16, C18) as acyl donors (By similarity).
Autophagy factor required for autophagosome formation.
Component of the 43S pre-initiation complex (43S PIC), which binds to the mRNA cap-proximal region, scans mRNA 5'-untranslated region, and locates the initiation codon. This protein enhances formation of the cap-proximal complex. Together with EIF1, facilitates scanning, start codon recognition, promotion of the assembly of 48S complex at the initiation codon (43S PIC becomes 48S PIC after the start codon is reached), and dissociation of aberrant complexes. After start codon location, together with EIF5B orients the initiator methionine-tRNA in a conformation that allows 60S ribosomal subunit joining to form the 80S initiation complex. Is released after 80S initiation complex formation, just after GTP hydrolysis by EIF5B, and before release of EIF5B. Its globular part is located in the A site of the 40S ribosomal subunit. Its interaction with EIF5 during scanning contribute to the maintenance of EIF1 within the open 43S PIC. In contrast to yeast orthologs, does not bind EIF1.
Belongs to the Diphthine--ammonia ligase family.
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. cAMP subfamily.
Belongs to the ubiquitin-activating E1 family. UBA5 subfamily.
E1-like enzyme which specifically catalyzes the first step in ufmylation. Activates ufm1 by first adenylating its C-terminal glycine residue with ATP, and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding a ufm1-E1 thioester and free AMP. Activates ufm1 via a trans-binding mechanism, in which ufm1 interacts with distinct sites in both subunits of the uba5 homodimer. Trans-binding also promotes stabilization of the uba5 homodimer, and enhances ATP-binding. Transfer of ufm1 from uba5 to the E2-like enzyme UFC1 also takes place using a trans mechanism. Ufmylation is involved in reticulophagy (also called ER-phagy) induced in response to endoplasmic reticulum stress.
Homodimer; homodimerization is required for ufm1 activation. Interacts (via UIS motif) with ufm1; binds ufm1 via a trans-binding mechanism in which ufm1 interacts with distinct sites in both subunits of the uba5 homodimer. Interacts (via C-terminus) with ufc1.
Belongs to the glycosyltransferase 16 (GT16) protein family.
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.
Plays an important role in regulating the left-right axis by blocking a tgfb1 cascade in the right posterior paraxial mesoderm. Functions as an inhibitor of bmp, tgfb1, nodal, activin and wnt signaling in the ectoderm. May inhibit mesodermal signals, probably through an inhibition of nodal/activin pathways. Seems to regulates cell fate specification and competence before the onset of neural induction. Expression in the entire ectodermal region prior to gastrulation might act to prevent fate specification in the ectoderm and ensure the maintenance of the stem-cell-like properties exhibited by ectodermal cells (By similarity).
Belongs to the WD repeat PROPPIN family.
Component of the autophagy machinery that controls the major intracellular degradation process by which cytoplasmic materials are packaged into autophagosomes and delivered to lysosomes for degradation. Binds phosphatidylinositol 3-phosphate (PtdIns3P), and other phosphoinositides including PtdIns(3,5)P2, forming on membranes of the endoplasmic reticulum upon activation of the upstream ULK1 and PI3 kinases and is recruited at phagophore assembly sites where it regulates the elongation of nascent phagophores downstream of WIPI2.
The L/FRRG motif is required for recruitment to PtdIns3P.
Putative Notch ligand involved in the mediation of Notch signaling.
Component of numerous DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which consist of a core of DDB1, cullin-4 (CUL4A or CUL4B), DDA1 and RBX1.
Functions as a component of numerous distinct DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. In the DCX complexes, acts as a scaffolding subunit required to stabilize the complex.
Responds to activation by environmental stress and pro-inflammatory cytokines by phosphorylating a number of transcription factors, and thus regulates transcriptional activity.
E3 ubiquitin-protein ligase that mediates ubiquitination of cd86 and MHC class II proteins, such as hla-dr alpha and beta, and promotes their subsequent endocytosis and sorting to lysosomes via multivesicular bodies.
The RING-CH-type zinc finger domain is required for E3 ligase activity.
Belongs to the fibroblast growth factor-binding protein family.
Homomultimers may associate with EGR1 bound to DNA.
Belongs to the GST superfamily. Alpha family.
Hydrolase highly specific for thiamine triphosphate (ThTP).
Acts both as a nuclear p53/TP53-cofactor and a cytoplasmic regulator of actin dynamics depending on conditions. In nucleus, acts as a cofactor that increases p53/TP53 response. Increases p53/TP53-dependent transcription and apoptosis, suggesting an important role in p53/TP53 stress response such as DNA damage. In cytoplasm, acts as a nucleation-promoting factor for both branched and unbranched actin filaments. Activates the Arp2/3 complex to induce branched actin filament networks. Also catalyzes actin polymerization in the absence of Arp2/3, creating unbranched filaments. Contributes to cell motility by controlling actin dynamics.
Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. Septin GTPase family.
Belongs to the intercrine beta (chemokine CC) 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.
Beta-1,3-N-acetylglucosaminyltransferase that plays a key role in the synthesis of lacto- or neolacto-series carbohydrate chains on glycolipids.
Belongs to the snRNP Sm proteins family.
LSm subunits form a heteromer with a doughnut shape.
Plays role in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex that is involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex). The heptameric LSM2-8 complex binds specifically to the 3'-terminal U-tract of U6 snRNA.
Regulates the GDP/GTP exchange reaction of most RAB proteins by inhibiting the dissociation of GDP from them, and the subsequent binding of GTP.
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.
Thin filament-associated protein that is implicated in the regulation and modulation of smooth muscle contraction. It is capable of binding to actin, calmodulin and tropomyosin. The interaction of calponin with actin inhibits the actomyosin Mg-ATPase activity.
Belongs to the ABC transporter superfamily. ABCC family. Conjugate transporter (TC 3.A.1.208) subfamily.
Belongs to the metallo-dependent hydrolases superfamily. Hydantoinase/dihydropyrimidinase family.
Carbamylation allows a single lysine to coordinate two divalent metal cations.
Belongs to the helicase family. RAD3/XPD subfamily.
Expressed throughout all the deep and superficial endoderm during gastrulation. Expression then declines rapidly after gastrulation, however a small patch of endoderm cells behind the cement gland maintains expression even into tailbud stages.
Interacts (via C-terminus) with ctnnb1/beta-catenin (via Armadillo repeats); this interaction is required for inhibition of wnt-signaling.
The 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors.
Transcription activator. Doesn't appear to bind to the consensus 5'-AACAAT-3' DNA binding site, but binds 5'-ATTGTT-3'. All of the sox17 proteins are required for embryonic endoderm development and gastrulation movements, and show some redundancy in function. In addition, the sox17 proteins have distinct but overlapping roles in later gut development. Acts downstream of vegt-signaling in endoderm differentiation to induce a range of endodermal genes both directly (including endodermin and dhh/chh) and indirectly. Also represses wnt-responsive genes to inhibit wnt/beta-catenin-mediated signaling (By similarity).
Heterodimer with IL12B; disulfide-linked. The heterodimer is known as interleukin IL-12.
May be involved in fusion of ER-derived transport vesicles with the Golgi complex.
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).
Belongs to the organo anion transporter (TC 2.A.60) family.
Belongs to the gastrin/cholecystokinin family.
Belongs to the potassium channel family. A (Shaker) (TC 1.A.1.2) subfamily. Kv1.2/KCNA2 sub-subfamily.
Belongs to the eukaryotic RPA49/POLR1E RNA polymerase subunit family.
Belongs to the LAPTM4/LAPTM5 transporter family.
Belongs to the eukaryotic ribosomal protein eL22 family.
Component of the large ribosomal subunit.
Component of the large ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell.
Expressed in the endoderm of mid-gastrula embryos. At neurula stage, expressed in the notochord and in ciliated cells of the epithelium. During tailbud stages, expressed throughout the endoderm as well as in the notochord and neural floor plate.
Belongs to the type IB topoisomerase family.
Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at the specific target site 5'-[CT]CCTTp site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(3'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 5'-OH DNA strand. The free DNA strand then undergoes passage around the unbroken strand thus removing DNA supercoils. Finally, in the religation step, the DNA 5'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone.
Belongs to the NAD-dependent glycerol-3-phosphate dehydrogenase family.
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.
Component of the biogenesis of lysosome-related organelles complex-2 (or BLOC2) composed of HPS3, HPS5 and HPS6.
May regulate the synthesis and function of lysosomes and of highly specialized organelles, such as melanosomes and platelet dense granules.
Belongs to the SNF2/RAD54 helicase family.
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.
May play a role in the response to environmental stress. Appears to act upstream of the JUN N-terminal pathway.
Component of the ribosome quality control complex (RQC), composed of at least the E3 ubiquitin ligase LTN1 and NEMF associated with the 60S ribosomal subunit. The complex probably also contains TCF25 as well as VCP/p97 and its ubiquitin-binding cofactors.
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. Within the RQC complex, LTN1 is recruited to stalled 60S ribosomal subunits by NEMF and mediates ubiquitination of stalled nascent chains (By similarity). Ubiquitination leads to VCP/p97 recruitment for extraction and degradation of the incomplete translation product (By similarity).
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.
Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3.
Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome. Acts as a chaperone that specifically mediates the integration of RPS19 in state post-A1. Direct regulator of SIRT1.
Required for proper homologous chromosome pairing and efficient cross-over and intragenic recombination during meiosis.
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 peptidase C69 family. Secernin subfamily.
Belongs to the protein kinase superfamily. CK1 Ser/Thr protein kinase family. Casein kinase I subfamily.
Belongs to the peroxisomal targeting signal receptor family.
Belongs to the glycoprotein hormones subunit beta family.
Catalyzes the dehydration of trans-3-hydroxy-L-proline to delta-1-pyrroline-2-carboxylate (Pyr2C).
In contrast to the T.cruzi proline racemase enzyme, lacks the conserved Cys at position 267 which is replaced by a Thr residue, transforming the racemase activity into dehydratase activity.
Specifically required for the pioneer round of mRNA translation mediated by the cap-binding complex (CBC), that takes place during or right after mRNA export via the nuclear pore complex (NPC). In contrast, it is not involved in steady state translation, that takes place when the CBC complex is replaced by cytoplasmic cap-binding protein eIF4E. Also required for nonsense-mediated mRNA decay (NMD), the pioneer round of mRNA translation mediated by the cap-binding complex playing a central role in nonsense-mediated mRNA decay (NMD) (By similarity).
Belongs to the Orn/Lys/Arg decarboxylase class-II family.
Belongs to the Clp1 family. Clp1 subfamily.
Component of the tRNA splicing endonuclease complex. Component of pre-mRNA cleavage complex II (CF-II).
Polynucleotide kinase that can phosphorylate the 5'-hydroxyl groups of double-stranded RNA (dsRNA), single-stranded RNA (ssRNA), double stranded DNA (dsDNA) and double-stranded DNA:RNA hybrids. dsRNA is phosphorylated more efficiently than dsDNA, and the RNA component of a DNA:RNA hybrid is phosphorylated more efficiently than the DNA component. Plays a role in both tRNA splicing and mRNA 3'-end formation. Component of the tRNA splicing endonuclease complex: phosphorylates the 5'-terminus of the tRNA 3'-exon during tRNA splicing; this phosphorylation event is a prerequisite for the subsequent ligation of the two exon halves and the production of a mature tRNA. Its role in tRNA splicing and maturation is required for cerebellar development. Component of the pre-mRNA cleavage complex II (CF-II), which seems to be required for mRNA 3'-end formation. Also phosphorylates the 5'-terminus of exogenously introduced short interfering RNAs (siRNAs), which is a necessary prerequisite for their incorporation into the RNA-induced silencing complex (RISC). However, endogenous siRNAs and microRNAs (miRNAs) that are produced by the cleavage of dsRNA precursors by dicer1 already contain a 5'-phosphate group, so this protein may be dispensible for normal RNA-mediated gene silencing (By similarity).
May act as a scaffold to regulate the recruitment and assembly of spindle midzone components.
Belongs to the iron-containing alcohol dehydrogenase family. Hydroxyacid-oxoacid transhydrogenase subfamily.
Catalyzes the cofactor-independent reversible oxidation of gamma-hydroxybutyrate (GHB) to succinic semialdehyde (SSA) coupled to reduction of 2-ketoglutarate (2-KG) to D-2-hydroxyglutarate (D-2-HG). L-3-hydroxybutyrate (L-3-OHB) is also a substrate for HOT when using 2-KG as hydrogen acceptor, resulting in the formation of D-2-HG (By similarity).
Belongs to the sterol desaturase family. TMEM195 subfamily.
Glyceryl-ether monooxygenase that cleaves the O-alkyl bond of ether lipids. Ether lipids are essential components of brain membranes (By similarity).
ESCRT-III-like protein required to recruit the ESCRT-III complex to the nuclear envelope during late anaphase. Together with SPAST, the ESCRT-III complex promotes nuclear envelope sealing and mitotic spindle disassembly during late anaphase. Plays a role in the endosomal sorting pathway.
Belongs to the WD repeat DDB2/WDR76 family.
Specifically binds 5-hydroxymethylcytosine (5hmC), suggesting that it acts as a specific reader of 5hmC.
Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. PKD subfamily.
Chaperone protein which promotes assembly of the 20S proteasome as part of a heterodimer with psmg2.
Degraded by the proteasome upon completion of 20S proteasome maturation.
Belongs to the glycosyltransferase 92 family.
Belongs to the RIN (Ras interaction/interference) family.
Belongs to the DNA photolyase class-1 family.
Interacts with ribonucleoprotein complex components. Interacts with cpeb (By similarity).
RNA-binding protein that acts as a translational repressor.
Required for the assembly of the V0 complex of the vacuolar ATPase (V-ATPase) in the endoplasmic reticulum.
Multi domain E3 ubiquitin ligase that also plays a role in DNA methylation and histone modifications.
The YDG domain mediates the interaction with histone H3.
The tudor-like regions specifically recognize and bind histone H3 unmethylated at 'Arg-2' (H3R2me0), while the PHD-type zinc finger specifically recognizes and binds histone H3 trimethylated at 'Lys-9' (H3K9me3).
Centrosomal protein required for establishing a robust mitotic centrosome architecture that can endure the forces that converge on the centrosomes during spindle formation. Required for stabilizing the expanded pericentriolar material around the centriole.
Belongs to the aldo/keto reductase family.
Involved in regulation of intracellular signaling pathways during development. Specifically thought to play a role in canonical and/or non-canonical Wnt signaling pathways through interaction with DSH (Dishevelled) family proteins. Binds to dvl2 and regulates the degradation of ctnnb1/beta-catenin, thereby modulating the transcriptional activation of target genes of the Wnt signaling pathway. May also bind to and directly stimulate the activity of tcf7l1 (By similarity).
The C-terminal PDZ-binding motif may mediate interaction with the PDZ domains of DSH (Dishevelled) family proteins.
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 protein kinase superfamily. Tyr protein kinase family. SYK/ZAP-70 subfamily.
Belongs to the DNA mismatch repair MutL/HexB family.
Belongs to the prostaglandin G/H synthase family.
Belongs to the G-protein coupled receptor 2 family.
Receptor for calcitonin-gene-related peptide (CGRP) (By similarity). Receptor specificity may be modulated by accessory proteins. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase (By similarity).
Receptor for calcitonin-gene-related peptide (CGRP). Receptor specificity may be modulated by accessory proteins. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.
Belongs to the clathrin light chain family.
Clathrin is the major protein of the polyhedral coat of coated pits and vesicles.
Belongs to the group II decarboxylase family.
Catalyzes the decarboxylation of L-aspartate, 3-sulfino-L-alanine (cysteine sulfinic acid), and L-cysteate to beta-alanine, hypotaurine and taurine, respectively. The preferred substrate is L-aspartate. Does not exhibit any decarboxylation activity toward glutamate.
Belongs to the intercrine alpha (chemokine CxC) family.
Regulates actin polymerization by inhibiting the actin-nucleating activity of the Arp2/3 complex; the function is competitive with nucleation promoting factors. Involved in steering cell migration by controlling its directional persistence (By similarity).
The acidic C-terminus is necessary and sufficient to inhibit ARP2/3 complex activity.
Catalyzes the transfer of endogenously produced octanoic acid from octanoyl-acyl-carrier-protein onto the lipoyl domains of lipoate-dependent enzymes, which catalyze essential redox reactions (By similarity). Lipoyl-ACP can also act as a substrate although octanoyl-ACP is likely to be the physiological substrate (By similarity).
In the reaction, the free carboxyl group of octanoic acid is attached via an amide linkage to the epsilon-amino group of a specific lysine residue of lipoyl domains of lipoate-dependent enzymes.
Belongs to the interleukin-1 receptor family.
Belongs to the AB hydrolase superfamily. ABHD17 family.
Hydrolyzes fatty acids from S-acylated cysteine residues in proteins.
Palmitoylated on cysteine residues located in a cysteine cluster at the N-terminus which promotes membrane localization.
Associated component of the WMM complex, a complex that mediates N6-methyladenosine (m6A) methylation of RNAs, a modification that plays a role in the efficiency of mRNA splicing and RNA processing.
Component of the WMM complex, a N6-methyltransferase complex composed of a catalytic subcomplex, named MAC, and of an associated subcomplex, named MACOM. Component of the MACOM subcomplex.
Component of a multi-subunit COQ enzyme complex, composed of at least COQ3, COQ4, COQ5, COQ6, COQ7 and COQ9. Interacts with ADCK4 and COQ7.
Component of a multi-subunit COQ enzyme complex, composed of at least coq3, coq4, coq5, coq6, coq7 and coq9. Interacts with coq8b 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.
Protects drg1 from proteolytic degradation.
Component of the cytosolic iron-sulfur (Fe-S) protein assembly (CIA) machinery required for the maturation of extramitochondrial Fe-S proteins. Part of an electron transfer chain functioning in an early step of cytosolic Fe-S biogenesis, facilitating the de novo assembly of a [4Fe-4S] cluster on the scaffold complex NUBP1-NUBP2. Electrons are transferred to CIAPIN1 from NADPH via the FAD- and FMN-containing protein NDOR1. NDOR1-CIAPIN1 are also required for the assembly of the diferric tyrosyl radical cofactor of ribonucleotide reductase (RNR), probably by providing electrons for reduction during radical cofactor maturation in the catalytic small subunit. Has anti-apoptotic effects in the cell. Involved in negative control of cell death upon cytokine withdrawal. Promotes development of hematopoietic cells.
Monomer. Interacts with ndor1. Interacts with chchd4.
The C-terminal domain binds 2 Fe-S clusters but is otherwise mostly in an intrinsically disordered conformation.
The N-terminal domain has structural similarity with S-adenosyl-L-methionine-dependent methyltransferases, but does not bind S-adenosyl-L-methionine. It is required for correct assembly of the 2 Fe-S clusters.
The twin Cx2C motifs are involved in the recognition by the mitochondrial CHCHD4/MIA40-GFER/ERV1 disulfide relay system. The formation of 2 disulfide bonds in the Cx2C motifs through dithiol/disulfide exchange reactions effectively traps the protein in the mitochondrial intermembrane space.
Belongs to the pyridoxine kinase family.
Acts as a transcriptional repressor. May be involved in DNA damage-inducible cell cycle arrests (checkpoints) (By similarity).
Acts as a transcriptional repressor. May be involved in DNA damage-inducible cell cycle arrests (checkpoints).
The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits.
Divalent metal cations. Prefers magnesium or manganese.
Has a particular type of basic domain (presence of a helix-interrupting proline) that binds to the N-box (CACNAG), rather than the canonical E-box (CANNTG).
The C-terminal WRPW motif is a transcriptional repression domain necessary for the interaction with Groucho/TLE family members, transcriptional corepressors recruited to specific target DNA by Hairy-related proteins. The WPRW motif is also required for the inductive function, independent of transcription regulation activity (By similarity).
Transcription repression requires formation of a complex with a corepressor protein of the Groucho/TLE family. Interacts with the bHLH protein hes6; this interaction may inhibit the transcriptional repressor activity. Binds DNA in the form of a heterodimer with the bHLH protein hey1/hrt1. Interacts (via Orange domain) with id3 (via HLH domain) (By similarity).
Transcriptional repressor. Binds DNA on N-box motifs: 5'-CACNAG-3'. Promotes floor plate development and prechordal plate development. Required for lens development as early as the stage of lens field formation, partly through regulation of gene expression of the cell cycle inhibitor cdknx/p27(xic1). Required for formation of the neural crest downstream of multiple signaling pathways, and acts at the neural plate border via both DNA-binding dependent and independent mechanisms. Also acts via repressor-dependent and repressor-independent mechanisms in early gastrulae to establish the prospective anterior prechordal mesoderm identity in the Spemann organizer; induces specific genes independently from direct transcriptional regulation, and represses the genes specific for neighboring tissues through direct transcriptional repression. Modulates lateral inhibition during notch signaling and regulates the cell context dependent effects of notch (which can have inhibitory, permissive or enhancing roles in muscle or neural differentiation). Inhibits myogenesis (By similarity).
As part of a BORC-like complex may play a role in lysosomes movement and localization at the cell periphery. Associated with the cytosolic face of lysosomes, this complex may couple lysosomes to microtubule plus-end-directed kinesin motor.
Plays a role in establishing and maintaining the asymmetric distribution of channels and receptors at the plasma membrane of polarized cells.
Belongs to the alpha-carbonic anhydrase family.
Catalyzes the 2-thiolation of uridine at the wobble position (U34) of mitochondrial tRNA(Lys), tRNA(Glu) and tRNA(Gln). Required for the formation of 5-taurinomethyl-2-thiouridine (tm5s2U) of mitochondrial tRNA(Lys), tRNA(Glu), and tRNA(Gln) at the wobble position. ATP is required to activate the C2 atom of the wobble base.
Homodimer; the homodimer is independent of 2Fe-2S clusters. Heterotrimer; forms a heterotrimeric complex composed by two bola2 molecules and one glrx3 molecule; linked by [2Fe-2S] clusters.
The thioredoxin domain lacks the two redox-active cysteines. This strongly suggests that it lacks thioredoxin activity.
Together with bola2, acts as a cytosolic iron-sulfur (Fe-S) cluster assembly factor that facilitates [2Fe-2S] cluster insertion into a subset of cytosolic proteins. Required for hemoglobin maturation. Does not possess any thyoredoxin activity since it lacks the conserved motif that is essential for catalytic activity.
Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. CDC5/Polo subfamily.
Serine/threonine-protein kinase that plays a central role in centriole duplication. Able to trigger procentriole formation on the surface of the parental centriole cylinder, leading to the recruitment of centriole biogenesis proteins such as sass6, cenpj/cpap, ccp110, cep135 and gamma-tubulin. When overexpressed, it is able to induce centrosome amplification through the simultaneous generation of multiple procentrioles adjoining each parental centriole during S phase. Its central role in centriole replication suggests a possible role in tumorigenesis, centrosome aberrations being frequently observed in tumors. Also involved in deuterosome-mediated centriole amplification in multiciliated that can generate more than 100 centrioles (By similarity).
Ubiquitinated; leading to its degradation by the proteasome.
Belongs to the protein kinase superfamily. NEK Ser/Thr protein kinase family. NIMA subfamily.
Putative cytoplasm-specific catalytic component of the RNA exosome complex which has 3'->5' exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events.
Homodimerization via the leucine zipper domains is required for autophosphorylation.
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.
Acts as a linker between gene transcription and histone H2B monoubiquitination at 'Lys-120' (H2BK120ub1). Positive regulator of amino acid starvation-induced autophagy. Positively regulates MTOR activity. May negatively regulate the ubiquitin proteasome pathway.
Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body.
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.
Constitutively interacts with CASP4; required for the localization of procaspase 4 to the ER.
Critical mediator, in cooperation with CASP4, of endoplasmic reticulum-stress induced apoptosis. Required or the activation of CASP4 following endoplasmic reticulum stress.
Belongs to the opioid neuropeptide precursor family.
Belongs to the zinc-containing alcohol dehydrogenase family.
Plays a role in the recruitment of the exosome to pre-rRNA to mediate the 3'-5' end processing of the 5.8S rRNA.
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.
Belongs to the TRAFAC class YlqF/YawG GTPase family. MTG1 subfamily.
Plays a role in the regulation of the mitochondrial ribosome assembly and of translational activity (By similarity). Displays mitochondrial GTPase activity (By similarity).
Belongs to the major facilitator superfamily. Monocarboxylate porter (TC 2.A.1.13) 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.
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 glycosyltransferase 2 family. GalNAc-T subfamily.
Catalyzes the formation of L-carnitine from gamma-butyrobetaine.
Belongs to the PtdIns transfer protein family. PI transfer class IIB subfamily.
Catalyzes the transfer of phosphatidylinositol (PI) and phosphatidic acid (PA) between membranes (By similarity). Binds PA derived from the phospholipase D signaling pathway and among the cellular PA species, preferably binds to the C16:0/16:1 and C16:1/18:1 PA species (By similarity).
Belongs to the pyrroline-5-carboxylate reductase family.
Belongs to the bZIP family. C/EBP subfamily.
Belongs to the Mrp/NBP35 ATP-binding proteins family.
The C-terminal WRPW motif is a transcriptional repression domain necessary for the interaction with Groucho/TLE family members, transcriptional corepressors recruited to specific target DNA by Hairy-related proteins.
The bHLH, as well as cooperation between the central Orange domain and the C-terminal WRPW motif, is required for transcriptional repressor activity.
Transcription repression requires formation of a complex with a corepressor protein of the Groucho/TLE family. Interacts with the bHLH protein hes2, and binds DNA in the form of a heterodimer with the bHLH protein hey1/hrt1. Interacts with the bHLH protein hes6; this interaction may inhibit the transcriptional repressor activity (By similarity).
Transcriptional repressor of a subset of early mesodermal genes including myod1 and t/bra. Binds DNA on N-box motifs: 5'-CACNAG-3'. Acts as a negative regulator of myogenesis, mediating Notch signaling to repress expression of myod1 (By similarity).
Autophosphorylated on tyrosine residues.
Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MNB/DYRK subfamily.
Dual-specificity kinase which possesses both serine/threonine and tyrosine kinase activities. Exhibits a substrate preference for proline at position P+1 and arginine at position P-3. Plays an important role in double-strand breaks (DSBs) repair following DNA damage. Mechanistically, phosphorylates RNF169 and increases its ability to block accumulation of TP53BP1 at the DSB sites thereby promoting homologous recombination repair (HRR). Also acts as a positive regulator of transcription by acting as a CTD kinase that mediates phosphorylation of the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAP II) POLR2A (By similarity). Modulates alternative splicing by phosphorylating the splice factor SRSF6 (By similarity). Phosphorylates SEPTIN4, SEPTIN5 and SF3B1 (By similarity).
The histidine-rich domain (HRD) region is intrinsically disordered and promotes the formation of phase-separated liquid droplets that enhance its ability to phosphorylate the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNA Pol II).
Arg-340 is the main determinant for regioselectivity, which segregates between initiases and elongases in all tubulin--tyrosine ligase family. A glutamine residue at this position is found in elongases TTLL6, TTLL9, TTLL11, TTLL13, TTLL10 and favors glutamate-chain elongation, whereas an arginine residue is found in initiases TTLL2, TTLL4, TTLL5, TTLL3, TTLL8 and favors initiation.
Monoglycylase which modifies alpha- and beta-tubulin, adding a single glycine on the gamma-carboxyl groups of specific glutamate residues to generate monoglycine side chains within the C-terminal tail of tubulin. Not involved in elongation step of the polyglycylation reaction (PubMed:28576883). Preferentially glycylates a beta-tail peptide over the alpha-tail, although shifts its preference toward alpha-tail as beta-tail glutamylation increases (PubMed:28576883). Competes with polyglutamylases for modification site on beta-tubulin substrate, thereby creating an anticorrelation between glycylation and glutamylation reactions (PubMed:28576883). Together with TTLL8, mediates microtubule glycylation of primary and motile cilia, which is essential for their stability and maintenance (By similarity).
TTLL3 and TTLL8 monoglycylase-mediated glycylation of tubulin was initially reported to play a role in ependymal motile ciliary maintenance (By similarity). However, contradictory results were later observed (By similarity).
Two conserved structural elements specific among monoglycylases, IS1 and IS2, are involved in glycyl chains initiation. Two conserved structural interfaces likely constitute the binding platforms for tubulin tail and microtubule.
Belongs to the GLI C2H2-type zinc-finger protein family.
Belongs to the eukaryotic ribosomal protein eS6 family.
May modify the assembly dynamics of microtubules, such that microtubules are slightly longer, but more dynamic.
Transcriptional activator that mediates FGF signaling during neural development (By similarity). Plays a role in the regulation of cell movement (By similarity). Does not bind DNA by itself (By similarity).
Belongs to the phosphohexose mutase family.
Citrate synthase is found in nearly all cells capable of oxidative metabolism.
Belongs to the glycosyl hydrolase 59 family.
Hydrolyzes the galactose ester bonds of glycolipids such as galactosylceramide and galactosylsphingosine.
Belongs to the sulfotransferase 1 family. Gal/GlcNAc/GalNAc subfamily.
Belongs to the histidine acid phosphatase family. MINPP1 subfamily.
Belongs to the bZIP family. NFIL3 subfamily.
Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. GSK-3 subfamily.
Belongs to the copper/topaquinone oxidase family.
Topaquinone (TPQ) is generated by copper-dependent autoxidation of a specific tyrosyl residue.
E3 ubiquitin-protein ligase that acts as a negative regulator of the Wnt signaling pathway by mediating the ubiquitination, endocytosis and subsequent degradation of Wnt receptor complex components Frizzled. Acts on both canonical and non-canonical Wnt signaling pathway (By similarity). Along with RSPO2 and ZNRF3, constitutes a master switch that governs limb specification (PubMed:29769720).
Simultaneous knockdown of RNF43 and ZNRF3 results in ectopic limb development.
Belongs to the glycerophosphoryl diester phosphodiesterase family.
Essential for the formation and stability of microtubules (MTs) (By similarity). Required for the organization of the mitotic spindle and for the proper attachment of kinetochores to MTs (By similarity). Promotes the recruitment of NUDC to the mitotic spindle for mitotic progression (By similarity).
Homotrimer; self-association is mediated by the N-terminal coiled coil.
Belongs to the retinoblastoma protein (RB) family.
This promotes the activity of RNA polymerase II.
Belongs to the prefoldin subunit beta family.
Belongs to the complex I LYR family. LYRM9 subfamily.
Core component of the 7SK RNP complex. Associates with box C/D small nucleolar ribonucleoprotein (snoRNP) complexes.
RNA-binding protein that specifically binds distinct small nuclear RNA (snRNAs) and regulates their processing and function. Specifically binds the 7SK snRNA (7SK RNA) and acts as a core component of the 7SK ribonucleoprotein (RNP) complex, thereby acting as a negative regulator of transcription elongation by RNA polymerase II. The 7SK RNP complex sequesters the positive transcription elongation factor b (P-TEFb) in a large inactive 7SK RNP complex preventing RNA polymerase II phosphorylation and subsequent transcriptional elongation (By similarity). The 7SK RNP complex also promotes snRNA gene transcription by RNA polymerase II via interaction with the little elongation complex (LEC). LARP7 specifically binds to the highly conserved 3'-terminal U-rich stretch of 7SK RNA; on stimulation, remains associated with 7SK RNA, whereas P-TEFb is released from the complex. LARP7 also acts as a regulator of mRNA splicing fidelity by promoting U6 snRNA processing. Specifically binds U6 snRNAs and associates with a subset of box C/D RNP complexes: promotes U6 snRNA 2'-O-methylation by facilitating U6 snRNA loading into box C/D RNP complexes. U6 snRNA 2'-O-methylation is required for mRNA splicing fidelity (By similarity).
The xRRM domain binds the 3' end of 7SK snRNA (7SK RNA) at the top of stem-loop 4.
Belongs to the Ca(2+):cation antiporter (CaCA) (TC 2.A.19) family. SLC24A subfamily.
The small GTPases Rab are key regulators in vesicle trafficking.
Involved in the synthesis of the GDP-mannose and dolichol-phosphate-mannose required for a number of critical mannosyl transfer reactions.
Belongs to the DEAD box helicase family. DDX47/RRP3 subfamily.
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.
May contribute to the regulation of cell proliferation.
Belongs to the TFIIF alpha subunit family.
TFIIF is a general transcription initiation factor that binds to RNA polymerase II and helps to recruit it to the initiation complex in collaboration with TFIIB. It promotes transcription elongation.
PCNA-binding protein that acts as a regulator of DNA repair during DNA replication. Following DNA damage, the interaction with pcna is disrupted, facilitating the interaction between monoubiquitinated pcna and the translesion DNA synthesis DNA polymerase eta (polh) at stalled replisomes, facilitating the bypass of replication-fork-blocking lesions. Also acts as a regulator of centrosome number (By similarity).
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.
Belongs to the pICln (TC 1.A.47) family.
Belongs to the Mediator complex subunit 18 family.
Belongs to the protein-tyrosine phosphatase family. Non-receptor class 4 subfamily.
Belongs to the Nudix hydrolase family. PCD1 subfamily.
Contaminating sequence. Sequence of unknown origin in the C-terminal part.
Inhibits amyloid precursor protein processing, probably by blocking BACE1 activity (By similarity). Enhances trafficking of the glutamate transporter SLC1A1/EAAC1 from the endoplasmic reticulum to the cell surface (By similarity). Plays a role in the translocation of SLC2A4/GLUT4 from intracellular membranes to the cell membrane which facilitates the uptake of glucose into the cell (By similarity).
Belongs to the protease inhibitor I47 (latexin) family.
Belongs to the sulfotransferase 3 family.
Belongs to the G-protein coupled receptor 3 family.
Component of the tRNA-splicing ligase complex.
Deubiquitinating enzyme that may play a role in the ubiquitin-dependent regulation of different cellular processes.
IGF-binding proteins prolong the half-life of the IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs on cell culture. They alter the interaction of IGFs with their cell surface receptors. Promotes cell migration.
Probably binds two or three calcium ions.
Belongs to the glycosyl hydrolase 63 family.
Cleaves the distal alpha 1,2-linked glucose residue from the Glc(3)Man(9)GlcNAc(2) oligosaccharide precursor.
Component of the DCX(DTL) E3 ubiquitin ligase complex, at least composed of cul4 (cul4a or cul4b), ddb1, dtl/cdt2 and rbx1.
Substrate-specific adapter of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex required for cell cycle control, DNA damage response and translesion DNA synthesis. The DCX(DTL) complex, also named CRL4(CDT2) complex, mediates the polyubiquitination and subsequent degradation of CDT1, CDKN1A/p21(CIP1), KMT5A and SDE2. CDT1 degradation in response to DNA damage is necessary to ensure proper cell cycle regulation of DNA replication. CDKN1A/p21(CIP1) degradation during S phase or following UV irradiation is essential to control replication licensing. KMT5A degradation is also important for a proper regulation of mechanisms such as TGF-beta signaling, cell cycle progression, DNA repair and cell migration. Most substrates require their interaction with PCNA for their polyubiquitination: substrates interact with PCNA via their PIP-box, and those containing the 'K+4' motif in the PIP box, recruit the DCX(DTL) complex, leading to their degradation. In undamaged proliferating cells, the DCX(DTL) complex also promotes the 'Lys-164' monoubiquitination of PCNA, thereby being involved in PCNA-dependent translesion DNA synthesis (PubMed:16949367). May play a role in the regulation of the circadian clock (By similarity).
Belongs to the polyadenylate-binding protein type-1 family.
Acts as a co-chaperone for HSP90 and is required for proper folding of the myosin motor domain (By similarity). Plays a role in sarcomere formation during muscle cell development. Is necessary for normal early lens development.
Contaminating sequence. Potential poly-A sequence.
Detected initially throughout the somites and the heart and gradually also expressed in the jaw, branchial arches and body wall muscles at later embryonic stages.
Probable GTP-binding protein. Functions in innate immunity and more specifically the inflammatory response as a regulator of the Toll-like receptor TLR2 and TLR4 signaling pathways.
Belongs to the dystrophin family. Dystrobrevin subfamily.
Belongs to the glucose-6-phosphate dehydrogenase family.
Catalyzes the rate-limiting step of the oxidative pentose-phosphate pathway, which represents a route for the dissimilation of carbohydrates besides glycolysis.
Belongs to the protein-tyrosine phosphatase family. Receptor class 2A subfamily.
Component of the ER membrane protein complex (EMC).
Catalyzes the hydrolytic deamination of adenosine and 2-deoxyadenosine. Plays an important role in purine metabolism and in adenosine homeostasis. Modulates signaling by extracellular adenosine, and so contributes indirectly to cellular signaling events. May act as a positive regulator of T-cell coactivation (By similarity).
Transcriptional repressor that is an essential upstream regulator of neural crest determination. Also acts in a negative auto-regulator loop by inhibiting the transcription of its own gene (By similarity).
Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.
Belongs to the histone-like Alba family.
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 enhancer of polycomb family.
May play a role in transcription or DNA repair.
Negative regulator of the canonical Wnt signaling pathway involved in neuroectodermal patterning. Acts by specifically binding phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2), translocating to the cell membrane and interacting with key regulators of the canonical Wnt signaling pathway, such as components of the beta-catenin destruction complex (By similarity).
Methylation at Lys-5 (H3K4me), Lys-37 (H3K36me) and Lys-80 (H3K79me) are linked to gene activation. Methylation at Lys-5 (H3K4me) facilitates subsequent acetylation of H3 and H4. Methylation at Lys-80 (H3K79me) is associated with DNA double-strand break (DSB) responses and is a specific target for tp53bp1. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are linked to gene repression. Methylation at Lys-10 (H3K9me) is a specific target for HP1 proteins (cbx1, cbx3 and cbx5) and prevents subsequent phosphorylation at Ser-11 (H3S10ph) and acetylation of H3 and H4. Methylation at Lys-5 (H3K4me) and Lys-80 (H3K79me) require preliminary monoubiquitination of H2B at 'Lys-120' (By similarity).
Phosphorylated at Thr-4 (H3T3ph) by HASPIN during prophase and dephosphorylated during anaphase. Phosphorylation at Ser-11 (H3S10ph) by aurkb is crucial for chromosome condensation and cell-cycle progression during mitosis and meiosis. In addition phosphorylation at Ser-11 (H3S10ph) by rps6ka4 and rps6ka5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or UV irradiation and result in the activation of genes, such as c-fos and c-jun. Phosphorylation at Ser-11 (H3S10ph), which is linked to gene activation, prevents methylation at Lys-10 (H3K9me) but facilitates acetylation of H3 and H4. Phosphorylation at Ser-11 (H3S10ph) by aurkb mediates the dissociation of HP1 proteins (cbx1, cbx3 and cbx5) from heterochromatin. Phosphorylation at Ser-11 (H3S10ph) is also an essential regulatory mechanism for neoplastic cell transformation. Phosphorylated at Ser-29 (H3S28ph) by map3k20 isoform 1, rps6ka5 or aurkb during mitosis or upon ultraviolet B irradiation. Phosphorylation at Thr-7 (H3T6ph) by prkcb is a specific tag for epigenetic transcriptional activation that prevents demethylation of Lys-5 (H3K4me) by lsd1/kdm1a. At centromeres, specifically phosphorylated at Thr-12 (H3T11ph) from prophase to early anaphase, by DAPK3 and PKN1. Phosphorylation at Thr-12 (H3T11ph) by PKN1 or isoform M2 of PKM (PKM2) is a specific tag for epigenetic transcriptional activation that promotes demethylation of Lys-10 (H3K9me) by kdm4c/jmjd2c. Phosphorylation at Tyr-42 (H3Y41ph) by jak2 promotes exclusion of cbx5 (HP1 alpha) from chromatin (By similarity).
Serine ADP-ribosylation by PARP1 or PARP2 constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage. Serine ADP-ribosylation at Ser-11 (H3S10ADPr) promotes recruitment of CHD1L. H3S10ADPr is mutually exclusive with phosphorylation at Ser-11 (H3S10ph) and impairs acetylation at Lys-10 (H3K9ac).
Key regulator of mitochondrial calcium uniporter (mcu) required for calcium entry into mitochondrion.
May modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes. Inhibits TNF-induced nfkb1 activation.
Belongs to the class-II aminoacyl-tRNA synthetase family.
Catalyzes the attachment of threonine to tRNA(Thr) in a two-step reaction: threonine is first activated by ATP to form Thr-AMP and then transferred to the acceptor end of tRNA(Thr). Also edits incorrectly charged tRNA(Thr) via its editing domain, at the post-transfer stage.
Belongs to the glycosyl hydrolase 13 family.
Acts as component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity.
Component of the mcm2-7 complex (RLF-M). The complex forms a toroidal hexameric ring with the proposed subunit order mcm2-mcm6-mcm4-mcm7-mcm3-mcm5. The heterodimer of mmcm3/mcm5 interacts with mcm4, mmcm6, mcm7 and weakly with mcm2. Component of the CMG helicase complex, composed of the mcm2-7 complex, the GINS complex and cdc45.
Hyperphosphorylated during mitosis in a mechanism requiring cdc2-cyclin B and other kinases. Undergoes dephosphorylation after exiting mitosis, existing in a partially phosphorylated state in the cytosolic interphase mcm complex which associates with the pre-replication complexes (pre-Rcs). Complete dephosphorylation inactivates the mcm complex, preventing its binding to chromatin. Becomes actively phosphorylated during S phase once the mcm complex is assembled on the chromatin. This chromatin-associated phosphorylation occurs during the activation of the pre-Rcs and is independent of cdks. Phosphorylated by the cdc7-dbf4b complex (By similarity).
Belongs to the class-I pyridoxal-phosphate-dependent aminotransferase family.
Transaminase involved in tyrosine breakdown. Converts tyrosine to p-hydroxyphenylpyruvate.
Belongs to the metallophosphoesterase superfamily. Purple acid phosphatase family.
Belongs to the parathyroid hormone family.
Component of the general transcription and DNA repair factor IIH (TFIIH) core complex which is involved in general and transcription-coupled nucleotide excision repair (NER) of damaged DNA.
Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.
Allosterically activated by ADP, AMP, or fructose 2,6-bisphosphate, and allosterically inhibited by ATP or citrate.
Belongs to the phosphofructokinase type A (PFKA) family. ATP-dependent PFK group I subfamily. Eukaryotic two domain clade "E" sub-subfamily.
Belongs to the phosphofructokinase type A (PFKA) family. ATP-dependent PFK group I subfamily. Eukaryotic two domain clade 'E' sub-subfamily.
Catalyzes the phosphorylation of D-fructose 6-phosphate to fructose 1,6-bisphosphate by ATP, the first committing step of glycolysis.
A cytochrome P450 monooxygenase that catalyzes the side-chain hydroxylation and cleavage of cholesterol to pregnenolone, the precursor of most steroid hormones. Catalyzes three sequential oxidation reactions of cholesterol, namely the hydroxylation at C22 followed with the hydroxylation at C20 to yield 20R,22R-hydroxycholesterol that is further cleaved between C20 and C22 to yield the C21-steroid pregnenolone and 4-methylpentanal. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate and reducing the second into a water molecule. Two electrons are provided by NADPH via a two-protein mitochondrial transfer system comprising flavoprotein FDXR (adrenodoxin/ferredoxin reductase) and nonheme iron-sulfur protein FDX1 or FDX2 (adrenodoxin/ferredoxin).
Belongs to the tRNA methyltransferase O family.
Belongs to the metallo-beta-lactamase superfamily. RNA-metabolizing metallo-beta-lactamase-like family. INTS11 subfamily.
This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that stimulate adenylate cyclase.
Belongs to the ATPase alpha/beta chains family.
Non-catalytic subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons. V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment.
V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex. The V1 complex consists of three catalytic AB heterodimers that form a heterohexamer, three peripheral stalks each consisting of EG heterodimers, one central rotor including subunits D and F, and the regulatory subunits C and H. The proton translocation complex V0 consists of the proton transport subunit a, a ring of proteolipid subunits c9c'', rotary subunit d, subunits e and f, and the accessory subunits.
Belongs to the protein-tyrosine phosphatase family. Non-receptor class subfamily.
Regulates negatively FAS-induced apoptosis and NGFR-mediated pro-apoptotic signaling.
Initiates blood coagulation by forming a complex with circulating factor VII or VIIa. The [TF:VIIa] complex activates factors IX or X by specific limited proteolysis. TF plays a role in normal hemostasis by initiating the cell-surface assembly and propagation of the coagulation protease cascade.
Interacts with HSPE; the interaction, inhibited by heparin, promotes the generation of activated factor X and activates coagulation in the presence of activated factor VII.
Belongs to the helicase family. RLR subfamily.
Belongs to the PMP-22/EMP/MP20 family. CACNG subfamily.
May be involved in pronephros development, after specification of the pronephros.
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.
Belongs to the SLAIN motif-containing family.
Microtubule plus-end tracking protein that might be involved in the regulation of cytoplasmic microtubule dynamics, microtubule organization and microtubule elongation.
Acts as a positive regulator of hedgehog signaling and regulates ciliary function.
Belongs to the universal ribosomal protein uS7 family.
Belongs to the PDGF/VEGF growth factor family.
Belongs to the thioesterase PaaI family.
Belongs to the class-II aminoacyl-tRNA synthetase family. Alax-L subfamily.
Binds GTP but lacks intrinsic GTPase activity and is resistant to Rho-specific GTPase-activating proteins.
Potential effector of the planar cell polarity signaling pathway. Plays a role in targeted membrane trafficking most probably at the level of vesicle fusion with membranes. Involved in cilium biogenesis by regulating the transport of cargo proteins to the basal body and to the apical tips of cilia. More generally involved in exocytosis in secretory cells.
Belongs to the eukaryotic ribosomal protein eS19 family.
Belongs to the bacterial ribosomal protein bL27 family.
Acts as a replication initiation factor that brings together the MCM2-7 helicase and the DNA polymerase alpha/primase complex in order to initiate DNA replication. Additionally, plays a role in preventing DNA damage during replication (By similarity).
Each zinc finger-like domain binds a zinc ion and is involved in both ssDNA and dsDNA binding, as is the OB-fold domain.
The N-terminal domain mediates homodimerization.
Belongs to the glutaminyl-peptide cyclotransferase family.
Essential component of the Ost-alpha/Ost-beta complex, a heterodimer that acts as the intestinal basolateral transporter responsible for the translocation of bile acids (such as taurocholate), steroids (such as estrone sulfate), and eicosanoids (such as prostaglandin E2).
Interacts with slc51b. The Ost-alpha/Ost-beta complex is a heterodimer composed of alpha (slc51a) and beta (slc51b) subunit (By similarity).
Belongs to the RecA family. DMC1 subfamily.
Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons. V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment (By similarity). May play a role in coupling of proton transport and ATP hydrolysis (By similarity). Regulator of osteoclast fusion and bone formation (By similarity).
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.
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.
Heterotetramer of two type I and two type II keratins. Keratin-18 associates with keratin-8 (By similarity).
Proteolytically cleaved by caspases during epithelial cell apoptosis.
There are two types of cytoskeletal and microfibrillar keratin: I (acidic; 40-55 kDa) and II (neutral to basic; 56-70 kDa).
When phosphorylated, plays a role in filament reorganization.
Belongs to the dynein light chain LC1-type family.
Interacts with DNAH5, a outer arm dynein heavy chain. Interacts with tubulin located within the A-tubule of the outer doublets in a ATP-independent manner.
Outer (ODAs) and inner (IDAs) dynein arms contain the molecular motors that generate the force to move cilia by ATP-dependent reactions. There are two mechanosensory systems that monitor and respond to the mechanical state (curvature) of the axoneme. One system involves the central pair microtubule complex and radial spokes and the second system involves the outer dynein arms.
Part of the multisubunit axonemal ATPase complexes that generate the force for cilia motility and govern beat frequency (By similarity). Component of the outer arm dynein (ODA). May be involved in a mechanosensory feedback mechanism controlling ODA activity based on external conformational cues by tethering the outer arm dynein heavy chain (DNAH5) to the microtubule within the axoneme (By similarity).
Belongs to the hcp beta-lactamase family.
May be required for assembly of mitochondrial respiratory chain complexes.
Required for assembly of mitochondrial respiratory chain complexes.
Belongs to the protein kinase superfamily. PAN3 family.
Contains a pseudokinase domain. The protein kinase domain is predicted to be catalytically inactive because some of the residues important for catalytic activity are substituted and it lacks the equivalent of the binding site for a peptide substrate. However, it has retained an ATP-binding site and ATP-binding is required for mRNA degradation, stimulating the activity of the PAN2 nuclease in vitro. The nucleotide-binding site is juxtaposed to the RNase active site of PAN2 in the complex and may actually bind nucleosides of a poly(A) RNA rather than ATP, feeding the poly(A)-tail to the active site of the deadenylase and thus increasing the efficiency with which this distributive enzyme degrades oligo(A) RNAs.
Homodimer. Forms a heterotrimer with a catalytic subunit PAN2 to form the poly(A)-nuclease (PAN) deadenylation complex. Interacts (via PAM-2 motif) with poly(A)-binding protein PABPC1 (via PABC domain), conferring substrate specificity of the enzyme complex. Interacts with the GW182 family proteins TNRC6A, TNRC6B and TNRC6C.
Regulatory subunit of the poly(A)-nuclease (PAN) deadenylation complex, one of two cytoplasmic mRNA deadenylases involved in general and miRNA-mediated mRNA turnover. PAN specifically shortens poly(A) tails of RNA and the activity is stimulated by poly(A)-binding protein (PABP). PAN deadenylation is followed by rapid degradation of the shortened mRNA tails by the CCR4-NOT complex. Deadenylated mRNAs are then degraded by two alternative mechanisms, namely exosome-mediated 3'-5' exonucleolytic degradation, or deadenlyation-dependent mRNA decaping and subsequent 5'-3' exonucleolytic degradation by XRN1. PAN3 acts as a positive regulator for PAN activity, recruiting the catalytic subunit PAN2 to mRNA via its interaction with RNA and PABP, and to miRNA targets via its interaction with GW182 family proteins.
Regulatory subunit of the poly(A)-nuclease (PAN) deadenylation complex, one of two cytoplasmic mRNA deadenylases involved in general and miRNA-mediated mRNA turnover. PAN specifically shortens poly(A) tails of RNA and the activity is stimulated by poly(A)-binding protein (PABP). PAN deadenylation is followed by rapid degradation of the shortened mRNA tails by the CCR4-NOT complex. Deadenylated mRNAs are then degraded by two alternative mechanisms, namely exosome-mediated 3'-5' exonucleolytic degradation, or deadenylation-dependent mRNA decaping and subsequent 5'-3' exonucleolytic degradation by XRN1. PAN3 acts as a positive regulator for PAN activity, recruiting the catalytic subunit PAN2 to mRNA via its interaction with RNA and PABP, and to miRNA targets via its interaction with GW182 family proteins.
The N-terminal zinc finger binds to poly(A) RNA.
The pseudokinase domain, the coiled-coil (CC), and C-terminal knob domain (CK) form a structural unit (PKC) that forms an extensive high-affinity interaction surface for PAN2.
Belongs to the calycin superfamily. Lipocalin family.
Component of the ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), a multisubunit enzyme composed of 3 respiratory subunits cytochrome b, cytochrome c1 and Rieske protein, 2 core protein subunits, and additional low-molecular weight protein subunits.
Component of the ubiquinol-cytochrome c oxidoreductase, a multisubunit transmembrane complex that is part of the mitochondrial electron transport chain which drives oxidative phosphorylation. The respiratory chain contains 3 multisubunit complexes succinate dehydrogenase (complex II, CII), ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII) and cytochrome c oxidase (complex IV, CIV), that cooperate to transfer electrons derived from NADH and succinate to molecular oxygen, creating an electrochemical gradient over the inner membrane that drives transmembrane transport and the ATP synthase. The cytochrome b-c1 complex catalyzes electron transfer from ubiquinol to cytochrome c, linking this redox reaction to translocation of protons across the mitochondrial inner membrane, with protons being carried across the membrane as hydrogens on the quinol. In the process called Q cycle, 2 protons are consumed from the matrix, 4 protons are released into the intermembrane space and 2 electrons are passed to cytochrome c.
Belongs to the phospholipase D family. MitoPLD/Zucchini subfamily.
In contrast to other members of the phospholipase D family, contains only one PLD phosphodiesterase domain, suggesting that it has a single half-catalytic and requires homodimerization to form a complete active site.
Presents phospholipase and nuclease activities, depending on the different physiological conditions. Plays a key role in mitochondrial fusion and fission via its phospholipase activity. In its phospholipase role, it uses the mitochondrial lipid cardiolipin as substrate to generate phosphatidate (PA or 1,2-diacyl-sn-glycero-3-phosphate), a second messenger signaling lipid. Production of PA facilitates Mitofusin-mediated fusion, whereas the cleavage of PA by the Lipin family of phosphatases produces diacylgycerol (DAG) which promotes mitochondrial fission. Regulates mitochondrial shape through facilitating mitochondrial fusion. During spermatogenesis, plays a critical role in PIWI-interacting RNA (piRNA) biogenesis (By similarity). piRNAs provide essential protection against the activity of mobile genetic elements. piRNA-mediated transposon silencing is thus critical for maintaining genome stability, in particular in germline cells when transposons are mobilized as a consequence of wide-spread genomic demethylation. Has been shown to be a backbone-non-specific, single strand-specific nuclease, cleaving either RNA or DNA substrates with similar affinity (By similarity). Produces 5' phosphate and 3' hydroxyl termini, suggesting it could directly participate in the processing of primary piRNA transcripts (By similarity). Has been proposed to act as a cardiolipin hydrolase to generate phosphatidic acid at mitochondrial surface. Although it cannot be excluded that it can act as a phospholipase in some circumstances, this activity could not be confirmed (By similarity).
Belongs to the proteasome subunit S14 family.
Belongs to the glycosyl hydrolase 27 family.
Belongs to the EGR C2H2-type zinc-finger protein family.
Binds to DNA motifs with the sequence 5'-GCG(T/G)GGGCG-3' via its C2H2-type zinc fingers. Starting from the N-terminus, the second zinc finger binds to the 3'-GCG motif, the middle zinc finger interacts with the central TGG motif, and the C-terminal zinc finger binds to the 5'-GCG motif. Binds double-stranded target DNA, irrespective of the cytosine methylation status. Has reduced affinity for target DNA where the cytosines have been oxidized to 5-hydroxymethylcytosine, 5-formylcytosine or 5-carboxylcytosine.
Transcription factor required for development of the vascular component of the pronephric kidney, the glomus; may repress tubule-specific gene expression in the portion of the pronephros fated to form the glomus (By similarity). Recognizes and binds to the DNA sequence 5'-GCG(T/G)GGGCG-3' (By similarity). Inhibits Wnt-signaling during embryonic development (By similarity).
Belongs to the DNA mismatch repair MutS family.
Component of the post-replicative DNA mismatch repair system (MMR).
Component of the CPC at least composed of survivin/birc5, incenp, cdca8/borealin and/or cdca9/dasra-A, and aurkb/aurora-B. Interacts with incenp (via N-terminus) (By similarity).
Component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly. Contributes to CPC function by facilitating loading of the CPC onto chromosomes (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.
Together with methyltransferase FTSJ1, methylates the 2'-O-ribose of nucleotides at position 32 of the anticodon loop of substrate tRNAs.
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.
E3 ubiquitin-protein ligase that specifically binds poly-ADP-ribosylated proteins and mediates their ubiquitination and subsequent degradation. May regulate many important biological processes, such as cell survival and DNA damage response. Acts as an activator of the Wnt signaling pathway by mediating the ubiquitination of poly-ADP-ribosylated proteins. Neuroprotective protein. Protects against cell death induced by DNA damaging agents and rescues cells from G1 arrest. Promotes cell survival after gamma-irradiation. Facilitates DNA repair.
The WWE domain mediates non-covalent poly(ADP-ribose)-binding.
Belongs to the glycosyltransferase 65 family.
Belongs to the UTP23/FCF1 family. FCF1 subfamily.
Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. IF-2 subfamily.
One of the essential components for the initiation of protein synthesis. Protects formylmethionyl-tRNA from spontaneous hydrolysis and promotes its binding to the 30S ribosomal subunits. Also involved in the hydrolysis of GTP during the formation of the 70S ribosomal complex.
Belongs to the nuclear hormone receptor family. NR0 subfamily.
Belongs to the damage-control phosphatase family. Sugar phosphate phosphatase III subfamily.
Human C6orf211 has been reportedly associated with a protein carboxyl methyltransferase activity, but whether this protein indeed has such an activity remains to be determined (By similarity). It has been later shown to belong to a family of metal-dependent phosphatases implicated in metabolite damage-control (By similarity).
Metal-dependent phosphatase that shows phosphatase activity against several substrates, including fructose-1-phosphate and fructose-6-phosphate (By similarity). Its preference for fructose-1-phosphate, a strong glycating agent that causes DNA damage rather than a canonical yeast metabolite, suggests a damage-control function in hexose phosphate metabolism (By similarity). Has also been shown to have O-methyltransferase activity that methylates glutamate residues of target proteins to form gamma-glutamyl methyl ester residues (By similarity). Possibly methylates PCNA, suggesting it is involved in the DNA damage response (By similarity).
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.
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.
In the C-terminal section; belongs to the Cu-Zn superoxide dismutase family.
Exhibits ester hydrolase activity on the substrate p-nitrophenyl acetate.
Belongs to the DapA family. NanA subfamily.
Catalyzes the cleavage of N-acetylneuraminic acid (sialic acid) to form pyruvate and N-acetylmannosamine via a Schiff base intermediate. It prevents sialic acids from being recycled and returning to the cell surface. Involved in the N-glycolylneuraminic acid (Neu5Gc) degradation pathway.
Component of the spliceosome A complex (also known as the prespliceosome). Appears to dissociate from the spliceosome upon formation of the spliceosome B complex (also known as the precatalytic spliceosome), in which the heterotrimeric U4/U6.U5 snRNPs are bound (By similarity).
Component of the spliceosome A complex. Regulates alternative splicing of a number of mRNAs. May modulate splice site pairing after recruitment of the U1 and U2 snRNPs to the 5' and 3' splice sites of the intron (By similarity).
Histone chaperone that facilitates histone deposition and histone exchange and removal during nucleosome assembly and disassembly.
Interacts with histone H3 and histone H4.
Belongs to the FAD-binding oxidoreductase/transferase type 4 family.
Belongs to the PIEZO (TC 1.A.75) family.
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. May play a role in cell proliferation.
Component of the CSN complex, probably composed of cops1, cops2, cops3, cops4, cops5, cops6, cops7, cops8 and cops9.
Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis.
Identified in the spliceosome C complex.
Belongs to the eukaryotic ribosomal protein eL28 family.
Transcription factor that controls hypaxial muscle development by down-regulating myod1 and cdkn1b/p27, thereby allowing myoblasts to proliferate before the onset of terminal differentiation.
Transcription factor that binds to the DNA sequence 5'-AACAAT-3' (By similarity). Acts as a transcriptional activator (By similarity). Plays a role together with nlk in neural induction during early embryogenesis (By similarity).
Belongs to the SLC13A/DASS transporter (TC 2.A.47) family. NADC 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.
Gamma-carboxyglutamate residues are formed by vitamin K dependent carboxylation. These residues are essential for the binding of calcium.
Requires vitamin K-dependent gamma-carboxylation for its function.
Belongs to the cyclic nucleotide phosphodiesterase family. PDE4 subfamily.
Required for mRNA export from the nucleus to the cytoplasm. Acts as an adapter that uses the ddx39b/uap56-nfx1 pathway to ensure efficient mRNA export and delivering to the nuclear pore (By similarity).
Belongs to the inositol 1,4,5-trisphosphate 5-phosphatase family.
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.
Belongs to the cyclin family. Cyclin AB subfamily.
Belongs to the NAD(P)-dependent epimerase/dehydratase family. GDP-mannose 4,6-dehydratase subfamily.
May be a centrosome-associated protein. Interacts with MYOC; affects its secretion and its aggregation.
Promotes CCP110 ubiquitination and proteasome-dependent degradation. By counteracting accumulation of CP110, maintains normal centriolar homeostasis and preventing formation of ectopic microtubular organizing centers (By similarity).
Ubiquitinated. This ubiquitination leads to proteasomal degradation (By similarity).
ATP-independent molecular chaperone preventing the aggregation of misfolded and hydrophobic patches-containing proteins. Functions as part of a cytosolic protein quality control complex, the bag6/bat3 complex, which maintains these client proteins in a soluble state and participates in their proper delivery to the endoplasmic reticulum or alternatively can promote their sorting to the proteasome where they undergo degradation. The bag6/bat3 complex is involved in the post-translational delivery of tail-anchored/type II transmembrane proteins to the endoplasmic reticulum membrane. Similarly, the bag6/bat3 complex also functions as a sorting platform for proteins of the secretory pathway that are mislocalized to the cytosol either delivering them to the proteasome for degradation or to the endoplasmic reticulum. The bag6/bat3 complex also plays a role in the endoplasmic reticulum-associated degradation (ERAD), a quality control mechanism that eliminates unwanted proteins of the endoplasmic reticulum through their retrotranslocation to the cytosol and their targeting to the proteasome. It maintains these retrotranslocated proteins in an unfolded yet soluble state condition in the cytosol to ensure their proper delivery to the proteasome. Also required for selective ubiquitin-mediated degradation of defective nascent chain polypeptides by the proteasome. Also involved in endoplasmic reticulum stress-induced pre-emptive quality control, a mechanism that selectively attenuates the translocation of newly synthesized proteins into the endoplasmic reticulum and reroutes them to the cytosol for proteasomal degradation. May ensure the proper degradation of these proteins and thereby protects the endoplasmic reticulum from protein overload upon stress. By stabilizing a large spectrum of proteins, may indirectly affect different biological processes including apoptosis. By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway.
When nuclear, may also act as a component of some chromatin regulator complex.
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.
Belongs to the D-isomer specific 2-hydroxyacid dehydrogenase family.
Adds the first Dol-P-Man derived mannose in an alpha-1,3 linkage to Man(5)GlcNAc(2)-PP-Dol.
Belongs to the glycosyltransferase 58 family.
C-terminus is required for spindle assembly.
Component of the CPC at least composed of survivin/birc5, incenp, cdca8/borealin and/or cdca9/dasra-A, and aurkb/aurora-B. Interacts directly with incenp (via N-terminus), and may weakly interact with aurkb (via N-terminus) to stabilize the complex. Interacts with GTP-bound ran in both the S and M phases of the cell cycle. Also found in a complex with ubiquitin-mediated signaling proteins including at least usp9x/xFAM, nploc4/npl4 and ufd1 (By similarity).
Component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly. Stimulates the mitotic kinase activity of aurkb/aurora-B in the CPC. Does not appear to exhibit anti-apoptotic activity (By similarity).
Ubiquitination is required for centrosome-targeting.
Part of the tectonic-like complex (also named B9 complex).
Involved in several stages of intracellular trafficking.
Belongs to the bacterial ribosomal protein bL35 family.
Belongs to the eukaryotic ribosomal protein eS10 family.
Nucleoside monophosphate (NMP) kinase that catalyzes the reversible transfer of the terminal phosphate group between nucleoside triphosphates and monophosphates. Has highest activity toward AMP, and weaker activity toward dAMP, CMP and dCMP. Also displays broad nucleoside diphosphate kinase activity.
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).
Belongs to the AB hydrolase superfamily. LDAH family.
Component of the glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex composed at least by PIGA, PIGC, PIGH, PIGP, PIGQ, PIGY and DPM2.
PREY is derived from the same bicistronic transcript that encodes these 2 different proteins.
Part of the glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex that catalyzes the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to phosphatidylinositol and participates in the first step of GPI biosynthesis. May act by regulating the catalytic subunit PIGA.
Catalyzes a 2-step reaction, involving the ATP-dependent carboxylation of the covalently attached biotin in the first step and the transfer of the carboxyl group to pyruvate in the second.
Belongs to the G-protein coupled receptor 1 family. Vasopressin/oxytocin receptor subfamily.
Belongs to the chondroitin N-acetylgalactosaminyltransferase family.
Belongs to the cytochrome c oxidase VIIa family.
Ubiquitin ligase protein which is a component of the N-end rule pathway. Recognizes and binds to proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation.
Belongs to the protein phosphatase inhibitor 1 family.
Required for ciliation. Recruits the RABL2B GTPase to the ciliary base to initiate ciliation.
Belongs to the myelin proteolipid protein family.
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.
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).
Lysophosphatidylserine (LPS) lipase that mediates the hydrolysis of lysophosphatidylserine, a class of signaling lipids that regulates immunological and neurological processes (By similarity). Represents a major lysophosphatidylserine lipase in the brain, thereby playing a key role in the central nervous system (By similarity). Also able to hydrolyze oxidized phosphatidylserine; oxidized phosphatidylserine is produced in response to severe inflammatory stress and constitutes a proapoptotic 'eat me' signal. Also has monoacylglycerol (MAG) lipase activity: hydrolyzes 2-arachidonoylglycerol (2-AG), thereby acting as a regulator of endocannabinoid signaling pathways. Has a strong preference for very-long-chain lipid substrates; substrate specificity is likely due to improved catalysis and not improved substrate binding (By similarity).
Monoubiquitination at Lys-87 prevents binding to phosphatidylinositol 3-phosphate (PI3P) and localization to early endosome membranes.
Negative regulator of epidermal growth factor receptor (EGFR) signaling. Acts by promoting EGFR degradation in endosomes when not monoubiquitinated (By similarity).
The FYVE-type zinc finger mediates the interaction with phosphatidylinositol 3-phosphate (PI3P) and localization to early endosome membranes when not monoubiquitinated at Lys-87.
Involved in pre-mRNA splicing, specifically in spliceosome disassembly during late-stage splicing events.
Belongs to the glycosyl hydrolase 85 family.
May be a regulator of keratinocyte proliferation or differentiation.
Belongs to the pyridoxal phosphate-binding protein YggS/PROSC family.
Pyridoxal 5'-phosphate (PLP)-binding protein, which may be involved in intracellular homeostatic regulation of pyridoxal 5'-phosphate (PLP), the active form of vitamin B6.
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.
Lipid transfer protein involved in autophagosome assembly. Tethers the edge of the isolation membrane (IM) to the endoplasmic reticulum (ER) and mediates direct lipid transfer from ER to IM for IM expansion. Binds to the ER exit site (ERES), which is the membrane source for autophagosome formation, and extracts phospholipids from the membrane source and transfers them to atg9 (atg9a or atg9b) to the IM for membrane expansion. Also regulates lipid droplets morphology and distribution within the cell.
The chorein N-terminal domain mediates lipid transfer activity.
Catalyzes the dehydration of the S-form of NAD(P)HX at the expense of ATP, which is converted to ADP. Together with NAD(P)HX epimerase, which catalyzes the epimerization of the S- and R-forms, the enzyme allows the repair of both epimers of NAD(P)HX, a damaged form of NAD(P)H that is a result of enzymatic or heat-dependent hydration.
Adds a myristoyl group to the N-terminal glycine residue of certain cellular proteins.
Acts early in neural crest formation, functioning redundantly with the other group E Sox factors sox8 and sox9 to induce neural crest progenitors. Acts downstream of wnt-signaling at the neural plate border. Involved in the specification of neural crest progenitors fated to form the pigment cell lineage (By similarity).
Interacts with the sumoylation factors ube2i/ubc9 and sumo1.
The transactivation domains TAM and TAC (for transactivation domain in the middle and at the C-terminus, respectively) are required to contact transcriptional coactivators and basal transcriptional machinery components and thereby induce gene transactivation.
May play a role in RNA metabolism in both nuclei and mitochondria. May bind mature mRNA in the nucleus outer membrane. In mitochondria binds to poly(A) mRNA. May be involved in transcription regulation. Binds single-stranded DNA (By similarity).
Belongs to the methyltransferase superfamily.
Belongs to the archaeal Rpo6/eukaryotic RPB6 RNA polymerase subunit family.
Component of the RNA polymerase I (Pol I), RNA polymerase II (Pol II) and RNA polymerase III (Pol III) complexes consisting of at least 13, 12 and 17 subunits, respectively.
Belongs to the JHDM1 histone demethylase family. JHDM1D subfamily.
Histone demethylase required for brain development. Specifically demethylates dimethylated 'Lys-9' and 'Lys-27' (H3K9me2 and H3K27me2, respectively) of histone H3 and monomethylated histone H4 'Lys-20' residue (H4K20Me1), thereby playing a central role in histone code (By similarity).
The PHD-type zinc finger mediates the binding to H3K4me3. Binding to H3K4me3 prevents its access to H3K9me2 (By similarity).
Acts as a component of the essential kinetochore-associated NDC80 complex, which is required for chromosome segregation and spindle checkpoint activity.
Acts as a component of the essential kinetochore-associated NDC80 complex, which is required for chromosome segregation and spindle checkpoint activity. Required for kinetochore integrity and the organization of stable microtubule binding sites in the outer plate of the kinetochore. The NDC80 complex synergistically enhances the affinity of the SKA1 complex for microtubules and may allow the NDC80 complex to track depolymerizing microtubules.
Component of the NDC80 complex, which is composed of ndc80, cdca1, spbc24 and spbc25. The NDC80 complex interacts with mis12 and zwint (By similarity).
May antagonize Nodal signaling and subsequent organization of axial structures during mesodermal patterning.
Component of a complex required to couple deglycosylation and proteasome-mediated degradation of misfolded proteins in the endoplasmic reticulum that are retrotranslocated in the cytosol. Involved in ubiquitin-proteasome systems (By similarity).
Belongs to the complexin/synaphin family.
Activated by diacylglycerol which in turn phosphorylates a range of cellular proteins.
Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2 domain.
Calcium-activated and phospholipid-dependent serine/threonine-protein kinase involved in various processes such as regulation of the B-cell receptor (BCR) signalosome, apoptosis and transcription regulation. Plays a key role in B-cell activation and function by regulating BCR-induced NF-kappa-B activation and B-cell survival. Required for recruitment and activation of the IKK kinase to lipid rafts and mediates phosphorylation of card11/carma1, leading to activate the NF-kappa-B signaling. Involved in apoptosis following oxidative damage: in case of oxidative conditions, specifically phosphorylates 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 (By similarity).
Phosphorylation on Thr-497 within the activation loop renders it competent to autophosphorylate. Subsequent autophosphorylation of Thr-638 maintains catalytic competence, and autophosphorylation on Ser-657 appears to release the kinase into the cytosol (By similarity).
Expression widely distributed both maternally and zygotically. During gastrulation, strong expression in the posterior end near the blastopore.
Interacts with lrp6. Interacts with casein kinases.
Morphants have defects in neural crest formation. At the tadpole stage, animals are often less pigmented with ventrally bent tails. Embryos develop smaller eyes and forebrain structures.
Promotes lrp6 phosphorylation by casein kinases and thereby plays a role in Wnt signaling. May be a membrane scaffold protein involved in the self-aggregation of lrp6 further enhancing its activity. Required for neural crest formation.
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.
Has a role in nuclear-cytoplasmic transport of proteins and mRNAs.
Belongs to the sepiapterin reductase family.
Catalyzes the final one or two reductions in tetra-hydrobiopterin biosynthesis to form 5,6,7,8-tetrahydrobiopterin.
Can form homomultimers. Interacts with prickle1. Interacts (via the PDZ domain) with ccdc88c/dal and dact1-B/dpr. Interacts (via the DIX domain) with ARP/Axin-related protein and dact1-A/frodo. Interacts with sdc4, possibly via fz7. Interacts directly (via the DEP domain) with efnb1/ephrin-B1. May interact indirectly with the phosphorylated ephrin receptors ephb1 and ephb2 via SH domain-containing adapters (By similarity).
Involved in at least 2 independent signaling cascades, controlling cell fate via canonical Wnt signaling and cell polarity via a planar cell polarity (PCP) cascade. Acts synergistically with dal/dapple-like to activate Wnt signaling, stabilizing ctnnb1/beta-catenin and leading to dorsal axis formation. Also prevents degradation of ctnnb1/beta-catenin by displacing gsk3 from a complex with ARP/Axin-related protein. Has an additional role in anterior-posterior (A/P) axis formation, specifying different neuroectodermal cell fates along the A/P axis in a dose-dependent manner by activating several early patterning genes. In the PCP pathway, required at the cell membrane for PCP-mediated neural and mesodermal convergent extension during gastrulation and subsequent neural tube closure, acting to activate jnk. Also involved in blastopore closure and archenteron elongation during early, but not late, gastrulation. Associates with ephrin receptors and ligands and acts as part of a downstream PCP pathway to mediate ephrin-mediated cell repulsion via activation of rhoa. Required for efnb1/ephrin-B1-driven movement of non-retinal progenitor cells into the retina during eye field formation. Patterns the hindbrain. Required for ciliogenesis. Controls the docking of basal bodies to the apical plasma membrane; mediates the activation, but not localization of rhoa at the apical surface of ciliated cells during basal body docking. Furthermore, required for the association of basal bodies with membrane-bound vesicles and the vesicle-trafficking protein exoc4/sec8, and this association is in turn required for basal body docking. Once basal bodies are docked, required for the planar polarization of basal bodies that underlies ciliary beating and the directional fluid flow across ciliated epithelia (By similarity).
Phosphorylated. Phosphorylation is controlled by frizzled proteins, correlates with the onset of embryo dorsalizing events and is higher in the dorsal half of early cleavage embryos. Phosphorylated on tyrosine residues in response to association with efnb1/ephrin-B1 (By similarity).
The C-terminal region containing the DEP domain is required for membrane accumulation and phosphorylation. Wnt signaling and axis induction requires the DIX domain. The C-terminus contributes to the localization at the cilia base (By similarity).
RNA-binding protein that plays a role in the regulation of alternative splicing.
Receptor for adenosine. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.
Belongs to the dynactin subunit 4 family.
Belongs to the carotenoid oxygenase family.
Belongs to the nucleoporin Nup84/Nup107 family.
Stores iron in a soluble, non-toxic, readily available form. Important for iron homeostasis. Iron is taken up in the ferrous form and deposited as ferric hydroxides after oxidation.
May be involved in forming the receptor site for cardiac glycoside binding or may modulate the transport function of the sodium ATPase.
Regulatory subunit of the sodium/potassium-transporting ATPase which is composed of a catalytic alpha subunit, an auxiliary non-catalytic beta subunit and an additional regulatory subunit.
Belongs to the universal ribosomal protein uL22 family.
In the C-terminal section; belongs to the NAD synthetase family.
Belongs to the Antp homeobox family. Labial subfamily.
Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. Acts on the anterior body structures. Acts downstream of meis3 to pattern the hindbrain (By similarity).
Belongs to the sirtuin family. Class III subfamily.
In contrast to class I sirtuins, class III sirtuins have only weak deacetylase activity. Difference in substrate specificity is probably due to a larger hydrophobic pocket with 2 residues (Tyr-101 and Arg-104) that bind to malonylated and succinylated substrates and define the specificity.
NAD-dependent lysine demalonylase, desuccinylase and deglutarylase that specifically removes malonyl, succinyl and glutaryl groups on target proteins. Has weak NAD-dependent protein deacetylase activity; however this activity may not be physiologically relevant in vivo.
Functions as a transporter for creatine and as well for its precursor guanidinoacetate. Transport of creatine and GAA is independent of resting membrane potential and extracellular Na(+), Cl(-), or pH. Contributes to the process of creatine biosynthesis and distribution.
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.
Required for vesicular transport between the endoplasmic reticulum and the Golgi apparatus.
Belongs to the eukaryotic ribosomal protein eL20 family.
Belongs to the peptidase C19 family. USP44 subfamily.
Deubiquitinase that plays a key role in the spindle checkpoint by preventing premature anaphase onset. Acts by specifically mediating deubiquitination of cdc20, a negative regulator of the anaphase promoting complex/cyclosome (APC/C) (By similarity).
Belongs to the YY transcription factor family.
Belongs to the Mediator complex subunit 19 family.
Binds the C-terminal sequence motif K-D-E-L in a hydrophilic cavity between the transmembrane domains. This triggers a conformation change that exposes a Lys-rich patch on the cytosolic surface of the protein (By similarity). This patch mediates recycling from the Golgi to the endoplasmic reticulum, probably via COPI vesicles (By similarity).
Receptor for the C-terminal sequence motif K-D-E-L that is present on endoplasmic reticulum resident proteins and that mediates their recycling from the Golgi back to the endoplasmic reticulum.
Component of the exocyst complex involved in the docking of exocytic vesicles with fusion sites on the plasma membrane.
Belongs to the distal-less homeobox family.
May function as an activator of the canonical Wnt signaling pathway upstream of ctnnb1/beta-catenin. May be required for dorsal axis formation (By similarity).
Neurotensin may play an endocrine or paracrine role in the regulation of fat metabolism. It causes contraction of smooth muscle.
Binds 1 potassium ion per subunit. The potassium ion interacts primarily with the substrate.
Binds 2 magnesium ions per subunit. The magnesium ions interact primarily with the substrate.
Catalyzes the formation of S-adenosylmethionine from methionine and ATP.
Belongs to the class-II aminoacyl-tRNA synthetase family. Type-1 seryl-tRNA synthetase subfamily.
Cytosolic 10-formyltetrahydrofolate dehydrogenase that catalyzes the NADP(+)-dependent conversion of 10-formyltetrahydrofolate to tetrahydrofolate and carbon dioxide. May also have an NADP(+)-dependent aldehyde dehydrogenase activity towards formaldehyde, acetaldehyde, propionaldehyde, and benzaldehyde (By similarity). Regulates reduced folate pools as well as glycine metabolism (By similarity).
In the C-terminal section; belongs to the aldehyde dehydrogenase family. ALDH1L subfamily.
In the N-terminal section; belongs to the GART family.
Phosphopantetheinylation at Ser-354 by AASDHPPT is required for the formyltetrahydrofolate dehydrogenase activity.
The C-terminal aldehyde dehydrogenase domain has an NADP-dependent dehydrogenase activity. It catalyzes the oxidation of formate, released by the hydrolysis of formyltetrahydrofolate, into CO2.
The N-terminal hydrolase domain has an NADP-independent formyltetrahydrofolate hydrolase activity, releasing formate and tetrahydrofolate.
The carrier domain is phosphopantetheinylated and uses the 4'-phosphopantetheine/4'-PP swinging arm to transfer the formyl group released by the N-terminal formyltetrahydrofolate hydrolase activity to the C-terminal aldehyde dehydrogenase domain that catalyzes its NADP-dependent oxidation into CO2. The overall NADP-dependent physiological reaction requires the 3 domains (N-terminal hydrolase, C-terminal aldehyde dehydrogenase and carrier domains) to convert formyltetrahydrofolate into tetrahydrofolate and CO2.
Belongs to the potassium channel family. KQT (TC 1.A.1.15) subfamily. Kv7.1/KCNQ1 sub-subfamily.
Belongs to the 5-formyltetrahydrofolate cyclo-ligase family.
Belongs to the DEAD box helicase family. DDX52/ROK1 subfamily.
During gastrulation, expressed on the dorsal side of the embryo and then in the neural plate and neural tube. At tailbud stages, expressed in the somites. Expressed in the neural tube later in development.
Inactivation in embryos by antisense morpholino causes paralysis and shortening of the body axis.
Microtubule-binding protein required to ensure proper cell division and nuclear envelope reassembly by sequestering the endoplasmic reticulum away from chromosomes during mitosis. Probably acts by clearing the endoplasmic reticulum membrane from metaphase chromosomes (By similarity). May play a role in the maintenance of both the nervous system and the musculature.
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. May also play a role in intracellular vesicle trafficking. As part of a BORC-like complex may play a role in lysosomes movement and localization at the cell periphery. Associated with the cytosolic face of lysosomes, this complex may couple lysosomes to microtubule plus-end-directed kinesin motor.
Component of the biogenesis of lysosome-related organelles complex 1 (BLOC-1).
Involved in calcium binding and microtubule stabilization.
Belongs to the prokaryotic/mitochondrial release factor family.
Interacts (via C-terminus) with clip1/clip-170, and cenpe.
Microtubule plus-end tracking protein that promotes the stabilization of dynamic microtubules during anaphase. Plays a crucial role in chromatin-induced microtubule formation. May also act at microtubule minus ends. May be involved in the nucleation of noncentrosomal microtubules originating from the trans-Golgi network (TGN) (By similarity).
Multifunctional RNA-binding protein involved in the regulation of pre-mRNA splicing, mRNA stability and mRNA translation important for cell fate decision and differentiation. Plays a major role in pre-mRNA alternative splicing regulation. Mediates preferentially muscle-specific exon inclusion in numerous mRNAs important for striated cardiac and skeletal muscle cell differentiation. Binds to intronic splicing enhancer (ISE) composed of stretches of GU-rich motifs localized in flanking intron of exon that will be included by alternative splicing. Involved in embryonic stem cell (ESC) transition to cardiac cell differentiation by promoting pre-mRNA alternative splicing events of several pluripotency and/or differentiation genes. Plays a role in the regulation of mRNA stability and mRNA translation to which it is bound. Involved in myogenic differentiation by regulating myog levels. Binds to a huge amount of mRNAs. Required for embryonic heart development, sarcomer and M-band formation in striated muscles.
The RRM domain is necessary for mRNA stability and mRNA translation regulation.
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.
Actin maturation protease that specifically mediates the cleavage of immature acetylated N-terminal actin, thereby contributing to actin maturation (By similarity). Cleaves N-terminal acetylated methionine of immature cytoplasmic beta- and gamma-actin after translation (By similarity). Cleaves N-terminal acetylated cysteine of muscle alpha-actin after canonical removal of N-terminal methionine (By similarity).
Plays a role in transport between endoplasmic reticulum and Golgi.
Possible role in transport between endoplasmic reticulum and Golgi.
Belongs to the metallo-dependent hydrolases superfamily. ATZ/TRZ family.
Catalyzes the hydrolytic deamination of guanine, producing xanthine and ammonia.
Belongs to the vacuolar ATPase subunit S1 family.
Belongs to the eukaryotic ribosomal protein eL13 family.
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.
Belongs to the PX domain-containing GAP family.
Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A3 subfamily.
Binds 1 Mg(2+) or Mn(2+) ion per subunit.
The potassium channel is probably composed of a homo- or heterotetrameric complex of pore-forming alpha subunits that can associate with modulating beta subunits.
Regulatory subunit of protein phosphatase 1.
E3 ubiquitin-protein ligase required for accumulation of repair proteins to sites of DNA damage. Acts with ube2n/ubc13 to amplify the rnf8-dependent histone ubiquitination. Recruited to sites of DNA damage at double-strand breaks (DSBs) by binding to ubiquitinated histone H2A and ubiquitinates histone H2A and H2AX, leading to amplify the rnf8-dependent H2A ubiquitination and promoting the formation of 'Lys-63'-linked ubiquitin conjugates. This leads to concentrate ubiquitinated histones H2A and H2AX at DNA lesions to the threshold required for recruitment of tp53bp1 and brca1. Catalyzes monoubiquitination of 'Lys-13' and 'Lys-15' of nucleosomal histone H2A (H2AK13Ub and H2AK15Ub, respectively).
The MIU motif (motif interacting with ubiquitin) mediates the interaction with both 'Lys-48'- and 'Lys-63'-linked ubiquitin chains. The UMI motif mediates interaction with ubiquitin with a preference for 'Lys-63'-linked ubiquitin. The specificity for different types of ubiquitin is mediated by juxtaposition of ubiquitin-binding motifs (MIU and UMI motifs) with LR motifs (LRMs).
Belongs to the type II topoisomerase family.
Key decatenating enzyme that alters DNA topology by binding to two double-stranded DNA molecules, generating a double-stranded break in one of the strands, passing the intact strand through the broken strand, and religating the broken strand.
Belongs to the argonaute family. Ago subfamily.
Required for RNA-mediated gene silencing (RNAi). Binds to short RNAs such as microRNAs (miRNAs) and represses the translation of mRNAs which are complementary to them. Lacks endonuclease activity and does not appear to cleave target mRNAs.
LSm subunits form a heteromer with a donut shape.
Probably involved with other LSm subunits in the general process of degradation of mRNAs.
Belongs to the tRNA pseudouridine synthase TruA family.
Stimulates the adrenal glands to release cortisol.
May act as an important regulator of the cell cycle that participates in the maintenance of genome integrity.
Belongs to the eukaryotic ribosomal protein eL31 family.
Belongs to the acireductone dioxygenase (ARD) family.
Binds either 1 Fe or Ni cation per monomer. Iron-binding promotes an acireductone dioxygenase reaction producing 2-keto-4-methylthiobutyrate, while nickel-binding promotes an acireductone dioxygenase reaction producing 3-(methylsulfanyl)propanoate.
Catalyzes 2 different reactions between oxygen and the acireductone 1,2-dihydroxy-3-keto-5-methylthiopentene (DHK-MTPene) depending upon the metal bound in the active site. Fe-containing acireductone dioxygenase (Fe-ARD) produces formate and 2-keto-4-methylthiobutyrate (KMTB), the alpha-ketoacid precursor of methionine in the methionine recycle pathway. Ni-containing acireductone dioxygenase (Ni-ARD) produces methylthiopropionate, carbon monoxide and formate, and does not lie on the methionine recycle pathway.
Belongs to the transcription factor STAT family.
Belongs to the reverse transcriptase family. Telomerase subfamily.
Telomerase is a ribonucleoprotein enzyme essential for the replication of chromosome termini in most eukaryotes. It elongates telomeres. It is a reverse transcriptase that adds simple sequence repeats to chromosome ends by copying a template sequence within the RNA component of the enzyme.
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.
Activated by RHOA binding. Inhibited by Y-27632.
Protein kinase which is a key regulator of actin cytoskeleton and cell polarity.
Transmembrane component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes. Required for ciliogenesis and sonic hedgehog/SHH signaling (By similarity).
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.
Associates with pre-60S ribosomal particles.
Belongs to the ZNF593/BUD20 C2H2-type zinc-finger protein family.
Involved in pre-60S ribosomal particles maturation by promoting the nuclear export of the 60S ribosome. Negatively modulates the DNA binding activity of Oct-2 and therefore its transcriptional regulatory activity.
The protein is largely disordered, with the exception of the zinc finger domain.
Belongs to the phosphoglycerate mutase family. BPG-dependent PGAM subfamily.
Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle.
The APC/C is composed of at least 12 subunits.
Acts as a molecular chaperone for G protein-coupled receptors, regulating their biogenesis and exit from the ER.
Belongs to the DEAD box helicase family. DEAH subfamily. FANCM sub-subfamily.
Belongs to the autoinducer-2 exporter (AI-2E) (TC 2.A.86) family.
Belongs to the ribonucleoside diphosphate reductase small chain family.
Structural component of the gap junctions and the hemichannels.
Functions as a cellular zinc transporter.
Belongs to the metallo-dependent hydrolases superfamily. HutI family.
Belongs to the histidine acid phosphatase family.
Responsible for the 2-O-dephosphorylation of xylose in the glycosaminoglycan-protein linkage region of proteoglycans thereby regulating the amount of mature glycosaminoglycan (GAG) chains. Sulfated glycosaminoglycans (GAGs), including heparan sulfate and chondroitin sulfate, are synthesized on the so-called common GAG-protein linkage region (GlcUAbeta1-3Galbeta1-3Galbeta1-4Xylbeta1-O-Ser) of core proteins, which is formed by the stepwise addition of monosaccharide residues by the respective specific glycosyltransferases. Xylose 2-O-dephosphorylation during completion of linkage region formation is a prerequisite for the initiation and efficient elongation of the repeating disaccharide region of GAG chains.
Belongs to the universal ribosomal protein uS8 family.
Involved in effecient integration of the N-module into mitochondrial respiratory chain complex I.
Adaptor protein complex 2 (AP-2) is a heterotetramer composed of two large adaptins (alpha-type subunit AP2A1 or AP2A2 and beta-type subunit AP2B1), a medium adaptin (mu-type subunit AP2M1) and a small adaptin (sigma-type subunit AP2S1).
Component of the adaptor protein complex 2 (AP-2). Adaptor protein complexes function in protein transport via transport vesicles in different membrane traffic pathways. Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation. AP-2 is involved in clathrin-dependent endocytosis in which cargo proteins are incorporated into vesicles surrounded by clathrin (clathrin-coated vesicles, CCVs) which are destined for fusion with the early endosome. The clathrin lattice serves as a mechanical scaffold but is itself unable to bind directly to membrane components. Clathrin-associated adaptor protein (AP) complexes which can bind directly to both the clathrin lattice and to the lipid and protein components of membranes are considered to be the major clathrin adaptors contributing the CCV formation. AP-2 also serves as a cargo receptor to selectively sort the membrane proteins involved in receptor-mediated endocytosis. AP-2 seems to play a role in the recycling of synaptic vesicle membranes from the presynaptic surface. AP-2 recognizes Y-X-X-[FILMV] (Y-X-X-Phi) and [ED]-X-X-X-L-[LI] endocytosis signal motifs within the cytosolic tails of transmembrane cargo molecules. AP-2 may also play a role in maintaining normal post-endocytic trafficking through the ARF6-regulated, non-clathrin pathway. The AP-2 alpha subunit binds polyphosphoinositide-containing lipids, positioning AP-2 on the membrane. The AP-2 alpha subunit acts via its C-terminal appendage domain as a scaffolding platform for endocytic accessory proteins. The AP-2 alpha and AP-2 sigma subunits are thought to contribute to the recognition of the [ED]-X-X-X-L-[LI] motif.
Belongs to the protein-tyrosine phosphatase family. Non-receptor class 1 subfamily.
May be involved in thermogenesis and glucose homeostasis.
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.
This is a larval (tadpole) alpha-globin.
Component of a calcium channel complex consisting of a pore-forming alpha subunit (CACNA1S) and the ancillary subunits CACNB1 or CACNB2, CACNG1 and CACNA2D1. The channel complex contains alpha, beta, gamma and delta subunits in a 1:1:1:1 ratio, i.e. it contains either CACNB1 or CACNB2.
Regulatory subunit of the voltage-gated calcium channel that gives rise to L-type calcium currents in skeletal muscle. Regulates channel inactivation kinetics.
Belongs to the SWEET sugar transporter family.
Mediates sugar transport across membranes.
Although the final Cys may be farnesylated, the terminal tripeptide is probably not removed, and the C-terminus is not methylated.
Phosphorylase b kinase catalyzes the phosphorylation of serine in certain substrates, including troponin I. The alpha chain may bind calmodulin.
Belongs to the FMN-dependent alpha-hydroxy acid dehydrogenase family.
Component of the SKA1 complex, a microtubule-binding subcomplex of the outer kinetochore that is essential for proper chromosome segregation. The SKA1 complex is a direct component of the kinetochore-microtubule interface and directly associates with microtubules as oligomeric assemblies. The complex facilitates the processive movement of microspheres along a microtubule in a depolymerization-coupled manner. In the complex, it mediates the microtubule-stimulated oligomerization. Affinity for microtubules is synergistically enhanced in the presence of the ndc-80 complex and may allow the ndc-80 complex to track depolymerizing microtubules.
Component of the SKA1 complex, composed of ska1, ska2 and ska3.
Belongs to the glycosyl hydrolase 37 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 non-histone proteins. In addition to protein deacetylase activity, also has protein-lysine deacylase activity: acts as a protein decrotonylase by mediating decrotonylation ((2E)-butenoyl) of histones.
Its activity is inhibited by trichostatin A (TSA) and butyrate, 2 well known histone deacetylase inhibitors.
Component of the spliceosome B complex. Interacts with ik.
Involved in pre-mRNA splicing as a component of the spliceosome (By similarity). Required for normal accumulation of ik (By similarity). Required for normal mitotic spindle assembly and normal progress through mitosis (By similarity).
The WD repeats assemble into a seven-bladed WD propeller.
Component of the dolichol-phosphate mannose (DPM) synthase complex.
Stabilizer subunit of the dolichol-phosphate mannose (DPM) synthase complex; tethers catalytic subunit to the ER.
Component of the cap-binding complex (CBC), which binds co-transcriptionally to the 5' cap of pre-mRNAs and is involved in various processes such as pre-mRNA splicing, translation regulation, nonsense-mediated mRNA decay, RNA-mediated gene silencing (RNAi) by microRNAs (miRNAs) and mRNA export. The CBC complex is involved in mRNA export from the nucleus, leading to the recruitment of the mRNA export machinery to the 5' end of mRNA and to mRNA export in a 5' to 3' direction through the nuclear pore. The CBC complex is also involved in mediating U snRNA and intronless mRNAs export from the nucleus. The CBC complex is essential for a pioneer round of mRNA translation, before steady state translation when the CBC complex is replaced by cytoplasmic cap-binding protein eIF4E. The pioneer round of mRNA translation mediated by the CBC complex plays a central role in nonsense-mediated mRNA decay (NMD), NMD only taking place in mRNAs bound to the CBC complex, but not on eIF4E-bound mRNAs. The CBC complex enhances NMD in mRNAs containing at least one exon-junction complex (EJC), promoting the interaction between upf1 and upf2. The CBC complex is also involved in 'failsafe' NMD, which is independent of the EJC complex, while it does not participate in Staufen-mediated mRNA decay (SMD). During cell proliferation, the CBC complex is also involved in microRNAs (miRNAs) biogenesis via its interaction with srrt/ars2, thereby being required for miRNA-mediated RNA interference. The CBC complex also acts as a negative regulator of parn, thereby acting as an inhibitor of mRNA deadenylation. In the CBC complex, ncbp2/cbp20 recognizes and binds capped RNAs (m7GpppG-capped RNA) but requires ncbp1/cbp80 to stabilize the movement of its N-terminal loop and lock the CBC into a high affinity cap-binding state with the cap structure. The conventional cap-binding complex with NCBP2 binds both small nuclear RNA (snRNA) and messenger (mRNA) and is involved in their export from the nucleus (By similarity).
Component of the nuclear cap-binding complex (CBC), a heterodimer composed of ncbp1/cbp80 and ncbp2/cbp20 that interacts with m7GpppG-capped RNA.
Belongs to the 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 GMC oxidoreductase family.
Belongs to the DNA polymerase type-B-like family.
May function as a homophilic adhesion molecule.
Belongs to the RecA family. RAD51 subfamily.
Negative regulator of sphingolipid synthesis.
Belongs to the eukaryotic ribosomal protein eL33 family.
Belongs to the universal ribosomal protein uS15 family.
RING-type zinc finger-containing E3 ubiquitin ligase that assembles with melanoma antigen protein (MAGE) to catalyze the direct transfer of ubiquitin from E2 ubiquitin-conjugating enzyme to a specific substrate. Involved in maintenance of genome integrity, DNA damage response and DNA repair.
RING-type zinc finger-containing E3 ubiquitin ligase that assembles with melanoma antigen protein (MAGE) to catalyze the direct transfer of ubiquitin from E2 ubiquitin-conjugating enzyme to a specific substrate. Within MAGE-RING ubiquitin ligase complex, MAGE stimulates and specifies ubiquitin ligase activity likely through recruitment and/or stabilization of the E2 ubiquitin-conjugating enzyme at the E3:substrate complex. Involved in maintenance of genome integrity, DNA damage response and DNA repair.
Belongs to the peptidase M67A family. CSN5 subfamily.
Probable protease subunit of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes. The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of E3 ligase complexes, leading to modify the Ubl ligase activity. In the complex, it probably acts as the catalytic center that mediates the cleavage of nedd8 from cullins. It however has no metalloprotease activity by itself and requires the other subunits of the CSN complex.
The CSN complex is associated with some 'Lys-63'-specific deubiquitination. Such activity is however not mediated by the core CSN complex but by the brcc3/brcc36 component of the BRISC complex (By similarity).
The JAMM motif is essential for the protease activity of the CSN complex resulting in deneddylation of cullins. It constitutes the catalytic center of the complex (By similarity).
Inhibits p53- and p73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain.
Belongs to the type I cytokine receptor family. Type 4 subfamily.
Belongs to the archaeal Rpo12/eukaryotic RPC10 RNA polymerase subunit family.
Belongs to the ALG6/ALG8 glucosyltransferase 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.
In eukaryotes there are cytoplasmic, mitochondrial and chloroplastic isozymes.
Belongs to the peptidase M28 family. M28B subfamily.
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 queuine tRNA-ribosyltransferase family.
Catalytic subunit of the queuine tRNA-ribosyltransferase (TGT) that catalyzes the base-exchange of a guanine (G) residue with queuine (Q) at position 34 (anticodon wobble position) in tRNAs with GU(N) anticodons (tRNA-Asp, -Asn, -His and -Tyr), resulting in the hypermodified nucleoside queuosine (7-(((4,5-cis-dihydroxy-2-cyclopenten-1-yl)amino)methyl)-7-deazaguanosine). Catalysis occurs through a double-displacement mechanism. The nucleophile active site attacks the C1' of nucleotide 34 to detach the guanine base from the RNA, forming a covalent enzyme-RNA intermediate. The proton acceptor active site deprotonates the incoming queuine, allowing a nucleophilic attack on the C1' of the ribose to form the product.
Belongs to the splicing factor SR family.
Component of a splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junction on mRNAs. The EJC is a dynamic structure consisting of a few core proteins and several more peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. Putative component of the spliceosome which enhances the formation of the ATP-dependent A complex of the spliceosome. May participate in mRNA 3'-end cleavage. Also mediates increase of mRNA abundance and translational efficiency (By similarity).
It is uncertain whether Met-1 or Met-26 is the initiator.
Catalyzes the synthesis of N-acetylaspartate acid (NAA) from L-aspartate and acetyl-CoA.
Involved in the lipid remodeling steps of GPI-anchor maturation. Required for stable expression of GPI-anchored proteins at the cell surface (By similarity).
Involved in the lipid remodeling steps of GPI-anchor maturation. Required for stable expression of GPI-anchored proteins at the cell surface.
Deletion of the TJP1/ZO1 interaction motif (ZIM) decreases but does not abolish colocalization with TJP1/ZO1.
It is uncertain whether Met-1 or Met-9 is the initiator.
Parallel homodimer (By similarity). Interacts with TJP1/ZO1 and TJP2/ZO2 (By similarity).
Probably plays a role in the formation and regulation of the tight junction (TJ) paracellular permeability barrier, possibly by linking ZO proteins to the actomyosin cytoskeleton.
Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family.
Belongs to the universal ribosomal protein uS13 family.
Composed of a heavy chain (beta) and a light chain (alpha). Component of an NADPH oxidase complex composed of a heterodimer formed by the membrane proteins CYBA and CYBB and the cytosolic subunits NCF1, NCF2 and NCF4. Interacts with NCF1 (via SH3 domain).
Critical component of the membrane-bound oxidase of phagocytes that generates superoxide. Associates with NOX3 to form a functional NADPH oxidase constitutively generating superoxide.
Belongs to the exonuclease superfamily. TREX family.
Belongs to the class IV-like SAM-binding methyltransferase superfamily. RNA methyltransferase NEP1 family.
The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues.
Belongs to the class I-like SAM-binding methyltransferase superfamily. MenG/UbiE family.
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).
Gamma-tubulin complex is necessary for microtubule nucleation at the centrosome.
Component of the endosomal sorting complex required for transport II (ESCRT-II), composed of snf8, vps36 and vps25.
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. The MVB pathway mediates delivery of transmembrane proteins into the lumen of the lysosome for degradation. The ESCRT-II complex is probably involved in the recruitment of the ESCRT-III complex (By similarity).
Belongs to the methyltransferase superfamily. METTL21 family.
Protein-lysine methyltransferase that selectively trimethylates residues in heat shock protein 70 (HSP70) family members.
Belongs to the metallo-dependent hydrolases superfamily. Peptidase M19 family.
Forms homooligomers. Identified in the CTLH complex that contains at least MAEA, RMND5A (or alternatively its paralog RMND5B), GID8, WDR26, and RANBP9 and/or RANBP10. Interacts with DDB1-CUL4A/B E3 ligase complexes.
G-beta-like protein involved in cell signal transduction. Acts as a negative regulator in MAPK signaling pathway. Functions as a scaffolding protein to promote G beta:gamma-mediated PLCB2 plasma membrane translocation and subsequent activation in leukocytes. Core component of the CTLH E3 ubiquitin-protein ligase complex that mediates ubiquitination and subsequent proteasomal degradation of target proteins (By similarity). Acts as a negative regulator of the canonical Wnt signaling pathway through preventing ubiquitination of beta-catenin CTNNB1 by the beta-catenin destruction complex, thus negatively regulating CTNNB1 degradation. Serves as a scaffold to coordinate PI3K/AKT pathway-driven cell growth and migration. Protects cells from oxidative stress-induced apoptosis via the down-regulation of AP-1 transcriptional activity as well as by inhibiting cytochrome c release from mitochondria (By similarity). Protects also cells by promoting hypoxia-mediated autophagy and mitophagy (By similarity).
Belongs to the protease inhibitor I35 (TIMP) family.
Aminocarboxypropyltransferase that catalyzes the aminocarboxypropyl transfer on pseudouridine at position 1248 (Psi1248) in 18S rRNA. It constitutes the last step in biosynthesis of the hypermodified N1-methyl-N3-(3-amino-3-carboxypropyl) pseudouridine (m1acp3-Psi) conserved in eukaryotic 18S rRNA.
Belongs to the TDD superfamily. TSR3 family.
Troponin T is the tropomyosin-binding subunit of troponin, the thin filament regulatory complex which confers calcium-sensitivity to striated muscle actomyosin ATPase activity.
Required for the formation of cilia. May also have pro-apoptotic function (By similarity).
Belongs to the glycoprotein hormones subunit alpha family.
Heterodimer of an alpha and a beta chain.
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.
May be involved in regulation of NF-kappa-B signaling. May be involved in copper-dependent atp7a trafficking between the trans-Golgi network and vesicles in the cell periphery (By similarity).
Belongs to the D-glucuronyl C5-epimerase family.
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. RAC subfamily.
Transcriptional repressor that binds to the promoter region of target genes. Plays a role in the regulation of the cell cycle and of the Wnt pathway. Binds preferentially to the sequence 5'-TTCATTCATTCA-3'. Binding to the histone H1.0 promoter is enhanced by interaction with RB1. Disrupts the interaction between DNA and TCF4.
Possible role in maturation and transport from the endoplasmic reticulum to the plasma membrane of functional dual oxidase.
Binds free ubiquitin non-covalently via its RING-type zinc finger. Ubiquitin-binding leads to enhance the E3 ubiquitin-protein ligase activity by stabilizing the ubiquitin-conjugating enzyme E2 (donor ubiquitin) in the 'closed' conformation and activating ubiquitin transfer.
E3 ubiquitin-protein ligase required for mesoderm patterning during embryonic development (By similarity). Acts as an enhancer of the transcriptional responses of the smad2/smad3 effectors, which are activated downstream of BMP. Acts by mediating ubiquitination and degradation of SMAD inhibitors such as smad7, inducing their proteasomal degradation and thereby enhancing the transcriptional activity of TGF-beta and BMP. Specifically binds polysumoylated chains via SUMO interaction motifs (SIMs) and mediates ubiquitination of sumoylated substrates (By similarity). The regulation of the BMP-SMAD signaling is however independent of sumoylation and is not dependent of SUMO interaction motifs (SIMs) (By similarity).
The RING-type zinc finger mediates the E3 ubiquitin-protein ligase activity and binds directly to free ubiquitin (By similarity). Non-covalent ubiquitin-binding stabilizes the ubiquitin-conjugating enzyme E2 (donor ubiquitin) in the 'closed' conformation and stimulates ubiquitin transfer (By similarity).
The SUMO interaction motifs (SIMs) mediates the binding to polysumoylated substrate.
Belongs to the cyclic nucleotide phosphodiesterase family. PDE1 subfamily.
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.
The protein contains 2 transactivation domains (TAD). Each of these domains may be required for transcriptional activation of a subset of target genes.
Transcription regulator that syncronizes transcriptional and translational programs to promote macrophage invasion of tissues.
Belongs to the 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.
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.
Positively regulates T-cell receptor signaling. Required for optimal conjugation between T-cells and antigen-presenting cells (By similarity).
Component of the SMC5-SMC6 complex, that promotes sister chromatid alignment after DNA damage and facilitates double-stranded DNA breaks (DSBs) repair via homologous recombination between sister chromatids.
Key negative regulator of Shh signaling during neural tube development. Recruited to primary cilia and acts as a regulator of the PKA-dependent basal repression machinery in Shh signaling by increasing cAMP levels, leading to promote the PKA-dependent processing of gli3 into gli3r and repress the Shh signaling. In presence of shh, it is removed from primary cilia, preventing its activity and allowing activation of the Shh signaling (By similarity).
Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. EF-Tu/EF-1A subfamily.
This protein promotes the GTP-dependent binding of aminoacyl-tRNA to the A-site of ribosomes during protein biosynthesis.
Interacts with bmp2; the interaction is blocked in presence of nog.
May act as a tumor suppressor. Cytokine that has an axial patterning activity. Acts like bone morpho-genetic protein (BMP) antagonist in embryonic explants. Blocks the bmp2 activity (By similarity).
Belongs to the class I-like SAM-binding methyltransferase superfamily. Cation-dependent O-methyltransferase family.
Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones.
Maternally and zygotically expressed. Zygotic expression increases after gastrula stage. Expressed predominantly in the endoderm.
Receptor for R-spondins that potentiates the canonical Wnt signaling pathway and acts as a stem cell marker of the intestinal epithelium and the hair follicle. Upon binding to R-spondins (RSPO1, RSPO2, RSPO3 or RSPO4), associates with phosphorylated LRP6 and frizzled receptors that are activated by extracellular Wnt receptors, triggering the canonical Wnt signaling pathway to increase expression of target genes. In contrast to classical G-protein coupled receptors, does not activate heterotrimeric G-proteins to transduce the signal. Involved in the development and/or maintenance of the adult intestinal stem cells during postembryonic development.
Belongs to the mitochondrion-specific ribosomal protein mL41 family.
Component of a ribonucleoprotein (RNP) complex, at least composed of cpeb1, lsm14b/rap55b, ddx6/Xp54, ybx2/frgy2, pat1/P100, eif4enif1/4E-T and eif4e1b. Different translationally-repressed mRNP complexes probably exist that contain either lsm14a/rap55a or lsm14b/rap55b depending on the developmental stage. Component of a ribonucleoprotein (RNP) complex, composed at least of elavl1/elrA and/or elavl2/elrB, igf2bp3/vg1RBP, ddx6/Xp54, ybx2/frgy2, lsm14b/rap55b and, in a subset of RNP complexes, stau1/staufen (By similarity).
May be involved in the storage of translationally inactive mRNAs and protect them from degradation (By similarity). Plays a role in control of mRNA translation (By similarity).
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 carnitine/choline acetyltransferase family.
Involved in the intramitochondrial synthesis of acylcarnitines from accumulated acyl-CoA metabolites. Reconverts acylcarnitines back into the respective acyl-CoA esters that can then undergo beta-oxidation, an essential step for the mitochondrial uptake of long-chain fatty acids and their subsequent beta-oxidation in the mitochondrion. Active with medium (C8-C12) and long-chain (C14-C18) acyl-CoA esters.
Arginine methyltransferase involved in the assembly or stability of mitochondrial NADH:ubiquinone oxidoreductase complex (complex I). Acts by mediating symmetric dimethylation of 'Arg-118' of ndufs2 after it assembles into the complex I, stabilizing the early intermediate complex.
Belongs to the paired homeobox family. Bicoid subfamily.
Belongs to the TGF-beta family. GDNF subfamily.
Neurotrophic factor that enhances survival and morphological differentiation of dopaminergic neurons and increases their high-affinity dopamine uptake.
Belongs to the proteasome inhibitor PI31 family.
DNA helicase that modulates androgen receptor (AR)-dependent transactivation in a promoter-dependent manner.
Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs are known to be important for the association with nuclear receptors.
May be required for efficient PLK4 centrosomal localization and PLK4-induced overduplication of centrioles. May play a role in cilium biogenesis.
In the central section; belongs to the metallo-dependent hydrolases superfamily. DHOase family. CAD subfamily.
Identified in the CTLH complex that contains at least MAEA, RMND5A (or alternatively its paralog RMND5B), GID8, WDR26, and RANBP9 and/or RANBP10.
May act as scaffolding protein, and as adapter protein to couple membrane receptors to intracellular signaling pathways. Acts as a mediator of cell spreading and actin cytoskeleton rearrangement. Core component of the CTLH E3 ubiquitin-protein ligase complex that mediates ubiquitination and subsequent proteasomal degradation of target proteins.
Belongs to the polypeptide deformylase family.
Removes the formyl group from the N-terminal Met of newly synthesized proteins.
May play an essential role for the assembly of the mitochondrial F1-F0 complex.
Part of the gamma-tubulin complex. Interacts with TUBG1 (By similarity).
Belongs to the proteasome subunit S5A family.
Possible splicing regulator involved in the control of cellular survival.
Belongs to the lipase maturation factor family.
Involved in the maturation of specific proteins in the endoplasmic reticulum.
Belongs to the peptidase C19 family. PAN2 subfamily.
Binds 2 metal cations per subunit in the catalytic exonuclease domain.
Catalytic subunit of the poly(A)-nuclease (PAN) deadenylation complex, one of two cytoplasmic mRNA deadenylases involved in general and miRNA-mediated mRNA turnover. PAN specifically shortens poly(A) tails of RNA and the activity is stimulated by poly(A)-binding protein (PABP). PAN deadenylation is followed by rapid degradation of the shortened mRNA tails by the CCR4-NOT complex. Deadenylated mRNAs are then degraded by two alternative mechanisms, namely exosome-mediated 3'-5' exonucleolytic degradation, or deadenlyation-dependent mRNA decaping and subsequent 5'-3' exonucleolytic degradation by XRN1.
Contains a pseudo-UCH domain. This ubiquitin C-terminal hydrolase (UCH)-like or ubiquitin specific protease (USP)-like domain is predicted to be catalytically inactive because it lacks the active site catalytic triad characteristic of thiol proteases, with residues at the equivalent structural positions that are incompatible with catalysis, and it cannot bind ubiquitin. It functions as a structural scaffold for intra- and intermolecular interactions in the complex.
Forms a heterotrimer with an asymmetric homodimer of the regulatory subunit PAN3 to form the poly(A)-nuclease (PAN) deadenylation complex.
Positively regulated by the regulatory subunit PAN3.
The linker, or PAN3 interaction domain (PID), between the WD40 repeats and the pseudo-UCH domain mediates interaction with PAN3.
Acts as component of the retromer cargo-selective complex (CSC). The CSC is believed to be the core functional component of retromer or respective retromer complex variants acting to prevent missorting of selected transmembrane cargo proteins into the lysosomal degradation pathway. Retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN).
Component of the heterotrimeric retromer cargo-selective complex (CSC) which is believed to associate with variable sorting nexins to form functionally distinct retromer complex variants.
Belongs to the AAA ATPase family. MSP1 subfamily.
Outer mitochondrial translocase required to remove mislocalized tail-anchored transmembrane proteins on mitochondria (By similarity). Specifically recognizes and binds tail-anchored transmembrane proteins: acts as a dislocase that mediates the ATP-dependent extraction of mistargeted tail-anchored transmembrane proteins from the mitochondrion outer membrane (By similarity). Also plays a critical role in regulating the surface expression of AMPA receptors (AMPAR), thereby regulating synaptic plasticity and learning and memory (By similarity).
Plays a role as translation enhancer and involved in cell cycle regulation.
The PUA RNA-binding domain is critical for cap binding, but not sufficient for translation enhancer function.
Belongs to the complex I subunit 5 family.
Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor. Essential for the catalytic activity and assembly of complex I.
Belongs to the grh/CP2 family. CP2 subfamily.
Component of the multiprotein chromatin-remodeling complexes SWI/SNF. Component of neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex) (By similarity). Component of the BAF (SWI/SNF) chromatin remodeling complex. Component of the SWI/SNF-B (PBAF) chromatin remodeling complex. Binds to double-stranded DNA (By similarity).
Involved in chromatin-remodeling. Core component of the BAF (SWI/SNF) complex. This ATP-dependent chromatin-remodeling complex plays important roles in cell proliferation and differentiation, in cellular antiviral activities and inhibition of tumor formation. Belongs to the neural progenitors-specific chromatin remodeling complex (npBAF complex) and the neuron-specific chromatin remodeling complex (nBAF complex) and may play a role in neural development (By similarity).
The N-terminal DNA-binding region is structurally similar to winged helix domains.
Homodimer; disulfide-linked. Seems to also exist as monomers.
Regulator of G protein-coupled receptor (GPCR) signaling. Probably acts by regulating the activity of some 'R7' family protein (RGS6, RGS7, RGS9 and/or RGS11).
May play a role in the regulation of insulin-dependent IRS1 tyrosine phosphorylation in adipocytes.
Belongs to the ubiquitin-activating E1 family. ULA1 subfamily.
Regulatory subunit of the dimeric UBA3-NAE1 E1 enzyme. E1 activates NEDD8 by first adenylating its C-terminal glycine residue with ATP, thereafter linking this residue to the side chain of the catalytic cysteine, yielding a NEDD8-UBA3 thioester and free AMP. E1 finally transfers NEDD8 to the catalytic cysteine of UBE2M.
Belongs to the small GTPase superfamily. Ras family.
Receptor for neuropeptide Y and peptide YY. The activity of this receptor is mediated by G proteins that inhibit adenylate cyclase activity. Seems to be associated with food intake. Could be involved in feeding disorders.
Expressed around the blastopore through gastrula stages. Expressed in the neural tube (posterior dorsal neuroectoderm and the posterior ventral ectoderm) at late neurula stage 20. Expressed in the posterior tip of the neural tube and the posterior wall of the neuroenteric canal at tail bud stage 30. Expressed in the developing gut at stage 40.
Plays a role in transcriptional regulation. Involved in activated KRAS-mediated transcriptional activation of PRKD1. Binds to the PRKD1 promoter. Could play a role in the terminal differentiation of the intestine. Binds preferentially to methylated DNA.
Belongs to the glycosyltransferase 8 family.
Belongs to the indoleamine 2,3-dioxygenase family.
Belongs to the chloride channel (TC 2.A.49) family.
Part of TORC1 complex. Part of the TORC2 complex.
Part of the mechanistic target of rapamycin complex 1 (mTORC1) which contains MTOR, MLST8 and RPTOR. Part of the mechanistic target of rapamycin complex 2 (mTORC2) which contains MTOR, MLST8, PRR5, RICTOR, MAPKAP1 and DEPTOR.
Subunit of TORC1 and TORC2, which regulate cell growth and survival in response to nutrient and hormonal signals.
Subunit of both mTORC1 and mTORC2, which regulates cell growth and survival in response to nutrient and hormonal signals. mTORC1 is activated in response to growth factors or amino acids. In response to nutrients, mTORC1 is recruited to the lysosome membrane and promotes protein, lipid and nucleotide synthesis by phosphorylating several substrates, such as ribosomal protein S6 kinase (RPS6KB1 and RPS6KB2) and EIF4EBP1 (4E-BP1). In the same time, it inhibits catabolic pathways by phosphorylating the autophagy initiation components ULK1 and ATG13, as well as transcription factor TFEB, a master regulators of lysosomal biogenesis and autophagy. The mTORC1 complex is inhibited in response to starvation and amino acid depletion. Within mTORC1, LST8 interacts directly with MTOR and enhances its kinase activity. In nutrient-poor conditions, stabilizes the MTOR-RPTOR interaction and favors RPTOR-mediated inhibition of MTOR activity. mTORC2 is also activated by growth factors, but seems to be nutrient-insensitive. mTORC2 seems to function upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors. mTORC2 promotes the serum-induced formation of stress-fibers or F-actin.
Regulates the activity of L-type calcium channels that contain CACNA1C as pore-forming subunit (By similarity). Regulates the trafficking and gating properties of AMPA-selective glutamate receptors (AMPARs). Promotes their targeting to the cell membrane and synapses and modulates their gating properties by slowing their rates of activation, deactivation and desensitization and by mediating their resensitization. Shows specificity only for GRIA1 and GRIA2.
Belongs to the bacterial ribosomal protein bL33 family.
PP1 comprises a catalytic subunit, and one or several targeting or regulatory subunits.
May play a role in microtubule-mediated transport or vesicle function.
Extracellular matrix serine protease that plays a role in layering of neurons in the cerebral cortex and cerebellum. Regulates microtubule function in neurons and neuronal migration. Affects migration of sympathetic preganglionic neurons in the spinal cord, where it seems to act as a barrier to neuronal migration. Enzymatic activity is important for the modulation of cell adhesion. Binding to the extracellular domains of lipoprotein receptors VLDLR and LRP8/APOER2 induces tyrosine phosphorylation of DAB1 and modulation of TAU phosphorylation.
Oligomer of disulfide-linked homodimers. Binds to the ectodomains of VLDLR and LRP8/APOER2.
Expressed both maternally and zygotically.
Forms a repression complex on the promoters of the nodal/nr1 and siamois genes with the maternal factors tcf7l1/tcf3 and pouf5.1/oct-25. Interacts (via C-terminus) with tcf7l1/tcf3 (via N-terminus). Also interacts with the other POU-domain transcription factors pou5f1.2/oct-91 and pou5f1.3/oct-60 (By similarity).
Transcription factor required for both mesoderm and endoderm formation in the embryo; signaling determinants and concentration levels may determine which germ layer is formed. Acts together with beta-catenin to activate genes that are responsible for mesoderm induction including wnt-8, eomes t/bra, siamois, mix1 and sox17. Directly binds to promoter DNA. Patterns the mesoderm along the dorsoventral and posterior axis. Activates siamois gene transcription when alone or in combination with beta-catenin, but inhibits siamois transcription in combination with pou5f1.1/oct-25 (By similarity).
Vegetally localized in oocytes and expressed in the presumptive endoderm and mesoderm at early gastrula stage. Expression is down-regulated in the endoderm by the end of gastrulation but maintained in the lateral and ventral mesoderm of the blastopore lip.
Regulates localization of phosphatidylinositol 4-kinase (PI4K) to the plasma membrane.
RNA-binding component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is involved in protein synthesis of a specialized repertoire of mRNAs and, together with other initiation factors, stimulates binding of mRNA and methionyl-tRNAi to the 40S ribosome. The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation.
Belongs to the peptidase C12 family. BAP1 subfamily.
Deubiquitinating enzyme that plays a key role in chromatin by mediating deubiquitination of histone H2A. Catalytic component of the PR-DUB complex, a complex that specifically mediates deubiquitination of histone H2A monoubiquitinated at 'Lys-119' (H2AK119ub1) (By similarity).
Belongs to the acetyltransferase family. GNAT subfamily.
May act as an inhibitor of TGF-beta signaling.
Phosphorylates Ins(1,3,4,5,6)P5 at position 2 to form Ins(1,2,3,4,5,6)P6 (InsP6 or phytate).
The EXKPK motif is conserved in inositol-pentakisphosphate 2-kinases of both family 1 and 2.
Belongs to the zinc-containing alcohol dehydrogenase family. Class-III subfamily.
The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes.
Subunit of non-clathrin- and clathrin-associated adaptor protein complex 3 (AP-3) that plays a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or endosomes. The AP complexes mediate both the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules. AP-3 appears to be involved in the sorting of a subset of transmembrane proteins targeted to lysosomes and lysosome-related organelles. In concert with the BLOC-1 complex, AP-3 is required to target cargos into vesicles assembled at cell bodies for delivery into neurites and nerve terminals.
Adapter molecule that plays a key role in the activation of pro-inflammatory NF-kappa-B signaling following detection of bacterial pathogen-associated molecular pattern metabolites (PAMPs) (By similarity). Promotes activation of an innate immune response by inducing the oligomerization and polyubiquitination of TRAF6, which leads to the activation of TAK1 and IKK through a proteasome-independent mechanism (By similarity).
Belongs to the archaeal rpoM/eukaryotic RPA12/RPB9/RPC11 RNA polymerase family.
Component of the RNA polymerase I (Pol I) complex consisting of at least 13 subunits.
DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase I which synthesizes ribosomal RNA precursors.
Belongs to the mitochondrion-specific ribosomal protein mS33 family.
Belongs to the WD repeat coronin family.
Belongs to the eukaryotic RPB7/RPC8 RNA polymerase subunit family.
DNA-dependent RNA polymerase which catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates.
Interacts with sae2, ube2i, ranbp2, pias1 and pias2 (By similarity). Interacts with sox9 and sox10 (By similarity). Covalently attached to a number of proteins (By similarity).
Ubiquitin-like protein that can be covalently attached to proteins as a monomer or a lysine-linked polymer (By similarity). Covalent attachment via an isopeptide bond to its substrates requires prior activation by the E1 complex sae1-sae2 and linkage to the E2 enzyme ube2i. This post-translational modification on lysine residues of proteins plays a crucial role in a number of cellular processes such as nuclear transport, DNA replication and repair, mitosis and signal transduction. Polymeric sumo1 chains are also susceptible to polyubiquitination which functions as a signal for proteasomal degradation of modified proteins (By similarity).
Component of complex II composed of four subunits: the flavoprotein (FP) SDHA, iron-sulfur protein (IP) SDHB, and a cytochrome b560 composed of SDHC and SDHD.
Membrane-anchoring subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q).
Belongs to the replication factor A protein 3 family.
Catalyzes the transfer of a dimethylallyl group onto the adenine at position 37.
Inhibits amyloid precursor protein processing, probably by blocking BACE1 activity.
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.
Component of the PAF1 complex (By similarity). Component of the SKI complex (By similarity).
Component of the PAF1 complex (PAF1C) which has multiple functions during transcription by RNA polymerase II and is implicated in regulation of development and maintenance of embryonic stem cell pluripotency. PAF1C associates with RNA polymerase II through interaction with POLR2A CTD non-phosphorylated and 'Ser-2'- and 'Ser-5'-phosphorylated forms and is involved in transcriptional elongation, acting both independently and synergistically with TCEA1 and in cooperation with the DSIF complex and HTATSF1. Also acts as a component of the SKI complex, a multiprotein complex that assists the RNA-degrading exosome during the mRNA decay and quality-control pathways. The SKI complex catalyzes mRNA extraction from 80S ribosomal complexes in the 3'-5' direction and channels mRNA to the cytosolic exosome for degradation.
RNA-binding protein implicated in the regulation of several post-transcriptional events. May be involved in pre-mRNA alternative splicing, mRNA translation repression and stability (By similarity).
Mitochondrial intermembrane chaperone that participates in the import and insertion of some multi-pass transmembrane proteins into the mitochondrial inner membrane. Also required for the transfer of beta-barrel precursors from the TOM complex to the sorting and assembly machinery (SAM complex) of the outer membrane. Acts as a chaperone-like protein that protects the hydrophobic precursors from aggregation and guide them through the mitochondrial intermembrane space.
The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space.
Belongs to the DNA polymerase epsilon subunit B family.
Participates in DNA repair and in chromosomal DNA replication.
Belongs to the synaptophysin/synaptobrevin family.
Receptor for inositol 1,4,5-trisphosphate, a second messenger that mediates the release of intracellular calcium.
The receptor contains a calcium channel in its C-terminal extremity. Its large N-terminal cytoplasmic region has the ligand-binding site in the N-terminus and modulatory sites in the middle portion immediately upstream of the channel region.
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. Able to cleave wnt8. Required for head formation.
Was named TIKI in reference to large-headed humanoid in Polynesian mythology.
Probable peripherally associated component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids (By similarity).
Probable peripherally associated component of the endosomal sorting required for transport complex III (ESCRT-III).
Belongs to the POU transcription factor family. Class-2 subfamily.
Probable mitochondrial transporter required for glutathione import into mitochondria. Glutathione, which plays key roles in oxidative metabolism, is produced exclusively in the cytosol and is imported in many organelles (By similarity). Mitochondrial glutathione is required for the activity and stability of proteins containing iron-sulfur clusters (By similarity).
May be involved in the transcriptional activity of NFKB1. May regulate WWOX role as tumor suppressor.
Negatively regulates TGF-beta signaling.
Protein O-mannose kinase that specifically mediates phosphorylation at the 6-position of an O-mannose of the trisaccharide (N-acetylgalactosamine (GalNAc)-beta-1,3-N-acetylglucosamine (GlcNAc)-beta-1,4-mannose) to generate phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-beta-1,3-N-acetylglucosamine-beta-1,4-(phosphate-6-)mannose). Phosphorylated O-mannosyl trisaccharide is a carbohydrate structure present in alpha-dystroglycan (DAG1), which is required for binding laminin G-like domain-containing extracellular proteins with high affinity. Only shows kinase activity when the GalNAc-beta-3-GlcNAc-beta-terminus is linked to the 4-position of O-mannose, suggesting that this disaccharide serves as the substrate recognition motif.
Belongs to the glycosyltransferase 11 family.
Transcription factor. Essential for ventral specification of the early cephalic (head) ectoderm during gastrulation, playing a role in the 'non-neural' versus 'neural' cell fate choice. Binds to DNA via the target sequence 5'-[AG]TAAA[CT]A-3', with 5'-ATAAACA-3' being the preferred binding site (By similarity).
Transfers N-acetylgalactosamine (GalNAc) from UDP-GalNAc to N-acetylglucosamine-beta-benzyl with a beta-1,4-linkage to form N,N'-diacetyllactosediamine, GalNAc-beta-1,4-GlcNAc structures in N-linked glycans and probably O-linked glycans.
Belongs to the eukaryotic-type primase small subunit family.
Belongs to the complex I NDUFB4 subunit 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 HAD-like hydrolase superfamily. EYA family.
Activated by phosphorylation on Thr-201 during M phase.
Interacts with plk1 and kif2a. Interacts with fbxo5.
Plays multiple essential roles during mitosis. Phosphorylates the N-terminal domain of cdc25, which leads to cyclin b-cdc2 activation and mitotic entry. Also required for organization of bipolar spindles, and for exit from mitosis. Phosphorylates tpx2 (By similarity).
Protein levels are down-regulated by proteasomal degradation in anaphase.
Belongs to the dynein intermediate chain family.
Belongs to the glycosyl hydrolase 18 family.
Belongs to the cytochrome c oxidase subunit 6B.
Belongs to the methyltransferase superfamily. NTM1 family.
Distributive alpha-N-methyltransferase that methylates the N-terminus of target proteins containing the N-terminal motif [Ala/Gly/Pro/Ser]-Pro-Lys when the initiator Met is cleaved. Specifically catalyzes mono-, di- or tri-methylation of the exposed alpha-amino group of the Ala, Gly or Ser residue in the [Ala/Gly/Ser]-Pro-Lys motif and mono- or di-methylation of Pro in the Pro-Pro-Lys motif. Required during mitosis for normal bipolar spindle formation and chromosome segregation via its action on target proteins.
Belongs to the inositol 3,4-bisphosphate 4-phosphatase family.
Belongs to the DEAD box helicase family. DDX41 subfamily.
Belongs to the TDD superfamily. DTWD1 family.
Catalyzes the formation of 3-(3-amino-3-carboxypropyl)uridine (acp3U) at position 20 in the D-loop of several cytoplasmic tRNAs (acp3U(20)).
Belongs to the PC-esterase family. CASD1 subfamily.
Belongs to the myo-inositol oxygenase family.
The tandem UIM domains form a continuous 60 Angstrom-long alpha-helix and mediate binding to 'Lys-63'-linked ubiquitins. UIM1 and UIM2 bind to the proximal and distal ubiquitin moieties and recognize an 'Ile-44'-centered hydrophobic patch. Since UIMs don't interact with the 'Lys-63' isopeptide bond the UIM-linker region between the 2 UIM domains determines the selectivity for 'Lys-63'-linkage, and its length is very important for specificity (By similarity).
Ubiquitin-binding protein that specifically recognizes and binds 'Lys-63'-linked ubiquitin. Plays a central role in the BRCA1-A complex by specifically binding 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the brca1-bard1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). The BRCA1-A complex also possesses deubiquitinase activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX. Also weakly binds monoubiquitin but with much less affinity than 'Lys-63'-linked ubiquitin (By similarity).
Belongs to the pseudouridine synthase TruD family.
Belongs to the WD repeat G protein beta family. Ribosomal protein RACK1 subfamily.
Belongs to the D-glutamate cyclase family.
Belongs to the round spermatid basic protein 1 family.
Lysine-specific demethylase that specifically demethylates methylated lysine residues of proteins.
Belongs to the grh/CP2 family. Grainyhead subfamily.
GRHL genes (GRHL1, GRHL2 and GRHL3) show a paradoxal lack of redundancy despite their extensive sequence identity in the DNA-binding and protein dimerization domains and the fact that the core consensus DNA binding sites are identical. They have related but remarkably different functions during embryogenesis because of their differential spatiotemporal expression patterns during development.
Transcription factor playing an important role in primary neurulation and in epithelial development. Binds directly to the consensus DNA sequence 5'-AACCGGTT-3' acting as an activator and repressor on distinct target genes.
Forms a complex composed of PDGFRL, TNK2 and GRB2.
Component of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histone H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. Component of HBO1 complexes, which specifically mediate acetylation of histone H3 at 'Lys-14' (H3K14ac), and have reduced activity toward histone H4. Component of the MOZ/MORF complex which has a histone H3 acetyltransferase activity (By similarity).
Component of the NuA4 histone acetyltransferase complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histone H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. Component of HBO1 complexes, which specifically mediate acetylation of histone H3 at 'Lys-14' (H3K14ac), and have reduced activity toward histone H4. Component of the MOZ/MORF complex which has a histone H3 acetyltransferase activity.
Component of the NuA4 histone acetyltransferase complex. Component of the hbo1 complex. Component of the moz/morf complex (By similarity).
Component of the NuA4 histone acetyltransferase complex. Component of the hbo1 complex. Component of the moz/morf complex.
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 peptidase C19 family. USP47 subfamily.
Ubiquitin-specific protease that specifically deubiquitinates monoubiquitinated DNA polymerase beta (polb), stabilizing polb thereby playing a role in base-excision repair (BER).
Belongs to the N-acetylmuramoyl-L-alanine amidase 2 family.
Innate immunity protein that plays several important functions in antimicrobial and antitumor defense systems.
Belongs to the clathrin heavy chain family.
Transcriptional repressor. Binds with MAX to form a sequence-specific DNA-binding protein complex which recognizes the core sequence 5'-CAC[GA]TG-3' (By similarity).
Belongs to the chloride channel MCLC family.
Belongs to the short-chain dehydrogenases/reductases (SDR) family. ERG27 subfamily.
Multidrug efflux pump that functions as a H(+)/organic cation antiporter. Mediates the secretion of cationic compounds including drugs, toxins and endogenous metabolites. Plays a role physiological role in the excretion of drugs, toxins and endogenous metabolites through the kidney and liver, into urine and bile respectively.
In the C-terminal section; belongs to the peptidyl-alpha-hydroxyglycine alpha-amidating lyase family.
In the N-terminal section; belongs to the copper type II ascorbate-dependent monooxygenase family.
Metallocarboxypeptidase that mediates protein deglutamylation of tubulin and non-tubulin target proteins. Catalyzes the removal of polyglutamate side chains present on the gamma-carboxyl group of glutamate residues within the C-terminal tail of alpha- and beta-tubulin. Specifically cleaves tubulin long-side-chains, while it is not able to remove the branching point glutamate. Also catalyzes the removal of polyglutamate residues from the carboxy-terminus of alpha-tubulin as well as non-tubulin proteins.
Component of ribosome-associated complex (RAC).
Component of the ribosome-associated complex (RAC), a complex involved in folding or maintaining nascent polypeptides in a folding-competent state.
Acts as a negative mediator of apoptosis.
Probable component of a centromeric complex involved in assembly of kinetochore proteins, mitotic progression and chromosome segregation.
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.
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.
Belongs to the calcium channel beta subunit family.
Belongs to the glutamine synthetase family.
Belongs to the protein sulfotransferase family.
Catalyzes the O-sulfation of tyrosine residues within acidic motifs of polypeptides, using 3'-phosphoadenylyl sulfate (PAPS) as cosubstrate.
Part of the multisubunit TRAPP (transport protein particle) complex.
Homodimer or homotetramer; both forms have similar enzymatic activities.
Belongs to the complex I NDUFA2 subunit 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.
Autoubiquitinated. Ubiquitinated by SH3RF2, leading to proteasome-mediated degradation.
Has E3 ubiquitin-protein ligase activity. In the absence of an external substrate, it can catalyze self-ubiquitination. Acts as a scaffold protein that contributes to the effective activation of the JNK signaling pathway.
The RING finger domain is required for ubiquitin ligase activity and autoubiquitination.
Acts as a co-chaperone with HSPA8/Hsc70; required to promote protein folding and trafficking, prevent aggregation of client proteins, and promote unfolded proteins to endoplasmic reticulum-associated degradation (ERAD) pathway. Acts by determining hspa8/Hsc70's ATPase and polypeptide-binding activities. Can also act independently of hspa8/Hsc70: together with dnajb12, acts as a chaperone that promotes maturation of potassium channels by stabilizing nascent channel subunits and assembling them into tetramers. While stabilization of nascent channel proteins is dependent on hspa8/Hsc70, the process of oligomerization of channel subunits is independent of hspa8/Hsc70.
Belongs to the DnaJ family. DNAJB12/DNAJB14 subfamily.
Homodimeric or heterodimeric through association with alpha and beta subunits, linked by one or more disulfide bonds. Inhibins are heterodimers of one alpha and one beta subunit. Activins are homo- or heterodimers of beta subunits only.
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 WD repeat WDR5/wds family.
Contributes to histone modification. May position the N-terminus of histone H3 for efficient trimethylation at 'Lys-4'. As part of the MLL1/MLL complex it is involved in methylation and dimethylation at 'Lys-4' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. As part of the NSL complex it may be involved in acetylation of nucleosomal histone H4 on several lysine residues. May regulate osteoblasts differentiation (By similarity).
Interacts with HCFC1. Probable component of complexes involved in histone modification such as the MLL1/MLL complex and the NSL complex.
Belongs to the GTP cyclohydrolase I family.
Belongs to the TALE/MEIS homeobox family.
Belongs to the glyceraldehyde-3-phosphate dehydrogenase family.
Belongs to the AB hydrolase superfamily. AB hydrolase 4 family.
Belongs to the peptidase C78 family. ZUFSP subfamily.
Probable hormone that may attenuate cell proliferation and induce senescence in the central nervous system.
Generally pentameric. There are five types of GABA(A) receptor chains: alpha, beta, gamma, delta, and rho. Interacts with SQSTM1.
Transcription factor involved in chondrocytes differentiation and cartilage formation. Specifically binds the 5'-AACAAT-3' DNA motif present in enhancers and super-enhancers and promotes expression of genes important for chondrogenesis. Required for overt chondrogenesis when condensed prechondrocytes differentiate into early stage chondrocytes: sox5 and sox6 cooperatively bind with sox9 on active enhancers and super-enhancers associated with cartilage-specific genes, and thereby potentiate sox9's ability to transactivate. Not involved in precartilaginous condensation, the first step in chondrogenesis, during which skeletal progenitors differentiate into prechondrocytes.
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 bacterial ribosomal protein bL17 family.
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 potassium channel family. D (Shal) (TC 1.A.1.2) subfamily. Kv4.2/KCND2 sub-subfamily.
The active site is a redox-active disulfide bond.
Belongs to the aggrecan/versican proteoglycan family.
Acts partially redundantly with other irx members in neural patterning. Required for formation of the posterior forebrain, midbrain, hindbrain, and to a lesser extent, spinal cord. Both up-regulates and down-regulates gene expression during neural development. Acts early in neural plate development to induce proneural gene expression and specify a neural precursor state. Also up-regulates repressors that prevent neuronal differentiation. Required during at least two stages of pronephros kidney development; during neurula stages, maintains transcription of key renal genes to define the size and identity of the pronephric anlage, probably in part through regulation of bmp-signaling. Subsequently required for proper formation of the intermediate tubule segment of the pronephros.
Expressed in the neural plate in overlapping patterns with other irx members, which all share an anterior border of expression. Outside the nervous system and at tailbud stages, expressed in the developing otic vesicle, branchial arches, prospective heart region and pronephros.
Belongs to the copper type II ascorbate-dependent monooxygenase family.
AP-1 family transcription factor that controls the differentiation of lineage-specific cells in the immune system: specifically mediates the differentiation of T-helper 17 cells (Th17), follicular T-helper cells (TfH), CD8(+) dendritic cells and class-switch recombination (CSR) in B-cells.
Catalyzes a base-exchange reaction in which the polar head group of phosphatidylethanolamine (PE) is replaced by L-serine.
Catalyzes a base-exchange reaction in which the polar head group of phosphatidylethanolamine (PE) or phosphatidylcholine (PC) is replaced by L-serine (By similarity). Catalyzes the conversion of phosphatatidylethanolamine and does not act on phosphatidylcholine (By similarity). Can utilize both phosphatidylethanolamine (PE) plasmalogen and diacyl PE as substrate and the latter is six times better utilized, indicating the importance of an ester linkage at the sn-1 position (By similarity). Although it shows no sn-1 fatty acyl preference, exhibits significant preference towards docosahexaenoic acid (22:6n-3) compared with 18:1 or 20:4 at the sn-2 position (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.
Belongs to the universal ribosomal protein uL3 family.
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 eukaryotic ribosomal protein eS12 family.
Belongs to the protein kinase superfamily. Tyr protein kinase family. ROR subfamily.
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 eukaryotic ATPase epsilon family.
Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core, and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Part of the complex F(1) domain and of the central stalk which is part of the complex rotary element. Rotation of the central stalk against the surrounding alpha(3)beta(3) subunits leads to hydrolysis of ATP in three separate catalytic sites on the beta subunits.
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.
May control cell migration by relaying extracellular chemotactic signals to the microtubule cytoskeleton. Mediator of ERBB2 signaling (By similarity).
Forms part of a macromolecular complex that catalyzes the attachment of specific amino acids to cognate tRNAs during protein synthesis.
Monomer; also part of a multisubunit complex that groups tRNA ligases for Arg, Asp, Glu, Gln, Ile, Leu, Lys, Met and Pro.
The alpha-helical N-terminus (residues 1-72) mediates interaction with AIMP1 and thereby contributes to the assembly of the multisynthetase complex.
Belongs to the GHMP kinase family. GalK subfamily.
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.
Proteolytically cleaved by a furin-like convertase to generate a persistent C-terminal fragment found in almost the entire cartilage matrix, and affecting osteoblast differentiation.
Belongs to the avidin/streptavidin family.
Belongs to the glycosyl hydrolase 56 family.
Belongs to the 'GDSL' lipolytic enzyme family. Phospholipase B1 subfamily.
Involved in the biogenesis of the 60S ribosomal subunit in the nucleus.
Belongs to the MICOS complex subunit Mic19 family. Metazoan Mic25 subfamily.
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.
May play a role in membrane regeneration and repair.
Belongs to the ubiquitin-conjugating enzyme family. FTS subfamily.
Lacks the conserved Cys residue necessary for ubiquitin-conjugating enzyme E2 activity.
May function to promote vesicle trafficking and/or fusion. May also regulate apoptosis (By similarity).
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.
Belongs to the universal ribosomal protein uS2 family.
Belongs to the thiolase-like superfamily. HMG-CoA synthase family.
Catalyzes the condensation of acetyl-CoA with acetoacetyl-CoA to form HMG-CoA.
Essential for Wnt/beta-catenin-mediated formation of the Spemann organizer and for induction of the organizer precursor, the Nieuwkoop center. Acts as a transcriptional activator, cooperating with TGFbeta signals to induce a program of organizer-specific gene expression and to generate an organizer with both head- and trunk-inducing activity. Activates the head organizer gene cer1 by acting synergistically with otx2 and mix-A/mix.1 through the 5'-TAATCT-3' element of the cer1 promoter. Also binds as a complex with lhx1/lim1 and mix-A/mix.1 to the 3x 5'-TAAT-3' element of the cer1 promoter. Required for subsequent dorsoventral axis formation in the embryo, dorsalizing ventral mesoderm and cooperating with t/bra to induce dorsal mesoderm. Also involved in neural induction, inducing the cement gland and neural tissue in overlying ectoderm. Later in development, has the second function of indirectly repressing ventral genes, probably by activating the expression of a transcriptional repressor (By similarity).
Proposed core component of the chromatin remodeling Ino80 complex which exhibits DNA- and nucleosome-activated ATPase activity and catalyzes ATP-dependent nucleosome sliding.
Belongs to the complex I subunit 4 family.
Belongs to the type II pantothenate kinase family.
In the N-terminal section; belongs to the type II pantothenate kinase family.
Belongs to the NAD(P)-dependent epimerase/dehydratase family. UDP-glucuronic acid decarboxylase subfamily.
Catalyzes the NAD-dependent decarboxylation of UDP-glucuronic acid to UDP-xylose. Necessary for the biosynthesis of the core tetrasaccharide in glycosaminoglycan biosynthesis.
Belongs to the CoA-transferase III family.
Belongs to the ribonucleoside diphosphate reductase large chain family.
Provides the precursors necessary for DNA synthesis. Catalyzes the biosynthesis of deoxyribonucleotides from the corresponding ribonucleotides.
May be involved in N-linked oligosaccharide assembly.
May be involved in N-linked oligosaccharide assembly. May participate in the translocation of oligosaccharide from the cytoplasmic side to the lumenal side of the endoplasmic reticulum membrane (By similarity).
Belongs to the complex I subunit 2 family.
Multifunctional protein that is involved in the regulation of many processes.
Belongs to the tyrosyl-DNA phosphodiesterase family.
Belongs to the eIF-2B gamma/epsilon subunits family.
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).
Part of the endoplasmic reticulum membrane protein complex (EMC) that enables the energy-independent insertion into endoplasmic reticulum membranes of newly synthesized membrane proteins. Preferentially accommodates proteins with transmembrane domains that are weakly hydrophobic or contain destabilizing features such as charged and aromatic residues. Involved in the cotranslational insertion of multi-pass membrane proteins in which stop-transfer membrane-anchor sequences become ER membrane spanning helices. It is also required for the post-translational insertion of tail-anchored/TA proteins in endoplasmic reticulum membranes. By mediating the proper cotranslational insertion of N-terminal transmembrane domains in an N-exo topology, with translocated N-terminus in the lumen of the ER, controls the topology of multi-pass membrane proteins. By regulating the insertion of various proteins in membranes, it is indirectly involved in many cellular processes.
Transposase-derived protein that may have nuclease activity (Potential). Does not have transposase activity.
Belongs to the nucleoporin interacting component (NIC) family.
Plays a role in the nuclear pore complex (NPC) assembly and/or maintenance.
Belongs to the small GTPase superfamily. Ran family.
GTP-binding protein involved in nucleocytoplasmic transport. Required for the import of protein into the nucleus and also for RNA export. Involved in chromatin condensation and control of cell cycle.
GTPase involved in nucleocytoplasmic transport, participating both to the import and the export from the nucleus of proteins and RNAs. Switches between a cytoplasmic GDP- and a nuclear GTP-bound state by nucleotide exchange and GTP hydrolysis. Nuclear import receptors such as importin beta bind their substrates only in the absence of GTP-bound RAN and release them upon direct interaction with GTP-bound RAN, while export receptors behave in the opposite way. Thereby, RAN controls cargo loading and release by transport receptors in the proper compartment and ensures the directionality of the transport. Interaction with RANBP1 induces a conformation change in the complex formed by XPO1 and RAN that triggers the release of the nuclear export signal of cargo proteins. RAN (GTP-bound form) triggers microtubule assembly at mitotic chromosomes and is required for normal mitotic spindle assembly and chromosome segregation. Required for normal progress through mitosis.
Mg(2+) interacts primarily with the phosphate groups of the bound guanine nucleotide.
Monomer. Interacts with rangap1, which promotes ran-mediated GTP hydrolysis. Interacts with kpnb1. Interaction with kpnb1 inhibits rangap1-mediated stimulation of GTPase activity. Interacts with rcc1 which promotes the exchange of ran-bound GDP by GTP. Interaction with kpnb1 inhibits rcc1-mediated exchange of ran-bound GDP by GTP. Interacts (GTP-bound form) with tnpo1; the interaction is direct. Interacts (GTP-bound form) with tnpo3; the interaction is direct. Interacts with kpnb1 and with tnpo1; both inhibit ran GTPase activity. Interacts (via C-terminus) with ranbp1, which alleviates the inhibition of ran GTPase activity. Interacts with rangrf, which promotes the release of bound guanine nucleotide. Rangrf and rcc1 compete for an overlapping binding site on ran. Identified in a complex with kpna2 and cse1l; interaction with ranbp1 mediates dissociation of ran from this complex. Interaction with both ranbp1 and kpna2 promotes dissociation of the complex between ran and kpnb1. Identified in a complex composed of ran, rangap1 and ranbp1. Identified in a complex that contains tnpo1, ran and ranbp1. Identified in a nuclear export complex with xpo1. Interaction with ranbp1 or ranbp2 induces a conformation change in the complex formed by xpo1 and ran that triggers the release of the nuclear export signal of cargo proteins. Component of a nuclear export receptor complex composed of kpnb1, ran, snupn and xpo1 (By similarity).
Belongs to the SRC/p160 nuclear receptor coactivator family.
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.
Binds 1 heme c group covalently per subunit.
Electron carrier protein. The oxidized form of the cytochrome c heme group can accept an electron from the heme group of the cytochrome c1 subunit of cytochrome reductase. Cytochrome c then transfers this electron to the cytochrome oxidase complex, the final protein carrier in the mitochondrial electron-transport chain (By similarity).
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.
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.
Belongs to the WD repeat NOL10/ENP2 family.
Belongs to the activator 1 small subunits family.
Binds 2 divalent metal cations per subunit with RNAase activity being higher in presence of Mn(2+) than of Mg(2+) or Co(2+).
Has 3'-5' poly(A) exoribonuclease activity for synthetic poly(A) RNA substrate. Catalytic component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. During miRNA-mediated repression the complex seems also to act as translational repressor during translational initiation. Additional complex functions may be a consequence of its influence on mRNA expression.
Belongs to the eukaryotic ribosomal protein eS26 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.
Involved in the cytoplasmic maturation steps of pre-60S ribosomal particles by promoting the release of shuttling protein RSL24D1/RLP24 from the pre-ribosomal particles.
Plays an important role in endoplasmic reticulum-associated degradation (ERAD) that mediates ubiquitin-dependent degradation of misfolded endoplasmic reticulum proteins. Involved in inhibition of lipid droplet degradation. Involved in stress granule disassembly.
Contributes to the regulation of the Wnt signaling pathway. Down-regulates CTNNB1-mediated transcriptional activation of target genes. May be involved in neuron differentiation (By similarity).
Contributes to the regulation of the Wnt signaling pathway. Down-regulates CTNNB1-mediated transcriptional activation of target genes. May be involved in neuron differentiation.
Belongs to the eukaryotic ribosomal protein eS7 family.
Belongs to the SEC23/SEC24 family. SEC23 subfamily.
Component of the coat protein complex II (COPII) which promotes the formation of transport vesicles from the endoplasmic reticulum (ER). The coat has two main functions, the physical deformation of the endoplasmic reticulum membrane into vesicles and the selection of cargo molecules.
Belongs to the bacterial ribosomal protein bS18 family. Mitochondrion-specific ribosomal protein mS40 subfamily.
Belongs to the vitamin-B12 dependent methionine synthase family.
Catalyzes the transfer of a methyl group from methylcob(III)alamin (MeCbl) to homocysteine, yielding enzyme-bound cob(I)alamin and methionine in the cytosol. MeCbl is an active form of cobalamin (vitamin B12) used as a cofactor for methionine biosynthesis. Cob(I)alamin form is regenerated to MeCbl by a transfer of a methyl group from 5-methyltetrahydrofolate. The processing of cobalamin in the cytosol occurs in a multiprotein complex composed of at least MMACHC, MMADHC, MTRR (methionine synthase reductase) and MTR which may contribute to shuttle safely and efficiently cobalamin towards MTR in order to produce methionine.
Modular enzyme with four functionally distinct domains. The isolated Hcy-binding domain catalyzes methyl transfer from free methylcobalamin to homocysteine. The Hcy-binding domain in association with the pterin-binding domain catalyzes the methylation of cob(I)alamin by methyltetrahydrofolate and the methylation of homocysteine. The B12-binding domain binds the cofactor. The AdoMet activation domain binds S-adenosyl-L-methionine. Under aerobic conditions cob(I)alamin can be converted to inactive cob(II)alamin. Reductive methylation by S-adenosyl-L-methionine and flavodoxin regenerates methylcobalamin.
Belongs to the AspA/AstE family. Aspartoacylase subfamily.
Plays an important role in deacetylating mercapturic acids in kidney proximal tubules.
Acts as a negative regulator of transcription. May function as a switch in neuronal development (By similarity).
Belongs to the endothelin/sarafotoxin family.
Belongs to the DDOST 48 kDa subunit family.
Subunit of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophosphate to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains, the first step in protein N-glycosylation (By similarity). 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 (By similarity). Required for the assembly of both SST3A- and SS3B-containing OST complexes (By similarity).
Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. WEE1 subfamily.
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 sodium channel (TC 1.A.1.10) family.
Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient.
Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A4 subfamily.
Belongs to the class IV-like SAM-binding methyltransferase superfamily. TRM10 family.
S-adenosyl-L-methionine-dependent guanine N(1)-methyltransferase that catalyzes the formation of N(1)-methylguanine at position 9 (m1G9) in tRNAs. Probably not able to catalyze formation of N(1)-methyladenine at position 9 (m1A9) in tRNAs.
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.
Homodimer; forms a homodimer in absence of cyclic nucleotide (c-di-GMP or cGAMP). Homotetramer; in presence of cyclic nucleotide (c-di-GMP or cGAMP), forms tetramers and higher-order oligomers through side-by-side packing.
In absence of cGAMP, the transmembrane and cytoplasmic regions interact to form an integrated, domain-swapped dimeric assembly (By similarity). In absence of cyclic nucleotide (c-di-GMP or cGAMP), the protein is autoinhibited by an intramolecular interaction between the cyclic dinucleotide-binding domain (CBD) and the C-terminal tail (CTT) (By similarity). Following cGAMP-binding, the cyclic dinucleotide-binding domain (CBD) is closed, leading to a 180 degrees rotation of the CBD domain relative to the transmembrane domain. This rotation is coupled to a conformational change in a loop on the side of the CBD dimer, which leads to the formation of the STING1 tetramer and higher-order oligomers through side-by-side packing (By similarity).
Sensor of cytosolic DNA from bacteria and viruses that promotes autophagy. Acts by recognizing and binding cyclic GMP-AMP (cGAMP), a messenger produced by CGAS in response to DNA in the cytosol (PubMed:26300263, PubMed:30842662). Following cGAMP-binding, promotes the formation of autophagosomes, leading to target cytosolic DNA for degradation by the lysosome (PubMed:30842662). Exhibits guanine base-specific ligand recognition. Binds 3'-3'linked cGAMP, 2'-3' linked cGAMP and 3'-3' linked c-di-GMP with much greater affinity as compared to 3'-3' linked c-di-AMP (PubMed:26300263). Lacks the C-terminal tail (CTT) found in other vertebrate orthologs which is essential for interferon signaling (PubMed:26300263).
The N-terminal domain interacts with glycerophospholipids and phospholipids.
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)).
Belongs to the ferredoxin--NADP reductase type 1 family.
Serves as the first electron transfer protein in all the mitochondrial P450 systems including cholesterol side chain cleavage in all steroidogenic tissues, steroid 11-beta hydroxylation in the adrenal cortex, 25-OH-vitamin D3-24 hydroxylation in the kidney, and sterol C-27 hydroxylation in the liver.
Belongs to the nucleosome assembly protein (NAP) 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 sulfur carrier required for molybdopterin biosynthesis. Component of the molybdopterin synthase complex that catalyzes the conversion of precursor Z into molybdopterin by mediating the incorporation of 2 sulfur atoms into precursor Z to generate a dithiolene group. In the complex, serves as sulfur donor by being thiocarboxylated (-COSH) at its C-terminus by MOCS3. After interaction with MOCS2B, the sulfur is then transferred to precursor Z to form molybdopterin.
Belongs to the MoaD family. MOCS2A subfamily.
C-terminal thiocarboxylation occurs in 2 steps, it is first acyl-adenylated (-COAMP) via the hesA/moeB/thiF part of MOCS3, then thiocarboxylated (-COSH) via the rhodanese domain of MOCS3.
Heterotetramer; composed of 2 small (MOCS2A) and 2 large (MOCS2B) subunits.
This protein is produced by a bicistronic gene which also produces the large subunit (MOCS2B).
GTPase-activating protein that plays a role in the early steps of endocytosis.
Belongs to the ClpA/ClpB family. Torsin subfamily.
Belongs to the small GTPase superfamily. RGK family.
Belongs to the pectinacetylesterase family. Notum subfamily.
In the N-terminal section; belongs to the FGAMS family.
Belongs to the tenascin family. Teneurin subfamily.
Belongs to the ubiquitin-conjugating enzyme family. UEV subfamily.
Belongs to the universal ribosomal protein uL24 family.
IGF-binding proteins prolong the half-life of the IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs on cell culture. They alter the interaction of IGFs with their cell surface receptors (By similarity).
Receptor for MSH (alpha, beta and gamma) and ACTH. The activity of this receptor is mediated by G proteins which activate adenylate cyclase. This receptor is a possible mediator of the immunomodulation properties of melanocortins.
Belongs to the DZIP C2H2-type zinc-finger protein family.
The H protein shuttles the methylamine group of glycine from the P protein to the T protein.
The glycine cleavage system catalyzes the degradation of glycine. The H protein (GCSH) shuttles the methylamine group of glycine from the P protein (GLDC) to the T protein (GCST).
The glycine cleavage system is composed of four proteins: P, T, L and H.
pH-dependent, voltage-insensitive, background potassium channel protein.
Accepts the ubiquitin-like proteins sumo1, sumo2 and sumo3 from the uble1a-uble1b E1 complex and catalyzes their covalent attachment to other proteins with the help of an E3 ligase such as ranbp2 or cbx4. Essential for nuclear architecture and chromosome segregation.
Forms a tight complex with rangap1 and ranbp2. Interacts with sox9 and sox10 (By similarity).
As a component of the AMPAR complex, modifies AMPA receptor (AMPAR) gating.
Belongs to the NADP-dependent oxidoreductase L4BD family.
Belongs to the HIBADH-related family. NP60 subfamily.
Cytokine-like nuclear factor with chromatin gene reader activity involved in chromatin modification and regulation of gene expression. Acts as a nucleosome-destabilizing factor that is recruited to genes during transcriptional activation. Recognizes and binds histone H3 without a preference for specific epigenetic markers and also binds DNA. Interacts with KDM1B and promotes its histone demethylase activity by facilitating the capture of H3 tails, they form a multifunctional enzyme complex that modifies transcribed chromatin and facilitates Pol II transcription through nucleosomes.
Homotetramere. Binds to mononucleosomes.
In the dehydrogenase domain, the conserved NAD(P)H-binding sites and sequence similarity to plant dehydrogenases suggest that this protein may have oxidoreductase activity. However, since the active site is not conserved, the dehydrogenase domain seems to serve as a catalytically inert oligomerization module.
The A.T hook DNA-binding domain is required for the interaction with MAPK14.
The PWWP domain is a H3 reader and strongly binds DNA.
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 glycosyl hydrolase 13 family. GlgB subfamily.
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. GPRK subfamily.
As a component of the GATOR1 complex functions as an inhibitor of the amino acid-sensing branch of the TORC1 pathway.
Belongs to the U1 small nuclear ribonucleoprotein C family.
Component of the U1 snRNP. The U1 snRNP is composed of the U1 snRNA and the 7 core Sm proteins snrpb, snrpd1, snrpd2, snrpd3, snrpe, snrpf and snrpg that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP, and at least 3 U1 snRNP-specific proteins snrnp70/U1-70K, snrpa/U1-A and snrpc/U1-C. snrpc/U1-C interacts with U1 snRNA and the 5' splice-site region of the pre-mRNA.
Component of the spliceosomal U1 snRNP, which is essential for recognition of the pre-mRNA 5' splice-site and the subsequent assembly of the spliceosome. snrpc/U1-C is directly involved in initial 5' splice-site recognition for both constitutive and regulated alternative splicing. The interaction with the 5' splice-site seems to precede base-pairing between the pre-mRNA and the U1 snRNA. Stimulates commitment or early (E) complex formation by stabilizing the base pairing of the 5' end of the U1 snRNA and the 5' splice-site region.
Regulates ADAM17 protease, a sheddase of the epidermal growth factor (EGF) receptor ligands and TNF, thereby plays a role in sleep, cell survival, proliferation, migration and inflammation. Does not exhibit any protease activity on its own.
Belongs to the proteasome subunit p27 family.
Transforming growth factor beta-1 proprotein: Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-1 (TGF-beta-1) chains, which constitute the regulatory and active subunit of TGF-beta-1, respectively.
Belongs to the krueppel C2H2-type zinc-finger protein family.
Transcription repressor. Involved in the development of the forebrain region (By similarity).
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.
Activator of the canonical Wnt signaling pathway by acting as a ligand for lgr4-6 receptors. Upon binding to lgr4-6 (lgr4, lgr5 or lgr6), lgr4-6 associate with phosphorylated lrp6 and frizzled receptors that are activated by extracellular Wnt receptors, triggering the canonical Wnt signaling pathway to increase expression of target genes. Acts both in the canonical. Wnt/beta-catenin-dependent pathway and in non-canonical Wnt signaling pathway (By similarity). Activates neural markers and promotes muscle formation. Overexpression blocks activin, nodal and BMP4 signaling, suggesting that it may negatively regulate the TGF-beta pathway (By similarity). During embryonic development, plays a crucial role in limb specification, amplifying the Wnt signaling pathway independently of LGR4-6 receptors, possibly by acting as a direct antagonistic ligand to RNF43 and ZNRF3, hence governing the number of limbs an embryo should form (PubMed:29769720).
Mutant animals exhibit marked forelimb and hindlimb amelia.
The FU repeat is required for activation and stabilization of beta-catenin.
Belongs to the DPH1/DPH2 family. DPH1 subfamily.
Binds 1 [4Fe-4S] cluster per subunit. The cluster is coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine.
Catalyzes the first step of diphthamide biosynthesis, a post-translational modification of histidine which occurs in elongation factor 2.
May regulate certain MYC target genes, MYC seems to be a direct upstream transcriptional activator.
Belongs to the dienelactone hydrolase family.
Receptor for thyrotropin-releasing hormone (TRH). Upon ligand binding, this G-protein-coupled receptor triggers activation of the phosphatidylinositol (IP3)-calcium-protein kinase C (PKC) pathway.
In the C-terminal section; belongs to the peptidase M41 family.
In the N-terminal section; belongs to the AAA ATPase family.
Acts as a glycogen-targeting subunit for PP1 and regulates its activity. Activates glycogen synthase, reduces glycogen phosphorylase activity and limits glycogen breakdown (By similarity).
Interacts with PPP1CC catalytic subunit of PP1 and associates with glycogen. Forms complexes with glycogen phosphorylase, glycogen synthase and phosphorylase kinase which is necessary for its regulation of PP1 activity (By similarity).
The N-terminal region is required for binding to PP1, the central region is required for binding to glycogen and the C-terminal region is required for binding to glycogen phosphorylase, glycogen synthase and phosphorylase kinase.
Belongs to the glycosyl hydrolase 79 family.
Negatively regulates Wnt/beta-catenin signaling during development.
Ubiquitin-binding protein that specifically recognizes and binds 'Lys-63'-linked ubiquitin. Does not bind 'Lys-48'-linked ubiquitin. Positively regulates the internalization of ligand-activated EGFR by binding to the Ub moiety of ubiquitinated EGFR at the cell membrane.
May regulate a number of protein-protein interactions by competing for PDZ domain binding sites.
Plays a role in the reorganization of the cytoskeleton, endocytosis and cellular vesicle trafficking, both during interphase and at the end of mitotic cell divisions. Required for efficient progress through mitosis and cytokinesis. Required for normal formation of the cleavage furrow at the end of mitosis. Modulates endocytosis of cell-surface proteins. Promotes membrane tubulation (in vitro). May promote the formation of macropinosomes (By similarity).
The PX and BAR domains mediate association with membranes and are required for membrane tubulation.
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. cGMP 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 formation and regulation of the tight junction (TJ) paracellular permeability barrier.
Component of the PI3K (PI3KC3/PI3K-III/class III phosphatidylinositol 3-kinase) complex (By similarity).
May be proteolytically processed by caspases; the C-terminal fragment(s) may induce apoptosis.
Plays a central role in autophagy (By similarity). Acts as core subunit of different PI3K complex forms that mediate formation of phosphatidylinositol 3-phosphate and are believed to play a role in multiple membrane trafficking pathways: PI3KC3-C1 is involved in initiation of autophagosomes and PI3KC3-C2 in maturation of autophagosomes and endocytosis (By similarity). Involved in regulation of degradative endocytic trafficking and required for the abcission step in cytokinesis, probably in the context of PI3KC3-C2 (By similarity). Essential for the formation of PI3KC3-C2 but not PI3KC3-C1 PI3K complex forms (By similarity). Involved in endocytosis including endosome formation in neuronal cells (By similarity).
Belongs to the glycosyl hydrolase 35 family.
Belongs to the mitochondrion-specific ribosomal protein mL45 family.
Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins.
Oligomeric complex that consists of at least the alpha, beta, beta', gamma, delta, epsilon and zeta subunits.
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.
The coatomer is a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Golgi network. Coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins (By similarity).
Belongs to the NAD(P)H dehydrogenase (quinone) family.
Belongs to the PUR DNA-binding protein family.
Belongs to the TRAFAC class translation factor GTPase superfamily. Classic translation factor GTPase family. EF-G/EF-2 subfamily.
Mitochondrial GTPase that mediates the disassembly of ribosomes from messenger RNA at the termination of mitochondrial protein biosynthesis. Acts in collaboration with MRRF. GTP hydrolysis follows the ribosome disassembly and probably occurs on the ribosome large subunit. Not involved in the GTP-dependent ribosomal translocation step during translation elongation.
Specifically required during spermatogenesis for flagellum morphogenesis and sperm motility.
Both ATG8-interaction motifs (AIM1 and AIM2) are required for the association with ATG8 family proteins.
Component of the signaling pathway of IL-1 and Toll-like receptors. Inhibits cell activation by microbial products. Connects the ubiquitin pathway to autophagy by functioning as a ubiquitin-ATG8 family adapter and thus mediating autophagic clearance of ubiquitin conjugates. The TOLLIP-dependent selective autophagy pathway plays an important role in clearance of cytotoxic polyQ proteins aggregates (By similarity). In a complex with TOM1, recruits ubiquitin-conjugated proteins onto early endosomes (By similarity). Binds to phosphatidylinositol 3-phosphate (PtdIns(3)P) (By similarity).
Interacts with ATG8 family proteins (via AIM motifs), and ubiquitin (via CUE domain). Found in a complex with TOM1; interacts (via N-terminus) with TOM1 (via GAT domain); the interactions leads to TOM1-recruitment to endosomes and inhibition of TOLLIP binding to PtdIns(3)P (By similarity).
The N-terminal TOM1-binding domain (residues 1-53) is a disordered domain that partially folds when bound to the GAT domain of TOM1.
May play a role in mdm2-dependent p53/TP53 homeostasis in unstressed cells. Inhibits autoubiquitination of mdm2, thereby enhancing mdm2 stability. This promotes mdm2-mediated ubiquitination of p53/TP53 and its subsequent degradation (By similarity).
Belongs to the immunoglobulin superfamily. LISCH7 family.
Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex.
Catalyzes the cleavage of citrate into oxaloacetate and acetyl-CoA, the latter serving as common substrate for de novo cholesterol and fatty acid synthesis.
In the C-terminal section; belongs to the succinate/malate CoA ligase alpha subunit family.
In the N-terminal section; belongs to the succinate/malate CoA ligase beta subunit family.
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.
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. Involved in late stages of cytokinesis. Plays a role in endosomal sorting/trafficking of EGF receptor (By similarity).
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III). ESCRT-III components are thought to multimerize to form a flat lattice on the perimeter membrane of the endosome. Several assembly forms of ESCRT-III may exist that interact and act sequentially (By similarity).
Functions as a dosage-dependent inducer in mitotic control. Tyrosine protein phosphatase required for progression of the cell cycle.
Acts as component of the THO subcomplex of the TREX complex which is thought to couple mRNA transcription, processing and nuclear export, and which specifically associates with spliced mRNA and not with unspliced pre-mRNA. TREX is recruited to spliced mRNAs by a transcription-independent mechanism, binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5' end of the mRNA where it functions in mRNA export to the cytoplasm via the TAP/NFX1 pathway (By similarity).
Component of the THO subcomplex of the transcription/export (TREX) complex which seems to have a dynamic structure involving ATP-dependent remodeling. Interacts with thoc7 (By similarity).
May be involved in cell differentiation.
Involved in nucleolar processing of pre-18S ribosomal RNA.
Belongs to the inositol 1,4,5-trisphosphate 5-phosphatase type II family.
Belongs to the ferroportin (FP) (TC 2.A.100) family. SLC40A subfamily.
May be involved in iron transport and iron homeostasis.
Belongs to the ATPase epsilon chain family.
Belongs to the carbon-nitrogen hydrolase superfamily. BTD/VNN family.
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.
'Pegasus' was the winged horse in Greek mythology.
Belongs to the Ikaros C2H2-type zinc-finger protein family.
Transcriptional repressor that binds the core 5'GNNTGTNG-3' DNA consensus sequence (By similarity).
Can form homo- and heteropolymers with other CLDN. Homopolymers interact with CLDN1 and CLDN2 homopolymers. Directly interacts with TJP1/ZO-1, TJP2/ZO-2 and TJP3/ZO-3.
Plays a role in the process of neurogenesis.
Has apparently no steroid dehydrogenase activity.
Produces ATP from ADP in the presence of a proton gradient across the membrane.
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 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 anion channel-forming bestrophin (TC 1.A.46) family. Calcium-sensitive chloride channel subfamily.
Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PDPK1 subfamily.
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.
Novel PKCs (PRKCD, PRKCE, PRKCH and PRKCQ) are calcium-insensitive, but activated by diacylglycerol (DAG) and phosphatidylserine.
Involved in nucleolar processing of pre-18S ribosomal RNA. Has a role in the nuclear export of 40S pre-ribosomal subunit to the cytoplasm.
Belongs to the natriuretic peptide family.
Belongs to the immunoglobulin superfamily. DCC 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.
Essential component of the TORC2 complex, which plays a critical role in akt1 'Ser-473' phosphorylation, and may modulate the phosphorylation of pkca and regulate actin cytoskeleton organization. May interact with a MAP kinase. May act on Ras-regulated pathways (By similarity).
Part of the target of rapamycin 2 complex (TORC2).
Probable component of the wybutosine biosynthesis pathway. Wybutosine is a hyper modified guanosine with a tricyclic base found at the 3'-position adjacent to the anticodon of eukaryotic phenylalanine tRNA. Catalyzes the condensation of N-methylguanine with 2 carbon atoms from pyruvate to form the tricyclic 4-demethylwyosine, an intermediate in wybutosine biosynthesis.
Promotes the cell surface stability of RHBDF1 and RHBDF2 and prevents their degradation via the endolysosomal pathway. By acting on RHBDF proteins, involved in ADAM17-mediated ligand shedding (By similarity). May negatively regulate Wnt signaling (By similarity).
Cell adhesion molecule involved in the establishment and/or maintenance of cell integrity. May play a role in vamp3-mediated vesicular transport and recycling of different receptor molecules. May be involved in the formation and regulation of the tight junction (TJ) paracellular permeability barrier in epithelial cells. May induce primordial adhesive contact and aggregation of epithelial cells in a Ca(2+)-independent manner. May be involved in epithelial movement during corneal sheet formation and regeneration. May play a role in the regulation of cell shape and movement by modulating the Rho-GTPase activity. May be involved in skeletal muscle and heart development as well as in the maintenance of heart function. May also be involved in striated muscle regeneration and in the regulation of cell spreading (By similarity).
Belongs to the bZIP family. PAR subfamily.
Belongs to the MINDY deubiquitinase family. FAM188 subfamily.
Hydrolase that can remove 'Lys-48'-linked conjugated ubiquitin from proteins.
Belongs to the transient receptor (TC 1.A.4) family. LTrpC subfamily. TRPM2 sub-subfamily.
Transcription factor which plays a key role in defining the composition of the RNA polymerase II (RNAPII) elongation complex and in modulating the production of mature mRNA transcripts.
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.
Antiporter that exchanges vesicular protons for cytosolic 4-aminobutanoate or to a lesser extend glycine, thus allowing their secretion from nerve terminals. The transport is equally dependent on the chemical and electrical components of the proton gradient (By similarity). May also transport beta-alanine (By similarity). Acidification of GABAergic synaptic vesicles is a prerequisite for 4-aminobutanoate uptake (By similarity).
Belongs to the amino acid/polyamine transporter 2 family.
Juge et al. shows that SLC32A1 is a symporter of both 4-aminobutanoate or glycine or beta-alanine with Cl(-) that operates according an electrical gradient without the need for a chemical gradient (By similarity). However Farsi et al. and Egashira et al. confirm that SLC32A1 is an antiporter that exchanges vesicular protons for cytosolic 4-aminobutanoate or glycine and exclude any coupling with chloride (By similarity).
In the C-terminal section; belongs to the GART family.
In the N-terminal section; belongs to the GARS family.
In the central section; belongs to the AIR synthase family.
Plays a role in mitotic bipolar spindle formation. Binds mRNA. May function in nucleocytoplasmic transport and in directly or indirectly attaching cytoplasmic mRNPs to the cytoskeleton.
Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A12 subfamily.
Belongs to the DNA polymerase type-B family.
Belongs to the protein kinase superfamily. Tyr protein kinase family. JAK subfamily.
Belongs to the FAM175 family. Abraxas subfamily.
Component of the BRCA1-A complex. Component of the BRISC complex. Interacts directly (when phosphorylated at Ser-405) with brca1. Homodimer. The phosphorylated homodimer can interact directly with two brca1 chains, giving rise to a heterotetramer (By similarity).
Involved in DNA damage response and double-strand break (DSB) repair. Component of the BRCA1-A complex, acting as a central scaffold protein that assembles the various components of the complex and mediates the recruitment of brca1. The BRCA1-A complex specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesion sites, leading to target the brca1-bard1 heterodimer to sites of DNA damage at DSBs. This complex also possesses deubiquitinase activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX (By similarity).
Phosphorylation of Ser-405 of the pSXXF motif by ATM or ATR constitutes a specific recognition motif for the BRCT domain of BRCA1.
Belongs to the alkaline ceramidase family.
Hydrolyzes the sphingolipid ceramide into sphingosine and free fatty acid.
DNA polymerase II participates in chromosomal DNA replication.
Belongs to the cysteine dioxygenase family.
Catalyzes the oxidation of cysteine to cysteine sulfinic acid with addition of molecular dioxygen.
Belongs to the eukaryotic ribosomal protein eL8 family.
Identified in the spliceosome B complex. Component of the U4/U6-U5 tri-snRNP complex. Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3 (By similarity).
Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome. Involved in pre-mRNA splicing as component of the spliceosome. Binds to the 5'-stem-loop of U4 snRNA and thereby contributes to spliceosome assembly. The protein undergoes a conformational change upon RNA-binding.
Component of the CPC at least composed of survivin/birc5, incenp, cdca8/borealin and/or cdca9/dasra-A, and aurkb/aurora-B. Interacts directly with incenp (via N-terminus). Interacts with rxra; the interaction is stronger in the absence of 9-cis retinoic acids (By similarity).
Component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly. Does not appear to exhibit anti-apoptotic activity. Plays a role in increasing blood vessel size during development (By similarity).
The BIR2 domain is required for vascular development.
Belongs to the universal ribosomal protein uS12 family.
Belongs to the universal ribosomal protein uL1 family.
Acts as component of the mcm2-7 complex (mcm complex) which is the putative 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. The existence of maternal and zygotic forms of mcm3 and mcm6 suggests that specific forms of mcm2-7 complexes may be used during different stages of development. May replace mmcm6 in the mcm2-7 complex (By similarity).
Component of the mcm2-7 complex (RLF-M). The complex forms a toroidal hexameric ring with the proposed subunit order mcm2-mcm6-mcm4-mcm7-mcm3-mcm5. Begins to associate with zmcm3, mcm4 and mcm7 into mcm complexes at the neurula stage (By similarity).
Required for the export of mRNAs containing poly(A) tails from the nucleus into the cytoplasm. May be involved in the terminal step of the mRNA transport through the nuclear pore complex (NPC).
Belongs to the potassium channel KCNE family.
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.
Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins.
Belongs to the Glu/Leu/Phe/Val dehydrogenases family.
Putative sodium-dependent amino acid/proton antiporter.
Belongs to the universal ribosomal protein uL23 family.
Expressed in the anterior endomesoderm of the early gastrula with expression expanded laterally around the margin at the endoderm/mesoderm boundary.
Expressed in the gastrula stage of embryos but becomes absent by late neurula stage.
Inhibits wnt, nodal/nr-1 and bmp signaling in the embryo to promote head formation and anterior neural induction. Within the endoderm, acts as an essential mediator of nodal/nr-1-induced cardiogenesis in the overlying mesoderm (By similarity).
The long chain interacts with nodal/nr-1, bmp4 and wnt8, thereby inhibiting their function. The short chain interacts with nodal/nr-1 but not bmp4 or wnt8 (By similarity).
Belongs to the metallothionein superfamily. Type 1 family.
Metallothioneins have a high content of cysteine residues that bind various heavy metals.
Acts as one of several non-catalytic accessory components of the cytoplasmic dynein 1 complex that are thought to be involved in linking dynein to cargos and to adapter proteins that regulate dynein function. Cytoplasmic dynein 1 acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. May play a role in binding dynein to membranous organelles or chromosomes.
Belongs to the dynein light intermediate chain family.
Homodimer. The cytoplasmic dynein 1 complex consists of two catalytic heavy chains (HCs) and a number of non-catalytic subunits presented by intermediate chains (ICs).
Involved in mitochondrial ribosome large subunit biogenesis.
Plays a role in the translocation of terminally misfolded proteins from the endoplasmic reticulum lumen to the cytoplasm and their degradation by the proteasome (By similarity). Plays a role in lipid droplet formation (By similarity). Induces lipid droplet clustering (By similarity).
Belongs to the G-alpha family. G(q) subfamily.
Belongs to the methyltransferase superfamily. Fibrillarin family.
Belongs to the cytidine and deoxycytidylate deaminase family. ADAT2 subfamily.
Probably participates in deamination of adenosine-34 to inosine in many tRNAs.
Belongs to the Mediator complex subunit 6 family.
Belongs to the chloride channel CLIC family.
Members of this family may change from a globular, soluble state to a state where the N-terminal domain is inserted into the membrane and functions as chloride channel. A conformation change of the N-terminal domain is thought to expose hydrophobic surfaces that trigger membrane insertion.
Belongs to the universal ribosomal protein uL18 family.
Belongs to the phenylalanyl-tRNA synthetase beta subunit family. Type 2 subfamily.
Belongs to the glycosyl hydrolase 31 family.
Belongs to the WD repeat LIS1/nudF family.
Can self-associate. Component of the cytosolic PAF-AH (I) heterotetrameric enzyme, which is composed of PAFAH1B1 (beta), PAFAH1B2 (alpha2) and PAFAH1B3 (alpha1) subunits. The catalytic activity of the enzyme resides in the alpha1 (PAFAH1B3) and alpha2 (PAFAH1B2) subunits, whereas the beta subunit (PAFAH1B1) has regulatory activity. Trimer formation is not essential for the catalytic activity (By similarity). Interacts with dynein, dynactin, nde1 and ndel1.
Dimerization mediated by the LisH domain may be required to activate dynein.
Regulatory subunit (beta subunit) of the cytosolic type I platelet-activating factor (PAF) acetylhydrolase (PAF-AH (I)), an enzyme that catalyzes the hydrolyze of the acetyl group at the sn-2 position of PAF and its analogs and participates in the PAF inactivation (By similarity). Positively regulates the activity of the minus-end directed microtubule motor protein dynein. May enhance dynein-mediated microtubule sliding by targeting dynein to the microtubule plus end. Required for several dynein- and microtubule-dependent processes such as the maintenance of Golgi integrity, the peripheral transport of microtubule fragments and the coupling of the nucleus and centrosome. May be required for proliferation of neuronal precursors and neuronal migration.
Crucial regulator of the mitotic cell cycle and development. At prophase, required for dynein anchoring to the nuclear envelope important for proper centrosome-nucleus coupling. At G2/M phase, may be required for proper spindle formation and execution of cytokinesis. 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 (By similarity). Plays a role in gastrulation and early embryogenesis (By similarity).
Centriole-enriched microtubule-binding protein involved in centriole biogenesis. In collaboration with CEP295 and POC1B, is required for the centriole-to-centrosome conversion by ensuring the formation of bona fide centriole wall. Functions as a linker component that maintains centrosome cohesion. Associates with CROCC and regulates its stability and localization to the centrosome.
Belongs to the bacterial ribosomal protein bL34 family.
Expressed in both male and female gonads from after metamorphosis through to adult stages. In the testis, expression is restricted to the supporting Sertoli-like cells. Conversely in the ovary, expression is localized to primary oocytes (at protein level). In developing limbs, expressed before chrondrocytes form (stage 52 tadpoles) and throughout the cartilaginous anlagen until stage 56, after which expression ceases in the enlarged cells of the diaphysis. At later stages, expression continues in the chondrocytes of the epiphysis and metaphysis, and weak expression is seen in most of the diaphysis.
Sumoylated. Lys-370 is the major site of sumoylation, although sumoylation at Lys-61 also occurs. Sumoylation plays a key role in regulating formation of the neural crest and otic placode (By similarity).
Transcription factor that plays a key role in chondrocytes differentiation and skeletal development. Specifically binds the 5'-ACAAAG-3' DNA motif present in enhancers and super-enhancers and promotes expression of genes important for chondrogenesis, including COL2A1. Plays a central role in successive steps of chondrocyte differentiation. Absolutely required for precartilaginous condensation, the first step in chondrogenesis during which skeletal progenitors differentiate into prechondrocytes. Together with SOX5 and SOX6, required for overt chondrogenesis when condensed prechondrocytes differentiate into early stage chondrocytes, the second step in chondrogenesis. Later, required to direct hypertrophic maturation and block osteoblast differentiation of growth plate chondrocytes: maintains chondrocyte columnar proliferation, delays prehypertrophy and then prevents osteoblastic differentiation of chondrocytes. Also required for chondrocyte hypertrophy, both indirectly, by keeping the lineage fate of chondrocytes, and directly, by remaining present in upper hypertrophic cells. Low lipid levels are the main nutritional determinant for chondrogenic commitment of skeletal progenitor cells: when lipids levels are low, FOXO transcription factors promote expression of SOX9, which induces chondrogenic commitment and suppresses fatty acid oxidation. In addition to cartilage development, also acts as a regulator of proliferation and differentiation in epithelial stem/progenitor cells (By similarity). Unlikely to play a role in sex determination but may function during testicular and ovarian differentiation (PubMed:18692165, PubMed:18816826).
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.
Acts as a GTPase-activating protein (GAP) for tubulin in concert with tubulin-specific chaperone C, but does not enhance tubulin heterodimerization.
Belongs to the bacterial ribosomal protein bL20 family.
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.
Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIA subfamily.
Belongs to the thymidylate kinase family.
Belongs to the 2H phosphoesterase superfamily. USB1 family.
Phosphodiesterase responsible for the U6 snRNA 3' end processing. Acts as an exoribonuclease (RNase) responsible for trimming the poly(U) tract of the last nucleotides in the pre-U6 snRNA molecule, leading to the formation of mature U6 snRNA.
Belongs to the 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.
Belongs to the amino acid-polyamine-organocation (APC) superfamily. L-type amino acid transporter (LAT) (TC 2.A.3.8) family.
Disulfide-linked heterodimer with the amino acid transport protein SLC3A2/4F2hc.
Heterodimer with SLC3A2, that functions as an antiporter which operates as an efflux routeby exporting cationic amino acids such as L-arginine from inside the cells in exchange with neutral amino acids like L-leucine, L-glutamine and isoleucine, plus sodium ions and may participate in nitric oxide synthesis. Also exchanges L-arginine with L-lysine in a sodium-independent manner. The transport mechanism is electroneutral and operates with a stoichiometry of 1: 1 (By similarity). Contributes to ammonia-induced increase of L-arginine uptake in cerebral cortical astrocytes leading to ammonia-dependent increase of nitric oxide (NO) production via inducible nitric oxide synthase (iNOS) induction, and protein nitration (By similarity). May mediate transport of ornithine in retinal pigment epithelial (RPE) cells (By similarity). May also transport glycine betaine in a sodium dependent manner from the cumulus granulosa into the enclosed oocyte (By similarity).
Does not bind lactose, and may not bind carbohydrates.
Most of the residues in the galectin domain that have been shown to be critical for carbohydrate-binding in other galectins are not conserved.
Heterohexamer; composed of 3 copies of TIMM9 and 3 copies of TIMM10/TIM10A, named soluble 70 kDa complex. The complex forms a 6-bladed alpha-propeller structure and associates with the TIMM22 component of the TIM22 complex. Interacts with multi-pass transmembrane proteins in transit (By similarity).
Mitochondrial intermembrane chaperone that participates in the import and insertion of multi-pass transmembrane proteins into the mitochondrial inner membrane. May also be required for the transfer of beta-barrel precursors from the TOM complex to the sorting and assembly machinery (SAM complex) of the outer membrane. Acts as a chaperone-like protein that protects the hydrophobic precursors from aggregation and guide them through the mitochondrial intermembrane space (By similarity).
The twin CX3C motif contains 4 conserved Cys residues that form 2 disulfide bonds in the mitochondrial intermembrane space. However, during the transit of TIMM10 from cytoplasm into mitochondrion, the Cys residues probably coordinate zinc, thereby preventing folding and allowing its transfer across mitochondrial outer membrane (By similarity).
Belongs to the trans-sulfuration enzymes family.
Involved in the degradation process of misfolded endoplasmic reticulum (ER) luminal proteins. Participates in the transfer of misfolded proteins from the ER to the cytosol, where they are destroyed by the proteasome in a ubiquitin-dependent manner (By similarity).
Belongs to the TRAPP small subunits family. Sedlin subfamily.
Belongs to the ubiquitin-activating E1 family. UBA3 subfamily.
Catalytic subunit of the dimeric E1 enzyme, which activates NEDD8.
In extracellular secreted form, promotes proliferation and activation of T cells, suggesting a cytokine-like function. May inhibit ERK and JNK signaling activity and suppress cell migration and invasion activity. Has a critical role in the regulation of osteogenesis and bone development.
In the nucleus, enhances activity of the PCAF histone acetyltransferase (HAT) complex.
Belongs to the major facilitator superfamily. MFSD6 family.
Component of the lysosomal folliculin complex (LFC).
GTPase-activating activity is inhibited in the folliculin complex (LFC), which stabilizes the GDP-bound state of RagA/RRAGA (or RagB/RRAGB), because Arg-164 is located far from the RagC/RRAGC or RagD/RRAGD nucleotide pocket. Disassembly of the LFC complex upon amino acid restimulation liberates the GTPase-activating activity.
Multi-functional protein, involved in both the cellular response to amino acid availability and in the regulation of glycolysis. GTPase-activating protein that plays a key role in the cellular response to amino acid availability through regulation of the non-canonical mTORC1 signaling cascade controlling the MiT/TFE factors tfeb and tfe3. Activates mTORC1 by acting as a GTPase-activating protein: specifically stimulates GTP hydrolysis by RagC/RRAGC or RagD/RRAGD, promoting the conversion to the GDP-bound state of RagC/RRAGC or RagD/RRAGD, and thereby activating the kinase activity of mTORC1. The GTPase-activating activity is inhibited during starvation and activated in presence of nutrients. Acts as a key component for non-canonical mTORC1-dependent control of the MiT/TFE factors tfeb and tfe3, while it is not involved in mTORC1-dependent phosphorylation of canonical RPS6KB1/S6K1 and EIF4EBP1/4E-BP1. In low-amino acid conditions, the lysosomal folliculin complex (LFC) is formed on the membrane of lysosomes, which inhibits the GTPase-activating activity of flcn, inactivates mTORC1 and maximizes nuclear translocation of tfeb and tfe3. Upon amino acid restimulation, RagA/RRAGA (or RagB/RRAGB) nucleotide exchange promotes disassembly of the LFC complex and liberates the GTPase-activating activity of flcn, leading to activation of mTORC1 and subsequent cytoplasmic retention of tfeb and tfe3. Required for the exit of hematopoietic stem cell from pluripotency by promoting mTOR-dependent cytoplasmic retention of tfe3, thereby increasing Wnt signaling. Acts as an inhibitor of browning of adipose tissue by regulating mTOR-dependent cytoplasmic retention of tfe3. In response to flow stress, regulates STK11/LKB1 accumulation and mTORC1 activation through primary cilia. Required for starvation-induced perinuclear clustering of lysosomes by promoting association of rilp with its effector rab34. Involved in the control of embryonic stem cells differentiation; together with lamtor1 it is necessary to recruit and activate RagC/RRAGC and RagD/RRAGD at the lysosomes, and to induce exit of embryonic stem cells from pluripotency via non-canonical, mTOR-independent tfe3 inactivation. Regulates glycolysis by binding to lactate dehydrogenase ldha, acting as an uncompetitive inhibitor.
Monomer. Interacts with pre-ribosome complex. May bind to RNA. Interacts with NOL8. Interacts with FTSJ3 (By similarity).
Required for proper 34S pre-rRNA processing and 60S ribosome subunit assembly.
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.
Probable hydrolase that can remove 'Lys-48'-linked conjugated ubiquitin from proteins.
Binds and protects the poly(A) tail of mRNA with or without an AU-rich element (ARE) and prevents mRNA deadenylation. Stimulates the translation of mRNAs to which it is bound during early development (By similarity).
Interacts with dazl in an RNA-independent manner. The C-terminus can self-associate and also interact with the C-terminus of pabpc1, independently of RNA. RRM 1 and RRM 2 interact with both eif4g1 and paip1, and the C-terminus also interacts with paip1. Prior to oocyte maturation, found in a complex with dazl and pum2 proteins and spdy1 mRNA; pum2 dissociates from the complex during maturation. Interacts with the translation termination factor sup35/erf3 (By similarity).
Part of the SNAPc complex composed of 5 subunits: SNAPC1, SNAPC2, SNAPC3, SNAPC4 and SNAPC5. SNAPC3 interacts with SNAPC1.
Part of the SNAPc complex required for the transcription of both RNA polymerase II and III small-nuclear RNA genes. Binds to the proximal sequence element (PSE), a non-TATA-box basal promoter element common to these 2 types of genes. Recruits TBP and BRF2 to the U6 snRNA TATA box.
Belongs to the protein-tyrosine phosphatase family. Receptor class 3 subfamily.
Belongs to the fatty acyl-CoA reductase family.
Catalyzes the reduction of fatty acyl-CoA to fatty alcohols.
Negative regulator of the Wnt signaling pathway. Inhibits Wnt signaling in a cell-autonomous manner and functions upstream of beta-catenin (By similarity).
Positively regulates lysosome peripheral distribution and ruffled border formation in osteoclasts. Involved in bone resorption.
Belongs to the cAMP-dependent kinase regulatory chain family.
Belongs to the universal ribosomal protein uS11 family.
Component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes. Required for ciliogenesis and sonic hedgehog/SHH signaling (By similarity).
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 E3 ligase complexes, leading to modify the Ubl ligase activity (By similarity).
Belongs to the amiloride-sensitive sodium channel (TC 1.A.6) family.
Belongs to the uracil-DNA glycosylase (UDG) superfamily. SMUG1 family.
Belongs to the myo-inositol 1-phosphate synthase family.
Plays a role in valine and pyrimidine metabolism. Binds fatty acyl-CoA.
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. 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.
Transcriptional activator. Induces neural-specific gene expression to act as a key regulator of neural differentiation (By similarity).
Associates with cyclin-T to form P-TEFb.
Member of the cyclin-dependent kinase pair (CDK9/cyclin-T) complex, also called positive transcription elongation factor B (P-TEFb), which is proposed to facilitate the transition from abortive to production elongation by phosphorylating the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAP II) and SUPT5H.
E3 ubiquitin-protein ligase which may be involved in endosomal trafficking. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfer the ubiquitin to targeted substrates.
Belongs to the G-protein coupled receptor 3 family. GABA-B receptor subfamily.
Belongs to the mitochondrion-specific ribosomal protein mS26 family.
Belongs to the archaeal Rpo11/eukaryotic RPB11/RPC19 RNA polymerase subunit family.
DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Component of RNA polymerase II which synthesizes mRNA precursors and many functional non-coding RNAs. Pol II is the central component of the basal RNA polymerase II transcription machinery. It is composed of mobile elements that move relative to each other. RPB11 is part of the core element with the central large cleft.
Mediates the endoplasmic reticulum-associated degradation (ERAD) of inositol 1,4,5-trisphosphate receptors (IP3Rs). Involved in regulation of cellular cholesterol homeostasis by regulation the SREBP signaling pathway. Binds cholesterol and may promote ER retention of the SCAP-SREBF complex.
Activity is regulated by phosphorylation at Ser-49 and Ser-52, which stabilizes the eIF-2/GDP/eIF-2B complex and prevents the eIF-2B-mediated exchange of GDP for GTP, thereby preventing the formation of the 43S pre-initiation complex (PIC). This results in the global attenuation of 5' cap-dependent protein synthesis and concomitant translation of ISR-specific mRNAs that contain a short upstream open reading frame (uORF) in their 5' UTR.
Functions in the early steps of protein synthesis by forming a ternary complex with GTP and initiator tRNA. This complex binds to a 40S ribosomal subunit, followed by mRNA binding to form a 43S pre-initiation complex. Junction of the 60S ribosomal subunit to form the 80S initiation complex is preceded by hydrolysis of the GTP bound to eIF-2 and release of an eIF-2-GDP binary complex. In order for eIF-2 to recycle and catalyze another round of initiation, the GDP bound to eIF-2 must exchange with GTP by way of a reaction catalyzed by eIF-2B. EIF2S1/eIF-2-alpha is a key component of the integrated stress response (ISR), required for adaptation to various stress: phosphorylation by metabolic-stress sensing protein kinases in response to stress converts EIF2S1/eIF-2-alpha in a global protein synthesis inhibitor, leading to a attenuation of cap-dependent translation, while concomitantly initiating the preferential translation of ISR-specific mRNAs, such as the transcriptional activators ATF4 and QRICH1.
Heterotrimer composed of an alpha, a beta and a gamma chain.
Phosphorylation at Ser-49 and Ser-52 stabilizes the eIF-2/GDP/eIF-2B complex and prevents GDP/GTP exchange reaction, thus impairing the recycling of eIF-2 between successive rounds of initiation and leading to global inhibition of translation, while concomitantly initiating the preferential translation of integrated stress response (ISR)-specific mRNAs.
Component of the swi5-sfr1 complex, a complex required for double-strand break repair via homologous recombination.
Involved in the cellular defense against the biological effects of O6-methylguanine (O6-MeG) and O4-methylthymine (O4-MeT) in DNA. Repairs the methylated nucleobase in DNA by stoichiometrically transferring the methyl group to a cysteine residue in the enzyme. This is a suicide reaction: the enzyme is irreversibly inactivated.
Belongs to the DNA polymerase type-Y family.
Deoxycytidyl transferase involved in DNA repair. Transfers a dCMP residue from dCTP to the 3'-end of a DNA primer in a template-dependent reaction. May assist in the first step in the bypass of abasic lesions by the insertion of a nucleotide opposite the lesion. Required for normal induction of mutations by physical and chemical agents.
May act as a positive regulator of ERK phosphorylation downstream of fibroblast growth factor-receptor activation. May induce both caspase-dependent apoptosis and caspase-independent cell death. May play a role in the embryonic development.
In the N-terminal section; belongs to the AlaDH/PNT family.
Belongs to the cytochrome b5 family. MAPR subfamily.
Heme-binding protein which promotes neuronal but not astrocyte differentiation.
The cytochrome b5 heme-binding domain was proven to bind heme, although it lacks the conserved iron-binding His residues at position 82 and 124.
Belongs to the prefoldin subunit alpha 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.
Heterohexamer of two PFD-alpha type and four PFD-beta type subunits.
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 XPG/RAD2 endonuclease family. FEN1 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.
Structure-specific nuclease with 5'-flap endonuclease and 5'-3' exonuclease activities involved in DNA replication and repair. During DNA replication, cleaves the 5'-overhanging flap structure that is generated by displacement synthesis when DNA polymerase encounters the 5'-end of a downstream Okazaki fragment. It enters the flap from the 5'-end and then tracks to cleave the flap base, leaving a nick for ligation. Also involved in the long patch base excision repair (LP-BER) pathway, by cleaving within the apurinic/apyrimidinic (AP) site-terminated flap. Acts as a genome stabilization factor that prevents flaps from equilibrating into structures that lead to duplications and deletions. Also possesses 5'-3' exonuclease activity on nicked or gapped double-stranded DNA, and exhibits RNase H activity. Also involved in replication and repair of rDNA and in repairing mitochondrial DNA.
Belongs to the peptidase S26 family. IMP2 subfamily.
Heterodimer of 2 subunits, IMMPL1 and IMMPL2.
May play a role in erythroid cell differentiation.
Belongs to the aspartyl/asparaginyl beta-hydroxylase family.
Associates with NCBP1/CBP80 to form an alternative cap-binding complex (CBC) which plays a key role in mRNA export. NCBP3 serves as adapter protein linking the capped RNAs (m7GpppG-capped RNA) to NCBP1/CBP80. Unlike the conventional CBC with NCBP2 which binds both small nuclear RNA (snRNA) and messenger (mRNA) and is involved in their export from the nucleus, the alternative CBC with NCBP3 does not bind snRNA and associates only with mRNA thereby playing a role in only mRNA export.
Component of an alternative cap-binding complex (CBC) composed of NCBP1/CBP80 and NCBP3.
Belongs to the liprin family. Liprin-beta subfamily.
Belongs to the class-III pyridoxal-phosphate-dependent aminotransferase family.
Probable component of the NALCN channel complex, a channel that regulates the resting membrane potential and controls neuronal excitability.
Belongs to the nucleotide-sugar transporter family. SLC35B subfamily.
Interacts (via coiled coil domain) with BMP1 and (via olfactomedin-like domain) CHRD.
Secreted scaffold protein that plays an essential role in dorsoventral patterning during early development. Stabilizes axial formation by restricting chordin (CHRD) activity on the dorsal side. Acts by facilitating the association between the tolloid protease BMP1 and its substrate chordin (CHRD), leading to enhance chordin (CHRD) degradation by BMP1 (By similarity).
Component of the centrioles that acts as a positive regulator of centriole elongation. Promotes assembly of centriolar distal appendage, a structure at the distal end of the mother centriole that acts as an anchor of the cilium. Required for primary cilium formation (By similarity).
Catalytic subunit of the SLX1-SLX4 structure-specific endonuclease that resolves DNA secondary structures generated during DNA repair and recombination. Has endonuclease activity towards branched DNA substrates, introducing single-strand cuts in duplex DNA close to junctions with ss-DNA.
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.
Identified in the spliceosome C complex. Component of the minor spliceosome, which splices U12-type introns (By similarity).
Involved in pre-mRNA splicing as component of the spliceosome.
Belongs to the kynurenine formamidase family.
Catalyzes the hydrolysis of N-formyl-L-kynurenine to L-kynurenine, the second step in the kynurenine pathway of tryptophan degradation. Kynurenine may be further oxidized to nicotinic acid, NAD(H) and NADP(H). Required for elimination of toxic metabolites.
The main chain amide nitrogen atoms of the second glycine and its adjacent residue in the HGGXW motif define the oxyanion hole, and stabilize the oxyanion that forms during the nucleophilic attack by the catalytic serine during substrate cleavage.
Forms a complex with PECAM1 and GNAQ. Interacts with PECAM1.
Receptor for bradykinin. It is associated with G proteins that activate a phosphatidylinositol-calcium second messenger system.
Belongs to the selenoprotein M/F family.
Binds to poly-U elements and AU-rich elements (AREs) in the 3'-UTR of target mRNAs. Required for the vegetal localization of vg1 mRNA. Probably required for nervous system development (By similarity).
Part of a ribonucleoprotein (RNP) complex, at least composed of elavl1/elrA and/or elavl2/elrB, igf2bp3/vg1RBP, ddx6/Xp54, ybx2/frgy2, lsm14b/rap55b and, in a subset of RNP complexes, stau1/staufen. Binds RNA as a homooligomer (By similarity).
Belongs to the teashirt C2H2-type zinc-finger protein family.
Involved in autophagic vesicle formation. Conjugation with ATG12, through a ubiquitin-like conjugating system involving ATG7 as an E1-like activating enzyme and ATG10 as an E2-like conjugating enzyme, is essential for its function. The ATG12-ATG5 conjugate acts as an E3-like enzyme which is required for lipidation of ATG8 family proteins and their association to the vesicle membranes. Involved in mitochondrial quality control after oxidative damage, and in subsequent cellular longevity. Plays a critical role in multiple aspects of lymphocyte development and is essential for both B and T lymphocyte survival and proliferation. Required for optimal processing and presentation of antigens for MHC II. Involved in the maintenance of axon morphology and membrane structures, as well as in normal adipocyte differentiation. Promotes primary ciliogenesis through removal of OFD1 from centriolar satellites and degradation of IFT20 via the autophagic pathway.
May play an important role in the apoptotic process, possibly within the modified cytoskeleton. Its expression is a relatively late event in the apoptotic process, occurring downstream of caspase activity. Plays a crucial role in IFN-gamma-induced autophagic cell death by interacting with FADD.
Belongs to the glycine N-acyltransferase family.
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 major facilitator superfamily. Organophosphate:Pi antiporter (OPA) (TC 2.A.1.4) family.
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.
Belongs to the XRCC4-XLF family. XLF subfamily.
Belongs to the glycosyl hydrolase 1 family.
ATP-binding component of the Arp2/3 complex, a multiprotein complex that mediates actin polymerization upon stimulation by nucleation-promoting factor (NPF) (By similarity). The Arp2/3 complex mediates the formation of branched actin networks in the cytoplasm, providing the force for cell motility (By similarity). Seems to contact the pointed end of the daughter actin filament (By similarity). In addition to its role in the cytoplasmic cytoskeleton, the Arp2/3 complex also promotes actin polymerization in the nucleus, thereby regulating gene transcription and repair of damaged DNA (By similarity). The Arp2/3 complex promotes homologous recombination (HR) repair in response to DNA damage by promoting nuclear actin polymerization, leading to drive motility of double-strand breaks (DSBs) (By similarity).
Belongs to the actin family. ARP2 subfamily.
Component of the Arp2/3 complex composed of actr2/arp2, actr3/arp3, arpc1b, arpc2, arpc3, arpc4 and arpc5.
Sialate:O-sulfotransferase which catalyzes 8-O-sulfation at the Sia-glycan level using 3'-phosphoadenosine 5'-phosphosulfate (PAPS) as a donor, forming 8-O-sulfated Sia (Sia8S)-glycans.
Belongs to the phosphatase and actin regulator family.
Belongs to the Nudix hydrolase family. DIPP subfamily.
Functions as transcription repressor, probably via its interaction with histone deacetylase complexes. Involved in the functional recruitment of the class 1 Sin3-histone deacetylase complex (HDAC) to the nucleolus. Binds DNA, apparently without sequence-specificity, and bends bound double-stranded DNA. Binds phosphoinositol phosphates (phosphoinositol 3-phosphate, phosphoinositol 4-phosphate and phosphoinositol 5-phosphate) via the same basic sequence motif that mediates DNA binding and nuclear import.
Interacts with components of the histone deacetylase complex sin3a, hdac1 and hdac2. Binds histones and nucleosomes.
The zinc-finger domain mediates direct interaction with DNA and phosphoinositol phosphates (phosphoinositol 3-phosphate, phosphoinositol 4-phosphate and phosphoinositol 5-phosphate). In vitro oxydation causes reversible disulfide bond formation between Cys residues in the zinc-finger domain and reversible loss of zinc ion binding.
Belongs to the universal ribosomal protein uL30 family.
Belongs to the 3-hydroxyacyl-CoA dehydrogenase family.
Belongs to the connexin family. Gamma-type subfamily.
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.
E3 ubiquitin-protein ligase component of the CTLH complex.
Identified in the CTLH complex that contains at least RANBP9, MKLN1, MAEA, RMND5A, GID8 and ARMC8.
Has a stimulatory effect on the ATPase activity of HSP70 in a dose-dependent and time-dependent manner and hence acts as a co-chaperone of HSP70. Plays an indispensable role in the organization of KRT8/KRT18 filaments. Acts as an endogenous molecular chaperone for neuronal proteins including huntingtin. Suppresses aggregation and toxicity of polyglutamine-containing, aggregation-prone proteins. Also reduces cellular toxicity and caspase-3 activity.
Belongs to the lambda interferon family.
Guanine nucleotide exchange factor (GEF) with specificity for rap2a and other Ras family proteins (in vitro).
May act as a nuclear transcription factor that negatively regulates the expression of cardiac genes.
Belongs to the tigger transposable element derived protein family.
Belongs to the serpin family. Ov-serpin subfamily.
May not exhibit serine protease inhibitory activity.
The OTU domain mediates the deubiquitinating activity.
The RanBP2-type zinc fingers, also called NZFs, mediate the interaction with ubiquitin and determine linkage specificity. RanBP2-type zinc fingers 1 and 2 (also named NZF1 and NZF2) specifically recognize and bind 'Lys-29'- and 'Lys-33'-linked ubiquitin. RanBP2-type zinc finger 3 (also named NZF3) binds 'Lys-33'-linked ubiquitin and shows weak binding to 'Lys-6'-, 'Lys-48'- and 'Lys-63'-linked ubiquitin chains but it does not interact with 'Lys-29'-linked chains.
The second ankyrin repeat ANK 2 is termed AnkUBD, it interacts with ubiquitin hydrophobic patch and contributes to linkage specificity.
Ubiquitin thioesterase, which specifically hydrolyzes 'Lys-29'-linked and 'Lys-33'-linked diubiquitin (By similarity). Also cleaves 'Lys-63'-linked chains, but with 40-fold less efficiency compared to 'Lys-29'-linked ones (By similarity). Positive regulator of the Wnt signaling pathway that deubiquitinates apc protein, a negative regulator of Wnt-mediated transcription (By similarity). Acts as a regulator of autophagy by mediating deubiquitination of pik3c3/vps34, thereby promoting autophagosome maturation (By similarity). Plays a role in the regulation of cell morphology and cytoskeletal organization (By similarity). Required in the stress fiber dynamics and cell migration (By similarity).
Belongs to the formin homology family. Diaphanous subfamily.
Belongs to the bacterial ribosomal protein bL32 family.
It is uncertain whether Met-1 or Met-3 is the initiator.
Probably involved in transcriptional repression (By similarity). May play a role in the maintenance of the circadian clock periodicity.
The RRM domains can bind to both DNA and RNA.
Belongs to the arylamine N-acetyltransferase family.
Belongs to the deoxyhypusine synthase family.
Plays a role in neuronal plasticity and the proteolytic action may subserve structural reorganizations associated with learning and memory operations.
Belongs to the complex I NDUFC2 subunit family.
Cell surface proteoglycan that bears heparan sulfate.
O-glycosylated with heparan sulfate side chains.
Adaptor protein complex 2 (AP-2) is a heterotetramer composed of two large adaptins (alpha-type subunit and beta-type subunit), a medium adaptin (mu-type subunit) and a small adaptin (sigma-type subunit).
Belongs to the adaptor complexes medium subunit family.
Component of the adaptor complexes which link clathrin to receptors in coated vesicles. Clathrin-associated protein complexes are believed to interact with the cytoplasmic tails of membrane proteins, leading to their selection and concentration. AP50 is a subunit of the plasma membrane adaptor. The complex binds polyphosphoinositide-containing lipids.
Belongs to the gamma-glutamyltransferase family.
Cleaves the gamma-glutamyl peptide bond of glutathione and glutathione conjugates.
Belongs to the universal ribosomal protein uS9 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 (By similarity). V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment (By similarity). Required for assembly and activity of the vacuolar ATPase (By similarity).
V-ATPase is a heteromultimeric enzyme made up of two complexes: the ATP-hydrolytic V1 complex and the proton translocation V0 complex (By similarity). The V1 complex consists of three catalytic AB heterodimers that form a heterohexamer, three peripheral stalks each consisting of EG heterodimers, one central rotor including subunits D and F, and the regulatory subunits C and H (By similarity). The proton translocation complex V0 consists of the proton transport subunit a, a ring of proteolipid subunits c9c'', rotary subunit d, subunits e and f, and two accessory subunits (By similarity).
Probable large-conductance Ca(2+)-activated chloride channel.
May be a substrate recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.
The SOCS box domain mediates the interaction with the Elongin BC complex, an adapter module in different E3 ubiquitin ligase complexes.
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.
Belongs to the Nudix hydrolase family. DCP2 subfamily.
Belongs to the aerobic coproporphyrinogen-III oxidase family.
Controls reversibly actin polymerization and depolymerization in a pH-sensitive manner. It has the ability to bind G- and F-actin in a 1:1 ratio of cofilin to actin. It is the major component of intranuclear and cytoplasmic actin rods (By similarity).
Phosphorylates uridine and cytidine to uridine monophosphate and cytidine monophosphate. Does not phosphorylate deoxyribonucleosides or purine ribonucleosides. Can use ATP or GTP as a phosphate donor.
May play a role in the formation of the epithelial barrier.
Component of the UV-DDB complex which includes ddb1 and ddb2 (By similarity). Component of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex that includes cul4a, or cul4b, ddb1, ddb2 and rbx1. A large number of other DCX complexes may also exist in which an alternate substrate targeting subunit replaces ddb2. These targeting subunits are generally known as DCAF (ddb1- and cul4-associated factor) or CDW (cul4-ddb1-associated WD40-repeat) proteins (By similarity).
Interblade loops of the WD repeat region mediate most of the interaction with DNA. A hairpin between blades 5 and 6 inserts into DNA minor groove and mediates recognition of lesions and separation of the damaged and undamaged strands (By similarity).
Protein, which is both involved in DNA repair and protein ubiquitination, as part of the UV-DDB complex and DCX (DDB1-CUL4-X-box) complexes, respectively. Core component of the UV-DDB complex (UV-damaged DNA-binding protein complex), a complex that recognizes UV-induced DNA damage and recruit proteins of the nucleotide excision repair pathway (the NER pathway) to initiate DNA repair. The UV-DDB complex preferentially binds to cyclobutane pyrimidine dimers (CPD), 6-4 photoproducts (6-4 PP), apurinic sites and short mismatches. Also functions as the substrate recognition module for the DCX (DDB2-CUL4-X-box) E3 ubiquitin-protein ligase complex DDB2-CUL4-ROC1 (also known as CUL4-DDB-ROC1 and CUL4-DDB-RBX1). The DDB2-CUL4-ROC1 complex may ubiquitinate histone H2A, histone H3 and histone H4 at sites of UV-induced DNA damage. The ubiquitination of histones may facilitate their removal from the nucleosome and promote subsequent DNA repair.
The DWD box is required for interaction with ddb1.
Transcriptional regulator which may play a role in the differentiation and maintenance of meso-diencephalic dopaminergic (mdDA) neurons.
Required for several aspects of embryonic development including normal development of the eye.
Catalyzes the transfer of a farnesyl moiety from farnesyl diphosphate to a cysteine at the fourth position from the C-terminus of several proteins. The beta subunit is responsible for peptide-binding.
Interacts with sae2 and ube2i. Covalently attached to a number of proteins, including top2 (By similarity).
Ubiquitin-like protein that can be covalently attached to proteins as a monomer or as a lysine-linked polymer. Covalent attachment via an isopeptide bond to its substrates requires prior activation by the E1 complex sae1-sae2 and linkage to the E2 enzyme ube2i, and can be promoted by an E3 ligase such as pias1-4. This post-translational modification on lysine residues of proteins plays a crucial role in a number of cellular processes such as nuclear transport, DNA replication and repair, mitosis and signal transduction. Polymeric sumo2 chains are also susceptible to polyubiquitination which functions as a signal for proteasomal degradation of modified proteins (By similarity).
Belongs to the UNC119-binding protein family.
Interacts with unc119 family proteins; interaction preferentially takes place when unc119 proteins are unliganded with myristoylated proteins.
May play a role in immune regulation through regulation of the macrophage function (By similarity). May also play a role in trafficking of proteins via its interaction with unc119 family cargo adapters (By similarity). May play a role in ciliary membrane localization (By similarity).
Belongs to the cysteine synthase/cystathionine beta-synthase family.
Component of multiple BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes formed of cul3, rbx1 and a variable BTB domain-containing protein acting as both, adapter to cullin and substrate recognition subunit (By similarity). Interacts with btbd6 (By similarity).
Neddylated. Attachment of NEDD8 is required for the E3 ubiquitin-protein ligase activity of the SCF-like complex.
Probable core component of cullin-based SCF-like E3 ubiquitin-protein ligase complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins (By similarity). The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit (By similarity). Involved in ER-Golgi transport by regulating the size of COPII coats, thereby playing a key role in collagen export, which is required for embryonic stem (ES) cells division (By similarity). May play a role in the regulation of mittotic entry via ubiquitination of aurka (By similarity).
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids (By similarity).
Probable core component of the endosomal sorting required for transport complex III (ESCRT-III). ESCRT-III components are thought to multimerize to form a flat lattice on the perimeter membrane of the endosome (By similarity).
Disulfide bond formation at Cys-244 occurs in case of membrane damage that cause the entry of the oxidized milieu of the extracellular space, resulting in homooligomerization.
Muscle-specific protein that plays a central role in cell membrane repair by nucleating the assembly of the repair machinery at injury sites. Specifically binds phosphatidylserine. Acts as a sensor of oxidation: upon membrane damage, entry of extracellular oxidative environment results in disulfide bond formation and homooligomerization at the injury site. This oligomerization acts as a nucleation site for recruitment of TRIM72-containing vesicles to the injury site, leading to membrane patch formation. Probably acts upstream of the Ca(2+)-dependent membrane resealing process (By similarity).
Actins are highly conserved proteins that are involved in various types of cell motility.
Oxidation of Met-46 and Met-49 by MICALs (mical1, mical2 or mical3) to form methionine sulfoxide promotes actin filament depolymerization. Mical1 and mical2 produce the (R)-S-oxide form. The (R)-S-oxide form is reverted by msrb1 and msrb2, which promote actin repolymerization (By similarity).
Polymerization of globular actin (G-actin) leads to a structural filament (F-actin) in the form of a two-stranded helix. Each actin can bind to 4 others.
Shows a different expression pattern to Xenopus laevis act2. Expressed in stage 24 and 42 embryos as well as in adult heart, but not adult skeletal muscle.
The cardiac versus skeletal expression patterns of actins are probably sequence-dependent. For example, cardiac actins contain a Glu at position 3 of the mature peptide, whereas skeletal actins contain an Asp at this position.
Xenopus contains at least three sarcomeric alpha actin genes that are preferentially expressed in either heart or skeletal muscle.
Involved in endoplasmic reticulum to Golgi apparatus trafficking at a very early stage.
Catalyzes the transfer of one adenosine molecule from an ATP to an mRNA poly(A) tail bearing a 3'-OH terminal group in an ATP hydrolysis-dependent manner and participates in cytoplasmic polyadenylation (PubMed:34048638). May be involved in maintaining the translation efficiency of at least some genes through preventing degradation of their mRNAs (By similarity).
Belongs to the methyltransferase superfamily. Arsenite methyltransferase 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. Preferentially accommodates proteins with transmembrane domains that are weakly hydrophobic or contain destabilizing features such as charged and aromatic residues. Involved in the cotranslational insertion of multi-pass membrane proteins in which stop-transfer membrane-anchor sequences become ER membrane spanning helices. It is also required for the post-translational insertion of tail-anchored/TA proteins in endoplasmic reticulum membranes. By mediating the proper cotranslational insertion of N-terminal transmembrane domains in an N-exo topology, with translocated N-terminus in the lumen of the ER, controls the topology of multi-pass membrane proteins like the G protein-coupled receptors. By regulating the insertion of various proteins in membranes, it is indirectly involved in many cellular processes.
Belongs to the MICOS complex subunit Mic10 family.
Component of the mitochondrial contact site and cristae organizing system (MICOS) complex.
Inhibits programmed -1 ribosomal frameshifting (-1PRF) of a variety of mRNAs from viruses and cellular genes. Interacts with the -1PRF signal of target mRNA and translating ribosomes and causes premature translation termination at the frameshifting site. May exhibit antiviral activity.
Belongs to the nucleoporin Nup85 family.
Component of the nuclear pore complex (NPC) that seems to be required for NPC assembly and maintenance (By similarity). Involved in nephrogenesis (PubMed:30179222).
Component of the nuclear pore complex (NPC).
Morpholino knockdown of nup85 results in abnormal pronephric development characterized by underdeveloped to completely absent pronephros.
Adapter protein implicated in the regulation of a large spectrum of both general and specialized signaling pathways. Binds to a large number of partners, usually by recognition of a phosphoserine or phosphothreonine motif. Binding generally results in the modulation of the activity of the binding partner (By similarity).
Homodimer, and heterodimer with other family members.
Belongs to the glycosyltransferase 4 family.
Catalyzes the initial step of dolichol-linked oligosaccharide biosynthesis in N-linked protein glycosylation pathway: transfers GlcNAc-1-P from UDP-GlcNAc onto the carrier lipid dolichyl phosphate (P-dolichol), yielding GlcNAc-P-P-dolichol.
Belongs to the connexin family. Alpha-type (group II) subfamily.
Mitochondrial NAD(+) kinase that phosphorylates NAD(+) to yield NADP(+). Can use both ATP or inorganic polyphosphate as the phosphoryl donor (By similarity).
Mitochondrial NAD(+) kinase that phosphorylates NAD(+) to yield NADP(+). Can use both ATP or inorganic polyphosphate as the phosphoryl donor.
May act as a regulator of myogenesis (By similarity). Promotes the repair of DNA double-strand breaks (DSBs) through the homologous recombination pathway by facilitating the recruitment of the DNA endonuclease RBBP8 to the DSBs (By similarity).
Involved in postimplantation and gastrulation stages of development. Binds to DNA and RNA (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.
Component of the signal peptidase complex (SPC) which catalyzes the cleavage of N-terminal signal sequences from nascent proteins as they are translocated into the lumen of the endoplasmic reticulum (By similarity). Enhances the enzymatic activity of SPC and facilitates the interactions between different components of the translocation site (By similarity).
Component of the signal peptidase complex paralog A (SPC-A) composed of a catalytic subunit sec11a and three accessory subunits spcs1, spcs2 and spcs3. Component of the signal peptidase complex paralog C (SPC-C) composed of a catalytic subunit sec11c and three accessory subunits spcs1, spcs2 and spcs3. The complex induces a local thinning of the ER membrane which is used to measure the length of the signal peptide (SP) h-region of protein substrates. This ensures the selectivity of the complex towards h-regions shorter than 18-20 amino acids.
Component of the PEX2-PEX10-PEX12 retrotranslocation channel.
Belongs to the universal ribosomal protein uL10 family.
Ribosomal protein P0 is the functional equivalent of E.coli protein L10.
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.
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.
N-terminal cleavage of acetylated methionine of immature cytoplasmic actin by ACTMAP.
Oxidation of Met-44 and Met-47 by MICALs (mical1, mical2 or mical3) to form methionine sulfoxide promotes actin filament depolymerization. Mical1 and mical2 produce the (R)-S-oxide form. The (R)-S-oxide form is reverted by msrb1 and msrb2, which promote actin repolymerization.
Centrosomal protein involved in regulation of centriole duplication. Required to limit centriole duplication to once per cell cycle by preventing centriole reduplication (By similarity).
Centrosomal protein involved in regulation of centriole duplication. Required to limit centriole duplication to once per cell cycle by preventing centriole reduplication.
Allosterically inhibited by the N-terminal domain. Inhibited by phloretin.
Electroneutral Na(+) Li(+)/H(+) antiporter that extrudes Na(+) or Li(+) in exchange for external protons across the membrane (By similarity). Uses the proton gradient/membrane potential to extrude sodium (By similarity). Contributes to the regulation of intracellular pH and sodium homeostasis (By similarity). Also able to mediate Na(+)/Li(+) antiporter activity in kidney (By similarity).
Homodimer; dimerization is essential for SLC9B2 activity. Lipids seem to play a role in the stabilization of the dimerization subdomain.
The subcellular localization of SLC9B2 remains controversial. Was initially thought to partially localize to mitochondria. However SLC9B2 does not seem to contain a mitochondrial targeting sequence. It was later established that its localizes predominantly in plasma membrane or intracellularly to endosomes and lysosomes (By similarity). In another recent study, endogenous SLC9B2 in the distal tubular cell line mpkDCT4 is detected in recycling endosomes but absent in plasma membrane (By similarity).
Belongs to the VAMP-associated protein (VAP) (TC 9.B.17) family.
Belongs to the GST superfamily. Pi family.
Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.
May act as a GTPase-activating protein for Rab family protein(s). Involved in neuronal projections development, probably through a negative modulation of ARF6 function. Involved in the regulation of synaptic vesicle trafficking.
The Rab-GAP TBC domain is essential for phosphatidylinositol binding.
Interacts with ripply2.2/bowline. Associates with tle4 in the presence of ripply2.2/bowline (By similarity).
Transcriptional activator. Plays a role in ventral mesoderm specification and acts together with nog during muscle differentiation. Mediates posterior pattern formation of the embryo, including specification of posterior mesoderm, via activation of the Wnt and Fgf signaling pathways (By similarity).
Required for the assembly of the ubiquinol-cytochrome c reductase complex (mitochondrial respiratory chain complex III or cytochrome b-c1 complex), mediating cytochrome b recruitment and probably stabilization within the complex. Thereby, plays an important role in ATP production by mitochondria. Cardiolipin-binding protein, it may also control the cardiolipin composition of mitochondria membranes and their morphology.
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.
Belongs to the SNF2/RAD54 helicase family. ISWI subfamily.
Belongs to the GSK-3-binding protein family.
Regulates the magnitude of NFAT-driven transcription of a specific subset of cytokine genes.
Homotetramer. Dimer of dimers. In the homotetramer, subunits assemble around a central channel that can accommodate two ligand molecules. Interacts with rbp4 (By similarity).
Sulfonation of the reactive cysteine Cys-33 enhances the stability of the native conformation of TTR, avoiding misassembly of the protein leading to amyloid formation.
The N-terminus strongly influences thyroid hormone-binding properties.
Thyroid hormone-binding protein, with a much higher binding affinity for triiodothyronine (T3) than for thyroxine (T4). Probably transports triiodothyronine from the bloodstream to the brain (By similarity).
May associate with CD21. May regulate the release of Ca(2+) from intracellular stores.
Component of the ribosomal small subunit (SSU) processome.
Interacts with SDHA within the SDH catalytic dimer.
Plays an essential role in the assembly of succinate dehydrogenase (SDH), an enzyme complex (also referred to as respiratory complex II) that is a component of both the tricarboxylic acid (TCA) cycle and the mitochondrial electron transport chain, and which couples the oxidation of succinate to fumarate with the reduction of ubiquinone (coenzyme Q) to ubiquinol. Required for flavinylation (covalent attachment of FAD) of the flavoprotein subunit SDHA of the SDH catalytic dimer.
Detectable at stage 9 and prominently expressed from stage 10 (early gastrula) to stage 30 (tadpole). Restricted to the dorsal segment of the gastrula. At stage 10, expressed exclusively in the dorsal blastopore lip and the Spemann-Mangold organizer. Excluded from the dorsal margin of the Spemann-Mangold organizer. At stage 11, expressed in the anterior prechordal plate. By blastopore closure, expression restricted to the anterior midline. At early neurula, expressed in the midline anterior to the tip of the notochord in cells of the endoderm and overlying neural ectoderm.
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.
Metalloprotease that acts as a negative regulator of the Wnt signaling pathway: expressed in the Spemann-Mangold organizer and is required for anterior-neural patterning in head formation in embryos. Acts 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. Able to cleave wnt8.
Zygotically expressed in the Spemann-Mangold organizer, in particular in the head Spemann-Mangold organizer region responsible for anterior patterning.
Component of the ARISC complex, at least composed of uimc1/rap80, abraxas1, brcc3/brcc36, babam2 and babam1/nba1. Component of the BRCA1-A complex, at least composed of brca1, bard1, uimc1/rap80, abraxas1, brcc3/brcc36, babam2 and babam1/nba1. In the BRCA1-A complex, interacts directly with abraxas1, brcc3/brcc36 and babam1/nba1. Binds polyubiquitin. Component of the BRISC complex, at least composed of abraxas2, brcc3/brcc36, babam2 and babam1/nba1.
Component of the BRCA1-A complex, a complex that specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the brca1-bard1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). The BRCA1-A complex also possesses deubiquitinase activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX. In the BRCA1-A complex, it acts as an adapter that bridges the interaction between babam1/nba1 and the rest of the complex, thereby being required for the complex integrity and modulating the E3 ubiquitin ligase activity of the brca1-bard1 heterodimer. Component of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys-63'-linked ubiquitin in various substrates. Within the BRISC complex, acts as an adapter that bridges the interaction between babam1/nba1 and the rest of the complex, thereby being required for the complex integrity. The BRISC complex is required for normal mitotic spindle assembly and microtubule attachment to kinetochores via its role in deubiquitinating numa1. The BRISC complex plays a role in interferon signaling via its role in the deubiquitination of the interferon receptor ifnar1; deubiquitination increases ifnar1 activity by enhancing its stability and cell surface expression. Down-regulates the response to bacterial lipopolysaccharide (LPS) via its role in ifnar1 deubiquitination. May play a role in homeostasis or cellular differentiation in cells of neural, epithelial and germline origins. May also act as a death receptor-associated anti-apoptotic protein, which inhibits the mitochondrial apoptotic pathway.
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.
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 (By similarity).
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.
Belongs to the eukaryotic RPC7 RNA polymerase subunit family.
Component of the RNA polymerase III (Pol III) complex.
Belongs to the bacterial ribosomal protein bL12 family.
Required for the formation of a threonylcarbamoyl group on adenosine at position 37 (t(6)A37) in mitochondrial tRNAs that read codons beginning with adenine. Probably involved in the transfer of the threonylcarbamoyl moiety of threonylcarbamoyl-AMP (TC-AMP) to the N6 group of A37. Involved in mitochondrial genome maintenance.
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).
May function as 2-oxoglutarate-dependent dioxygenase.
Belongs to the threonine aldolase family.
Belongs to the potassium channel family. B (Shab) (TC 1.A.1.2) subfamily. Kv2.2/KCNB2 sub-subfamily.
In the mitochondria, together with PHB, forms large ring complexes (prohibitin complexes) in the inner mitochondrial membrane (IMM) and functions as chaperone protein that stabilizes mitochondrial respiratory enzymes and maintains mitochondrial integrity in the IMM, which is required for mitochondrial morphogenesis, neuronal survival, and normal lifespan.
In the nucleus, serves as transcriptional co-regulator.
Protein with pleiotropic attributes mediated in a cell-compartment- and tissue-specific manner, which include the plasma membrane-associated cell signaling functions, mitochondrial chaperone, and transcriptional co-regulator of transcription factors and sex steroid hormones in the nucleus.
The mitochondrial prohibitin complex consists of two subunits (PHB1 and PHB2), assembled into a membrane-associated ring-shaped supercomplex of approximately 1 mDa.
Belongs to the apolipoprotein O/MICOS complex subunit Mic27 family.
Regulatory subunit of serine/threonine-protein phosphatase 4 (PP4).
Belongs to the UPL family. K-HECT subfamily.
E3 ubiquitin-protein ligase involved in ubiquitin fusion degradation (UFD) pathway and regulation of DNA repair. Part of the ubiquitin fusion degradation (UFD) pathway, a process that mediates ubiquitination of protein at their N-terminus, regardless of the presence of lysine residues in target proteins.
E3 ubiquitin-protein ligase involved in ubiquitin fusion degradation (UFD) pathway and regulation of DNA repair. Part of the ubiquitin fusion degradation (UFD) pathway, a process that mediates ubiquitination of protein at their N-terminus, regardless of the presence of lysine residues in target proteins. Acts as a key regulator of DNA damage response by acting as a suppressor of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites, thereby acting as a guard against excessive spreading of ubiquitinated chromatin at damaged chromosomes.
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.
Belongs to the Mediator complex subunit 20 family.
Belongs to the G-protein coupled receptor 1 family. FSH/LSH/TSH subfamily.
G protein-coupled receptor for follitropin, the follicle-stimulating hormone. Through cAMP production activates the downstream PI3K-AKT and ERK1/ERK2 signaling pathways.
Homotrimer; trimerization probably requires binding to phosphatidylinositol 4,5-bisphosphate (PIP2).
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.
Belongs to the JARID1 histone demethylase family.
Channel-forming protein essential for import of protein precursors into mitochondria.
Forms part of the preprotein translocase complex of the outer mitochondrial membrane (TOM complex). Interacts with mitochondrial targeting sequences (By similarity).
Belongs to the WD repeat Groucho/TLE family.
Belongs to the 'GDXG' lipolytic enzyme family.
Belongs to the IMPDH/GMPR family. GuaC type 1 subfamily.
Catalyzes the irreversible NADPH-dependent deamination of GMP to IMP. It functions in the conversion of nucleobase, nucleoside and nucleotide derivatives of G to A nucleotides, and in maintaining the intracellular balance of A and G nucleotides.
Plays a role in regulating placenta growth. May act via its PH domain that competes with other PH domain-containing proteins, thereby preventing their binding to membrane lipids (By similarity).
The PH domain binds phosphoinositides with a broad specificity. It may compete with the PH domain of some other proteins, thereby interfering with their binding to phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol 3,4,5-trisphosphate (PIP3) (By similarity).
Belongs to the eIF4E-binding protein family.
Plays a role in processing of mitochondrial RNA precursors and in stabilization of a subset of mature mitochondrial RNA species. May play a role in cell cycle progression.
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.
Binds 3 Ca(2+) ions per subunit. Two of the Ca(2+) ions are bound to the C2 domain.
Belongs to the flavoprotein pyridine nucleotide cytochrome reductase family.
NADH-cytochrome b5 reductase involved in endoplasmic reticulum stress response pathway.
Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome. Positively regulates dimethylation of two adjacent adenosines in the loop of a conserved hairpin near the 3'-end of 18S rRNA.
Component of the small nucleolar ribonucleoprotein particle containing H/ACA-type snoRNAs (H/ACA snoRNPs). Component of the telomerase holoenzyme complex.
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 (By similarity).
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.
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.
Belongs to the cation transport ATPase (P-type) (TC 3.A.3) family. Type IIC subfamily.
Acts as a transcription factor (By similarity). May play a role in neuronal differentiation (By similarity).
Belongs to the phytoene/squalene synthase family.
Catalyzes the condensation of 2 farnesyl pyrophosphate (FPP) moieties to form squalene.
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.
Esterifies acyl-group from acyl-ACP to the sn-1 position of glycerol-3-phosphate, an essential step in glycerolipids biosynthesis such as triglycerides, phosphatidic acids and lysophosphatidic acids.
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.
Catalyzes the hydrolysis of nucleoside triphosphates and diphosphates in a calcium- or magnesium-dependent manner. Preferentially hydrolyzes nucleoside 5'-triphosphates, with substrate preference for UTP > GTP > CTP. Hydrolyzes ATP and nucleoside diphosphates only to a minor extent.
Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome. Its dissociation from the complex determines the transition from state pre-A1 to state pre-A1* (By similarity). May inhibit mRNA translation (By similarity).
Belongs to the extended synaptotagmin family.
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.
May play a role in the reorganization of neuronal actin structure.
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.
Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis.
DNA helicase that possesses intrinsic ATP-dependent nucleosome-remodeling activity and is both required for DNA repair and heterochromatin organization. Promotes DNA end resection of double-strand breaks (DSBs) following DNA damage: probably acts by weakening histone DNA interactions in nucleosomes flanking DSBs. Required for the restoration of heterochromatin organization after replication (By similarity).
Belongs to the eutherian X-chromosome-specific Armcx family.
E3 ubiquitin ligase which accepts ubiquitin and transfers it to substrates thereby promoting their degradation by the endoplasmic reticulum-associated degradation (ERAD) pathway which is a pathway involved in ubiquitin-dependent degradation of misfolded endoplasmic reticulum proteins (By similarity). May regulate the unfolded protein response to reduce endoplasmic reticulum stress (By similarity).
Homodimer. Secreted homodimers form a complex with wnt5a homodimers; tyrosine sulfation of both wnt11 and wnt5a by tpst1 is required for this interaction. Interacts with the transmembrane receptor fzd7/fz7. Interacts with lrp6 and ryk. Interacts with tdgf1/frl1. Interacts weakly with frzb1 and strongly with frzb2/crescent. Interaction with frzb2/crescent antagonizes wnt11 function in the neuroectoderm, but enhances it in mesodermal tissue (By similarity).
Ligand for the frizzled7 transmembrane receptor. Primarily acts via non-canonical Wnt pathways mediated by either Ca(2+) and PKC, or by JNK and dvl2/dsh. Depending on the cellular context, can also signal via the canonical Wnt pathway mediated by beta-catenin and dvl2/dsh. May also inhibit canonical Wnt signaling. Maternally initiates dorsal/ventral axis formation by a canonical route, which signals via lrp6. In a complex with wnt5a, activates the canonical and non-canonical processes involved in axis formation. In the non-canonical pathway, acts through fzd7/fz7 to induce phosphorylation of dvl2/dsh. Signals through a non-canonical Wnt pathway to regulate convergent extension movements during gastrulation. Interactions with the secreted Wnt antagonist sfrp5 to coordinate foregut development, acting via a non-canonical wnt pathway whereby sfrp5 restricts wnt11b activity to prevent inappropriate foregut formation. Mediates cardiogenesis via non-canonical Wnt signaling involving JNK-activation and PKC. Acts redundantly with wnt11/wnt11r during pronephros induction (By similarity).
Xenopus and other lower vertebrates contain duplicated wnt11 genes (wnt11 and wnt11b) resulting from an ancient gene duplication event, but the second copy has since been lost in mammals. In addition, X.tropicalis has two very similar wnt11b genes suggesting a further recent duplication event.
E3 ubiquitin-protein ligase that acts in the endoplasmic reticulum (ER)-associated degradation (ERAD) pathway, which targets misfolded proteins that accumulate in the endoplasmic reticulum (ER) for ubiquitination and subsequent proteasome-mediated degradation. Protects cells from ER stress-induced apoptosis.
Calsequestrin is a high-capacity, moderate affinity, calcium-binding protein and thus acts as an internal calcium store in muscle.
Sodium-dependent lysophosphatidylcholine (LPC) symporter, which plays an essential role for blood-brain barrier formation and function. Specifically expressed in endothelium of the blood-brain barrier of micro-vessels and transports LPC into the brain. Transport of LPC is essential because it constitutes the major mechanism by which docosahexaenoic acid (DHA), an omega-3 fatty acid that is essential for normal brain growth and cognitive function, enters the brain. Transports LPC carrying long-chain fatty acids such LPC oleate and LPC palmitate with a minimum acyl chain length of 14 carbons. Does not transport docosahexaenoic acid in unesterified fatty acid.
Plays a role in endocytic trafficking. Required for receptor recycling from endosomes, both to the trans-Golgi network and the plasma membrane.
Belongs to the universal ribosomal protein uL15 family.
Belongs to the V-ATPase H subunit family.
Subunit of the V1 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons. V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments.
Component of the signal recognition particle (SRP) complex, a ribonucleoprotein complex that mediates the cotranslational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER). SRP9 together with SRP14 and the Alu portion of the SRP RNA, constitutes the elongation arrest domain of SRP. The complex of SRP9 and SRP14 is required for SRP RNA binding.
Belongs to the carnosine N-methyltransferase family.
Component of the U1 snRNP. The U1 snRNP is composed of the U1 snRNA and the 7 core Sm proteins snrpb, snrpd1, snrpd2, snrpd3, snrpe, snrpf and snrpg that assemble in a heptameric protein ring on the Sm site of the small nuclear RNA to form the core snRNP, and at least three U1 snRNP-specific proteins snrnp70/U1-70K, snrpa/U1-A and snrpc/U1-C.
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. snrnp70 binds to the loop I region of U1-snRNA.
The RRM domain mediates interaction with U1 RNA.
Acts at least in part as component of the WASH complex which seems to regulate washc1 nucleation-promoting factor (NPF) activity and is required for its membrane targeting during endosomal sorting.
Belongs to the prenylcysteine oxidase family.
Belongs to the aldo/keto reductase family. Glutamate--cysteine ligase light chain subfamily.
Heterodimer of a catalytic heavy chain and a regulatory light chain.
May act as a GTPase-activating protein for Rab family protein(s).
Component of the RNA polymerase II (Pol II) complex consisting of 12 subunits.
May play a role in the response to environmental stress and cytokines. Appears to regulate translation by phosphorylating EIF4E, thus increasing the affinity of this protein for the 7-methylguanosine-containing mRNA cap (By similarity).
Belongs to the EGF-CFC (Cripto-1/FRL1/Cryptic) family.
Plays a role in short-term synaptic plasticity in a subset of GABAergic neurons in the brain.
Belongs to the apolipoprotein A1/A4/E family.
May negatively regulate aerobic respiration through mitochondrial protein lysine-acetylation.
Belongs to the integrin beta chain family.
Regulates the trafficking and gating properties of AMPA-selective glutamate receptors (AMPARs). Promotes their targeting to the cell membrane and synapses and modulates their gating properties by slowing their rates of activation, deactivation and desensitization and by mediating their resensitization. Does not show subunit-specific AMPA receptor regulation and regulates all AMPAR subunits.
Involved in cell shape and neuronal morphogenesis, positively regulating the establishment and maintenance of dendritic spines. Plays a role in cellular protein transport (By similarity).
Belongs to the DNA polymerase type-B-like family. GLD2 subfamily.
Component of a complex at least composed of cpeb1, cpsf1, tent2/gld2, pabpc1/ePAB, parn and sympk. Following oocyte maturation, parn is expelled from the complex. Interacts with rbm9 and sympk (By similarity).
Cytoplasmic poly(A) RNA polymerase that adds successive AMP monomers to the 3'-end of specific RNAs, forming a poly(A) tail. In contrast to the canonical nuclear poly(A) RNA polymerase, it only adds poly(A) to selected cytoplasmic mRNAs during oocyte maturation. Plays a central role during oocyte maturation by mediating polyadenylation of dormant mRNAs, which contain 5'AAUAAA-3' sequence in their 3'-UTR. In immature oocytes, polyadenylation of poly(A) tails is counteracted by the ribonuclease parn. During maturation parn is excluded from the ribonucleoprotein complex, allowing poly(A) elongation and activation of mRNAs. May not play a role in replication-dependent histone mRNA degradation (By similarity).
Ubiquitin-like protein involved in autophagic vesicle formation.
Belongs to the Engrailed homeobox family.
Belongs to the immunoglobulin superfamily. Contactin family.
Belongs to the peptidase M67A family. BRCC36 subfamily.
Component of the BRCA1-A complex, at least composed of brca1, bard1, uimc1/rap80, abraxas1, brcc3/brcc36, babam2 and babam1/nba1. In the BRCA1-A complex, interacts directly with abraxas1 and babam2. Component of the BRISC complex, at least composed of abraxas2, brcc3/brcc36, babam2 and babam1/nba1. Within the complex, interacts directly with abraxas2. Both the BRCA1-A complex and the BRISC complex bind polyubiquitin (By similarity).
Metalloprotease that specifically cleaves 'Lys-63'-linked polyubiquitin chains. Does not have activity toward 'Lys-48'-linked polyubiquitin chains. Component of the BRCA1-A complex, a complex that specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the brca1-bard1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). In the BRCA1-A complex, it specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX, antagonizing the rnf8-dependent ubiquitination at double-strand breaks (DSBs). Catalytic subunit of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys-63'-linked ubiquitin in various substrates. Mediates the specific 'Lys-63'-specific deubiquitination associated with the COP9 signalosome complex (CSN), via the interaction of the BRISC complex with the CSN complex. The BRISC complex is required for normal mitotic spindle assembly and microtubule attachment to kinetochores via its role in deubiquitinating numa1. Plays a role in interferon signaling via its role in the deubiquitination of the interferon receptor ifnar1; deubiquitination increases ifnar1 activity by enhancing its stability and cell surface expression. Acts as a regulator of the NLRP3 inflammasome by mediating deubiquitination of nlrp3. Down-regulates the response to bacterial lipopolysaccharide (LPS) via its role in ifnar1 deubiquitination.
Belongs to the HAD-like hydrolase superfamily. SerB family.
Expressed in the neural tube closure, with strongest expression in the floorplate. Expressed in ciliated epidermal cells.
Interacts with rsg1 (PubMed:19767740). Interacts with intu and wdpcp; fuz, intu and wdpcp probably form the core CPLANE (ciliogenesis and planar polarity effectors) complex (By similarity).
Knockdown of fy disrupted Hedgehog signaling and caused defects in neural tube closure, including exencephaly, spina bifida, and holoprosencephaly-like features.
Probable planar cell polarity effector involved in cilium biogenesis. Proposed to function as core component of the CPLANE (ciliogenesis and planar polarity effectors) complex involved in the recruitment of peripheral IFT-A proteins to basal bodies. May regulate protein and membrane transport to the cilium. May control the organization of the apical actin cytoskeleton, which is essential for the normal orientation of elongating ciliary microtubules.
Belongs to the eukaryotic ribosomal protein eL24 family.
Displays phosphatase activity for serine/threonine residues. Has apparently no phosphoglycerate mutase activity. May be regulator of mitochondrial dynamics (By similarity). May be a central mediator for programmed necrosis (By similarity).
Phosphorylated by the RIPK1/RIPK3 complex under necrotic conditions. This phosphorylation increases PGAM5 phosphatase activity (By similarity).
The N-terminal 35 amino acids, including the potential transmembrane alpha-helix, function as a non-cleaved mitochondrial targeting sequence that targets the protein to the cytosolic side of the outer mitochondrial membrane.
Involved in specifying the paraxial, but not dorsal, mesoderm. May regulate the expression of T-box transcription factors required for mesoderm formation and differentiation, such as brachyury T, wnt8, vegt and eomes (By similarity).
Belongs to the eukaryotic/archaeal RNase P protein component 3 family.
Belongs to the metallo-dependent hydrolases superfamily. Phosphotriesterase family.
Binds 2 divalent metal cations per subunit.
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.
May act as a component of endosomal retrieval machinery that is involved in protein transport from early endosomes to either recycling endosomes or the trans-Golgi network.
Component of a retrotranslocation channel required for peroxisome organization by mediating export of the PEX5 receptor from peroxisomes to the cytosol, thereby promoting PEX5 recycling.
Stimulates the RNA helicase activity of EIF4A in the translation initiation complex. Binds weakly mRNA.
Plays a role in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex that is involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex).
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.
In the C-terminal section; belongs to the formate--tetrahydrofolate ligase family.
In the N-terminal section; belongs to the tetrahydrofolate dehydrogenase/cyclohydrolase 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.
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.
Component of some SCF (SKP1-cullin-F-box) protein ligase complex that plays a central role in G1 arrest following DNA damage. Specifically recognizes phosphorylated cyclin-D1 (ccnd1), promoting its ubiquitination and degradation by the proteasome, resulting in G1 arrest (By similarity).
Part of a SCF (SKP1-cullin-F-box) protein ligase complex.
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.
Divalent metal cation. Prefers Mn(2+) over Mg(2+).
Protein that can both mediate the addition of adenosine 5'-monophosphate (AMP) to specific residues of target proteins (AMPylation), and the removal of the same modification from target proteins (de-AMPylation), depending on the context (By similarity). The side chain of Glu-222 determines which of the two opposing activities (AMPylase or de-AMPylase) will take place (By similarity). Acts as a key regulator of the ERN1/IRE1-mediated unfolded protein response (UPR) by mediating AMPylation or de-AMPylation of HSPA5/BiP (By similarity). In unstressed cells, acts as an adenylyltransferase by mediating AMPylation of HSPA5/BiP at 'Thr-518', thereby inactivating it (By similarity). In response to endoplasmic reticulum stress, acts as a phosphodiesterase by mediating removal of ATP (de-AMPylation) from HSPA5/BiP at 'Thr-518', leading to restore HSPA5/BiP activity (By similarity).
The fido domain mediates the adenylyltransferase activity.
The side chain of Glu-222 determines which of the two opposing activities (AMPylase or de-AMPylase) will take place. In response to endoplasmic reticulum stress, mediates de-AMPylase activity (By similarity). Adenylyltransferase activity is inhibited by the inhibitory helix present at the N-terminus: Glu-222 binds ATP and competes with ATP-binding at Arg-362, thereby preventing adenylyltransferase activity (By similarity). In unstressed cells, disengagement of Glu-222 promotes adenylyltransferase activity (By similarity). Activation dissociates ATP-binding from Glu-222, allowing ordered binding of the entire ATP moiety with the alpha-phosphate in an orientation that is productive for accepting an incoming target hydroxyl side chain (By similarity).
Belongs to the protein kinase superfamily. RIO-type Ser/Thr kinase family.
Gamma-carboxyglutamate residues are formed by vitamin K dependent carboxylation by GGCX. These residues are essential for the binding of calcium.
The carboxylated form is one of the main organic components of the bone matrix, which constitutes 1-2% of the total bone protein (By similarity). The carboxylated form binds strongly to apatite and calcium (By similarity).
Belongs to the MsrA Met sulfoxide reductase family.
Belongs to the G-protein coupled receptor 5 family.
Belongs to the eukaryotic initiation factor 4E family.
Belongs to the TNF receptor-associated factor family. A subfamily.
E3 ubiquitin ligase that, together with UBE2N and UBE2V1, mediates the synthesis of 'Lys-63'-linked-polyubiquitin chains conjugated to proteins, such as IKBKG, IRAK1, AKT1 and AKT2. Also mediates ubiquitination of free/unanchored polyubiquitin chain that leads to MAP3K7 activation.
The MATH/TRAF domain binds to receptor cytoplasmic domains.
The coiled coil domain mediates homo- and hetero-oligomerization.
May act as a repressor of nr2c2-mediated transactivation by suppressing the binding between nr2c2 and its response element in target genes.
Functions as a negative regulator of the PI3 kinase/PI3K activity associated with endosomal membranes. By modifying the phosphatidylinositol 3-phosphate/PtdInsP3 content of endosomal membranes may regulate endosome fusion, recycling, sorting and early to late endosome transport.
B regulatory subunit of protein phosphatase 2A (PP2A) that plays a key role in cell cycle by controlling mitosis entry and exit. The activity of PP2A complexes containing ppp2r2d (PR55-delta) fluctuate during the cell cycle: the activity is high in interphase and low in mitosis. During mitosis, activity of PP2A is inhibited via interaction with phosphorylated ensa and arpp19 inhibitors. PP2A complexes containing ppp2r2d (PR55-delta) also regulate the activity of TGF-beta/Activin/Nodal signaling by restricting receptor activity. Within the PP2A complexes, the B regulatory subunits modulate substrate selectivity and catalytic activity, and may also direct the localization of the catalytic enzyme to a particular subcellular compartment (By similarity).
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. Interacts with ensa (when phosphorylated at 'Ser-67') and arpp19 (when phosphorylated at 'Ser-67'), leading to inhibit PP2A activity (By similarity).
Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.
Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. TrmE GTPase family.
Belongs to the bZIP family. Jun subfamily.
Belongs to the nucleotide pyrophosphatase/phosphodiesterase family.
Hydrolyzes extracellular Ap3A into AMP and ADP, and Ap4A into AMP and ATP. Ap3A and Ap4A are diadenosine polyphosphates thought to induce proliferation of vascular smooth muscle cells. Acts as a procoagulant, mediating platelet aggregation at the site of nascent thrombus via release of ADP from Ap3A and activation of ADP receptors (By similarity).
Sodium-independent transporter of chloride and iodide.
Belongs to the class-I pyridine nucleotide-disulfide oxidoreductase family. PYROXD1 subfamily.
Belongs to the class I-like SAM-binding methyltransferase superfamily. EFM4 family.
Protein-lysine methyltransferase that selectively catalyzes the trimethylation of EEF1A at 'Lys-318'.
Belongs to the protein-tyrosine phosphatase family. Non-receptor class CDC14 subfamily.
Belongs to the LDH/MDH superfamily. LDH family.
The POU domain controls nuclear translocation.
Transcription factor that binds to the octamer motif (5'-ATTTGCAT-3') and activates the promoters of the genes for some small nuclear RNAs (snRNA) and histone H2B. Acts downstream of Notch signaling during radial glia formation. Regulates apoptosis, possibly via an FGF-signaling pathway (By similarity).
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.
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. May act as an adapter protein linking the dynein motor complex to various cargos (By similarity).
Belongs to the immunoglobulin superfamily. BTN/MOG family.
Belongs to the glycosyl hydrolase 20 family.
Microtubule-binding protein that localizes to the microtubular manchette of elongating spermatids.
Belongs to the transaldolase family. Type 1 subfamily.
Catalyzes the rate-limiting step of the non-oxidative phase in the pentose phosphate pathway. Catalyzes the reversible conversion of sedheptulose-7-phosphate and D-glyceraldehyde 3-phosphate into erythrose-4-phosphate and beta-D-fructose 6-phosphate.
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.
Belongs to the mitochondrial pyruvate carrier (MPC) (TC 2.A.105) family.
Mediates the uptake of pyruvate into mitochondria.
Transcriptional activator. May be involved in the dorso-ventral patterning of the mesoderm (By similarity).
Actin-binding protein involved in motile and morphological processes. Inhibits actin polymerization, likely by sequestering G-actin (By similarity).
Belongs to the actin-binding proteins ADF family. Twinfilin subfamily.
Component of the nuclear pore complex (NPC)-associated TREX-2 complex (transcription and export complex 2). Component of the SAGA transcription coactivator-HAT complex. Within the SAGA complex, participates in a subcomplex of SAGA called the DUB module (deubiquitination module) (By similarity).
Involved in mRNA export coupled transcription activation by association with both the TREX-2 and the SAGA complexes. The transcription regulatory histone acetylation (HAT) complex SAGA is a multiprotein complex that activates transcription by remodeling chromatin and mediating histone acetylation and deubiquitination. Within the SAGA complex, participates in a subcomplex that specifically deubiquitinates histones. The SAGA complex is recruited to specific gene promoters by activators, where it is required for transcription. The TREX-2 complex functions in docking export-competent ribonucleoprotein particles (mRNPs) to the nuclear entrance of the nuclear pore complex (nuclear basket). TREX-2 participates in mRNA export and accurate chromatin positioning in the nucleus by tethering genes to the nuclear periphery (By similarity).
Belongs to the phage and mitochondrial RNA polymerase family.
Belongs to the vasopressin/oxytocin family.
N-alpha-acetyltransferase that acetylates the N-terminus of proteins that retain their initiating methionine. Has a broad substrate specificity: able to acetylate the initiator methionine of most peptides, except for those with a proline in second position. Also displays N-epsilon-acetyltransferase activity by mediating acetylation of the side chain of specific lysines on proteins. The relevance of N-epsilon-acetyltransferase activity is however unclear. Required for sister chromatid cohesion during mitosis by promoting binding of CDCA5/sororin to cohesin.
ATP-dependent serine protease that mediates the selective degradation of misfolded, unassembled or oxidatively damaged polypeptides as well as certain short-lived regulatory proteins in the mitochondrial matrix. May also have a chaperone function in the assembly of inner membrane protein complexes. Participates in the regulation of mitochondrial gene expression and in the maintenance of the integrity of the mitochondrial genome. Binds to mitochondrial DNA in a site-specific manner.
Homohexamer or homoheptamer. Organized in a ring with a central cavity.
Required for S phase entry of the cell cycle.
Lipid-binding protein involved in the biosynthesis of coenzyme Q, also named ubiquinone, an essential lipid-soluble electron transporter for aerobic cellular respiration. Binds a phospholipid of at least 10 carbons in each acyl group.
Structurally similar to the bacterial FadR protein (fatty acid metabolism regulator protein).
In tailbud embryos, expressed in embryonic muscle (myotomes).
The cardiac versus skeletal expression patterns of actins are probably sequence-dependent; Xenopus cardiac actins contain a Glu at position 3 of the mature peptide, whereas skeletal actins contain an Asp at this position.
Unlike Xenopus laevis act3, expression is restricted to embryonic and tadpole stages. Not expressed in adults.
Xenopus contains at least three different sarcomeric alpha actin genes that are preferentially expressed in either heart or skeletal muscle.
Involved in the modulation of the mitochondrial apoptotic pathway by ensuring the accumulation of cardiolipin (CL) in mitochondrial membranes. The triap1:prelid1 complex probably functions as a phosphatidic acid (PA) transporter across the mitochondrion intermembrane space to provide PA for cardiolipin CL synthesis in the inner membrane. Likewise, the triap1:prelid3a complex mediates the transfer of phosphatidic acid (PA) between liposomes (in vitro) and probably functions as a PA transporter across the mitochondrion intermembrane space (in vivo). Mediates cell survival by inhibiting activation of caspase-9 which prevents induction of apoptosis (By similarity). Required for pronephros development; probably involved at an early stage in the formation of pronephric components derived from the somatic layer (PubMed:18472403).
Monomer. Forms a complex with prelid1 in the mitochondrion intermembrane space. Interacts with prelid3a.
May play some role in mitochondrial processes.
Has antibacterial activity against a variety of bacteria including S.aureus, P.aeruginosa and M.tuberculosis. Acts by inducing bacterial membrane breakage (By similarity).
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 (By similarity).
Required for the processing of the 27S pre-rRNA.
Belongs to the alkaline phosphatase family.
Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components.
Laminin is a complex glycoprotein, consisting of three different polypeptide chains (alpha, beta, gamma), which are bound to each other by disulfide bonds into a cross-shaped molecule comprising one long and three short arms with globules at each end.
Belongs to the bile acid:sodium symporter (BASS) (TC 2.A.28) family.
Component of intercellular desmosome junctions. Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion.
May be involved in the intracellular transport of sterols or other lipids. May bind cholesterol or other sterols.
May function as a negative regulator of endoplasmic reticulum-stress induced autophagy.
Acts on tyrosine phosphorylated proteins, low-MW aryl phosphates and natural and synthetic acyl phosphates.
Belongs to the low molecular weight phosphotyrosine protein phosphatase family.
May act as the primary docking protein directing membrane turnover and assembly of the transient receptor potential channels trpc4 and trpc5. Binds phospholipids (By similarity).
May be involved in collagen fiber assembly.
Binds specifically to the 3'-terminal U-tract of U6 snRNA.
Belongs to the glycosyltransferase 41 family. O-GlcNAc transferase subfamily.
Transcription elongation factor implicated in the maintenance of proper chromatin structure in actively transcribed regions.
Component of the signal recognition particle (SRP) complex, a ribonucleoprotein complex that mediates the cotranslational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER). The SRP complex interacts with the signal sequence in nascent secretory and membrane proteins and directs them to the membrane of the ER.
Belongs to the acetyltransferase family. NAA40 subfamily.
Synthesizes selenophosphate from selenide and ATP.
Protein kinase that may play an important role in cellular stress response (By similarity). Plays an important role in activating certain potassium, sodium, and chloride channels, suggesting an involvement in the regulation of processes such as cell survival, neuronal excitability, and renal sodium excretion.
Belongs to the glycosyltransferase 13 family.
Initiates complex N-linked carbohydrate formation. Essential for the conversion of high-mannose to hybrid and complex N-glycans.
The cofactor is mostly bound to the substrate.
Contains 2 C-terminal transcription activation domains (AD1 and AD2) that can function independently.
Contains three Leu-Xaa-Xaa-Leu-Leu (LXXLL) motifs. The LXXLL motifs are essential for the association with nuclear receptors and are, at least in part, functionally redundant.
The LLXXLXXXL motif is involved in transcriptional coactivation and CREBBP/CBP binding.
Transcriptional coactivator for steroid receptors and nuclear receptors. Coactivator of the steroid binding domain (AF-2) but not of the modulating N-terminal domain (AF-1). Required in a nuclear receptor pathway to suppress expression of dorsal mesoderm genes. May play a role in the positive regulation of the circadian clock.
Belongs to the Mediator complex subunit 14 family.
May be involved in copper-dependent atp7a trafficking between the trans-Golgi network and vesicles in the cell periphery.
Belongs to the ABC transporter superfamily. ABCC family. CFTR transporter (TC 3.A.1.202) subfamily.
Epithelial ion channel that plays an important role in the regulation of epithelial ion and water transport and fluid homeostasis. Mediates the transport of chloride ions across the cell membrane. Channel activity is coupled to ATP hydrolysis. The ion channel is also permeable to HCO(3-); selectivity depends on the extracellular chloride concentration. Exerts its function also by modulating the activity of other ion channels and transporters. Contributes to the regulation of the pH and the ion content of the epithelial fluid layer.
Homodimer in endoplasmic reticulum, endoplasmic reticulum-Golgi intermediate compartment and cis-Golgi network. Interacts with IL1RL1. Interacts with RNF26; this interaction is important to modulate innate immune signaling through the cGAS-STING pathway.
Potential role in vesicular protein trafficking, mainly in the early secretory pathway. May act as a cargo receptor at the lumenal side for incorporation of secretory cargo molecules into transport vesicles and may be involved in vesicle coat formation at the cytoplasmic side. Plays a positive role in IL-33-mediated IL-8 and IL-6 production by interacting with interleukin-33 receptor IL1RL1. Plays also a role in the modulation of innate immune signaling through the cGAS-STING pathway by interacting with RNF26.
Belongs to the peptidase M24 family. SPT16 subfamily.
IGF-binding proteins prolong the half-life of the IGFs and have been shown to either inhibit or stimulate the growth promoting effects of the IGFs on cell culture. They alter the interaction of IGFs with their cell surface receptors.
Belongs to the archaeal Rpo3/eukaryotic RPB3 RNA polymerase subunit family.
Histone demethylase required for G2/M phase cell cycle progression (By similarity). Specifically demethylates dimethylated 'Lys-36' (H3K36me2) of histone H3, an epigenetic repressive mark, thereby acting as a transcription activator (By similarity). May play a role in the regulation of the circadian clock (By similarity).
Belongs to the spermidine/spermine synthase family.
Functions as a chaperone necessary for a stable expression of the CYBA and CYBB subunits of the cytochrome b-245 heterodimer.
Belongs to the adaptor complexes medium subunit family. Delta-COP subfamily.
Involved in the second step of GPI biosynthesis. De-N-acetylation of N-acetylglucosaminyl-phosphatidylinositol.
Accepts electrons from ETF and reduces ubiquinone.
Plasma membrane reductase that uses cytoplasmic ascorbate as an electron donor to reduce extracellular Fe(3+) into Fe(2+). It is also able to reduce extracellular monodehydro-L-ascorbate and may be involved in extracellular ascorbate regeneration (By similarity). May also function as a cupric transmembrane reductase (By similarity).
Antiparallel disulfide-linked heterodimer of an alpha chain and a beta chain. Self-associates and forms higher oligomers.
Functions as extracellular chaperone that prevents aggregation of non native proteins. Prevents stress-induced aggregation of blood plasma proteins.
Interacts with UBC9, RAN, RBM8A, eIF-1A and PAX6.
Belongs to the zinc-containing alcohol dehydrogenase family. Quinone oxidoreductase subfamily.
Belongs to the concentrative nucleoside transporter (CNT) (TC 2.A.41) family.
Belongs to the major facilitator superfamily. Sugar transporter (TC 2.A.1.1) family. Glucose transporter subfamily.
Facilitative glucose transporter required for the development of the cardiovascular system.
Endonuclease that specifically degrades the RNA of RNA-DNA hybrids.
Belongs to the radical SAM superfamily. RSAD2 family.
Phosphorylation at Thr-752 by CDK1 during M phase activates its kinase activity. Maximum phosphorylation occurs in prometaphase (By similarity).
Serine/threonine kinase that plays a key role in M phase by acting as a regulator of mitosis entry and maintenance. Acts by promoting the inactivation of protein phosphatase 2A (PP2A) during M phase: does not directly inhibit PP2A but acts by mediating phosphorylation and subsequent activation of arpp19 and ensa at 'Ser-67', 2 phosphatase inhibitors that specifically inhibit the ppp2r2d (PR55-delta) subunit of PP2A. Inactivation of PP2A during M phase is essential to keep cyclin-B1-CDK1 activity high. Following DNA damage, it is also involved in checkpoint recovery by being inhibited (By similarity).
Belongs to the class I-like SAM-binding methyltransferase superfamily. EEF2KMT family.
Despite its name, it does not contain any EF-hand domains.
Belongs to the adenylosuccinate synthetase family.
Component of the purine nucleotide cycle (PNC), which interconverts IMP and AMP to regulate the nucleotide levels in various tissues, and which contributes to glycolysis and ammoniagenesis. Catalyzes the first committed step in the biosynthesis of AMP from IMP.
Required for the assembly of the ubiquinol-cytochrome c reductase complex (mitochondrial respiratory chain complex III or cytochrome b-c1 complex). May play a role in the modulation of respiratory chain activities such as oxygen consumption and ATP production. May be involved in cytochrome b translation and/or stability.
Belongs to the nonaspanin (TM9SF) (TC 9.A.2) family.
Belongs to the TRAFAC class YlqF/YawG GTPase family.
In contrast to other GTP-binding proteins, this family is characterized by a circular permutation of the GTPase motifs described by a G4-G1-G3 pattern.
May play a role in regulating cellular proliferation.
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 a cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex that mediates the ubiquitination of target proteins, leading most often to their proteasomal degradation.
Homodimer. Part of cullin-RING-based BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes that contain CUL3 and SPOP, plus a target protein (By similarity).
The BTB (POZ) domain mediates dimerization and interaction with CUL3.
The MATH domain mediates interaction with protein-ubiquitin ligase substrates.
Belongs to the snRNP Sm proteins family. SmF/LSm6 subfamily.
Only one single gene encoding glyoxalase II has been identified in vertebrates. In yeast and higher plants, separate genes encode the cytosolic and mitochondrial forms of glyoxalase II.
Produced by alternative initiation at Met-54 of isoform 1. Alternative initiation has been proven in human.
Thiolesterase that catalyzes the hydrolysis of S-D-lactoyl-glutathione to form glutathione and D-lactic acid.
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). Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3.
Component of the small ribosomal subunit. The ribosome is a large ribonucleoprotein complex responsible for the synthesis of proteins in the cell. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome (By similarity). May play a role during erythropoiesis (By similarity).
G-protein coupled receptor for 5-hydroxytryptamine (serotonin).
Seems to promote the survival of visceral and proprioceptive sensory neurons.
Belongs to the eukaryotic AdoMetDC family.
Essential for biosynthesis of the polyamines spermidine and spermine. Promotes maintenance and self-renewal of embryonic stem cells, by maintaining spermine levels.
Belongs to the constitutive coactivator of PPAR-gamma family.
May be involved in the regulation of cellular senescence through a positive feedback loop with TP53.
Heterodimer; heterodimerizes with mettl3 to form an antiparallel heterodimer that constitutes an active methyltransferase. Component of the WMM complex, a N6-methyltransferase complex composed of a catalytic subcomplex, named MAC, and of an associated subcomplex, named MACOM. The MAC subcomplex is composed of mettl3 and mettl14.
The METTL3-METTL14 heterodimer forms a N6-methyltransferase complex that methylates adenosine residues at the N(6) position of some mRNAs and regulates the circadian clock, differentiation of embryonic stem cells and cortical neurogenesis. In the heterodimer formed with mettl3, mettl14 constitutes the RNA-binding scaffold that recognizes the substrate rather than the catalytic core. N6-methyladenosine (m6A), which takes place at the 5'-[AG]GAC-3' consensus sites of some mRNAs, plays a role in mRNA stability and processing.
Functions as component of the Arp2/3 complex which is involved in regulation of actin polymerization and together with an activating nucleation-promoting factor (NPF) mediates the formation of branched actin networks. Arp2/3 complex plays a critical role in the control of cell morphogenesis via the modulation of cell polarity development.
Belongs to the complex I LYR family. SDHAF3 subfamily.
Interacts with the iron-sulfur protein subunit within the SDH catalytic dimer.
Plays an essential role in the assembly of succinate dehydrogenase (SDH), an enzyme complex (also referred to as respiratory complex II) that is a component of both the tricarboxylic acid (TCA) cycle and the mitochondrial electron transport chain, and which couples the oxidation of succinate to fumarate with the reduction of ubiquinone (coenzyme Q) to ubiquinol. Promotes maturation of the iron-sulfur protein subunit of the SDH catalytic dimer, protecting it from the deleterious effects of oxidants. May act together with SDHAF1.
Belongs to the peptidase M67A family. MYSM1 subfamily.
Acts as an activator of hypoxia-induced mitophagy, an important mechanism for mitochondrial quality control.
Belongs to the small leucine-rich proteoglycan (SLRP) family. SLRP class III subfamily.
Belongs to the sauvagine/corticotropin-releasing factor/urotensin I family.
ATP-dependent microtubule severing protein that specifically recognizes and cuts microtubules that are polyglutamylated. Preferentially recognizes and acts on microtubules decorated with short polyglutamate tails: severing activity increases as the number of glutamates per tubulin rises from one to eight, but decreases beyond this glutamylation threshold. Microtubule severing promotes reorganization of cellular microtubule arrays and the release of microtubules from the centrosome following nucleation. Required for membrane traffic from the endoplasmic reticulum (ER) to the Golgi and for completion of the abscission stage of cytokinesis. Also plays a role in axon growth and the formation of axonal branches.
Belongs to the AAA ATPase family. Spastin subfamily.
Homohexamer. The homohexamer is stabilized by ATP-binding. The homohexamer may adopt a ring conformation through which microtubules pass prior to being severed. Interacts with microtubules.
A NAD(P)H-dependent oxidoreductase that acts as a key inhibitor of ferroptosis. At the plasma membrane, catalyzes reduction of coenzyme Q/ubiquinone-10 to ubiquinol-10, a lipophilic radical-trapping antioxidant that prevents lipid oxidative damage and consequently ferroptosis. Acts in parallel to GPX4 to suppress phospholipid peroxidation and ferroptosis. This anti-ferroptotic function is independent of cellular glutathione levels. Also acts as a potent radical-trapping antioxidant by mediating warfarin-resistant vitamin K reduction in the canonical vitamin K cycle: catalyzes NAD(P)H-dependent reduction of vitamin K (phylloquinone, menaquinone-4 and menadione) to hydroquinone forms. Hydroquinones act as potent radical-trapping antioxidants inhibitor of phospholipid peroxidation and ferroptosis. May play a role in mitochondrial stress signaling. Upon oxidative stress, associates with the lipid peroxidation end product 4-hydroxy-2-nonenal (HNE) forming a lipid adduct devoid of oxidoreductase activity, which then translocates from mitochondria into the nucleus triggering DNA damage and cell death.
Belongs to the FAD-dependent oxidoreductase family.
N-myristoylation at Gly-2 mediates the recruitment to lipid droplets and plasma membrane.
The modification by 4-hydroxy-2-nonenal (HNE) adduction in mitochondria results in loss of the oxidoreductase activity and activation of a novel function in mitochondrial oxidative stress signaling.
Belongs to the cytochrome c oxidase subunit 6A family.
Component of the PAF1 complex (PAF1C) which has multiple functions during transcription by RNA polymerase II (By similarity). PAF1C associates with RNA polymerase II, is involved in transcriptional elongation and in histone modifications including methylation on histone H3 'Lys-4' (H3K4me3) (By similarity).
Component of the PAF1 complex, which at least consists of cdc73, paf1, leo1, ctr9 and rtf1 (By similarity). The PAF1 complex interacts with PHF5A (By similarity).
Associates with the mitochondrial contact site and cristae organizing system (MICOS) complex (also known as MINOS or MitOS complex).
Its C-terminal part seems to contain many membrane-spanning sided beta-sheets, that have the potential to adopt a transmembrane beta-barrel type structure.
May play a role in the maintenance of the structure of mitochondrial cristae.
Belongs to the GST superfamily. Kappa family.
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.
Recognizes and binds the 7-methylguanosine-containing mRNA cap during an early step in the initiation of protein synthesis.
eIF4F is a multi-subunit complex, the composition of which varies with external and internal environmental conditions. It is composed of at least eIF4A, eIF4E and eIF4G (By similarity).
Mediates high-affinity intracellular uptake of the rare oligo-element molybdenum.
Belongs to the pterin-4-alpha-carbinolamine dehydratase family.
Belongs to the class I-like SAM-binding methyltransferase superfamily. BUD23/WBSCR22 family.
Phospholipid scramblase involved in lipid homeostasis and membrane dynamics processes. Has phospholipid scramblase activity toward cholesterol and phosphatidylserine, as well as phosphatidylethanolamine and phosphatidylcholine. Required for autophagosome formation: participates in early stages of autophagosome biogenesis at the endoplasmic reticulum (ER) membrane by reequilibrating the leaflets of the ER as lipids are extracted by atg2 (atg2a or atg2b) to mediate autophagosome assembly. In addition to autophagy, involved in other processes in which phospholipid scramblase activity is required. Modulates ER contacts with lipid droplets, mitochondria and endosomes.
The VTT domain was previously called the SNARE-assoc domain. As there is no evidence that this domain associates with SNARE proteins, it was renamed as VMP1, TMEM41, and TVP38 (VTT) domain.
Belongs to the aconitase/IPM isomerase family.
Binds 1 [4Fe-4S] cluster per subunit. [4Fe-4S]-binding affects RNA-binding activity, thereby inhibiting activity of the protein.
RNA-binding protein that binds to iron-responsive elements (IRES), which are stem-loop structures found in the 5'-UTR of ferritin, and delta aminolevulinic acid synthase mRNAs, and in the 3'-UTR of transferrin receptor mRNA. Binding to the IRE element in ferritin results in the repression of its mRNA translation. Binding of the protein to the transferrin receptor mRNA inhibits the degradation of this otherwise rapidly degraded mRNA.
Ubiquitinated and degraded by the proteasome in presence of high level of iron and oxygen.
May function in the epidermal growth factor receptor/EGFR signaling pathway.
Belongs to the TFIIF beta subunit family.
TFIIF is a general transcription initiation factor that binds to RNA polymerase II and helps to recruit it to the initiation complex in collaboration with TFIIB.
Belongs to the fibrillar collagen family.
Contains 3-hydroxyproline at a few sites. This modification occurs on the first proline residue in the sequence motif Gly-Pro-Hyp, where Hyp is 4-hydroxyproline.
Contains mostly 4-hydroxyproline. Prolines at the third position of the tripeptide repeating unit (G-X-P) are 4-hydroxylated in some or all of the chains.
Lysine residues at the third position of the tripeptide repeating unit (G-X-Y) are 5-hydroxylated in some or all of the chains.
O-glycosylated on hydroxylated lysine residues. The O-linked glycan consists of a Glc-Gal disaccharide.
The C-terminal propeptide, also known as COLFI domain, have crucial roles in tissue growth and repair by controlling both the intracellular assembly of procollagen molecules and the extracellular assembly of collagen fibrils. It binds a calcium ion which is essential for its function (By similarity).
Type II collagen is specific for cartilaginous tissues. It is essential for the normal embryonic development of the skeleton, for linear growth and for the ability of cartilage to resist compressive forces (By similarity).
Belongs to the band 7/mec-2 family. Flotillin subfamily.
Belongs to the phosphoglycerate kinase family.
Belongs to the cyclophilin-type PPIase family. PPIL2 subfamily.
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 class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. PR/SET subfamily.
Protein-lysine N-methyltransferase that monomethylates both histones and non-histone proteins. Specifically monomethylates 'Lys-20' of histone H4 (H4K20me1). H4K20me1 is enriched during mitosis and represents a specific tag for epigenetic transcriptional repression. Mainly functions in euchromatin regions, thereby playing a central role in the silencing of euchromatic genes. Required for cell proliferation, probably by contributing to the maintenance of proper higher-order structure of DNA during mitosis. Involved in chromosome condensation and proper cytokinesis. Nucleosomes are preferred as substrate compared to free histones. Mediates monomethylation of p53/TP53 at 'Lys-382', leading to repress p53/TP53-target genes. Plays a negative role in TGF-beta response regulation and a positive role in cell migration.
Central component of the receptor complex responsible for the recognition and translocation of cytosolically synthesized mitochondrial preproteins. Together with tom22 functions as the transit peptide receptor at the surface of the mitochondrion outer membrane and facilitates the movement of preproteins into the tom40 translocation pore (By similarity).
Forms part of the preprotein translocase complex of the outer mitochondrial membrane (TOM complex). Interacts with tom22 (By similarity).
Forms a distorted beta-barrel structure, with two helices that are packed against the outer surface of the barrel. Porphyrins are expected to bind to a hydrophobic patch on the outer surface of the beta-barrel structure (By similarity).
May bind free porphyrinogens that may be present in the cell and thus facilitate removal of these potentially toxic compound. Binds with a high affinity to one molecule of heme or porphyrins. It binds metalloporphyrins, free porphyrins and N-methylprotoporphyrin with similar affinities (By similarity).
Removes 5-oxoproline from various penultimate amino acid residues except L-proline.
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).
Belongs to the Mediator complex subunit 28 family.
Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family.
Has a role in pre-mRNA splicing. Phosphorylates SF2/ASF.
Stimulates membrane curvature formation and subsequent endoplasmic reticulum exit site (ERES) establishment by recruiting PI3K complex I, leading to COPII vesicle-mediated transport (By similarity). Promotes endoplasmic reticulum (ER) exit of cGAMP-activated STING1 oligomers (By similarity).
RNA-binding protein that regulates alternative splicing events.
Belongs to the cholesterol 7-desaturase family.
Accepts the ubiquitin-like protein NEDD8 from the UBA3-NAE1 E1 complex and catalyzes its covalent attachment to other proteins. The specific interaction with the E3 ubiquitin ligase rbx1, but not rbx2, suggests that the rbx1-ube2m complex neddylates specific target proteins, such as cul1, cul2, cul3 and cul4. Involved in cell proliferation.
Belongs to the ubiquitin-conjugating enzyme family. UBC12 subfamily.
Both the N-terminal docking peptide and the catalytic core domain must bind the uba3-nae1 complex simultaneously for optimal transfer of nedd8.
The acetylation of Met-1 increases affinity for DCUN1D1 by about 2 orders of magnitude and is crucial for NEDD8 transfer to cullins.
Demethylates proteins that have been reversibly carboxymethylated. Demethylates PPP2CB (in vitro) and PPP2CA. Binding to PPP2CA displaces the manganese ion and inactivates the enzyme.
Belongs to the glycosyltransferase 47 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.
Protein component of the very low density lipoprotein (VLDL) of egg-laying females. Potent lipoprotein lipase inhibitor, preventing the loss of triglycerides from VLDL on their way from the liver to the growing oocytes.
Belongs to the opioid growth factor receptor family.
Belongs to the ABC transporter superfamily. ABCD family. Peroxisomal fatty acyl CoA transporter (TC 3.A.1.203) subfamily.
Plays a role in mitochondrial aerobic respiration. Regulates mitochondrial organization and fission.
Belongs to the phosphatase 2A regulatory subunit B56 family.
Belongs to the immunoglobulin superfamily. AMIGO family.
Belongs to the DEAD box helicase family. eIF4A subfamily.
Some glutamate residues at the C-terminus are polyglutamylated, resulting in polyglutamate chains on the gamma-carboxyl group (By similarity). Polyglutamylation plays a key role in microtubule severing by spastin (SPAST). SPAST preferentially recognizes and acts on microtubules decorated with short polyglutamate tails: severing activity by SPAST increases as the number of glutamates per tubulin rises from one to eight, but decreases beyond this glutamylation threshold (By similarity).
Some glutamate residues at the C-terminus are polyglycylated, resulting in polyglycine chains on the gamma-carboxyl group. Glycylation is mainly limited to tubulin incorporated into axonemes (cilia and flagella) whereas glutamylation is prevalent in neuronal cells, centrioles, axonemes, and the mitotic spindle. Both modifications can coexist on the same protein on adjacent residues, and lowering polyglycylation levels increases polyglutamylation, and reciprocally. The precise function of polyglycylation is still unclear.
The MREI motif is common among all beta-tubulin isoforms and may be critical for tubulin autoregulation.
Required for replication-independent chromatin assembly and for the periodic repression of histone gene transcription during the cell cycle.
Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing.
Molecular chaperone which facilitates proper subunit assembly andsurface trafficking of alpha-7 (CHRNA7) and alpha-8 (CHRNA8) nicotinic acetylcholine receptors (By similarity). May also promote functional expression of homomeric serotoninergic 5-HT3 receptors, and of heteromeric acetylcholine receptors (By similarity).
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 DNA2/NAM7 helicase family. SDE3 subfamily.
Belongs to the eukaryotic ribosomal protein eL37 family.
Required for axonemal dynein assembly and ciliary motility in ciliated organs, including Kupffer's vesicle, during embryogenesis. Facilitates the onset of robust cilia motility during development.
Nuclear chaperone required for maturation and nuclear export of pre-60S ribosome subunits.
May play a role in the regulation of the epithelial-mesenchymal transition.
Plays a role in regulating cardiac sodium current.
Belongs to the proton-activated chloride channel family.
Proton-activated chloride channel that mediates import of chloride ion in response to extracellular acidic pH.
As part of a cytosolic protein quality control complex, the bag6/bat3 complex, maintains misfolded and hydrophobic patches-containing proteins in a soluble state and participates in their proper delivery to the endoplasmic reticulum or alternatively can promote their sorting to the proteasome where they undergo degradation. The bag6/bat3 complex is involved in the post-translational delivery of tail-anchored/type II transmembrane proteins to the endoplasmic reticulum membrane. Similarly, the bag6/bat3 complex also functions as a sorting platform for proteins of the secretory pathway that are mislocalized to the cytosol either delivering them to the proteasome for degradation or to the endoplasmic reticulum. The bag6/bat3 complex also plays a role in the endoplasmic reticulum-associated degradation (ERAD), a quality control mechanism that eliminates unwanted proteins of the endoplasmic reticulum through their retrotranslocation to the cytosol and their targeting to the proteasome. It maintains these retrotranslocated proteins in an unfolded yet soluble state condition in the cytosol to ensure their proper delivery to the proteasome.
Belongs to the glycosyltransferase 3 family.
Transfers the glycosyl residue from UDP-Glc to the non-reducing end of alpha-1,4-glucan.
Component of the THO subcomplex of the transcription/export (TREX) complex which seems to have a dynamic structure involving ATP-dependent remodeling.
Required for efficient export of polyadenylated RNA. Acts as component of the THO subcomplex of the TREX complex which is thought to couple mRNA transcription, processing and nuclear export, and which specifically associates with spliced mRNA and not with unspliced pre-mRNA. TREX is recruited to spliced mRNAs by a transcription-independent mechanism, binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5' end of the mRNA where it functions in mRNA export to the cytoplasm via the TAP/NFX1 pathway.
Belongs to the PpiC/parvulin rotamase family. PIN4 subfamily.
May be involved as a ribosomal RNA processing factor in ribosome biogenesis. Binds to DNA (By similarity).
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.
Functions as a negative regulator of the TORC1 signaling pathway.
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.
May be required for the dynein-mediated transport of pericentriolar proteins to the centrosome. Required for microtubule anchoring at the centrosome but not for microtubule nucleation. Required for ciliogenesis (By similarity).
Belongs to the nuclear hormone receptor family. NR6 subfamily.
Probable orphan nuclear receptor. Binds to a response element containing repeats of the motif 5'-AGGTCA-3'. Required for anterior-posterior patterning during organogenesis. Acts with chordin to play a role in patterning the midbrain-hindbrain. Isoform Em is required for integrin-mediated cell matrix interaction during neurulation and for the morphogenetic movements leading to formation of the neural tube. Also mediates the effect of retinoic acid on primary neurogenesis (By similarity).
Binds 1 myo-inositol hexakisphosphate (IP6) per subunit.
Specifically deaminates adenosine-37 to inosine in tRNA-Ala.
In the N-terminal section; belongs to the calycin superfamily. Lipocalin family.
Belongs to the eukaryotic ribosomal protein eL6 family.
Induces disassembly of actin filaments in conjunction with ADF/cofilin family proteins. Doesn't sever actin filaments alone, but caps the barbed ends of filaments severed by cofilin, which blocks annealing and depolymerization and allows more extensive severing by cofilin (By similarity).
Activates acetoacetate to acetoacetyl-CoA.
Part of the EJC core complex that contains casc3, eif4a3, magoh and rbm8a. Identified in the spliceosome C complex.
Required for pre-mRNA splicing as component of the spliceosome (By similarity). Core component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junctions on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. The EJC marks the position of the exon-exon junction in the mature mRNA for the gene expression machinery and the core components remain bound to spliced mRNAs throughout all stages of mRNA metabolism thereby influencing downstream processes including nuclear mRNA export, subcellular mRNA localization, translation efficiency and nonsense-mediated mRNA decay (NMD). Its removal from cytoplasmic mRNAs requires translation initiation from EJC-bearing spliced mRNAs. Associates preferentially with mRNAs produced by splicing. Does not interact with pre-mRNAs, introns, or mRNAs produced from intronless cDNAs. Associates with both nuclear mRNAs and newly exported cytoplasmic mRNAs (By similarity).
Regulator of microtubule dynamic that has microtubule bundling activity.
May regulate the stability of some mitochondrial mRNA species.
The RAP domain seems to regulate mitochondrial mRNA levels.
Belongs to the eukaryotic RPC9 RNA polymerase subunit family.
Belongs to the eukaryotic-type N-acetylglucosamine kinase family.
Belongs to the class-V pyridoxal-phosphate-dependent aminotransferase family.
May be required for insulin-stimulated glucose transport and glucose transporter SLC2A4/GLUT4 translocation from intracellular glucose storage vesicle (GSV) to the plasma membrane (PM) in adipocytes. May bind phospholipid membranes in a calcium-dependent manner (By similarity).
The C2 domain binds to calcium and membrane lipids.
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.
Binds to WNT proteins and inhibits their activities. May be involved in mesoderm segmentation.
Component of ribonuclease P, a protein complex that generates mature tRNA molecules by cleaving their 5'-ends.
Converts proline to delta-1-pyrroline-5-carboxylate.
Belongs to the TALE/PBX homeobox family.
Transcriptional activator that binds the sequence 5'-ATCAATCAA-3'.
Belongs to the liprin family. Liprin-alpha subfamily.
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.
Belongs to the chaperonin (HSP60) family.
Component of a DCX (DDB1-CUL4-X-box) protein ligase complex.
Substrate recognition component of a DCX (DDB1-CUL4-X-box) E3 protein ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins, such as MEIS2 (Probable). Normal degradation of key regulatory proteins is required for normal limb outgrowth and expression of the fibroblast growth factor FGF8. Maintains presynaptic glutamate release and consequently cognitive functions, such as memory and learning, by negatively regulating large-conductance calcium-activated potassium (BK) channels in excitatory neurons. Likely to function by regulating the assembly and neuronal surface expression of BK channels via its interaction with KCNT1 (By similarity). May also be involved in regulating anxiety-like behaviors via a BK channel-independent mechanism (By similarity).
Arginine methyltransferase that methylates (mono and asymmetric dimethylation) the guanidino nitrogens of arginyl residues present in target proteins. Constitutes the main enzyme that mediates monomethylation and asymmetric dimethylation of histone H4 'Arg-4' (H4R3me1 and H4R3me2a, respectively), a specific tag for epigenetic transcriptional activation. Methylates ilf3 to regulate its DNA-binding activity. Required for neural induction, playing a key role in the control of epidermal versus neural cell fate choice (By similarity). Methylates cirbp to regulate its subcellular location. Acts transiently during metamorphosis as a transcription coactivator, enhancing thyroid hormone (T3) receptor (TR)-mediated transcription by enhancing TR binding to the T3 response element (TRE), and histone modification through recruitment of other coactivators.
Belongs to the class I-like SAM-binding methyltransferase superfamily. Protein arginine N-methyltransferase family.
Homodimer. Homooctamer; individual homodimers associates to form a homooctamer and homooligomerization is required for proper localization to the cell membrane. Individual homodimers can associate to form a homohexamer (By similarity). Component of a complex with lsm14a/rap55a. Interacts with cirbp (By similarity).
Belongs to the FPP/GGPP synthase family.
Component of the pre-catalytic and catalytic spliceosome complexes. Component of the postcatalytic spliceosome P complex.
Required for pre-mRNA splicing as component of the activated spliceosome. Involved in the first step of pre-mRNA splicing. Binds directly to the internal stem-loop (ISL) domain of the U6 snRNA and to the pre-mRNA intron near the 5' splice site during the activation and catalytic phases of the spliceosome cycle.
The C-terminal RRM domain and the zinc finger motif are necessary for RNA-binding.
Belongs to the polyprenol kinase family.
Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. NIM1 subfamily.
Catalyzes the formation of GDP-mannose, an essential precursor of glycan moieties of glycoproteins and glycolipids.
Molecular scaffold protein for various multimeric protein complexes. Acts as a module in the assembly of a multicomponent scaffold for the ERK pathway, linking ERK responses to specific agonists. Also involved in response to hypoxia by acting as a negative regulator of HIF1A/HIF-1-alpha (By similarity).
Belongs to the protein kinase superfamily. Tyr protein kinase family. Fibroblast growth factor receptor subfamily.
Belongs to the ANT/ATPSC lysine N-methyltransferase family.
Belongs to the strictosidine synthase family.
Interacts with EME1 to form a DNA structure-specific endonuclease with substrate preference for branched DNA structures with a 5'-end at the branch nick. Typical substrates include 3'-flap structures, D-loops, replication forks and nicked Holliday junctions. May be required in mitosis for the processing of stalled or collapsed replication fork intermediates. May be required in meiosis for the repair of meiosis-specific double strand breaks subsequent to single-end invasion (SEI).
Interacts with eme1 and eme2 to form a DNA structure-specific endonuclease with substrate preference for branched DNA structures with a 5'-end at the branch nick. Typical substrates include 3'-flap structures, replication forks and nicked Holliday junctions. May be required in mitosis for the processing of stalled or collapsed replication forks (By similarity).
Belongs to the twisted gastrulation protein family.
Expressed in the most dorsoanterior endomesoderm of the blastula and gastrula embryo, and later is restricted to the forming liver diverticulum.
Recognizes the DNA sequence 5'-ATTAA-3'. Transcriptional repressor. Regulates the differentiation of both endothelial and blood cells. Probably plays a role in the proliferation of vascular endothelial cells during blood vessel development. Establishes anterior identity at two levels; acts early to enhance canonical wnt-signaling by repressing expression of tle4, and acts later to inhibit nodal-signaling by directly targeting nodal/nr1 and nodal2/nr2. May play a role in liver development. Induces heart development (By similarity).
Belongs to the flavin monoamine oxidase family.
Belongs to the peroxiredoxin family. Prx5 subfamily.
Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively. Plays a role in cell protection against oxidative stress by detoxifying peroxides and as sensor of hydrogen peroxide-mediated signaling events.
Although related to peptidase S1 family, lacks the conserved active Ser residue in position 667 which is replaced by a Thr, suggesting that it has no protease activity.
May play a role in regeneration of skeletal muscle.
Belongs to the adenomatous polyposis coli (APC) family.
As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs.
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.
Belongs to the fatty acid desaturase type 1 family. DEGS subfamily.
Belongs to the JHDM1 histone demethylase family.
Histone demethylase that specifically demethylates 'Lys-36' of histone H3, thereby playing a central role in histone code. Preferentially demethylates dimethylated H3 'Lys-36' residue while it has weak or no activity for mono- and tri-methylated H3 'Lys-36'. May also recognize and bind to some phosphorylated proteins and promote their ubiquitination and degradation. Required to maintain the heterochromatic state. Associates with centromeres and represses transcription of small non-coding RNAs that are encoded by the clusters of satellite repeats at the centromere. Required to sustain centromeric integrity and genomic stability, particularly during mitosis (By similarity). May play a role in the regulation of circadian gene expression (By similarity).
The CXXC zinc finger preferentially recognizes nonmethylated CpG DNA, and binding is blocked when the CpG DNA is methylated.
The JmjC domain mediates demethylation activity and is required for satellite silencing.
Sodium-independent sulfate anion transporter. Can transport other anions including bicarbonate, thiosulfate and oxalate.
Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols. Displays enzymatic activity towards endogenous metabolites such as aromatic and aliphatic aldehydes, ketones, monosaccharides and bile acids. Acts as an aldehyde-detoxification enzyme (By similarity). Displays no reductase activity towards retinoids (By similarity).
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.
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 (By similarity).
Involved in the regulation of cellular calcium homeotasis.
Key component of the Ragulator complex, a multiprotein complex involved in amino acid sensing and activation of mTORC1, a signaling complex promoting cell growth in response to growth factors, energy levels, and amino acids. Activated by amino acids through a mechanism involving the lysosomal V-ATPase, the Ragulator plays a dual role for the small GTPases Rag (RagA/RRAGA, RagB/RRAGB, RagC/RRAGC and/or RagD/RRAGD): it (1) acts as a guanine nucleotide exchange factor (GEF), activating the small GTPases Rag and (2) mediates recruitment of Rag GTPases to the lysosome membrane. Activated Ragulator and Rag GTPases function as a scaffold recruiting mTORC1 to lysosomes where it is in turn activated. LAMTOR1 is directly responsible for anchoring the Ragulator complex to the lysosomal membrane. LAMTOR1 wraps around the other subunits of the Ragulator complex to hold them in place and interacts with the Rag GTPases, thereby playing a key role in the recruitment of the mTORC1 complex to lysosomes.
N-terminal myristoylation and palmitoylation mediates its recruitment to lysosome membranes, thereby promoting localization of the Ragulator complex to lysosomes. N-myristoylation by NMT1 is required for palmitoylation at Cys-3 and Cys-4.
Probably involved in the organization of the actin cytoskeleton.
Key transcription factor required for motile ciliogenesis. Activates genes essential for motile cilia formation and function.
Belongs to the major facilitator superfamily. Sodium/anion cotransporter family. VGLUT subfamily.
Chloride channel activity is allosterically activated by lumenal H(+) and Cl(-) leading to synaptic vesicles acidification. The L-glutamate transport activity is allosterically activated by lumenal H(+) and Cl(-). The allosteric activation by H(+) efficiently prevents non-vesicular efflux across the plasma membrane, thereby restricting L-glutamate transport activity to acidic membranes such as synaptic vesicles.
Martineau M. et al. show that may function as a L-glutamate/H(+) antiporter (By similarity). However, according to Eriksen J. et al., H(+) is an allosteric activator (By similarity).
Multifunctional transporter that transports L-glutamate as well as multiple ions such as chloride, proton, potassium, sodium and phosphate. At the synaptic vesicle membrane, mainly functions as an uniporter which transports preferentially L-glutamate but also phosphate from the cytoplasm into synaptic vesicles at presynaptic nerve terminals of excitatory neural cells. The L-glutamate or phosphate uniporter activity is electrogenic and is driven by the proton electrochemical gradient, mainly by the electrical gradient established by the vacuolar H(+)-ATPase across the synaptic vesicle membrane. In addition, functions as a chloride channel that allows a chloride permeation through the synaptic vesicle membrane that affects the proton electrochemical gradient and promotes synaptic vesicles acidification. Moreover, may function as a K(+)/H(+) antiport allowing to maintain the electrical gradient and to decrease chemical gradient and therefore sustain vesicular glutamate uptake. The vesicular K(+)/H(+) antiport activity is electroneutral. At the plasma membrane, following exocytosis, functions as a symporter of Na(+) and phosphate from the extracellular space to the cytoplasm allowing synaptic phosphate homeostasis regulation. The symporter activity is driven by an inside negative membrane potential and is electrogenic (By similarity). Is necessary for synaptic signaling of visual-evoked responses from photoreceptors (By similarity).
Belongs to the alpha-ketoglutarate dehydrogenase family.
Enhancer of SUMO conjugation. Increases SUMO conjugation to proteins by promoting the: binding of E1 and E2 enzymes, thioester linkage between SUMO and ube2i/ubc9 and transfer of SUMO to specific target proteins which include hif1a, pias, nfkbia, nr3c1 and top1. Has no effect on ubiquitination (By similarity).
The RWD domain is required for the sumoylation enhancement activity.
Belongs to the bZIP family. ATF subfamily.
Probable regulator of creb1 transcriptional activity which is involved in adipose cells differentiation. May also play a regulatory role in the cell cycle (By similarity).
RNA-binding protein involved in pre-mRNA splicing. Interacts with the PRP19C/Prp19 complex/NTC/Nineteen complex which is part of the spliceosome. Involved in regulating splice site selection. Binds preferentially RNA with A/C rich sequences and poly-C stretches.
The C-terminal part is necessary for the interaction with the PRP19C/Prp19 complex/NTC/Nineteen complex.
Acetylation of alpha chains at Lys-40 is located inside the microtubule lumen. This modification has been correlated with increased microtubule stability, intracellular transport and ciliary assembly.
Detyrosination is involved in metaphase plate congression by guiding chromosomes during mitosis (By similarity). Detyrosination increases microtubules-dependent mechanotransduction in dystrophic cardiac and skeletal muscle. In cardiomyocytes, detyrosinated microtubules are required to resist to contractile compression during contraction (By similarity).
The MREC motif may be critical for tubulin autoregulation.
Tyrosination promotes microtubule interaction with CAP-Gly microtubule plus-end tracking proteins. Tyrosinated tubulins regulate the initiation of dynein-driven motility.
Undergoes a tyrosination/detyrosination cycle, the cyclic removal and re-addition of a C-terminal tyrosine residue by the enzymes tubulin tyrosine carboxypeptidase (MATCAP, VASH1 or VASH2) and tubulin tyrosine ligase (TTL), respectively.
May for an interface between the RNA polymerase II enzyme and chaperone/scaffolding protein.
Interacts with fuz and wdpcp; fuz, intu and wdpcp probably form the core CPLANE (ciliogenesis and planar polarity effectors) complex.
Plays a role in the definition of cell polarity via the planar cell polarity (PCP) cascade. Required for ciliogenesis by controlling the organization of the apical actin cytoskeleton and the positioning of the basal bodies at the apical cell surface, which in turn is essential for the normal orientation of elongating ciliary microtubules. Proposed to function as core component of a functional module called CPLANE (ciliogenesis and planar polarity effectors) involved in recruitment of peripheral IFT-A proteins to basal bodies. Controls the localization of both rhoa and disheveled in multi-ciliated cells. Has an indirect effect on hedgehog signaling (By similarity).
Regulates the activity of L-type calcium channels that contain CACNA1C as pore-forming subunit.
The GINS complex plays an essential role in the initiation of DNA replication.
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.
Regulates cell junction organization in epithelial cells. May play a role in the transition from adherens junction to tight junction assembly.
Belongs to the eukaryotic ribosomal protein eL32 family.
Component of the ribosomal small subunit processome for the biogenesis of ribosomes, functions in pre-ribosomal RNA (pre-rRNA) processing (By similarity). Essential for embryonic development in part through the regulation of p53 pathway. Controls the expansion growth of digestive organs and liver (By similarity). Also involved in the sympathetic neuronal development (By similarity). Mediates, with CAPN3, the proteasome-independent degradation of p53/TP53 (By similarity).
Interacts with CAPN3; the interaction is required for CAPN3 translocation to the nucleolus.
Phosphorylated. Phosphorylation is required to promote p53/TP53 degradation in the nucleolus which promotes cell cycle progression and liver development.
A cytochrome P450 monooxygenase involved in the metabolism of retinoates (RAs), the active metabolites of vitamin A, and critical signaling molecules in animals (By similarity). RAs exist as at least four different isomers: all-trans-RA (atRA), 9-cis-RA, 13-cis-RA, and 9,13-dicis-RA, where atRA is considered to be the biologically active isomer, although 9-cis-RA and 13-cis-RA also have activity (By similarity). Catalyzes the hydroxylation of atRA primarily at C-4 and C-18, thereby contributing to the regulation of atRA homeostasis and signaling (By similarity). Hydroxylation of atRA limits its biological activity and initiates a degradative process leading to its eventual elimination (By similarity). Involved in the convertion of atRA to all-trans-4-oxo-RA. Can oxidize all-trans-13,14-dihydroretinoate (DRA) to metabolites which could include all-trans-4-oxo-DRA, all-trans-4-hydroxy-DRA, all-trans-5,8-epoxy-DRA, and all-trans-18-hydroxy-DRA (By similarity).
Component of the SSP (stage selector protein) complex, which appears to be a heteromer of TFCP2 and 2 copies of NFE4.
Binds 1 divalent metal cation per subunit; can use either Mg(2+) or Mn(2+).
Pyrophosphatase that hydrolyzes the non-canonical purine (dITP) as well as 2'-deoxy-N-6-hydroxylaminopurine triphosphate (dHAPTP) and xanthosine 5'-triphosphate (XTP) to their respective monophosphate derivatives. The enzyme does not distinguish between the deoxy- and ribose forms. Probably excludes non-canonical purines from RNA and DNA precursor pools, thus preventing their incorporation into RNA and DNA and avoiding chromosomal lesions.
Belongs to the adipolin/erythroferrone family.
Insulin-sensitizing adipocyte-secreted protein (adipokine) that regulates glucose metabolism in liver and adipose tissue.
Belongs to the OHCU decarboxylase family.
Catalyzes the stereoselective decarboxylation of 2-oxo-4-hydroxy-4-carboxy-5-ureidoimidazoline (OHCU) to (S)-allantoin.
Antiporter that transports inorganic anions (sulfate, sulfite, thiosulfate and phosphate) and, to a lesser extent, a variety of dicarboxylates (e.g. malonate, malate and citramalate) and, even more so, aspartate. The sulfate/sulfate exchange is much higher than the phosphate/phosphate and malate/malate exchanges. The transport affinities is higher for sulfate and thiosulfate than for any other substrate. May catalyze the export of sulfite and thiosulfate (the hydrogen sulfide degradation products) from the mitochondria, thereby modulating the level of the hydrogen sulfide. Also may mediate a very low unidirectional transport of sulfate, phosphate and (S)-malate.
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.
Important for normal spermatogenesis and male fertility. Specifically required for progression to the post-meiotic stages of spermatocyte development. Seems to be necessary for normal expression levels of a number of testis-expressed gene transcripts, although its role in this process is unclear.
Occurs in almost all aerobically respiring organisms and serves to protect cells from the toxic effects of hydrogen peroxide.
Guanine nucleotide exchange factor (GEF), which can activate some, but not all, G-alpha proteins by exchanging bound GDP for free GTP.
Guanine nucleotide exchange factor (GEF), which can activate some, but not all, G-alpha proteins by exchanging bound GDP for free GTP. Involved in regulation of microtubule pulling forces during mitotic movement of chromosomes by stimulating G(i)-alpha protein (By similarity).
Interacts with some GDP-bound G alpha proteins. Does not interact with G-alpha proteins when they are in complex with subunits beta and gamma (By similarity).
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.
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).
Belongs to the universal ribosomal protein uL29 family.
Lectin involved in the quality control of the secretory pathway. As a member of the endoplasmic reticulum-associated degradation lumenal (ERAD-L) surveillance system, targets misfolded endoplasmic reticulum lumenal glycoproteins for degradation.
Controlled by regulated intramembrane proteolysis (RIP). A fragment containing the cytoplasmic transcription factor domain is released by proteolysis. The cleavage seems to be performed sequentially by site-1 and site-2 proteases (PS1 and PS2) (By similarity).
Histone chaperone that stabilizes pre-existing histone tetramers and regulates replication-independent histone exchange on chromatin. Required for normal chromatin refolding in the coding region of transcribed genes, and for the suppression of spurious transcription. Binds DNA and histones and promotes nucleosome assembly (in vitro). Facilitates formation of tetrameric histone complexes containing histone H3 and H4 (By similarity). Modulates RNA polymerase 1-mediated transcription (By similarity). Binds DNA, with a preference for branched DNA species, such as Y-form DNA and Holliday junction DNA (By similarity).
Interacts with histones. Interacts with a heterotetrameric complex formed by histone H3 and H4, especially when the histone tetramer is not bound to DNA.
The acidic C-terminal domain mediates interaction with histone H3/H4 complexes.
Acetylated on Lys-5, Lys-8 and Lys-12 when associated with the 5'-end of active genes.
Monoubiquitination of Lys-122 gives a specific tag for epigenetic transcriptional repression.
The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA. H2A or its variant 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).
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.
Beta-1,3-N-acetylgalactosaminyltransferase that synthesizes a unique carbohydrate structure, GalNAc-beta-1-3GlcNAc, on N- and O-glycans. Has no galactose nor galactosaminyl transferase activity toward any acceptor substrate. Involved in alpha-dystroglycan (dag1) glycosylation (By similarity).
Belongs to the bacterial ribosomal protein bL9 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. Key component of the proton channel; it may play a direct role in the translocation of protons across the membrane.
Translation initiation regulator which may repress repeat-associated non-AUG (RAN) initiated translation probably by acting as a competitive inhibitor of eukaryotic translation initiation factor 5 (EIF5) function (By similarity). Enhances histone H4 gene transcription but does not seem to bind DNA directly (By similarity).
Belongs to the MsrB Met sulfoxide reductase family.
Lectin that binds to various sugars: galactose > mannose = fucose > N-acetylglucosamine > N-acetylgalactosamine.
Belongs to the palmitoyl-protein thioesterase family.
May play a role in anchoring the cytoskeleton to the plasma membrane.
Belongs to the complex I NDUFB2 subunit family.
Mutarotase that catalyzes the interconversion of beta-D-galactose and alpha-D-galactose during galactose metabolism.
Farnesylation is required for nuclear envelope localization.
Nuclear envelope-associated factor that is involved in the nuclear envelope ruptures during interphase (NERDI) repair.
Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXO9).
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 acts as a regulator of mTOR signaling.
Belongs to the eukaryotic ribosomal protein eS8 family. Ribosome biogenesis protein NSA2 subfamily.
Component of the pre-66S ribosomal particle.
Involved in the biogenesis of the 60S ribosomal subunit. May play a part in the quality control of pre-60S particles.
Involved in the initiation of DNA replication. Also participates in checkpoint controls that ensure DNA replication is completed before mitosis is initiated.
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.
Belongs to the small GTPase superfamily. SAR1 family.
Belongs to the PI3/PI4-kinase family. Type II PI4K subfamily.
Membrane-bound phosphatidylinositol-4 kinase (PI4-kinase) that catalyzes the phosphorylation of phosphatidylinositol (PI) to phosphatidylinositol 4-phosphate (PI4P), a lipid that plays important roles in endocytosis, Golgi function, protein sorting and membrane trafficking. Besides, phosphorylation of phosphatidylinositol (PI) to phosphatidylinositol 4-phosphate (PI4P) is the first committed step in the generation of phosphatidylinositol 4,5-bisphosphate (PIP2), a precursor of the second messenger inositol 1,4,5-trisphosphate (InsP3).
Component of ORC, a complex composed of at least 6 subunits: ORC1, ORC2, ORC3, ORC4, ORC5 and ORC6. ORC is regulated in a cell-cycle dependent manner. It is sequentially assembled at the exit from anaphase of mitosis and disassembled as cells enter S phase.
Forms heterodimers with a number of antiapoptotic Bcl-2 proteins including MCL1, BCL2, BCL2L1 isoform Bcl-X(L), BCL2A1/BFL-1.
Interacts with myosin VIIa and the cadherin-catenins complex.
Plays a pivotal role in the establishment of adherens junctions and their maintenance in adult life.
Belongs to the fatty acid desaturase type 1 family.
The histidine box domains are involved in binding the catalytic metal ions.
Belongs to the class-IV pyridoxal-phosphate-dependent aminotransferase family.
Belongs to the eukaryotic/archaeal PrmC-related family.
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 NDUFA3 subunit family.
Multiubiquitin chain receptor involved in modulation of proteasomal degradation. Involved in nucleotide excision repair.
CNTF is a survival factor for various neuronal cell types. Seems to prevent the degeneration of motor axons after axotomy.
Calcium-regulated non-lysosomal thiol-protease.
Belongs to the Integrator subunit 10 family.
Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. Aurora subfamily.
Disordered region at the C-terminus undergoes liquid-liquid phase separation (LLPS) for the formation of a membraneless compartment that stores mRNAs.
Required for somite formation by undergoing liquid-liquid phase separation to assemble target mRNAs into cytoplasmic ribonucleoprotein granules.
Shows tissue-specific expression during embryonic development (PubMed:15968590). At stage 23, expressed preferentially in structures that will develop into muscle (mesodermal) and neural (ectodermal) tissue (PubMed:15968590). From stage 37 onwards, highly expressed in neurons and skeletal muscle tissue (PubMed:15968590). Expression remains tissue-specific in adults, being localized to neurons of the central nervous system (CNS), all spermatogenic cells of the testis and skeletal muscle (PubMed:15968590). Within skeletal muscle, expression appears to be localized to costameres (PubMed:15968590).
mRNA-binding protein that acts as a regulator of mRNAs translation and/or stability, and which is required for various processes, such as neurogenesis and muscle development (By similarity). Specifically binds to AU-rich elements (AREs) in the 3'-UTR of target mRNAs (By similarity). Promotes formation of some phase-separated membraneless compartment by undergoing liquid-liquid phase separation upon binding to AREs-containing mRNAs, leading to assemble mRNAs into cytoplasmic ribonucleoprotein granules that concentrate mRNAs with associated regulatory factors (By similarity).
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.
Forms a ternary complex with the intracellular domain (ICD) of notch1 and rbpj/suh.
Promotes loss of intracellular domain (ICD) of Notch1 in embryos. By down-regulating ICD levels, could function as a negative feedback regulator of Notch signaling that attenuates ICD-mediated transcription (By similarity). Involved in angiogenesis. May be involved in somitogenesis (By similarity).
ATP-dependent serine protease that mediates the selective degradation of misfolded and unassembled polypeptides in the peroxisomal matrix. Necessary for type 2 peroxisome targeting signal (PTS2)-containing protein processing and facilitates peroxisome matrix protein import.
Belongs to the glutamate-gated ion channel (TC 1.A.10.1) family. NR1/GRIN1 subfamily.
Divalent metal ions. Mg(2+) is the most effective.
Belongs to the nuclear hormone receptor family. NR5 subfamily.
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 peroxiredoxin family. Prx6 subfamily.
Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively.
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.
Belongs to the eukaryotic ribosomal protein eS28 family.
Belongs to the eukaryotic ribosomal protein eS25 family.
Belongs to the eukaryotic ribosomal protein eL19 family.
Belongs to the chloride channel (TC 2.A.49) family. ClC-3/CLCN3 subfamily.
May be involved in cell cycle regulation.
Belongs to the endoribonuclease YbeY family.
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 in 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 (By similarity). In conditions where the essential linoleic and alpha linoleic fatty acids are lacking it is also involved in the synthesis of Mead acid from oleic acid (By similarity).
Catalyzes the attachment of alanine to tRNA(Ala) in a two-step reaction: alanine is first activated by ATP to form Ala-AMP and then transferred to the acceptor end of tRNA(Ala). Also edits incorrectly charged tRNA(Ala) via its editing domain.
Consists of three domains; the N-terminal catalytic domain, the editing domain and the C-terminal C-Ala domain. The editing domain removes incorrectly charged amino acids, while the C-Ala domain, along with tRNA(Ala), serves as a bridge to cooperatively bring together the editing and aminoacylation centers thus stimulating deacylation of misacylated tRNAs.
Monomer. Interacts with ANKRD16; the interaction is direct.
Required for the assembly of axonemal inner and outer dynein arms. Involved in preassembly of dyneins into complexes before their transport into cilia.
Necessary for the survival of cerebellar neurons. Induces neuritogenesis by activating the Ras-MAP kinase pathway. May play a role in the maintenance of a critical intracellular glycosylation level and homeostasis.
Transcriptional repressor that down-regulates bmp4 signaling in both mesoderm and ectoderm. Regulates mesoderm patterning by repressing ventral mesoderm genes and promoting the expression of dorsolateral genes. Can also neuralize ectodermal cells directly. Inhibits neural crest migration. The transcription factors foxd1 and foxg1 mutually repress each other to pattern the forebrain (By similarity).
Belongs to the glycosyl hydrolase 99 family.
RNA-binding component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is involved in protein synthesis of a specialized repertoire of mRNAs and, together with other initiation factors, stimulates binding of mRNA and methionyl-tRNAi to the 40S ribosome. The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation. This subunit can bind 18S rRNA.
Interacts with DDX4, PIWIL1, RANBP9 and TDRD1.
Acts as a regulator of endocytic traffic by participating in membrane delivery. Required for the abcission step in cytokinesis, possibly by acting as an 'address tag' delivering recycling endosome membranes to the cleavage furrow during late cytokinesis (By similarity).
Homodimer. Forms a complex with Rab11 (rab11a or rab11b) and arf6 (By similarity).
The RBD-FIP domain mediates the interaction with Rab11 (rab11a or rab11b).
Belongs to the class I-like SAM-binding methyltransferase superfamily. RsmB/NOP family. TRM4 subfamily.
RNA cytosine C(5)-methyltransferase that methylates cytosine to 5-methylcytosine (m5C) in various RNAs, such as tRNAs, mRNAs and some long non-coding RNAs (lncRNAs). Involved in various processes, such as epidermal stem cell differentiation, testis differentiation and maternal to zygotic transition during early development: acts by increasing protein synthesis; cytosine C(5)-methylation promoting tRNA stability and preventing mRNA decay. Methylates cytosine to 5-methylcytosine (m5C) at positions 34 and 48 of intron-containing tRNA(Leu)(CAA) precursors, and at positions 48, 49 and 50 of tRNA(Gly)(GCC) precursors. tRNA methylation is required generation of RNA fragments derived from tRNAs (tRFs). Also mediates C(5)-methylation of mitochondrial tRNAs. Catalyzes cytosine C(5)-methylation of mRNAs, leading to stabilize them and prevent mRNA decay. Cytosine C(5)-methylation of mRNAs also regulates mRNA export. Also mediates cytosine C(5)-methylation of non-coding RNAs, such as vault RNAs (vtRNAs), promoting their processing into regulatory small RNAs. Required for proper spindle assembly and chromosome segregation, independently of its methyltransferase activity.
Belongs to the bacterial ribosomal protein bL28 family.
Belongs to the cytochrome c oxidase subunit 5A family.
Component of the cytochrome c oxidase (complex IV, CIV), a multisubunit enzyme composed of a catalytic core of 3 subunits and several supernumerary subunits. The complex exists as a monomer or a dimer and forms supercomplexes (SCs) in the inner mitochondrial membrane with ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII).
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.
Histone methyltransferase that specifically methylates 'Lys-4' of histone H3, when part of the SET1 histone methyltransferase (HMT) complex, but not if the neighboring 'Lys-9' residue is already methylated. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation.
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.
Monomer (By similarity). Homodimer; disulfide-linked (By similarity). Occurs in both reduced and oxidized monomeric form (By similarity). Oxidative conditions increase homodimerization (By similarity).
The di-lysine motif confers endoplasmic reticulum localization for type I membrane proteins.
The thioredoxin domain lacks the 2 redox-active cysteines, suggesting that it lacks thioredoxin activity.
Negative regulator of katanin-mediated microtubule severing and release from the centrosome. Required for central spindle formation and the completion of cytokinesis. Negative regulator of the Wnt signaling pathway. Represses beta-catenin-mediated transcriptional activation by promoting the nuclear exclusion of beta-catenin.
Component of the ESCRT-II complex (endosomal sorting complex required for transport 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).
High-affinity transporter for the intake of thiamine.
At late neurula stage (stage 20), strongly expressed in the developing cement gland and in the bilateral heart primordia. Expression in the cement gland decreases from stage 25 onward, while expression continues to be strongly detected in the developing heart. In the heart-forming region at stage 25, expression seen in the heart field formed by fusion of the bilateral heart primordia and also seen in the hindbrain (rhombencephalon) at this stage, corresponding to the second and fourth rhombomeres. At stage 29/30, expression persists in these regions and also weakly detected in a more posterior region of the hindbrain. At stage 33, when heart looping is initiated, broadly expressed in the heart tube, ventricle, atrium and both branches of the sinus venosus. During heart looping (stage 36), expressed at a higher level in the atrium than in the ventricle.
Transcriptional regulator that may be involved in heart developmental processes.
Belongs to the arginase family. Agmatinase subfamily.
Belongs to the protein kinase superfamily. ADCK protein kinase 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 eukaryotic ribosomal protein eL29 family.
Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRA2 sub-subfamily.
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.
Outer dense fibers are filamentous structures located on the outside of the axoneme in the midpiece and principal piece of the mammalian sperm tail. May help to maintain the passive elastic structures and elastic recoil of the sperm tail.
Belongs to the thiolase-like superfamily. Beta-ketoacyl-ACP synthases family.
In the N-terminal section; belongs to the enoyl-CoA hydratase/isomerase family.
Belongs to the ROX family. MINA53 subfamily.
Oxygenase that can act as both a histone lysine demethylase and a ribosomal histidine hydroxylase.
The SET domain is degenerated, suggesting that it has lost methyltransferase activity.
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.
Catalyzes the ATP-dependent amination of UTP to CTP with either L-glutamine or ammonia as the source of nitrogen.
Belongs to the complex I 51 kDa subunit family.
Belongs to the peptidase S26 family. IMP1 subfamily.
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.
In the C-terminal section; belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Myosin family.
DNA-binding protein which may repress cyclin D1 transcription by recruiting HDAC1 to its promoter, thereby diminishing H3K9ac, H3S10ph and H4K8ac levels. Promotes activation, which causes cell cycle arrest (By similarity).
Part of a specialized transcription system that mediates the transcription of most ribosomal proteins through the 5'-TCT-3' motif which is a core promoter element at these genes. Seems to also mediate the transcription of NF1. Does not bind the TATA box. Members of the TBP family are differentially required to regulate transcription and development during early embryogenesis. Particularly regulates genes that have a role in catabolism (By similarity).
Probably involved in transcriptional regulation.
Belongs to the universal ribosomal protein uL4 family.
Belongs to the glycosyltransferase 2 family.
Belongs to the CDP-alcohol phosphatidyltransferase class-II family.
Functions in the biosynthesis of the anionic phospholipids phosphatidylglycerol and cardiolipin.
Belongs to the ubiquitin-activating E1 family.
Stabilizes the cyclin H-CDK7 complex to form a functional CDK-activating kinase (CAK) enzymatic complex.
Belongs to the threonine synthase family.
Catalyzes the dephosphorylation of the nucleoside 5'-monophosphates deoxyadenosine monophosphate (dAMP), deoxycytidine monophosphate (dCMP), deoxyguanosine monophosphate (dGMP) and deoxythymidine monophosphate (dTMP).
Homodimer; disulfide-linked. Also forms heterodimers with other TGF-beta family members including nodal2/nr-2 and bmp4 (By similarity).
Required for posterior mesoderm formation during embryogenesis. Acts indirectly to suppress head formation by altering mesodermal patterning. Also involved in the establishment of left-right axis asymmetry, acting upstream of nodal/nr-1. Can exert long-range effects in the embryo (By similarity).
The full-length protein can bind eight Ca(2+) ions via the annexin repeats. Calcium binding causes a major conformation change that modifies dimer contacts and leads to surface exposure of the N-terminal phosphorylation sites; in the absence of Ca(2+), these sites are buried in the interior of the protein core. The N-terminal region becomes disordered in response to calcium-binding.
Belongs to the eIF-2B alpha/beta/delta subunits family. MtnA subfamily.
Catalyzes the interconversion of methylthioribose-1-phosphate (MTR-1-P) into methylthioribulose-1-phosphate (MTRu-1-P).
Belongs to the metallo-dependent hydrolases superfamily. TatD-type hydrolase family.
Belongs to the Mediator complex subunit 25 family.
Belongs to the peroxidase family. XPO subfamily.
Binds 1 heme b (iron(II)-protoporphyrin IX) group covalently per subunit.
Catalyzes the two-electron oxidation of bromide by hydrogen peroxide and generates hypobromite as a reactive intermediate which mediates the formation of sulfilimine cross-links between methionine and hydroxylysine residues within an uncross-linked collagen IV/COL4A1 NC1 hexamer and participates to the basement membrane integrity. Moreover brominates alpha2 collagen IV chain/COL4A2 and leads to bromine enrichment of the basement membranes.
Homotrimer; disulfide-linked. The homotrimer form is predominant. Homooligomer; disulfide-linked. Oligomerization occurs intracellularly before C-terminal proteolytic cleavage.
Maternal expression is localized to the animal hemisphere where it persists through early cleavage stages. Initial zygotic expression is detected in the developing neural tube and becomes localized to the hindbrain and midbrain. Expressed in the primordium of the pronephric kidney and expression persists in the pronephric tubules and duct throughout development.
Processed by FURIN and the proteolytic processing largely depends on the peroxidase activity of PXDN (By similarity). The proteolytic cleavage occurs after intracellular homotrimerization and releases into the extracellular matrix a large, catalytically active fragment and a smaller fragment consisting primarily of the C-terminal VWFC domain. The processing enhances both peroxidase activity and sulfilimine cross-links formation (By similarity).
The VWFC domain mediates the covalent links between monomers throught disulfide bridges. Ig-like C2-type domains are required to sulfilimine bond formation. The VWFC domain is not required for trimerization. The LRR domain mediates high affinity binding to laminin-1.
Catalyzes the hydrolysis of queuosine 5'-phosphate, releasing the nucleobase queuine (q). Is required for salvage of queuine from exogenous queuosine (Q) that is imported and then converted to queuosine 5'-phosphate intracellularly.
Belongs to the WD repeat striatin family.
Belongs to the peptidase C19 family. USP20/USP33 subfamily.
Deubiquitinating enzyme involved in beta-2 adrenergic receptor (adrb2) recycling. Acts as a regulator of G-protein coupled receptor (GPCR) signaling by mediating the deubiquitination beta-2 adrenergic receptor (adrb2). Plays a central role in adrb2 recycling and resensitization after prolonged agonist stimulation by constitutively binding adrb2, mediating deubiquitination of adrb2 and inhibiting lysosomal trafficking of adrb2. Mediates deubiquitination of both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains (By similarity).
The UBP-type zinc finger binds 3 zinc ions. However, it does not bind ubiquitin, probably because the conserved Arg in position 55 is replaced by a Glu residue (By similarity).
Belongs to the MICU1 family. MICU1 subfamily.
Homohexamer; in absence of calcium. Forms a homohexamer in absence of calcium and rearranges into a heterodimer in presence of calcium. Heterodimer; disulfide-linked; heterodimerizes with MICU2. The heterodimer formed with MICU2 associates with MCU at low calcium concentration and dissociates from MCU at high calcium level. Component of the uniplex complex.
Key regulator of mitochondrial calcium uniporter (MCU) that senses calcium level via its EF-hand domains. micu1 and micu2 form a disulfide-linked heterodimer that stimulates and inhibits mcu activity, depending on the concentration of calcium. Micu1 acts both as an activator or inhibitor of mitochondrial calcium uptake. Acts as a gatekeeper of mcu at low concentration of calcium, preventing channel opening. Enhances mcu opening at high calcium concentration, allowing a rapid response of mitochondria to calcium signals generated in the cytoplasm.
The C-helix is required for assembling the Ca(2+)-free homohexamer. It also plays a key role in mitochondrial calcium uptake, probably by mediating interaction with MICU2.
The EF-hand domains have high affinity for calcium and act as sensors of calcium levels.
May be involved in membrane trafficking in the early secretory pathway.
Belongs to the V-ATPase proteolipid subunit family.
Proton-conducting pore forming of the V0 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates protons. V-ATPase is responsible for acidifying and maintaining the pH of intracellular compartments and in some cell types, is targeted to the plasma membrane, where it is responsible for acidifying the extracellular environment.
Heterotetramer of TRAP-alpha, TRAP-beta, TRAP-delta and TRAP-gamma.
TRAP proteins are part of a complex whose function is to bind calcium to the ER membrane and thereby regulate the retention of ER resident proteins.
Belongs to the nuclear hormone receptor family. NR2 subfamily.
Required for calcium-mediated regulation of ciliary beat frequency in the airway.
Homodimer. The active form is probably a hexamer composed of 3 homodimers.
Auto-ubiquitinated, and degraded in a 2-step mechanism; a caspase-independent first step and a caspase-dependent second step.
Phosphorylated via MAPK-dependent and CDK-dependent pathways during oocyte maturation. Phosphorylation does not appear to affect caspase inhibition or autoubiquitination activity.
The BIR2 domain is required for caspase-inhibition.
The C-terminal region containing the RING finger domain is required for the initial degradation step, and the final digestion of cleavage fragments.
Weak apoptotic suppressor. Has E3 ubiquitin-protein ligase activity. Weak inhibitor of caspase activity.
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.
Orphan nuclear receptor. Binds the IR7 element in the promoter of its own gene in an autoregulatory negative feedback mechanism. Primarily repressor of a broad range of genes. Binds to hormone response elements (HREs) consisting of two 5'-AGGTCA-3' half site direct repeat consensus sequences (By similarity).
Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. EZ subfamily.
Polycomb group (PcG) protein. Catalytic subunit of the prc2/eed-ezh2 complex, which methylates 'Lys-9' and 'Lys-27' of histone H3, leading to transcriptional repression of the affected target gene. May regulate the circadian clock via histone methylation at the promoter of the circadian genes.
Acts as a transcriptional corepressor for snai1 and snai2/slug and plays a role in regulating neural crest development.
Binds with high affinity to CRF receptors 2-alpha and 2-beta.
Suppresses food intake, delays gastric emptying and decreases heat-induced edema. Might represent an endogenous ligand for maintaining homeostasis after stress.
May negatively regulate myogenesis and skeletal muscle regeneration.
Belongs to the galactose-1-phosphate uridylyltransferase type 1 family.
Belongs to the class IV-like SAM-binding methyltransferase superfamily.
Belongs to the complex I NDUFA11 subunit family.
Belongs to the glycosyltransferase 68 family.
In the N-terminal section; belongs to the HesA/MoeB/ThiF family. UBA4 subfamily.
Plays a central role in 2-thiolation of mcm(5)S(2)U at tRNA wobble positions of cytosolic tRNA(Lys), tRNA(Glu) and tRNA(Gln). Also essential during biosynthesis of the molybdenum cofactor. Acts by mediating the C-terminal thiocarboxylation of sulfur carriers URM1 and MOCS2A. Its N-terminus first activates URM1 and MOCS2A as acyl-adenylates (-COAMP), then the persulfide sulfur on the catalytic cysteine is transferred to URM1 and MOCS2A to form thiocarboxylation (-COSH) of their C-terminus. The reaction probably involves hydrogen sulfide that is generated from the persulfide intermediate and that acts as nucleophile towards URM1 and MOCS2A. Subsequently, a transient disulfide bond is formed. Does not use thiosulfate as sulfur donor; NFS1 probably acting as a sulfur donor for thiocarboxylation reactions.
Component of the nexin-dynein regulatory complex (N-DRC), a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes.
Belongs to the Mediator complex subunit 7 family.
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 PIGG/PIGN/PIGO family. PIGO subfamily.
Belongs to the deoxyhypusine hydroxylase family.
Catalyzes the hydroxylation of the N(6)-(4-aminobutyl)-L-lysine intermediate to form hypusine, an essential post-translational modification only found in mature eIF-5A factor.
Receptor for NPAF (A-18-F-amide) and NPFF (F-8-F-amide) neuropeptides, also known as morphine-modulating peptides. Can also be activated by a variety of naturally occurring or synthetic FMRF-amide like ligands. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system.
Catalyzes the isomerization of citrate to isocitrate via cis-aconitate.
Belongs to the V-ATPase E subunit family.
Homodimer (By similarity). Binds DNA as a dimer (By similarity).
May act as a transcriptional regulator of a number of proteins of the circadian clock.
Regulates the activity of the neutrophil proteases.
RNA-binding protein that specifically bind the 3'-UTR of VegT transcripts, leading to maintain their stability and stimulate their translation, thereby playing a role in germ layer formation. VegT is a localized maternal determinant essentially required for endoderm formation. Also has some proneural function in the open neural plate and in the context of retinogenesis. May also act as a mRNA splicing factor. May play a role in myogenic differentiation (By similarity).
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.
Acetyl group-binding receptor which shows a calcium-dependent binding to acetylated structures such as chitin, some N-acetylated carbohydrates, and amino acids.
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.
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.
Replisome component that maintains genome stability by protecting stalled or damaged replication forks. After the induction of replication stress, required for the stabilization of stalled replication forks, the efficient activation of the intra-S-phase and G/2M cell-cycle checkpoints and the maintenance of genome stability.
May play a role in the regulation of centrosome and Golgi apparatus positioning.
Catalyzes the ferrous insertion into protoporphyrin IX.
Deubiquitinating enzyme that may function as negative regulator of the innate immune system. Has peptidase activity towards 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains. Can also cleave 'Lys-11'-linked ubiquitin chains (in vitro) (By similarity).
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.
Plus-end tracking protein (+TIP) that binds to the plus-end of microtubules and regulates the dynamics of the microtubule cytoskeleton. Promotes cytoplasmic microtubule nucleation and elongation. Involved in mitotic spindle positioning by stabilizing microtubules and promoting dynamic connection between astral microtubules and the cortex during mitotic chromosome segregation.
May play a role in Golgi structure maintenance.
Metallocarboxypeptidase that mediates deglutamylation of target proteins. Catalyzes the deglutamylation of polyglutamate side chains generated by post-translational polyglutamylation in proteins such as tubulins. Also removes gene-encoded polyglutamates from the carboxy-terminus of target proteins such as MYLK. Does not show detyrosinase or deglycylase activities from the carboxy-terminus of tubulin.
Metallocarboxypeptidase that mediates deglutamylation of tubulin and non-tubulin target proteins. Catalyzes the removal of polyglutamate side chains present on the gamma-carboxyl group of glutamate residues within the C-terminal tail of tubulin protein. Specifically cleaves tubulin long-side-chains, while it is not able to remove the branching point glutamate. Also catalyzes the removal of polyglutamate residues from the carboxy-terminus of non-tubulin proteins.
Was initially shown to catalyze the removal of carboxy-terminus tyrosine from alpha-tubulin (By similarity). However, later studies did not identified any detyrosinase or deglycylase activities from the carboxy-terminus of tubulin (By similarity).
Was originally thought to have detyrosinating activity from C-terminal positions on tubulin.
Belongs to the proteasome subunit p55 family.
Belongs to the helicase family. Dicer subfamily.
Binds 2 magnesium or manganese ions per subunit.
Component of the RISC loading complex (RLC), or micro-RNA (miRNA) loading complex (miRLC), which is composed of dicer1, ago2 and tarbp2; dicer1 and tarbp2 are required to process precursor miRNAs (pre-miRNAs) to mature miRNAs and then load them onto ago2. Note that the trimeric RLC/miRLC is also referred to as RISC (By similarity).
Double-stranded RNA (dsRNA) endoribonuclease playing a central role in short dsRNA-mediated post-transcriptional gene silencing. Cleaves naturally occurring long dsRNAs and short hairpin pre-microRNAs (miRNA) into fragments of twenty-one to twenty-three nucleotides with 3' overhang of two nucleotides, producing respectively short interfering RNAs (siRNA) and mature microRNAs. SiRNAs and miRNAs serve as guide to direct the RNA-induced silencing complex (RISC) to complementary RNAs to degrade them or prevent their translation. Gene silencing mediated by siRNAs, also called RNA interference, controls the elimination of transcripts from mobile and repetitive DNA elements of the genome but also the degradation of exogenous RNA of viral origin for instance. The miRNA pathway on the other side is a mean to specifically regulate the expression of target genes (By similarity).
Double-stranded RNA (dsRNA) endoribonuclease playing a central role in short dsRNA-mediated post-transcriptional gene silencing. Cleaves naturally occurring long dsRNAs and short hairpin pre-microRNAs (miRNA) into fragments of twenty-one to twenty-three nucleotides with 3' overhang of two nucleotides, producing respectively short interfering RNAs (siRNA) and mature microRNAs. SiRNAs and miRNAs serve as guide to direct the RNA-induced silencing complex (RISC) to complementary RNAs to degrade them or prevent their translation. Gene silencing mediated by siRNAs, also called RNA interference, controls the elimination of transcripts from mobile and repetitive DNA elements of the genome but also the degradation of exogenous RNA of viral origin for instance. The miRNA pathway on the other side is a mean to specifically regulate the expression of target genes.
Belongs to the AAA ATPase family. RarA/MGS1/WRNIP1 subfamily.
Component of 2 distinct SNARE complexes.
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.
Protein-lysine N-methyltransferase that methylates both histones and non-histone proteins, including p53/TP53 and RB1. Specifically trimethylates histone H3 'Lys-4' (H3K4me3) in vivo. The activity requires interaction with HSP90alpha. Shows even higher methyltransferase activity on p53/TP53. Monomethylates 'Lys-370' of p53/TP53, leading to decreased DNA-binding activity and subsequent transcriptional regulation activity of p53/TP53. Monomethylates RB1 at 'Lys-860'.
Appears to be a negative regulator of angiotensin II type I receptor-mediated signaling.
Involved in pre-mRNA splicing as a component of the spliceosome.
Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is involved in protein synthesis and, together with other initiation factors, stimulates binding of mRNA and methionyl-tRNAi to the 40S ribosome.
Conjugated to atg12 at Lys-241. ATG12-conjugation plays a role in regulation of mitochondrial homeostasis and cell death, while it is not involved in PE-conjugation to ATG8-like proteins and autophagy (By similarity).
E2 conjugating enzyme required for the cytoplasm to vacuole transport (Cvt), autophagy, and mitochondrial homeostasis. Responsible for the E2-like covalent binding of phosphatidylethanolamine to the C-terminal Gly of atg8-like proteins (gabarap, gabarapl1, gabarapl2 or map1lc3a). The atg12-atg5 conjugate plays a role of an E3 and promotes the transfer of atg8-like proteins from atg3 to phosphatidylethanolamine (PE). This step is required for the membrane association of atg8-like proteins. The formation of the atg8-phosphatidylethanolamine conjugates is essential for autophagy and for the cytoplasm to vacuole transport (Cvt). Also acts as an autocatalytic E2-like enzyme, catalyzing the conjugation of atg12 to itself, atg12 conjugation to atg3 playing a role in mitochondrial homeostasis but not in autophagy. atg7 (E1-like enzyme) facilitates this reaction by forming an E1-E2 complex with atg3 (By similarity).
Interacts with atg7 and atg12. The complex composed of atg3 and atg7 plays a role in the conjugation of atg12 to atg5.
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.
G-protein coupled opioid receptor that functions as receptor for the endogenous neuropeptide nociceptin. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Signaling via G proteins mediates inhibition of adenylate cyclase activity and calcium channel activity. Arrestins modulate signaling via G proteins and mediate the activation of alternative signaling pathways that lead to the activation of MAP kinases. Plays a role in modulating nociception and the perception of pain. Plays a role in the regulation of locomotor activity by the neuropeptide nociceptin.
Required during ciliogenesis for tubulin glutamylation in cilium. Probably acts by participating in the transport of tubulin polyglutamylases between the basal body and the cilium (By similarity).
Belongs to the UDP-glucose/GDP-mannose dehydrogenase family.
Involved in the biosynthesis of glycosaminoglycans; hyaluronan, chondroitin sulfate, and heparan sulfate.
Belongs to the eukaryotic RPB4 RNA polymerase subunit family.
Component of the TFIID basal transcription factor complex, composed of TATA-box-binding protein tbp, and a number of TBP-associated factors (TAFs).
The TFIID basal transcription factor complex plays a major role in the initiation of RNA polymerase II (Pol II)-dependent transcription. TFIID recognizes and binds promoters with or without a TATA box via its subunit tbp, a TATA-box-binding protein, and promotes assembly of the pre-initiation complex (PIC). The TFIID complex consists of tbp and TBP-associated factors (TAFs). Mediates both basal and activator-dependent transcription.
Essential for the control of the cell cycle at the G2/M (mitosis) transition.
Adapter involved in the TLR2 and TLR4 signaling pathways in the innate immune response.
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.
Belongs to the aldolase class II family. MtnB subfamily.
Catalyzes the dehydration of methylthioribulose-1-phosphate (MTRu-1-P) into 2,3-diketo-5-methylthiopentyl-1-phosphate (DK-MTP-1-P). Functions in the methionine salvage pathway. May play a role in apoptosis.
Belongs to the selenophosphate synthase 1 family. Class II subfamily.
The conserved active site Cys (or selenocysteine) residue in position 29 is replaced by a Thr. However, as function in selenoprotein synthesis is probable, it is possible Cys-31 is the active site.
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.
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.
Transcription factor that binds to DNA at the consensus sequence 5'-AACAAT-3'.
Belongs to the short-chain dehydrogenases/reductases (SDR) family. 2,4-dienoyl-CoA reductase subfamily.
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.
S-adenosyl-L-methionine-dependent methyltransferase that mediates RNA cap1 2'-O-ribose methylation to the 5'-cap structure of RNAs. Methylates the ribose of the first nucleotide of a m(7)GpppG-capped mRNA to produce m(7)GpppNmp (cap1).
S-adenosyl-L-methionine-dependent methyltransferase that mediates mRNA cap1 2'-O-ribose methylation to the 5'-cap structure of mRNAs. Methylates the ribose of the first nucleotide of a m(7)GpppG-capped mRNA and small nuclear RNA (snRNA) to produce m(7)GpppRm (cap1). Displays a preference for cap0 transcripts. Cap1 modification is linked to higher levels of translation. May be involved in the interferon response pathway.
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.
Lipid phosphatase which dephosphorylates phosphatidylinositol 3-monophosphate (PI3P) and phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2).
The GRAM domain mediates binding to PI(3,5)P2 and, with lower affinity, to other phosphoinositides.
Belongs to the acetyltransferase family. ARD1 subfamily.
Endoplasmic reticulum-Golgi intermediate compartment
Belongs to the DNA/RNA non-specific endonuclease family.
Belongs to the universal ribosomal protein uL14 family.
mRNA splicing factor that regulates the formation of epithelial cell-specific isoforms. Specifically regulates the expression of FGFR2-IIIb, an epithelial cell-specific isoform of fgfr2. Acts by directly binding specific sequences in mRNAs. Binds the GU-rich sequence motifs in the ISE/ISS-3, a cis-element regulatory region present in the mRNA of fgfr2 (By similarity).
Belongs to the dermatan-sulfate isomerase family.
May regulate transcription of undefined genes.
Precursor of the Latency-associated peptide (LAP) and Transforming growth factor beta-2 (TGF-beta-2) chains, which constitute the regulatory and active subunit of TGF-beta-2, respectively.
Homodimer. Heterodimer; with a rar molecule.
Receptor for retinoic acid that acts as a transcription factor. Forms homo- or heterodimers with retinoic acid receptors (rars) and binds to target response elements in response to their ligands, all-trans or 9-cis retinoic acid, to regulate gene expression in various biological processes.
Mediates H(+)-dependent pyridoxine transport.
Actin is a highly conserved protein that polymerizes to produce filaments that form cross-linked networks in the cytoplasm of cells. Actin exists in both monomeric (G-actin) and polymeric (F-actin) forms, both forms playing key functions, such as cell motility and contraction. In addition to their role in the cytoplasmic cytoskeleton, G- and F-actin also localize in the nucleus, and regulate gene transcription and motility and repair of damaged DNA.
Methylation at His-73 by SETD3. Methylation stabilizes actin filaments.
Polymerization of globular actin (G-actin) leads to a structural filament (F-actin) in the form of a two-stranded helix (By similarity). Each actin can bind to 4 others (By similarity).
Belongs to the protein kinase superfamily. Tyr protein kinase family. Fes/fps subfamily.
Heterodimer of sae1 and uba2/sae2. The heterodimer corresponds to the two domains that are encoded on a single polypeptide chain in ubiquitin-activating enzyme E1. Interacts with ube2i (By similarity).
Sumoylated with SUMO1 and SUMO2/3 and by UBC9. Sumoylation at Lys-236 inhibits enzymatic activity. Sumoylation at the C-terminal lysine cluster plays an essential role in nuclear trafficking (By similarity).
The heterodimer acts as an E1 ligase for sumo1, sumo2, and sumo3. It mediates ATP-dependent activation of sumo proteins followed by formation of a thioester bond between a sumo protein and a conserved active site cysteine residue on uba2/sae2 (By similarity).
Plays a role in vesicle-mediated protein trafficking to lysosomal compartments including the endocytic membrane transport and autophagic pathways. Believed to act as a core component of the putative HOPS and CORVET endosomal tethering complexes.
Belongs to the Mrp/NBP35 ATP-binding proteins family. NUBP1/NBP35 subfamily.
Binds 4 [4Fe-4S] clusters per heterotetramer. Contains two stable clusters in the N-termini of nubp1 and two labile, bridging clusters between subunits of the nubp1-nubp2 heterotetramer.
Component of the cytosolic iron-sulfur (Fe/S) protein assembly (CIA) machinery. Required for maturation of extramitochondrial Fe-S proteins. The nubp1-nubp2 heterotetramer forms a Fe-S scaffold complex, mediating the de novo assembly of an Fe-S cluster and its transfer to target apoproteins.
Heterotetramer of 2 nubp1 and 2 nubp2 chains.
Acts partially redundantly with other irx members in neural patterning. Required for formation of the posterior forebrain, midbrain, hindbrain, and to a lesser extent, spinal cord. Acts early in neural plate development to induce expression of some but not all proneural genes, and specify a neural precursor state. Also up-regulates repressors that prevent neuronal differentiation. Patterns the neuroectoderm in both the anterior/posterior and dorsal/ventral axes. Acts primarily as a transcriptional repressor during neural development, and binds to the bmp4 promoter to repress gene expression and thus mediate down-regulation of bmp4 by wnt signaling. Controls multiple processes through bmp4-repression including neural plate development, neural crest specification and Spemann organizer development. Involved in the specification of the preplacodal field at the anterior border of the neural plate. Regulates the genetic cascade of interactions that are necessary for positioning the isthmus organizer and the formation of the midbrain-hindbrain boundary. Required during at least two stages of pronephros kidney development; during neurula stages, maintains transcription of key renal genes to define the size and identity of the pronephric anlage, probably in part through regulation of bmp-signaling. Subsequently required for proper formation of the intermediate tubule segment of the pronephros. Acts principally as a transcriptional activator during pronephros development.
Expressed in the neural plate in overlapping patterns with other irx members, which all share an anterior border of expression. Also expressed in the mesoderm, placodes and notochord. Broadly expressed in the tailbud rhombencephalon (hindbrain). Outside the nervous system and at tailbud stages, expressed in the developing otic vesicle, branchial arches, prospective heart region and pronephros.
Catalyzes the covalent attachment of ubiquitin to other proteins. Acts as an essential factor of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated ubiquitin ligase that controls progression through mitosis. Acts by specifically elongating 'Lys-11'-linked polyubiquitin chains initiated by the E2 enzyme ube2c/ubch10 on APC/C substrates, enhancing the degradation of APC/C substrates by the proteasome and promoting mitotic exit.
Belongs to the eukaryotic ribosomal protein eL42 family.
Essential component of the renin-angiotensin system (RAS), a potent regulator of blood pressure, body fluid and electrolyte homeostasis.
Regulates the trafficking and gating properties of AMPA-selective glutamate receptors (AMPARs).
Belongs to the methylenetetrahydrofolate reductase family.
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.
Acts partially redundantly with other irx members in neural patterning. Required for formation of the posterior forebrain, midbrain, hindbrain, and to a lesser extent, spinal cord. Acts early in neural plate development to induce expression of some but not all proneural genes, and specify a neural precursor state. Also up-regulates repressors that prevent neuronal differentiation. Patterns the neuroectoderm in both the anterior/posterior and dorsal/ventral axes. Probably dispensable for pronephric kidney development.
Expressed in the neural plate in overlapping patterns with other irx members, which all share an anterior border of expression. Also expressed in the placodes. Broadly expressed in the tailbud rhombencephalon (hindbrain). Outside the nervous system and at tailbud stages, expressed in the developing otic vesicle, branchial arches, prospective heart region and pronephros.
Belongs to the TRAFAC class YlqF/YawG GTPase family. NOG2 subfamily.
GTPase that associates with pre-60S ribosomal subunits in the nucleolus and is required for their nuclear export and maturation.
Catalyzes the deacetylation of N-acetylaspartic acid (NAA) to produce acetate and L-aspartate.
Belongs to the dynactin subunits 5/6 family. Dynactin subunit 5 subfamily.
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.
Belongs to the G-alpha family. G(s) subfamily.
Belongs to the Mediator complex subunit 11 family.
May be involved in fusion of retrograde transport vesicles derived from an endocytic compartment with the Golgi complex.
Component of a ribonucleoprotein (RNP) complex, at least composed of lsm14a/rap55a, ybx2/frgy2, ddx6/Xp54 and eif4enif1/4E-T. Also forms a complex with prmt1 independently of ybx2/frgy2. Interacts with ddx6/Xp54 but does not appear to directly bind ybx2/frgy2. Different translationally-repressed mRNP complexes probably exist that contain either lsm14a/rap55a or lsm14b/rap55b depending on the developmental stage (By similarity).
RNA-binding component of messenger ribonucleoprotein complexes (mRNPs), storage particles that mask maternal mRNAs from the translational apparatus during oocyte maturation. Acts as a repressor of mRNA translation. Probably involved in the storage of translationally inactive mRNAs in the cytoplasm in order to prevent their degradation.
The RGG repeats are required for interaction with ddx6/Xp54 and accumulation in ribonucleoprotein complexes.
E3 ubiquitin-protein ligase that plays an essential role in stimulus-induced inositol 1,4,5-trisphosphate receptor (ITPR) ubiquitination and degradation via the endoplasmic reticulum-associated degradation (ERAD) pathway. Also involved in ITPR turnover in resting cells.
Required for gamma-tubulin complex recruitment to the centrosome.
Catalyzes the oxidative ring opening of 3-hydroxyanthranilate to 2-amino-3-carboxymuconate semialdehyde, which spontaneously cyclizes to quinolinate.
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).
Poly-ADP-ribosyltransferase that mediates poly-ADP-ribosylation of proteins and plays a key role in DNA repair.
Belongs to the metallophosphoesterase superfamily. CPPED1 family.
Protein phosphatase involved in the dephosphorylation of AKT kinase family.
General regulator of phagocytosis. Required to uptake Gram negative bacterium by macrophages.
Involved in trafficking and recycling of synaptic vesicles.
E3 ubiquitin-protein ligase involved in ER-associated protein degradation, preferentially associates with the E2 enzyme UBE2J2.
Integral component of ER-resident dislocation complexes.
The RING-type zinc finger domain is responsible for E3 ubiquitin ligase activity.
Belongs to the helicase family. RAD25/XPB subfamily.
Belongs to the class I-like SAM-binding methyltransferase superfamily. Glycine N-methyltransferase family.
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.
Membrane receptor involved in phagocytosis. May also regulate homotypic retinal neuron repulsion. May play role in cell adhesion and motility. May also be an essential factor in the regulation of myogenesis, controlling the balance between skeletal muscle satellite cells proliferation and differentiation (By similarity).
May play a central role in the initial events of axis formation and in particular in specifying anterior head regions and their spatial relationship with trunk structures. Activates the head organizer gene cer1 by acting synergistically with siamois and mix-A/mix.1 through the 5'-TAATCT-3' element of the cer1 promoter. Also binds as a complex with lhx1/lim1 and ldb1 to the gsc promoter to stimulate expression (By similarity).
Transcription factor that acts synergistically with tal1/scl and gata1 to specify embryonic dorsal mesoderm to a hematopoietic fate. Induces globin gene expression together with fgf (By similarity).
Involved in DNA double-strand break repair (DSBR). Possesses single-strand endonuclease activity and double-strand-specific 3'-5' exonuclease activity. Also involved in meiotic DSB processing.
Belongs to the SLC34A transporter family.
Belongs to the complex I 23 kDa subunit family.
In mitochondria, S-adenosylmethionine-dependent methyltransferase chaperone that supports both coenzyme Q biosynthesis and NADH:ubiquinone oxidoreductase complex (complex I, MT-ND1) assembly.
PIGY is derived from the same bicistronic transcript that encodes these 2 different proteins.
Involved in the fragmentation of the mitochondrial network and its perinuclear clustering.
The C-terminus is required for mitochondrial localization, while the N-terminus is necessary for mitochondrial fission.
Belongs to the ribose 5-phosphate isomerase family.
Belongs to the WWC family. KIBRA subfamily.
May play a role in the regulation of the Hippo signaling pathway.
The C2-domain mediates homodimerization.
Belongs to the class I-like SAM-binding methyltransferase superfamily. DOT1 family.
Histone methyltransferase that specifically trimethylates histone H3 to form H3K79me3. This methylation is required for telomere silencing and for the pachytene checkpoint during the meiotic cell cycle by allowing the recruitment of RAD9 to double strand breaks. Nucleosomes are preferred as substrate compared to free histone.
In contrast to other lysine histone methyltransferases, it does not contain a SET domain, suggesting the existence of another mechanism for methylation of lysine residues of histones.
Cilium- and flagellum-specific protein that plays a role in axonemal structure organization and motility. Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating. Involved in the regulation of the size and morphology of cilia. Required for axonemal microtubules polyglutamylation.
Belongs to the anaerobic coproporphyrinogen-III oxidase family. HemW subfamily.
May be a heme chaperone, appears to bind heme. Homologous bacterial proteins do not have oxygen-independent coproporphyrinogen-III oxidase activity. Binds 1 [4Fe-4S] cluster. The cluster is coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine.
Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility.
Belongs to the homogentisate dioxygenase family.
Acts as guanine nucleotide exchange factor (GEF) for CDC42. Promotes formation of GPHN clusters.
Following synaptic activity, forms amyloid-like oligomers (By similarity). Aggregation requires an intact actin cytoskeleton (By similarity).
In embryos, expressed in the central nervous system, and intermediate and distal pronephric tubule segments of the embryonic kidney.
Sequence-specific RNA-binding protein which acts as a translational repressor in the basal unstimulated state but, following neuronal stimulation, acts as a translational activator (By similarity). Does not bind to the cytoplasmic polyadenylation element (CPE), a uridine-rich sequence element within the mRNA 3'-UTR, but binds to a U-rich loop within a stem-loop structure (By similarity). Required for the consolidation and maintenance of hippocampal-based long term memory (By similarity). Inhibits differentiation of intermediate mesoderm from an early stage to inhibit pronephric differentiation but induce neural differentiation (PubMed:18472403).
The N-terminal Gln-rich region is required for the formation of amyloid-like oligomers and for the stability of long-term potentiation and spatial memory.
Belongs to the PPP phosphatase family. PP-5 (PP-T) subfamily.
Oxysterol-binding protein that mediates feedback control of cholesterol synthesis by controlling both endoplasmic reticulum to Golgi transport of scap and degradation of hmgcr. Acts as a negative regulator of cholesterol biosynthesis by mediating the retention of the SCAP-SREBP complex in the endoplasmic reticulum, thereby blocking the processing of sterol regulatory element-binding proteins (SREBPs). Binds oxysterol, including 25-hydroxycholesterol, regulating interaction with scap and retention of the SCAP-SREBP complex in the endoplasmic reticulum. In presence of oxysterol, interacts with scap, retaining the SCAP-SREBP complex in the endoplasmic reticulum, thereby preventing scap from escorting SREBPs to the Golgi. Sterol deprivation reduces oxysterol-binding, disrupting the interaction between insig1 and scap, thereby promoting Golgi transport of the SCAP-SREBP complex, followed by processing and nuclear translocation of SREBPs. Also regulates cholesterol synthesis by regulating degradation of hmgcr.
Belongs to the CCR4/nocturin family. TTRAP/TDP2 subfamily.
Binds 1 magnesium or manganese ion per subunit.
DNA repair enzyme that can remove a variety of covalent adducts from DNA through hydrolysis of a 5'-phosphodiester bond, giving rise to DNA with a free 5' phosphate. Catalyzes the hydrolysis of dead-end complexes between DNA and the topoisomerase 2 (top2) active site tyrosine residue. Hydrolyzes 5'-phosphoglycolates on protruding 5' ends on DNA double-strand breaks (DSBs) due to DNA damage by radiation and free radicals.
Transcriptional activator. Participates in neural induction (By similarity).
May play a role in mitochondrial dynamics by controlling mitochondrial membrane fission.
Pro-inflammatory cytokine. Involved in the innate immune response to bacterial pathogens. The expression of MIF at sites of inflammation suggests a role as mediator in regulating the function of macrophages in host defense. Has phenylpyruvate tautomerase and dopachrome tautomerase activity (in vitro), but the physiological substrate is not known. It is not clear whether the tautomerase activity has any physiological relevance, and whether it is important for cytokine activity (By similarity).
May play a role in anterograde transport of membrane proteins from the endoplasmic reticulum to the Golgi.
Belongs to the PI3/PI4-kinase family. TRA1 subfamily.
Required during spermiogenesis to participate in the repression transposable elements and prevent their mobilization, which is essential for the germline integrity. Probably acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and govern the methylation and subsequent repression of transposons (By similarity).
Belongs to the complex I NDUFA1 subunit family.
Transcription factor with sequence-specific DNA binding activity. Binds to the consensus sequence 5'-[AT][AT]CAA[AT]G-3', showing a preference for 5'-AACAAT-3' and 5'-AACAAAG-3'. Inhibits beta-catenin-mediated dorsal axis specification by binding to sites within the promoter of the beta-catenin-regulated gene nodal5. Maternally derived sox3 acts as a transcriptional repressor of nodal5 and nodal6 to restrict their expression to the vegetal hemisphere of early embryos and thus establish germ layer formation. Acts at multiple points to inhibit nodal signaling, repressing the expression of the other mesoderm-inducing nodal genes nodal, nodal2 and nodal4, and also acting downstream to induce expression of genes including trim33/ectodermin, ema and coco, whose products repress nodal signaling (By similarity).
Expressed ubiquitously throughout the embryo. Shows tissue-specific expression in adults, being abundant in most neurons of the central nervous system (CNS) and in all spermatogenic cells of the testis.
Multifunctional polyribosome-associated RNA-binding protein that plays a central role in neuronal development and synaptic plasticity through the regulation of alternative mRNA splicing, mRNA stability, mRNA dendritic transport and postsynaptic local protein synthesis of target mRNAs. Acts as an mRNA regulator by mediating formation of some phase-separated membraneless compartment: undergoes liquid-liquid phase separation upon binding to target mRNAs, leading to assemble mRNAs into cytoplasmic ribonucleoprotein granules that concentrate mRNAs with associated regulatory factors (By similarity). Binds poly(G) and poly(U), and to a lower extent poly(A) and poly(C) (By similarity).
The C-terminal disordered region undergoes liquid-liquid phase separation (LLPS) for the formation of a membraneless compartment that concentrates mRNAs with associated regulatory factors.
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.
May act by regulating membrane trafficking and cellular morphogenesis.
Belongs to the metallo-dependent hydrolases superfamily. Adenosine and AMP deaminases family. ADGF subfamily.
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.
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. 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.
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).
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.
Adenosyl-L-methionine (AdoMet)-dependent tRNA (uracil-O(2)-)-methyltransferase.
Probable adenosyl-L-methionine (AdoMet)-dependent tRNA (uracil-O(2)-)-methyltransferase.
Belongs to the protein-tyrosine phosphatase family.
May act as a transcriptional regulator. Plays a role in noradrenergic neuron, pancreatic and gastrointestinal endocrine cells differentiation during embryonic development (By similarity).
Component of complexes involved in DNA repair and protein ubiquitination. May play a role in the regulation of the circadian clock.
The core of the protein consists of three WD40 beta-propeller domains.
Belongs to the P-Pant transferase superfamily. AcpS family.
Belongs to the transient receptor (TC 1.A.4) family. STrpC subfamily. TRPC1 sub-subfamily.
Thought to form a receptor-activated non-selective calcium permeant cation channel. Probably is operated by a phosphatidylinositol second messenger system activated by receptor tyrosine kinases or G-protein coupled receptors. Seems to be also activated by intracellular calcium store depletion.
Acts as a central player within a network of stress response pathways promoting cellular adaptability. Functions as a negative regulator of TP53/P53 in the cellular response to telomere erosion and probably also DNA damage.
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.
Plays an important role in the degradation of dermatan and keratan sulfates.
Secretory protein that plays a role in various cellular processes. Acts as a chemorepellent acting on gonadotropin-releasing hormone (GnRH) expressing neurons regulating their migration to the hypothalamus. Also promotes neuron migration, growth and survival as well as neurite outgrowth and is involved in the development of the olfactory system. May also act through the regulation of growth factors activity and downstream signaling (By similarity). Also regulates extracellular matrix assembly and cell adhesiveness (By similarity). Promotes endothelial cell survival, vessel formation and plays an important role in the process of revascularization through NOS3-dependent mechanisms (By similarity).
Functions as actin-binding component of the Arp2/3 complex which is involved in regulation of actin polymerization and together with an activating nucleation-promoting factor (NPF) mediates the formation of branched actin networks.
Belongs to the calcium channel flower family.
Belongs to the protein-tyrosine phosphatase family. Receptor class 8 subfamily.
Regulates autophagy by controlling the spatial distribution and levels of the intracellular phosphatidylinositol 4-phosphate (PtdIns(4)P) pools (By similarity). Modulates (PtdIns(4)P) levels by regulating the ER-to-Golgi trafficking of the phosphatidylinositide phosphatase SACM1L (By similarity).
Active in presence of diverse metals including Fe(2+), Zn(2+), Mn(2+) (By similarity). Also activated by Ca(2+) (By similarity). Binds two metal cations in two adjacent alpha and beta metal-binding pockets (By similarity).
Belongs to the lariat debranching enzyme family.
Cleaves the 2'-5' phosphodiester linkage at the branch point of excised lariat intron RNA and converts them into linear molecules that can be subsequently degraded, thereby facilitating ribonucleotide turnover. Linked to its role in pre-mRNA processing mechanism, may also participate in retrovirus replication and have an antiviral cell-intrinsic defense function.
Interacts with csnk1e, ctnnb1, ctbp, dact1 and gsk3b. May interact with ase and tle4 (By similarity).
Participates in the Wnt signaling pathway. Binds to DNA and acts as a repressor in the absence of ctnnb1, and as an activator in its presence. Required early in development for the establishment of the dorsal body axis in response to maternal Wnt signaling (By similarity).
Phosphorylated. Phosphorylation by csnk1e promotes binding to ctnnb1 while phosphorylation by gsk3b may reverse this effect (By similarity).
Single-stranded DNA-dependent ATP-dependent helicase.
Belongs to the fatty acid desaturase CarF family.
Lacks most of the conserved residues that are essential for binding the metal cofactor and hence for dihydropyrimidinase activity. Its enzyme activity is therefore unsure.
Necessary for signaling by class 3 semaphorins and subsequent remodeling of the cytoskeleton. Plays a role in axon guidance, neuronal growth cone collapse and cell migration (By similarity).
Small GTPase required for proper nuclear import of RNA polymerase II (RNAPII). May act at an RNAP assembly step prior to nuclear import.
Component of the ESCRT-I complex (endosomal sorting complex required for transport I), a regulator of vesicular trafficking process.
Component of the Mediator complex, a coactivator involved in regulated gene transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. Binds to and activates cyclin-dependent kinase cdk8 that phosphorylates the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAp II), which may inhibit the formation of a transcription initiation complex (By similarity).
Component of the Mediator complex. The cylin/CDK pair formed by ccnc/cdk8 also associates with the large subunit of RNA polymerase II (By similarity).
Adds a GMP to the 5'-end of tRNA(His) after transcription and RNase P cleavage.
Belongs to the tRNA(His) guanylyltransferase family.
Belongs to the NAD(P)-dependent epimerase/dehydratase family.
Catalyzes two distinct but analogous reactions: the reversible epimerization of UDP-glucose to UDP-galactose and the reversible epimerization of UDP-N-acetylglucosamine to UDP-N-acetylgalactosamine. The reaction with UDP-Gal plays a critical role in the Leloir pathway of galactose catabolism in which galactose is converted to the glycolytic intermediate glucose 6-phosphate. It contributes to the catabolism of dietary galactose and enables the endogenous biosynthesis of both UDP-Gal and UDP-GalNAc when exogenous sources are limited. Both UDP-sugar interconversions are important in the synthesis of glycoproteins and glycolipids.
Belongs to the nucleobase:cation symporter-2 (NCS2) (TC 2.A.40) family.
Sodium/ascorbate cotransporter. Mediates electrogenic uptake of vitamin C, with a stoichiometry of 2 Na(+) for each ascorbate.
Belongs to the complex I LYR family. SDHAF1 subfamily.
Farnesylation is required for Golgi targeting.
Palmitoylated; catalyzes its own palmitoylation. Palmitoylation is required for Golgi targeting.
The longin domain regulates palmitoylation and membrane targeting.
Vesicular soluble NSF attachment protein receptor (v-SNARE) mediating vesicle docking and fusion to a specific acceptor cellular compartment. Functions in endoplasmic reticulum to Golgi transport; as part of a SNARE complex composed of GOSR1, GOSR2 and STX5. Functions in early/recycling endosome to TGN transport; as part of a SNARE complex composed of BET1L, GOSR1 and STX5. Has a S-palmitoyl transferase activity.
Component of the BCR(TNFAIP1) E3 ubiquitin ligase complex, at least composed of cul3, tnfaip1/bacurd2 and rbx1.
Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complex involved in regulation of cytoskeleton structure. The BCR(TNFAIP1) E3 ubiquitin ligase complex mediates the ubiquitination of target proteins, leading to their degradation by the proteasome (By similarity).
Probable peripherally associated component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids.
Belongs to the eukaryotic NMN adenylyltransferase family.
Autocatalytically cleaved in response to double-stranded DNA-binding: autocatalytic cleavage takes place in trans and leads to inactivation.
DNA-binding activates the protease activity: single-stranded DNA-binding specifically activates ability to cleave covalent DNA-protein cross-links (DPCs). In contrast, double-stranded DNA-binding specifically activates autocatalytic cleavage, and subsequent inactivation.
DNA-dependent metalloendopeptidase that mediates the proteolytic cleavage of covalent DNA-protein cross-links (DPCs) during DNA synthesis, thereby playing a key role in maintaining genomic integrity (By similarity). DPCs are highly toxic DNA lesions that interfere with essential chromatin transactions, such as replication and transcription, and which are induced by reactive agents, such as UV light or formaldehyde. Associates with the DNA replication machinery and specifically removes DPCs during DNA synthesis. Acts as a pleiotropic protease for DNA-binding proteins cross-linked with DNA, such as top1, top2a, histones H3 and H4 (By similarity). Mediates degradation of DPCs that are not ubiquitinated, while it is not able to degrade ubiquitinated DPCs. SPRTN activation requires polymerase collision with DPCs followed by helicase bypass of DPCs (By similarity). May also act as a 'reader' of ubiquitinated pcna: facilitates chromatin association of rad18 and is required for efficient pcna monoubiquitination, promoting a feed-forward loop to enhance pcna ubiquitination and translesion DNA synthesis. Acts as a regulator of translesion DNA synthesis by recruiting vcp/p97 to sites of DNA damage (By similarity).
The UBZ4-type zinc fingers mediate binding to 'Lys-48'- and 'Lys-63'-linked polyubiquitin.
Interacts with PTBP2; the interaction is direct.
Expressed diffusely through much of gastrula and neurula stage embryos. At stage 23 (late neurula), limited to the otic vesicle. By stage 28 (tailbud), also expressed transiently in the presumptive nephrostomes of the pronephros. At stage 35 (early tadpole), expressed broadly in the head and strongly expressed in the developing gill structures.
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 eukaryotic ribosomal protein eL30 family.
Probably acts as a transcriptional activator. May bind to the minimal GLI-consensus sequence 5'-GGGTGGTC-3'. Can determine the ectodermal cell fate and promote the earliest step of neural and neural crest development. Involved in establishing left-right asymmetry in the embryo (By similarity).
The C2H2-type 3, 4 and 5 zinc finger domains are necessary for transcription activation. The zinc fingers and the N-terminus are independently important for establishing the L/R axis (By similarity).
Belongs to the RNase H2 subunit B family.
Non catalytic subunit of RNase H2, an endonuclease that specifically degrades the RNA of RNA:DNA hybrids. Participates in DNA replication, possibly by mediating the removal of lagging-strand Okazaki fragment RNA primers during DNA replication. Mediates the excision of single ribonucleotides from DNA:RNA duplexes (By similarity).
Non catalytic subunit of RNase H2, an endonuclease that specifically degrades the RNA of RNA:DNA hybrids. Participates in DNA replication, possibly by mediating the removal of lagging-strand Okazaki fragment RNA primers during DNA replication. Mediates the excision of single ribonucleotides from DNA:RNA duplexes.
The RNase H2 complex is a heterotrimer composed of the catalytic subunit RNASEH2A and the non-catalytic subunits RNASEH2B and RNASEH2C.
May play role in the regulation of alternative splicing. May have hydrolase activity.
Involved in ciliogenesis. It is required for appropriate acetylation and polyglutamylation of ciliary microtubules, and regulation of cilium length (By similarity). Acts as a positive regulator of hedgehog (Hh)signaling (By similarity).
Belongs to the PPase class C family. Prune subfamily.
Inhibited by N-methyl-D-glucamine. Inhibited by choline. Allosteric regulation of sodium ions binding by pH.
Symporter that cotransports neutral amino acids and sodium ions from the extraccellular to the intracellular side of the cell membrane. The trasnport is pH-sensitive, Li(+)-intolerant, electrogenic, driven by the Na(+) electrochemical gradient and cotransports of neutral amino acids and sodium ions with a stoichiometry of 1:1.
The extracellular C-terminal domain controls the voltage dependence for amino acid transports activity.
Adhesion plaque protein. May be a component of a signal transduction pathway that mediates adhesion-stimulated changes in gene expression. Suppresses the transcription-repressing activity of hesx1/anf1 (By similarity).
Interacts (via LIM2 domain) with hesx1/anf1.
Transcriptional corepressor which does not bind directly to DNA and may regulate transcription through recruitment of histone deacetylases to gene promoters. Regulates cell adhesion, migration and proliferation (By similarity). Involved in specification of the lateral neural plate border (NPB) (By similarity). May be required for segmental gene expression during hindbrain development (By similarity).
5'->3' DNA exonuclease which digests single-stranded DNA (ssDNA) (By similarity). Regulates inflammatory cytokine responses via the degradation of nucleic acids, by reducing the concentration of ssDNA able to stimulate TLR9, a nucleotide-sensing receptor in collaboration with PLD4 (By similarity). May be important in myotube formation. Plays a role in lysosomal homeostasis. Involved in the regulation of endosomal protein sorting (By similarity).
It was initially thought that PDL3 has phospholipase D activity due to its HKD motifs. The second HKD motif contains Glu instead of the canonical Asp. Its enzyme activity is therefore unsure. Catalytic phospholipase D activity is still controversial (By similarity). Its closest homolog PLD4, exhibits no phospholipase activity (By similarity).
Proteolytically processed to a soluble form that is stable within endosomes and lysosomes. During transport through the secretory pathway becomes proteolysed by cysteine proteases, thereby releasing a stable soluble lysosomal lumenal polypeptide, whereas the transmembrane-bound fragment is rapidly degraded. Its transport route to lysosomes involves ubiquitination and the ESCRT complex.
Ubiquitinated. Ubiquitination mediates sorting into lysosomes.
Belongs to the krueppel C2H2-type zinc-finger protein family. ZBTB18 subfamily.
Transcriptional repressor that plays a role in various developmental processes. Specifically binds the consensus DNA sequence 5'-[AC]ACATCTG[GT][AC]-3' which contains the E box core, and acts by recruiting chromatin remodeling multiprotein complexes (By similarity).
Belongs to the pseudouridine synthase TruB family.
Essential component of the RMI complex, a complex that plays an important role in the processing of homologous recombination intermediates to limit DNA crossover formation in cells. Promotes TOP3A binding to double Holliday junctions (DHJ) and hence stimulates TOP3A-mediated dissolution. Required for BLM phosphorylation during mitosis. Within the BLM complex, required for BLM and TOP3A stability.
Component of the RNA polymerase III (Pol III) complex consisting of 17 subunits.
Cilium-specific protein required for the stability of the ciliary architecture. Plays a role in cytoplasmic preassembly of dynein arms. Involved in regulation of microtubule-based cilia and actin-based brush border microvilli.
Belongs to the DNA polymerase type-X family.
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 DOK family. Type B subfamily.
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.
May act as a p53/TP53-apoptotic effector.
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. 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 (By similarity).
Exhibits phosphohistidine phosphatase activity.
May play an important role in centriole assembly and/or stability and ciliogenesis.
Belongs to the Mediator complex subunit 30 family.
Plays a role in mitochondrial morphogenesis.
Belongs to the ETF alpha-subunit/FixB family.
The electron transfer flavoprotein serves as a specific electron acceptor for several dehydrogenases, including five acyl-CoA dehydrogenases, glutaryl-CoA and sarcosine dehydrogenase. It transfers the electrons to the main mitochondrial respiratory chain via ETF-ubiquinone oxidoreductase (ETF dehydrogenase).
Belongs to the flagellar radial spoke RSP9 family.
Component of axonemal radial spoke complexes.
Functions as part of axonemal radial spoke complexes that play an important part in the motility of sperm and cilia (By similarity). Essential for both the radial spoke head assembly and the central pair microtubule stability in ependymal motile cilia (By similarity). Required for motility of olfactory and neural cilia and for the structural integrity of ciliary axonemes in both 9+0 and 9+2 motile cilia (By similarity).
Probable regulator of exocrine pancreas development.
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 (By similarity).
Belongs to the purine/pyrimidine phosphoribosyltransferase family.
Lacks the conserved active site Asp and is not expected to have phosphoribosyltransferase activity.
Zinc ion transporter mediating zinc entry from the cytosol into the lumen of organelles along the secretory pathway. By contributing to zinc ion homeostasis within the early secretory pathway, regulates the activation and folding of enzymes like alkaline phosphatases.
Belongs to the PIGG/PIGN/PIGO family. PIGG subfamily.
Chromatin reader component of the NuA4 histone acetyltransferase complex, a multiprotein complex involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. The NuA4 complex plays a direct role in repair of DNA double-strand breaks (DSBs) by promoting homologous recombination (HR). MBTD1 specifically recognizes and binds monomethylated and dimethylated 'Lys-20' on histone H4 (H4K20me1 and H4K20me2, respectively). In the NuA4 complex, MBTD1 promotes recruitment of the complex to H4K20me marks by competing with TP53BP1 for binding to H4K20me. Following recruitment to H4K20me at DNA breaks, the NuA4 complex catalyzes acetylation of 'Lys-15' on histone H2A (H2AK15), blocking the ubiquitination mark required for TP53BP1 localization at DNA breaks, thereby promoting homologous recombination (HR).
Monomer. Component of the NuA4 histone acetyltransferase complex.
Belongs to the SIMIBI class G3E GTPase family. ArgK/MeaB subfamily.
Involved in the positive regulation of histone H3-K9 dimethylation.
Belongs to the AAA ATPase family. PCH2 subfamily.
Plays a key role in chromosome recombination and chromosome structure development during meiosis. Required at early steps in meiotic recombination that leads to non-crossovers pathways. Also needed for efficient completion of homologous synapsis by influencing crossover distribution along the chromosomes affecting both crossovers and non-crossovers pathways (By similarity).
Plays a key role in chromosome recombination and chromosome structure development during meiosis. Required at early steps in meiotic recombination that leads to non-crossovers pathways. Also needed for efficient completion of homologous synapsis by influencing crossover distribution along the chromosomes affecting both crossovers and non-crossovers pathways.
Belongs to the complex I 30 kDa subunit family.
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.
Transcription elongation factor that enhances transcription elongation by RNA polymerase II (RNAPII).
Belongs to the glycosyl hydrolase 38 family.
Belongs to the complex I NDUFB7 subunit family.
Receptor for apelin receptor early endogenous ligand (apela) and apelin (apln) hormones coupled to G proteins that inhibit adenylate cyclase activity. Plays a key role in early development such as gastrulation, blood vessels formation and heart morphogenesis by acting as a receptor for apela hormone, promoting endoderm and mesendoderm cell migration and regulating the migration of cells fated to become myocardial progenitors, respectively. Promotes angioblast migration toward the embryonic midline, i.e. the position of the future vessel formation, during vasculogenesis. May promote sinus venosus (SV)-derived endothelial cells migration into the developing heart to promote coronary blood vessel development. Required for cardiovascular development, particularly for intersomitic vein angiogenesis. Plays also a role in various processes in adults such as regulation of blood vessel formation, blood pressure, heart contractility, and heart failure. Acts upstream of the i/o type of G-alpha proteins in the differentiation of endothelium, erythroid cells, myeloid cells and cardiomyocytes.
E3 ubiquitin-protein ligase that mediates ubiquitination oF target proteins. Depending on the associated E2 ligase, mediates 'Lys-48'- and 'Lys-63'-linked polyubiquitination of substrates. Part of a BAG6-dependent quality control process ensuring that proteins of the secretory pathway that are mislocalized to the cytosol are degraded by the proteasome. Probably acts by providing the ubiquitin ligase activity associated with the BAG6 complex and be responsible for ubiquitination of the hydrophobic mislocalized proteins and their targeting to the proteasome.
Protein-lysine methyltransferase that selectively mono-, di- and trimethylates 'Lys-165' of the translation elongation factors EEF1A1 and EEF1A2 in an aminoacyl-tRNA and GTP-dependent manner. EEF1A1 methylation by EEF1AKMT3 is dynamic as well as inducible by stress conditions, such as ER-stress, and plays a regulatory role on mRNA translation.
Probable component of a E3 ubiquitin ligase complex.
Belongs to the CMP-NeuNAc synthase family.
Plays a role in U6 snRNP assembly and function. Binds to the 3' end of U6 snRNA.
Belongs to the GTP-binding SRP family. SRP54 subfamily.
Component of the signal recognition particle (SRP) complex, a ribonucleoprotein complex that mediates the cotranslational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER).
The M domain binds the 7SL RNA in presence of SRP19 and binds the signal sequence of presecretory proteins.
The NG domain, also named G domain, is a special guanosine triphosphatase (GTPase) domain, which binds GTP and forms a guanosine 5'-triphosphate (GTP)-dependent complex with a homologous NG domain in the SRP receptor subunit SRPRA. The two NG domains undergo cooperative rearrangements upon their assembly, which culminate in the reciprocal activation of the GTPase activity of one another. SRP receptor compaction upon binding with cargo-loaded SRP and GTPase rearrangement drive SRP-mediated cotranslational protein translocation into the ER.
Component of the signal peptidase complex.
Receptor for Dickkopf proteins. Cooperates with DKK1/2 to inhibit Wnt/beta-catenin signaling by promoting the endocytosis of Wnt receptors LRP5 and LRP6.
Belongs to the SNF2/RAD54 helicase family. CHD8 subfamily.
DNA helicase that acts as a chromatin remodeling factor and regulates transcription. Acts as a transcription repressor by remodeling chromatin structure and recruiting histone H1 to target genes. Suppresses p53/TP53-mediated apoptosis by recruiting histone H1 and preventing p53/TP53 transactivation activity. Acts as a negative regulator of Wnt signaling pathway by regulating beta-catenin (CTNNB1) activity. Negatively regulates CTNNB1-targeted gene expression by being recruited specifically to the promoter regions of several CTNNB1 responsive genes. May also act as a transcription activator by participating in efficient U6 RNA polymerase III transcription.
Involved in the catabolism of quinolinic acid (QA).
Although the makorin-type Cys-His region lacks the final His residue, the following Asp residue may be able to coordinate Zn(2+).
E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins (By similarity). Inhibits neurogenesis and axis formation during embryonic development by modulating the phosphatidylinositol 3-kinase (PI3K) pathway (By similarity). Acts downstream of PI3K and akt1 to up-regulate gsk3b mRNA expression (By similarity).
Belongs to the eukaryotic/archaeal RNase P protein component 1 family.
Component of nuclear RNase P and RNase MRP.
Component of ribonuclease P, a ribonucleoprotein complex that generates mature tRNA molecules by cleaving their 5'-ends.
Belongs to the glycosyltransferase 54 family.
Glycosyltransferase that catalyze the transfer of GlcNAc from UDP-GlcNAc to the GlcNAcbeta1-2Manalpha1-3 arm of the core structure of N-linked glycans through a beta1-4 linkage and participates in the production of tri- and tetra-antennary N-linked sugar chains (By similarity). Involved in glucose transport by mediating SLC2A2/GLUT2 glycosylation, thereby controlling cell-surface expression of SLC2A2 in pancreatic beta cells (By similarity).
Belongs to the V-ATPase D subunit family.
Belongs to the Rieske iron-sulfur protein family.
The Rieske protein is a high potential 2Fe-2S protein.
Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ11 subfamily.
Belongs to the acetyltransferase family. GCN5 subfamily.
Factor involved in transcription-coupled nucleotide excision repair (TC-NER), a mechanism that rapidly removes RNA polymerase II-blocking lesions from the transcribed strand of active genes. Facilitates the ubiquitination of the elongating form of RNA polymerase II (RNA pol IIo) at DNA damage sites, thereby promoting RNA pol IIo backtracking and access by the TC-NER machinery to lesion sites (By similarity).
Monoubiquitinated at Lys-432 in response to transcription stress; this promotes efficient transfer of TFIIH to stalled RNA polymerase II.
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.
Belongs to the actin-binding proteins ADF family. GMF subfamily.
Belongs to the complex I subunit 1 family.
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. This alpha-1B subunit gives rise to N-type calcium currents. N-type calcium channels belong to the 'high-voltage activated' (HVA) group. They are involved in pain signaling. Calcium channels containing alpha-1B subunit may play a role in directed migration of immature neurons.
Plays an important role in regulating the size of autophagosomes during the formation process.
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.
Required for pre-mRNA splicing as component of the activated spliceosome. May have a scaffolding role in the spliceosome assembly as it contacts all other components of the core complex.
May function in combinations with OTX1/2 to specify cell fates in the developing central nervous system.
As a component of 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. Involved in retrograde ciliary transport along microtubules from the ciliary tip to the base.
Mediates the intracellular transfer of ceramide-1-phosphate (C1P) between organelle membranes and the cell membrane. Required for normal structure of the Golgi stacks. Can bind phosphoceramides with a variety of aliphatic chains, but has a preference for lipids with saturated C16:0 or monounsaturated C18:1 aliphatic chains, and is inefficient with phosphoceramides containing lignoceryl (C24:0). Plays a role in the regulation of the cellular levels of ceramide-1-phosphate, and thereby contributes to the regulation of phospholipase PLA2G4A activity and the release of arachidonic acid. Has no activity with galactosylceramide, lactosylceramide, sphingomyelin, phosphatidylcholine, phosphatidic acid and ceramide. C1P transfer is stimulated by phosphatidylserine in C1P source vesicles. Regulates autophagy and pyroptosis, but not apoptosis.
Plays a role in vesicular protein sorting.
Belongs to the aspartate/ornithine carbamoyltransferase superfamily.
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.
Component of the ctf18-RFC complex which consists of ctf18, ctf8, dscc1 and the RFC complex.
Loads pcna onto primed templates regulating velocity, spacing and restart activity of replication forks. May couple DNA replication to sister chromatid cohesion (By similarity).
Component of TFIIIB complexes. Interacts with TBP and forms a ternary complex with TBp and target DNA sequences.
General activator of RNA polymerase III transcription. Factor exclusively required for RNA polymerase III transcription of genes with promoter elements upstream of the initiation sites. Contributes to the regulation of gene expression; functions as activator in the absence of oxidative stress. Down-regulates expression of target genes in response to oxidative stress. Overexpression protects cells against apoptosis in response to oxidative stress.
In response to oxidative stress, a Cys-residue is reversibly oxidized to cysteine sulfenic acid. This impairs formation of a ternary complex with TBP and DNA and down-regulates expression of target genes in response to oxidative stress.
Component of the Mediator complex, a coactivator involved in regulated gene transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional pre-initiation complex with RNA polymerase II and the general transcription factors. Phosphorylates the CTD (C-terminal domain) of the large subunit of RNA polymerase II (RNAp II), which may inhibit the formation of a transcription initiation complex (By similarity).
Component of the Mediator complex. Interacts with ccnc.
Essential for male and female fertility, playing a crucial role in regulating germ cell development by ensuring the proper progression of meiosis prophase I.
Acts as guanine nucleotide exchange factor (GEF) for RhoA and RhoB GTPases.
Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A6 subfamily.
Binds two metal ions per subunit. Two metal binding sites with different affinities are located in the enzyme active site and can be occupied in vitro by different metals: site 1 is occupied by Zn(2+), Mn(2+), Mg(2+) or Co(2+), while the tight binding site 2 can be occupied by only Zn(2+) or Co(2+). One Zn(2+) ion is tightly bound to site 2 and essential for enzyme activity in vivo, while site 1 can be occupied by different metals to give different enzymatic activities. Mn(2+) is required for Cys-Gly hydrolysis activity. A third metal binding site may serve a structural role, possibly stabilizing part of the interface between the N-terminal and the catalytic domain.
Cytosolic metallopeptidase that catalyzes the removal of unsubstituted N-terminal hydrophobic amino acids from various peptides. The presence of Zn(2+) ions is essential for the peptidase activity, and the association with other cofactors can modulate the substrate spectificity of the enzyme. For instance, in the presence of Mn(2+), it displays a specific Cys-Gly hydrolyzing activity of Cys-Gly-S-conjugates. Involved in the metabolism of glutathione and in the degradation of glutathione S-conjugates, which may play a role in the control of the cell redox status.
May function as a linker between cadherin adhesion receptors and the cytoskeleton to regulate cell-cell adhesion and differentiation in the nervous system.
Homotetramer (in vitro). Heterotetramer with HSD17B8; contains two molecules each of HSD17B8 and CBR4.
The heterotetramer with HSD17B8 has NADH-dependent 3-ketoacyl-acyl carrier protein reductase activity, and thereby plays a role in mitochondrial fatty acid biosynthesis. Within the heterotetramer, HSD17B8 binds NADH; CBR4 binds NADPD. The homotetramer has NADPH-dependent quinone reductase activity. Both homotetramer and the heterotetramer have broad in vitro substrate specificity and can reduce 9,10-phenanthrenequinone, 1,4-benzoquinone and various other o-quinones and p-quinones.
Component of the BCR(KLHL25) E3 ubiquitin ligase complex, at least composed of cul3, klhl25 and rbx1.
Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex involved in various processes, such as translation homeostasis and lipid synthesis. The BCR(KLHL25) ubiquitin ligase complex acts by mediating ubiquitination of hypophosphorylated eif4ebp1 (4E-BP1): ubiquitination and subsequent degradation of hypophosphorylated EIF4EBP1 (4E-BP1) probably serves as a homeostatic mechanism to maintain translation and prevent eIF4E inhibition when eIF4E levels are low. The BCR(KLHL25) complex also acts as a regulator of lipid synthesis by mediating ubiquitination and degradation of ACLY, thereby inhibiting lipid synthesis.
Belongs to the RFamide neuropeptide family.
Belongs to the uroporphyrinogen-III synthase 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.
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 metallo-dependent hydrolases superfamily. Allantoinase family.
Catalyzes the covalent attachment of ubiquitin to other proteins. May be involved in apoptosis regulation.
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 H2A.Zl 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 required at gastrulation for correct mesoderm formation (By similarity).
Functions as a component of the PCAF complex. The PCAF complex is capable of efficiently acetylating histones in a nucleosomal context (By similarity).
Involved in the 5-carboxymethylaminomethyl modification (mnm(5)s(2)U34) of the wobble uridine base in mitochondrial tRNAs.
May play a role in regulating axonal regeneration and plasticity in the adult central nervous system.
Required for Ca(2+) flux in immune cells and plays a role in T-cell proliferation and in T-cell and neutrophil migration (By similarity). Involved in endoplasmic reticulum-associated degradation (ERAD) of soluble glycosylated proteins (By similarity). Required for cell surface expression of CD36 and involved in macrophage uptake of low-density lipoprotein and in foam cell formation (By similarity). Required for palmitoylation (By similarity).
Belongs to the sirtuin family. Class I subfamily.
Adapter protein of the Toll-like and IL-1 receptor signaling pathway that is involved in the activation of NF-kappa-B.
Required for efficient assembly of mitochondrial NADH:ubiquinone oxidoreductase.
Electroneutral transporter of the plasma membrane mediating the cellular uptake of the divalent metal cations zinc, manganese and iron that are important for tissue homeostasis, metabolism, development and immunity (By similarity). Functions as an energy-dependent symporter, transporting through the membranes an electroneutral complex composed of a divalent metal cation and two bicarbonate anions. Beside these endogenous cellular substrates, can also import cadmium a non-essential metal which is cytotoxic and carcinogenic (By similarity).
Scaffold subunit of some HBO1 complexes, which have a histone H4 acetyltransferase activity.
In the C-terminal section; belongs to the eukaryotic ribosomal protein eL40 family.
May play a role in dendrite formation by melanocytes.
Acyl-CoA binding protein which acts as the peroxisome receptor for pexophagy but is dispensable for aggrephagy and nonselective autophagy. Binds medium- and long-chain acyl-CoA esters (By similarity).
Acyl-CoA binding protein which acts as the peroxisome receptor for pexophagy but is dispensable for aggrephagy and nonselective autophagy. Binds medium- and long-chain acyl-CoA esters.
Component of the SKA1 complex, a microtubule-binding subcomplex of the outer kinetochore that is essential for proper chromosome segregation. Required for timely anaphase onset during mitosis, when chromosomes undergo bipolar attachment on spindle microtubules leading to silencing of the spindle checkpoint. The SKA1 complex is a direct component of the kinetochore-microtubule interface and directly associates with microtubules as oligomeric assemblies. The complex facilitates the processive movement of microspheres along a microtubule in a depolymerization-coupled manner. Affinity for microtubules is synergistically enhanced in the presence of the ndc-80 complex and may allow the ndc-80 complex to track depolymerizing microtubules. In the complex, it mediates the interaction with microtubules.
Interacts (when phosphorylated at Ser-67) with ppp2r2d.
Phosphorylation at Ser-67 by gwl during mitosis is essential for interaction with PPP2R2D (PR55-delta) and subsequent inactivation of PP2A.
Protein phosphatase inhibitor that specifically inhibits protein phosphatase 2A (PP2A) during mitosis. When phosphorylated at Ser-67 during mitosis, specifically interacts with ppp2r2d (PR55-delta) and inhibits its activity, leading to inactivation of PP2A, an essential condition to keep cyclin-B1-CDK1 activity high during M phase (By similarity).
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. Preferentially accommodates proteins with transmembrane domains that are weakly hydrophobic or contain destabilizing features such as charged and aromatic residues. Involved in the cotranslational insertion of multi-pass membrane proteins in which stop-transfer membrane-anchor sequences become ER membrane spanning helices. It is also required for the post-translational insertion of tail-anchored/TA proteins in endoplasmic reticulum membranes. By mediating the proper cotranslational insertion of N-terminal transmembrane domains in an N-exo topology, with translocated N-terminus in the lumen of the ER, controls the topology of multi-pass membrane proteins like the G protein-coupled receptors (By similarity). By regulating the insertion of various proteins in membranes, it is indirectly involved in many cellular processes. May be involved in Mg(2+) transport (By similarity).
Possible role in the regulation of cell death.
Belongs to the glycosyl hydrolase 30 family.
Involved in the tethering of the SIN3 complex to core histone proteins.
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.
Belongs to the phosphatidylethanolamine-binding protein family.
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.
Homodimer and heterodimer with SSTR3 and SSTR5. Heterodimerization with SSTR3 inactivates SSTR3 receptor function. Heterodimerization with SSTR5 is enhanced by agonist stimulation of SSTR2 and increases SSTR2 cell growth inhibition activity. Following agonist stimulation, homodimers dissociate into monomers which is required for receptor internalization. Interacts with beta-arrestin; this interaction is necessary for receptor internalization and is destabilized by heterodimerization with SSTR5 which results in increased recycling of SSTR2 to the cell surface. Interacts (via C-terminus) with SHANK1 (via PDZ domain).
Receptor for somatostatin-14 and -28. This receptor is coupled via pertussis toxin sensitive G proteins to inhibition of adenylyl cyclase. In addition it stimulates phosphotyrosine phosphatase and PLC via pertussis toxin insensitive as well as sensitive G proteins. Inhibits calcium entry by suppressing voltage-dependent calcium channels. Acts as the functionally dominant somatostatin receptor in pancreatic alpha- and beta-cells where it mediates the inhibitory effect of somatostatin-14 on hormone secretion. Inhibits cell growth through enhancement of MAPK1 and MAPK2 phosphorylation and subsequent up-regulation of CDKN1B. Stimulates neuronal migration and axon outgrowth and may participate in neuron development and maturation during brain development. Mediates negative regulation of insulin receptor signaling through PTPN6. Inactivates SSTR3 receptor function following heterodimerization.
Belongs to the glycosyltransferase 28 family.
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.
Required for the formation of N(7)-methylguanine at position 46 (m7G46) in tRNA. In the complex, it is required to stabilize and induce conformational changes of the catalytic subunit.
Belongs to the DNA polymerase delta/II small subunit family.
Belongs to the 5'-3' exonuclease family. XRN2/RAT1 subfamily.
Aquaporins facilitate the transport of water and small neutral solutes across cell membranes.
Component of the BCR(KLHL40) E3 ubiquitin ligase complex.
Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that acts as a key regulator of skeletal muscle development.
Belongs to the WD repeat WDR90/POC16 family.
Required for efficient primary cilium formation.
Belongs to the biotin--protein ligase family.
Belongs to the inositol 1,4,5-trisphosphate 5-phosphatase type I family.
During embryonic development, interferes with neural crest formation. Inhibits AP2 transcriptional activity by interaction with its activation domain (By similarity).
Interacts with TFAP2A; this interaction inhibits TFAP2A transcriptional activation.
Belongs to the universal ribosomal protein uL6 family.
Belongs to the ADP-ribosylglycohydrolase family.
Belongs to the eukaryotic RPA43 RNA polymerase subunit family.
Belongs to the helicase family. RecQ subfamily.
May function in clathrin-mediated endocytosis. Has both a membrane binding/tubulating activity and the ability to recruit proteins essential to the formation of functional clathrin-coated pits. Has a preference for membranes enriched in phosphatidylserine and phosphoinositides and is required for the endocytosis of the transferrin receptor. May also bind tubulin. May play a role in the regulation of energy homeostasis.
May promote appropriate targeting of ribosome-nascent polypeptide complexes.
Belongs to the cytochrome c oxidase subunit 6c family.
Component of the cytochrome c oxidase (complex IV, CIV), a multisubunit enzyme composed of 14 subunits. The complex is composed of a catalytic core of 3 subunits MT-CO1, MT-CO2 and MT-CO3, encoded in the mitochondrial DNA, and 11 supernumerary subunits COX4I, COX5A, COX5B, COX6A, COX6B, COX6C, COX7A, COX7B, COX7C, COX8 and NDUFA4, which are encoded in the nuclear genome. The complex exists as a monomer or a dimer and forms supercomplexes (SCs) in the inner mitochondrial membrane with NADH-ubiquinone oxidoreductase (complex I, CI) and ubiquinol-cytochrome c oxidoreductase (cytochrome b-c1 complex, complex III, CIII), resulting in different assemblies (supercomplex SCI(1)III(2)IV(1) and megacomplex MCI(2)III(2)IV(2)).
Regulates the activity of L-type calcium channels that contain CACNA1C as pore-forming subunit (By similarity). Regulates the trafficking and gating properties of AMPA-selective glutamate receptors (AMPARs), including GRIA1 and GRIA4. Promotes their targeting to the cell membrane and synapses and modulates their gating properties by slowing their rates of activation, deactivation and desensitization and by mediating their resensitization.
Component of the MCM8-MCM9 complex, a complex involved in homologous recombination repair following DNA interstrand cross-links and plays a key role during gametogenesis. The MCM8-MCM9 complex probably acts as a hexameric helicase required to process aberrant forks into homologous recombination substrates and to orchestrate homologous recombination with resection, fork stabilization and fork restart. In eggs, required for elongation during DNA replication by facilitating the recruitment of rpa2/rpa34 and stimulating the processivity of DNA polymerases at replication foci. Probably not required for DNA replication in other cells (By similarity).
Component of the MCM8-MCM9 complex, which forms a hexamer composed of mcm8 and mcm9.
The N-terminal region is required for repressor function.
Transcriptional repressor. Cooperates with vent2 in a ventral signaling pathway downstream of bmp4, which antagonizes the Spemann organizer and dorsal mesoderm formation, and leads to ventral mesoderm formation. Acts downstream of bmp4 to repress transcription of foxa4-B/XFD-1'. Binds to DNA with preference for the target sequence 5'-CTATT[T/C]G-3'. Also binds 5'-TGCATTTTG-3' at a lower frequency, and occasionally 5'-TTGATC-3'. Binds to the homeobox 2 (HBX2) repressor element in the promoter of the myf5 gene (By similarity). Cooperates with vent2 to repress myf5 expression in the ventral domain.
Belongs to the formin homology family. Cappuccino subfamily.
Scaffold protein that connects plasma membrane proteins with members of the ezrin/moesin/radixin family and thereby helps to link them to the actin cytoskeleton and to regulate their surface expression.
Binds calmodulin. Interacts with NDUFAF3.
Part of the endoplasmic reticulum membrane protein complex (EMC) that enables the energy-independent insertion into endoplasmic reticulum membranes of newly synthesized membrane proteins. Preferentially accommodates proteins with transmembrane domains that are weakly hydrophobic or contain destabilizing features such as charged and aromatic residues. Involved in the cotranslational insertion of multi-pass membrane proteins in which stop-transfer membrane-anchor sequences become ER membrane spanning helices. It is also required for the post-translational insertion of tail-anchored/TA proteins in endoplasmic reticulum membranes. By mediating the proper cotranslational insertion of N-terminal transmembrane domains in an N-exo topology, with translocated N-terminus in the lumen of the ER, controls the topology of multi-pass membrane proteins like the G protein-coupled receptors. By regulating the insertion of various proteins in membranes, it is indirectly involved in many cellular processes. Promotes angiogenesis and tissue repair in the heart after myocardial infarction. Stimulates cardiac endothelial cell migration and outgrowth via the activation of p38 MAPK, PAK and MAPK2 signaling pathways.
Belongs to the type I cytokine receptor family. Type 1 subfamily.
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.
This is a receptor for the anterior pituitary hormone prolactin.
Belongs to the protein phosphatase inhibitor 2 family.
Plays an important role in centriole assembly and/or stability and ciliogenesis. Involved in early steps of centriole duplication, as well as in the later steps of centriole length control.
Belongs to the gluconokinase GntK/GntV family.
ATPase activity is stimulated by microtubules, which promote homooligomerization. ATP-dependent microtubule severing is stimulated by interaction with katnb1.
Belongs to the AAA ATPase family. Katanin p60 subunit A1 subfamily.
Can homooligomerize into hexameric rings, which may be promoted by interaction with microtubules. Interacts with katnb1, which may serve as a targeting subunit.
Catalytic subunit of a complex which severs microtubules in an ATP-dependent manner. Microtubule severing may promote rapid reorganization of cellular microtubule arrays and the release of microtubules from the centrosome following nucleation.
Functions in replication-dependent translation of histone mRNAs which differ from other eukaryotic mRNAs in that they do not end with a poly-A tail but a stem-loop. May participate in circularizing those mRNAs specifically enhancing their translation (By similarity).
Interacts with eif4g1, eif4g2 and slbp; probably tethered by SLBP to the 3'-end of mRNAs ending with the histone stem-loop, it also interacts with eif4g1 which is bound to their 5'-end.
ATP-dependent transporter that catalyzes the transport of a broad-spectrum of porphyrins from the cytoplasm to the extracellular space through the plasma membrane or into the vesicle lumen. May also function as an ATP-dependent importer of porphyrins from the cytoplasm into the mitochondria, in turn may participate in the de novo heme biosynthesis regulation and in the coordination of heme and iron homeostasis during phenylhydrazine stress. May also play a key role in the early steps of melanogenesis producing PMEL amyloid fibrils. In vitro, it confers to cells a resistance to toxic metal such as arsenic and cadmium and against chemotherapeutics agent such as 5-fluorouracil, SN-38 and vincristin (By similarity). In addition may play a role in the transition metal homeostasis (By similarity).
Belongs to the ABC transporter superfamily. ABCB family. Heavy Metal importer (TC 3.A.1.210) subfamily.
Contains two independently folding units, the N-terminal transmembrane domain (residues 1-205) and the ABC-core domain (206-842) are respectively responsible for the lysosomal targeting and the ATPase activity.
To date, the intracellular localization of ABCB6 is a matter of debate, with conflicting reports suggesting mitochondrial or endolysosomal localization, therefore questioning the requirement of ABCB6 in the mitochondrial import of porphyrins.
Homodimer; mediated via the coiled-coil region.
Proteolytically cleaved by caspase-3 during apoptosis at Asp-326 resulting in a 37 kDa form. Proteolytic cleavage results in kinase activation and nuclear translocation of the truncated form (MST1/N) (By similarity).
Stress-activated, pro-apoptotic kinase which, following caspase-cleavage, enters the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation. Key component of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein stk3/mst2 and stk4/mst1, in complex with its regulatory protein sav1, phosphorylates and activates lats1/2 in complex with its regulatory protein mob1, which in turn phosphorylates and inactivates yap1 oncoprotein and wwtr1/taz. Phosphorylation of yap1 by lats2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. Phosphorylates 'Ser-14' of histone H2B (H2BS14ph) during apoptosis.
The C-terminal non-catalytic region inhibits the kinase activity, the enzyme is activated by caspase-cleavage. Homodimerization and autophosphorylation of Thr-183 is also required for full activation (By similarity).
Belongs to the universal ribosomal protein uS14 family.
Belongs to the glucosamine/galactosamine-6-phosphate isomerase family. 6-phosphogluconolactonase subfamily.
Hydrolysis of 6-phosphogluconolactone to 6-phosphogluconate.
Required for assembly of dynein regulatory complex (DRC) and inner dynein arm (IDA) complexes, which are responsible for ciliary beat regulation, thereby playing a central role in motility in cilia and flagella. Probably acts together with ccdc40 to form a molecular ruler that determines the 96 nanometer (nm) repeat length and arrangements of components in cilia and flagella. Not required for outer dynein arm complexes assembly.
Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3. May be a component of the proposed t-UTP subcomplex of the ribosomal small subunit (SSU) processome.
Ribosome biogenesis factor. Involved in nucleolar processing of pre-18S ribosomal RNA. Required for optimal pre-ribosomal RNA transcription by RNA polymerase I. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome.
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.
Forms a regulatory protein-RNA complex, consisting of RCC1L, NGRN, RPUSD3, RPUSD4, TRUB2, FASTKD2 and 16S mt-rRNA. Interacts with 16S mt-rRNA; this interaction is direct.
Plays an essential role in mitochondrial ribosome biogenesis. As a component of a functional protein-RNA module, consisting of RCC1L, NGRN, RPUSD3, RPUSD4, TRUB2, FASTKD2 and 16S mitochondrial ribosomal RNA (16S mt-rRNA), controls 16S mt-rRNA abundance and is required for intra-mitochondrial translation of core subunits of the oxidative phosphorylation system.
May play a role into cellular response to oxidative stress. May decrease cell proliferation (By similarity).
Component of the general transcription and DNA repair factor IIH (TFIIH) core complex, which is involved in general and transcription-coupled nucleotide excision repair (NER) of damaged DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II. In NER, TFIIH acts by opening DNA around the lesion to allow the excision of the damaged oligonucleotide and its replacement by a new DNA fragment. In transcription, TFIIH has an essential role in transcription initiation. When the pre-initiation complex (PIC) has been established, TFIIH is required for promoter opening and promoter escape. Phosphorylation of the C-terminal tail (CTD) of the largest subunit of RNA polymerase II by the kinase module CAK controls the initiation of transcription.
Part of a TFIID-containing RNA polymerase II pre-initiation complex that is composed of TBP and at least GTF2A1, GTF2A2, GTF2E1, GTF2E2, GTF2F1, GTF2H2, GTF2H3, GTF2H4, GTF2H5, GTF2B, TCEA1, ERCC2, ERCC3, TAF1, TAF2, TAF3, TAF4, TAF5, TAF6, TAF7, TAF8, TAF9, TAF10, TAF11, TAF12 and TAF13. Component of the 7-subunit TFIIH core complex composed of XPB/ERCC3, XPD/ERCC2, GTF2H1, GTF2H2, GTF2H3, GTF2H4 and GTF2H5, which is active in NER. The core complex associates with the 3-subunit CDK-activating kinase (CAK) module composed of CCNH/cyclin H, CDK7 and MNAT1 to form the 10-subunit holoenzyme (holo-TFIIH) active in transcription. Interacts with RARA; the interaction requires prior phosphorylation of RARA on 'Ser-369' which then enhances interaction of RARA with CDK7.
Mediates the post-translational oxidative deamination of lysine residues on target proteins leading to the formation of deaminated lysine (allysine). Acts as a transcription corepressor and specifically mediates deamination of trimethylated 'Lys-4' of histone H3 (H3K4me3), a specific tag for epigenetic transcriptional activation. Shows no activity against histone H3 when it is trimethylated on 'Lys-9' (H3K9me3) or 'Lys-27' (H3K27me3) or when 'Lys-4' is monomethylated (H3K4me1) or dimethylated (H3K4me2). Also mediates deamination of methylated TAF10, a member of the transcription factor IID (TFIID) complex, which induces release of TAF10 from promoters, leading to inhibition of TFIID-dependent transcription. LOXL2-mediated deamination of TAF10 results in transcriptional repression of genes required for embryonic stem cell pluripotency. Involved in epithelial to mesenchymal transition (EMT) and participates in repression of E-cadherin, probably by mediating deamination of histone H3. When secreted into the extracellular matrix, promotes cross-linking of extracellular matrix proteins by mediating oxidative deamination of peptidyl lysine residues in precursors to fibrous collagen and elastin. Acts as a regulator of sprouting angiogenesis, probably via collagen IV scaffolding. Acts as a regulator of chondrocyte differentiation, probably by regulating expression of factors that control chondrocyte differentiation.
Molecular adapter that acts as a bridge between proteins, and which is involved skeletal muscle development. Functions as signal transducer for MSTN during skeletal muscle regeneration and myogenesis.
Belongs to the ligand-gated ion channel (TC 1.A.9) family. Glycine receptor (TC 1.A.9.3) subfamily. GLRA1 sub-subfamily.
Belongs to the DEAD box helicase family. DDX21/DDX50 subfamily.
Belongs to the methyltransferase superfamily. Trimethylguanosine synthase family.
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. This channel gives rise to T-type calcium currents. T-type calcium channels belong to the "low-voltage activated (LVA)" group and are strongly blocked by nickel and mibefradil. A particularity of this type of channels is an opening at quite negative potentials, and a voltage-dependent inactivation. T-type channels serve pacemaking functions in both central neurons and cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle. They may also be involved in the modulation of firing patterns of neurons which is important for information processing as well as in cell growth processes.
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.
Component of a probable ECS E3 ubiquitin-protein ligase complex that contains the Elongin BC complex.
Probable substrate-recognition component of a SCF-like ECS (Elongin-Cullin-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins.
Transcription activator. Doesn't appear to bind to the consensus 5'-AACAAT-3' DNA binding site, but binds 5'-ATTGTT-3'. All of the sox17 proteins are required for embryonic endoderm development and gastrulation movements, and show some redundancy in function. In addition, the sox17 proteins have distinct but overlapping roles in later gut development. Acts downstream of vegt-signaling in endoderm differentiation to induce a range of endodermal genes both directly and indirectly. Also represses wnt-responsive genes to inhibit wnt/beta-catenin-mediated signaling (By similarity).
Belongs to the GTP-binding elongation factor family. EF-G/EF-2 subfamily.
Mitochondrial GTPase that catalyzes the GTP-dependent ribosomal translocation step during translation elongation. During this step, the ribosome changes from the pre-translocational (PRE) to the post-translocational (POST) state as the newly formed A-site-bound peptidyl-tRNA and P-site-bound deacylated tRNA move to the P and E sites, respectively. Catalyzes the coordinated movement of the two tRNA molecules, the mRNA and conformational changes in the ribosome. Does not mediate the disassembly of ribosomes from messenger RNA at the termination of mitochondrial protein biosynthesis.
Catalytic subunit of the NatB complex which catalyzes acetylation of the N-terminal methionine residues of peptides beginning with Met-Asp, Met-Glu, Met-Asn and Met-Gln. Proteins with cell cycle functions are overrepresented in the pool of NatB substrates. Required for maintaining the structure and function of actomyosin fibers and for proper cellular migration.
Component of the N-terminal acetyltransferase B (NatB) complex which is composed of naa20 and naa25.
GTPase-activating protein (GAP) for rhoa and cdc42.
Essential regulator of oogenesis required for female meiotic progression to repress transposable elements and preventing their mobilization, which is essential for the germline integrity.
Involved in teeth and skeletal development. Has an essential role in the biosynthesis and trafficking of glycosaminoglycans and glycoproteins to produce a proper functioning extracellular matrix. Required for extracellular matrix mineralization. Also involved in the regulation of cellular calcium homeostasis. Does not show transport activity towards bile acids or steroid sulfates.
Regulates cell growth, proliferation and survival via inhibition of the activity of the mammalian target of rapamycin complex 1 (mTORC1). Inhibition of mTORC1 is mediated by a pathway that involves ddit4/redd1, akt1, the tsc1-tsc2 complex and the GTPase rheb. Plays an important role in responses to cellular energy levels and cellular stress, including responses to hypoxia and DNA damage, via its effect on mTORC1 activity. Plays a role in neuronal differentiation, neuron migration during embryonic brain development and in neuronal cell death (By similarity).
Belongs to the WD repeat WDR12/YTM1 family.
Component of the PeBoW complex, composed of bop1, pes1 and wdr12. The complex is held together by bop1, which interacts with pes1 via its N-terminal domain and with wdr12 via a high-affinity interaction between the seven-bladed beta-propeller domains of the 2 proteins. The PeBoW complex associates with the 66S pre-ribosome. Interacts (via UBL domain) with mdn1 (via VWFA/MIDAS domain).
Belongs to the mitochondrion-specific ribosomal protein mL43 family.
Belongs to the lyase 1 family. Argininosuccinate lyase subfamily.
In the C-terminal section; belongs to the sulfate adenylyltransferase family.
In the N-terminal section; belongs to the APS kinase family.
Belongs to the Mediator complex subunit 13 family.
Component of the Mediator complex, a coactivator involved in regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors.
Involved in the regulation of homocysteine metabolism.
Belongs to the ATP-dependent DNA ligase family.
Necessary for the splicing of pre-mRNA. Has a role in the recognition of the branch site (5'-UACUAAC-3'), the pyrimidine tract and the 3'-splice site at the 3'-end of introns.
Probably functions as cargo-recognition protein that couples cytoplasmic vesicles to the transport machinery. Contributes to retrograde melanosome transport from the cell periphery to the center. Overexpression causes accumulation of late endosomes and/or lysosomes at the microtubule organising center (MTOC) at the center of the cell. Probably binds cholesterol and requires the presence of cholesterol in membranes to function in microtubule-mediated retrograde organelle transport. Binds phosphatidylinositol 3-phosphate, phosphatidylinositol 4-phosphate, phosphatidylinositol 5-phosphate and phosphatidylinositol 3,5-bisphosphate.
May be involved in vesicle transport between the ER and the Golgi complex.
Belongs to the activator 1 large subunit family.
Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2 domains.
May have a regulatory role in the membrane interactions during trafficking of synaptic vesicles at the active zone of the synapse. It binds acidic phospholipids with a specificity that requires the presence of both an acidic head group and a diacyl backbone.
First detected during early neural plate formation (stage 13) and increased at the early tailbud stage (stage 28) (PubMed:23716681). Expression is higher around the anterior neuropore in the neural plate than in the rest of the embryo, and as embryogenesis proceeds, is present in the forebrain, midbrain, and presumptive eye of the embryo (PubMed:23716681).
Uniporter that promotes Zn(2+) import from the extracellular space to the cytoplasm across the cell membrane. The transport activity is temperature dependent (By similarity). May play a role in neurulation and neurite extension (By similarity) (PubMed:23716681).
Involved in G protein-coupled receptors (GPCRs) trafficking from the endoplasmic reticulum to the cell surface; it promotes the exit of GPCRs from the early secretory pathway, likely through interaction with the COPII machinery.
Proteolytically removes the C-terminal three residues of farnesylated proteins.
Component of the TSC-TBC complex (also named Rhebulator complex), composed of 2 molecules of TSC1, 2 molecules of TSC2 and 1 molecule of TBC1D7.
Non-catalytic component of the TSC-TBC complex, a multiprotein complex that acts as a negative regulator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolecule biosynthesis to promote cellular biomass generation and growth. The TSC-TBC complex acts as a GTPase-activating protein (GAP) for the small GTPase RHEB, a direct activator of the protein kinase activity of mTORC1. In absence of nutrients, the TSC-TBC complex inhibits mTORC1, thereby preventing phosphorylation of ribosomal protein S6 kinase (RPS6KB1 and RPS6KB2) and EIF4EBP1 (4E-BP1) by the mTORC1 signaling. The TSC-TBC complex is inactivated in response to nutrients, relieving inhibition of mTORC1.
Acts as a negative regulator of the Wnt signaling pathway required for anterior neural structure formation (By similarity). Binds preferentially to DNA containing cytidine-phosphate-guanosine (CpG) dinucleotides over CpH (H=A, T, and C), hemimethylated-CpG and hemimethylated-hydroxymethyl-CpG (By similarity).
The CXXC zinc finger mediates binding to CpG-DNA.
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.
Belongs to the WD repeat CDC20/Fizzy family.
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.
Oocyte-specific protein tyrosine kinase that phosphorylates and inhibits cdk1 and acts as a regulator of meiosis. Required to maintain meiotic arrest in oocytes by phosphorylating cdk1 at 'Tyr-15', leading to inhibit cdk1 activity and prevent meiotic reentry (By similarity).
Belongs to the complex I NDUFB3 subunit family.
Plays a role in vesicle-mediated protein trafficking to lysosomal compartments including the endocytic membrane transport pathways.
Probable component of the nuclear pore complex (NPC).
Required for the export of mRNAs containing poly(A) tails from the nucleus into the cytoplasm.
The FG repeats are interaction sites for karyopherins (importins, exportins) and form probably an affinity gradient, guiding the transport proteins unidirectionally with their cargo through the NPC.
Belongs to the RNA 3'-terminal cyclase family. Type 2 subfamily.
The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO2.
Belongs to the DEAD box helicase family. DDX59 subfamily.
Interacts with uba5. Interacts with ufc1.
Ubiquitin-like modifier which can be covalently attached via an isopeptide bond to lysine residues of substrate proteins as a monomer or a lysine-linked polymer. The so-called ufmylation, requires the ufm1-activating E1 enzyme uba5, the ufm1-conjugating E2 enzyme ufc1, and the ufm1-ligase E3 enzyme ufl1. Ufmylation is involved in reticulophagy (also called ER-phagy) induced in response to endoplasmic reticulum stress.
Mediates the rate-limiting, proton-dependent, lysosomal efflux of lysophospholipids. Selective for zwitterionic headgroups such as lysophosphatidylcholine (LPC) and lysophosphatidylethanolamine (LPE) (By similarity). Essential player in lysosomal homeostasis (By similarity).
Involved in protein trafficking. May serve as a receptor for ARFRP1.
Belongs to the type II (or gamma) interferon family.
Acts as component of the MCM2-7 complex (MCM complex) which is the replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity. Required for the entry in S phase and for cell division.
Component of the mcm2-7 complex (RLF-M). The complex forms a toroidal hexameric ring with the proposed subunit order mcm2-mcm6-mcm4-mcm7-mcm3-mcm5 (By similarity). Component of the replisome complex (By similarity). Component of the CMG helicase complex, composed of the mcm2-7 complex, the GINS complex and cdc45 (By similarity).
May be in a phosphorylated state in the mitotic mcm complex. Phosphorylated in the interphase mcm complex. Phosphorylated by the cdc7-dbf4 and cdc7-dbf4b complexes (By similarity).
Belongs to the SRP receptor beta subunit family.
Accessory subunit that is involved in the functional assembly of the mitochondrial respiratory chain complex I. Complex I has an NADH dehydrogenase activity with ubiquinone as an immediate electron acceptor and mediates the transfer of electrons from NADH to the respiratory chain.
Belongs to the complex I NDUFB10 subunit family.
Heterodimer with SLC30A6/ZNT6; form a functional zinc ion transmembrane transporter.
Together with SLC30A6 forms a functional proton-coupled zinc ion antiporter mediating zinc entry into the lumen of organelles along the secretory pathway. By contributing to zinc ion homeostasis within the early secretory pathway, regulates the activation and folding of enzymes like alkaline phosphatases and enzymes involved in phosphatidylinositol glycan anchor biosynthesis.
Transcriptional activator. Functions as a switch in neuronal development, participating in the differentiation of embryonic neuroectodermal cells into neural tissues by making the ectodermal cells responsive to FGF-neuralizing signals (By similarity). Downstream SRRT target that mediates the promotion of neural stem cell self-renewal (By similarity).
May be a negative regulator of NF-kappa-B and p53-mediated gene transcription.
Was originally thought to originate from X.laevis. However, sequence identity with X.tropicalis is much higher than with X.laevis, suggesting that the sequence is from X.tropicalis.
Maternally and zygotically expressed. Zygotic expression increases after gastrula stage. Expressed in all three germ layers.
Receptor for R-spondins that potentiates the canonical Wnt signaling pathway and is involved in the formation of various organs. Upon binding to R-spondins (RSPO1, RSPO2, RSPO3 or RSPO4), associates with phosphorylated LRP6 and frizzled receptors that are activated by extracellular Wnt receptors, triggering the canonical Wnt signaling pathway to increase expression of target genes. In contrast to classical G-protein coupled receptors, does not activate heterotrimeric G-proteins to transduce the signal. Its function as activator of the Wnt signaling pathway is required for the development of various organs, including liver, kidney, intestine, bone, reproductive tract and eye. May play a role in regulating the circadian rhythms of plasma lipids (By similarity). Required for proper development of GnRH neurons (gonadotropin-releasing hormone expressing neurons) that control the release of reproductive hormones from the pituitary gland (By similarity).
Homooligomer. Interacts with banf1-a and banf1-b. Interacts with ran-gtp.
In concert with ran, required for proper eye development. May be involved in the expression of early eye marker genes. Contributes to nuclear envelope stiffness in germ cells (By similarity). Required for fertility (By similarity).
The transmembrane domains are required and sufficient for its oligomerization.
Belongs to the methyltransferase superfamily. RsmH 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. Plays a role in intracellular vesicle trafficking and synaptic vesicle recycling.
Catalyzes the last step of tRNA splicing, the transfer of the splice junction 2'-phosphate from ligated tRNA to NAD to produce ADP-ribose 1''-2'' cyclic phosphate.
Component of the ARISC complex, at least composed of uimc1/rap80, abraxas1, brcc3/brcc36, BABAM2 and babam1/nba1. Component of the BRCA1-A complex, at least composed of brca1, bard1, uimc1/rap80, abraxas1, brcc3/brcc36, BABAM2 and babam1/nba1. In the BRCA1-A complex, interacts directly with abraxas1 and BABAM2. Component of the BRISC complex, at least composed of abraxas2, brcc3/brcc36, babam2 and babam1/nba1.
Component of the BRCA1-A complex, a complex that specifically recognizes 'Lys-63'-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). The BRCA1-A complex also possesses deubiquitinase activity that specifically removes 'Lys-63'-linked ubiquitin on histones H2A and H2AX. In the BRCA1-A complex, it is required for the complex integrity and its localization at DSBs. Component of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys-63'-linked ubiquitin in various substrates. In these 2 complexes, it is probably required to maintain the stability of BABAM2 and help the 'Lys-63'-linked deubiquitinase activity mediated by brcc3/brcc36 component. The BRISC complex is required for normal mitotic spindle assembly and microtubule attachment to kinetochores via its role in deubiquitinating numa1. Plays a role in interferon signaling via its role in the deubiquitination of the interferon receptor ifnar1; deubiquitination increases ifnar1 activity by enhancing its stability and cell surface expression. Down-regulates the response to bacterial lipopolysaccharide (LPS) via its role in ifnar1 deubiquitination.
The VWFA-like region is similar to the VWFA domain. Its presence reveals similarities between the structure of the 19S proteasome and the BRCA1-A complexes.
Belongs to the adenosylhomocysteinase family.
Associates with microtubules. Interacts with aurka and plk1. Interacts with kif15 (By similarity).
Phosphorylated during mitosis. Hyperphosphorylated upon assembly of microtubules (By similarity).
Spindle assembly factor. Required for normal assembly of mitotic spindles. Mediates the binding kif15 and aurka to spindle microtubules. Required for targeting kif15 to microtubule minus ends. Activates aurka by promoting its autophosphorylation and protects the phosphorylated residue against dephosphorylation (By similarity).
Belongs to the learning-associated protein family.
Regulates dendritic and spine growth and synaptic transmission.
Transcriptional activator. Activates ectoderm, in addition to inhibiting mesoderm and endoderm formation; required at the blastula stage for normal formation of both the central nervous system and epidermis, the two early derivatives of the ectoderm. In addition, also required to maintain the regional identity of the animal cells of the blastula, the cells that are precursors of ectodermal structures. Also plays a role in differential adhesion, which limits cell mixing as primary germ layers become specified (By similarity).
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).
Syntaxin that may be involved in targeting and fusion of Golgi-derived retrograde transport vesicles with the ER.
May regulate intracellular cholesterol transport.
Endoplasmic reticulum (ER)-shaping membrane protein that plays a role in determining ER morphology. Involved in the stabilization of nascent three-way ER tubular junctions within the ER network. May also play a role as a curvature-stabilizing protein within three-way ER tubular junction network (By similarity).
Homodimer; homodimerization requires the C4-type zinc finger motif and decreases during mitosis in a phosphorylation-dependent manner.
Phosphorylated. Phosphorylation at Thr-159 occurs during interphase. Phosphorylation at Ser-177, Ser-179, Ser-188, Thr-198, Ser-206, Ser-215, Thr-219, Ser-222 and Ser-231 occurs during mitosis; these phosphorylations reduce both its homodimerization and the ER three-way tubular junction formation.
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.
The transmembrane domain 1 and 2 function as a signal-anchor and stop-transfer sequence, respectively, generating a double-spanning integral membrane protein with a N- and C-terminal cytoplasmic orientation. Transmembrane domain 1 and 2 are probably sufficient to mediate membrane translocation and topology formation in a N-myristoylation-independent manner. Transmembrane domain 2 is sufficient to block the protein secretion pathway. The two coiled-coil domains are necessary for its endoplasmic reticulum (ER) three-way tubular junction localization. The C4-type zinc finger motif is necessary both for its ER three-way tubular junction localization and formation.
Belongs to the cyclin-dependent kinase 5 activator family.
Belongs to the DNA polymerase type-A family.
Involved in the replication of mitochondrial DNA. Associates with mitochondrial DNA.
Deubiquitinating enzyme involved in various processes such as centrosome duplication, cellular migration and beta-2 adrenergic receptor/ADRB2 recycling. Involved in regulation of centrosome duplication by mediating deubiquitination of ccp110 in S and G2/M phase, leading to stabilize ccp110 during the period which centrioles duplicate and elongate. Involved in cell migration via its interaction with intracellular domain of robo1, leading to regulate the Slit signaling. Plays a role in commissural axon guidance cross the ventral midline of the neural tube in a Slit-dependent manner, possibly by mediating the deubiquitination of robo1. Acts as a regulator of G-protein coupled receptor (GPCR) signaling by mediating the deubiquitination of beta-arrestins (arrb1 and arrb2) and beta-2 adrenergic receptor (adrb2). Deubiquitinates dio2, thereby regulating thyroid hormone regulation. Mediates deubiquitination of both 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains (By similarity).
Acts as a transcriptional activator in complex with isoform 2 of meis1, to induce posterior neural and neural crest gene expression, and thereby specify hindbrain and neural crest cell fate. Binds to a highly conserved region in the promoter of the neural crest gene zic3. Required for the nuclear transport or retention of meis1 (By similarity).
Forms a heterodimer with meis1; the interaction is necessary for neural fate induction.
The displayed sequence corresponds to the ortholog of the mammalian isoform B sequences. There is currently no X.tropicalis ortholog sequence for isoform A.
Catalyzes two steps in the biosynthesis of the molybdenum cofactor. In the first step, molybdopterin is adenylated. Subsequently, molybdate is inserted into adenylated molybdopterin and AMP is released.
In the C-terminal section; belongs to the MoeA family.
In the N-terminal section; belongs to the MoaB/Mog 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.
Tetrahedron-shaped homododecamer built from six homodimers.
Transcriptional repressor that plays a central role for embryogenesis and the pluripotency of embryonic stem (ES) cells. Sequence-specific DNA-binding factor that represses gene expression in pluripotent ES cells by directly binding to key genetic loci and recruiting epigenetic modifiers (By similarity).
Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating.
Catalyzes the conversion of 4-hydroxyphenylpyruvic acid to homogentisic acid, one of the steps in tyrosine catabolism.
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 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 complex I NDUFB8 subunit family.
Belongs to the casein kinase 2 subunit beta family.
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. Participates in Wnt signaling.
Tetramer of two alpha and two beta subunits.
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 (By similarity).
Belongs to the potassium channel family. A (Shaker) (TC 1.A.1.2) subfamily. Kv1.4/KCNA4 sub-subfamily.
Belongs to the small GTPase superfamily. Ras family. KappaB-Ras subfamily.
Belongs to the SLC41A transporter family.
Belongs to the heme-copper respiratory oxidase family.
Homodimer. The monomeric form is inactive while the homodimer is active.
Component of the uniplex complex. Interacts (via the transmembrane region) with mcu (via the first transmembrane region); the interaction is direct.
Essential regulatory subunit of the mitochondrial calcium uniporter complex (uniplex), a complex that mediates calcium uptake into mitochondria. Plays a central role in regulating the uniplex complex response to intracellular calcium signaling.
mRNA-binding protein involved in proper cytoplasmic distribution of mitochondria. Specifically binds mRNAs of nuclear-encoded mitochondrial proteins in the cytoplasm and regulates transport or translation of these transcripts close to mitochondria, playing a role in mitochondrial biogenesis.
Belongs to the MMS22 family. MMS22L subfamily.
Belongs to the WD repeat DCAF13/WDSOF1 family.
Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3. Component of the DCX(DCAF13) E3 ubiquitin ligase complex, at least composed of CUL4 (CUL4A or CUL4B), DDB1, DCAF13 and RBX1.
Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome.
Substrate-recognition component of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex.
The coatomer is a cytosolic protein complex that binds to dilysine motifs and reversibly associates with Golgi non-clathrin-coated vesicles, which further mediate biosynthetic protein transport from the ER, via the Golgi up to the trans Golgi network. The coatomer complex is required for budding from Golgi membranes, and is essential for the retrograde Golgi-to-ER transport of dilysine-tagged proteins.
Involved in peroxisome biosynthesis and integrity. Assembles membrane vesicles before the matrix proteins are translocated. As a docking factor for PEX19, is necessary for the import of peroxisomal membrane proteins in the peroxisomes.
Belongs to the complex I subunit 6 family.
Calcium-dependent mitochondrial solute carrier.
May regulate actin polymerization, filopodia dynamics and arborization of neurons.
Required for biogenesis of the 60S ribosomal subunit.
Belongs to the CMP-Neu5Ac hydroxylase family.
Sialic acids are components of carbohydrate chains of glycoconjugates and are involved in cell-cell recognition and cell-pathogen interactions. Catalyzes the conversion of CMP-N-acetylneuraminic acid (CMP-Neu5Ac) into its hydroxylated derivative CMP-N-glycolylneuraminic acid (CMP-Neu5Gc), a sialic acid abundantly expressed at the surface of many cells.
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.
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.
Forms a 1:1 stoichiometric complex with pancreatic lipase.
Negatively regulates Ras signaling pathways and downstream activation of MAP kinases.
Monomer. Oligomerizes upon binding of cytochrome c and dATP.
Oligomeric Apaf-1 mediates the cytochrome c-dependent autocatalytic activation of pro-caspase-9 (Apaf-3), leading to the activation of caspase-3 and apoptosis. This activation requires ATP.
Belongs to the N-CoR nuclear receptor corepressors family.
Interacts with CHGA (By similarity). Interacts with secretogranin II/SCG2 (By similarity). Interacts (via C-terminus) with CPE (By similarity).
Member of the granin protein family that regulates the biogenesis of secretory granules (By similarity). Acts as a sorting receptor for intragranular proteins including chromogranin A/CHGA (By similarity). May also play a role in angiogenesis. Promotes endothelial proliferation, migration and tube formation through MEK/ERK signaling pathway (By similarity).
Probable adapter protein that bind to and organize the subcellular localization of a variety of membrane proteins containing some PDZ recognition sequence. Involved in the clustering of various receptors, possibly by acting at the receptor internalization level. Plays a role in synaptic plasticity by regulating the trafficking and internalization of AMPA receptors. May be regulated upon PRKCA activation. May regulate ASIC1/ASIC3 channel. Regulates actin polymerization by inhibiting the actin-nucleating activity of the Arp2/3 complex; the function is competitive with nucleation promoting factors and is linked to neuronal morphology regulation and AMPA receptor (AMPAR) endocytosis. Via interaction with the Arp2/3 complex involved in regulation of synaptic plasicity of excitatory synapses and required for spine shrinkage during long-term depression (LTD). Involved in regulation of astrocyte morphology, antagonistic to Arp2/3 complex activator WASL/N-WASP function.
Belongs to the mitochondrion-specific ribosomal protein mS38 family.
Belongs to the phospholipase B-like family.
Substrate recognition component of the SCF(CCNF) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (By similarity). The SCF(CCNF) E3 ubiquitin-protein ligase complex is an integral component of the ubiquitin proteasome system (UPS) and links proteasome degradation to the cell cycle (By similarity). Mediates the substrate recognition and the proteasomal degradation of various target proteins during G2 phase involved in the regulation of cell cycle progression and in the maintenance of genome stability (By similarity).
The D box motifs (amino acid sequence RxxL) are involved in substrate binding, and may be ubiquitinated.
The nuclear localization signals mediate the localization to the nucleus.
Belongs to the AAA ATPase family. Katanin p60 subunit A1 subfamily. A-like 1 sub-subfamily.
Regulates microtubule dynamics in Sertoli cells, a process that is essential for spermiogenesis and male fertility. Severs microtubules in an ATP-dependent manner, promoting rapid reorganization of cellular microtubule arrays.
Catalyzes a salvage reaction resulting in the formation of AMP, that is energically less costly than de novo synthesis.
Associates with the RNA polymerase II complex.
Protein phosphatase that displays CTD phosphatase activity and regulates transcription of snRNA genes. Recognizes and binds phosphorylated 'Ser-7' of the C-terminal heptapeptide repeat domain (CTD) of the largest RNA polymerase II subunit POLR2A, and mediates dephosphorylation of 'Ser-5' of the CTD, thereby promoting transcription of snRNA genes.
DNA-binding protein involved in single-strand DNA break repair, double-strand DNA break repair and base excision repair. Resolves abortive DNA ligation intermediates formed either at base excision sites, or when DNA ligases attempt to repair non-ligatable breaks induced by reactive oxygen species. Catalyzes the release of adenylate groups covalently linked to 5'-phosphate termini, resulting in the production of 5'-phosphate termini that can be efficiently rejoined. Also able to hydrolyze adenosine 5'-monophosphoramidate (AMP-NH(2)) and diadenosine tetraphosphate (AppppA), but with lower catalytic activity (By similarity). Likewise, catalyzes the release of 3'-linked guanosine (DNAppG) and inosine (DNAppI) from DNA, but has higher specific activity with 5'-linked adenosine (AppDNA) (By similarity).
The C2H2-type zinc finger mediates DNA-binding.
The HIT domain is required for enzymatic activity.
The histidine triad, also called HIT motif, forms part of the binding loop for the alpha-phosphate of purine mononucleotide.
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. Has also methyltransferase activity toward non-histone proteins.
The SET domain is necessary but not sufficient for histone methyltransferase activity.
May play a role in the trafficking of a subset of G-protein coupled receptors.
Expressed throughout the deep and superficial endoderm during gastrulation. During neural and early tail bud stages, expression declines significantly in the anterior endoderm, except in the endoderm behind the cement gland. Strong expression persists in the endoderm posterior to the liver diverticulum until late tail bud stage. By late tailbud, expression is undetectable in most of the endoderm but is maintained in the presumptive gall bladder region and the extreme posterior region. In addition, expressed in endothelial cells in the head and along the flank of the embryo.
Transcription activator. Binds to the DNA sequence 5'-AACAAT-3'. All of the sox17 proteins are required for embryonic endoderm development and gastrulation movements, and show some redundancy in function. In addition, the sox17 proteins have distinct but overlapping roles in later gut development. Acts downstream of vegt-signaling in endoderm differentiation to induce a range of endodermal genes both directly (including endodermin and dhh/chh) and indirectly. Also represses wnt-responsive genes to inhibit wnt/beta-catenin signaling (By similarity).
Has a particular type of basic domain which includes a helix-interrupting proline.
Transcription repression requires formation of a complex with a corepressor protein of the Groucho/TLE family.
Transcriptional repressor. Represses transcription from both N box- and E box-containing promoters. Demarcates the prospective midbrain-hindbrain boundary (MHB) region in the neuroectoderm in early gastrulae embryos by repressing transcription of a number of target genes (By similarity).
Dephosphorylates a range of proteins, and thereby regulates cellular signaling cascades.
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 (By similarity). 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 (By similarity).
Forms an alpha-helical dimer with monomers associated via an antiparallel alpha-helical coiled coil composed of residues 78-109, leaving each N-terminal inhibitory region (residues 27-56) accessible for interaction with an F1 catalytic domain. The inhibitory N-terminal region (residues 27-56) 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 (By similarity).
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 (By similarity).
Belongs to the class-II aminoacyl-tRNA synthetase family. Phe-tRNA synthetase alpha subunit type 2 subfamily.
Plays an important role in cell protection against oxidative stress and in the regulation of redox-related calcium homeostasis. Regulates the calcium level of the ER by protecting the calcium pump ATP2A2 against the oxidoreductase ERO1A-mediated oxidative damage. Acts as a modulator of ryanodine receptor (RyR) activity. Plays an important role in muscle development and differentiation during early development.
Found in a complex with p53/TP53 and CABLES1.
Participates in the apoptotic response to DNA damage. Isoforms containing the transactivation domain are pro-apoptotic, isoforms lacking the domain are anti-apoptotic and block the function of p53 and transactivating p73 isoforms. May be a tumor suppressor protein.
Autophosphorylates. Phosphorylated by plk1/plx1, suggesting the existence of a feedback loop with plk1/plx1. activation of the protein (By similarity).
May act as a polo kinase kinase by mediating phosphorylation of plk1/plx1 and subsequent activation of plk1/plx1 during oocyte maturation.
NADH-cytochrome b5 reductases are involved in desaturation and elongation of fatty acids, cholesterol biosynthesis and drug metabolism.
Although strongly related to the abraxas1 protein, lacks the C-terminal pSXXF that constitutes a specific recognition motif for the BRCT domain of brca1.
Belongs to the FAM175 family. Abro1 subfamily.
Component of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys-63'-linked polyubiquitin, leaving the last ubiquitin chain attached to its substrates. May act as a central scaffold protein that assembles the various components of the BRISC complex and retains them in the cytoplasm (By similarity). Plays a role in regulating the onset of apoptosis via its role in modulating 'Lys-63'-linked ubiquitination of target proteins (By similarity). Required for normal mitotic spindle assembly and microtubule attachment to kinetochores via its role in deubiquitinating numa1 (By similarity).
Component of the BRISC complex, at least composed of ABRAXAS2 and the catalytic subunit brcc3/brcc36. Interacts with brcc3/brcc36; the interaction is direct. The BRISC complex binds monoubiquitin and polyubiquitin.
Copper metallochaperone essential for the synthesis and maturation of cytochrome c oxidase subunit II (MT-CO2/COX2). Involved in transporting copper to the Cu(A) site on MT-CO2/COX2. Also acts as a thiol-disulfide oxidoreductase to regulate the redox state of the cysteines in SCO1 during maturation of MT-CO2/COX2.
Belongs to the bombesin/neuromedin-B/ranatensin family.
ATP-dependent RNA helicase. Involved in pre-mRNA splicing as component of the spliceosome. Core component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junctions on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. The EJC marks the position of the exon-exon junction in the mature mRNA for the gene expression machinery and the core components remain bound to spliced mRNAs throughout all stages of mRNA metabolism thereby influencing downstream processes including nuclear mRNA export, subcellular mRNA localization, translation efficiency and nonsense-mediated mRNA decay (NMD). Binds spliced mRNA in sequence-independent manner, 20-24 nucleotides upstream of mRNA exon-exon junctions (By similarity). Involved in craniofacial development (By similarity).
Identified in the spliceosome C complex. Part of the mRNA splicing-dependent exon junction complex (EJC) complex; the core complex contains casc3, eif4a3, magoh and rbm8a.
Non-catalytic component of the proteasome.
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 eIF-2B alpha/beta/delta subunits family.
Acts specifically as a negative regulator of skeletal muscle growth.
Key enzyme involved in DNA replication and DNA repair. Involved in Okazaki fragments processing by cleaving long flaps that escape FEN1: flaps that are longer than 27 nucleotides are coated by replication protein A complex (RPA), leading to recruit DNA2 which cleaves the flap until it is too short to bind RPA and becomes a substrate for FEN1. Also involved in 5'-end resection of DNA during double-strand break (DSB) repair by mediating the cleavage of 5'-ssDNA.
Contributes to the overall PI4-kinase activity of the cell. This contribution may be especially significant in plasma membrane, endosomal and Golgi compartments. The phosphorylation of phosphatidylinositol (PI) to PI4P is the first committed step in the generation of phosphatidylinositol 4,5-bisphosphate (PIP2), a precursor of the second messenger inositol 1,4,5-trisphosphate (InsP3).
Acts both as a regulator of telomere function and as a transcription regulator. Involved in the regulation of telomere length and protection as a component of the shelterin complex (telosome). Does not bind DNA directly: recruited to telomeric double-stranded 5'-TTAGGG-3' repeats via its interaction with terf2. Independently of its function in telomeres, also acts as a transcription regulator: recruited to extratelomeric 5'-TTAGGG-3' sites via its association with terf2 or other factors, and regulates gene expression (By similarity).
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.
Homodimer. Component of the shelterin complex (telosome). Interacts with terf2; the interaction is direct (By similarity).
Belongs to the MoaE family. MOCS2B subfamily.
Catalytic subunit of the molybdopterin synthase complex, a complex that catalyzes the conversion of precursor Z into molybdopterin. Acts by mediating the incorporation of 2 sulfur atoms from thiocarboxylated MOCS2A into precursor Z to generate a dithiolene group.
This protein is produced by a bicistronic gene which also produces the large subunit (MOCS2A).
Belongs to the SSU72 phosphatase family.
Protein phosphatase that catalyzes the dephosphorylation of the C-terminal domain of RNA polymerase II. Plays a role in RNA processing and termination.
Belongs to the TFIIE beta subunit family.
Tetramer of two alpha and two beta chains.
May be involved in the translation of target mRNAs by scanning and recognition of the initiation codon. Involved in translation initiation; promotes recruitment of aminoacetyled initiator tRNA to P site of 40S ribosomes. Can promote release of deacylated tRNA and mRNA from recycled 40S subunits following ABCE1-mediated dissociation of post-termination ribosomal complexes into subunits (By similarity).
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.
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 (By similarity).
Belongs to the IspD/TarI cytidylyltransferase family. IspD subfamily.
Cytidylyltransferase required for protein O-linked mannosylation (By similarity). Catalyzes the formation of CDP-ribitol nucleotide sugar from D-ribitol 5-phosphate. CDP-ribitol is a substrate of FKTN during the biosynthesis of the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-beta-3-N-acetylglucosamine-beta-4-(phosphate-6-)mannose), a carbohydrate structure present in alpha-dystroglycan (DAG1), which is required for binding laminin G-like domain-containing extracellular proteins with high affinity (By similarity). Shows activity toward other pentose phosphate sugars and mediates formation of CDP-ribulose or CDP-ribose using CTP and ribulose-5-phosphate or ribose-5-phosphate, respectively (By similarity). Not involved in dolichol production (By similarity).
Belongs to the Mediator complex subunit 29 family.
Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating (By similarity). May play a role in the control of meiotic division and germ cell differentiation through regulation of pairing and recombination during meiosis (By similarity). Required for sperm flagella assembly (By similarity). May play a role in the assembly and function of the outer dynein arm-docking complex (ODA-DC). ODA-DC mediates outer dynein arms (ODA) binding onto the axonemal doublet microtubules (By similarity).
Belongs to the TRAFAC class OBG-HflX-like GTPase superfamily. OBG GTPase family. NOG subfamily.
Involved in the biogenesis of the 60S ribosomal subunit.
Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility. Within the PRC1-like complex, regulates RNF2 ubiquitin ligase activity.
Expression begins in the newly forming dorsal mesoderm and is maintained during gastrulation at the dorsal blastopore lip (Spemann organizer). At the early neurula stages, expressed in a row of cells along the dorsal midline that are destined to become the fllor plate of the neural tube. At late neurula, expressed within the anterior and posterior poles of the embryo. After neural closure, expression is detected only in the tailtip, the otic vesicle and at the midbrain/hindbrain boundary.
Required to suppress inappropriate homologous recombination, thereby playing a central role DNA repair and in the maintenance of genomic stability.
Involved in the lipid remodeling steps of GPI-anchor maturation.
Belongs to the iron/manganese superoxide dismutase family.
Destroys superoxide anion radicals which are normally produced within the cells and which are toxic to biological systems.
Belongs to the peptidase C19 family. USP16 subfamily.
Specifically deubiquitinates 'Lys-120' of histone H2A (H2AK119Ub), a specific tag for epigenetic transcriptional repression, thereby acting as a coactivator. Deubiquitination of histone H2A is a prerequisite for subsequent phosphorylation at 'Ser-11' of histone H3 (H3S10ph), and is required for chromosome segregation when cells enter into mitosis. Regulates Hox gene expression via histone H2A deubiquitination. Prefers nucleosomal substrates. Does not deubiquitinate histone H2B.
The UBP-type zinc finger binds 3 zinc ions that form a pair of cross-braced ring fingers encapsulated within a third zinc finger in the primary structure. It recognizes the C-terminal tail of free ubiquitin.
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.
Probable sodium-dependent amino acid/proton antiporter, could be a neuronal transporter for glutamate.
Homooligomer. Part of either the minor and major complexes respectively composed of 4 sets of ATG12-ATG5 and ATG16L1 (400 kDa) or 8 sets of ATG12-ATG5 and ATG16L1 (800 kDa).
Plays an essential role in autophagy: interacts with ATG12-ATG5 to mediate the conjugation of phosphatidylethanolamine (PE) to LC3 (MAP1LC3A, MAP1LC3B or MAP1LC3C), to produce a membrane-bound activated form of LC3 named LC3-II. Thereby, controls the elongation of the nascent autophagosomal membrane.
Belongs to the TRAFAC class dynamin-like GTPase superfamily. Dynamin/Fzo/YdjA family.
Functions as a receptor for membrane-bound ligands Jagged-1 (JAG1), Jagged-2 (JAG2) and Delta-1 (DLL1) to regulate cell-fate determination. Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects the implementation of differentiation, proliferation and apoptotic programs. Involved in angiogenesis; negatively regulates endothelial cell proliferation and migration and angiogenic sprouting. Involved in the maturation of both CD4(+) and CD8(+) cells in the thymus. Important for follicular differentiation and possibly cell fate selection within the follicle. During cerebellar development, functions as a receptor for neuronal DNER and is involved in the differentiation of Bergmann glia. Represses neuronal and myogenic differentiation. May play an essential role in postimplantation development, probably in some aspect of cell specification and/or differentiation. May be involved in mesoderm development, somite formation and neurogenesis (By similarity). Involved in determination of left/right symmetry by modulating the balance between motile and immotile (sensory) cilia at the left-right organiser (LRO).
O-glycosylated on the EGF-like domains. Contains both O-linked fucose and O-linked glucose. O-linked glycosylation by galnt11 is involved in determination of left/right symmetry: glycosylation promotes activation of notch1, possibly by promoting cleavage by adam17, modulating the balance between motile and immotile (sensory) cilia at the left-right organiser (LRO).
Synthesized in the endoplasmic reticulum as an inactive form which is proteolytically cleaved by a furin-like convertase in the trans-Golgi network before it reaches the plasma membrane to yield an active, ligand-accessible form. Cleavage results in a C-terminal fragment N(TM) and a N-terminal fragment N(EC). Following ligand binding, it is cleaved by adam17 to yield a membrane-associated intermediate fragment called notch extracellular truncation (NEXT). Following endocytosis, this fragment is then cleaved by presenilin dependent gamma-secretase to release a Notch-derived peptide containing the intracellular domain (NICD) from the membrane (By similarity).
Belongs to the cyclophilin-type PPIase family. PPIL4 subfamily.
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.
The C-terminal UBZ-type zinc fingers function as ubiquitin-binding domains.
Belongs to the peptidase C19 family. USP10 subfamily.
Hydrolase that can remove conjugated ubiquitin from target proteins such as p53/tp53, rps2/us5, rps3/us3, rps10/eS10, becn1, snx3 and cftr. Acts as an essential regulator of p53/tp53 stability: in unstressed cells, specifically deubiquitinates p53/tp53 in the cytoplasm, leading to counteracts MDM2 action and stabilize p53/tp53. Following DNA damage, translocates to the nucleus and deubiquitinates p53/tp53, leading to regulate the p53/TP53-dependent DNA damage response. Component of a regulatory loop that controls autophagy and p53/tp53 levels. Plays a key role in 40S ribosome subunit recycling when a ribosome has stalled during translation: acts both by inhibiting formation of stress granules, which store stalled translation pre-initiation complexes, and mediating deubiquitination of 40S ribosome subunits. Deubiquitinates cftr in early endosomes, enhancing its endocytic recycling.
Belongs to the peroxiredoxin-like PRXL2 family. Prostamide/prostaglandin F synthase subfamily.
Catalyzes the reduction of prostaglandin-ethanolamide H(2) (prostamide H(2)) to prostamide F(2alpha) with NADPH as proton donor. Also able to reduce prostaglandin H(2) to prostaglandin F(2alpha) (By similarity).
Component of a CRL2 E3 ubiquitin-protein ligase complex, also named ECS (Elongin BC-CUL2/5-SOCS-box protein) complex, composed of CUL2, Elongin BC (ELOB and ELOC), RBX1 and substrate-specific adapter KLHDC10.
Substrate-recognition component of a Cul2-RING (CRL2) E3 ubiquitin-protein ligase complex of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation. The C-degron recognized by the DesCEND pathway is usually a motif of less than ten residues and can be present in full-length proteins, truncated proteins or proteolytically cleaved forms. The CRL2(KLHDC10) complex specifically recognizes proteins with a proline-glycine (Pro-Gly) or an alanine tail (CAT tail) at the C-terminus, leading to their ubiquitination and degradation. The CRL2(KLHDC10) complex is involved in the ribosome-associated quality control (RQC) pathway, which mediates the extraction of incompletely synthesized nascent chains from stalled ribosomes: CRL2(KLHDC10) acts downstream of NEMF and recognizes CAT tails associated with stalled nascent chains, leading to their ubiquitination and degradation.
Contributes to various developmental events through its interactions with multiple signaling pathways. Dorsalizing factor which functions as an inhibitor of bone morphogenetic proteins (BMP) during gastrulation. Promotes dll1-dependent activation of Notch signaling and is required for neural crest formation. Induces endoderm and dorsal mesoderm formation by enhancing nodal2/Xnr2 activity while inhibiting ventrolateral mesoderm formation through inhibition of fgf8.
Interacts with bmp4. Interacts with dll1 (via extracellular region). Interacts with fgf8; inhibits fgf8 signaling. Interacts with nodal2/Xnr2; enhances nodal2 activity.
This factor is named 'Tsukushi' because its expression pattern in chick embryos is similar to the shape of the Japanese horsetail plant, tsukushi.
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.
May play an essential role for mitochondrial structure and function.
Catalytic subunit of an S-adenosyl-L-methionine-dependent tRNA methyltransferase complex that mediates the methylation of the guanosine nucleotide at position 10 (m2G10) in tRNAs.
Belongs to the HMG-CoA reductase family.
Cell autonomous antagonist of the canonical Wnt signaling pathway.
Belongs to the mitochondrion-specific ribosomal protein mL42 family.
Belongs to the adenylate kinase family. AK2 subfamily.
Catalyzes the reversible transfer of the terminal phosphate group between ATP and AMP. Plays an important role in cellular energy homeostasis and in adenine nucleotide metabolism. Adenylate kinase activity is critical for regulation of the phosphate utilization and the AMP de novo biosynthesis pathways. Plays a key role in hematopoiesis.
Belongs to the myelin basic protein family.
Generates hydrogen peroxide which is required for the activity of thyroid peroxidase/TPO and lactoperoxidase/LPO. Plays a role in thyroid hormones synthesis and lactoperoxidase-mediated antimicrobial defense at the surface of mucosa. May have its own peroxidase activity through its N-terminal peroxidase-like domain.
In the N-terminal section; belongs to the peroxidase family.
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.
Belongs to the class I-like SAM-binding methyltransferase superfamily. mRNA cap 0 methyltransferase family.
Catalytic subunit of the mRNA-capping methyltransferase RNMT:RAMAC complex that methylates the N7 position of the added guanosine to the 5'-cap structure of mRNAs. Binds RNA containing 5'-terminal GpppC.
Belongs to the proteasome subunit S2 family.
Binds to the intracellular domain of tumor necrosis factor type 1 receptor. The binding domain of TRAP1 and TRAP2 resides outside the death domain of TNFR1.
Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP).
Belongs to the Nudix hydrolase family. NudC subfamily.
Binds to DNA motifs with the sequence 5'-GCG(T/G)GGGCG-3' via its C2H2-type zinc fingers. The first, most N-terminal zinc finger binds to the 3'-GCG motif, the middle zinc finger interacts with the central TGG motif, and the C-terminal zinc finger binds to the 5'-GCG motif. Binds double-stranded target DNA, irrespective of the cytosine methylation status. Has reduced affinity for target DNA where the cytosines have been oxidized to 5-hydroxymethylcytosine. Does not bind target DNA where the cytosines have been oxidized to 5-formylcytosine or 5-carboxylcytosine.
Transcriptional regulator. Recognizes and binds to the DNA sequence 5'-GCG(T/G)GGGCG-3'(EGR-site) in the promoter region of target genes (By similarity). Binds double-stranded target DNA, irrespective of the cytosine methylation status (By similarity). Regulates the transcription of numerous target genes, and thereby plays an important role in regulating the response to growth factors, DNA damage, and ischemia. Plays a role in the regulation of cell survival, proliferation and cell death. Mediates responses to ischemia and hypoxia; regulates the expression of proteins that are involved in inflammatory processes (By similarity). Plays a role in regulating the expression of circadian clock genes (By similarity).
Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXL15).
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. Acts as a positive regulator of the BMP signaling pathway. Required for dorsal/ventral pattern formation (By similarity).
Deubiquitinating enzyme that acts as a key inhibitor of mitophagy by counteracting the action of parkin (PRKN).
Belongs to the chromogranin/secretogranin protein family.
Belongs to the PPP phosphatase family. PP-1 subfamily.
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.
Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. SETD6 subfamily.
Specific component of the STT3A-containing form of the oligosaccharyl transferase (OST) complex that catalyzes the initial transfer of a defined glycan (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-pyrophosphate to an asparagine residue within an Asn-X-Ser/Thr consensus motif in nascent polypeptide chains, the first step in protein N-glycosylation. N-glycosylation occurs cotranslationally and the complex associates with the Sec61 complex at the channel-forming translocon complex that mediates protein translocation across the endoplasmic reticulum (ER). All subunits are required for a maximal enzyme activity.
Specific component of the STT3A-containing form of the oligosaccharyltransferase (OST) complex.
Belongs to the gamma-glutamylcyclotransferase family.
Catalyzes the formation of 5-oxo-L-proline from L-gamma-glutamyl-L-epsilon-lysine.
Lipid transporter that specifically mediates export of sphingosine-1-phosphate (sphing-4-enine 1-phosphate, S1P) and sphinganine-1-phosphate.
Promotes the survival of neuronal populations that are all located either in the central nervous system or directly connected to it.
A component of a ybx2/frgy2-containing mRNA-ribonucleoprotein (mRNP) complex. Also a component of the CCAAT box transcription factor (CBTF) complex.
Methylated by protein arginine N-methyltransferase 1 (prmt1b) in the RGG-rich domain. Methylation decreases DNA-binding and thereby decreases transcription of the gata2 gene, but does not regulate dsRNA binding or subcellular localization.
Phosphorylated. Phosphorylation affects nuclear translocation.
RNA-binding protein that plays an essential role in the biogenesis of circular RNAs (circRNAs) which are produced by back-splicing circularization of pre-mRNAs. Within the nucleus, promotes circRNAs processing by stabilizing the regulatory elements residing in the flanking introns of the circularized exons. Plays thereby a role in the back-splicing of a subset of circRNAs. As a consequence, participates in a wide range of transcriptional and post-transcriptional processes. Binds to poly-U elements and AU-rich elements (AREs) in the 3'-UTR of target mRNAs (By similarity). Upon viral infection, ILF3 accumulates in the cytoplasm and participates in the innate antiviral response. Mechanistically, ILF3 becomes phosphorylated and activated by the double-stranded RNA-activated protein kinase/PKR which releases ILF3 from cellular mature circRNAs. In turn, unbound ILF3 molecules are able to interact with and thus inhibit viral mRNAs. Has a cytoplasmic role early in development as part of a ribonucleoprotein (mRNP) complex which may regulate mRNA transport and/or translation. Following nuclear localization at the mid-blastula transition, acts as a transcription factor and binds the 5'-CCAAT-3' promoter sequence to regulate transcription of the gata2 gene as a subunit of the CCAAT box transcription factor (CBTF). Its role as an mRNP component negatively regulates its activity as a transcription factor by precluding its nuclear localization.
Component of the pre-catalytic and post-catalytic spliceosome complexes.
Required for pre-mRNA splicing as component of the spliceosome (By similarity). Binds double-stranded RNA (By similarity).
Alpha-L-fucosidase is responsible for hydrolyzing the alpha-1,6-linked fucose joined to the reducing-end N-acetylglucosamine of the carbohydrate moieties of glycoproteins.
Belongs to the glycosyl hydrolase 29 family.
Exhibits mesoderm-dorsalizing activity and neural-inducing activity, but lacks mesoderm-inducing activity. Regulates the expression of specific mesodermal and neural genes. Induces convergent extension movements at the embryonic midline by activating the fgf signaling pathway to induce t/bra expression in the organizer region. Acts with wnt11 to induce Spemann organizer cells and induce axis formation (By similarity). The unprocessed protein antagonizes bmp-signaling.
Expressed in the dorsal marginal region of late blastula, becoming restricted to the Spemann organizer at the early gastrula stage.
First detected at the blastula stage (stage 8). Expression peaks through the mid-blastula (stage 8.5) to early gastrula (stage 10) and then decreases during gastrulation.
Monomer (By similarity). The propeptide region interacts with bmp4 in a non-covalent manner.
The propeptide region is both necessary and sufficient for bmp-inhibitory activity. The propeptide region and the N- and C-terminal thirds of the mature protein are necessary for neural induction activity. Although cleavage doesn't appear essential for activity, residues surrounding the cleavage site are necessary for activity (By similarity).
COPII is composed of at least five proteins: the Sec23/24 complex, the Sec13/31 complex and Sar1.
Component of the coat protein complex II (COPII) which promotes the formation of transport vesicles from the endoplasmic reticulum (ER). The coat has two main functions, the physical deformation of the endoplasmic reticulum membrane into vesicles and the selection of cargo molecules for their transport to the Golgi complex.
The Gelsolin-like repeat mediates interaction with proteins containing PPP motifs.
Plays a role in axonemal structure organization and motility. Involved in axonemal pre-assembly of inner and outer dynein arms (IDA and ODA, respectively) for proper axoneme building for cilia motility. May act by indirectly regulating transcription of dynein proteins.
Belongs to the VEFS (VRN2-EMF2-FIS2-SU(Z)12) family.
Polycomb group (PcG) protein. Component of the prc2/eed-ezh2 complex, which methylates 'Lys-9' (H3K9me) and 'Lys-27' (H3K27me) of histone H3, leading to transcriptional repression of the affected target gene (By similarity).
Appears to be essential for maintaining mitochondrial cristae formation and mitochondrial function by acting via YME1L1 in a kinase-independent manner to regulate essential mitochondrial structural proteins OPA1 and IMMT (By similarity). The action of this enzyme is not yet clear. It is not known if it has protein kinase activity and what type of substrate it would phosphorylate (Ser, Thr or Tyr) (Probable).
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.
Involved in dynein arm assembly, is important for expression and transporting outer dynein arm (ODA) proteins from the cytoplasm to the cilia.
Component of the SMG1C complex composed of smg1, smg8 and smg9.
Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons. Is recruited by release factors to stalled ribosomes together with smg1 and smg9 (forming the SMG1C protein kinase complex) and, in the SMG1C complex, is required to mediate the recruitment of smg1 to the ribosome:SURF complex and to suppress smg1 kinase activity until the ribosome:SURF complex locates the exon junction complex (EJC). Acts as a regulator of kinase activity (By similarity).
Belongs to the glycosyl hydrolase 18 family. Chitinase class II subfamily.
Belongs to the acetyltransferase family. GNA1 subfamily.
Belongs to the bacterial ribosomal protein bS18 family.
In the C-terminal section; belongs to the LDH/MDH superfamily.
In the N-terminal section; belongs to the ubiquitin-conjugating enzyme family. UEV subfamily.
Possible negative regulator of polyubiquitination.
Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO), such as platelet dense granules and melanosomes. Plays a role in intracellular vesicle trafficking (By similarity).
Component of the BLOC-1 complex, a complex that is required for normal biogenesis of lysosome-related organelles (LRO).
Belongs to the protein kinase superfamily. Alpha-type protein kinase family.
Undergoes calcium/calmodulin-dependent intramolecular autophosphorylation, and this results in it becoming partially calcium/calmodulin-independent.
Required for 60S pre-ribosomal subunits export to the cytoplasm.
Minor enzyme contributing to the isomerization of uridine to pseudouridine (pseudouridylation) of specific mitochondrial mRNAs (mt-mRNAs) such as COXI and COXIII mt-mRNAs, modulating the efficiency of mitochondrial protein synthesis without changes in transcript abundance or stability (By similarity). Also catalyzes pseudouridylation of some tRNAs, including synthesis of pseudouridine(55) from uracil-55, in the psi GC loop of a subset of tRNAs (By similarity).
Substrate-binding subunit of tRNA (adenine-N1-)-methyltransferase, which catalyzes the formation of N1-methyladenine at position 58 (m1A58) in initiator methionyl-tRNA.
Belongs to the DNA glycosylase MPG family.
Hydrolysis of the deoxyribose N-glycosidic bond to excise 3-methyladenine, and 7-methylguanine from the damaged DNA polymer formed by alkylation lesions.
Secreted protein that functions as cytokine and growth factor and mediates its signal through cell-surface proteoglycan and non-proteoglycan receptors. Binds cell-surface proteoglycan receptors via their chondroitin sulfate (CS) groups. Thereby regulates many processes like inflammatory response, cell proliferation, cell adhesion, cell growth, cell survival, tissue regeneration, cell differentiation and cell migration (By similarity). Inhibits mesoderm formation and promotes neural formation during development. Plays a role in development of the neuromuscular junction (NMJ). Has antibacterial activity against both Gram-positive and Gram-negative bacteria (By similarity).
Belongs to the CorA metal ion transporter (MIT) (TC 1.A.35) family.
IGF1 rapidly induces phosphorylation of Thr-28, Ser-240 and Ser-303. Phosphorylation of Ser-240 decreases DNA-binding activity and promotes the phosphorylation of Thr-28, and Ser-303, which leads to nuclear exclusion and loss of function. Phosphorylation of Ser-313 is independent of IGF1 and leads to reduced function (By similarity).
Phosphorylated by AKT1; insulin-induced.
Transcription factor that regulates metabolic homeostasis in response to oxidative stress. Binds to the consensus sequence 5'-TT[G/A]TTTTG-3' and the related Daf-16 family binding element (DBE) with consensus sequence 5'-TT[G/A]TTTAC-3'. Main regulator of redox balance and osteoblast numbers and controls bone mass. Orchestrates the endocrine function of the skeleton in regulating glucose metabolism. Also acts as a key regulator of chondrogenic commitment of skeletal progenitor cells in response to lipid availability: when lipids levels are low, translocates to the nucleus and promotes expression of sox9, which induces chondrogenic commitment and suppresses fatty acid oxidation. Acts synergistically with atf4 to suppress osteocalcin/bglap activity, increasing glucose levels and triggering glucose intolerance and insulin insensitivity. Also suppresses the transcriptional activity of runx2, an upstream activator of osteocalcin/bglap.
Histone binding is mediated by the concave surface of the LRR region.
Multifunctional protein working as a cell cycle progression factor as well as a cell survival factor. Required for the progression from the G1 to the S phase. Anti-apoptotic protein which functions as a caspase-3 inhibitor. Has no phosphatase 2A (PP2A) inhibitor activity. Exhibits histone chaperone properties, stimulating core histones to assemble into a nucleosome (By similarity).
Component of the prc2/eed-ezh2 complex. May interact with ezh2, hdac1, taf9 and yy1.
Polycomb group (PcG) protein. Component of the prc2/eed-ezh2 complex, which methylates 'Lys-9' and 'Lys-27' of histone H3, leading to transcriptional repression of the affected target gene (By similarity).
Belongs to the complex I 20 kDa subunit family.
Binds 2 divalent metal cations per subunit. Has a high-affinity and a low affinity metal-binding site. The true nature of the physiological cofactor is under debate. The enzyme is active with cobalt, zinc, manganese or divalent iron ions.
Inhibits potassium fluxes in cells, possibly by retaining potassium channels in the cytoplasm.
Histone demethylase that can demethylate both 'Lys-4' (H3K4me) and 'Lys-9' (H3K9me) of histone H3, thereby acting as a coactivator or a corepressor, depending on the context. Acts by oxidizing the substrate by FAD to generate the corresponding imine that is subsequently hydrolyzed. Acts as a corepressor by mediating demethylation of H3K4me, a specific tag for epigenetic transcriptional activation. Demethylates both mono- (H3K4me1) and di-methylated (H3K4me2) H3K4me. May play a role in the repression of neuronal genes. Alone, it is unable to demethylate H3K4me on nucleosomes and requires the presence of RCOR1/CoREST to achieve such activity.
The SWIRM domain may act as an anchor site for a histone tail.
Belongs to the eukaryotic ribosomal protein eS24 family.
Belongs to the eukaryotic ribosomal protein eL39 family.
Belongs to the SMC family. SMC2 subfamily.
Belongs to the SOS response-associated peptidase family.
Glu-129 is involved in sensing abasic sites in single-stranded DNA (ssDNA). His-203 stabilizes the abasic sites by forming a hydrogen bond with the O4' hydroxyl group.
Sensor of abasic sites in single-stranded DNA (ssDNA) required to preserve genome integrity by promoting error-free repair of abasic sites. Acts as an enzyme that recognizes and binds abasic sites in ssDNA at replication forks and chemically modifies the lesion by forming a covalent cross-link with DNA: forms a stable thiazolidine linkage between a ring-opened abasic site and the alpha-amino and sulfhydryl substituents of its N-terminal catalytic cysteine residue. The HMCES DNA-protein cross-link is then degraded by the proteasome. Promotes error-free repair of abasic sites by acting as a 'suicide' enzyme that is degraded, thereby protecting abasic sites from translesion synthesis (TLS) polymerases and endonucleases that are error-prone and would generate mutations and double-strand breaks. Has preference for ssDNA, but can also accommodate double-stranded DNA with 3' or 5' overhang (dsDNA), and dsDNA-ssDNA 3' junction (By similarity). Acts as a protease: mediates autocatalytic processing of its N-terminal methionine in order to expose the catalytic cysteine (By similarity).
Belongs to the sulfatase-modifying factor family.
May act as a growth inhibitor. May be involved in maintaining chromosomal stability.
E3 ubiquitin-protein ligase that acts as a negative regulator of the Wnt signaling pathway by mediating the ubiquitination and subsequent degradation of Wnt receptor complex components (By similarity). Along with RSPO2 and RNF43, constitutes a master switch that governs limb specification (PubMed:29769720).
Monomer. Can form dimers (By similarity).
Receptor for the C-X-C chemokine cxcl12/sdf-1. Transduces a signal by increasing the intracellular calcium ion level. Signaling with cxcl12/sdf-1 mediates the directional movement of mesodermal cells during gastrulation. May play a role in the migration of embryonic presumptive primordial germ cells (pPGCs). May also be involved in regulating migration of hematopoietic stem cells into the larval liver (By similarity).
Sulfation is required for efficient binding of cxcl12/sdf-1alpha and promotes its dimerization.
Binds to the IL-1 type I receptor following IL-1 engagement, triggering intracellular signaling cascades leading to transcriptional up-regulation and mRNA stabilization.
Interacts with MYD88. IL-1 stimulation leads to the formation of a signaling complex which dissociates from the IL-1 receptor following the binding of PELI1.
Acts as an E3 ubiquitin-protein ligase specific for ldb1, mediating ubiquitination and proteasome-dependent degradation of excess ldb1 in a RING-dependent manner. Does not degrade ldb1 bound to lhx1/lim1, nor lim1 itself and thus contributes to the establishment of proper ldb1-lhx1/lim1 stoichiometry and the formation of a ldb1-lhx1/lim1 complex. Interferes with Spemann organizer function and suppresses secondary axis formation induced by ldb1 and lhx1/lim1.
Forms homodimers through the C-terminal region. The N-terminus interacts with the homeobox of LIM/homeobox factor lhx1/lim1, with lhx3/lim3 and lhx5/lim5, and with the N-terminus of ldb1 (By similarity).
Belongs to the Mediator complex subunit 8 family.
Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. May play a role as a target recruitment subunit in E3 ubiquitin-protein ligase complexes and thus in ubiquitination and subsequent proteasomal degradation of target proteins (By similarity).
Component of the Mediator complex. May be part of a multisubunit E3 ubiquitin-protein ligase complex (By similarity).
Transcription elongation factor which increases mitochondrial RNA polymerase processivity. Regulates transcription of the mitochondrial genome, including genes important for the oxidative phosphorylation machinery.
Component of the DCX(DCAF12) E3 ubiquitin ligase complex, at least composed of cul4 (cul4a or cul4b), ddb1, dcaf12 and rbx1.
Substrate-recognition component of a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex of the DesCEND (destruction via C-end degrons) pathway, which recognizes a C-degron located at the extreme C terminus of target proteins, leading to their ubiquitination and degradation. The C-degron recognized by the DesCEND pathway is usually a motif of less than ten residues and can be present in full-length proteins, truncated proteins or proteolytically cleaved forms. The DCX(DCAF12) complex specifically recognizes proteins with a diglutamate (Glu-Glu) at the C-terminus leading to their ubiquitination and degradation. Also directly recognizes the C-terminal glutamate-leucine (Glu-Leu) degron as an alternative degron in proteins leading to their ubiquitination and degradation.
Belongs to the dolichyldiphosphatase family.
Required for efficient N-glycosylation. Necessary for maintaining optimal levels of dolichol-linked oligosaccharides. Hydrolyzes dolichyl pyrophosphate at a very high rate and dolichyl monophosphate at a much lower rate. Does not act on phosphatidate.
Belongs to the G-alpha family. G(12) subfamily.
Transcription repressor. Component of the regulatory cascade that controls the development of dopaminergic (DA) and serotonergic (5HT) neurons (By similarity).
Belongs to the GST superfamily. Mu family.
Belongs to the eukaryotic GSH synthase family.
Belongs to the class-I pyridoxal-phosphate-dependent aminotransferase family. Alanine aminotransferase subfamily.
Catalyzes the reversible transamination between alanine and 2-oxoglutarate to form pyruvate and glutamate.
Decarboxylates ethylmalonyl-CoA, a potentially toxic metabolite, to form butyryl-CoA, suggesting it might be involved in metabolite proofreading. Acts preferentially on (S)-ethylmalonyl-CoA but has also some activity on the (R)-isomer. Also has methylmalonyl-CoA decarboxylase activity at lower level.
Plays a role in the organization of the endoplasmic reticulum exit sites (ERES), also known as transitional endoplasmic reticulum (tER). Required for secretory cargo traffic from the endoplasmic reticulum to the Golgi apparatus.
SEC16A and SEC16B are each present in multiple copies in a heteromeric complex.
Arginine methyltransferase that methylates the guanidino nitrogens of arginyl residues in proteins such as histones. Involved in growth regulation. Involved in embryonic dorsal development.
Belongs to the eukaryotic ribosomal protein eS27 family.
Belongs to the Cob(I)alamin adenosyltransferase family.
Component of the cap-binding complex (CBC), which binds cotranscriptionally to the 5'-cap of pre-mRNAs and is involved in various processes such as pre-mRNA splicing, translation regulation, nonsense-mediated mRNA decay, RNA-mediated gene silencing (RNAi) by microRNAs (miRNAs) and mRNA export. The CBC complex is involved in mRNA export from the nucleus, leading to the recruitment of the mRNA export machinery to the 5'-end of mRNA and to mRNA export in a 5' to 3' direction through the nuclear pore. The CBC complex is also involved in mediating U snRNA and intronless mRNAs export from the nucleus. The CBC complex is essential for a pioneer round of mRNA translation, before steady state translation when the CBC complex is replaced by cytoplasmic cap-binding protein eIF4E. The pioneer round of mRNA translation mediated by the CBC complex plays a central role in nonsense-mediated mRNA decay (NMD), NMD only taking place in mRNAs bound to the CBC complex, but not on eIF4E-bound mRNAs. The CBC complex enhances NMD in mRNAs containing at least one exon-junction complex (EJC), promoting the interaction between UPF1 and UPF2. The CBC complex is also involved in 'failsafe' NMD, which is independent of the EJC complex, while it does not participate in Staufen-mediated mRNA decay (SMD). During cell proliferation, the CBC complex is also involved in microRNAs (miRNAs) biogenesis via its interaction with SRRT/ARS2 and is required for miRNA-mediated RNA interference. The CBC complex also acts as a negative regulator of parn, thereby acting as an inhibitor of mRNA deadenylation. In the CBC complex, ncbp1/cbp80 does not bind directly capped RNAs (m7GpppG-capped RNA) but is required to stabilize the movement of the N-terminal loop of ncbp2/cbp20 and lock the CBC into a high affinity cap-binding state with the cap structure. Associates with NCBP3 to form an alternative cap-binding complex (CBC) which plays a key role in mRNA export. The conventional CBC with NCBP2 binds both small nuclear RNA (snRNA) and messenger (mRNA) and is involved in their export from the nucleus whereas the alternative CBC with NCBP3 does not bind snRNA and associates only with mRNA thereby playing a role only in mRNA export (By similarity).
Component of the nuclear cap-binding complex (CBC), a heterodimer composed of ncbp1/cbp80 and ncbp2/cbp20 that interacts with m7GpppG-capped RNA. Component of an alternative nuclear cap-binding complex (CBC) composed of ncbp1/cbp80 and ncbp3 (By similarity).
Involved in the processing of hormone and other protein precursors at sites comprised of pairs of basic amino acid residues. Substrates include POMC, renin, enkephalin, dynorphin, somatostatin, insulin and AGRP.
Belongs to the universal ribosomal protein uS5 family.
Cold-inducible mRNA binding protein. Acts cooperatively with elavl1/elrA to stabilize AU-rich element (ARE)-containing mRNAs by binding to themm and inhibiting their deadenylation. Essential for embryonic gastrulation and neural development, acting to maintain the expression of a set of adhesion molecules, and cell movement during embryogenesis. Required for pronephros development (By similarity).
Interacts with prmt1. Interacts with elavl1/elrA (via RRM3). Associates with ribosomes (By similarity).
Methylated on arginine residues within RGG motifs. Methylation by prmt1 promotes cytoplasmic accumulation (By similarity).
The glycine-rich domain, which contains a number of RGG motifs, is necessary to regulate nucleocytoplasmic localization.
Potent and specific cellular inhibitor of CaM-kinase II (CAMK2). Traps Ca(2+)/calmodulin on CAMK2 (By similarity).
Heterodimer with IL12A; disulfide-linked. The heterodimer is known as interleukin IL-12.
Belongs to the purine nucleoside phosphorylase YfiH/LACC1 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.
Plays a role in promoting cell proliferation in response to pro-inflammatory stimuli.
Regulates COPI-mediated retrograde protein traffic at the interface between the Golgi apparatus and the endoplasmic reticulum. Involved in the maintenance of the Golgi apparatus morphology. Has no detectable kinase activity in vitro.
The protein kinase domain is predicted to be catalytically inactive.
Probable transcription factor. Promotes both hatching gland and neural crest cell fates, two of the cell populations that arise from the neural plate border. Acts downstream of msx1 to induce the neural crest, cooperating with zic1 and mediating signals from both the wnt and fgf8 signaling pathways. Induction of hatching gland cell fate is independent of zic1 (By similarity).
Tethering factor involved in autophagy. Involved in autophagosome maturation by promoting the autophagosome fusion with lysosomes. Binds phosphatidylinositol-3-phosphate (PtdIns(3)P) present at the surface of autophagosomes (By similarity).
The PH domain mediates the binding to phosphatidylinositol-3-phosphate (PtdIns(3)P).
Dephosphorylates 26S nuclear proteasomes, thereby decreasing their proteolytic activity. Recruited to the 19S regulatory particle of the 26S proteasome where it dephosphorylates 19S component psmc2 which impairs psmc2 ATPase activity and disrupts 26S proteasome assembly. Has also been reported to stimulate the proteolytic activity of the 26S proteasome.
The Ubiquitin-like domain mediates interaction with proteasomes.
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.
Phosphorylates D-xylulose to produce D-xylulose 5-phosphate, a molecule that may play an important role in the regulation of glucose metabolism and lipogenesis.
Splice factor that binds to the single-stranded 3'AG at the exon/intron border and promotes its utilization in the second catalytic step. Involved in the regulation of alternative splicing and the utilization of cryptic splice sites.
Transcriptional activator. Activates the gene for selenocysteine tRNA (tRNAsec). Binds to the activator element (AE) motif of the selenocysteine tRNA gene promoter (By similarity).
Belongs to the myelin P0 protein family.
Creation of an extracellular membrane face which guides the wrapping process and ultimately compacts adjacent lamellae.
A disulfide bond locks the enzyme in the closed conformation preventing substrate entry into the catalytic chamber.
Belongs to the peptidase M16 family. PreP subfamily.
Mainly exists in a closed and catalytically competent conformation but a closed-to-open switch allows substrate entry into the catalytic chamber. Substrate binding induces closure and dimerization. A disulfide bond may lock the enzyme in a closed conformation preventing substrate entry into the catalytic chamber, participating in redox regulation of the enzyme. Inhibited by metal-chelating agents. Inhibited by nickel and zinc excess, and slightly activated by manganese.
Metalloendopeptidase of the mitochondrial matrix that functions in peptide cleavage and degradation rather than in protein processing. Has an ATP-independent activity. Specifically cleaves peptides in the range of 5 to 65 residues. Shows a preference for cleavage after small polar residues and before basic residues, but without any positional preference. Degrades the transit peptides of mitochondrial proteins after their cleavage. Also degrades other unstructured peptides.
Monomer and homodimer; homodimerization is induced by binding of the substrate.
Belongs to the immunoglobulin superfamily.
Activated when phosphorylated and inactivated when dephosphorylated.
Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. I-kappa-B kinase subfamily.
Phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. Phosphorylates 'Ser-10' of histone H3 at NF-kappa-B-regulated promoters during inflammatory responses triggered by cytokines.
Element of the TORC1 signaling pathway that acts as a mediator of diverse signals and that represses RNA polymerase III transcription. Inhibits the de novo assembly of TFIIIB onto DNA.
Belongs to the complex I NDUFA10 subunit family.
Complex I is composed of 45 different subunits. This a component of the hydrophobic protein fraction.
Belongs to the small G protein signaling modulator family.
Belongs to the class VI-like SAM-binding methyltransferase superfamily. PEMT/PEM2 methyltransferase family.
Catalyzes the three sequential steps of the methylation pathway for the biosynthesis of phosphatidylcholine, a critical and essential component for membrane structure. Uses S-adenosylmethionine (S-adenosyl-L-methionine, SAM or AdoMet) as the methyl group donor for the methylation of phosphatidylethanolamine (1,2-diacyl-sn-glycero-3-phosphoethanolamine, PE) to phosphatidylmonomethylethanolamine (1,2-diacyl-sn-glycero-3-phospho-N-methylethanolamine, PMME), PMME to phosphatidyldimethylethanolamine (1,2-diacyl-sn-glycero-3-phospho-N,N-dimethylethanolamine, PDME), and PDME to phosphatidylcholine (1,2-diacyl-sn-glycero-3-phosphocholine, PC), producing S-adenosyl-L-homocysteine in each step.
Belongs to the methyltransferase superfamily. METL family.
S-adenosyl-L-methionine-dependent methyltransferase.
Belongs to the peptidase M24A family. Methionine aminopeptidase eukaryotic type 2 subfamily.
Binds EIF2S1 at low magnesium concentrations. Interacts strongly with the eIF-2 gamma-subunit EIF2S3.
Contains approximately 12 O-linked N-acetylglucosamine (GlcNAc) residues. O-glycosylation is required for EIF2S1 binding.
Protects eukaryotic initiation factor EIF2S1 from translation-inhibiting phosphorylation by inhibitory kinases such as EIF2AK2/PKR and EIF2AK1/HCR. Plays a critical role in the regulation of protein synthesis.
Regulator of deubiquitinating complexes, which acts as a strong activator of usp1, usp12 and usp46. Enhances the usp1-mediated deubiquitination of fancd2; usp1 being almost inactive by itself. Activates deubiquitination by increasing the catalytic turnover without increasing the affinity of deubiquitinating enzymes for the substrate. Also activates deubiquitinating activity of complexes containing usp12. Together with rad51ap1, promotes DNA repair by stimulating rad51-mediated homologous recombination. Binds single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA). DNA-binding is required both for usp1-mediated deubiquitination of fancd2 and stimulation of rad51-mediated homologous recombination: both wdr48/uaf1 and rad51ap1 have coordinated role in DNA-binding during these processes. Together with atad5 and by regulating usp1 activity, has a role in pcna-mediated translesion synthesis (TLS) by deubiquitinating monoubiquitinated pcna. Together with atad5, has a role in recruiting rad51 to stalled forks during replication stress.
The WD repeats are required for the interaction with deubiquitinating enzymes USP1, USP12 and USP46.
AP-4 forms a non clathrin-associated coat on vesicles departing the trans-Golgi network (TGN) and may be involved in the targeting of proteins from the trans-Golgi network (TGN) to the endosomal-lysosomal system.
Adaptor protein complex 4 (AP-4) is a heterotetramer composed of two large adaptins, a medium adaptin and a small adaptin.
Belongs to the Mediator complex subunit 26 family.
Component of the U5 snRNP complex that is required for spliceosome assembly and for pre-mRNA splicing.
Involved in epithelial-mesenchymal interactions in kidney and lung morphogenesis that include epithelial differentiation and branching morphogenesis.
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 class-V pyridoxal-phosphate-dependent aminotransferase family. SerC subfamily.
Catalyzes the reversible conversion of 3-phosphohydroxypyruvate to phosphoserine and of 3-hydroxy-2-oxo-4-phosphonooxybutanoate to phosphohydroxythreonine.
Associated component of the mcm complex that acts as a regulator of DNA replication. Binds to the MCM complex during late S phase and promotes the disassembly of the mcm complex from chromatin, thereby acting as a key regulator of pre-replication complex (pre-RC) unloading from replicated DNA. Can dissociate the mcm complex without addition of ATP; probably acts by destabilizing interactions of each individual subunits of the mcm complex. Required for sister chromatid cohesion (By similarity).
Interacts with the mcm complex: associates with the mcm3-7 complex which lacks mcm2, while it does not interact with the mcm complex when mcm2 is present (mcm2-7 complex).
Binding, as a tetramer, through its N-terminal region, with the bZIP domain of creb1 enhances recruitment of taf4 to the promoter. 'Arg-300' in the bZIP domain of creb1 is essential for this interaction (By similarity).
Transcriptional coactivator for creb1 which activates transcription through both consensus and variant cAMP response element (CRE) sites. Acts as a coactivator, in the SIK/TORC signaling pathway, being active when dephosphorylated and acts independently of creb1 'Ser-119' phosphorylation. Enhances the interaction of creb1 with taf4. Regulates the expression of specific CREB-activated genes such as the steroidogenic gene, StAR. Potent coactivator of ppargc1a and inducer of mitochondrial biogenesis in muscle cells (By similarity).
Interleukin-16 stimulates a migratory response in CD4+ lymphocytes, monocytes, and eosinophils. Primes CD4+ T-cells for IL-2 and IL-15 responsiveness. Also induces T-lymphocyte expression of interleukin 2 receptor. Ligand for CD4.
Belongs to the V-ATPase F subunit family.
Belongs to the nucleoporin NSP1/NUP62 family.
Expressed in the embryonic pronephric sinus as well as posterior cardinal veins.
Transcription factor. Binds to the DNA sequence 5'-AACAAT-3'. Acts downstream of vegt and upstream of nodal signaling to promote endodermal and mesodermal differentiation by promoting vegt-induced expression of both endodermal genes (including endodermin) and mesodermal genes (including snai1/snail and snai2/slug). Induces expression of multiple nodal genes (including nodal, nodal2, nodal4, nodal5 and nodal6) and binds directly to sites within the promoter of the nodal5 gene. The endodermal and mesodermal specification pathways then interact to initiate cardiogenesis. Acts partially redundantly with sox18 during cardiogenesis. Also acts as an antagonist of beta-catenin signaling (By similarity). Regulates (possibly indirectly) development of the pronephros, the functional larval kidney.
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 complex I NDUFA8 subunit family.
Inhibits translesion DNA synthesis by preventing monoubiquitination of PCNA, this is necessary to counteract damage due to ultraviolet light-induced replication stress (By similarity). SDE2 is cleaved following PCNA binding, and its complete degradation is necessary to allow S-phase progression following DNA damage (By similarity).
Plays a role in pre-mRNA splicing by facilitating excision of relatively short introns featuring weak 3'-splice sites (ss) and high GC content (By similarity). May recruit CACTIN to the spliceosome (By similarity).
Plays a role in ribosome biogenesis by enabling SNORD3- and SNORD118-dependent cleavage of the 47S rRNA precursor (By similarity). Binds ncRNA (non-coding RNA) including the snoRNAs SNORD3 and SNORD118 (By similarity).
The PIP-box (PCNA interacting peptide) motif mediates both the interaction with PCNA and cleavage of the SDE2 precursor by a deubiquitinating enzyme.
The SAP domain is necessary for specific binding to DNA.
The propeptide displays a ubiquitin-like fold.
Upon binding to PCNA, the N-terminal UBL (ubiquitin-like) propeptide is cleaved at Gly-71 by an unidentified deubiquitinating enzyme; the resulting mature SDE2 is degraded by the DCX(DTL) complex in a cell cycle- and DNA damage dependent manner.
Belongs to the SMC family. SMC3 subfamily.
Central component of cohesin, a complex required for chromosome cohesion during the cell cycle. The cohesin complex may form a large proteinaceous ring within which sister chromatids can be trapped. At anaphase, the complex is cleaved and dissociates from chromatin, allowing sister chromatids to segregate. Cohesion is coupled to DNA replication and is involved in DNA repair. The cohesin complex also plays an important role in spindle pole assembly during mitosis and in chromosomes movement.
DNA-binding transcription regulator that regulates endothelial cell proliferation and G1/S cell-cycle progression. Specifically binds the 5'-[AT]NTNN[GT]GGCA[AGT]-3' core DNA sequence and acts by modulating expression of pRB-E2F cell-cycle target genes (By similarity).
Acts as a translational repressor. Can mediate repression affecting different steps in the translation process: cap-driven, IRES-driven, polyadenylated RNAs or nonpolyadenylated RNAs. Essential for the development of primordial germ cells (PGCs) by ensuring their proper migration and survival (By similarity).
The Nanos-type zinc finger is composed of two C2HC motifs, each motif binding one molecule of zinc. It is essential for the translation repression activity of the protein.
Binds and promotes bundling of vimentin filaments originating from the Golgi.
Folate-dependent enzyme, that displays both transferase and deaminase activity. Serves to channel one-carbon units from formiminoglutamate to the folate pool.
Homooctamer, including four polyglutamate binding sites. The subunits are arranged as a tetramer of dimers, and form a planar ring-shaped structure.
In the C-terminal section; belongs to the cyclodeaminase/cyclohydrolase family.
In the N-terminal section; belongs to the formiminotransferase family.
Endoplasmic reticulum transmembrane protein involved in vesicle-mediated transport, which is required for neutrophil function.
Protein with a unique structure having two opposing regulatory activities toward small GTP-binding proteins. The C-terminus is a GTPase-activating protein domain which stimulates GTP hydrolysis by RAC1, RAC2 and CDC42. Accelerates the intrinsic rate of GTP hydrolysis of RAC1 or CDC42, leading to down-regulation of the active GTP-bound form. The central Dbl homology (DH) domain functions as guanine nucleotide exchange factor (GEF) that modulates the GTPases CDC42, RHOA and RAC1. Promotes the conversion of CDC42, RHOA and RAC1 from the GDP-bound to the GTP-bound form.
The central Dbl homology (DH) domain functions as guanine nucleotide exchange factor (GEF) that modulates the GTPases CDC42, RHOA and RAC1. Promotes the conversion of CDC42, RHOA and RAC1 from the GDP-bound to the GTP-bound form. The C-terminus is a Rho-GAP domain which stimulates GTP hydrolysis by RAC1, RAC2 and CDC42. The protein has a unique structure having two opposing regulatory activities toward small GTP-binding proteins.
Belongs to the TMEM97/sigma-2 receptor family.
Intracellular orphan receptor that binds numerous drugs and which is highly expressed in various proliferating cells. Corresponds to the sigma-2 receptor, which is thought to play important role in regulating cell survival, morphology and differentiation. May play a role as a regulator of cellular cholesterol homeostasis. May function as sterol isomerase. May alter the activity of some cytochrome P450 proteins.
Sigma receptors are classified into two subtypes (Sigma-1 and Sigma-2) based on their different pharmacological profile. Sigma-2 receptors are identified by radioligand-binding studies as a binding site with high affinity for di-o-tolylguanidine (DTG) and haloperidol.
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).
Hydrolyzes deoxynucleoside triphosphates (dNTPs) to the corresponding nucleoside monophosphates. Has a strong preference for dCTP and its analogs including 5-iodo-dCTP and 5-methyl-dCTP for which it may even have a higher efficiency. May protect DNA or RNA against the incorporation of these genotoxic nucleotide analogs through their catabolism.
Belongs to the GST superfamily. Zeta family.
Belongs to the Mediator complex subunit 16 family.
Belongs to the nucleoporin Nup133 family.
RNA-binding protein that binds to AU-rich sequences (AREs) of target mRNAs. May also bind poly-A tracts via RRM 3. May be involved in neuronal differentiation and maintenance (By similarity).
RRM 1 and RRM 2 bind cooperatively to AU-rich sequences in target mRNAs. RRM 3 binds to poly-A mRNA sequences (By similarity).
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 protein-tyrosine phosphatase family. Receptor class 5 subfamily.
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.
Regulatory subunit of the dolichol-phosphate mannose (DPM) synthase complex; essential for the ER localization.
Component of the CPC at least composed of survivin/birc5, incenp, cdca8/borealin and/or cdca9/dasra-A, and aurkb/aurora-B Interacts with incenp (via N-terminus).
Plays an important role in the control of DNA replication and the maintenance of replication fork stability.
Divalent metal cations. Mg(2+) confers the highest activity.
Nicotinamide/nicotinate-nucleotide adenylyltransferase that acts as an axon maintenance factor. Axon survival factor required for the maintenance of healthy axons: acts by delaying Wallerian axon degeneration, an evolutionarily conserved process that drives the loss of damaged axons. Catalyzes the formation of NAD(+) from nicotinamide mononucleotide (NMN) and ATP. Can also use the deamidated form; nicotinic acid mononucleotide (NaMN) as substrate but with a lower efficiency. Also catalyzes the reverse reaction, i.e. the pyrophosphorolytic cleavage of NAD(+). For the pyrophosphorolytic activity prefers NAD(+), NADH and NaAD as substrates and degrades nicotinic acid adenine dinucleotide phosphate (NHD) less effectively. Also acts as an activator of ADP-ribosylation by supporting the catalytic activity of PARP16 and promoting mono-ADP-ribosylation of ribosomes by PARP16.
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.
Belongs to the cyclin family. Cyclin-like FAM58 subfamily.
Associates with the pre-60S ribosomal particle.
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 AB hydrolase superfamily. Epoxide hydrolase family.
Catalyzes the hydrolysis of epoxide-containing fatty acids. Active in vitro against epoxyeicosatrienoic acids (EETs) including 8,9-EET, 9,10-EET, 11,12-EET and 14,15-EET and leukotoxin.
Inhibited by 1-(1-acetylpiperidin-4-yl)-3-(4-(trifl uoromethoxy)phenyl)urea (TPAU), 1-cyclohexyl-3-dodecylurea (CDU), 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA), 1-((3S, 5S, 7S)-adamantan-1-yl)-3-(5-(2-(2-ethoxyethoxy) ethoxy)pentyl)urea (AEPU) and to a lesser extent by 8-(3-((3S, 5S, 7S)-adamantan-1-yl)ureido) octanoic acid (AUOA).
Belongs to the dynactin subunits 5/6 family. Dynactin subunit 6 subfamily.
Member of the pointed-end complex of the dynactin shoulder complex which contains dctn4, dctn5 and dctn6 subunits and Actr10. Within the complex dctn6 forms a heterodimer with dctn5. Interacts with plk1 (By similarity).
Part of the dynactin complex that activates the molecular motor dynein for ultra-processive transport along microtubules.
Belongs to the class V-like SAM-binding methyltransferase superfamily. SETD3 actin-histidine methyltransferase family.
Protein-histidine N-methyltransferase that specifically mediates 3-methylhistidine (tele-methylhistidine) methylation of actin at 'His-73'. Does not have protein-lysine N-methyltransferase activity and probably only catalyzes histidine methylation of actin.
The SET domain specifically recognizes and binds actin, suggesting that it does not accommodate substrates diverging from actin.
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.
Binds 2 [4Fe-4S] clusters. 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.
Atypical E3 ubiquitin-protein ligase which ubiquitinates TLR2 at 'Lys-754' leading to its degradation by the proteasome. Inhibitor of protein phosphatase 1.
Belongs to the class I-like SAM-binding methyltransferase superfamily. Trm1 family.
Component of the DRB sensitivity-inducing factor complex (DSIF complex), which regulates transcription elongation by RNA polymerase II.
Belongs to the ELO family. ELOVL2 subfamily.
Catalyzes the first and rate-limiting reaction of the four reactions that constitute the long-chain fatty acids elongation cycle. This endoplasmic reticulum-bound enzymatic process allows the addition of 2 carbons to the chain of long- and very long-chain fatty acids (VLCFAs) per cycle. Acts specifically toward polyunsaturated acyl-CoA with the higher activity toward C20:4(n-6) acyl-CoA. Condensing enzyme that catalyzes the synthesis of polyunsaturated very long chain fatty acid (C20- and C22-PUFA). May participate to the production of polyunsaturated VLCFAs of different chain lengths that are involved in multiple biological processes as precursors of membrane lipids and lipid mediators.
Catalyzes the addition of sialic acid in alpha 2,8-linkage to the sialic acid moiety of the ganglioside GM3 to form ganglioside GD3; gangliosides are a subfamily of complex glycosphinglolipds that contain one or more residues of sialic acid (By similarity). Glycosphingolipids are required for convergence extension movements during early development (By similarity). Can catalyze the addition of a second alpha-2,8- sialic acid to GD3 to form GT3 (By similarity). Can use GM1b, GD1a and GT1b as acceptor substrates to synthesize GD1c, GT1a and GQ1b respectively (By similarity).
Belongs to the zona pellucida-binding protein Sp38 family.
Exhibits trypsin-like activity as defined by cleavage of synthetic substrates with Arg or Lys as the P1 site.
Belongs to the mitochondrion-specific ribosomal protein mS29 family.
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.
Belongs to the class I-like SAM-binding methyltransferase superfamily. RNA M5U methyltransferase family.
Belongs to the NUP186/NUP192/NUP205 family.
Belongs to the complex I NDUFS4 subunit family.
Regulatory subunit for cdc7 which activates its kinase activity thereby playing a central role in DNA replication and cell proliferation. Not required during the initiation of DNA replication in egg and during early embryonic development but is required later throughout development. The complex cdc7-dbf4a phosphorylates mcm2 subunit (By similarity).
Interacts with PIH1D1; the interaction associates DNAAF10 with the R2TP complex (By similarity). Interacts with several dynein axonemal assembly factors (By similarity).
Key assembly factor specifically required for the stability of axonemal dynein heavy chains in cytoplasm.
Peroxisomal protease that mediates both the removal of the leader peptide from proteins containing a PTS2 target sequence and processes several PTS1-containing proteins. Catalyzes the processing of PTS1-proteins involved in the peroxisomal beta-oxidation of fatty acids.
The full-lengh TYSND1 is the active the proteolytic processing of PTS1- and PTS2-proteins and in self-cleavage, and intermolecular self-cleavage of TYSND1 down-regulates its protease activity.
May play a role in protection against oxidative stress.
Required for initiation of chromosomal DNA replication. Core component of CDC45-MCM-GINS (CMG) helicase, the molecular machine that unwinds template DNA during replication, and around which the replisome is built.
Component of the PEX13-PEX14 docking complex, a translocon channel that specifically mediates the import of peroxisomal cargo proteins bound to PEX5 receptor. The PEX13-PEX14 docking complex forms a large import pore which can be opened to a diameter of about 9 nm. Mechanistically, PEX5 receptor along with cargo proteins associates with the PEX14 subunit of the PEX13-PEX14 docking complex in the cytosol, leading to the insertion of the receptor into the organelle membrane with the concomitant translocation of the cargo into the peroxisome matrix.
Binds target DNA that contains at least one unmethylated cytosine via the CXXC-type zinc-finger domain.
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. Conversion of 5mC into 5hmC probably constitutes the first step in cytosine demethylation. Selectively binds to the promoter region of target genes and contributes to regulate the expression of numerous developmental genes, including pax6, rax, sox9 and six3. May also contribute to the regulation of target genes in ways that do not require its enzyme activity.
Catalyzes uridine to pseudouridine isomerization (pseudouridylation) of different mitochondrial RNA substrates. Acts on position 1397 in 16S mitochondrial ribosomal RNA (16S mt-rRNA). This modification is required for the assembly of 16S mt-rRNA into a functional mitochondrial ribosome. Acts on position 39 in mitochondrial tRNA(Phe). Also catalyzes pseudouridylation of mRNAs in nucleus: acts as a regulator of pre-mRNA splicing by mediating pseudouridylation of pre-mRNAs at locations associated with alternatively spliced regions. Pseudouridylation of pre-mRNAs near splice sites directly regulates mRNA splicing and mRNA 3'-end processing.
Homodimer or heterodimer (Potential). But, in contrast to other members of this family, cannot be disulfide-linked.
Possible role in regulating endocytosis of the transferrin receptor at the plasma membrane. Alternatively, may function as a negative regulator of the amino acid-induced TOR signaling by inhibiting the formation of active Rag GTPase complexes. Preferentially binds inactive Rag GTPase complexes and prevents their interaction with the mTORC1 complex inhibiting its relocalization to lysosomes and its activation. Thereby, may indirectly regulate cell growth, proliferation and autophagy (By similarity).
The SH3 domain mediates localization to the clathrin-coated pits and vesicles.
Has probably no intrinsic transporter activity but together with SLC30A5 forms a functional zinc ion:proton antiporter heterodimer, mediating zinc entry into the lumen of organelles along the secretory pathway. As part of that zinc ion:proton antiporter, contributes to zinc ion homeostasis within the early secretory pathway and regulates the activation and folding of enzymes like alkaline phosphatases and enzymes involved in phosphatidylinositol glycan anchor biosynthesis.
Heterodimer with SLC30A5; form a functional zinc ion transmembrane transporter.
Hydrophilic histidine residues that participate to zinc binding in transporters of the family are not conserved in SLC30A6.
Belongs to the WD repeat RBAP46/RBAP48/MSI1 family.
Binds directly to helix 1 of the histone fold of histone H4, a region that is not accessible when H4 is in chromatin.
Core histone-binding subunit that may target chromatin remodeling factors, histone acetyltransferases and histone deacetylases to their histone substrates in a manner that is regulated by nucleosomal DNA. Component of several complexes which regulate chromatin metabolism.
Belongs to the Gfo/Idh/MocA family. Biliverdin reductase subfamily.
Reduces the gamma-methene bridge of the open tetrapyrrole, biliverdin IX alpha, to bilirubin with the concomitant oxidation of a NADH or NADPH cofactor.
Mediator of sterol homeostasis involved in sterol uptake, trafficking and distribution into membranes.
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 mitochondrion-specific ribosomal protein mL40 family.
Component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes (By similarity). The CSN complex is an essential regulator of the ubiquitin (Ubl) conjugation pathway by mediating the deneddylation of the cullin subunits of E3 ligase complexes, leading to modify the Ubl ligase activity (By similarity).
The glycine cleavage system catalyzes the degradation of glycine.
Component of the nuclear pore complex (NPC), which plays a key role in de novo assembly and insertion of NPC in the nuclear envelope. Required for NPC and nuclear envelope assembly, possibly by forming a link between the nuclear envelope membrane and soluble nucleoporins, thereby anchoring the NPC in the membrane.
Involved in early neuronal development; required for cell cycle exit and differentiation of primary neurons (By similarity). Cooperates synergistically with pak3 to promote primary neural differentiation within the neural plate (By similarity). May play a role in promoting megakaryocyte differentiation (By similarity).
May function in lipid transport from the endoplasmic reticulum and be involved in a wide array of cellular functions probably through regulation of the biogenesis of lipid microdomains at the plasma membrane. May regulate calcium efflux at the endoplasmic reticulum (By similarity).
Sigma receptors are classified into two subtypes (Sigma-1 and Sigma-2) based on their different pharmacological profile.
The C-terminal helices form a flat, hydrophobic surface that is probably tightly associated with the cytosolic surface of the endoplasmic reticulum membrane.
Belongs to the eukaryotic ribosomal protein eL21 family.
Mitochondrial S-adenosyl-L-methionine/S-adenosyl-L-homocysteine antiporter. Mediates the exchange of cytosolic S-adenosyl-L-methionine, the predominant methyl-group donor for macromolecule methylation processes, for mitochondrial S-adenosylhomocysteine(SAH), a by-product of methylation reactions.
Filament-forming cytoskeletal GTPase. Required for normal organization of the actin cytoskeleton. Plays a role in the biogenesis of polarized columnar-shaped epithelium. Required for the progression through mitosis through regulation of chromosome congression. During anaphase, may be required for chromosome segregation and spindle elongation. Plays a role in ciliogenesis and collective cell movements including convergent extension during gastrulation. In cilia, required for the integrity of the diffusion barrier at the base of the primary cilium that prevents diffusion of transmembrane proteins between the cilia and plasma membranes. Controls cell shape and not polarization of cells during convergent extension (By similarity).
Septins polymerize into heterooligomeric protein complexes that form filaments, and associate with cellular membranes, actin filaments and microtubules. GTPase activity is required for filament formation. Can form heterooligomers with other family members and form filaments. Interacts with wdpcp (By similarity).
Dynein-attachment factor required for cilia motility.
Catalyzes the ATP-dependent ligation of cysteine to tRNA(Cys).
Belongs to the mitochondrion-specific ribosomal protein mL53 family.
Interacts with clip1, mis12, ndc80 and zwint. Interacts with gamma-tubulin (By similarity).
Required for spindle microtubule attachment to both kinetochores and centrosomes. Also functions to tether minus-ends of spindle microtubules to centrosomes. May act by forming ring-like structures around microtubules, or by serving as a cross-linker or scaffold at the attachment site (By similarity).
Belongs to the Mediator complex subunit 17 family.
Belongs to the Integrator subunit 2 family.
Binds 1 5,10-methenyltetrahydrofolate (MTHF) per subunit.
The RNA gate region regulates mRNA cap recognition to prevent promiscuous mRNA-binding before assembly of eif3d into the full eukaryotic translation initiation factor 3 (eIF-3) complex.
mRNA cap-binding component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is involved in protein synthesis of a specialized repertoire of mRNAs and, together with other initiation factors, stimulates binding of mRNA and methionyl-tRNAi to the 40S ribosome. The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation. In the eIF-3 complex, eif3d specifically recognizes and binds the 7-methylguanosine cap of a subset of mRNAs.
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.
Belongs to the chloride channel (TC 2.A.49) family. ClC-5/CLCN5 subfamily.
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.
Serine hydrolase involved in the detoxification of formaldehyde.
Belongs to the eukaryotic ribosomal protein eL36 family.
Expressed in developing embryos and adults.
In tailbud embryos, expressed in embryonic muscle (myotomes). In adults, expressed in adult limb muscle.
Monomethylation at Lys-86 (K86me1) regulates actin-myosin interaction and actomyosin-dependent processes. Demethylation by ALKBH4 is required for maintaining actomyosin dynamics supporting normal cleavage furrow ingression during cytokinesis and cell migration.
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.
Homopentamer. Forms a complex with GCH1 where a GCH1 homodecamer is sandwiched by two GFRP homopentamers (By similarity).
Mediates tetrahydrobiopterin inhibition of GTP cyclohydrolase 1.
Histone methyltransferase involved in left-right axis specification in early development and mitosis. Specifically trimethylates 'Lys-9' of histone H3 (H3K9me3). H3K9me3 represents a specific tag for epigenetic transcriptional repression by recruiting HP1 (CBX1, CBX3 and/or CBX5) proteins to methylated histones. Contributes to H3K9me3 in both the interspersed repetitive elements and centromere-associated repeats. Plays a role in chromosome condensation and segregation during mitosis (By similarity).
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.
Component of the 60-80S U3 small nucleolar ribonucleoprotein (U3 snoRNP). Required for the early cleavages during pre-18S ribosomal RNA processing.
Involved in the histone deacetylase (HDAC1)-dependent transcriptional repression activity.
Component of the Golgi-associated retrograde protein (GARP) complex Component of the endosome-associated retrograde protein (EARP) complex.
Involved in retrograde transport from early and late endosomes to the late Golgi. The GARP complex is required for the maintenance of protein retrieval from endosomes to the TGN, acid hydrolase sorting, lysosome function, endosomal cholesterol traffic and autophagy. Acts as component of the EARP complex that is involved in endocytic recycling.
Functions in endoplasmic reticulum to Golgi vesicle-mediated transport and regulates the proper organization of the endoplasmic reticulum and the Golgi (By similarity). Plays a key role in targeting to neuronal dendrites receptors such as HTR1A (By similarity). Plays also a role in primary cilium and sperm flagellum assembly probably through protein transport to these compartments (By similarity).
Belongs to the TtcA family. CTU1/NCS6/ATPBD3 subfamily.
Plays a central role in 2-thiolation of mcm(5)S(2)U at tRNA wobble positions of tRNA(Lys), tRNA(Glu) and tRNA(Gln). Directly binds tRNAs and probably acts by catalyzing adenylation of tRNAs, an intermediate required for 2-thiolation. It is unclear whether it acts as a sulfurtransferase that transfers sulfur from thiocarboxylated urm1 onto the uridine of tRNAs at wobble position.
Belongs to the Odd C2H2-type zinc-finger protein family.
Embryos show a down-regulation of early pronephric markers lhx1/lim1 and pax8, and disruption of pronephric development.
Transcriptional repressor (By similarity). Required for pronephric kidney development.
Plays a central role during spermatogenesis by repressing transposable elements and preventing their mobilization, which is essential for the germline integrity. Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and governs the methylation and subsequent repression of transposons. Its association with piP-bodies suggests a participation in the secondary piRNAs metabolic process. Required for the localization of germ-cell factors to the meiotic nuage (By similarity).
Interacts with AP5Z1, AP5B1, AP5S1 and SPG11. Interacts with TTC19 and KIF13A.
Phosphatidylinositol 3-phosphate-binding protein required for the abcission step in cytokinesis: recruited to the midbody during cytokinesis and acts as a regulator of abcission. May also be required for efficient homologous recombination DNA double-strand break repair.
Belongs to the proteasome subunit S5B/HSM3 family.
RNA-binding protein that regulates alternative splicing events by binding to 5'-UGCAUGU-3' elements. Regulates alternative splicing of tissue-specific exons (By similarity).
Belongs to the glucosamine/galactosamine-6-phosphate isomerase family.
Plays a role as an effector of the ADP-ribosylation factor-like protein 2, ARL2.
Converted into plasmin by plasminogen activators, both plasminogen and its activator being bound to fibrin.
Plasmin dissolves the fibrin of blood clots and acts as a proteolytic factor in a variety of other processes including embryonic development, tissue remodeling, tumor invasion, and inflammation. In ovulation, weakens the walls of the Graafian follicle. It activates the urokinase-type plasminogen activator, collagenases and several complement zymogens, such as C1 and C5. Cleavage of fibronectin and laminin leads to cell detachment and apoptosis. Also cleaves fibrin, thrombospondin and von Willebrand factor. Its role in tissue remodeling and tumor invasion may be modulated by CSPG4. Binds to cells.
7-dehydrocholesterol reductase of the cholesterol biosynthetic pathway reducing the C7-C8 double bond of cholesta-5,7-dien-3beta-ol (7-dehydrocholesterol/7-DHC) and cholesta-5,7,24-trien-3beta-ol, two intermediates in that pathway.
Required for cis-Golgi integrity and efficient ER to Golgi transport.
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). Subunit C is necessary for the assembly of the catalytic sector of the enzyme and is likely to have a specific function in its catalytic activity (By similarity).
Belongs to the Integrator subunit 12 family.
Belongs to the multiprotein complex Integrator.
Component of the Integrator complex, a complex involved in the small nuclear RNAs (snRNA) U1 and U2 transcription and in their 3'-box-dependent processing.
Belongs to the TFIID complex together with the TBP-associated factors (TAFs). Binds DNA as monomer.
General transcription factor that functions at the core of the DNA-binding multiprotein factor TFIID. Binding of TFIID to the TATA box is the initial transcriptional step of the pre-initiation complex (PIC), playing a role in the activation of eukaryotic genes transcribed by RNA polymerase II. Members of the TBP family are differentially required to regulate transcription and development during early embryogenesis (By similarity). Binds to the promoters of select genes.
The N-terminal domain is extensively phosphorylated.
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).
Acts in a planar cell polarity (PCP) complex; polarization along the apical/basal axis of epithelial cells. Regulates the polarized assembly of fibronectrin on the surface of the mesoderm during gastrulation. Essential for gastrulation cell movements, cooperating with dvl2/dsh to activate jnk. Acts together with tes to control axial elongation (By similarity).
Tethers the endoplasmic reticulum to the cell membrane and promotes the formation of appositions between the endoplasmic reticulum and the cell membrane. Binds glycerophospholipids in a barrel-like domain and may play a role in cellular lipid transport (By similarity).
The SMP-LTD domain is a barrel-like domain that binds glycerophospholipids in its interior (By similarity).
Belongs to the tryptophan 2,3-dioxygenase family.
Heme-dependent dioxygenase that catalyzes the oxidative cleavage of the L-tryptophan (L-Trp) pyrrole ring and converts L-tryptophan to N-formyl-L-kynurenine. Catalyzes the oxidative cleavage of the indole moiety.
Tubulin-binding protein that acts as a negative regulator of Notch signaling pathway. Shuttles between the cytoplasm and the nucleus and mediates the nuclear export of RBPJ/RBPSUH, thereby preventing the interaction between RBPJ/RBPSUH and NICD product of Notch proteins (Notch intracellular domain), leading to down-regulate Notch-mediated transcription. May play a role in neurogenesis.
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.
Part of the 43S pre-initiation complex (PIC).
Required for proper chromosome biorientation through the detection or correction of syntelic attachments in mitotic spindles.
Belongs to the glycosyltransferase 14 family. XylT subfamily.
Heterodimer of a B chain and an A chain linked by two disulfide bonds.
Insulin decreases blood glucose concentration. It increases cell permeability to monosaccharides, amino acids and fatty acids. It accelerates glycolysis, the pentose phosphate cycle, and glycogen synthesis in liver.
Belongs to the CRF-binding protein family.
Binds CRF and inactivates it. May prevent inappropriate pituitary-adrenal stimulation in pregnancy.
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 eRF1-eRF3-GTP ternary complex, composed of ETF1/ERF1 and eRF3 (GSPT1/ERF3A or GSPT2/ERF3B) and GTP.
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.
Negative regulator of the mitochondrial respiratory chain (By similarity). Plays a role in the translocation of proteins across the mitochondrial inner membrane (By similarity). Involved in pronephric kidney development at the early tadpole stage.
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.
Required for mannose-6-phosphate-dependent trafficking of lysosomal enzymes. LYSET bridges GlcNAc-1-phosphate transferase (GNPTAB), to the membrane-bound transcription factor site-1 protease (MBTPS1), thus allowing proteolytic activation of the GNPTAB. GNPTAB is involved in the regulation of M6P-dependent Golgi-to-lysosome trafficking of lysosomal enzymes. LYSET is thus an essential factor for maturation and delivery of lysosomal hydrolases.
Belongs to the 'GDSL' lipolytic enzyme family. IAH1 subfamily.
Acts as a glycogen-targeting subunit for phosphatase PP1. Facilitates interaction of the PP1 with enzymes of the glycogen metabolism and regulates its activity. Suppresses the rate at which PP1 dephosphorylates (inactivates) glycogen phosphorylase and enhances the rate at which it activates glycogen synthase and therefore limits glycogen breakdown (By similarity).
Interacts with glycogen, PPP1CC catalytic subunit of PP1 and PYGL. Associates with glycogen particles. Forms complexes with debranching enzyme, glycogen phosphorylase, glycogen synthase and phosphorylase kinase which is necessary for its regulation of PP1 activity (By similarity).
Interacts with glycogen, PPP1CC catalytic subunit of PP1 and PYGL. Associates with glycogen particles. Forms complexes with debranching enzyme, glycogen phosphorylase, glycogen synthase and phosphorylase kinase which is necessary for its regulation of PP1 activity.
LIF has the capacity to induce terminal differentiation in leukemic cells. Its activities include the induction of hematopoietic differentiation in normal and myeloid leukemia cells, the induction of neuronal cell differentiation, and the stimulation of acute-phase protein synthesis in hepatocytes.
Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4), and some other non-histone substrates. Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Participates in the BCL6 transcriptional repressor activity by deacetylating the H3 'Lys-27' (H3K27) on enhancer elements, antagonizing EP300 acetyltransferase activity and repressing proximal gene expression. Also functions as deacetylase for non-histone targets. In addition to protein deacetylase activity, also acts as protein-lysine deacylase by recognizing other acyl groups: catalyzes removal of (2E)-butenoyl (crotonyl) and 2-hydroxyisobutanoyl (2-hydroxyisobutyryl) acyl groups from lysine residues, leading to protein decrotonylation and de-2-hydroxyisobutyrylation, respectively.
Belongs to the neutral ceramidase family.
Acylated. Acylation may be a prerequisite for conversion of the monomeric 37 kDa laminin receptor precursor (37LRP) to the mature dimeric 67 kDa laminin receptor (67LR), and may provide a mechanism for membrane association.
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.
Required for the assembly and/or stability of the 40S ribosomal subunit. Required for the processing of the 20S rRNA-precursor to mature 18S rRNA in a late step of the maturation of 40S ribosomal subunits. Also functions as a cell surface receptor for laminin. Plays a role in cell adhesion to the basement membrane and in the consequent activation of signaling transduction pathways. May play a role in cell fate determination and tissue morphogenesis.
This protein appears to have acquired a second function as a laminin receptor specifically in the vertebrate lineage.
Belongs to the eukaryotic RPC3/POLR3C RNA polymerase subunit family.
DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Specific core component of RNA polymerase III which synthesizes small RNAs, such as 5S rRNA and tRNAs.
Heterodimers with gpn1 or gpn3. Binds to RNA polymerase II (RNAPII).
Small GTPase required for proper localization of RNA polymerase II and III (RNAPII and RNAPIII). May act at an RNAP assembly step prior to nuclear import.
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.
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. Negatively control the initiation of oocyte maturation (By similarity).
Might be involved in growth regulation, and in myelinization in the peripheral nervous system.
Required for recruitment of CENPA to centromeres and normal chromosome segregation during mitosis.
Belongs to the mitochondrial carrier (TC 2.A.29) family. SLC25A38 subfamily.
May play a role as pro-apoptotic protein that induces caspase-dependent apoptosis.
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 mitochondrial matrix. Required during erythropoiesis.
Essential for the assembly of the distal half of centrioles, required for centriole elongation.
Interacts with homodimeric PDGFA, PDGFB and PDGFC, and with heterodimers formed by PDGFA and PDGFB. Monomer in the absence of bound ligand.
Present in an inactive conformation in the absence of bound ligand. Binding of PDGFA and/or PDGFB leads to dimerization and activation by autophosphorylation on tyrosine residues.
Tyrosine-protein kinase that acts as a cell-surface receptor for PDGFA, PDGFB and PDGFC and plays an essential role in the regulation of embryonic development, cell proliferation, survival and chemotaxis. Depending on the context, promotes or inhibits cell proliferation and cell migration. Plays an important role in the differentiation of bone marrow-derived mesenchymal stem cells. Required for normal skeleton development.
ATPase activity is inhibited or reduced by lowering pH from 9.0 to 7.0, and by addition of Ca(2+), EDTA, KNO(3) or by treatment with N-ethylmaleimide (NEM).
Homohexamer. Forms a ring-shaped particle of 12.5 nm diameter, that displays 6-fold radial symmetry. Interacts with the FACT/DUF complex, which includes subunits ssrp1/duf87 and supt16h/duf140 (By similarity).
Necessary for the fragmentation of Golgi stacks during mitosis and for their reassembly after mitosis. Involved in the formation of the nuclear envelope, and of the transitional endoplasmic reticulum (tER). The transfer of membranes from the endoplasmic reticulum to the Golgi apparatus occurs via 50-70 nm transition vesicles which derive from part-rough, part-smooth transitional elements of the endoplasmic reticulum (tER). Vesicle budding from the tER is an ATP-dependent process. Involved in endoplasmic reticulum stress-induced pre-emptive quality control, a mechanism that selectively attenuates the translocation of newly synthesized proteins into the endoplasmic reticulum and reroutes them to the cytosol for proteasomal degradation. Involved in clearance process by mediating G3BP1 extraction from stress granules (By similarity). Also involved in DNA damage response: recruited to double-strand breaks (DSBs) sites and promotes the recruitment of tp53bp1 at DNA damage sites (By similarity). Together with sprtn metalloprotease, involved in the repair of covalent DNA-protein cross-links (DPCs) during DNA synthesis (By similarity). Involved in interstrand cross-link repair in response to replication stress by mediating unloading of the ubiquitinated CMG helicase complex (By similarity). Enhances cell cycle progression and inhibits apoptosis at low temperatures (By similarity). Essential for the maturation of ubiquitin-containing autophagosomes and the clearance of ubiquitinated protein by autophagy (By similarity). Acts as a negative regulator of type I interferon production by promoting ubiquitination of rigi (By similarity). May play a role in the ubiquitin-dependent sorting of membrane proteins to lysosomes where they undergo degradation (By similarity). May more particularly play a role in caveolins sorting in cells (By similarity). By controlling the steady-state expression of the IGF1R receptor, indirectly regulates the insulin-like growth factor receptor signaling pathway (By similarity).
Belongs to the FIT family. FIT2 subfamily.
Fatty acyl-coenzyme A (CoA) diphosphatase that hydrolyzes fatty acyl-CoA to yield acyl-4'-phosphopantetheine and adenosine 3',5'-bisphosphate (By similarity). Preferentially hydrolyzes unsaturated long-chain acyl-CoA substrates in the endoplasmic reticulum (ER) lumen (By similarity). This catalytic activity is required for maintaining ER structure and for lipid droplets (LDs) biogenesis, which are lipid storage organelles involved in maintaining lipid and energy homeostasis (By similarity). May directly bind to diacylglycerol (DAGs) and triacylglycerol, which is also important for LD biogenesis (By similarity). May support directional budding of nacent LDs from the ER into the cytosol by reducing DAG levels at sites of LD formation (By similarity). May play a role in the regulation of cell morphology, ER morphology and cytoskeletal organization (By similarity).
Has a pivotal role in cytoprotective cellular mechanisms triggered by oxygen deprivation. May play a role as a molecular chaperone and participate in protein folding.
Belongs to the class-II aminoacyl-tRNA synthetase family. Type 2 subfamily.
Catalyzes the specific attachment of an amino acid to its cognate tRNA in a 2 step reaction: the amino acid (AA) is first activated by ATP to form AA-AMP and then transferred to the acceptor end of the tRNA.
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.
Regulates insulin-mediated adipose tissue glucose uptake and transport by modulation of SLC2A4 recycling.
Aberrant left-right patterning resulting in abnormal cardiac loops, including leftward and symmetric/midline loops.
Polypeptide N-acetylgalactosaminyltransferase that catalyzes the initiation of protein O-linked glycosylation and is involved in left/right asymmetry by mediating O-glycosylation of NOTCH1. O-glycosylation of NOTCH1 promotes activation of NOTCH1, modulating the balance between motile and immotile (sensory) cilia at the left-right organiser (LRO). Polypeptide N-acetylgalactosaminyltransferases catalyze the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor.
The ricin B-type lectin domain binds to GalNAc and contributes to the glycopeptide specificity.
There are two conserved domains in the glycosyltransferase region: the N-terminal domain (domain A, also called GT1 motif), which is probably involved in manganese coordination and substrate binding and the C-terminal domain (domain B, also called Gal/GalNAc-T motif), which is probably involved in catalytic reaction and UDP-Gal binding.
Transcription factor playing important roles in primary neurulation and in the differentiation of stratified epithelia of both ectodermal and endodermal origin. Binds directly to the consensus DNA sequence 5'-AACCGGTT-3' acting as an activator and repressor on distinct target genes.
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 NAD(P)-dependent epimerase/dehydratase family. Fucose synthase subfamily.
Catalyzes the two-step NADP-dependent conversion of GDP-4-dehydro-6-deoxy-D-mannose to GDP-fucose, involving an epimerase and a reductase reaction.
Catalyzes both phosphatidylcholine and phosphatidylethanolamine biosynthesis from CDP-choline and CDP-ethanolamine, respectively. Involved in protein-dependent process of phospholipid transport to distribute phosphatidyl choline to the lumenal surface. Has a higher cholinephosphotransferase activity than ethanolaminephosphotransferase activity.
Belongs to the protein kinase superfamily. Tyr protein kinase family. AXL/UFO subfamily.
May be involved in cell adhesion processes, particularly in the central nervous system.
Tyrosine phosphorylated upon receptor stimulation.
Belongs to the acyl carrier protein (ACP) family.
Carrier of the growing fatty acid chain in fatty acid biosynthesis.
Belongs to the thymidine/pyrimidine-nucleoside phosphorylase family.
Catalyzes the reversible phosphorolysis of thymidine. The produced molecules are then utilized as carbon and energy sources or in the rescue of pyrimidine bases for nucleotide synthesis.
Involved in the early part of the secretory pathway.
Expressed constantly during oogenesis from the previtellogenic (stage I) oocyte to the mature (stage VI) oocyte, and after fertilization until the early tadpole stage.
Germ-line specific; expressed in adult testis and ovary. Localized specifically to the oocyte and embryonic germ plasm and to migrating primordial germ cells (PGCs).
Interacts with the C-terminus of pabp1 and with epabp. Prior to oocyte maturation, found in a complex with epabp and pum2 proteins and spdy1 mRNA; pum2 dissociates from the complex during maturation (By similarity).
RNA-binding protein that is required for primordial germ cell (PGC) differentiation and indirectly necessary for the migration of PGCs through the endoderm. May promote meiotic cell division during spermatogenesis. Shows a preference for G- and U-rich RNAs and probably binds the 3'-UTR of target mRNAs. Stimulates the initiation of translation of mRNAs through the recruitment of poly(A)-binding proteins (PABPs) (By similarity).
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.
Core component of the DBIRD complex, a multiprotein complex that acts at the interface between core mRNP particles and RNA polymerase II (RNAPII) and integrates transcript elongation with the regulation of alternative splicing.
Belongs to the calcineurin regulatory subunit family. CHP subfamily.
Binds calcium via its EF-hands. Calcium-binding mediates a conformational change. Can also bind magnesium (By similarity).
Functions as an integral cofactor in cell pH regulation by controlling plasma membrane-type Na(+)/H(+) exchange activity. Promotes the induction of hematopoietic stem cell differentiation toward megakaryocytic lineage. Essential for the coupling of ERK cascade activation with the expression of ETS family genes in megakaryocytic differentiation. Also involved in granulocytic differentiation in a ERK-dependent manner. Inhibits the phosphatase activity of calcineurin (By similarity).
Monomer (By similarity). Homodimer (By similarity).
Part of a SCF (SKP1-cullin-F-box) protein ligase complex (By similarity). Interacts with btrc. Interacts with skp1. Interacts with cdc20. Interacts with pin1; stabilizes fbxo5 by preventing its association with btrc in an isomerization-dependent pathway; this interaction is present during G2 phase and prevents fbxo5 degradation. Interacts with plk1 (By similarity).
Proteolysed; proteolysis is induced by both cyclin B-cdk1 and cyclin A-cdk1/2 complex through probable phosphorylation. Proteolysis is inhibited by pin1 during G2.
Regulates progression through early mitosis by inhibiting the anaphase promoting complex/cyclosome (APC). Binds to the APC activators cdc20 to prevent APC activation. Can also bind directly to the APC to inhibit substrate-binding. Required to arrest unfertilized eggs at metaphase of meiosis II, by preventing their release from metaphase of meiosis II, through inhibition of APC-dependent cyclin B destruction leading to stabilization of cyclin B-cdk1 complex activity.
The C-terminal region is required for APC inhibition.
Homodimer (By similarity). Heterodimer with other HLH proteins. Interacts (via HLH domain) with the bHLH protein hes4/hairy2 (via Orange domain). Interacts with stat3 (By similarity).
Transcriptional regulator (lacking a basic DNA binding domain) which negatively regulates the basic helix-loop-helix (bHLH) transcription factors by forming heterodimers and inhibiting their DNA binding and transcriptional activity. Influences cell fate decisions in the embryo by sequestering and blocking the activity of the bHLH transcription factors that control these decisions. Inhibits the binding of myogenic bHLH-containing complexes to E-box DNA, thereby preventing activation of muscle-specific target genes. Also inhibits the activity of neurogenic factor neurod1/neuroD. Plays a role in cell cycle progression and survival of neural crest progenitors; binding to either hes4-B/hairy2b or stat3 blocks the formation of transcription factor complexes and the repressor function of hes4-B/hairy2B, to allow neural crest progenitors to differentiate. May play a role in the regulation of the circadian rhythm (By similarity).
Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like GTPase superfamily. EngB GTPase family.
Belongs to the adenylate kinase family. AK1 subfamily.
Catalyzes the reversible transfer of the terminal phosphate group between ATP and AMP. Also displays broad nucleoside diphosphate kinase activity. Plays an important role in cellular energy homeostasis and in adenine nucleotide metabolism.
Belongs to the glycosyltransferase 61 family.
O-linked mannose beta-1,4-N-acetylglucosaminyltransferase that transfers UDP-N-acetyl-D-glucosamine to the 4-position of the mannose to generate N-acetyl-D-glucosamine-beta-1,4-O-D-mannosylprotein. Involved in the biosynthesis of the phosphorylated O-mannosyl trisaccharide (N-acetylgalactosamine-beta-3-N-acetylglucosamine-beta-4-(phosphate-6-)mannose), a carbohydrate structure present in alpha-dystroglycan (DAG1), which is required for binding laminin G-like domain-containing extracellular proteins with high affinity (By similarity).
Belongs to the TDD superfamily. DTWD2 family.
Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ5 subfamily.
Belongs to the ETF beta-subunit/FixA family.
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.
Component of the elongator complex which is required for multiple tRNA modifications, including mcm5U (5-methoxycarbonylmethyl uridine), mcm5s2U (5-methoxycarbonylmethyl-2-thiouridine), and ncm5U (5-carbamoylmethyl uridine). The elongator complex catalyzes the formation of carboxymethyluridine in the wobble base at position 34 in tRNAs.
Folds into a two seven-bladed beta-propeller structure which is required for elongator complex assembly.
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.
Lysosomal modulator of autophagy that plays a central role in p53/TP53-mediated apoptosis.
At stage 25, expressed throughout the eye field. At stage 40, expression becomes restricted to the retinal pigment epithelium.
May be involved in endothelial cell morphology changes during cell spreading. Required for eye pigmentation. In the retinal pigment epithelium, regulates the biogenesis of melanosomes and promotes their association with the apical cell surface by inducing gamma-tubulin redistribution.
The ASD1 domain mediates F-actin binding.
Belongs to the DEAD box helicase family. DDX54/DBP10 subfamily.
Adapter protein able to interact with different proteins and involved in different biological processes. Mediates the interaction between the error-prone DNA polymerase zeta catalytic subunit rev3l and the inserter polymerase rev1, thereby mediating the second polymerase switching in translesion DNA synthesis. Translesion DNA synthesis releases the replication blockade of replicative polymerases, stalled in presence of DNA lesions. May also play a role in signal transduction in response to DNA damage. May regulate the activation of the anaphase promoting complex APC thereby regulating progression through the cell cycle. Through transcriptional regulation may play a role in epithelial-mesenchymal transdifferentiation (By similarity).
Homooligomer. Interacts with rev1. Interacts with rev3l. Interacts with fzr1 (in complex with the anaphase promoting complex APC). May interact with cdc20 (By similarity).
Catalyzes the formation of diacylglycerol from 2-monoacylglycerol and fatty acyl-CoA.
Acts as a specific nuclear import carrier for hsp70 proteins following heat-shock stress: acts by mediating the nucleoporin-dependent translocation of ATP-bound hsp70 proteins into the nucleus. hsp70 proteins import is required to protect cells from heat shock damages (By similarity).
Gap-filling polymerase involved in repair of DNA double-strand breaks by non-homologous end joining (NHEJ).
Catalyzes the formation of diacylglycerol from 2-monoacylglycerol and fatty acyl-CoA. Probably not involved in absorption of dietary fat in the small intestine.
Belongs to the phosphoglycerate mutase family.
Fructose-bisphosphatase hydrolyzing fructose-2,6-bisphosphate as well as fructose-1,6-bisphosphate. Acts as a negative regulator of glycolysis by lowering intracellular levels of fructose-2,6-bisphosphate in a p53/TP53-dependent manner, resulting in the pentose phosphate pathway (PPP) activation and NADPH production. Contributes to the generation of reduced glutathione to cause a decrease in intracellular reactive oxygen species (ROS) content, correlating with its ability to protect cells from oxidative or metabolic stress-induced cell death. May play a role in mitophagy inhibition.
Not expected to have any kinase activity.
Belongs to the mitochondrion-specific ribosomal protein mS25 family.
Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. LKB1 subfamily.
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 formation of carboxymethyluridine in the wobble base at position 34 in tRNAs (By similarity).
Plays a role in neuronal differentiation.
Involved in an early step of the mitochondrial complex IV assembly process.
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.
Associates with the EF-Tu.GDP complex and induces the exchange of GDP to GTP. It remains bound to the aminoacyl-tRNA.EF-Tu.GTP complex up to the GTP hydrolysis stage on the ribosome.
Has intrinsic E3 ubiquitin ligase activity and promotes ubiquitination.
Belongs to the dihydrofolate reductase family.
Interacts with PPIF; the interaction is impaired by CsA.
Required for normal ciliary development and function. Inhibits disheveled-1-induced canonical Wnt-signaling activity and may also play a role in the control of non-canonical Wnt signaling that regulates planar cell polarity. Probably acts as a molecular switch between different Wnt signaling pathways. Required for proper convergent extension cell movements (By similarity).
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 FAD-dependent oxidoreductase 2 family. FRD/SDH subfamily.
Component of complex II composed of four subunits: a flavoprotein (FP), an iron-sulfur protein (IP), and a cytochrome b composed of a large and a small subunit.
Flavoprotein (FP) subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q).
Plays an important role in maintenance of mitochondrial morphology and in mediating either calcium or potassium/proton antiport (By similarity). Mediates proton-dependent calcium efflux from mitochondrion (By similarity). Functions also as an electroneutral mitochondrial proton/potassium exchanger (By similarity). Required for the maintenance of the tubular shape and cristae organization (By similarity).
Lipid transporter that specifically mediates export of sphingosine-1-phosphate in red blood cells and platelets. Sphingosine-1-phosphate is a signaling sphingolipid and its export from red blood cells into in the plasma is required for red blood cell morphology. Sphingosine-1-phosphate export from platelets is required for platelet aggregation and thrombus formation. In addition to export, also able to mediate S1P import.
Belongs to the connexin family. Beta-type (group I) subfamily.
Belongs to the GST superfamily. Theta family.
Component of a complex that binds and activates STK11/LKB1. In the complex, required to stabilize the interaction between CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta) and STK11/LKB1.
Component of a trimeric complex composed of STK11/LKB1, STRAD (STRADA or STRADB) and CAB39/MO25 (CAB39/MO25alpha or CAB39L/MO25beta): the complex tethers STK11/LKB1 in the cytoplasm and stimulates its catalytic activity.
RNA-binding protein involved in pre-mRNA splicing.
Acts as an important adapter that promotes epithelial cell polarity and tight junction formation. Involved in the assembly of protein complexes at sites of cell-cell contact (By similarity).
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 (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) (By similarity). In the elongator complex, acts as a tRNA uridine(34) acetyltransferase by mediating formation of carboxymethyluridine in the wobble base at position 34 in tRNAs (By similarity). Stabilizes transcriptional repressor snai1 by inhibiting its ubiquitination which promotes neural crest cell migration (By similarity).
Component of the elongator complex (By similarity). Interacts with transcriptional repressors snai1 and snai2; interaction with snai1 inhibits its ubiquitination and stabilizes it (By similarity).
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.
Although related to the peptidase M67A family, it lacks the JAMM motif that probably constitutes the catalytic center and therefore it probably does not have a protease activity.
Belongs to the peptidase M67A family. CSN6 subfamily.
Component of the COP9 signalosome complex (CSN), a complex involved in various cellular and developmental processes.
Belongs to the class I-like SAM-binding methyltransferase superfamily. HNMT family.
Inactivates histamine by N-methylation. Plays an important role in degrading histamine and in regulating the airway response to histamine.
Involved in cytokinesis and spindle organization. May play a role in actin cytoskeleton organization and microtubule stabilization and hence required for proper cell adhesion and migration (By similarity).
Involved in cytokinesis and spindle organization. May play a role in actin cytoskeleton organization and microtubule stabilization and hence required for proper cell adhesion and migration.
May interact with both microtubules and actin cytoskeleton.
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 (By similarity). Hydrolyzes lysyl-AMP (AMP-N-epsilon-(N-alpha-acetyl lysine methyl ester)) generated by lysine tRNA ligase (By similarity).
Forms dimers to octamers and even larger oligomer.
Belongs to the potassium channel family. A (Shaker) (TC 1.A.1.2) subfamily. Kv1.5/KCNA5 sub-subfamily.
Belongs to the AP endonuclease 2 family.
Identified in the spliceosome C complex. Component of the mRNA splicing-dependent exon junction complex (EJC), which contains at least casc3, eif4a3, magoh, nxf1 and rbm8a (By similarity). Forms homooligomers (By similarity).
Required for pre-mRNA splicing as component of the spliceosome. Core component of the splicing-dependent multiprotein exon junction complex (EJC) deposited at splice junctions on mRNAs. The EJC is a dynamic structure consisting of core proteins and several peripheral nuclear and cytoplasmic associated factors that join the complex only transiently either during EJC assembly or during subsequent mRNA metabolism. The EJC marks the position of the exon-exon junction in the mature mRNA for the gene expression machinery and the core components remain bound to spliced mRNAs throughout all stages of mRNA metabolism thereby influencing downstream processes including nuclear mRNA export, subcellular mRNA localization, translation efficiency and nonsense-mediated mRNA decay (NMD). Binds spliced mRNA in sequence-independent manner, 20-24 nucleotides upstream of mRNA exon-exon junctions.
Belongs to the eukaryotic ribosomal protein eS17 family.
Probable transcription factor. Required for smooth muscle (visceral mesoderm) differentiation during gut development. Also required for normal proliferation of the lateral plate mesoderm. Acts as a downstream mediator of bmp4-signaling (By similarity).
During interphase, required for microtubule organizing and anchoring activities. During mitosis, required for the organization and stabilization of the spindle pole. May promote cell cycle arrest and DNA repair.
Belongs to the lyase 1 family. Adenylosuccinate lyase subfamily.
Catalyzes two non-sequential steps in de novo AMP synthesis: converts (S)-2-(5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamido)succinate (SAICAR) to fumarate plus 5-amino-1-(5-phospho-D-ribosyl)imidazole-4-carboxamide, and thereby also contributes to de novo IMP synthesis, and converts succinyladenosine monophosphate (SAMP) to AMP and fumarate.
Homotetramer. Residues from neighboring subunits contribute catalytic and substrate-binding residues to each active site.
Binds DNA as a dimer (By similarity). Interacts with dscr6/ripply3.
In early neurulae (stage 13), regionally restricted expression seen in a broad anterior domain surrounding the anterior end of the mediodorsal groove of the neural plate. Within this broad ectodermal domain, expression seen in two bilateral patches flanking the mediodorsal groove. In late neurulae (stage 19), a strong expression is seen in the anterior ectoderm. At early tail bud stage (stage 25), expressed in three distinct areas within the pharyngeal region and in the ventral region of each otic vesicle. At stage 33, expression within the otic vesicles extends further laterally. However, in subsequent stages (stages 40, 47) expression remains restricted to the ventral and lateral regions of the vesicles.
Probable transcriptional regulator involved in developmental processes (By similarity). Binds to the palindromic T site 5'-TTCACACCTAGGTGTGAA-3' DNA sequence (By similarity). Induces pre-placodal ectoderm (PPE) gene expression in regions where RIPPLY3 is absent. Plays a role in the formation of the anteroposterior (AP) axis during embryonic development; required to establish the posterolateral border of the pre-placodal ectoderm (PPE) acting downstream of the retinoic acid receptor (RAR) signaling (By similarity).
Belongs to the mitochondrion-specific ribosomal protein mL49 family.
Belongs to the XPG/RAD2 endonuclease family. XPG subfamily.
Belongs to the potassium channel family. Calcium-activated (TC 1.A.1.3) subfamily. KCa1.1/KCNMA1 sub-subfamily.
Acts as a chaperone for the linker histone to facilitate deposition of histone B4 onto linker DNA. Required for both remodeling of sperm chromatin into nucleosomes, and linker histone binding to nucleosome core dimers. Plays a role in tissue-specific gene regulation. Required for primitive hemopoiesis, acting upstream of tal1/scl (By similarity).
Forms homomultimers. Interacts with histone B4. Interacts with the B-type cyclins ccnb1 and ccnb2 (By similarity).
Phosphorylated by cyclin B-cdc2 kinase complexes.
The NAP1L motif is required for the histone chaperone activity.
The acidic domains are probably involved in the interaction with histones.
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.
Acts as an ATP-dependent RNA helicase, able to unwind both RNA-RNA and RNA-DNA duplexes. Possesses 5' single-stranded RNA overhang nuclease activity. Acts as a positive regulator of transcription. May be involved in 3'-end cleavage and polyadenylation of pre-mRNAs. Binds DNA and RNA. Component of the tRNA-splicing ligase complex required to facilitate the enzymatic turnover of catalytic subunit rtcb. Binds (via helicase ATP-binding domain) on both short and long poly(I:C) dsRNA (By similarity).
Belongs to the DEAD box helicase family. DDX1 subfamily.
The helicase domain is involved in the stimulation of RELA transcriptional activity.
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 (By similarity).
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.
Acts as a component of the essential kinetochore-associated NDC80 complex, which is required for chromosome segregation and spindle checkpoint activity. Required for kinetochore integrity and the organization of stable microtubule binding sites in the outer plate of the kinetochore. The NDC80 complex synergistically enhances the affinity of the SKA1 complex for microtubules and may allow the NDC80 complex to track depolymerizing microtubules. May play a role in chromosome congression and may be essential for the end-on attachment of the kinetochores to spindle microtubules.
Component of the NDC80 complex, which is composed of ndc80, cdca1, spbc24 and spbc25. The NDC80 complex interacts with mis12 and zwint. Interacts with cep57r (By similarity).
Belongs to the cytochrome c oxidase subunit 2 family.
May regulate calcium-dependent activities in the endoplasmic reticulum lumen or post-ER compartment.
Belongs to the protein-tyrosine phosphatase family. Receptor class 4 subfamily.
Enzyme responsible for the N-acetyl-histidine (NAH) synthesis, which is a major constituent of brain and lens of ectothermic vertebrates.
Strong histidine N-acetyltransferase activity has been detected in ectothermic vertebrates and not in endothermic birds and mammals.
Acts as a negative regulator of G1 to S cell cycle phase progression by inhibiting cyclin-dependent kinases. Inhibitory effects are additive with GADD45 proteins but occurs also in the absence of GADD45 proteins. Acts as a repressor of the orphan nuclear receptor NR4A1 by inhibiting AB domain-mediated transcriptional activity. May be involved in the hormone-mediated regulation of NR4A1 transcriptional activity. May play a role in mitochondrial protein synthesis.
Belongs to the mitochondrion-specific ribosomal protein mL64 family.
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.
ARF1 contains 2 smad2s, 1 smad4 and 1 foxh1/fast-1 protein. Interaction with smad4 is most likely indirect through interaction with the MH2 domain of smad2. Binds to the MH2 domain of smad3, which can incorporate into the ARF1 complex. The ARF1 and ARF2 complexes are activated by distinct TGF-beta family members; formation of ARF1 is promoted by activin. Interacts (via Fork-head domain) with gtf2ird1/wbscr11 (via repeats 4-5) (By similarity).
The FM region is required for binding smad2/smad4 complexes. FM2 is more effective than FM1 and only interacts with phosphorylated smad2 that is in an activated smad complex (By similarity).
Transcriptional activator. Recognizes and binds to the DNA sequence 5'-TGT[GT][GT]ATT-3'. Upon TGF-beta induction, forms a transcriptionally active complex with smad2 and smad4 called activin-responsive factor 1 (ARF1), which binds a site on the mix-B/mix.2 promoter called the activin response element (ARE). Binds to activated smads and the ARE with much lower affinity than fast3. Necessary for the first steps in mesoderm specification, directly inducing mesodermal genes. Acts with fast3 to control the convergent extension movements of gastrulation. Binds to the proximal element (PE) of the gsc gene and cooperates with gtf2ird1/wbscr11 and SMAD proteins to regulate gsc transcription (By similarity).
Belongs to the uroporphyrinogen decarboxylase family.
Associates with ribosomes; preventing translation. Interacts with eiF5a (eif5a and eif5a2); preventing translation.
Ribosome-binding protein that promotes ribosome hibernation, a process during which ribosomes are stabilized in an inactive state and preserved from proteasomal degradation. Acts via its association with eiF5a (eif5a and eif5a2) at the polypeptide exit tunnel of the ribosome, preventing mRNA translation. Plays a key role in ribosome hibernation in the mature egg by preventing mRNA translation, leading to ribosome inactivation. Ribosomes, which are produced in large quantities during oogenesis, are stored and translationally repressed in the egg and early embryo.
Directly interacts with tubulin-gamma; this interaction determines centrosomal localization.
Plays a role in the organization of both preexisting and nascent microtubules in interphase cells. During mitosis, required for the organization and orientation of the mitotic spindle.
Belongs to the DEAD box helicase family. DEAH subfamily. DDX15/PRP43 sub-subfamily.
Binds target DNA via the HMG box domain.
Transcription factor. Binds to the consensus DNA sequence 5'-AACAAT-3'. Also binds 5'-CACAAT-3' and 5'-AATAAT-3' but with a lower affinity. Acts partially redundantly with sox7 during cardiogenesis, acting indirectly through nodal-signaling to induce mesodermal, organizer and endodermal tissues, which then interact to initiate cardiogenesis. Also acts as an antagonist of beta-catenin signaling (By similarity).
Belongs to the shisa family. SHISA9 subfamily.
Component of some AMPA receptors (ionotropic glutamate receptors) complex.
Regulator of short-term neuronal synaptic plasticity in the dentate gyrus. Associates with AMPA receptors (ionotropic glutamate receptors) in synaptic spines and promotes AMPA receptor desensitization at excitatory synapses (By similarity).
Belongs to the proteasome subunit S9 family.
Component of the 19S proteasome regulatory particle complex. The 26S proteasome consists of a 20S core particle (CP) and two 19S regulatory subunits (RP). The regulatory particle is made of a lid composed of 9 subunits including PSMD11, a base containing 6 ATPases and few additional components.
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. In the complex, PSMD11 is required for proteasome assembly. Plays a key role in increased proteasome activity in embryonic stem cells (ESCs): its high expression in ESCs promotes enhanced assembly of the 26S proteasome, followed by higher proteasome activity.
Catalyzes the transfer of a single N-acetylglucosamine from UDP-GlcNAc to a serine or threonine residue in extracellular proteins resulting in their modification with a beta-linked N-acetylglucosamine (O-GlcNAc). Specifically glycosylates the Thr residue located between the fifth and sixth conserved cysteines of folded EGF-like domains.
Belongs to the RNase HII family. Eukaryotic subfamily.
Catalytic subunit of RNase HII, an endonuclease that specifically degrades the RNA of RNA:DNA hybrids. Participates in DNA replication, possibly by mediating the removal of lagging-strand Okazaki fragment RNA primers during DNA replication. Mediates the excision of single ribonucleotides from DNA:RNA duplexes.
Manganese or magnesium. Binds 1 divalent metal ion per monomer in the absence of substrate. May bind a second metal ion after substrate binding.
Belongs to the flagellar radial spoke RSP3 family.
Belongs to the MICOS complex subunit Mic13 family.
Belongs to the eukaryotic ribosomal protein eL15 family.
Belongs to the complex I 49 kDa subunit family.
Participates in the initial step of the glucosylceramide-based glycosphingolipid/GSL synthetic pathway at the cytosolic surface of the Golgi. Catalyzes the transfer of glucose from UDP-glucose to ceramide to produce glucosylceramide/GlcCer (such as beta-D-glucosyl-(1<->1')-N-acylsphing-4-enine). Glucosylceramide is the core component of glycosphingolipids/GSLs, amphipathic molecules consisting of a ceramide lipid moiety embedded in the outer leaflet of the membrane, linked to one of hundreds of different externally oriented oligosaccharide structures. Glycosphingolipids are essential components of membrane microdomains that mediate membrane trafficking and signal transduction. They are implicated in many fundamental cellular processes, including growth, differentiation, migration, morphogenesis, cell-to-cell and cell-to-matrix interactions (By similarity). Catalyzes the synthesis of xylosylceramide/XylCer (such as beta-D-xylosyl-(1<->1')-N-acylsphing-4-enine) using UDP-Xyl as xylose donor (By similarity).
The D1, D2, D3, (Q/R)XXRW motif is a critical part of the GCS active site, involved in catalysis and UDP-sugar binding.
Mannosyltransferase involved in glycosylphosphatidylinositol-anchor biosynthesis.
Component of the BCR(KLHL22) E3 ubiquitin ligase complex, at least composed of cul3, klhl22 and rbx1.
Substrate-specific adapter of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex. The BCR(KLHL22) ubiquitin ligase complex could mediate the monoubiquitination of PLK1 and regulate its activity in spindle assembly checkpoint (SAC) and chromosome segregation. The BCR(KLHL22) ubiquitin ligase complex may also be responsible for the ubiquitin-dependent proteasomal degradation of DEPDC5 and the activation of the TORC1 pathway.
In the C-terminal section; belongs to the OMP decarboxylase family.
In the N-terminal section; belongs to the purine/pyrimidine phosphoribosyltransferase family.
Component of the origin recognition complex (ORC) that binds origins of replication. DNA-binding is ATP-dependent, however specific DNA sequences that define origins of replication have not been identified so far. ORC is required to assemble the pre-replication complex necessary to initiate DNA replication.
Essential multidomain scaffolding protein required for normal development. Recruits channels, receptors and signaling molecules to discrete plasma membrane domains in polarized cells. May play a role in adherens junction assembly, signal transduction and cell proliferation (By similarity).
Necessary for protein translocation in the endoplasmic reticulum.
Belongs to the glycogen debranching enzyme family.
Multifunctional enzyme acting as 1,4-alpha-D-glucan:1,4-alpha-D-glucan 4-alpha-D-glycosyltransferase and amylo-1,6-glucosidase in glycogen degradation.
Belongs to the TRAFAC class OBG-HflX-like GTPase superfamily. OBG GTPase family.
Interacts with MRAP; increasing ligand-sensitivity and generation of cAMP. Interacts with MRAP2; competing with MRAP for binding to MC2R and impairing the binding of corticotropin (ACTH).
Required for organization of the cellular microtubule array and microtubule anchoring at the centrosome. Positively regulates the activity of the minus-end directed microtubule motor protein dynein. May enhance dynein-mediated microtubule sliding by targeting dynein to the microtubule plus end. Positively regulates lysosome peripheral distribution and ruffled border formation in osteoclasts.
Each subunit of the homodimer independently transports zinc ions in a pH-dependent manner. The cytosolic pH promotes binding of zinc ions to the transporter binding site. Upon change into the organelle-facing conformation, the two histidines of the zinc-binding site get protonated at lumenal lower pH, triggering zinc release into the organelle. The transporter then moves back to the cytosolic-facing conformation where the two histidines get deprotonated at higher pH, resulting in a net antiport of 2 protons.
Proton-coupled zinc ion antiporter mediating the entry of zinc into the lumen of pancreatic beta cell secretory granules, thereby regulating insulin secretion.
Although it belongs to the enolase family, Leu-332 is present instead of the conserved Glu which is expected to be an active site residue.
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 inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ2 subfamily.
ATP-dependent RNA helicase that is an integral component of messenger ribonucleoprotein complexes (mRNPs), storage particles that mask maternal mRNAs from the translational apparatus during oocyte maturation.
Belongs to the DEAD box helicase family. DDX6/DHH1 subfamily.
Component of a ribonucleoprotein (RNP) complex, composed at least of cpeb1, lsm14b/rap55b, ddx6/Xp54, ybx2/frgy2, pat1/P100, eif4enif1/4E-T and eif4e1b. Component of a ribonucleoprotein (RNP) complex, composed at least of elavl1/elrA and/or elavl2/elrB, igf2bp3/vg1RBP, ddx6/Xp54, ybx2/frgy2, lsm14b/rap55b and, in a subset of RNP complexes, stau1/staufen. Component of a ribonucleoprotein (RNP) complex, composed at least of lsm14a/rap55a, ybx2/frgy2, ddx6/Xp54 and eif4enif1/4E-T. Interacts with lsm14a/rap55a (By similarity).
Adapter protein that links membrane-bound small G-proteins to cytoplasmic effector proteins. Necessary for CDC42-mediated reorganization of the actin cytoskeleton and for RAC1-mediated membrane ruffling. Involved in the regulation of the actin cytoskeleton by WASF family members and the Arp2/3 complex. Plays a role in neurite growth. Acts syngeristically with ENAH to promote filipodia formation. Plays a role in the reorganization of the actin cytoskeleton in response to bacterial infection. Participates in actin bundling when associated with EPS8, promoting filopodial protrusions.
Required for the quantitative accumulation of H/ACA ribonucleoproteins (RNPs).
Mitochondrial membrane ATP synthase (F1F0 ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F1 - containing the extramembraneous catalytic core, and F0 - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F1 is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Part of the complex F0 domain. Minor subunit located with subunit a in the membrane.
Belongs to the cyclin family. Cyclin L subfamily.
Contains a RS region (arginine-serine dipeptide repeat) within the C-terminal domain which is the hallmark of the SR family of splicing factors. This region probably plays a role in protein-protein interactions (By similarity).
Acts as a transcriptional corepressor. Negative regulator of the transcriptional activity of tbx1 that plays a key role in pharyngeal development. Plays a role in the formation of the anteroposterior (AP) axis during embryonic development; required to establish the posterolateral border of the pre-placodal ectoderm (PPE) acting downstream of the retinoic acid receptor (RAR) signaling (By similarity).
The Ripply homology domain and the WRPW motif are both necessary for its transcriptional corepressor activity on the transcription activator tbx1.
The WRPW motif is required for binding to tle/groucho proteins.
Component of the telomerase ribonucleoprotein (RNP) complex that is essential for the replication of chromosome termini.
The PINc domain confers endonuclease activity and is expected to bind the catalytic metal ion.
Kinesin family member that is involved in spindle formation and the movements of chromosomes during mitosis and meiosis. Binds to microtubules and to DNA.
Ubiquitinated, leading to its subsequent proteasomal degradation.
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.
Belongs to the metallo-dependent hydrolases superfamily. NagA family.
Contributes to the neddylation of all cullins by transferring NEDD8 from N-terminally acetylated NEDD8-conjugating E2s enzyme to different cullin C-terminal domain-RBX complexes. At the cell membrane, can promote and as well inhibit cullins neddylation.
May interact (via the DCUN1 domain) with unneddylated cullins.
The DCUN1 domain, also known as PONY domain, mediates the interaction with different cullins.
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. Catalyzes monoubiquitination of 26S proteasome subunit PSMC2/RPT1.
Belongs to the complex I subunit 3 family.
Core subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I) which catalyzes electron transfer from NADH through the respiratory chain, using ubiquinone as an electron acceptor. Essential for the catalytic activity of complex I.
Belongs to the DOK family. Type A subfamily.
Heterodimer with gpn1. Binds to RNA polymerase II (RNAPII).
Small GTPase required for proper localization of RNA polymerase II (RNAPII). May act at an RNAP assembly step prior to nuclear import.
Required for the assembly and stability of the mitochondrial ubiquinol-cytochrome c reductase complex (complex III (CIII) or cytochrome b-c1 complex), a multisubunit transmembrane complex that is part of the mitochondrial electron transport chain (ETC) which drives oxidative phosphorylation.
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).
Catalyzes the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PtdIns-4,5-P2) to phosphatidylinositol-4-phosphate (PtdIns-4-P).
Essential bifunctional enzyme that catalyzes both the N-deacetylation and the N-sulfation of glucosamine (GlcNAc) of the glycosaminoglycan in heparan sulfate. Modifies the GlcNAc-GlcA disaccharide repeating sugar backbone to make N-sulfated heparosan, a prerequisite substrate for later modifications in heparin biosynthesis. Plays a role in determining the extent and pattern of sulfation of heparan sulfate.
Belongs to the calcineurin regulatory subunit family.
Catalyzes the NADPH-dependent reduction of trans-2-enoyl thioesters in mitochondrial fatty acid synthesis (fatty acid synthesis type II). Fatty acid chain elongation in mitochondria uses acyl carrier protein (ACP) as an acyl group carrier, but the enzyme accepts both ACP and CoA thioesters as substrates in vitro (By similarity). Functions in pronephros development, regulating late differentiation of all pronephric tubule segments (PubMed:18472403).
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.
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.
Inhibits calcineurin-dependent transcriptional responses by binding to the catalytic domain of calcineurin A. Could play a role during central nervous system development.
Belongs to the glycosyltransferase 23 family.
Catalyzes the addition of fucose in alpha 1-6 linkage to the first GlcNAc residue, next to the peptide chains in N-glycans.
Belongs to the class I-like SAM-binding methyltransferase superfamily. TRM61 family.
Catalytic subunit of tRNA (adenine-N(1)-)-methyltransferase, which catalyzes the formation of N(1)-methyladenine at position 58 (m1A58) in initiator methionyl-tRNA.
Belongs to the WD repeat PRL1/PRL2 family.
Associates with the 60S ribosomal subunit.
Required for the assembly of mature ribosomes and ribosome biogenesis. Together with EFL1, triggers the GTP-dependent release of eif6 from 60S pre-ribosomes in the cytoplasm, thereby activating ribosomes for translation competence by allowing 80S ribosome assembly and facilitating eif6 recycling to the nucleus, where it is required for 60S rRNA processing and nuclear export. Required for normal levels of protein synthesis. May play a role in cellular stress resistance. May play a role in cellular response to DNA damage. May play a role in cell proliferation (By similarity).
Component of the chromosomal passenger complex (CPC).
Kinase activity is stimulated by cell-cycle specific phosphorylation.
Serine/threonine-protein kinase component of the chromosomal passenger complex (CPC), a complex that acts as a key regulator of mitosis. The CPC complex has essential functions at the centromere in ensuring correct chromosome alignment and segregation and is required for chromatin-induced microtubule stabilization and spindle assembly. Involved in the bipolar attachment of spindle microtubules to kinetochores and is a key regulator for the onset of cytokinesis during mitosis. Required for central/midzone spindle assembly and cleavage furrow formation. Key component of the cytokinesis checkpoint, a process required to delay abscission to prevent both premature resolution of intercellular chromosome bridges and accumulation of DNA damage. Phosphorylates 'Ser-10' of histone H3 during mitosis.
Non-catalytic component of the RNA exosome complex which has 3'->5' exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events.
Catalyzes the methylation of 5-carboxymethyl uridine to 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in tRNA via its methyltransferase domain. Catalyzes the last step in the formation of 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in target tRNA. Has a preference for tRNA(Arg) and tRNA(Glu), and does not bind tRNA(Lys). Binds tRNA and catalyzes the iron and alpha-ketoglutarate dependent hydroxylation of 5-methylcarboxymethyl uridine at the wobble position of the anticodon loop in tRNA via its dioxygenase domain, giving rise to 5-(S)-methoxycarbonylhydroxymethyluridine; has a preference for tRNA(Gly). Required for normal survival after DNA damage. May inhibit apoptosis and promote cell survival and angiogenesis (By similarity).
Acts as an adapter protein linking the dynein motor complex to various cargos and converts dynein from a non-processive to a highly processive motor in the presence of dynactin. Facilitates the interaction between dynein and dynactin and activates dynein processivity (the ability to move along a microtubule for a long distance without falling off the track). Predominantly recruits 2 dyneins, which increases both the force and speed of the microtubule motor. Component of secretory vesicle machinery in developing neurons that acts as a regulator of neurite outgrowth. Regulates the secretory vesicle transport by controlling the accumulation of Rab6-containing secretory vesicles in the pericentrosomal region restricting anterograde secretory transport during the early phase of neuronal differentiation, thereby inhibiting neuritogenesis.
Part of a tripartite complex with dynein and dynactin, acts an adapter linking the dynein motor complex and dynactin. Interacts with KIF1C. Interacts with RAB6A and RAB6B; interaction is specific to Rab6.
Could be involved in the unfolded protein response (UPR) pathway.
Despite its name it is related to the unc-93 family and not to the major facilitator superfamily.
Probably part of the adaptor protein complex 5 (AP-5) a tetramer composed of AP5B1, AP5M1, AP5S1 and AP5Z1.
Belongs to the eukaryotic ribosomal protein eL27 family.
The regulatory loop blocks the catalytic center by bridging the methyltransferase domain and the C-terminal CCHC-type zinc finger, resulting in an autoinhibitory conformation.
rRNA N6-methyltransferase that specifically methylates the adenine in position 4220 of 28S rRNA. N6-methylation of adenine(4220) in 28S rRNA is required for translation.
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 CNF-like-inhibitor family.
Autophosphorylated on serine and threonine residues.
Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. Central component of the circadian clock. May act as a negative regulator of circadian rhythmicity by phosphorylating per1 and per2, which may lead to their degradation. Participates in wnt signaling (By similarity).
Exhibits substrate-dependent heparin activation.
Monomer (By similarity). Interacts with per1 and per2. Component of the circadian core oscillator (By similarity).
Component of the transcription factor SL1/TIF-IB complex, composed of TBP and at least TAF1A, TAF1B, TAF1C and TAF1D. Interacts with UBTF.
Component of the transcription factor SL1/TIF-IB complex, which is involved in the assembly of the PIC (preinitiation complex) during RNA polymerase I-dependent transcription. The rate of PIC formation probably is primarily dependent on the rate of association of SL1/TIF-IB with the rDNA promoter. SL1/TIF-IB is involved in stabilization of nucleolar transcription factor 1/UBTF on rDNA. Formation of SL1/TIF-IB excludes the association of TBP with TFIID subunits.
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 universal ribosomal protein uS17 family.
Catalyzes the reversible isomerization between hydroxypyruvate and 2-hydroxy-3-oxopropanoate (also termed tartronate semialdehyde).
Belongs to the class I-like SAM-binding methyltransferase superfamily. RMT2 methyltransferase family.
Converts guanidinoacetate to creatine, using S-adenosylmethionine as the methyl donor. Important in nervous system development.
Nucleolar protein that acts as a modulator of rRNA synthesis. Plays a central role during organogenesis.
Belongs to the mitochondrion-specific ribosomal protein mS39 family.
Mitochondrial protein that may have a role in mitochondrial translation.
Monomer (By similarity). May form homodimers; homodimerization may enhance autophosphoylation and enzymatic activity (By similarity). Heterodimer with TLK1 (By similarity).
Phosphorylated (By similarity). Autophosphorylated; phosphorylation promotes the assembly of higher order oligomers and enzymatic activity (By similarity).
Serine/threonine-protein kinase involved in the process of chromatin assembly and probably also DNA replication, transcription, repair, and chromosome segregation (By similarity). Negative regulator of amino acid starvation-induced autophagy (By similarity).
Accepts the ubiquitin-like protein NEDD8 from the uba3-nae1 E1 complex and catalyzes its covalent attachment to other proteins. The specific interaction with the E3 ubiquitin ligase rbx2, but not rbx1, suggests that the rbx2-ube2f complex neddylates specific target proteins, such as cul5.
Belongs to the ubiquitin-conjugating enzyme family. UBE2F subfamily.
Belongs to the delta-EF1/ZFH-1 C2H2-type zinc-finger family.
Belongs to the helicase family. PIF1 subfamily.
DNA-dependent ATPase and 5'-3' DNA helicase required for the maintenance of both mitochondrial and nuclear genome stability.
In the central section; belongs to the inositol 1,4,5-trisphosphate 5-phosphatase family.
EF-1 is composed of four subunits: alpha, beta, delta, and gamma.
Probably plays a role in anchoring the complex to other cellular components.
Component of the RNA polymerase II (Pol II) complex consisting of 12 subunits. RPB4 and RPB7 form a subcomplex that protrudes from the 10-subunit Pol II core complex.
Autoinhibited by the ariadne domain, which masks the second RING-type zinc finger that contains the active site and inhibits the E3 activity. Inhibition is relieved upon binding to neddylated cullin-RING ubiquitin ligase complexes, which activate the E3 ligase activity of ARIH1.
Belongs to the RBR family. Ariadne subfamily.
E3 ubiquitin-protein ligase, which catalyzes ubiquitination of target proteins together with ubiquitin-conjugating enzyme E2 ube2l3. Acts as an atypical E3 ubiquitin-protein ligase by working together with cullin-RING ubiquitin ligase (CRL) complexes and initiating ubiquitination of CRL substrates: associates with CRL complexes and specifically mediates addition of the first ubiquitin on CRLs targets. The initial ubiquitin is then elongated. E3 ubiquitin-protein ligase activity is activated upon binding to neddylated cullin-RING ubiquitin ligase complexes.
Interacts (via the first RING-type zinc finger) with ube2l3. Associates with cullin-RING ubiquitin ligase (CRL) complexes containing neddylated cullin.
Members of the RBR family are atypical E3 ligases. They interact with the E2 conjugating enzyme UBE2L3 and function like HECT-type E3 enzymes: they bind E2s via the first RING-type zinc finger, but require an obligate trans-thiolation step during the ubiquitin transfer, requiring a conserved active site Cys residue in the second RING-type zinc finger. The active site probably forms a thioester intermediate with ubiquitin taken from the active-site cysteine of the E2 before ultimately transferring it to a Lys residue on the substrate.
The Ariadne domain inhibits activity by masking the second RING-type zinc finger that contains the active site.
Belongs to the aromatic-ring hydroxylase family. KMO subfamily.
Catalyzes the hydroxylation of L-kynurenine (L-Kyn) to form 3-hydroxy-L-kynurenine (L-3OHKyn). Required for synthesis of quinolinic acid.
Belongs to the acetyltransferase ATAT1 family.
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. May be involved in neuron development.
Functions as actin-binding component of the Arp2/3 complex which is involved in regulation of actin polymerization and together with an activating nucleation-promoting factor (NPF) mediates the formation of branched actin networks. Seems to contact the mother actin filament.
A subset of this protein primarily localized at the spindle pole is phosphorylated by NEK6 during mitosis.
Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. BimC subfamily.
Heterotetramer of two heavy and two light chains. Interacts with aurka (By similarity).
Phosphorylated on a serine residue by aurka.
Phosphorylation of Thr-937 during mitosis controls the association of this protein with the spindle apparatus.
Plus end-directed motor protein required for establishing a bipolar spindle. Associates with both interphase and mitotic spindle microtubules. May be involved in nuclear divisions taking place during the development of unfertilized eggs. Required in non-mitotic cells for transport of secretory proteins from the Golgi complex to the cell surface.
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.
As a component of the GATOR2 complex, functions as an activator of the amino acid-sensing branch of the mTORC1 signaling pathway. The GATOR2 complex indirectly activates mTORC1 through the inhibition of the GATOR1 subcomplex. GATOR2 probably acts as a E3 ubiquitin-protein ligase toward GATOR1. In the presence of abundant amino acids, the GATOR2 complex mediates ubiquitination of the NPRL2 core component of the GATOR1 complex, leading to GATOR1 inactivation. In the absence of amino acids, GATOR2 is inhibited, activating the GATOR1 complex.
Component of the Nup107-160 subcomplex of the nuclear pore complex (NPC). The Nup107-160 subcomplex includes NUP160, NUP133, NUP107, NUP98, NUP85, NUP43, NUP37, SEH1 and SEC13. Component of the GATOR2 subcomplex, composed of MIOS, SEC13, SEH1L, WDR24 and WDR59. The GATOR2 complex interacts with CASTOR1 and CASTOR2; the interaction is negatively regulated by arginine. The GATOR2 complex interacts with SESN1, SESN2 and SESN3; the interaction is negatively regulated by amino acids.
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.
The GATOR2 complex is negatively regulated by the upstream amino acid sensors CASTOR1 and SESN2, which sequester the GATOR2 complex in absence of amino acids. In the presence of abundant amino acids, GATOR2 is released from CASTOR1 and SESN2 and activated.
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.
ATP dependent phosphorylation of adenosine and other related nucleoside analogs to monophosphate derivatives.
Homodimer. Heterodimer; heterodimerizes with other rfx proteins.
Transcription factor that acts as a key regulator of ciliogenesis. Specifically regulates expression of genes required for cilium assembly and function. Recognizes and binds the X-box, a regulatory motif with DNA sequence 5'-GTNRCC(0-3N)RGYAAC-3' present on promoters. Required for neural tube closure and neural ciliogenesis.
Regulatory component of the SET1 complex implicated in the tethering of this complex to transcriptional start sites of active genes. Facilitates histone H3 'Lys-4' methylation (H3K4me) via recruitment of the SETD1A or SETD1B to the 'Ser-5' phosphorylated C-terminal domain (CTD) of RNA polymerase II large subunit (POLR2A). Part of a transcription termination checkpoint that promotes transcription termination of long non-coding RNAs (lncRNAs).
Involved in spliceosome assembly (By similarity).
The Tudor domain mediates association with dimethylarginines, which are common in snRNP proteins.
May play an important role in spermatogenesis and/or testis development.
Transcriptional regulator (lacking a basic DNA binding domain) which negatively regulates the basic helix-loop-helix (bHLH) transcription factors by forming heterodimers and inhibiting their DNA binding and transcriptional activity. Inhibits the activity of both neurogenic (neurod1/neuroD) and myogenic (myod1/myoD) bHLH factors. May play a role in the regulation of the circadian clock (By similarity).
May be involved in the ribosome maturation process.
RNA-binding protein that is involved in the post-transcriptional regulation of mRNAs (By similarity). Plays a role in the regulation of mRNA stability, alternative splicing and translation (By similarity). Binds to AU-rich element (ARE) sequences in the 3' untranslated region (3'UTR) of target mRNAs (By similarity). Mainly plays a role in neuron-specific RNA processing (By similarity).
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 tRNA nucleotidyltransferase/poly(A) polymerase family.
Interacts with XAF1, the interaction increases XAF1 stability and proapoptotic effects, and may regulate IFN signaling.
Part of the complex catalyzing the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to phosphatidylinositol, the first step of GPI biosynthesis.
Belongs to the replication factor A protein 1 family.
Component of the heterotrimeric canonical replication protein A complex (RPA).
Component of the heterotrimeric canonical replication protein A complex (RPA). Interacts with rpain-a (By similarity).
Component of some SCF (SKP1-cullin-F-box) protein ligase complex that plays a central role in iron homeostasis by promoting the ubiquitination and subsequent degradation of ireb2/irp2. Upon high iron and oxygen level, it specifically recognizes and binds ireb2/irp2, promoting its ubiquitination and degradation by the proteasome (By similarity).
The hemerythrin-like region acts as an oxygen and iron sensor by binding oxygen through a diiron metal-center. In absence of oxygen and iron, the protein is ubiquitinated and degraded (By similarity).
Ubiquitinated upon iron and oxygen depletion, leading to its degradation by the proteasome. Ubiquitination is regulated by the hemerythrin-like region that acts as an oxygen and iron sensor (By similarity).
Contains one covalently linked retinal chromophore.
Transcription factor involved in specification of neuronal cell types and which is required for inner ear and hypothalamus development. Binds to the 5'-CAAGTG-3' core sequence. May act as a stage-specific inhibitor of anf1 in the anterior neural plate during the development (By similarity).
DNA-binding protein that specifically recognizes consensus sequences at the breakpoint junctions in chromosomal translocations, mostly involving immunoglobulin (Ig)/T-cell receptor gene segments. Seems to recognize single-stranded DNA ends generated by staggered breaks occurring at recombination hot spots.
Exhibits both single-stranded and double-stranded endoribonuclease activity. May act as an activator of RNA-induced silencing complex (RISC) by facilitating endonucleolytic cleavage of the siRNA passenger strand.
Ring-shaped heterooctamer of six TSN and two TSNAX subunits, DNA/RNA binding occurs inside the ring.
Belongs to the folylpolyglutamate synthase family.
Catalyzes conversion of folates to polyglutamate derivatives allowing concentration of folate compounds in the cell and the intracellular retention of these cofactors, which are important substrates for most of the folate-dependent enzymes that are involved in one-carbon transfer reactions involved in purine, pyrimidine and amino acid synthesis.
Molecular chaperone which mediates the proper assembly and functional expression of the nicotinic acetylcholine receptors (nAChRs) throughout the brain (By similarity). Essential for the proper folding, assembly, function and surface trafficking of alpha-7 (CHRNA7), alpha-4-beta-2, alpha-3-beta-2 and alpha-3-beta-4 receptors (By similarity).
Belongs to the eukaryotic ribosomal protein eL38 family.
Acts as a sulfur carrier required for 2-thiolation of mcm(5)S(2)U at tRNA wobble positions of cytosolic tRNA(Lys), tRNA(Glu) and tRNA(Gln). Serves as sulfur donor in tRNA 2-thiolation reaction by being thiocarboxylated (-COSH) at its C-terminus by MOCS3. The sulfur is then transferred to tRNA to form 2-thiolation of mcm(5)S(2)U. Also acts as a ubiquitin-like protein (UBL) that is covalently conjugated via an isopeptide bond to lysine residues of target proteins. The thiocarboxylated form serves as substrate for conjugation and oxidative stress specifically induces the formation of UBL-protein conjugates.
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.
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.
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.
Linker region/H9 could directly block the transport of substrates across the transporter.
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.
May be a regulator of serine/threonine-protein phosphatases 2A (PP2A) and 4 (PP4).
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.
Belongs to the thymidylate synthase family.
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.
May induce G2 arrest and apoptosis. May also increase cell sensitivity to apoptotic stimuli.
Chemoattractant. Activates the C-X-C chemokine receptor cxcr4 to induce a rapid and transient rise in the level of intracellular calcium ions, and chemotaxis. Signaling with cxcr4 mediates the directional movement of mesodermal cells during gastrulation. Binds to the allosteric site (site 2) of integrins and activates them in a cxcr4-independent manner.
Monomer or homodimer; in equilibrium. Dimer formation is induced by non acidic pH and the presence of multivalent anions, and by binding to cxcr4 or heparin (By similarity).
Cysteine protease that plays a key role in autophagy by mediating both proteolytic activation and delipidation of ATG8 family proteins. The protease activity is required for proteolytic activation of ATG8 family proteins: cleaves the C-terminal amino acid of ATG8 proteins to reveal a C-terminal glycine (By similarity). Exposure of the glycine at the C-terminus is essential for ATG8 proteins conjugation to phosphatidylethanolamine (PE) and insertion to membranes, which is necessary for autophagy (By similarity). In addition to the protease activity, also mediates delipidation of ATG8 family proteins. Catalyzes delipidation of PE-conjugated forms of ATG8 proteins during macroautophagy (By similarity).
Belongs to the ribonuclease III family. Mitochondrion-specific ribosomal protein mL44 subfamily.
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.
Belongs to the transthyretin family. 5-hydroxyisourate hydrolase subfamily.
Transcription factor required for smad1 and smad2-mediated responses to TGFbeta during mesoderm induction.
Component of a calcium channel complex with CACNA1S.
Required for normal excitation-contraction coupling in skeletal muscle and for normal muscle contraction in response to membrane depolarization. Required for normal Ca(2+) release from the sarcplasmic reticulum, which ultimately leads to muscle contraction. Probably functions via its effects on muscle calcium channels. Increases CACNA1S channel activity, in addition to its role in enhancing the expression of CACNA1S at the cell membrane. Has a redundant role in promoting the expression of the calcium channel CACNA1S at the cell membrane.
ATPase required for the post-translational delivery of tail-anchored (TA) proteins to the endoplasmic reticulum. Recognizes and selectively binds the transmembrane domain of TA proteins in the cytosol. This complex then targets to the endoplasmic reticulum by membrane-bound receptors GET1/WRB and CAMLG/GET2, where the tail-anchored protein is released for insertion. This process is regulated by ATP binding and hydrolysis. ATP binding drives the homodimer towards the closed dimer state, facilitating recognition of newly synthesized TA membrane proteins. ATP hydrolysis is required for insertion. Subsequently, the homodimer reverts towards the open dimer state, lowering its affinity for the GET1-CAMLG receptor, and returning it to the cytosol to initiate a new round of targeting.
Homodimer. Component of the Golgi to ER traffic (GET) complex, which is composed of GET1/WRB, CAMLG/GET2 and GET3/TRC40. Within the complex, CAMLG and GET1 form a heterotetramer which is stabilized by phosphatidylinositol binding and which binds to the GET3 homodimer.
Belongs to the NADPH-dependent diflavin oxidoreductase NDOR1 family.
Interacts with CIAPIN1; as part of the cytosolic iron-sulfur (Fe-S) protein assembly (CIA) machinery.
NADPH-dependent reductase which is a central component of the cytosolic iron-sulfur (Fe-S) protein assembly (CIA) machinery. Transfers electrons from NADPH via its FAD and FMN prosthetic groups to the [2Fe-2S] cluster of CIAPIN1, another key component of the CIA machinery. In turn, this reduced cluster provides electrons for assembly of cytosolic iron-sulfur cluster proteins. It can also reduce the [2Fe-2S] cluster of CISD1 and activate this protein implicated in Fe/S cluster repair.
Belongs to the proteasome subunit S1 family.
Myristoylated in vitro; myristoylation is not essential for protein targeting to Golgi compartment.
Necessary for correct organization of Golgi apparatus.
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.
Adapter protein that provides a critical link between cell surface growth factor receptors and the Ras signaling pathway. Promotes meiotic reinitiation during oocyte maturation.
The two SH3 domains and the SH2 domain are necessary for the reinitiation of oocyte meiosis.
Belongs to the glycosyl hydrolase 39 family.
Mannosyltransferase involved in glycosylphosphatidylinositol-anchor biosynthesis. Transfers the first alpha-1,4-mannose to GlcN-acyl-PI during GPI precursor assembly (By similarity).
Mannosyltransferase involved in glycosylphosphatidylinositol-anchor biosynthesis. Transfers the first alpha-1,4-mannose to GlcN-acyl-PI during GPI precursor assembly.
Belongs to the POU transcription factor family. Class-5 subfamily.
Interacts with components of the transcription complex that assembles on the vent2-B gene, including vent2 (via C-terminus), smad1 and smad4. Forms a repression complex on the promoters of the gsc and mix2 genes via interactions with the nodal/activin signaling pathway transducers foxh1/fast1, gtf2ird1/wbscr11 and smad2. Forms a repression complex on the promoters of the nodal/nr1 and siamois genes with the maternal factors tcf7l1/tcf3 and vegt (By similarity).
Transcription factor that binds to the octamer motif (5'-ATTTGCAT-3'). Activates transcription when directly bound to the octamer DNA sequence, but can form repression complexes with other proteins at the promoter site to inhibit transcription. Binds to the promoter of the vent2-B gene to activate transcription when in the presence of other BMP signaling factors also bound to the promoter. Inhibits the competence of ectodermal cells to respond to BMP during embryogenesis thereby inhibiting epidermal differentiation and promoting neural induction. Antagonizes the activity of nodal/activin signaling by forming a transcriptional repression complex on the gsc and mix2 gene promoters to inhibit their transcription, and thus maintain the undifferentiated state of embryonic cells to prevent them from differentiating prematurely. Acts maternally to inhibit vegt and beta-catenin-activated gene transcription by forming a transcriptional repression complex on the nodal/nr1 and siamois promoters to inhibit their transcription (By similarity).
Binds to the LIM domain of a wide variety of LIM domain-containing transcription factors. Acts as a coactivator together with otx2 to stimulate lhx1/lim1-mediated activation of the gsc promoter in the Spemann organizer. Acts synergistically with lhx1/lim1 and ssbp in axis formation (By similarity).
Forms homodimers and heterodimers. Interacts with and activates lhx1/lim1. The stoichiometry of lhx1/lim1 and ldb1 is important for their function and an excess of ldb1 can inhibit lhx1/lim1 function. When bound to lhx1/lim1, escapes degradation by rnf12. Interacts with the N-terminal region of rnf12 (By similarity).
The dimerization domain is located in the N-terminus.
Undergoes rnf12-mediated ubiquitin-proteasome-dependent degradation.
Belongs to the WD repeat peroxin-7 family.
Belongs to the sirtuin family. Class II subfamily.
NAD-dependent protein deacylase. Catalyzes the NAD-dependent hydrolysis of acyl groups from lysine residues.
Chaperone protein which promotes assembly of the 20S proteasome as part of a heterodimer with PSMG1.
Belongs to the cytochrome c oxidase VIIb family.
Plays an important role in the synaptic function of specific neuronal systems. Associates with proteins involved in vesicle docking and membrane fusion.
Although this protein contains the conserved Asp-247 that functions as an active site, this protein does not have proteolytic activity, and may therefore be catalytically inactive.
Aspartic protease that mediates the cleavage of NFE2L1/NRF1 at 'Leu-104', thereby promoting release of NFE2L1/NRF1 from the endoplasmic reticulum membrane. Ubiquitination of NFE2L1/NRF1 is a prerequisite for cleavage, suggesting that DDI2 specifically recognizes and binds ubiquitinated NFE2L1/NRF1. Seems to act as a proteasomal shuttle which links the proteasome and replication fork proteins like RTF2. Required for cellular survival following replication stress.
Belongs to the acetate uptake transporter (AceTr) (TC 2.A.96) family.
Belongs to the protease inhibitor I27 (calpastatin) family.
Specific inhibition of calpain (calcium-dependent cysteine protease). Plays a key role in postmortem tenderization of meat and have been proposed to be involved in muscle protein degradation in living tissue.
Component of the N-terminal acetyltransferase C (NatC) complex, which is composed of NAA35, NAA38 and NAA30.
Iodination and coupling of the hormonogenic tyrosines in thyroglobulin to yield the thyroid hormones T(3) and T(4).
Belongs to the acetyltransferase family. NAA60 subfamily.
Monomer and homodimer; monomer in presence of substrate and homodimer in its absence.
N-alpha-acetyltransferase that specifically mediates the acetylation of N-terminal residues of the transmembrane proteins, with a strong preference for N-termini facing the cytosol. Displays N-terminal acetyltransferase activity towards a range of N-terminal sequences including those starting with Met-Lys, Met-Val, Met-Ala and Met-Met. Required for normal chromosomal segregation during anaphase. May also show histone acetyltransferase activity; such results are however unclear in vivo and would require additional experimental evidences.
Probably catalyzes the deacetylation of acetylated carbohydrates an important step in the degradation of oligosaccharides.
Belongs to the oligoribonuclease family.
Belongs to the amidase family. GatA subfamily.
Metallocarboxypeptidase that mediates deglutamylation of tubulin and non-tubulin target proteins. Catalyzes the removal of polyglutamate side chains present on the gamma-carboxyl group of glutamate residues within the C-terminal tail of alpha- and beta-tubulin. Cleaves alpha- and gamma-linked polyglutamate tubulin side-chain, as well as the branching point glutamate. Also catalyzes the removal of alpha-linked glutamate residues from the carboxy-terminus of alpha-tubulin.
TATA box-binding transcription factor. Members of the TBP family are differentially required to regulate transcription and development during early embryogenesis. Required for gastrulation. Regulates a large subset of genes that are ventrally expressed (By similarity). Binds to a subset of promoters.
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 (By similarity). 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 (By similarity). 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 (By similarity).
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 (By similarity). Selenium-binding protein which may be involved in the sensing of reactive xenobiotics in the cytoplasm. May be involved in intra-Golgi protein transport (By similarity).
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 protein kinase superfamily. TKL Ser/Thr protein kinase family. RAF subfamily.
Mediates the voltage-dependent proton permeability of excitable membranes. Forms a proton-selective channel through which protons may pass in accordance with their electrochemical gradient (By similarity).
The C-terminal coiled coil region mediates homodimerization. It is essential for normal subcellular localization (By similarity).
The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position. Unlike other voltage-gated ion channels it lacks the pore domain (By similarity).
In the C-terminal section; belongs to the saccharopine dehydrogenase family.
Transcriptional repressor involved in embryonic nervous system development. Plays a role in the induction and patterning of the anterior-posterior neural axis. Involved in the establishment of floor plate differentiation from neural plate cells during gastrulation. Binds the anf1 promoter sequence to restrict expression of anf1 to the anterior of the neural plate, thereby patterning the forebrain. Can bind to the HNF-3-alpha DNA target sequence. Cooperates with t/bra in a dose-dependent manner to specify dorsal mesoderm formation, including notochord. May be involved in the dorso-ventral patterning of the mesoderm. Binds to DNA via the target sequence 5'-[GA]TAAA[TC]A-3', with 5'-GTAAATA-3' being the preferred binding site (By similarity).
Probable component of the PAM complex at least composed of a mitochondrial HSP70 protein, GRPE, TIMM44, TIMM16/PAM16 and TIMM14. Associates with the TIM23 complex.
Regulates ATP-dependent protein translocation into the mitochondrial matrix.
The J-like region, although related to the J domain does not have co-chaperone activity.
Belongs to the complex I NDUFB5 subunit family.
Belongs to the UPL family. TOM1/PTR1 subfamily.
Interacts with several SH3 domain-containing proteins and with poly-ubiquitinated proteins.
The RING-type zinc finger domain mediates binding to an E2 ubiquitin-conjugating enzyme.
The UBA domain interacts with poly-ubiquitinated proteins.
This protein has one functional calcium-binding site.
Belongs to the flagellar radial spoke RSP4/6 family.
Component of sperm axonemal radial spoke complexes.
Functions as part of radial spoke complexes in the axoneme of sperm flagella that play an important part in motility. The triple radial spokes (RS1, RS2 and RS3) are required to modulate beating of the sperm flagellum.
Involved in the 3'-end formation of mRNA precursors (pre-mRNA) by the addition of a poly(A) tail of 200-250 nt to the upstream cleavage product. Stimulates poly(A) polymerase (PAPOLA) conferring processivity on the poly(A) tail elongation reaction and controls also the poly(A) tail length. Increases the affinity of poly(A) polymerase for RNA. Binds to poly(A) and to poly(G) with high affinity. May protect the poly(A) tail from degradation.
Monomer and homooligomer. Binds RNA as a monomer and oligomerizes when bound to poly(A) (By similarity).
The RRM domain is essential for specific adenine bases recognition in the poly(A) tail but not sufficient for poly(A) binding.
PP1 comprises a catalytic subunit, ppp1c1, ppp1cb or ppp1cc, which is folded into its native form by inhibitor 2 and glycogen synthetase kinase 3, and then is complexed to one or several targeting or regulatory subunits.
Protein phosphatase 1 (PP1) is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Promotes nuclear envelope reassembly by targeting nuclear membrane vesicles to chromatin at the end of mitosis. Acts by dephosphorylating membrane proteins such as lamin B receptor (lbr) to regulate the binding of membrane proteins to chromatin (By similarity).
Adapter protein involved in the Toll-like receptor and IL-1 receptor signaling pathway in the innate immune response.
The intermediate domain (ID) is required for the phosphorylation and activation of IRAK.
The CLIR and LIR-like motifs are required for interaction with AT8 family proteins.
Xenophagy-specific receptor required for autophagy-mediated intracellular bacteria degradation (By similarity). Acts as an effector protein of galectin-sensed membrane damage that restricts the proliferation of infecting pathogens upon entry into the cytosol by targeting galectin-associated bacteria for autophagy (By similarity). Initially orchestrates bacteria targeting to autophagosomes and subsequently ensures pathogen degradation by regulating pathogen-containing autophagosome maturation (By similarity). May play a role in ruffle formation and actin cytoskeleton organization and seems to negatively regulate constitutive secretion (By similarity).
Among the many cysteines in the lumenal domain, most are probably involved in disulfide bonds.
tRNA nucleus export receptor which facilitates tRNA translocation across the nuclear pore complex.
Belongs to the Mediator complex subunit 31 family.
Probably mediates the hydrolysis of some nucleoside diphosphate derivatives.
Auxillary component of the N-terminal acetyltransferase C (NatC) complex which catalyzes acetylation of N-terminal methionine residues.
May play a role in preventing exon skipping, ensuring the accuracy of splicing and regulating alternative splicing.
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1E gives rise to R-type calcium currents.
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 Mediator complex subunit 15 family.
Transporter for the divalent cation Zn(2+). Mediates the influx of Zn(2+) into cells from extracellular space.
May protect the cells against DNA damage caused by exposure to the cold-warming stress and facilitates tissue damage repair during the recovery phase.
Interacts with bmpr1a, bmpr1b and bmpr2.
Serine/threonine protein phosphatase that may dephosphorylate and activate lipins. Lipins are phosphatidate phosphatases that catalyze the conversion of phosphatidic acid to diacylglycerol and control the metabolism of fatty acids at different levels. May indirectly modulate the lipid composition of nuclear and/or endoplasmic reticulum membranes and be required for proper nuclear membrane morphology and/or dynamics. May also indirectly regulate the production of lipid droplets and triacylglycerol. Induces neuronal differentiation by antagonizing BMP signaling. Acts both by dephosphorylating BMPR1A and by promoting BMPR2 proteasomal degradation (By similarity).
Component of some SAGA transcription coactivator-HAT complexes. Within the SAGA complex, participates to a subcomplex of SAGA called the DUB module (deubiquitination module).
Component of the transcription regulatory histone acetylation (HAT) complex SAGA, a multiprotein complex that activates transcription by remodeling chromatin and mediating histone acetylation and deubiquitination. Within the SAGA complex, participates in a subcomplex that specifically deubiquitinates histone H2B. The SAGA complex is recruited to specific gene promoters by activators, where it is required for transcription.
The C-terminal SGF11-type zinc-finger domain forms part of the 'catalytic lobe' of the SAGA deubiquitination module.
The long N-terminal helix forms part of the 'assembly lobe' of the SAGA deubiquitination module.
Homomultimerizes and interacts with various extracellular matrix components.
Incorporated into fibronectin-containing matrix fibers. May play a role in cell adhesion and migration along protein fibers within the extracellular matrix (ECM). Could be important for certain developmental processes and contribute to the supramolecular organization of ECM architecture, in particular to those of basement membranes.
Component of the DREAM complex, a multiprotein complex that can both act as a transcription activator or repressor depending on the context. Specifically recognizes the consensus motif 5'-TTYRAA-3' in target DNA.
The CRC domain mediates DNA-binding. It contains two CXC subdomains (joined by a flexible linker) which are both required for efficient association with target DNA. Each CXC subdomain coordinates three Zn(2+) ions.
Component of mitochondrial ribonuclease P. Interacts with HSD17B10/MRPP2.
Mitochondrial tRNA N(1)-methyltransferase involved in mitochondrial tRNA maturation. Component of mitochondrial ribonuclease P, which cleaves tRNA molecules in their 5'-ends. Together with hsd17b10/mrpp2, forms a subcomplex of the mitochondrial ribonuclease P, named MRPP1-MRPP2 subcomplex, which displays functions that are independent of the ribonuclease P activity. The MRPP1-MRPP2 subcomplex catalyzes the formation of N(1)-methylguanine and N(1)-methyladenine at position 9 (m1G9 and m1A9, respectively) in tRNAs; trmt10c/mrpp1 acting as the catalytic N(1)-methyltransferase subunit. The MRPP1-MRPP2 subcomplex also acts as a tRNA maturation platform: following 5'-end cleavage by the mitochondrial ribonuclease P complex, the MRPP1-MRPP2 subcomplex enhances the efficiency of 3'-processing catalyzed by ELAC2, retains the tRNA product after elac2 processing and presents the nascent tRNA to the mitochondrial CCA tRNA nucleotidyltransferase TRNT1 enzyme. In addition to tRNA N(1)-methyltransferase activity, trmt10c/mrpp1 also acts as a mRNA N(1)-methyltransferase by mediating methylation of adenosine residues at the N(1) position of MT-ND5 mRNA.
Belongs to the KIF-binding protein family.
Required for organization of axonal microtubules, and axonal outgrowth and maintenance during peripheral and central nervous system development.
Has peptide-independent ATPase activity.
Transcriptional coactivator or corepressor of the p300/CBP-mediated transcription complex. May be involved in sex determination, early gonad development, left-right patterning during embryogenesis and differentiation of the adrenal cortex (By similarity).
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.
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.
Oligomer. Oligomerization is required for RNA-binding and EDEN-dependent deadenylation.
Phosphorylated during oocyte maturation and dephosphorylated following egg activation. Dephosphorylation is calcium dependent and correlates with the increase in the activity of EDEN-dependent deadenylation (By similarity).
RNA-binding protein implicated in the regulation of several post-transcriptional events. May be involved in pre-mRNA alternative splicing, mRNA translation activation and stability (By similarity). Mediates the rapid and sequence-specific cytoplasmic deadenylation of EDEN-containing maternal mRNAs following fertilization. Binds to AU-rich sequences (AREs) of jun mRNA. Binds to the embryonic deadenylation element (EDEN) motif localized in the 3'-UTR of maternal mRNAs. Binds to RNA containing several repeats of the consensus sequence 5'-UGU-3'. EDEN-dependent deadenylation is enhanced by the presence of an additional cis element composed of three AUU repeats (By similarity).
The 2 N-terminal RRMs and a part of the linker region (between RRM2 and RRM3) are necessary for binding to EDEN of mos mRNA.
Catalyzes the oxidation of sulfite to sulfate, the terminal reaction in the oxidative degradation of sulfur-containing amino acids.
Belongs to the dihydropyrimidine dehydrogenase family.
Binds 4 [4Fe-4S] clusters. Contains approximately 16 iron atoms per subunit.
Involved in pyrimidine base degradation. Catalyzes the reduction of uracil and thymine.
Belongs to the eukaryotic ribosomal protein eL34 family.
Catalyzes the exchange of eukaryotic initiation factor 2-bound GDP for GTP.
Complex of five different subunits; alpha, beta, gamma, delta and epsilon.
Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation upon binding with glial cell derived neurotrophic factor family ligands.
Belongs to the sterol desaturase family. SCS7 subfamily.
Binds 2 Zn(2+) ions per subunit that likely form a catalytic dimetal center.
Catalyzes stereospecific hydroxylation of free fatty acids at the C-2 position to produce (R)-2-hydroxy fatty acids, which are building blocks of sphingolipids and glycosphingolipids common in neural tissue and epidermis. Plays an essential role in the synthesis of galactosphingolipids of the myelin sheath. Responsible for the synthesis of sphingolipids and glycosphingolipids involved in the formation of epidermal lamellar bodies critical for skin permeability barrier. Participates in the synthesis of glycosphingolipids and a fraction of type II wax diesters in sebaceous gland, specifically regulating hair follicle homeostasis. Involved in the synthesis of sphingolipids of plasma membrane rafts, controlling lipid raft mobility and trafficking of raft-associated proteins.
Belongs to the CWC16 family. YJU2 subfamily.
Component of the spliceosome. Present in the activated B complex, the catalytically activated B* complex which catalyzes the branching, the catalytic step 1 C complex catalyzing the exon ligation, and the postcatalytic P complex containing the ligated exons (mRNA) and the excised lariat intron.
Part of the spliceosome which catalyzes two sequential transesterification reactions, first the excision of the non-coding intron from pre-mRNA and then the ligation of the coding exons to form the mature mRNA. Plays a role in stabilizing the structure of the spliceosome catalytic core and docking of the branch helix into the active site, producing 5'-exon and lariat intron-3'-intermediates. May protect cells from TP53-dependent apoptosis upon dsDNA break damage through association with PRP19-CD5L complex.
Also able to convert testosterone (T) into 5-alpha-dihydrotestosterone (DHT).
Belongs to the steroid 5-alpha reductase family. Polyprenol reductase subfamily.
Plays a key role in early steps of protein N-linked glycosylation by being required for the conversion of polyprenol into dolichol. Dolichols are required for the synthesis of dolichol-linked monosaccharides and the oligosaccharide precursor used for N-glycosylation. Acts as a polyprenol reductase that promotes the reduction of the alpha-isoprene unit of polyprenols into dolichols in a NADP-dependent mechanism.
Plays a key role in early steps of protein N-linked glycosylation by being required for the conversion of polyprenol into dolichol. Dolichols are required for the synthesis of dolichol-linked monosaccharides and the oligosaccharide precursor used for N-glycosylation. Acts as a polyprenol reductase that promotes the reduction of the alpha-isoprene unit of polyprenols into dolichols in a NADP-dependent mechanism. Also able to convert testosterone (T) into 5-alpha-dihydrotestosterone (DHT).
Transcription repressor that specifically binds the 5'-GGAG[GA]A[GA]A-3' consensus sequence. Represses transcription by recruiting the chromatin multiprotein complex NuRD to target promoters. Negatively regulates expression of EGFR, a gene involved in cell proliferation, survival and migration (By similarity).
Arginine methyltransferase that can catalyze the formation of both omega-N monomethylarginine (MMA) and asymmetrical dimethylarginine (aDMA), with a strong preference for the formation of aDMA. Preferentially methylates arginyl residues present in a glycine and arginine-rich domain and displays preference for monomethylated substrates. Specifically mediates the asymmetric dimethylation of histone H3 'Arg-2' to form H3R2me2a. H3R2me2a represents a specific tag for epigenetic transcriptional repression and is mutually exclusive with methylation on histone H3 'Lys-4' (H3K4me2 and H3K4me3). Acts as a transcriptional repressor of various genes such as HOXA2, THBS1 and TP53. Repression of TP53 blocks cellular senescence. Also methylates histone H2A and H4 'Arg-3' (H2AR3me and H4R3me, respectively). Acts as a regulator of DNA base excision during DNA repair by mediating the methylation of DNA polymerase beta (POLB), leading to the stimulation of its polymerase activity by enhancing DNA binding and processivity. Methylates HMGA1. Regulates alternative splicing events. Acts as a transcriptional coactivator of a number of steroid hormone receptors including ESR1, ESR2, PGR and NR3C1.
Belongs to the class I-like SAM-binding methyltransferase superfamily. Protein arginine N-methyltransferase family. PRMT6 subfamily.
Inhibited competitively by AMP and IMP and non-competitively by fructose 1,6-bisphosphate.
Plays an important role in the de novo pathway and in the salvage pathway of purine nucleotide biosynthesis. Catalyzes the first commited step in the biosynthesis of AMP from IMP.
Plays an important role in the de novo pathway and in the salvage pathway of purine nucleotide biosynthesis. Catalyzes the first committed step in the biosynthesis of AMP from IMP.
Plays an important role in the de novo pathway of purine nucleotide biosynthesis.
Belongs to the CND2 H2 (condensin-2 subunit 2) family.
Component of the condensin-2 complex, which contains the smc2 and smc4 heterodimer, and three non SMC subunits, ncapg2, ncaph2 and ncapd3 that probably regulate the complex.
Regulatory subunit of the condensin-2 complex, a complex that seems to provide chromosomes with an additional level of organization and rigidity and in establishing mitotic chromosome architecture.
This is one of the enzymes that catalyzes the last step of the mitochondrial beta-oxidation pathway, an aerobic process breaking down fatty acids into acetyl-CoA. Using free coenzyme A/CoA, catalyzes the thiolytic cleavage of medium- to long-chain 3-oxoacyl-CoAs into acetyl-CoA and a fatty acyl-CoA shortened by two carbon atoms. The activity of the enzyme is reversible and it can also catalyze the condensation of two acetyl-CoA molecules into acetoacetyl-CoA. Thereby, it plays a major role in ketone body metabolism.
Belongs to the importin beta family. Importin beta-1 subfamily.
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 universal ribosomal protein uL5 family.
Belongs to the Mediator complex subunit 27 family.
May mediate the intracellular trafficking of ceramide in a non-vesicular manner.
The PH domain targets the Golgi apparatus.
The START domain recognizes ceramide and mediates the intermembrane transfer of ceramide.
Belongs to the Golgi pH regulator (TC 1.A.38) family.
Induces CD27-mediated apoptosis. Inhibits BCL2L1 isoform Bcl-x(L) anti-apoptotic activity. Inhibits activation of NF-kappa-B and promotes T-cell receptor-mediated apoptosis.
Belongs to the SPTSS family. SPTSSA subfamily.
Component of the serine palmitoyltransferase (SPT) complex, which is composed of SPTLC1, SPTLC2 or SPTLC3 and SPTSSA or SPTSSB. The heterodimer consisting of SPTLC1 and SPTLC2/SPTLC3 forms the catalytic core of the enzyme, while SPTSSA or SPTSSB subunits determine substrate specificity. SPT also interacts with ORMDL proteins, especially ORMDL3, which negatively regulate SPT activity in the presence of ceramides.
Component of the serine palmitoyltransferase multisubunit enzyme (SPT) that catalyzes the initial and rate-limiting step in sphingolipid biosynthesis by condensing L-serine and activated acyl-CoA (most commonly palmitoyl-CoA) to form long-chain bases. The SPT complex is composed of SPTLC1, SPTLC2 or SPTLC3 and SPTSSA or SPTSSB. Within this complex, the heterodimer consisting of SPTLC1 and SPTLC2/SPTLC3 forms the catalytic core. Within the SPT complex, SPTSSA stimulates the catalytic activity and plays a role in substrate specificity, which depends upon the overall complex composition. The SPTLC1-SPTLC2-SPTSSA complex shows a strong preference for C16-CoA substrate, while the SPTLC1-SPTLC3-SPTSSA isozyme uses both C14-CoA and C16-CoA as substrates, with a slight preference for C14-CoA. Independently of its action as a SPT component, may be involved in MBOAT7 localization to mitochondria-associated membranes, a membrane bridge between the endoplasmic reticulum and mitochondria, may hence affect MBOAT7-catalyzed incorporation of arachidonic acid into phosphatidylinositol.
Belongs to the L-aspartate dehydrogenase family.
Has a role in non-canonical Wnt/planar cell polarity (PCP) signaling; can recruit dvl/dsh and prickle from the cytoplasm to the plasma membrane. Acts in a PCP complex to regulate the polarized assembly of fibronectrin on the surface of the mesoderm during gastrulation. Regulates convergent extension in both dorsal mesoderm and neural tissue without affecting cell fate. Regulates neural fold closure during neurulation. May be required for cell surface localization of fzd3 and fzd6 in the inner ear (By similarity).
Interacts with dvl/dsh (By similarity). Interacts with prickle3 (By similarity).
Belongs to the transcriptional coactivator PC4 family.
General coactivator that functions cooperatively with TAFs and mediates functional interactions between upstream activators and the general transcriptional machinery. May be involved in stabilizing the multiprotein transcription complex. Binds single-stranded DNA. Also binds, in vitro, non-specifically to double-stranded DNA (ds DNA).
Belongs to the DEAD box helicase family. DDX5/DBP2 subfamily.
Necessary for efficient adipogenesis. Does not show ion channel activity.
Belongs to the TRAFAC class myosin-kinesin ATPase superfamily. Kinesin family. KIN-12 subfamily.
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.
Acts as a negative regulator of autophagy.
The PHD-type zinc-finger domain is required for negative regulation of autophagy.
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.
Forms a complex with PIGT, PIGS, PIGU and GAA1.
Has sphingolipid-delta-4-desaturase activity. Converts D-erythro-sphinganine to D-erythro-sphingosine (E-sphing-4-enine) (By similarity). Catalyzes the equilibrium isomerization of retinols (By similarity).
Interacts with RLBP1; the interaction increases synthesis of chromophore-precursors by DEGS1.
Belongs to the Rab3-GAP regulatory subunit family.
Belongs to the RING-Cys relay (RCR) family.
Acts as a transcriptional activator during early development, limiting the extent of mesoderm formation in the gastrula. Binds to DNA via the target sequence 5'-GT[AC]AACA-3', with 5'-GTAAACA-3' being the preferred binding site (By similarity).
Regulates G protein-coupled receptor signaling cascades, including signaling downstream of the N-formylpeptide chemoattractant receptors and leukotriene receptors. Inhibits B cell chemotaxis (By similarity). Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form (By similarity).
May be involved in the calcium-dependent regulation of rhodopsin phosphorylation. Binds three calcium ions (By similarity).
The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2).
Belongs to the eukaryotic ribosomal protein eS8 family.
Ion channel involved in sensing mechanical pain. Contributes to mechanosensitive currents in nocireceptors and detecting mechanical pain stimuli. May also be required for efficient adipogenesis.
Radial spoke stalk protein that binds heme under oxidizing conditions. Required for the coordinated beating of multiple cilia maybe by functioning in a redox signaling pathway.
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.
ppGpp hydrolyzing enzyme involved in starvation response.
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.
Belongs to the Integrator subunit 7 family.
Belongs to the methylthiotransferase family. MiaB subfamily.
May form with the serine/threonine protein phosphatase ctdnep1 an active complex dephosphorylating and activating lipins. Lipins are phosphatidate phosphatases that catalyze the conversion of phosphatidic acid to diacylglycerol and control the metabolism of fatty acids at different levels. May indirectly modulate the lipid composition of nuclear and/or endoplasmic reticulum membranes and be required for proper nuclear membrane morphology and/or dynamics. May also indirectly regulate the production of lipid droplets and triacylglycerol (By similarity).
Associates with the cleavage and polyadenylation specificity factor (CPSF) complex.
Poly(A) polymerase that creates the 3'-poly(A) tail of specific pre-mRNAs. In addition to polyadenylation, it is also required for the 3'-end cleavage of pre-mRNAs: binds to the 3'UTR of targeted pre-mRNAs and promotes the recruitment and assembly of the CPSF complex on the 3'UTR of pre-mRNAs. In addition to adenylyltransferase activity, also has uridylyltransferase activity. However, the ATP ratio is higher than UTP in cells, suggesting that it functions primarily as a poly(A) polymerase.
The RRM domain is required for terminal uridylyltransferase activity. Together with the zinc-finger domain, binds the 5'-area of U6 snRNA.
The zinc-finger domain is required for terminal uridylyltransferase activity. Together with the RRM domain, binds the 5'-area of U6 snRNA.
Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed to be not involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone.
Mammalian complex I is composed of 45 different subunits.
In the C-terminal section; belongs to the MoaC family.
In the N-terminal section; belongs to the radical SAM superfamily. MoaA family.
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.
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 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.
Component of the CCR4-NOT complex which is one of the major cellular mRNA deadenylases and is linked to various cellular processes including bulk mRNA degradation, miRNA-mediated repression, translational repression during translational initiation and general transcription regulation. Additional complex functions may be a consequence of its influence on mRNA expression. Involved in down-regulation of MYB- and JUN-dependent transcription. Enhances ligand-dependent transcriptional activity of nuclear hormone receptors. May play a role in cell differentiation.
Homodimer. Component of the CCR4-NOT complex.
Seems to play a negative regulatory role in 5-phosphoribose 1-diphosphate synthesis.
Acts as a negative regulator of innate and adaptive immunity by maintaining immune homeostasis. Negative regulator of Toll-like receptor and T-cell receptor function. Prevents hyperresponsiveness of the immune system and maintains immune homeostasis. Inhibits jun/ap1 and NF-kappa-B activation. Promotes Fas-induced apoptosis (By similarity).
Belongs to the TNFAIP8 family. TNFAIP8L2 subfamily.
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).
S-adenosyl-L-methionine-dependent methyltransferase that mediates N(3)-methylcytidine modification of residue 32 of the tRNA anticodon loop of tRNA(Thr)(UGU) and tRNA(Arg)(CCU). N(3)-methylcytidine methylation by mettl2 requires the N6-threonylcarbamoylation of tRNA (t6A37) by the EKC/KEOPS complex as prerequisite.
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.
The Tudor domain specifically recognizes and binds asymmetric dimethylation of histone H3 'Arg-17' (H3R17me2a) and histones H4 'Arg-3', 2 tags for epigenetic transcriptional activation.
May play a role in cell-cell adhesion and epithelium development through its interaction with proteins of the beta-catenin family (By similarity). May play an important role in cortical development, especially in the maintenance of radial glia (By similarity).
Probable GTP-binding protein that possesses GTPase activity. May play a role in endothelial cell polarity and endothelial barrier function (By similarity).
Essential for Golgi structural integrity.
Plays a role in the regulation of cell shape and polarity. Plays a role in cellular protein transport, including protein transport away from primary cilia. Neuroprotective protein (By similarity).
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.
May be involved in MAP kinase activation, epithelial sodium channel (ENaC) down-regulation and cell cycling.
Belongs to the terpene cyclase/mutase family.
Central component of a redox-sensitive mitochondrial intermembrane space import machinery which is required for the biogenesis of respiratory chain complexes (By similarity). Functions as chaperone and catalyzes the formation of disulfide bonds in substrate proteins, such as COX17 or MICU1. Required for the import and folding of small cysteine-containing proteins (small Tim) in the mitochondrial intermembrane space (IMS). Precursor proteins to be imported into the IMS are translocated in their reduced form into the mitochondria.
The CHCH domain contains a conserved twin Cys-X(9)-Cys motif which is required for import and stability of MIA40 in mitochondria.
Belongs to the mannose-6-phosphate isomerase type 1 family.
Catalyzes the oxidation of uric acid to 5-hydroxyisourate, which is further processed to form (S)-allantoin.
Plays a role in cytokinesis. Displays serine/threonine protein kinase activity.
Probable transcription factor. Involved in kidney development, acting synergistically with lhx1/lim-1 to establish the pronephric primordium in late gastrulae/early neurulae (By similarity).
Belongs to the complex I NDUFB6 subunit family.
Component of the origin recognition complex (ORC) that binds origins of replication.
Belongs to the methyltransferase superfamily. HEN1 family.
Methyltransferase that adds a 2'-O-methyl group at the 3'-end of piRNAs, a class of 24 to 30 nucleotide RNAs that are generated by a Dicer-independent mechanism and are primarily derived from transposons and other repeated sequence elements. This probably protects the 3'-end of piRNAs from uridylation activity and subsequent degradation. Stabilization of piRNAs is essential for gametogenesis.
Component of the cleavage and polyadenylation specificity factor (CPSF) complex that play a key role in pre-mRNA 3'-end formation, recognizing the AAUAAA signal sequence and interacting with poly(A) polymerase and other factors to bring about cleavage and poly(A) addition. Cpsf4 binds RNA polymers with a preference for poly(U) (By similarity).
Component of the cleavage and polyadenylation specificity factor (CPSF) complex, composed of cpsf1, cpsf2, cpsf3, cpsf4 and fip1l1.
Component of the NuA4 histone acetyltransferase (HAT) complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histone H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription (By similarity). NuA4 may also play a direct role in DNA repair when directly recruited to sites of DNA damage (By similarity).
Interacts with H3K4me3 and to a lesser extent with H3K4me2. Component of the NuA4 histone acetyltransferase complex.
Belongs to the Mediator complex subunit 23 family.
Autophagy factor required for autophagosome formation. 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.
Belongs to the ATG13 family. Metazoan subfamily.
Phosphorylated under nutrient-rich conditions; dephosphorylated during starvation or following treatment with rapamycin.
Belongs to the archaeal Rpo5/eukaryotic RPB5 RNA polymerase subunit family.
DNA-dependent RNA polymerase catalyzes the transcription of DNA into RNA using the four ribonucleoside triphosphates as substrates. Common component of RNA polymerases I, II and III which synthesize ribosomal RNA precursors, mRNA precursors and many functional non-coding RNAs, and small RNAs, such as 5S rRNA and tRNAs, respectively. Pol II is the central component of the basal RNA polymerase II transcription machinery. Pols are composed of mobile elements that move relative to each other. In Pol II, POLR2E/RPB5 is part of the lower jaw surrounding the central large cleft and thought to grab the incoming DNA template. Seems to be the major component in this process.
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.
Regulates the trafficking and gating properties of AMPA-selective glutamate receptors (AMPARs). Promotes their targeting to the cell membrane and synapses and modulates their gating properties by slowing their rates of activation, deactivation and desensitization. Does not show subunit-specific AMPA receptor regulation and regulates all AMPAR subunits. Thought to stabilize the calcium channel in an inactivated (closed) state.
Mediates the endoplasmic reticulum-associated degradation (ERAD) of inositol 1,4,5-trisphosphate receptors (IP3Rs). Promotes sterol-accelerated ERAD of HMGCR. Involved in regulation of cellular cholesterol homeostasis by regulation the SREBP signaling pathway (By similarity).
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.
Component of specific cytoplasmic RNA granules involved in post-transcriptional regulation of specific genes: probably acts by binding to specific mRNAs and regulating their translation. Probably required during spermatogenesis (By similarity).
Acts as a transcriptional regulator. Binds DNA and RNA (By similarity).
Belongs to the SelWTH family. Selenoprotein T subfamily.
May contain a selenide-sulfide bond between Cys-51 and Sec-54. This bond is speculated to serve as redox-active pair (By similarity).
Selenoprotein with thioredoxin reductase-like oxidoreductase activity.
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.
Plays a role in the regulatory network through which muscle cells coordinate their structural and functional states during growth, adaptation, and repair.
Involved in poly(A) tail length control in neuronal cells. Binds the polyadenosine RNA oligonucleotides.
Potent suppressor of cytokine production that acts as a regulator of innate immune signaling and inflammation. Acts as a key negative regulator of select cytokine and chemokine responses elicited by TRIF-independent Toll-like receptors (TLRs), thereby limiting inflammatory cytokine responses to minor insults (By similarity). Has ribonuclease activity (By similarity).
Inactive when phosphorylated. Phosphorylation levels vary during development. Dephosphorylated by pdxp (By similarity).
May play a role in the regulation of cell morphology and cytoskeletal organization (By similarity). Binds to F-actin and exhibits pH-sensitive F-actin depolymerizing activity. Required for formation of the cleavage furrow during cytokinesis.
Belongs to the Dus family. Dus3 subfamily.
Catalyzes the synthesis of dihydrouridine, a modified base, in various RNAs, such as tRNAs, mRNAs and some long non-coding RNAs (lncRNAs). Mainly modifies the uridine in position 47 (U47) in the D-loop of most cytoplasmic tRNAs. Also able to mediate the formation of dihydrouridine in some mRNAs, thereby regulating their translation.
Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ6 subfamily.
Involved in ciliary process assembly. May play a role in the trafficking of ciliary membrane proteins from the Golgi complex to the cilium. Regulates the platelet-derived growth factor receptor-alpha (PDGFRA) signaling pathway. Plays an important role in spermatogenesis, particularly spermiogenesis, when germ cells form flagella.
3'-5'-exoribonuclease that specifically recognizes RNAs polyuridylated at their 3' end and mediates their degradation. Component of an exosome-independent RNA degradation pathway that mediates degradation of both mRNAs and miRNAs that have been polyuridylated by a terminal uridylyltransferase. Essential for correct mitosis, and negatively regulates cell proliferation.
Belongs to the RNR ribonuclease family. DIS3L2 subfamily.
Specifically recognizes and binds polyuridylated RNAs via 3 RNA-binding regions (named U-zone 1, U-zone 2 and U-zone 3) that form an open funnel on one face of the catalytic domain, allowing RNA to navigate a path to the active site.
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 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.
Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. Catalyzes monoubiquitination. Involved in degradation of misfolded chaperone substrate and DNA repair.
May bee involved in the oxidative stress-induced survival signaling. Binds RNA. May participate in mRNA transport in the cytoplasm (By similarity).
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).
Required for KRAS signaling regulation and modulation of cell proliferation (By similarity). Regulator of KRAS prenylation, and probably prenylation of other small GTPases (By similarity). Required for lymphocyte development and function (By similarity). Not required for myeloid cell development (By similarity).
Template-independent DNA polymerase which catalyzes the random addition of deoxynucleoside 5'-triphosphate to the 3'-end of a DNA initiator.
Acts as an adapter for the XPO1/CRM1-mediated export of the 60S ribosomal subunit.
Belongs to the cytochrome c-type heme lyase family.
Lyase that catalyzes the covalent linking of the heme group to the cytochrome C apoprotein to produce the mature functional cytochrome.
Involved in the signal transduction pathway mediated by multiple Wnt genes (By similarity). Required during ciliogenesis for the docking of basal bodies to the apical plasma membrane (By similarity).
Non-catalytic component of the KPC complex, a E3 ubiquitin-protein ligase complex that mediates polyubiquitination of target proteins, such as CDKN1B and NFKB1. Within the KPC complex, UBAC1 acts as an adapter that promotes the transfer of target proteins that have been polyubiquitinated by RNF123/KPC1 to the 26S proteasome.
The UBA domains recognize and bind polyubiquitinated proteins.
Tachykinins are active peptides which excite neurons, evoke behavioral responses, are potent vasodilators and secretagogues, and contract (directly or indirectly) many smooth muscles.
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.
Forms a beta-barrel structure that accommodates hydrophobic ligands in its interior.
Hydrolase that removes conjugated ubiquitin from target proteins and regulates various pathways such as the TGF-beta receptor signaling and NF-kappa-B pathways. Acts as a key regulator of TGF-beta receptor signaling pathway, but the precise mechanism is still unclear: according to a report, acts by promoting deubiquitination of monoubiquitinated R-SMADs, thereby alleviating inhibition of R-SMADs and promoting activation of TGF-beta target genes. According to another reports, regulates the TGF-beta receptor signaling pathway by mediating deubiquitination and stabilization of tgfbr1, leading to an enhanced TGF-beta signal. May also regulate gene expression and/or DNA repair through the deubiquitination of histone H2B. Involved in endosome organization by mediating deubiquitination of rnf26 target(s), releasing vesicles that are restrained in the perinuclear region.
Endonuclease that mediates miRNA decay of both protein-free and AGO2-loaded miRNAs.
Transcription factor involved in epidermis differentiation.
Belongs to the eukaryotic ribosomal protein eS21 family.
Calretinin is a calcium-binding protein which is abundant in auditory neurons.
A caudalizing protein which is required to pattern the anterior/posterior (A/P) axis during central nervous system (CNS) formation. Inhibits anterior neural expression and acts as a transcriptional activator to induce posterior neural gene expression. Maintains a proper A/P balance required for hindbrain formation by activating the FGF/MAPK pathway, which modulates the planar cell polarity (PCP) pathway. Interacts with retinoid signaling during hindbrain patterning (By similarity).
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.
Essential component of glycosylphosphatidylinositol-mannosyltransferase 1 which transfers the first of the 4 mannoses in the GPI-anchor precursors during GPI-anchor biosynthesis.
E3 ubiquitin-protein ligase involved in Golgi membrane fusion and regulation of small GTPases. Acts as a regulator of Golgi membrane dynamics during the cell cycle: recruited to Golgi membrane by Rab proteins and regulates postmitotic Golgi membrane fusion. Acts by mediating ubiquitination during mitotic Golgi disassembly, ubiquitination serving as a signal for Golgi reassembly later, after cell division.
Interacts with FLNA (via filamin repeat 21); increases PKA-mediated phosphorylation of FLNA.
This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium.
E3 ubiquitin-protein ligase that functions in the antephase checkpoint by actively delaying passage into mitosis in response to microtubule poisons. Acts in early prophase before chromosome condensation, when the centrosome move apart from each other along the periphery of the nucleus. Probably involved in signaling the presence of mitotic stress caused by microtubule poisons by mediating the 'Lys-48'-linked ubiquitination of target proteins, leading to their degradation by the proteasome. May also promote the formation of 'Lys-63'-linked polyubiquitin chains and functions with the specific ubiquitin-conjugating ubc13-mms2 (ube2n-ube2v2) heterodimer. Substrates that are polyubiquitinated at 'Lys-63' are usually not targeted for degradation, but are rather involved in signaling cellular stress.
The FHA domain plays a key role in the anti-proliferative properties of the protein and is involved in initiating a cell cycle arrest at G2/M.
The PBZ-type zinc finger (also named CYR) mediates non-covalent poly(ADP-ribose)-binding. Poly(ADP-ribose)-binding is dependent on the presence of zinc and is required for its function in antephase checkpoint.
Utilization of purines as secondary nitrogen sources, when primary sources are limiting.
Belongs to the complex I NDUFA7 subunit family.
Belongs to the ATPase delta chain family.
Mitochondrial membrane ATP synthase (F(1)F(0) ATP synthase or Complex V) produces ATP from ADP in the presence of a proton gradient across the membrane which is generated by electron transport complexes of the respiratory chain. F-type ATPases consist of two structural domains, F(1) - containing the extramembraneous catalytic core and F(0) - containing the membrane proton channel, linked together by a central stalk and a peripheral stalk. During catalysis, ATP synthesis in the catalytic domain of F(1) is coupled via a rotary mechanism of the central stalk subunits to proton translocation. Part of the complex F(0) domain and the peripheric stalk, which acts as a stator to hold the catalytic alpha(3)beta(3) subcomplex and subunit a/ATP6 static relative to the rotary elements.
Belongs to the 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.
Component of the multi-pass translocon (MPT) complex that mediates insertion of multi-pass membrane proteins into the lipid bilayer of membranes. The MPT complex takes over after the SEC61 complex: following membrane insertion of the first few transmembrane segments of proteins by the SEC61 complex, the MPT complex occludes the lateral gate of the SEC61 complex to promote insertion of subsequent transmembrane regions.
Component of the multi-pass translocon (MPT) complex.
Belongs to the phosphoenolpyruvate carboxykinase [GTP] family.
Adenine glycosylase active on G-A mispairs.
Homodimerizes, the dimers can polymerize end-to-end to form filamentous structures. Interacts with GTP-bound cdc42 and wasl/n-wasp (By similarity).
Required to coordinate membrane tubulation with reorganization of the actin cytoskeleton during endocytosis. Promotes cdc42-induced actin polymerization by activating the wasl-waspip complex, the predominant form of wasl/n-wasp in cells. Essential for autophagy of intracellular bacterial pathogens (By similarity).
The F-BAR domain binds the phospholipid membrane with its concave surface. The end-to-end polymerization of dimers of these domains provides a curved surface that fits best membranes with around 600 A diameter, and may drive tubulation (By similarity).
May play a role in the development of the central system.
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 (By similarity).
Directs RNA polymerase II nuclear import.
Interacts (via cytoplasmic region) with ILK.
Transmembrane receptor that senses neutrophil extracellular traps (NETs) and triggers the ILK-PARVB pathway to enhance cell motility. NETs are mainly composed of DNA fibers and are released by neutrophils to bind pathogens during inflammation. Specifically binds NETs on its extracellular region, in particular the 8-OHdG-enriched DNA present in NETs, and recruits ILK, initiating the ILK-PARVB cascade to induce cytoskeleton rearrangement and directional migration of cells.
Receptor for the C-terminal sequence motif K-D-E-L that is present on endoplasmic reticulum resident proteins and that mediates their recycling from the Golgi back to the endoplasmic reticulum (By similarity). Binding is pH dependent, and is optimal at pH 5-5.4 (By similarity).
Heterodimer of a catalytic subunit and a regulatory subunit.
Belongs to the argonaute family. Piwi subfamily.
Endoribonuclease that plays a central role during spermatogenesis by repressing transposable elements and preventing their mobilization, which is essential for the germline integrity. Plays an essential role in meiotic differentiation of spermatocytes, germ cell differentiation and in self-renewal of spermatogonial stem cells. Acts via the piRNA metabolic process, which mediates the repression of transposable elements during meiosis by forming complexes composed of piRNAs and Piwi proteins and govern the methylation and subsequent repression of transposons. During piRNA biosynthesis, plays a key role in the piRNA amplification loop, also named ping-pong amplification cycle, by acting as a 'slicer-competent' piRNA endoribonuclease that cleaves primary piRNAs, which are then loaded onto 'slicer-incompetent' piwil4. Piwil2 slicing produces a pre-miRNA intermediate, which is then processed in mature piRNAs, and as well as a 16 nucleotide by-product that is degraded. Required for piwil4/miwi2 nuclear localization and association with secondary piRNAs antisense. Represses circadian rhythms by promoting the stability and activity of core clock components BMAL1 and CLOCK (By similarity).
Expressed in oocytes, testis and liver (at protein level).
Methylated on arginine residues; required for the interaction with Tudor domain-containing protein and subsequent localization to the meiotic nuage, also named P granule.
Belongs to the mitochondrion-specific ribosomal protein mL51 family.
Component of the mitochondrial ribosome large subunit (39S) which comprises a 16S rRNA and about 50 distinct proteins (By similarity).
Retinol dehydrogenase with a clear preference for NADP. Converts all-trans-retinol to all-trans-retinal. Has no detectable activity towards 11-cis-retinol, 9-cis-retinol and 13-cis-retinol (By similarity).
Binds preferentially to dsRNA, but also to RNA-DNA hybrids.
The zinc-finger domains are required for binding to dsRNA, and also for nuclear localization.
Forms homotrimers. In the presence of substrate, may form higher-order multimers in a PDZ-independent manner.
Serine protease with a variety of targets, including extracellular matrix proteins and proteoglycans such as biglycan, syndecan-4 and glypican-4. Through cleavage of proteoglycans, may release soluble FGF-glycosaminoglycan complexes that promote the range and intensity of FGF signals in the extracellular space. Consequently, facilitates inductive processes in the developing embryo, such as posteriorization, mesoderm induction and neuronal differentiation. Regulates the availability of insulin-like growth factors (IGFs) by cleaving IGF-binding proteins. Inhibits signaling mediated by TGF-beta family members. Consequently, may regulate many physiological processes. Intracellularly, degrades TSC2, leading to the activation of TSC2 downstream targets (By similarity).
Belongs to the ubiquitin-conjugating enzyme family. UFC1 subfamily.
E1-like enzyme which specifically catalyzes the second step in ufmylation. Ufmylation is involved in reticulophagy (also called ER-phagy) induced in response to endoplasmic reticulum stress.
Required for the post-translational delivery of tail-anchored (TA) proteins to the endoplasmic reticulum. Together with GET1/WRB, acts as a membrane receptor for soluble GET3/TRC40, which recognizes and selectively binds the transmembrane domain of TA proteins in the cytosol. Required for the stability of GET1. Stimulates calcium signaling in T cells through its involvement in elevation of intracellular calcium. Essential for the survival of peripheral follicular B cells.
Interacts with the transcription factors tcf7l1/tcf3 and vegt.
Transcription factor that binds to the octamer motif (5'-ATTTGCAT-3'). Antagonizes the activity of nodal/activin signaling during gastrulation to suppress mesendoderm formation. Acts maternally to inhibit vegt and beta-catenin-activated gene transcription, probably by forming a transcriptional repression complex on the promoters of target genes. Binds to an octamer motif in interspersed RNA (By similarity).
Belongs to the GHMP kinase family. Mevalonate kinase subfamily.
Catalyzes the phosphorylation of mevalonate to mevalonate 5-phosphate, a key step in isoprenoid and cholesterol biosynthesis.
Component of the intraflagellar transport (IFT) complex B required for transport of proteins in the motile cilium. Required for transport of specific ciliary cargo proteins related to motility, while it is neither required for IFT complex B assembly or motion nor for cilium assembly. Plays a key role in maintaining the integrity of the IFT complex B and the proper ciliary localization of the IFT complex B components. Essential for maintaining proper microtubule organization within the ciliary axoneme.
Belongs to the eukaryotic release factor 1 family. Pelota subfamily.
Component of the Pelota-HBS1L complex, a complex that recognizes stalled ribosomes and triggers the No-Go Decay (NGD) pathway. In the Pelota-HBS1L complex, pelo recognizes ribosomes stalled at the 3' end of an mRNA and engages stalled ribosomes by destabilizing mRNA in the mRNA channel.
May play a role in motor coordination and exploratory behavior.
Belongs to the radical SAM superfamily. Lipoyl synthase family.
Binds 2 [4Fe-4S] clusters per subunit. One cluster is coordinated with 3 cysteines and an exchangeable S-adenosyl-L-methionine.
Catalyzes the radical-mediated insertion of two sulfur atoms into the C-6 and C-8 positions of the octanoyl moiety bound to the lipoyl domains of lipoate-dependent enzymes, thereby converting the octanoylated domains into lipoylated derivatives.
Functions as an U snRNP-specific nuclear import adapter. Involved in the trimethylguanosine (m3G)-cap-dependent nuclear import of U snRNPs. Binds specifically to the terminal m3G-cap U snRNAs.
Poly(U)-specific endoribonuclease involved in the processing of intron-encoded box C/D snoRNAs, such as U16 and U86. Releases products that have 2',3'-cyclic phosphate termini at the 3'-end.
Belongs to the methyltransferase superfamily. RRP8 family.
Probable methyltransferase required to silence rDNA.
Belongs to the MICOS complex subunit Mic60 family.
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.
Inhibits estrogen-induced cell proliferation.
Receptor for lutropin-choriogonadotropic hormone. The activity of this receptor is mediated by G proteins which activate adenylate cyclase.
Component of the PAF1 complex (PAF1C) which has multiple functions during transcription by RNA polymerase II. PAF1C associates with RNA polymerase II, is involved in transcriptional elongation and in histone modifications including methylation on histone H3 'Lys-4' (H3K4me3) (By similarity).
May play a role in mitochondrial respiratory chain complex IV assembly. Probably involved in the biogenesis of the COX complex.
Belongs to the Mrp/NBP35 ATP-binding proteins family. NUBP2/CFD1 subfamily.
Activates the Jnk signaling pathway. Dephosphorylates and deactivates p38 and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) (By similarity).
May function as a transcription factor involved in cell differentiation.
Hydrolyzes 3-hydroxyisobutyryl-CoA (HIBYL-CoA), a saline catabolite. Has high activity toward isobutyryl-CoA. Could be an isobutyryl-CoA dehydrogenase that functions in valine catabolism. Also hydrolyzes 3-hydroxypropanoyl-CoA (By similarity).
Hydrolyzes 3-hydroxyisobutyryl-CoA (HIBYL-CoA), a saline catabolite. Has high activity toward isobutyryl-CoA. Could be an isobutyryl-CoA dehydrogenase that functions in valine catabolism. Also hydrolyzes 3-hydroxypropanoyl-CoA.
Forms a large corepressor complex that contains sin3a/b, histone deacetylases hdac1 and hdac2, rbbp4 and possibly rbbp7. Interacts with the thyroid receptor (TR, composed of rxra and thrb) and the retinoid acid receptor (RAR, composed of rxra and rara) in the absence of ligand. Interacts with tbl1xr1. Interacts with zbtb33/kaiso (By similarity).
Mediates transcriptional repression by certain nuclear receptors. Participates in complexes which promote histone deacetylation and the formation of repressive chromatin structures which may impede access by the basal transcription machinery (By similarity). In association with hdac3, may play a role in the regulation of the circadian clock (By similarity).
The CORNR box motifs in the C-terminal region may be necessary and sufficient for binding to unligated nuclear hormone receptors. Sequences flanking these motifs may determine the precise nuclear hormone receptor specificity (By similarity).
Modulator of macroautophagy that causes accumulation of autophagosomes under basal conditions and enhances autophagic flux (By similarity). Represses cell death and promotes long-term clonogenic survival of cells grown in the absence of glucose in a macroautophagy-independent manner (By similarity). May have some role in extracellular matrix engulfment or growth factor receptor recycling, both of which can modulate cell survival (By similarity).
ATP-binding subunit of the mitochondrial potassium channel located in the mitochondrial inner membrane. Together with CCDC51/MITOK, forms a protein complex localized in the mitochondria that mediates ATP-dependent potassium currents across the inner membrane (that is, mitoK(ATP) channel) (By similarity). Plays a role in mitochondrial iron transport. Required for maintenance of normal cardiac function, possibly by influencing mitochondrial iron export and regulating the maturation of cytosolic iron sulfur cluster-containing enzymes (By similarity).
Belongs to the ABC transporter superfamily. ABCB family. Multidrug resistance exporter (TC 3.A.1.201) subfamily.
Component of the mitochondrial potassium channel (mitoK(ATP)).
Involved in the regulation of homocysteine metabolism. Converts betaine and homocysteine to dimethylglycine and methionine, respectively. This reaction is also required for the irreversible oxidation of choline (By similarity).
Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. TRX/MLL subfamily.
Associates with translationally inactive ribosomes in the nonrotated state.
Ribosome-binding protein involved in ribosome hibernation: associates with translationally inactive ribosomes and stabilizes the nonrotated conformation of the 80S ribosome, thereby promoting ribosome preservation and storage.
Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. Within the complex, functions as a proteasomal ubiquitin receptor.
Belongs to the ERCC1/RAD10/SWI10 family.
May participate in suppression of cell proliferation and induces apoptotic cell death through activation of interleukin-1-beta converting enzyme (ICE)-like proteases.
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.
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. Plays a role in differentiation of neuronal cells by stimulating neurite outgrowth.
Belongs to the apolipoprotein C2 family.
Component of chylomicrons, very low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL) in plasma. Plays an important role in lipoprotein metabolism as an activator of lipoprotein lipase.
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.
Has a glutathione-disulfide oxidoreductase activity in the presence of NADPH and glutathione reductase. Reduces low molecular weight disulfides and proteins.
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.
Accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (Complex I), that is believed not to be involved in catalysis. Complex I functions in the transfer of electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. May be the terminally assembled subunit of Complex I.
Belongs to the complex I NDUFV3 subunit family.
Complex I is composed of 45 different subunits. This is a component of the flavoprotein-sulfur (FP) fragment of the enzyme.
Essential acyltransferase that catalyzes the terminal and only committed step in triacylglycerol synthesis by using diacylglycerol and fatty acyl CoA as substrates. Required for synthesis and storage of intracellular triglycerides. Probably plays a central role in cytosolic lipid accumulation (By similarity).
Involved in the retrieval of endoplasmic reticulum membrane proteins from the early Golgi compartment.
Belongs to the Mediator complex subunit 9 family.
Promotes apoptosis. Acts by opposing the inhibitory activity of inhibitor of apoptosis proteins (IAP) (By similarity).
Plays a role in microtubule organization.
Belongs to the transglutaminase-like superfamily. PNGase family.
Specifically deglycosylates the denatured form of N-linked glycoproteins in the cytoplasm and assists their proteasome-mediated degradation. Cleaves the beta-aspartyl-glucosamine (GlcNAc) of the glycan and the amide side chain of Asn, converting Asn to Asp. Prefers proteins containing high-mannose over those bearing complex type oligosaccharides. Can recognize misfolded proteins in the endoplasmic reticulum that are exported to the cytosol to be destroyed and deglycosylate them, while it has no activity toward native proteins. Deglycosylation is a prerequisite for subsequent proteasome-mediated degradation of some, but not all, misfolded glycoproteins.
Belongs to the PIH1 family. Kintoun subfamily.
Required for cytoplasmic pre-assembly of axonemal dyneins, thereby playing a central role in motility in cilia and flagella. Involved in pre-assembly of dynein arm complexes in the cytoplasm before intraflagellar transport loads them for the ciliary compartment.
Binds 2 zinc divalent cations per subunit.
Homodimer. Bile acids promote the assembly of inactive monomers into an active dimer and enable catalysis.
Catalyzes the decomposition of L-selenocysteine to L-alanine and elemental selenium.
Belongs to the thiamine pyrophosphokinase family.
Phosphatidylinositol 5-phosphate 4-kinase with low enzymatic activity. May be a GTP sensor, has higher GTP-dependent kinase activity than ATP-dependent kinase activity.
Phosphorylated, phosphorylation is induced by EGF.
Transfers mannose from GDP-mannose to dolichol monophosphate to form dolichol phosphate mannose (Dol-P-Man) which is the mannosyl donor in pathways leading to N-glycosylation, glycosyl phosphatidylinositol membrane anchoring, and O-mannosylation of proteins; catalytic subunit of the dolichol-phosphate mannose (DPM) synthase complex.
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.
Belongs to the complex I NDUFA5 subunit family.
Belongs to the SLC43A transporter (TC 2.A.1.44) family.
Uniporter that mediates the transport of the stereospecific L-phenylalanine, L-methionine and L-branched-chain amino acids, between the extracellular space and the cytoplasm and may control the transepithelial (re)absorption of neutral amino acid in kidney and small intestine. The transport activity is mediated through facilitated diffusion and is sodium ions-, chloride ions- and pH-independent.
ADP-ribosylhydrolase that preferentially hydrolyzes the scissile alpha-O-linkage attached to the anomeric C1'' position of ADP-ribose and acts on different substrates, such as proteins ADP-ribosylated on serine and threonine, free poly(ADP-ribose) and O-acetyl-ADP-D-ribose. Specifically acts as a serine mono-ADP-ribosylhydrolase by mediating the removal of mono-ADP-ribose attached to serine residues on proteins, thereby playing a key role in DNA damage response. Serine ADP-ribosylation of proteins constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage. Does not hydrolyze ADP-ribosyl-arginine, -cysteine, -diphthamide, or -asparagine bonds. Also able to degrade protein free poly(ADP-ribose), which is synthesized in response to DNA damage: free poly(ADP-ribose) acts as a potent cell death signal and its degradation by ADPRHL2 protects cells from poly(ADP-ribose)-dependent cell death, a process named parthanatos (By similarity). Also hydrolyzes free poly(ADP-ribose) in mitochondria. Specifically digests O-acetyl-ADP-D-ribose, a product of deacetylation reactions catalyzed by sirtuins. Specifically degrades 1''-O-acetyl-ADP-D-ribose isomer, rather than 2''-O-acetyl-ADP-D-ribose or 3''-O-acetyl-ADP-D-ribose isomers.
The protein undergoes a dramatic conformational switch from closed to open states upon substrate-binding, which enables specific substrate recognition for the 1''-O-linkage. The glutamate flap (Glu-27) blocks substrate entrance to Mg(2+) in the unliganded closed state. In presence of substrate, Glu-27 is ejected from the active site: this closed-to-open transition significantly widens the substrate-binding channel and precisely positions the scissile 1''-O-linkage for cleavage while securing tightly 2'- and 3'-hydroxyls of ADP-ribose.
Belongs to the non-repetitive/WGA-negative nucleoporin family.
Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons. Is recruited by release factors to stalled ribosomes together with smg1 and smg8 (forming the SMG1C protein kinase complex) and, in the SMG1C complex, is required for the efficient association between smg1 and smg8 (By similarity).
As part of the MCIA complex, involved in the assembly of the mitochondrial complex I.
Cyclin-dependent kinase that phosphorylates the C-terminal domain (CTD) of the large subunit of RNA polymerase II (POLR2A), thereby acting as a key regulator of transcription elongation. Regulates the expression of genes involved in DNA repair and is required for the maintenance of genomic stability. Preferentially phosphorylates 'Ser-5' in CTD repeats that are already phosphorylated at 'Ser-7', but can also phosphorylate 'Ser-2'. Required for RNA splicing, possibly by phosphorylating srsf1/sf2 (By similarity).
Belongs to the uracil-DNA glycosylase (UDG) superfamily. UNG family.
Excises uracil residues from the DNA which can arise as a result of misincorporation of dUMP residues by DNA polymerase or due to deamination of cytosine.
Acts as a nucleation-promoting factor at the surface of endosomes, where it recruits and activates the Arp2/3 complex to induce actin polymerization, playing a key role in the fission of tubules that serve as transport intermediates during endosome sorting.
The VCA (verprolin, cofilin, acidic) domain promotes actin polymerization by the Arp2/3 complex in vitro.
Heterodimer with SRP9; binds RNA as heterodimer. Component of a signal recognition particle (SRP) complex that consists of a 7SL RNA molecule of 300 nucleotides and six protein subunits: SRP72, SRP68, SRP54, SRP19, SRP14 and SRP9.
Converts 1-acyl-sn-glycerol-3-phosphate (lysophosphatidic acid or LPA) into 1,2-diacyl-sn-glycerol-3-phosphate (phosphatidic acid or PA) by incorporating an acyl moiety at the sn-2 position of the glycerol backbone.
The HXXXXD motif is essential for acyltransferase activity and may constitute the binding site for the phosphate moiety of the glycerol-3-phosphate.
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.
Belongs to the complex I 75 kDa subunit family.
Regulatory subunit of the condensin-2 complex, a complex which establishes mitotic chromosome architecture and is involved in physical rigidity of the chromatid axis.
Promotes cell proliferation. Modulates apoptotic pathways. Increases mitogen-activated protein kinase activity. Important for cell migration, and for normal structure and assembly of the Golgi complex. Important for KDR/VEGFR2 signaling. Required for normal cardiovascular development. Required for normal angiogenesis, vasculogenesis and hematopoiesis during embryonic development.
Belongs to the NFYB/HAP3 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. NF-Y can function as both an activator and a repressor, depending on its interacting cofactors.
Essential factor for the assembly of mitochondrial NADH:ubiquinone oxidoreductase complex (complex I).
Belongs to the sodium:neurotransmitter symporter (SNF) (TC 2.A.22) family. SLC6A9 subfamily.
Component of the anaphase promoting complex/cyclosome (APC/C), a cell cycle-regulated E3 ubiquitin-protein ligase complex that controls progression through mitosis and the G1 phase of the cell cycle.
Belongs to the diphosphomevalonate decarboxylase family.
Catalyzes the ATP dependent decarboxylation of (R)-5-diphosphomevalonate to form isopentenyl diphosphate (IPP). Functions in the mevalonate (MVA) pathway leading to isopentenyl diphosphate (IPP), a key precursor for the biosynthesis of isoprenoids and sterol synthesis.
Plays a role in regulation of gastrulation, possibly by controlled reduction of cell adhesion in the periblastopore region which is necessary for optimal cell motility.
Functions as a regulator of the biosynthesis of TSH in the anterior pituitary gland and as a neurotransmitter/ neuromodulator in the central and peripheral nervous systems.
ATP-dependent DNA helicase implicated in telomere-length regulation, DNA repair and the maintenance of genomic stability. Acts as an anti-recombinase to counteract toxic recombination and limit crossover during meiosis. Regulates meiotic recombination and crossover homeostasis by physically dissociating strand invasion events and thereby promotes noncrossover repair by meiotic synthesis dependent strand annealing (SDSA) as well as disassembly of D loop recombination intermediates. Also disassembles T loops and prevents telomere fragility by counteracting telomeric G4-DNA structures, which together ensure the dynamics and stability of the telomere.
Belongs to the CND3 (condensin subunit 3) family.
Belongs to the ligand-gated ion channel (TC 1.A.9) family. Gamma-aminobutyric acid receptor (TC 1.A.9.5) subfamily. GABRG2 sub-subfamily.
Nicotinic acid adenine dinucleotide phosphate (NAADP) binding protein.
Lipoproteins are powerful coactivators of PM20D1 activity in vitro and NAA biosynthesis in vivo.
Secreted enzyme that regulates the endogenous N-fatty acyl amino acid (NAAs) tissue and circulating levels by functioning as a bidirectional NAA synthase/hydrolase. It condenses free fatty acids and free amino acids to generate NAAs and bidirectionally catalyzes the reverse hydrolysis reaction. Some of these NAAs stimulate oxidative metabolism via mitochondrial uncoupling, increasing energy expenditure in a UPC1-independent manner. Thereby, this secreted protein may indirectly regulate whole body energy expenditure. PM20D1 circulates in tight association with both low- and high-density (LDL and HDL,respectively) lipoprotein particles.
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).
May be involved in protection from oxidative damage.
Belongs to the FARP (FMRFamide related peptide) family.
Monomer. The propeptide region interacts with bmp4 in a non-covalent manner.
The propeptide region and the N- and C-terminal thirds of the mature protein are necessary for neural induction activity. Although cleavage doesn't appear essential for activity, residues surrounding the cleavage site are necessary for activity (By similarity). The propeptide region is both necessary and sufficient for bmp-inhibitory activity.
RNA-binding protein required for the microtubule-dependent transport of RNAs within polarized cell types.
The DRBM 3 domain appears to be the major RNA-binding determinant.
Component of the transition zone in primary cilia. Required for ciliogenesis.
Belongs to the class I-like SAM-binding methyltransferase superfamily. rRNA adenine N(6)-methyltransferase family. KsgA subfamily.
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. Stimulates transcription independently of the methyltransferase activity (By similarity).
Belongs to the SIMIBI class G3E GTPase family. ZNG1 subfamily.
May play a role in cardiomyocyte proliferation through paracrine signaling and activation of the PPI3K-AKT-CDK7 signaling cascade.
Belongs to the glycosyltransferase 49 family.
Catalyzes the final step in the metabolic pathway of hydroxyproline.
May be involved in photoreceptor outer segment disk morphogenesis.
Forms heterodimers either with the pro-apoptotic protein BAX or the anti-apoptotic protein BCL2.
Induces caspases and apoptosis. Counters the protective effect of BCL2.
Intact BH3 motif is required by BIK, BID, BAK, BAD and BAX for their pro-apoptotic activity and for their interaction with anti-apoptotic members of the Bcl-2 family.